Biodegradation of Benzene, Toluene, Ethylbