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    Bone mineral density after treatment for gastric cancer: Endoscopic treatment versus gastrectomy. Noh Hye-Mi,Yoo Jun-Hyun,Jeong Ji Young,Park Yong Soon Medicine Changes in bone metabolism among gastric cancer survivors have long been recognized. The aim of our study was to clarify the changes of bone mineral density (BMD) among gastric cancer survivors who underwent endoscopic resection or gastrectomy. Forty-nine patients diagnosed with tumor, node, and metastasis (TNM) stage 1 gastric cancer with pathologic confirmation, who underwent BMD measurement just before the procedure, and had no prior osteoporosis treatment, were studied. BMD was measured with dual energy x-ray absorptiometry before and after treatment. Laboratory tests were performed using fresh serum, and serum levels of alkaline phosphatase, albumin, calcium, and phosphorus were measured. We used a nested case-control design to compare groups. Of the 49 patients, 34 underwent gastrectomy and 15 underwent endoscopic treatment. There were no differences in baseline clinical characteristics, including BMD, and biochemical data between groups. The mean and median follow-up intervals for BMD measurement were 32.6 months (standard deviation, 16.5) and 31.0 months (interquartile range: 21.5, 41.0), respectively. The follow-up BMDs of the femoral neck and total hip were lower in the gastrectomy group (P = .010 and .011, respectively). The percentage changes in BMD for the lumbar spine, femoral neck, and total hip were -3.30%, -1.52%, and 0.40%, respectively, in the endoscopic treatment group, and -7.17%, -6.30%, and -3.49%, respectively, in the gastrectomy group. Bone loss of the lumbar spine and femoral neck were greater in the gastrectomy group (P = .028 and .022, respectively). BMD is lower after gastrectomy than after endoscopic treatment among early stage gastric cancer survivors. 10.1097/MD.0000000000009582
    Impact of induction chemoradiotherapy on pulmonary function after lobectomy for lung cancer. Nomori Hiroaki,Shiraishi Atsushi,Cong Yue,Shoji Kazufusa,Misawa Masafumi,Sugimura Hiroshi,Oyama Yu The Journal of thoracic and cardiovascular surgery OBJECTIVE:Our study aim was to determine whether there are differential changes in whole-lung and regional lung functions after lobectomy for lung cancer between propensity score-matched patients treated with and without induction chemoradiotherapy, by using single-photon emission computed tomography lung perfusion. METHODS:This study was a retrospective matched cohort study of consecutively acquired data. Pulmonary function test and perfusion scintigraphy were conducted before lobectomy and 6 months after lobectomy in patients treated with induction therapy (n = 72) and in those not treated (n = 170), for measuring functional changes of whole lung, contralateral lung, and lobes. After exact matching on resected lobe site, propensity scores for age, smoking status, preoperative pulmonary functions, and predicted postoperative pulmonary function were used to match the groups. RESULTS:After the matching, 46 patients were selected from the groups. Standardized mean differences of the 5 matched variables were <0.1. Whole lung function significantly decreased after lobectomy in the induction therapy group than in the noninduction therapy group (P < .001). Although ipsilateral preserved lobe function before surgery was not different between the groups (P = .33), postoperative value was significantly lower in the induction therapy group than in the noninduction therapy group (P < .001). Although both groups showed a significant increase of contralateral lung function after lobectomy (P < .01), the increases were not significantly different between the groups (P = .81). CONCLUSIONS:Induction chemoradiotherapy was associated with reduced pulmonary function after lobectomy because of a decrease in ipsilateral preserved lobe function, which could be caused by the chronic effects of the induction chemoradiotherapy. 10.1016/j.jtcvs.2017.12.081
    Tumor Response After Stereotactic Body Radiation Therapy to Nonspine Bone Metastases: An Evaluation of Response Criteria. McDonald Rachel,Probyn Linda,Poon Ian,Erler Darby,Brotherston Drew,Soliman Hany,Cheung Patrick,Chung Hans,Chu William,Loblaw Andrew,Thavarajah Nemica,Lang Catherine,Chin Lee,Chow Edward,Sahgal Arjun International journal of radiation oncology, biology, physics PURPOSE:To evaluate the applicability of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and University of Texas MD Anderson (MDA) Cancer Center criteria in the setting of stereotactic body radiation therapy (SBRT) to nonspine bone metastases. METHODS:Patients who were treated with SBRT to nonspine bone metastases were identified by retrospective chart review. An independent musculoskeletal radiologist evaluated response to treatment using computed tomography (CT) scans. RESULTS:Thirty-three patients were treated to 42 nonspine bone metastases. The most common primary cancer cites were renal cell carcinoma (RCC) (33.3%), lung (24.2%), and prostate (18.2%). Bone metastases were either mainly lytic (57.1%), mainly sclerotic (28.6%), or mixed (14.3%). When lytic and sclerotic lesions were evaluated according to RECIST 1.1, local control (LC) was 83%, 85%, 88%, and 80% for those with CT imaging between months 1 to 3, 4 to 6, 7 to 9, and 10 to 12, respectively. When evaluated by the MDA criteria by density, LC within each time period was slightly greater. Overall LC decreased considerably when evaluated by MDA in terms of size. CONCLUSIONS:Consensus definitions of response are required as they have implications on clinical trials and disease management. Without consistent response criteria, outcomes from clinical trials cannot be compared and treatment efficacy remains undetermined. 10.1016/j.ijrobp.2015.07.2288
    Fractures frequently occur in older cancer patients: the MD Anderson Cancer Center experience. Edwards Beatrice J,Sun Ming,Zhang Xiaotao,Holmes Holly M,Song Juhee,Khalil Peter,Karuturi Meghan,Shah Jay B,Dinney Colin P,Gagel Robert F,Valero Vicente,Champlin Richard E,Tripathy Debasish,Murphy William A Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE AND INTRODUCTION:A growing number of cancer patients are older adults aged 65 years and older. Patients with cancer are at increased risk for developing osteoporosis, falls, and fractures. We sought to identify the incidence of fractures in older adults who underwent cancer care between January 2013 and December 2015. METHODS:A comprehensive geriatric assessment was performed, and bone densitometry was measured at baseline, with a 2-year follow-up. RESULTS:In this study, among 304 patients with gastrointestinal, urologic, breast, lung, and gynecologic cancers we evaluated, and who completed the bone density testing (n = 199), 80% had osteoporosis or low bone mass (osteopenia). There was a higher prevalence of osteoporosis in cancer patients (40 vs. 16%, p = 0.05) than in population studies. Vitamin D insufficiency (< 30 ng/ml) was identified in 49% of tested cases (n = 245). Risk factors for low bone mass or osteoporosis were advanced age (p = 0.05), malnutrition (p = 0.04), and frailty (p = 0.01). Over the following 2 years (median follow-up 18 months), there was an incidence of fractures of 110 per 1000 person-years, or 2.8 times higher than reported in individuals without cancer. Risk factors for fractures included advanced age (70-79 vs. 60-69 years, p = 0.05) and frailty (p = 0.03). CONCLUSION:Most older cancer patients studied have osteoporosis or low bone mass, resulting in an almost 3-fold increase in fracture risk as compared to epidemiologic studies. Bone health issues are commonly seen in older cancer patients, we recommend universal bone density testing. The initiation of antiresorptive treatment when findings are of osteopenia or osteoporosis will reduce the risk of fractures. 10.1007/s00520-017-3962-7
    Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases. Siraj Ahsan,Desestret Virginie,Antoine Martine,Fromont Gaëlle,Huerre Michel,Sanson Marc,Camparo Philippe,Pichon Christophe,Planeix François,Gonin Julie,Radu Aurelian,Ghinea Nicolae BMC cancer BACKGROUND:The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. METHODS:We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. RESULTS:In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone receptor level, but not with either HER-2 or estrogen receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. CONCLUSION:FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors. 10.1186/1471-2407-13-246
    Zoledronic acid is unable to induce apoptosis, but slows tumor growth and prolongs survival for non-small-cell lung cancers. Li Ying-Ying,Chang John W-C,Chou Wen-Chi,Liaw Chuang-Chi,Wang Hung-Ming,Huang Jen-Seng,Wang Cheng-Hsu,Yeh Kun-Yun Lung cancer (Amsterdam, Netherlands) BACKGROUND:Although zoledronic acid (ZOL), a third-generation nitrogen-containing bisphosphonate, has been identified as an attractive therapeutic agent against breast cancer, prostate cancer, multiple myeloma as well as small-cell lung cancer (SCLC), as best as we are aware, the anti-tumor effect of ZOL upon non-small-cell lung cancer (NSCLC) remains to be effectively investigated. This study examined the effects of ZOL upon the line-1 tumor cell, using a murine lung adenocarcinoma cell line similar to the behavior of human lung adenocarcinoma. METHODS:We investigated the anti-tumor effects of ZOL (3-100 microM) on line-1 tumor cells in vitro, including cellular proliferation, by means of an MTT assay, cell-cycle analysis by flow cytometry and by assessing the level of apoptosis by annexin V/propidium iodide (PI) and 4'-6-diamidino-2-phenylindole (DAPI) staining. Further, we evaluated the growth and survival of line-1 tumor cells following ZOL treatment (1 microg/kg/week) using an animal model. We also examined the in vivo cell-cycle pattern using lacZ-expressing line-1 cells (line-1/lacZ). RESULTS:ZOL significantly slowed the line-1 tumor growth in a dose-dependent manner in vitro. The treated line-1 tumor cells typically arrested at the S/G2/M-phase of the cell-cycle following ZOL exposure, but no apoptotic cells could be detected by either annexin V/PI or DAPI staining. When the ZOL was washed out, the drug-inhibited cells continued to proliferate again and the cell-cycle prolongation elicited earlier by the drug, then disappeared. Within 72-96 h following drug removal, the cell-cycle of the treated cells revealed a similar distribution to that of the untreated controls. In vivo studies demonstrated that ZOL significantly slowed the line-1 tumor growth. Indeed, mice lived significantly longer when they had been ZOL-treated than was the case for untreated mice (p<0.05). Using line-1/lacZ cells, the in vivo cell-cycle distribution of line-1 tumor cells subsequent to ZOL exposure revealed S/G2/M-phase arrest that was identical to the in vitro culture. CONCLUSIONS:ZOL maintains the potential to reduce tumor burden and prolong survival for murine pulmonary adenocarcinoma. The flow cytometrical analysis of cell-cycle demonstrated that ZOL induces no apoptosis but is able to arrest line-1 tumor cells at the S/G2/M-phase. Although the clinical relevance of these results warrants verification for human lung cancer patients, ZOL combined with chemotherapy and/or radiotherapy appears to be a new therapeutic strategy for the effective treatment of NSCLC. 10.1016/j.lungcan.2007.08.026
    Macrophage stimulating protein promotes liver metastases of small cell lung cancer cells by affecting the organ microenvironment. Sato Seidai,Hanibuchi Masaki,Kuramoto Takuya,Yamamori Nodoka,Goto Hisatsugu,Ogawa Hirohisa,Mitsuhashi Atsushi,Van Trung The,Kakiuchi Soji,Akiyama Shin-ichi,Nishioka Yasuhiko,Sone Saburo Clinical & experimental metastasis The organ microenvironment significantly affects the processes of cancer metastasis. Elucidating the molecular mechanisms of interaction between tumor cells and the organ microenvironment is crucial for the development of effective therapeutic strategies to eradicate cancer metastases. Macrophage stimulating protein (MSP), an activator of macrophages, regulates a pleiotropic array of effects, including proliferation, cellular motility, invasiveness, angiogenesis, and resistance to anoikis. However, the role of MSP in cancer metastasis is still largely unknown. In this study, the action of MSP on the production of metastases was determined in a multiple-organ metastasis model. The murine MSP gene was transfected into two human SCLC cell lines, SBC-5 and H1048, to establish transfectants secreting biologically active MSP. MSP gene transduction did not affect cell proliferation and motility in vitro. Intravenously inoculated MSP transfectants produced significantly larger numbers of liver metastases than parental cells or vector control clones, while there were no significant differences in bone or lung metastases among them. Immunohistochemical analyses of liver metastases revealed that tumor-associated microvessel density and tumor-infiltrating macrophages were significantly increased in lesions produced by MSP transfectants. MSP could stimulate the migration of murine macrophages and endothelial cells in vitro. Consequently, MSP may be one of the major determinants that affects the properties of tumor stroma and that produces a permissive microenvironment to promote cancer metastasis. 10.1007/s10585-012-9540-y
    A Morphomic Index Is an Independent Predictor of Survival After Lung Cancer Resection. Ferguson Mark K,Mitzman Brian,Derstine Brian,Lee Sang Mee,Pienta Michael J,Wang Stewart C,Lin Jules The Annals of thoracic surgery BACKGROUND:Sarcopenia, visceral fat volume, and bone density have been associated with lung cancer survival. We developed a morphomic index based on computed tomographic measurements of these components, and assessed its relationship to survival after lung cancer resection. METHODS:Patients who underwent lung cancer resection from 1995 to 2014 were evaluated. A morphomic index (range of 0 to 3) was developed as the sum of the scores for three body components-dorsal muscle area, vertebral trabecular bone density, and visceral fat area-measured at vertebral levels T10 to T12, with a point assigned to each component when in the lowest tercile. The relationship of the morphomic index to overall survival was assessed by the log rank test. Overall survival was assessed using Cox proportional hazards models adjusted for relevant covariates. RESULTS:We included 944 patients (451 women; 48%). The mean age was 66.4 ± 10.3 years. Median follow-up was 4.5 years. Median survival was associated with the morphomic index scores on univariate analysis (P < .001). Morphomic index scores of 2 (P = .026) and 3 (P = .004) referenced to score 0 or 1 were independent predictors of survival on Cox regression analysis. CONCLUSIONS:A morphomic index is an independent predictor of survival after lung cancer resection. The index may help in calibrating patient expectations and in shared decision making regarding lung cancer surgery. 10.1016/j.athoracsur.2019.10.064
    Skeletal-related events in advanced lung adenocarcinoma patients evaluated EGFR mutations. Nagata Misato,Kudoh Shinzoh,Mitsuoka Shigeki,Suzumura Tomohiro,Umekawa Kanako,Tanaka Hidenori,Matsuura Kuniomi,Kimura Tatsuo,Yoshimura Naruo,Hirata Kazuto Osaka city medical journal BACKGROUND:The rate of lung cancer metastasis to the bone is high and skeletal-related events (SREs) decrease the quality of life in many patients. Recently, it was found that a subgroup of patients with non-small cell lung cancer (NSCLC) have specific mutations in the EGFR (epidermal growth factor receptor) gene. We assessed the SREs in advanced lung adenocarcinoma patients that evaluated EGFR mutations in whom bone metastasis was present. METHODS:We retrospectively investigated the clinical records of 377 patients with advanced NSCLC. Patients were evaluated for the presence of EGFR mutations, bone metastases, the incidence of SREs, and treatment history before the first SRE. RESULTS:A total of 78 patients who were evaluated for EGFR mutations had bone metastasis from lung adenocarcinoma. The most frequent site of bone metastasis was the spine (36.2%). SREs occurred in 37 patients (47.4%), the most common of which was bone radiotherapy (41.0%). Significant differences were not observed in the sites of bone metastases or the patterns of SREs between patients with and without EGFR mutations. The median time from bone metastasis to the first SRE was 5.8 months in all of the subjects, history of EGFR-tyrosine kinase inhibitor (TKI) treatment was significantly associated with longer median time to first SRE (14.2 months vs 1.3 months, p < 0.0001), and the median time to first SRE of patients with PS 0-1 was longer (8.5 months vs 0.9 months, p = 0.0023). CONCLUSIONS:We found that SRE patterns have no difference between EGFR mutation positive and negative, and that the time from bone metastasis to the first SRE was longer in advanced lung adenocarcinoma patients with good PS and history of EGFR-TKI treatment.
    Retrospective evaluation of the clinical benefit of long-term continuous use of zoledronic acid in patients with lung cancer and bone metastases. Henk Henry J,Kaura Satyin,Teitelbaum April Journal of medical economics BACKGROUND:For patients with bone metastases, skeletal-related events including fracture are common, can cause considerable morbidity, and may reduce overall survival (OS). This retrospective analysis assessed the effect of Zometa (zoledronic acid, ZOL), an intravenous bisphosphonate (IV-BP), on fracture risk and OS in patients with bone metastases from lung cancer (LC). (Zometa is a registered trademark of Novartis Pharmaceuticals Corporation, USA.) METHODS:A claims-based analysis using commercial and Medicare Advantage data from >45 US managed-care plans was used to evaluate the association between fracture risk and treatment persistency (31-90, 91-180, 181-365, and ≥366 days) and follow-up duration in LC patients diagnosed with bone metastases between 01/01/2001 and 12/31/2006 and treated with ZOL or without (no IV-BP). Persistency was defined as the absence of a >45-day gap between ZOL treatments. Analysis of variance tests were used to compare follow-up duration, a proxy for OS, between ZOL persistency groups. The effect of time to treatment with ZOL was also assessed. RESULTS:In 9874 LC patients with bone metastases (n = 1090 ZOL; n = 8784 no IV-BP) the unadjusted relative fracture risk was reduced by 40% with ZOL vs no IV-BP; fracture risk decreased consistently with increasing duration of ZOL treatment. Even short-term (31-90 days) ZOL significantly reduced fracture risk (47%) vs no IV-BP (p = 0.005) with adjustment for differences in demographic and clinical characteristics. Delaying ZOL until after bone metastases were diagnosed significantly increased fracture risk (p = 0.0017). For a sub-set of patients included in a survival analysis (n = 550 ZOL; n = 4512 no IV-BP), mortality was significantly lower (mean, 38.6 vs 46.8 deaths/100 person-years; p = 0.038) in those treated with ZOL vs no IV-BP. LIMITATIONS:Interpretation of this claims-based analysis must be tempered by the inherent limitations of observational data, such as limited clinical information and the ability to control for prognostic factors. CONCLUSIONS:This retrospective analysis demonstrates that LC patients with bone metastases receiving ZOL had significantly reduced risk of fracture (p = 0.005) and death (p < 0.038) vs patients receiving no IV-BP. Longer ZOL persistency consistently yielded better outcomes, with ≥12 months' treatment producing the greatest benefit. 10.3111/13696998.2011.650489
    A comparative study of intravenous ibandronate and pamindronate in patients with bone metastases from breast or lung cancer: effect on metastatic bone pain. Heras Panagiotis,Hatzopoulos Antonios,Heras Vasilios,Kritikos Nikolaos,Karagiannis Stefanos,Kritikos Konstantinos American journal of therapeutics We compared the effects of ibandronate and pamindronate in patients with bone metastases from breast or lung cancer and we found that ibandronate is superior to pamindronate in alleviating pain, improving mobility and quality of life, and reducing bone resorption indices in patients with bone metastases from breast or lung cancer. 10.1097/MJT.0b013e3181e70c38
    Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages. Hiraoka Koji,Zenmyo Michihisa,Watari Kousuke,Iguchi Haruo,Fotovati Abbas,Kimura Yusuke N,Hosoi Fumihito,Shoda Takanori,Nagata Kensei,Osada Hiroyuki,Ono Mayumi,Kuwano Michihiko Cancer science Attention has recently focused on the critical role of inflammatory responses in the tumor stroma that provide favorable conditions for cancer-cell growth and invasion/metastasis. In particular, macrophages recruited into the tumor stroma and activated, known as tumor-associated macrophages, are suggested to promote tumorigenesis. In this study, we examined the effect of a decrease in the number of monocytes/macrophages in peripheral blood and the tumor stroma on the development of bone and muscle metastases by lung cancer cells. Treatment with clodronate encapsulated by liposomes (Cl(2)MDP-LIP) has been developed for the depletion of monocytes/macrophages in an animal model. Subcutaneous administration of Cl(2)MDP-LIP markedly reduced the number of monocytes in peripheral blood, resulting in efficient suppression of both bone metastasis and muscle metastasis when lung cancer HARA-B cells were injected into the left cardiac ventricle of mice. Treatment with Cl(2)MDP-LIP significantly reduced the number of macrophages in tumors and the number of osteoclasts in bone marrow, as well as peripheral monocytes in mice harboring lung cancer cells. In contrast, treatment with an osteoclast-targeting antibiotic, reveromycin A, inhibited bone metastasis by lung cancer cells, but not muscle metastasis. The survival of human macrophages in culture was found to be specifically blocked by Cl(2)MDP-LIP, but not by reveromycin A. Cl(2)MDP-LIP thus exerted antimetastatic effects in both bone and muscle whereas reveromycin A did so only in bone. Liposome-encapsulated bisphosphonate may modulate metastasis through decreasing the number of monocytes/macrophages in both peripheral blood and the tumor stroma, suggesting that tumor-associated macrophages might be suitable targets for antimetastatic therapy. 10.1111/j.1349-7006.2008.00880.x
    Marrow cell genetic phenotype change induced by human lung cancer cells. Del Tatto Michael,Ng Thomas,Aliotta Jason M,Colvin Gerald A,Dooner Mark S,Berz David,Dooner Gerri J,Papa Elaine F,Hixson Douglas C,Ramratnam Bharat,Aswad Bassam I,Sears Edmund H,Reagan John,Quesenberry Peter J Experimental hematology Microvesicles have been shown to mediate varieties of intercellular communication. Work in murine species has shown that lung-derived microvesicles can deliver mRNA, transcription factors, and microRNA to marrow cells and alter their phenotype. The present studies evaluated the capacity of excised human lung cancer cells to change the genetic phenotype of human marrow cells. We present the first studies on microvesicle production by excised cancers from human lung and the capacity of these microvesicles to alter the genetic phenotype of normal human marrow cells. We studied 12 cancers involving the lung and assessed nine lung-specific mRNA species (aquaporin, surfactant families, and clara cell-specific protein) in marrow cells exposed to tissue in co-culture, cultured in conditioned media, or exposed to isolated lung cancer-derived microvesicles. We assessed two or seven days of co-culture and marrow which was unseparated, separated by ficoll density gradient centrifugation or ammonium chloride lysis. Under these varying conditions, each cancer derived from lung mediated marrow expression of between one and seven lung-specific genes. Microvesicles were identified in the pellet of ultracentrifuged conditioned media and shown to enter marrow cells and induce lung-specific mRNA expression in marrow. A lung melanoma and a sarcoma also induced lung-specific mRNA in marrow cells. These data indicate that lung cancer cells may alter the genetic phenotype of normal cells and suggest that such perturbations might play a role in tumor progression, tumor recurrence, or metastases. They also suggest that the tissue environment may alter cancer cell gene expression. 10.1016/j.exphem.2011.08.008
    Osteoblasts remotely supply lung tumors with cancer-promoting SiglecF neutrophils. Engblom Camilla,Pfirschke Christina,Zilionis Rapolas,Da Silva Martins Janaina,Bos Stijn A,Courties Gabriel,Rickelt Steffen,Severe Nicolas,Baryawno Ninib,Faget Julien,Savova Virginia,Zemmour David,Kline Jaclyn,Siwicki Marie,Garris Christopher,Pucci Ferdinando,Liao Hsin-Wei,Lin Yi-Jang,Newton Andita,Yaghi Omar K,Iwamoto Yoshiko,Tricot Benoit,Wojtkiewicz Gregory R,Nahrendorf Matthias,Cortez-Retamozo Virna,Meylan Etienne,Hynes Richard O,Demay Marie,Klein Allon,Bredella Miriam A,Scadden David T,Weissleder Ralph,Pittet Mikael J Science (New York, N.Y.) Bone marrow-derived myeloid cells can accumulate within tumors and foster cancer outgrowth. Local immune-neoplastic interactions have been intensively investigated, but the contribution of the systemic host environment to tumor growth remains poorly understood. Here, we show in mice and cancer patients ( = 70) that lung adenocarcinomas increase bone stromal activity in the absence of bone metastasis. Animal studies reveal that the cancer-induced bone phenotype involves bone-resident osteocalcin-expressing (Ocn) osteoblastic cells. These cells promote cancer by remotely supplying a distinct subset of tumor-infiltrating SiglecF neutrophils, which exhibit cancer-promoting properties. Experimentally reducing Ocn cell numbers suppresses the neutrophil response and lung tumor outgrowth. These observations posit osteoblasts as remote regulators of lung cancer and identify SiglecF neutrophils as myeloid cell effectors of the osteoblast-driven protumoral response. 10.1126/science.aal5081
    Impact of chemotherapy on hypercalcemia in breast and lung cancer patients. Hassan Bassam Abdul Rasool,Yusoff Zuraidah Binti Mohd,Hassali Mohamed Azmi,Othman Saad Bin,Weiderpass Elisabete Asian Pacific journal of cancer prevention : APJCP INTRODUCTION:Hypercalcemia is mainly caused by bone resorption due to either secretion of cytokines including parathyroid hormone-related protein (PTHrP) or bone metastases. However, hypercalcemia may occur in patients with or without bone metastases. The present study aimed to describe the effect of chemotherapy treatment, regimens and doses on calcium levels among breast and lung cancer patients with hypercalcemia. METHODS:We carried a review of medical records of breast and lung cancer patients hospitalized in years 2003 and 2009 at Penang General Hospital, a public tertiary care center in Penang Island, north of Malaysia. Patients with hypercalcemia (defined as a calcium level above 10.5 mg/dl) at the time of cancer diagnosis or during cancer treatment had their medical history abstracted, including presence of metastasis, chemotherapy types and doses, calcium levels throughout cancer treatment, and other co-morbidity. The mean calcium levels at first hospitalization before chemotherapy were compared with calcium levels at the end of or at the latest chemotherapy treatment. Statistical analysis was conducted using the Chi-square test for categorical data, logistic regression test for categorical variables, and Spearman correlation test, linear regression and the paired sample t tests for continuous data. RESULTS:Of a total 1,023 of breast cancer and 814 lung cancer patients identified, 292 had hypercalcemia at first hospitalization or during cancer treatment (174 breast and 118 lung cancer patients). About a quarter of these patients had advanced stage cancers: 26.4% had mild hypercalcemia (10.5-11.9 mg/dl), 55.5% had moderate (12-12.9 mg/dl), and 18.2% severe hypercalcemia (13-13.9; 14-16 mg/dl). Chemotherapy lowered calcium levels significantly both in breast and lung cancer patients with hypercalcemia; in particular with chemotherapy type 5-flurouracil+epirubicin+cyclophosphamide (FEC) for breast cancer, and gemcitabine+cisplatin in lung cancer. CONCLUSION:Chemotherapy decreases calcium levels in breast and lung cancer cases with hypercalcemia at cancer diagnosis, probably by reducing PTHrP levels. 10.7314/apjcp.2012.13.9.4373
    Local effects of malignancy on bone. Brown Sue A,Clines Gregory A,Guise Theresa A Current opinion in endocrinology, diabetes, and obesity PURPOSE OF REVIEW:Skeletal-related complications occur commonly in many solid tumors including breast, prostate and lung cancer as well as multiple myeloma. In addition, malignancies and their associated treatment may result in bone loss or osteoporosis. This review will focus solely on recent data associated with metastatic bone disease with a focus on breast cancer, prostate cancer and multiple myeloma. Bone loss or osteoporosis associated with cancer will be covered in a separate article in this issue. RECENT FINDINGS:Recent progress in understanding the pathophysiology of bone metastases has pointed to several novel pathways: transforming growth factor beta; receptor activator of nuclear factor beta ligand and osteoprotegerin; and Wnt signaling pathways and associated factors such as dickkopf-1 and endothelin-1. SUMMARY:The identification of new pathways is important in metastatic bone disease from cancer and has allowed for the development of novel therapeutics aimed at preventing the devastating complications of bone metastases. Bisphosphonates remain the predominant therapy in use for the treatment and prevention of skeletal-related adverse effects from cancer. 10.1097/MED.0b013e3282f15419
    Osteoporosis and lung transplantation: a prospective study. Spira A,Gutierrez C,Chaparro C,Hutcheon M A,Chan C K Chest STUDY OBJECTIVE:Osteoporosis is a well-recognized complication of lung transplantation that may significantly impair the quality of life of transplant recipients. We performed a prospective study of bone mineral density (BMD) before and after transplantation to determine the degree of bone mass loss associated with lung transplantation Patients and design: We conducted a prospective study of BMD in 28 patients with various end-stage respiratory diseases pretransplantation and 6 to 12 months posttransplantation. The BMD of the lumbar spine (LS) and femoral neck (FN) were measured. All 28 patients were treated only with vitamin D and calcium supplementation posttransplant. The primary endpoint was the percentage change in BMD. The secondary endpoint was the incidence of fractures posttransplant. A univariate analysis was conducted to determine the various risk factors associated with bone mass loss pretransplant and posttransplant. RESULTS:Prior to transplantation, moderate to severe bone disease was evident. The mean (+/- SD) pretransplant T score (the number of SDs from the peak bone mass) and Z score (the number of SDs from the age-matched mean) for the LS were -1.72 +/- 1.37 and -1.44 +/- 1.31, respectively. The mean pretransplant T score and Z score for the FN were -2.65 +/- 1.01 and -1.5 +/- 1.43, respectively. Within 6 to 12 months posttransplant, the mean BMD for the LS decreased by 4.76% (p < 0.001), while the mean BMD for the FN decreased by 5.3% (p < 0.001). Five of the 28 patients (18%) suffered osteoporotic fractures posttransplant, while no fractures were documented pretransplant. The cumulative steroid dose posttransplant was associated with a drop in BMD for the LS and FN (r = 0.39, p = 0.039 and r = 0.63, p < 0.001, respectively), while a negative association was found between cumulative steroid use pretransplant and baseline LS and FN T scores (r = -0.4, p = 0. 02 and r = -0.43, p = 0.023, respectively). CONCLUSION:Within 6 to 12 months after lung transplantation, there is a significant decrease in BMD at both the LS and FN levels (approximately 5%) despite vitamin D and calcium supplementation. This drop in BMD is associated with a relatively high incidence of osteoporotic fractures posttransplant. 10.1378/chest.117.2.476
    The carcinogenicity of alendronate in patients with osteoporosis: evidence from cohort studies. Chen Ling-Xiao,Ning Guang-Zhi,Zhou Zhi-Rui,Li Yu-Lin,Zhang Di,Wu Qiu-Li,Zhang Tian-Song,Cheng Lei,Feng Shi-Qing PloS one CONTEXT:Alendronate may relate to the incidence of cancers, especially esophageal and colon cancer. But the results are inconsistent in different studies. OBJECTIVE:To quantify the association between the use of alendronate and the occurrence of different types of cancer. DATA SOURCES:We searched Embase, Pubmed, CENTRAL, SIGLE and clinicaltrials.gov, up to 2014 June. STUDY SELECTION:Cohort studies reporting association between alendronate or bisphosphonate therapy including alendronate in patients with osteoporosis and risk of cancer were selected by two authors. DATA EXTRACTION:Two authors independently extracted the data. The Chi-square test and the I-square test were used for testing heterogeneity between studies. DATA SYNTHESIS:Eight cohort studies were included in the meta-analysis. Meta-analysis result manifested that alendronate significantly increased the incidence of lung cancer (HR 1.23, 95%CI 1.03 to 1.47, P value = 0.03), nevertheless, there was no significant difference after we excluded either Lee's 2012 study (HR 1.17, 95%CI 0.95 to 1.44, P value = 0.13) or Chiang's 2012 study (HR 1.47, 95%CI 1 to 2.17, P value = 0.05). For the incidence of colorectal cancer, no significant difference occurred (HR 0.91, 95%CI 0.74 to 1.13, P value = 0.39), but there was a positive relationship when we used fixed model (HR 0.85, 95%CI 0.78 to 0.93, P value = 0.004). For the incidence of liver cancer, there was no significant difference (HR 1.36, 95%CI 0.9 to 2.04, P value = 0.14), however, the result changed after we excluded Chiang's 2012 study (HR 1.69, 95%CI 1.03 to 2.77, P value = 0.04). There was no significant difference in other types of cancer. CONCLUSION:Based on current evidences, alendronate therapy may be associated with a high risk of lung cancer, may with an excess risk of liver cancer, a low risk of colorectal and no related risk of other cancers. 10.1371/journal.pone.0123080
    The Role of Tumor Necrosis Factor Alpha and TNF Superfamily Members in Bone Damage in Patients with End-Stage Chronic Obstructive Lung Disease Prior to Lung Transplantation. Kochetkova Evgenia A,Nevzorova Vera A,Ugai Ludmila G,Maistrovskaia Yulia V,Massard Gilbert Calcified tissue international A disequilibrium of tumor necrosis superfamily (TNF) members, including the serum osteoprotegerin, soluble receptor activator of nuclear factor-κB ligand, soluble TNF-related apoptosis-inducing ligand and TNF-α, was associated with the occurrence of a reduced skeletal mass and osteoporosis in male patients with end-stage chronic obstructive pulmonary disease (COPD). The purpose of this study was to explore the associations between serum biomarkers of tumor necrosis factor (TNF) superfamily and body and bone compositions in end-stage COPD males. Pulmonary function, T-score at the lumbar spine and femoral neck, lean mass, serum osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL), TNF-α and its receptors (sTNFR-I, sTNFR-II) and soluble TNF-related apoptosis-inducing ligand (sTRAIL) levels were evaluated in 48 male patients with end-stage COPD and 36 healthy male volunteers. OPG was lower in male COPD patients than in control subjects, whereas sRANKL, TNF-α and its receptors were higher. The serum sTRAIL level showed a tendency to increase compared with that of healthy subjects (P = 0.062). Serum OPG showed a positive correlation with bone density. In contrast, serum TNF-α, sRANKL and sTRAIL were inversely associated with pretransplant bone density. We have noted the appearance of statistically significant inverse relationships between lean mass values and TNF-α, sTNFR-I and II and sRANKL levels in male COPD patients. Moreover, there was a negative correlation between sTRAIL levels with airway obstruction (P = 0.005) and hypercapnia (P = 0.042) in advanced COPD patients. Through a multiple linear regression analysis, our study revealed that a disequilibrium of TNF family members was strongly associated with the occurrence of a reduced skeletal mass and osteoporosis. These results provide further evidence that abnormal levels of TNF superfamily molecules may cause not only a decrease in BMD, but also lower muscle mass in end-stage COPD. 10.1007/s00223-016-0185-8
    Bone mass density, fracture history, self-reported osteoporosis as proxy variables for estrogen and the risk of non-small-cell lung cancer--a population based cohort study, the HUNT study: are proxy variables friends or faults? Hatlen Peter,Langhammer Arnulf,Forsmo Siri,Carlsen Sven M,Amundsen Tore Lung cancer (Amsterdam, Netherlands) Lung cancer has the highest mortality of all cancers. Patients with early stage disease have the best cure rates and that emphasizes the importance of early detection. About half of all non-small cell lung cancers (NSCLC) are estrogen receptor positive. The impact of estrogen and its receptors for NSCLC carcinogenesis has been studied but is still unclear. Low estrogen levels are associated with osteoporosis. We hypothesize that low bone mineral density (BMD), a positive history of fracture or self-reported osteoporosis, used as a proxy variable for life time estrogen exposure, are associated with a low incidence of NSCLC. We analyzed data from a cohort study, the Nord-Trøndelag Health Study 2 (1995-1997) linked to the Norwegian Cancer Registry. Using the logistic regression model we calculated the odds ratio (OR) with a 95% confidence interval (CI) for the risk of NSCLC for the three proxy variables, stratified by sex. Participants older than 50 years of age, having measured bone density (N = 18,156), having answered the questions on self-reported fracture (N = 37,883) and osteoporosis (N = 25,701) and known body mass index (BMI) (N = 29,291), were evaluated for inclusion. In 6996 participants all these information was available in addition to tobacco use, and in women also hormonal replacement therapy (HRT). Lung function (FEV1 percent of predicted) was included in a sensitivity analysis. We identified 132 (1.9%) cases of NSCLC, 59 (1.2%) and 73 (3.3%) cases in women and men, respectively. Low BMD was associated with a higher risk of NSCLC, OR: 2.38, 95% CI: 1.09-5.18 and OR: 2.67, 95% CI: 1.39-5.16 in women and men, respectively. No association was found between the two other proxy variables and the risk of NSCLC. Inclusion of lung function in the model did not change the results. Contrary to our hypothesis, women and men with low BMD had a higher risk for NSCLC. In addition the study demonstrates that the risk depends on which proxy variable was chosen, and we may ask: are proxy variables reliable? 10.1016/j.lungcan.2013.04.001
    MRI assessment of bone structure and microarchitecture. Chang Gregory,Boone Sean,Martel Dimitri,Rajapakse Chamith S,Hallyburton Robert S,Valko Mitch,Honig Stephen,Regatte Ravinder R Journal of magnetic resonance imaging : JMRI Osteoporosis is a disease of weak bone and increased fracture risk caused by low bone mass and microarchitectural deterioration of bone tissue. The standard-of-care test used to diagnose osteoporosis, dual-energy x-ray absorptiometry (DXA) estimation of areal bone mineral density (BMD), has limitations as a tool to identify patients at risk for fracture and as a tool to monitor therapy response. Magnetic resonance imaging (MRI) assessment of bone structure and microarchitecture has been proposed as another method to assess bone quality and fracture risk in vivo. MRI is advantageous because it is noninvasive, does not require ionizing radiation, and can evaluate both cortical and trabecular bone. In this review article, we summarize and discuss research progress on MRI of bone structure and microarchitecture over the last decade, focusing on in vivo translational studies. Single-center, in vivo studies have provided some evidence for the added value of MRI as a biomarker of fracture risk or treatment response. Larger, prospective, multicenter studies are needed in the future to validate the results of these initial translational studies. LEVEL OF EVIDENCE:5 Technical Efficacy: Stage 5 J. MAGN. RESON. IMAGING 2017;46:323-337. 10.1002/jmri.25647
    Antineoplastic treatment effect on bone mineral density in Mexican breast cancer patients. Monroy-Cisneros Karina,Esparza-Romero Julián,Valencia Mauro E,Guevara-Torres Alfonso G,Méndez-Estrada Rosa O,Anduro-Corona Iván,Astiazarán-García Humberto BMC cancer BACKGROUND:Breast cancer is the most deadly malignancy in Mexican women. Although treatment has improved, it may significantly affect bone mineral status in those who receive it. The aim of this study was to assess the impact of cancer treatment on bone mineral density (BMD) and bone mineral content (BMC), in patients with breast cancer and explore the interaction of menopausal status and clinical stage with cancer treatment on such changes. METHODS:A quasi-experimental design was applied with measurements before and after a chemotherapy treatment in 40 patients with primary diagnosis of invasive breast cancer. BMD and body composition measurements were taken by dual X-ray absorptiometry (DXA) and changes in these variables due to therapy were analyzed using mixed regression for repeated measurements. RESULTS:Significant loss was found in femoral neck and L2-L4 BMD (p < 0.001). Patients diagnosed with osteopenia or osteoporosis received calcium + vitamin D supplementation (600 mg/200 IU day). It showed a protective effect in the decrease of femoral neck BMD and total BMC. BMD loss in both femoral neck and L2-L4 BMD was higher in premenopausal women: 0.023 g/cm in femoral neck and 0.063 g/cm in L2-L4 (p < 0.001), while in postmenopausal women BMD loss was 0.015 g/cm in femoral neck and 0.035 g/cm in L2-L4 (p = 0.021 and p = 0.001 respectively). Change in lumbar spine BMD was prominent in premenopausal women with advanced clinical stage (IIB, IIIA, IIIB): 0.066 g/cm (p = 0.003). CONCLUSION:The antineoplastic breast cancer treatment with chemotherapy had a negative impact on BMD, in premenopausal women overall, although a differential effect was found according to clinical stage and calcium supplementation status. 10.1186/s12885-016-2905-x
    The change of bone mineral density and bone metabolism after gastrectomy for gastric cancer: a meta-analysis. Oh H J,Yoon B-H,Ha Y-C,Suh D-C,Lee S-M,Koo K-H,Lee Y-K Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA Bone mineral density (BMD) is significantly decreased after gastrectomy in patients with gastric cancer. Calcium malabsorption, secondary hyperparathyroidism, and dominant bone resorption appear to contribute to bone loss in these patients. Patients should undergo early surveillance and nutritional or pharmacologic intensive interventions for bone health. PURPOSE:Survivorship care, including bone health, has become an important issue in gastric cancer. We performed a meta-analysis of the available observational studies to determine whether and how osteoporosis risk is increased after gastrectomy in patients with gastric cancer. METHODS:A total of 1204 patients (802 men) from 19 cohort studies were included. We evaluated the prevalence of osteoporosis in postgastrectomy patients, comparing the incidence according to the type of gastrectomy and sex. Additionally, we evaluated changes in bone mineral density (BMD) and bone metabolism-related markers pre- to postoperatively and between patients who underwent gastrectomy and matched controls. Proportion meta-analysis was performed and pooled odds ratios (ORs) were calculated. RESULTS:The pooled incidence estimate was 36% [95% confidence interval (CI), 32-40]. The incidence of osteoporosis was significantly higher in women than in men (OR = 1.90, p < 0.001) but was similar between partial and total gastrectomy groups (OR = 0.983, p = 0.939). BMD was significantly decreased, and calcium, phosphorous, and parathyroid hormone levels were significantly increased in patients after gastrectomy compared to those before gastrectomy. BMD and calcium and 25OH-vitamin D levels were significantly decreased, and parathyroid hormone and 1,25OH-vitamin D levels were significantly increased in the gastrectomy group compared to that in the control group. CONCLUSION:We found that BMD is significantly decreased after gastrectomy in patients with gastric cancer. Vitamin D deficiency and secondary hyperparathyroidism are suggested to be common mechanism underlying BMD impairment. After resection, patients should undergo long-term nutritional and bone health surveillance, in addition to their oncological follow-up. 10.1007/s00198-019-05220-2
    Assessment and management of bone health in women with early breast cancer receiving endocrine treatment in the DATA study. van Hellemond Irene E G,Smorenburg Carolien H,Peer Petronella G M,Swinkels Astrid C P,Seynaeve Caroline M,van der Sangen Maurice J C,Kroep Judith R,de Graaf Hiltje,Honkoop Aafke H,Erdkamp Frans L G,van den Berkmortel Franchette W P J,de Boer Maaike,de Roos Wilfred K,Linn Sabine C,Imholz Alexander L T,Tjan-Heijnen Vivianne C G, International journal of cancer The phase III DATA study investigates the efficacy of adjuvant anastrozole (6 vs. 3 year) in postmenopausal women with breast cancer previously treated with 2-3 years of tamoxifen. This planned side-study assessed patterns of care regarding detection and treatment of osteopenia/osteoporosis, and trends in bone mineral density (BMD) during and after therapy. We registered all BMD measurements and bisphosphonate-use. Time to osteopenia/osteoporosis was analysed by Kaplan Meier methodology. For the trend in T-scores we used linear mixed models with random patients effects. Of 1860 eligible DATA patients, 910 (48.9%) had a baseline BMD measurement. Among patients with a normal baseline BMD (n = 417), osteopenia was observed in 53.5% and 55.4% in the 6- and 3-year group respectively (p = 0.18), during follow-up. Only two patients (3-year group) developed osteoporosis. Of the patients with osteopenia at baseline (n = 408), 24.4% and 20.4% developed osteoporosis respectively (p = 0.89). Three years after randomisation 18.3% and 18.2% used bisphosphonates in the 6- and 3-year groups respectively and 6 years after randomisation this was 23.7% and 20.9% respectively (p = 0.90) of which the majority used oral bisphosphonates. The yearly mean BMD-change during anastrozole in the lumbar spine showed a T-score decline of 0.075. After bisphosphonate addition the decline became less prominent (0.047 (p < 0.001)) and after anastrozole cessation, while continuing bisphosphonates, the mean BMD yearly increased (0.047 (p < 0.001)). In conclusion, extended anastrozole therapy was not associated with a higher incidence of osteoporosis. Anastrozole-use was associated with a BMD decrease; however, the decline was modest and partially reversible after anastrozole cessation. 10.1002/ijc.32205
    The reliability of measuring the density of the L1 vertebral body on CT imaging as a predictor of bone mineral density. Gerety E-L,Hopper M A,Bearcroft P W P Clinical radiology AIM:To determine whether the density of the L1 vertebra measured on computed tomography (CT) images correlates with the bone mineral density (BMD) as measured by quantitative computed tomography (QCT), and to determine the reliability of L1 density measurements by different observers to see if this measure could help identify patients who would benefit from formal BMD assessment. MATERIALS AND METHODS:Non-contrast CT along with a phantom for determination of BMD was performed on 30 healthy patients. The L1 density was measured by 3 observers at two time-points separated by at least 2 weeks. RESULTS:L1 density was well correlated to the QCT BMD (correlation coefficient 0.83; 95% confidence interval [CI]: 0.67-0.92). There was excellent intra- and interobserver agreement in L1 density measurements. There were excellent intra-class correlation coefficients for each observer's measurements at two separate time points with a coefficient for observer 1 of 0.94 (95% CI: 0.88-0.97) and for observer 2 and 3 of 0.99 (95% CI: 0.98-1). The interobserver measurements had an intra-class correlation coefficient of 0.98 (95% CI: 0.96-0.99). CONCLUSION:L1 vertebral density can be reliably measured on CT images and might be used as an indicator of BMD for opportunistic screening of patients with osteoporosis. Low bone density detected incidentally on CT imaging could be used to identify patients who should be further investigated and treated for osteoporosis. 10.1016/j.crad.2016.09.022
    Fatty infiltration of paraspinal muscles is associated with bone mineral density of the lumbar spine. Zhao Yinxia,Huang Mingqian,Serrano Sosa Mario,Cattell Renee,Fan Wei,Li Mianwen,Chen Jialing,Gao Meng,Zhou Quan,Li Shaolin,Zhang Xiaodong,Huang Chuan Archives of osteoporosis A total of 88 subjects were enrolled to investigate the relationship between paraspinal muscle fatty infiltration and lumbar bone mineral density (BMD) using chemical shift encoding-based water-fat MRI and quantitative computed tomography (QCT), respectively. A moderate inverse correlation between paraspinal muscle proton density fat fraction and lumbar QCT-BMD was found with age, sex, and BMI controlled. PURPOSE:To investigate the relationship between paraspinal muscle fatty infiltration and lumbar bone mineral density (BMD). METHODS:A total of 88 subjects were enrolled in this study (52 females, 36 males; age, 46.6 ± 14.2 years old; BMI, 23.2 ± 3.49 kg/m). Proton density fat fractions (PDFF) of paraspinal muscles (erector spinae, multifidus, and psoas) were measured at L2/3, L3/4, and L4/5 levels using chemical shift encoding-based water-fat MRI. Quantitative computed tomography (QCT) was used to assess BMD of L1, L2, and L3. The differences in paraspinal muscle PDFF among subjects with normal bone density, osteopenia, and osteoporosis were tested using one-way ANOVA. The relationship between paraspinal muscle PDFF and QCT-BMD was analyzed using linear regression with age, sex, and BMI variables. RESULTS:PDFF of the erector spinae, multifidus, and psoas of subjects with normal bone density were all significantly less than those with osteopenia and those with osteoporosis (all p < 0.001). There was an inverse correlation between paraspinal muscle PDFF and BMD after controlling for age, sex, and BMI (standardized beta coefficient, - 0.21~- 0.29; all p < 0.05). CONCLUSIONS:Paraspinal muscle fatty infiltration increased while lumbar BMD decreased after adjusting for age, sex, and BMI. Paraspinal muscles and vertebrae are interacting tissues. Paraspinal muscle fatty infiltration may be a marker of low lumbar BMD. Chemical shift imaging is an efficient and fast quantitative method and can be easily added to the clinical protocol to measure paraspinal muscle PDFF when the patient underwent the routine lumbar MRI with low-back pain. 10.1007/s11657-019-0639-5
    Technologies for assessment of bone reflecting bone strength and bone mineral density in elderly women: an update. Dhainaut Alvilde,Hoff Mari,Syversen Unni,Haugeberg Glenn Women's health (London, England) Reduced bone mineral density is a strong risk factor for fracture. The WHO's definition of osteoporosis is based on bone mineral density measurements assessed by dual x-ray absorptiometry. Several on other techniques than dual x-ray absorptiometry have been developed for quantitative assessment of bone, for example, quantitative ultrasound and digital x-ray radiogrammetry. Some of these techniques may also capture other bone properties than bone mass that contribute to bone strength, for example, bone porosity and microarchitecture. In this article we give an update on technologies which are available for evaluation primarily of bone mass and bone density, but also describe methods which currently are validated or are under development for quantitative assessment of other bone properties. 10.2217/whe.15.94
    Cortical Bone Thickness of the Distal Part of the Tibia Predicts Bone Mineral Density. Patterson Jason,Rungprai Chamnanni,Den Hartog Taylor,Gao Yubo,Amendola Annunziato,Phisitkul Phinit,Femino John The Journal of bone and joint surgery. American volume BACKGROUND:Poor bone density may affect surgical planning, treatment outcome, and postoperative protocols. Many patients with foot and ankle problems have not undergone a dual x-ray absorptiometry (DXA) scan, which is currently the gold standard for determining bone density. The purpose of this study was to determine if the cortical bone thickness (CBT) of the distal part of the tibia measured on radiographs correlated with bone mineral density. METHODS:After exclusion criteria were applied, 167 consecutive adult patients (mean age and standard deviation [SD], 62 ± 11.62 years) who had had standardized ankle radiographs and a DXA scan within 6 months of each other were included in this retrospective study. The CBT was measured with both the gauge and the average method on standardized anteroposterior, lateral, and hindfoot alignment radiographs. The relationship between CBT in the distal part of the tibia and DXA findings in the hip, proximal part of the femur, and lumbar spine was assessed with Pearson correlations. The interrater and intrarater reliability of CBT measurements was assessed with intraclass correlation coefficients. Subgroup analysis was performed to determine the ability of CBT thresholds to predict osteoporosis. RESULTS:Average CBT measurements on the anteroposterior, lateral, and hindfoot alignment views strongly correlated with DXA findings in the proximal part of the femur (r = 0.70, 0.64, and 0.55, respectively; p < 0.0001), the hip (r = 0.74, 0.67, and 0.53; p < 0.0001), and the lumbar spine (r = 0.61, 0.60, and 0.47; p < 0.0001). The interrater and intrarater reliability of the CBT measurements was excellent. Use of a 3.5-mm average CBT of the distal part of the tibia on the anteroposterior view as the threshold value for predicting osteoporosis (T score less than -2.5) had a sensitivity of 100%, a specificity of 25%, an accuracy of 33%, a positive predictive value of 19%, and a negative predictive value of 100%. CONCLUSIONS:Measurement of the average CBT of the distal part of the tibia is a quick and reliable method for obtaining information on bone quality. CBT measured on standard ankle radiographs correlated strongly with DXA results and may prove to be a useful screening tool for osteoporosis. LEVEL OF EVIDENCE:Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence. 10.2106/JBJS.15.00795
    The effect of exercise on bone mineral density in adult cancer survivors: a systematic review and meta-analysis. Dalla Via J,Daly R M,Fraser S F Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA PURPOSE:Certain cancer treatments are associated with bone loss and increased fracture risk. Weight-bearing impact exercise, resistance training or the combination, are recommended to preserve or improve bone mineral density (BMD) inhealthy older adults, but their efficacy in cancer survivors is less well understood. The aim of this systematic review with meta-analysis of randomised control trials (RCT) was to review the evidence regarding the role of exercise to counteract cancer treatment-induced bone loss. METHODS:Four databases were searched systematically with 12 RCTs of at least 6-month duration investigating the effects of exercise on BMD compared to a control group in adult cancer survivors identified. RESULTS:Meta-analysis was completed using available data from six studies enrolling 814 participants, with lumbar spine, femoral neck and/or total hip BMD as the primary outcome measures. Overall, there was no significant benefit of exercise compared to controls on BMD at the lumbar spine (0.0071 g/cm , 95% CI -0.0002 to 0.0145, p = 0.057), femoral neck (0.0044 g/cm , 95% CI -0.0005 to 0.0093, p = 0.077), or total hip (0.0024 g/cm , 95% CI -0.0038 to 0.0086, p = 0.443). Subgroup analysis revealed a positive effect on lumbar spine BMD in three studies implementing a combined resistance and impact exercise intervention (0.015 g/cm , 95% CI 0.003 to 0.028, p = 0.019). CONCLUSIONS:From the evidence available, exercise may not be sufficient to improve bone health in cancer survivors, but given the heterogeneity in the participant characteristics and several exercise programs which may not have been designed to specifically optimise bone health, these findings should be interpreted with caution. 10.1007/s00198-017-4237-3
    Changes in bone mineral density in women with breast cancer receiving aromatase inhibitor therapy. Kwan Marilyn L,Yao Song,Laurent Cecile A,Roh Janise M,Quesenberry Charles P,Kushi Lawrence H,Lo Joan C Breast cancer research and treatment PURPOSE:We assessed bone mineral density (BMD) change with aromatase inhibitor (AI) treatment in a contemporary cohort of women with breast cancer treated in Kaiser Permanente Northern California. METHODS:Percent and estimated annual percent changes in BMD at the total hip and lumbar spine were examined in 676 women receiving AI therapy who had two serial BMD reports available (at least 1 year apart) before and after AI initiation (N = 317) or during continued AI therapy (N = 359). BMD changes were examined at the total hip and lumbar spine and compared by age and clinical subgroups. RESULTS:Women experienced BMD declines after AI initiation or continued therapy, with median annual percent change - 1.2% (interquartile range, IQR - 2.4 to - 0.1%) at the hip and - 1.0% (IQR - 2.3 to 0.1%) at the spine after AI initiation, and - 1.1% (IQR - 2.4 to 0.1%) at the hip and - 0.9% (IQR - 2.4 to 0.5%) at the spine during continued therapy. Higher levels of bone loss were observed among younger (< 55 years) compared with older (≥ 75 years) women at the hip (- 1.6% vs. - 0.8%) and at the spine (- 1.5% vs. - 0.5%) after AI initiation, and at the hip (- 1.4% vs. - 1.2%) and at the spine (- 2.4% vs. - 0.001%) during continued therapy. CONCLUSIONS:Small but consistent declines in total hip and lumbar spine BMD were present in breast cancer patients following AI therapy initiation or continued AI therapy. Although the overall rates of osteoporosis were low, greater estimated levels of annual bone loss were evident among women < 55 years. 10.1007/s10549-017-4626-5
    Muscle strength is associated with bone health independently of muscle mass in postmenopausal women: the Japanese population-based osteoporosis study. Tachiki Takahiro,Kouda Katsuyasu,Dongmei Namiraa,Tamaki Junko,Iki Masayuki,Kitagawa Jun,Takahira Naonobu,Sato Yuho,Kajita Etsuko,Fujita Yuki,Yura Akiko,Kagamimori Sadanobu Journal of bone and mineral metabolism There are conflicting reports on whether muscle strength is associated with bone mineral density (BMD) independently of muscle mass. Here, we examined the association between muscle strength and BMD in a representative population of Japanese women. Cross-sectional data from 680 postmenopausal women, who were participants in the 15th-year follow-up survey of the Japanese Population-based Osteoporosis cohort study, were analyzed. Areal BMD (aBMD) at the femoral neck and lumbar spine, whole-body bone mineral density, and appendicular skeletal muscle mass (ASM, kg) were measured by dual-energy X-ray absorptiometry. The ASM index (ASMI, kg/m) was calculated as ASM divided by height squared (m). Grip strength (kg) was measured as an indicator of muscle strength. Grip strength showed significantly (P < 0.05) positive relationships with aBMDs at several skeletal sites after adjusting for ASMI and age (standardized partial regression coefficient (β) = 0.102 at femoral neck, β = 0.126 at lumbar spine). Adjusted means of aBMD at the femoral neck and lumbar spine showed significant increasing trends from the lowest to highest tertile of grip strength. Our findings indicate that muscle strength is associated with aBMD at several sites independently of muscle mass in Japanese postmenopausal women. Thus, postmenopausal women with strong muscle strength tend to have a healthy bone status regardless of muscle size. 10.1007/s00774-017-0895-7
    Changes in Bone Mineral Density in Women With Breast Cancer: A Prospective Cohort Study. Kim Soo Hyun,Cho Young Up,Kim Sei Joong,Han Mi Sook Cancer nursing BACKGROUND:Cancer treatment-induced bone loss is an important long-term effect among breast cancer survivors. Little is known, however, about the pattern of bone loss and the factors associated with it. OBJECTIVE:The aim of this study was to examine annual bone health changes and factors associated with bone loss for 3 years after diagnosis among women with breast cancer. METHODS:Ninety-nine newly diagnosed women with breast cancer (mean age, 51.1 years) were enrolled in a prospective longitudinal study. Bone mineral density (BMD) was measured with dual-energy x-ray absorptiometry at baseline and yearly for 3 years. RESULTS:During the 3-year follow-up, the proportion of women who had osteopenia or osteoporosis increased from 33.3% to 62.5%. The BMD of the participants significantly decreased 6.8% in the lumbar spine, 4.6% in the femur neck, and 3.5% in the total hip, with bone loss the greatest in the first year. In multiple linear regression analysis, chemotherapy was significantly associated with bone loss at all sites, and premenopausal status at diagnosis was significantly related to bone loss at the lumbar spine. We found no significant relationship between health behavior status and BMD change at any site. CONCLUSION:Women newly diagnosed with breast cancer can lose up to 6.8% of BMD during a 3-year follow-up. Chemotherapy and premenopausal status are important risk factors for bone loss. IMPLICATIONS FOR PRACTICE:Identification of premenopausal women at diagnosis and monitoring BMD before and after chemotherapy are key for promoting bone health in women with breast cancer. 10.1097/NCC.0000000000000586
    Change in bone mineral density during adjuvant chemotherapy for early-stage breast cancer. Christensen Carina Ørts,Cronin-Fenton Deirdre,Frøslev Trine,Hermann Anne Pernille,Ewertz Marianne Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Adjuvant chemotherapy has been associated with loss of bone mineral density (BMD) either as a direct effect or due to glucocorticoids used as supportive care medication. A prospective cohort study was conducted to evaluate changes in BMD from baseline to right after completion of chemotherapy, i.e., 4 months. METHODS:Dual-imaging X-ray absorptiometry (DXA) was performed at baseline and after completing anthracycline- and taxane-based chemotherapy to measure BMD in the spine, hip, and forearm in early-stage breast cancer patients. High-dose prednisolone was used at three weekly intervals to reduce nausea and vomiting. Patients were advised a daily calcium/vitamin D supplement. Linear regression was used to assess mean percentage change in BMD and 95 % confidence intervals (95 % CI) according to doses of prednisolone, menopausal status, smoking, and BMI. RESULTS:Eight patients were excluded: seven because of initiation of bisphosphonate treatment due to osteoporosis at baseline, and one had non-interpretable DXA. The final cohort included 97 patients with a mean age of 53 years (range 34-72). Mean cumulative prednisolone dose was 1308 mg (95 % CI 1255; 1362). BMD increased 1.36 % (95 % CI 0.7; 2.0, p < 0.001) in the spine and 1.27 % (95 % CI 0.9; 1.7, p < 0.001) in the hip. Forearm BMD did not change. Postmenopausal women had increases in spine BMD of 2.35 % (95 % CI 1.1; 3.6, p < 0.001) compared to premenopausal women. The spine BMD of current smokers decreased 1.67 % (95 % CI -3.3; -0.1, p = 0.04) compared to never/former smokers. CONCLUSIONS:Adjuvant chemotherapy supplemented with prednisolone was not associated with loss of BMD. Postmenopausal women gained bone mass, whereas current smokers lost bone mass. 10.1007/s00520-016-3250-y
    Silicosis decreases bone mineral density in rats. Hui Zhang,Dingjie Xu,Yuan Yuan,Zhongqiu Wei,Na Mao,Mingjian Bei,Yu Gou,Guangyuan Liu,Xuemin Gao,Shifeng Li,Yucong Geng,Fang Yang,Summer Ross,Hong Xu Toxicology and applied pharmacology Silicosis is the most common occupational lung disease in China, and is associated with a variety of complications, many of which are poorly understood. For example, recent data indicate that silicosis associates with the development of osteopenia, and in some cases this bone loss is severe, meeting criteria for osteoporosis. Although many factors are likely to contribute to this relationship, including a sedentary lifestyle in patients with advanced silicotic lung disease, we hypothesized that silica might directly reduce bone mineral density. In the present study, six Wistar rats were exposed to silica for 24 weeks in order to induce pulmonary silicosis and examine the relationship to bone mineral density. As expected, all rats exposed to silica developed severe pulmonary fibrosis, as manifested by the formation of innumerable silicotic nodules and the deposition of large amounts of interstitial collagen. Moreover, micro-CT results showed that bone mineral density (BMD) was also significantly reduced in rats exposed to silica when compared control animals and this associated with a modest reduction in serum calcium and 25-hydroxyvitamin D levels. In addition, we found that decreased BMD was also linked to increased osteoclast activity as well as fibrosis-like changes, and to the deposition of silica within bone marrow. In summary, our findings support the hypothesis that silicosis reduces bone mineral density and provide support for ongoing investigations into the mechanisms causing osteopenia in silicosis patients. 10.1016/j.taap.2018.04.023
    MiR-203 is essential for the shift from osteogenic differentiation to adipogenic differentiation of mesenchymal stem cells in postmenopausal osteoporosis. Qiao L,Liu D,Li C-G,Wang Y-J European review for medical and pharmacological sciences OBJECTIVE:The purpose of this study was to investigate how miR-203 promotes osteogenic differentiation of bone marrow mesenchymal cells (BMSCs) by regulating its target gene DKK1, thereby inhibiting the occurrence of osteoporosis. PATIENTS AND METHODS:A total of 60 cases with postmenopausal osteoporosis and 40 cases of normal individuals were recruited. The expression of miR-203 in serum of all cases was detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The capacity of osteogenesis and adipogenic differentiation of MSCs was determined by alizarin red staining and oil red staining, respectively. Transfection of miR-203 mimics and miR-203 inhibitor were mediated by Liposomes, and then the MSCs were induced osteogenic and adipogenic differentiation. MiR-203 mimic was co-transfected with wild-type or mutant DKK1 for luciferase reporter gene detection. In the osteoporosis model of rats, the tibia was taken for micro-CT examination of bone mineral density (BMD) and bone volume/structural parameters (BV/TV), while the femur was taken for the measurement of absorption parameters (Ob.S)./BS) and the number of osteoclasts per circumference of bone (N.Oc/B.Pm). RESULTS:The expression level of miR-203 was significantly lower in patients with postmenopausal osteoporosis than that in normal individuals. The osteogenic capacity of BMSCs in these patients was reduced, while their adipogenic capacity was enhanced. MiR-203 promoted the expression of osteogenic genes and inhibited that of adipogenic genes. Knockdown of miR-203 decreased the level of osteogenic related genes but increased that of adipogenic related genes, while overexpression of miR-203 led to the opposite results. Furthermore, miR-203 inhibited the protein expression of DKK1. In addition, bone density and bone volume/structural parameters were lower in ovariectomized rats than those in normal rats. Meanwhile, bone resorption parameters and the number of osteoclasts per bone circumference in ovariectomized rats were higher than those in normal rats. CONCLUSIONS:MiR-203 can promote osteogenic differentiation of mesenchymal stem cells by downregulating the gene expression of DKK1. 10.26355/eurrev_201809_15906
    ASSOCIATION OF BONE MINERAL DENSITY WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN POSTMENOPAUSAL WOMEN. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion BACKGROUND:Osteoporosis (OP) is common in patients with chronic obstructive pulmonary disease (COPD). The relationship between OP and COPD has been primarily studied in male patients, and few reports are available in postmenopausal women. OBJECTIVE:The purpose of this study was to investigate the association between bone mineral density (BMD) and COPD in postmenopausal women. METHODS:This cross-sectional study included 133 clinically stable female ex-smokers with confirmed COPD, and 31 age-matched "ex-smoker" female controls. We analyzed groups according to their airway obstruction category. BMD was measured on dual-energy X-ray absorptiometry images of the left femoral neck. RESULTS:Patients with COPD had lower T-scores and higher prevalence of osteopenia/OP than the control group. In the COPD group, the airway obstruction category was significantly associated with the T-score after adjustment for confounders. Multivariate logistic regression analysis showed COPD was an independent marker for increased risk of osteopenia/OP in postmenopausal women. CONCLUSIONS:COPD and airway obstruction category were strongly related to BMD. Postmenopausal women with COPD, especially those with severe airway obstruction, had a higher prevalence rate and a higher risk of osteopenia and OP than female controls without COPD. 10.24875/RIC.19002935
    Unsaturation level decreased in bone marrow fat of postmenopausal women with low bone density using high resolution magic angle spinning (HRMAS) H NMR spectroscopy. Li Xiaojuan,Shet Keerthi,Xu Kaipin,Rodríguez Juan Pablo,Pino Ana María,Kurhanewicz John,Schwartz Ann,Rosen Clifford J Bone There are increasing evidences suggesting bone marrow adiposity tissue (MAT) plays a critical role in affecting both bone quantity and quality. However, very limited studies that have investigated the association between the composition of MAT and bone mineral density (BMD). The goal of this study was to quantify MAT unsaturation profile of marrow samples from post-menopausal women using ex vivo high-resolution magic angle spinning (HRMAS) proton nuclear magnetic resonance (H NMR) spectroscopy, and to investigate the relationship between MAT composition and BMD. Bone marrow samples were obtained by iliac crest aspiration during surgical procedures from 24 postmenopausal women (65-89years) who had hip surgery due to bone fracture or arthroplasty. Marrow fat composition parameters, in particular, unsaturation level (UL), mono-unsaturation level (MUL) and saturation level (SL), were quantified using HRMAS H NMR spectroscopy. The patients were classified into three groups based on the DXA BMD T-scores: controls, osteopenia and osteoporosis. Marrow fat composition was compared between these three groups as well as between subjects with and without factures using ANOCOVA, adjusted for age. Subjects with lower BMD (n=17) had significantly lower MUL (P=0.003) and UL (P=0.039), and significantly higher SL (P=0.039) compared to controls (n=7). When separating lower BMD into osteopenia (n=9) and osteoporosis (n=8) groups, subjects with osteopenia had significantly lower MUL (P=0.002) and UL (P=0.010), and significantly higher SL (P=0.010) compared to healthy controls. No significant difference was observed between subjects with osteopenia and osteoporosis. Using HRMAS H NMR, significantly lower unsaturation and significantly higher saturation levels were observed in the marrow fat of subjects with lower BMD. HRMAS H NMR was shown to be a powerful tool for identifying novel MR markers of marrow fat composition that are associated with bone quality and potentially fracture, and other bone pathologies and changes after treatment. A better understanding of the relationship between bone marrow composition and bone quality in humans may identify novel treatment targets, and provide guidance on novel interventions and therapeutic strategies for bone preservation. 10.1016/j.bone.2017.08.014
    Long-term effect of exemestane therapy on bone mineral density supported by bisphosphonates: Results of 5-year adjuvant treatment in postmenopausal women with early-stage breast cancer. Hirano Akira,Inoue Hiroaki,Ogura Kaoru,Hattori Akinori,Yukawa Hiroko,Sakaguchi Shiho,Matsuoka Aya,Tanaka Natsuko,Kodera Asaka,Kamimura Mari,Naritaka Yoshihiko,Shimizu Tadao Asia-Pacific journal of clinical oncology PURPOSE:Unlike anastrozole, the effect of long-term exemestane (EXE) therapy on bone mineral density (BMD) is still unknown. We assessed changes in BMD from baseline to 5 years of EXE treatment. METHODS:Postmenopausal women with endocrine-responsive breast cancer receiving EXE as adjuvant therapy were enrolled in this study. EXE was administered for 5 years. The BMD of the lumbar spine (LS) and femoral neck (FN) was assessed by dual-energy X-ray absorptiometry at baseline and after 6 months and 1, 2, 3, 4, 5 and 6 years. Oral bisphosphonate (Bis) treatment was initiated when patients were diagnosed with osteoporosis with a T-score of -2.5 or lower. RESULTS:Eighty-one patients were enrolled in the study between 2005 and 2010. The median follow-up period was 54.9 months. Forty-two patients were administered Bis. Overall, the BMD of the LS increased by 7.3% from baseline and that of the FN increased by 3.4% with 5 years of EXE treatment. At the sixth year (i.e. 1 year after the treatment), BMD of the LS increased by 7.2% and that of the FN increased by 5.7%. Furthermore, the BMD of the FN increased by 12.0% in patients treated upfront with Bis and by 1.2% in those not treated with Bis (P = 0.0262). Fractures developed in nine patients (11.1%) and seven (8.6%) had fragility fractures. CONCLUSION:Oral Bis improves BMD of the FN in patients with osteoporosis. Five-year EXE treatment with proper addition of Bis helps maintain the BMD of the LS and FN at the sixth year. 10.1111/ajco.13034
    Relationship of anthropometric measures with bone mineral density in postmenopausal non-osteoporotic, osteopenic and osteoporotic women. Tariq Sundus,Tariq Saba,Lone Khalid Parvez JPMA. The Journal of the Pakistan Medical Association BACKGROUND AND OBJECTIVES:Body mass index (BMI) has been shown to be a more important predictor of bone mineral density (BMD). The objective of this study was to investigate the relationship of anthropometric measures including body mass index with bone mineral density in postmenopausal non-osteoporotic, osteopenic and osteoporotic women. METHODS:In this cross sectional study postmenopausal females between 50-70 years of age were recruited and divided into three groups: non-osteoporotic (n=52), osteopenic (n=69) and osteoporotic females (n=47). Anthropometric measures and bone mineral density were assessed. ANOVA was applied to compare groups while Post hoc Tuckey's test was used for multiple comparisons between the groups. Spearman's rho correlation was used to establish correlations. RESULTS:Body mass index (p = 0.034) and hip circumference (p = 0.013) were significantly higher in osteopenic as compared to osteoporotic females and waist to hip ratio was significantly higher (p = 0.005) in osteoporotic as compared to non-osteoporotic females. Significant positive correlation of body mass index was found with T-score (p = 0.022) and ultrasound bone profile index (p< 0.001) in postmenopausal females. CONCLUSIONS:High body mass index is associated with high bone mineral density and reduced fracture risk in postmenopausal females. Increasing age and high waist to hip ratio can also lead to reduced bone mineral density in postmenopausal females.
    Low bone mineral density is associated with breast cancer in postmenopausal women: a case-control study. Ferreira Poloni P,Vespoli H De Luca,Almeida-Filho B de Sousa,Bueloni-Dias F,Nahas-Neto J,Nahas E Aguiar Petri Climacteric : the journal of the International Menopause Society OBJECTIVE:To evaluate risk factors for low bone mineral density (BMD) in postmenopausal breast cancer survivors compared with postmenopausal women without breast cancer (controls). METHOD:In this study, 112 breast cancer survivors were compared to 224 women (controls). Inclusion criteria were amenorrhea ≥12 months, age 45-75 years, treated for breast cancer, and metastasis-free for at least 5 years. The control group consisted of women without breast cancer, matched by age and menopause status (in a proportion of 1: 2 as sample calculation). The risk factors for low BMD (osteopenia/osteoporosis) were assessed by interview. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine (L1-L4) and femoral neck. Logistic regression models (odds ratio, OR) were used to identify factors associated with low BMD. RESULTS:The mean (standard deviation) age of breast cancer survivors was 61.3 (9.7) years, with a mean follow-up of 10.2 (3.9) years. These women had a higher incidence of osteopenia (45.1%) and osteoporosis (22.3%) in the femoral neck than controls (39.3% and 9.0%, respectively) (p = 0.0005). Lumbar spine BMD did not differ between groups (p = 0.332). Univariate analysis adjusted for age and time since menopause revealed that chemotherapy (OR 6.90; 95% confidence interval (CI) 5.57-9.77) was associated with a higher risk of low BMD. Contrarily, regular physical exercise (OR 0.24; 95% CI 0.06-0.98) and a body mass index ≥30 kg/m (OR 0.09; 95% CI 0.02-0.37) reduced the risk among breast cancer survivors. CONCLUSION:Postmenopausal breast cancer survivors had a higher incidence of osteopenia and osteoporosis in the femoral neck than women without breast cancer. A history of chemotherapy was a risk factor for low BMD, whereas regular physical activity and high body mass index reduced the risk among breast cancer survivors. 10.1080/13697137.2017.1329290
    Targeting macrophages for cancer therapy disrupts bone homeostasis and impairs bone marrow erythropoiesis in mice bearing Lewis lung carcinoma tumors. Jing Weiqiang,Zhang Li,Qin Fei,Li XiuXiu,Guo Xing,Li Yue,Qiu Chunhong,Zhao Yunxue Cellular immunology Macrophages are represented in all tissues by phenotypically distinct resident populations that show great functional diversity. Macrophages generally play a protumoral role, and they are attractive targets for cancer therapy. In this study, we found that CD169 macrophages depletion inhibited the growth of established Lewis lung carcinoma tumors in mice. Benefits must be weighed against potential adverse effects in cancer therapy. Here, we investigated the adverse effects of CD169 macrophages depletion on bone and bone marrow in mice bearing Lewis lung carcinoma tumors. Our studies showed that depletion of CD169 macrophages in LLC tumor-bearing mice disrupted bone homeostasis, including bone weight loss and bone mineral density decrease. Further studies revealed that bone marrow erythropoiesis was severely impaired after depletion of CD169 macrophages in LLC tumor-bearing mice. Our findings suggest that depletion of macrophages for cancer therapy may be associated with potential adverse effects that need to be recognized, prevented, and optimally managed. 10.1016/j.cellimm.2017.09.006
    High-fat Diet Enhances and Plasminogen Activator Inhibitor-1 Deficiency Attenuates Bone Loss in Mice with Lewis Lung Carcinoma. Yan Lin,Nielsen Forrest H,Sundaram Sneha,Cao Jay Anticancer research This study determined the effects of a high-fat diet and plasminogen activator inhibitor-1 deficiency (Pai1(-/-)) on the bone structure in male C57BL/6 mice bearing Lewis lung carcinoma (LLC) in lungs. Significant reduction in bone volume fraction (BV/TV), trabecular number (Tb.N) and bone mineral density (BMD) in femurs and vertebrae were found in LLC-bearing mice compared to non-tumor-bearing mice. In LLC-bearing mice, the high-fat diet compared to the AIN93G control diet significantly reduced BV/TV, Tb.N and BMD in femurs and BV/TV in vertebrae. The high-fat diet significantly reduced BMD in vertebrae in wild-type mice but not in Pai1(-/-) mice. Compared to wild-type mice, PAI1 deficiency significantly increased BV/TV and Tb.N in femurs. The plasma concentration of osteocalcin was significantly lower and that of tartrate-resistant acid phosphatase 5b (TRAP5b) was significantly higher in LLC-bearing mice. The high-fat diet significantly reduced plasma osteocalcin and increased TRAP5b. Deficiency in PAI1 prevented the high-fat diet-induced increases in plasma TRAP5b. These findings demonstrate that a high-fat diet enhances, whereas PAI1 deficiency, attenuates metastasis-associated bone loss, indicating that a high-fat diet and PAI1 contribute to metastasis-associated bone deterioration.
    Paradoxical relationship between body mass index and bone mineral density in patients with non-small cell lung cancer with brain metastasis. Nam Min Woo,Kim Jae Min,Cheong Jin Hwan,Ryu Je Il,Han Myung-Hoon PloS one BACKGROUND AND PURPOSE:Low body mass index (BMI) at presentation has been reported to be associated with higher incidence and mortality of lung cancer, but studies on the relationship between brain metastasis and BMI at presentation are lacking. This study aimed to evaluate the association between brain metastasis and BMI and bone mineral density (BMD) in NSCLC. METHODS:We retrospectively enrolled patients with non-small cell lung cancer who underwent brain magnetic resonance imaging with contrast within 3 months of diagnosis. The BMI was collected, and the BMD was measured in Hounsfield unit (HU) on initial staging computed tomography scans. The independent relationship between BMI and BMD was assessed using multivariable linear regression according to the presence of brain metastasis. RESULTS:A total of 356 consecutive NSCLC patients were enrolled in the study over a 8-year period in a single institution. Lower BMI with higher BMD was an independent predictive factor for brain metastasis in patients with NSCLC, relative to the other group (HR, 2.03; 95% CI, 1.21 to 3.40; P = 0.007). We also found a significant negative correlation between BMI and BMD among patients with NSCLC with brain metastases (B, -3.343; 95% confidence interval, -6.352 to -0.333; P = 0.030). CONCLUSIONS:Brain metastasis may possibly be associated with lower BMI and higher BMD in NSCLC patients. We expect that these results may facilitate future predictions of brain metastases during the clinical course of NSCLC and enhance our understanding of the underlying mechanisms that link brain metastases and lung cancer. 10.1371/journal.pone.0218825
    Lung tumor cells inhibit bone mineralization and osteoblast activity. Berent Taylor E,Dorschner Jessica M,Craig Theodore A,Drake Matthew T,Westendorf Jennifer J,Kumar Rajiv Biochemical and biophysical research communications Patients with non-small cell lung cancer (NSLC) often develop skeletal complications and fractures. To understand mechanisms of bone loss, we developed a murine model of non-metastatic NSLC. Decreased bone mineral density, trabecular thickness and mineralization, without an increase in bone resorption, were observed in vivo in mice injected with Lewis lung adenocarcinoma (LLC1) cells in the absence of tumor cell metastases. A decrease in trabecular bone mineral density was observed in mice injected with cell-free LLC1 CM. Plasma osteoblast biomarkers and PTH-related peptide (PTHrP) were reduced, and parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, calcium and phosphate concentrations were normal in tumor-bearing mice. LLC1 cell conditioned medium (CM) inhibited alkaline phosphatase activity, osteoblast mineralization, and expression of Alpl and Ocn/Bglap mRNA in MC3T3 osteoblast cultures, whereas non-CM or CM from NIH/3T3 fibroblasts did not induce similar changes. LLC1 CM reduced Wnt3a-stimulated Tcf/Lef reporter plasmid activity and Wnt5A, Tcf1 and Lef1 mRNA expression in MC3T3 cells. Although concentrations of the Wnt inhibitor, DKK2, were increased in LLC1 CM compared to non-CM, depletion of DKK2 from LLC1 CM did not completely restore Wnt3a activity in MC3T3 cultures, and recombinant DKK2 failed to inhibit osteoblast mineralization. The data indicate that in a model of lung adenocarcinoma without bone metastases, tumor cells elaborate a secreted factor(s) that reduces bone mass, bone formation and osteoblast Wnt signaling without increases in bone resorption or calcium-regulating hormone concentrations. The factor(s) mediating this inhibition of osteoblast mineralization require further characterization. 10.1016/j.bbrc.2019.09.045
    Fat fraction mapping using magnetic resonance imaging: insight into pathophysiology. Bray Timothy Jp,Chouhan Manil D,Punwani Shonit,Bainbridge Alan,Hall-Craggs Margaret A The British journal of radiology Adipose cells have traditionally been viewed as a simple, passive energy storage depot for triglycerides. However, in recent years it has become clear that adipose cells are highly physiologically active and have a multitude of endocrine, metabolic, haematological and immune functions. Changes in the number or size of adipose cells may be directly implicated in disease (e.g. in the metabolic syndrome), but may also be linked to other pathological processes such as inflammation, malignant infiltration or infarction. MRI is ideally suited to the quantification of fat, since most of the acquired signal comes from water and fat protons. Fat fraction (FF, the proportion of the acquired signal derived from fat protons) has, therefore, emerged as an objective, image-based biomarker of disease. Methods for FF quantification are becoming increasingly available in both research and clinical settings, but these methods vary depending on the scanner, manufacturer, imaging sequence and reconstruction software being used. Careful selection of the imaging method-and correct interpretation-can improve the accuracy of FF measurements, minimize potential confounding factors and maximize clinical utility. Here, we review methods for fat quantification and their strengths and weaknesses, before considering how they can be tailored to specific applications, particularly in the gastrointestinal and musculoskeletal systems. FF quantification is becoming established as a clinical and research tool, and understanding the underlying principles will be helpful to both imaging scientists and clinicians. 10.1259/bjr.20170344
    Comparison of semi-quantitative and quantitative dynamic contrast-enhanced MRI evaluations of vertebral marrow perfusion in a rat osteoporosis model. Zhu Jingqi,Xiong Zuogang,Zhang Jiulong,Qiu Yuyou,Hua Ting,Tang Guangyu BMC musculoskeletal disorders BACKGROUND:This study aims to investigate the technical feasibility of semi-quantitative and quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the assessment of longitudinal changes of marrow perfusion in a rat osteoporosis model, using bone mineral density (BMD) measured by micro-computed tomography (micro-CT) and histopathology as the gold standards. METHODS:Fifty rats were randomly assigned to the control group (n=25) and ovariectomy (OVX) group whose bilateral ovaries were excised (n=25). Semi-quantitative and quantitative DCE-MRI, micro-CT, and histopathological examinations were performed on lumbar vertebrae at baseline and 3, 6, 9, and 12 weeks after operation. The differences between the two groups in terms of semi-quantitative DCE-MRI parameter (maximum enhancement, E), quantitative DCE-MRI parameters (volume transfer constant, K; interstitial volume, V; and efflux rate constant, K), micro-CT parameter (BMD), and histopathological parameter (microvessel density, MVD) were compared at each of the time points using an independent-sample t test. The differences in these parameters between baseline and other time points in each group were assessed via Bonferroni's multiple comparison test. A Pearson correlation analysis was applied to assess the relationships between DCE-MRI, micro-CT, and histopathological parameters. RESULTS:In the OVX group, the E values decreased significantly compared with those of the control group at weeks 6 and 9 (p=0.003 and 0.004, respectively). The K values decreased significantly compared with those of the control group from week 3 (p<0.05). However, the V values decreased significantly only at week 9 (p=0.032), and no difference in the K was found between two groups. The BMD values of the OVX group decreased significantly compared with those of the control group from week 3 (p<0.05). Transmission electron microscopy showed tighter gaps between vascular endothelial cells with swollen mitochondria in the OVX group from week 3. The MVD values of the OVX group decreased significantly compared with those of the control group only at week 12 (p=0.023). A weak positive correlation of E and a strong positive correlation of K with MVD were found. CONCLUSIONS:Compared with semi-quantitative DCE-MRI, the quantitative DCE-MRI parameter K is a more sensitive and accurate index for detecting early reduced perfusion in osteoporotic bone. 10.1186/s12891-017-1800-1
    Novel assessment tools for osteoporosis diagnosis and treatment. Gong Bo,Mandair Gurjit S,Wehrli Felix W,Morris Michael D Current osteoporosis reports This review describes new technologies for the diagnosis and treatment, including fracture risk prediction, of postmenopausal osteoporosis. Four promising technologies and their potential for clinical translation and basic science studies are discussed. These include reference point indentation (RPI), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and magnetic resonance imaging (MRI). While each modality exploits different physical principles, the commonality is that none of them require use of ionizing radiation. To provide context for the new developments, brief summaries are provided for the current state of biomarker assays, fracture risk assessment (FRAX), and other fracture risk prediction algorithms and quantitative ultrasound (QUS) measurements. 10.1007/s11914-014-0215-2
    Bone Marrow and Muscle Fat Infiltration Are Correlated among Postmenopausal Women With Osteoporosis: The AMBERS Cohort Study. Wong Andy K,Chandrakumar Abinaa,Whyte Rachel,Reitsma Shannon,Gillick Hana,Pokhoy Anthony,Papaioannou Alexandra,Adachi Jonathan D Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Bone and muscle have shown to interact, but little is known about fat within bone and muscle. Clinical studies have isolated fat within bone and muscle using MRI. In this cross-sectional study, we hypothesized that bone marrow adiposity and muscle adiposity are related and that this relationship is associated with osteoporosis. Postmenopausal women aged 60 to 85 years were recruited as part of the Appendicular Muscle and Bone Extension Research Study (AMBERS). Participants completed dual-energy X-ray absorptiometry (DXA) of the hip and spine to diagnose osteoporosis. Muscle adiposity was measured with MRI at the 66% site of the leg. Fat segmentation was achieved using a semi-automated iterative threshold-optimizing algorithm (error < 5%). Peripheral quantitative computed tomography measured marrow density of the 4% distal tibia (surrogate for marrow fat) by threshold-based, edge-detection segmentations and by examining residuals from trabecular bone density regressed on trabecular tissue mineral density. Muscle adiposity from MRI was regressed on marrow density using linear regression. Models were further examined with an interaction with osteoporosis status. Among 312 women (aged 75.4 ± 5.9 years, body mass index [BMI] 29.5 ± 5.7 kg/m ), a larger amount of muscle fat was associated with lower marrow density at the 66% mid-tibia (B = 84.08 [27.56], p = 0.002) and at the 4% distal tibia (B = 129.17 [55.96], p = 0.022) after accounting for age, height, weight, average daily energy expenditure, hypertension, and diabetes. Interactions of this relationship with osteoporosis status were also significant. Upon probing these interactions, the relationships were significant only in women with osteoporosis but not in those without osteoporosis. Fat from bone marrow and muscle may be related to one another through the same phenomenon, which is likely also responsible for osteoporosis, but independent of hypertension and diabetes. More research should focus on the potential abnormalities in muscle and bone fat metabolism and mesenchymal cell commitment to fat within patients with osteoporosis. © 2019 American Society for Bone and Mineral Research. 10.1002/jbmr.3910
    Texture analysis of vertebral bone marrow using chemical shift encoding-based water-fat MRI: a feasibility study. Burian E,Subburaj K,Mookiah M R K,Rohrmeier A,Hedderich D M,Dieckmeyer M,Diefenbach M N,Ruschke S,Rummeny E J,Zimmer C,Kirschke J S,Karampinos D C,Baum T Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA This feasibility study investigated the spatial heterogeneity of the lumbar vertebral bone marrow using chemical shift encoding-based water-fat MRI. Acquired texture features like contrast and dissimilarity allowed for differentiation of pre- and postmenopausal women and may serve as imaging biomarkers in the future. INTRODUCTION:While the vertebral bone marrow fat using chemical shift encoding water-fat magnetic resonance imaging (MRI) has been extensively studied, its spatial heterogeneity has not been analyzed yet. Therefore, this feasibility study investigated the spatial heterogeneity of the lumbar vertebral bone marrow by using texture analysis in proton density fat fraction (PDFF) maps. METHODS:Forty-one healthy pre- and postmenopausal women were recruited for this study (premenopausal (n = 15) 30 ± 7 years, postmenopausal (n = 26) 65 ± 7 years). An eight-echo 3D spoiled gradient echo sequence was used for chemical shift encoding-based water-fat separation at the lumbar spine. Vertebral bodies L1 to L5 were manually segmented. Mean PDFF values and texture features were extracted at each vertebral level, namely variance, skewness, and kurtosis, using statistical moments and second-order features (energy, contrast, correlation, homogeneity, dissimilarity, entropy, variance, and sum average). Parameters were compared between pre- and postmenopausal women and vertebral levels. RESULTS:PDFF was significantly higher in post- than in premenopausal women (49.37 ± 8.14% versus 27.76 ± 7.30%, p < 0.05). Furthermore, PDFF increased from L1 to L5 (L1 37.93 ± 12.85%, L2 38.81 ± 12.77%, L3 40.23 ± 12.72%, L4 42.80 ± 13.27%, L5 45.21 ± 14.55%, p < 0.05). Bone marrow heterogeneity based on texture analysis was significantly (p < 0.05) increased in postmenopausal women. Contrast and dissimilarity performed best in differentiating pre- and postmenopausal women (AUC = 0.97 and 0.96, respectively), not significantly different compared with PDFF (AUC = 0.97). CONCLUSION:Conclusively, an increased bone marrow heterogeneity could be observed in postmenopausal women. In the future, texture parameters might provide additional information to detect and monitor vertebral bone marrow alterations due to aging or hormonal changes beyond conventional anatomic imaging. 10.1007/s00198-019-04924-9
    Quantitative evaluation of vertebral marrow adipose tissue in postmenopausal female using MRI chemical shift-based water-fat separation. Li G-W,Xu Z,Chen Q-W,Tian Y-N,Wang X-Y,Zhou L,Chang S-X Clinical radiology AIM:To investigate the feasibility of assessing vertebral marrow adipose tissue using a magnetic resonance imaging (MRI) chemical shift-based water-fat separation technique at 3 T. MATERIAL AND METHODS:A modified Dixon technique was performed to obtain the vertebral marrow fat fraction (FF) in a study of 58 postmenopausal females (age range 49.2-77.4 years), including 24 normal bone density, 19 osteopaenia, and 15 osteoporosis as documented with dual-energy X-ray absorptiometry. The reliability of FF measurements performed by two radiologists independently was evaluated with the intraclass correlation coefficient (ICC). Ten participants were scanned twice to assess the reproducibility of FF measurements. FF values were compared between each vertebral level and between groups. RESULTS:The mean coefficient of variation of FF measurements was 2.1%. According to the ICC, the measurements were reliable (ICC = 0.900 for normal bone density, ICC = 0.937 for osteopaenia and ICC = 0.909 for osteoporosis, p < 0.001 for all). There was an inverse association between mean FF at L1-L4 vertebrae and lumbar spine BMD (r = -0.459, p = 0.006), which remained significant even after controlling for confounders (age, height, and body weight). FF values at different vertebral levels were significantly correlated to each other (r = 0.703-0.921, p < 0.05 for all). There was a general trend toward increased marrow adiposity for more inferior vertebral bodies. Patients with osteopaenia and osteoporosis had a higher marrow fat content compared with normal bone mass after adjusting for confounders, although no significant differences in each vertebral level and average marrow fat content were found between the osteopaenia and osteoporosis groups. CONCLUSION:Chemical shift-based water-fat separation enables the quantitation of vertebral marrow adiposity with excellent reproducibility, which appears to be a useful method to provide complementary information to osteoporosis-related research fields. 10.1016/j.crad.2013.10.005
    ACR Appropriateness Criteria Osteoporosis and Bone Mineral Density. ,Ward Robert J,Roberts Catherine C,Bencardino Jenny T,Arnold Erin,Baccei Steven J,Cassidy R Carter,Chang Eric Y,Fox Michael G,Greenspan Bennett S,Gyftopoulos Soterios,Hochman Mary G,Mintz Douglas N,Newman Joel S,Reitman Charles,Rosenberg Zehava S,Shah Nehal A,Small Kirstin M,Weissman Barbara N Journal of the American College of Radiology : JACR Osteoporosis is a considerable public health risk, with 50% of women and 20% of men >50 years of age experiencing fracture, with mortality rates of 20% within the first year. Dual x-ray absorptiometry (DXA) is the primary diagnostic modality by which to screen women >65 years of age and men >70 years of age for osteoporosis. In postmenopausal women <65 years of age with additional risk factors for fracture, DXA is recommended. Some patients with bone mineral density above the threshold for treatment may qualify for treatment on the basis of vertebral body fractures detected through a vertebral fracture assessment scan, a lateral spine equivalent generated from a commercial DXA machine. Quantitative CT is useful in patients with advanced degenerative bony changes in their spines. New technologies such as trabecular bone score represent an emerging role for qualitative assessment of bone in clinical practice. It is critical that both radiologists and referring providers consider osteoporosis in their patients, thereby reducing substantial morbidity, mortality, and cost to the health care system. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. 10.1016/j.jacr.2017.02.018
    Bilateral femoral neck fractures resulting from pregnancy-associated osteoporosis showed bone marrow edema on magnetic resonance imaging. Kasahara Kyoko,Kita Nobuyuki,Kawasaki Taku,Morisaki Shinsuke,Yomo Hiroko,Murakami Takashi The journal of obstetrics and gynaecology research Femoral neck fractures resulting from pregnancy-associated osteoporosis is a rare condition. Herein, we report an undoubted case of pregnancy-associated osteoporosis in a 38-year-old primiparous patient with pre-existing anorexia nervosa who suffered bilateral femoral neck fractures in the third trimester and early post-partum period. Magnetic resonance imaging revealed femoral neck fractures as well as diffuse marrow edema involving both femoral heads, which are considered under ordinary circumstances as characteristic imaging findings of transient osteoporosis of the hip. Based on our experience, we propose that pregnancy-associated osteoporosis might be present in femoral neck fractures attributed to transient osteoporosis of the hip in pregnancy. Conversely, bone status should be carefully and accurately estimated in cases of potential transient osteoporosis of the hip in pregnancy to reduce future fracture risk. 10.1111/jog.13313
    Chronic Exposure to Static Magnetic Fields from Magnetic Resonance Imaging Devices Deserves Screening for Osteoporosis and Vitamin D Levels: A Rat Model. Gungor Harun R,Akkaya Semih,Ok Nusret,Yorukoglu Aygun,Yorukoglu Cagdas,Kiter Esat,Oguz Emin O,Keskin Nazan,Mete Gulcin A International journal of environmental research and public health Technicians often receive chronic magnetic exposures from magnetic resonance imaging (MRI) devices, mainly due to static magnetic fields (SMFs). Here, we ascertain the biological effects of chronic exposure to SMFs from MRI devices on the bone quality using rats exposed to SMFs in MRI examining rooms. Eighteen Wistar albino male rats were randomly assigned to SMF exposure (A), sham (B), and control (C) groups. Group A rats were positioned within 50 centimeters of the bore of the magnet of 1.5 T MRI machine during the nighttime for 8 weeks. We collected blood samples for biochemical analysis, and bone tissue samples for electron microscopic and histological analysis. The mean vitamin D level in Group A was lower than in the other groups (p = 0.002). The mean cortical thickness, the mean trabecular wall thickness, and number of trabeculae per 1 mm2 were significantly lower in Group A (p = 0.003). TUNEL assay revealed that apoptosis of osteocytes were significantly greater in Group A than the other groups (p = 0.005). The effect of SMFs in chronic exposure is related to movement within the magnetic field that induces low-frequency fields within the tissues. These fields can exceed the exposure limits necessary to deteriorate bone microstructure and vitamin D metabolism. 10.3390/ijerph120808919
    Management of postmenopausal osteoporosis. Andreopoulou Panagiota,Bockman Richard S Annual review of medicine A hallmark of menopause, which follows the decline in the ovarian production of estrogen, is the aggressive and persistent loss of bone mineral and structural elements leading to loss of bone strength and increased fracture risk. This review focuses on newer methods of diagnosing osteoporosis and assessing fracture risk, as well as on novel management strategies for prevention and treatment. Fracture-risk prediction has been significantly enhanced by the development of methods such as the trabecular bone score, which helps assess bone microarchitecture and adds value to standard bone densitometry, and the Fracture Risk Assessment Tool (FRAX) algorithm techniques. The treatment of osteoporosis, which has the goals of fracture prevention and risk reduction, is moving beyond traditional monotherapies with antiresorptives and anabolic agents into new combination regimens. 10.1146/annurev-med-070313-022841
    Fluorosis increases the risk of postmenopausal osteoporosis by stimulating interferon γ. Lv Yun-Gang,Kang Li,Wu Guangyao Biochemical and biophysical research communications Estrogen deficiency in postmenopausal women frequently activates osteoclasts (OC), accelerates bone resorption, and leads to osteoporosis (OP). Previous studies have demonstrated that interferon γ (IFNγ) could increase bone resorption and may be involved in postmenopausal OP. Fluorosis also increased the risk of fractures and dental fluorosis, and fluoride may enhance osteoclast formation and induce osteoclastic bone destruction in postmenopausal women, but the underlying mechanisms are as yet unknown. Here, we show that serum fluoride and IFNγ levels are negatively correlated with bone mineral density (BMD) in postmenopausal women residing in a fluorotic area. Estrogen suppresses IFNγ, which is elevated by fluoride, playing a pivotal role in triggering bone loss in estrogen-deficient conditions. In vitro, IFNγ is inhibited by estrogen treatment and increased by fluoride in Raw264.7 cell, an osteoclast progenitor cell line. In ovariectomized (Ovx) mice, estrogen loss and IFNγ promote OC activation and subsequent bone loss in vivo. However, IFNγ deficiency prevents bone loss in Ovx mice even in fluoride conditions. Interestingly, fluoride fails to increase IFNγ expression in estrogen receptor α (ERα)-deficient conditions, but not in ERβ-deficient conditions. These findings demonstrate that fluorosis increases the bone loss in postmenopausal OP through an IFNγ-dependent mechanism. IFNγ signaling activates OC and aggravates estrogen deficiency inducing OP. Thus, stimulation of IFNγ production is a pivotal ''upstream'' mechanism by which fluoride promotes bone loss. Suppression of IFNγ levels may constitute a therapeutic approach for preventing bone loss. 10.1016/j.bbrc.2016.09.083
    Relationship between quantitative parameters of lumbar vertebral perfusion and bone mineral density (BMD) in postmenopausal women. Huang Zhenhuan,Lin Qi,Wang Jianwen,Zhan Zejuan,Tu Xuezhao Advances in clinical and experimental medicine : official organ Wroclaw Medical University BACKGROUND:Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive method to evaluate the microcirculation of bone marrow in local tissue, which will be a new tool for the diagnosis of osteoporosis. OBJECTIVES:To investigate the relationship between quantitative perfusion parameters (Ktrans, Kep and Ve) and bone mineral density (BMD) in postmenopausal women. MATERIAL AND METHODS:The subjects were divided into 3 groups according to T value: normal bone mass group (T value ≥-1.0); bone loss group (-2.5 < T <-1.0); and osteoporosis group (T ≤-2.5). Ktrans, Kep and Ve of the lumbar spine were measured using quantitative DCE-MRI. The relationship between these parameters and age was analyzed. RESULTS:Bone mineral density of the lumbar spine and femoral neck gradually decreased with age. The values of Ktrans, Kep and Ve significantly decreased with age. The values of Ktrans, Kep and Ve of the lumbar vertebrae in the osteoporosis group were lower than those in the bone loss and normal bone mass group. Bone mineral density was positively correlated with the Ktrans and Ve of the lumbar vertebrae. CONCLUSIONS:The incidences of bone loss and osteoporosis increased with age. The measurement of BMD was conducive to early diagnosis of osteoporosis. Ktrans, Kep and Ve values of the lumbar vertebra decreased with age, and have a positive correlation with lumbar BMD. The value of DCE-MRI may play a role in the diagnostic algorithm of osteoporosis. 10.17219/acem/94150
    Chemical shift-encoded MRI for assessment of bone marrow adipose tissue fat composition: Pilot study in premenopausal versus postmenopausal women. Martel Dimitri,Leporq Benjamin,Bruno Mary,Regatte Ravinder R,Honig Stephen,Chang Gregory Magnetic resonance imaging OBJECT:To quantify and compare subregional proximal femur bone marrow fat composition in premenopausal and postmenopausal women using chemical shift-encoded-MRI (CSE-MRI). MATERIALS AND METHODS:A multi gradient-echo sequence at 3 T was used to scan both hips of premenopausal (n = 9) and postmenopausal (n = 18) women. Subregional fat composition (saturation, poly-unsaturation, mono-unsaturation) was quantitatively assessed in the femoral head, femoral neck, Ward's triangle, greater trochanter, and proximal shaft in bone marrow adipose tissue and separately within red and yellow marrow adipose tissue. RESULTS:Significant differences in fat composition in postmenopausal compared to premenopausal women, which varied depending on the subregion analyzed, were found. Within both whole and yellow marrow adipose tissue, postmenopausal women demonstrated higher saturation (+14.7% to +43.3%), lower mono- (-11.4% to -33%) and polyunsaturation (-52 to -83%) (p < 0.05). Within red marrow adipose tissue, postmenopausal women demonstrated lower fat quantity (-16% to -24%) and decreased polyunsaturation (-80 to -120%) in the femoral neck, greater trochanter, and Ward's triangle (p < 0.05). CONCLUSION:CSE-MRI can be used to detect subregional differences in proximal femur marrow adipose tissue composition between pre- and post-menopausal women in clinically feasible scan times. 10.1016/j.mri.2018.07.001
    The Correlation between Osteoporosis and Blood Circulation Function Based on Magnetic Resonance Imaging. Qiu Xiaoming,Fu Yufei,Chen Jiao,Ye Yu,Wang Zhen,Ming Xianfang Journal of medical systems In order to investigate the relationship between changes in blood circulation and bone mineral density (BMD) loss, the characteristic parameters reflecting the function of tissue oxygen metabolism are obtained by means of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI), image processing and semi-quantitative analysis. The correlation and variance analysis of the characteristic parameters of different BMD groups are carried out, and the physiological parameters of bone marrow blood perfusion are obtained by dynamic enhanced MRI (DCE-MRI). Multivariate logistic regression analysis is carried out with the physiological parameters of blood oxygen metabolism function and bone marrow blood perfusion as independent variables and BMD as dependent variables. It is found that there are significant differences in oxygen metabolism between individual muscles in different BMD groups and between skeletal muscles of different types of muscle fibers. Age, total volume of bone marrow and oxygen metabolism ability of tibial anterior muscle have significant independent effects on osteoporosis. It shows that the changes of blood circulation in bone marrow and surrounding muscle tissue are indeed one of the causes of osteoporosis. 10.1007/s10916-019-1206-8
    Lumbar muscle volume in postmenopausal women with osteoporotic compression fractures: quantitative measurement using MRI. Huang Chi Wen C,Tseng Ing-Jy,Yang Shao-Wei,Lin Yen-Kuang,Chan Wing P European radiology OBJECTIVE:To investigate the relationship between paraspinal and psoas muscle volumes and acute osteoporotic or low-bone-mass compression fractures of the lumbar spine in postmenopausal women. METHODS:Patient data were retrieved retrospectively for postmenopausal women with L-spine magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry showing osteoporosis/low bone mass. Group 1 comprised eight women aged 60-80 years with MRI showing a single acute compression fracture. The age-matched group 2a (N = 12) and younger group 2b (N = 12) comprised of women whose MRIs showed no fractures. Cross-sectional MRIs of the paraspinal and psoas muscles and intramuscular fat volume for each muscle group were measured. Operator repeatability and reproducibility were obtained. RESULTS:Group 1 showed significantly smaller lean muscle volume for all muscle groups at L5/S1. Intramuscular fat volume was also smaller in most muscle groups in group 1, though only reaching statistical significance at variable muscle groups and levels. Measurements show both good intrarater repeatability and interrater reproducibility of lean muscle volume estimations (intraclass correlation coefficient (ICC), 0.999 for rater A and 0.997 for rater B; Cronbach's alpha 0.995) and intramuscular fat volume estimations (ICC, 0.995 for rater A and 0.982 for rater B; Cronbach's alpha was 0.981). CONCLUSIONS:This study provides the first quantitative evidence that compression fractures in postmenopausal women with underlying osteoporosis/low bone mass are associated with less paraspinal and psoas muscle volumes. Further longitudinal studies with larger cohorts are needed to verify this relationship. KEY POINTS:• The risk of osteoporotic compression fractures is higher in older women with smaller paraspinal muscle volume. • Older women show smaller paraspinal muscle volume and more intramuscular fat compared to younger controls. 10.1007/s00330-019-06034-w
    Is quantitative magnetic resonance imaging valuable in the assessment of trabecular bone structure in osteoporosis? Tokgöz Nil,Akdeniz Mualla,Uçar Murat,Kılıç Koray,Celik Azim Eklem hastaliklari ve cerrahisi = Joint diseases & related surgery OBJECTIVES:This study aims to evaluate the value of quantitative magnetic resonance imaging in the assessment of bone trabeculae in osteoporosis by comparing the results with dual-energy X-ray (DXA) absorptiometry. PATIENTS AND METHODS:The study consisted of 85 postmenopausal women (mean age 57.2 years; range 43 to 83 years) underwent both DXA absorptiometry and lumbar quantitative magnetic resonance imaging. T2 and T2* values were calculated by magnetic resonance imaging and the results were compared with bone mineral density. RESULTS:According to bone mineral density t-scores; there were 32 normal, 30 osteopenic, and 23 osteoporotic patients. T2 values of L1- L4 were different in normal with osteoporotic, and the osteopenic with osteoporotic groups. There were increased T2 values with reducing t-scores. Comparing the normal and osteopenic groups, no statistical difference was found in T2 measurements of lumbar vertebrae, except L4. T2* values of L1-L4 vertebrae were not statistically different between the study groups. CONCLUSION:T2 measurements of lumbar vertebra on quantitative magnetic resonance imaging may be useful in evaluation of bone trabeculae in osteoporosis, and may also be helpful in differentiation of osteoporotic from normal, and osteopenic from osteoporotic patients. 10.5606/ehc.2013.02
    Potential diagnostic role of the MRI-derived internal magnetic field gradient in calcaneus cancellous bone for evaluating postmenopausal osteoporosis at 3T. Rebuzzi Mauro,Vinicola Vincenzo,Taggi Franco,Sabatini Umberto,Wehrli Felix W,Capuani Silvia Bone INTRODUCTION:Bone mineral density (BMD) result has a low predictive value on patients' risk for future fractures. Thus, new approaches for examining patients at risk for developing osteoporosis would be desirable. Magnetic resonance (MR) investigations in cancellous bone have been shown to yield useful quantitative information on both trabecular-bone microstructure and bone marrow composition. This work was undertaken to address the hypothesis that the effective internal magnetic field gradient (IMFG), a new MR parameter, discriminates between healthy, osteopenic and osteoporotic postmenopausal women, classified on the basis of bone mineral density (BMD) criteria. The work builds on preliminary results indicating that IMFG, measured in trabecular-bone pores and quantified by spin-echo decay and water diffusion MR near the bone-bone marrow interface depends on both the bone marrow water rate of diffusion and the magnetic susceptibility difference (ΔX) between water and bone. MATERIALS AND METHODS:MR relaxometry, MR spectroscopy and diffusion-weighted MR imaging of the heel was performed in fifty-five women (mean age, 62.9±6.6years) at 3T. Moreover, in order to study the reproducibility of IMFG measurement, five young women (mean age 31.0±3.2years; age range, 28-36years) were scanned and rescanned. The study protocol was approved by the local Ethics Committee. Quantitative Computer Tomography (QCT) of the L1-L3 vertebral segments was performed to classify the postmenopausal women into three groups according to QCT BMD: healthy (n=8); osteopenic (n=25); and osteoporotic (n=22). In all subjects, BMD T-scores, marrow fat content (Mfc), T2*, apparent diffusion coefficient (ADC) and IMFG (estimated from the additional spin-echo decay due to diffusion of water in local magnetic field gradients), were assessed in the whole calcaneus as well as in three calcaneal subregions: subtalar, tuber calcaneus, and cavum calcaneus. Between-group comparisons to assess group differences and Pearson correlation analysis were performed. Short and long-term coefficients of variation (CVS and CVL, respectively) were evaluated in young subjects. RESULTS:Reproducibility of the IMFG measurement was satisfactory. No significant difference was found in the IMFG measurement performed in both calcaneus and subtalar calcaneal region between the two separate sessions comprised of five young women. Mfc did not significantly differ between groups. The IMFG in the subtalar region was significantly different between all three groups (P<0.01), being greatest in healthy women, intermediate in those with osteopenia, and lowest in osteoporotic subjects. Conversely neither T2* nor ADC is able to discriminate healthy subjects from those with osteopenia and osteoporosis. Increased inter-trabecular space, as it typically occurs in patients with osteoporosis, modifies water diffusion, conferring higher ADC values, thereby lowering the IMFG. CONCLUSION:The IMFG measured in the calcaneal subtalar region shows a high ability in identifying healthy subjects. The new quantitative MR method based on measurement of the IMFG may provide a new means for assessing patients with osteoporosis. 10.1016/j.bone.2013.07.027
    Bone susceptibility mapping with MRI is an alternative and reliable biomarker of osteoporosis in postmenopausal women. Chen Yanjun,Guo Yihao,Zhang Xintao,Mei Yingjie,Feng Yanqiu,Zhang Xiaodong European radiology OBJECTIVES:To investigate the efficacy of quantitative susceptibility mapping (QSM) in the assessment of osteoporosis for postmenopausal women. METHODS:Between May and September 2017, a total of 70 postmenopausal women who underwent MRI-based QSM and quantitative computed tomography (QCT) were consecutively enrolled in this prospective study. The measurement of QSM and QCT values was performed on the L3 vertebrae body. On the basis of QCT value, all individuals were divided into three groups (normal, osteopenia and osteoporosis). RESULTS:On the basis of QCT, 18 individuals were normal (25.7%), 26 osteopenic (37.1%) and 26 osteoporotic (37.1%). The QSM value was age-related (p = 0.04) and significantly higher in the osteoporosis group than in either the normal or osteopenia group (for all, p < 0.001). In addition, the QSM value was highly correlated with QCT value (r = - 0.720, p < 0.001). For QSM, the area under the curve (AUC), sensitivity and specificity for differentiating osteopenia from non-osteopenia were 0.88, 86.5% and 77.8%, respectively, and for differentiating osteoporosis from non-osteoporosis they were 0.86, 80.8% and 77.3%, respectively. CONCLUSIONS:MRI-based QSM could be used for quantifying susceptibility in vertebrae and has the potential to be a new biomarker in the assessment of osteoporosis for postmenopausal women. KEY POINTS:• Osteoporosis significantly increases risk of fracture for postmenopausal women. • QSM value was correlated with QCT value (r = - 0.72, p < 0.001). • QSM is feasible in the assessment of osteoporosis for postmenopausal women. • QSM offers the quantification of susceptibility within bone. 10.1007/s00330-018-5419-x
    Effect of Androgen-deprivation Therapy on Bone Mineral Density in Japanese Patients with Prostate Cancer. Miyazawa Yoshiyuki,Sekine Yoshitaka,Syuto Takahiro,Nomura Masashi,Koike Hidekazu,Matsui Hiroshi,Shibata Yasuhiro,Ito Kazuto,Suzuki Kazuhiro In vivo (Athens, Greece) BACKGROUND/AIM:To evaluate bone mineral density (BMD) in Japanese patients with prostate cancer (PCa) after administering androgen deprivation therapy (ADT) for 2 years. PATIENTS AND METHODS:A total of 84 Japanese patients with PCa were enrolled in this study during the period 2008-2011. BMD was measured by dual energy X-ray absorptiometry, every 6 months. The fracture risk assessment tool (FRAX) score was calculated before starting ADT. We evaluated the change in BMD over a 2-year period and the relationship between this change, the FRAX score, and the estimated glomerular filtration rate (eGFR). RESULTS:Compared to baseline, BMD decreased by 2.50% at 6 months after ADT, by 4.28% after 12 months, by 5.34% after 18 months, and by 6.16% after 2 years (all p<0.05). Multivariate analysis revealed that the eGFR, according to a threshold rate of 73.5 ml/min, was a significant factor in BMD. CONCLUSION:Lumbar BMD in Japanese patients with PCa decreased by 4.28% at 1 year after ADT and by 6.16% after 2 years. We found a correlation between the decrease in BMD and the eGFR before initiating ADT, suggesting a small BMD reduction in patients with PCa who have good renal function. 10.21873/invivo.11254
    Quantitative diagnosis of osteoporosis using lumbar spine signal intensity in magnetic resonance imaging. Shayganfar Azin,Khodayi Maede,Ebrahimian Shadi,Tabrizi Zhale The British journal of radiology OBJECTIVE:Osteoporosis is the most common metabolic bone disease that is not recognized in many elderly people. To determine the cause of low back pain, lumbosacral MRI is done for a large population who may not have gone under dual energy X-ray absorptiometry (DXA). The aim of this study was to predict bone density using lumbar spine signals in lumbosacral MRI in high risk patients for osteoporosis including post-menopausal females and calculate a threshold for a new quantitative MRI-based score to be used in estimation of lumbar spine bone mass density. METHODS:82 menopaused females, who had undergone DXA before, were selected and MRI was done within 6 months after DXA. 69 healthy females aged 20-29 years who had undergone lumbar MRI were selected as reference group. Results were analyzed and threshold and diagnostic performance of MRI-based score (M-score) on the method of T-score was calculated. RESULTS:Negative correlation between M-score and T-score was detected. Cut off point of 2.05 was found for M-score with near sensitivity of 90% and specificity of 87% for detecting osteoporotic patients from non-osteoporotic individuals. CONCLUSION:M-score is a MRI-based method which can identify patients at risk of osteoporosis. Early diagnosis of osteoporosis can reduce morbidity and mortality caused by it. ADVANCES IN KNOWLEDGE:The research introduced cut of points for M-score as a new MRI quantitative method to be used as an opportunistic technique for detecting osteoporotic patients. 10.1259/bjr.20180774
    Sensitivity and specificity assessment of DWI and ADC for the diagnosis of osteoporosis in postmenopausal patients. Momeni Mohammad,Asadzadeh Mohammad,Mowla Karim,Hanafi Mohammad Ghasem,Gharibvand Mohammad Momen,Sahraeizadeh Aliakbar La Radiologia medica OBJECTIVE:In this study, we prospectively investigated the diagnostic capability of diffusion-weighted magnetic resonance imaging (DWI) in assessing vertebral marrow changes in postmenopausal women with osteoporosis. MATERIALS AND METHODS:Sixty postmenopausal women (mean age 60.2 ± 6.11 years) underwent both dual-energy X-ray absorptiometry (DEXA) of the spine and MRI. Results were acquired from each patient's L2 to L4, for a total of 180 lumbar vertebrae. Based on bone mineral density (BMD) measurements obtained from DEXA, the vertebrae were divided into three groups as follows: normal (n = 52), osteopenic (n = 92), and osteoporotic (n = 36). DWI of the vertebral body was performed to assess the apparent diffusion coefficient (ADC). The ADC outcomes were compared among the three groups and correlated with BMD. RESULTS:ADC values (× 10 mm/s) were significantly lower in the osteoporotic group (135.67 ± 44.10) in comparison to the normal group (561.85 ± 190.37) (P = 0.0001). The results showed a positive correlation between ADC and BMD values (r = 0.748, P = 0.0001). In receiver operating characteristic (ROC) analysis, the area under the curve for DWI was 0.912 (P = 0.001). A cut-off value of 400 mm/s for the diagnosis of osteoporosis; had sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 90.90%, 83.34%, 88.89%, 93.75%, and 76.93%, respectively. CONCLUSION:ADC values correlated positively with BMD in women. DWI can allow quantitative evaluation of bone marrow changes and osteoporosis in postmenopausal women. 10.1007/s11547-019-01080-2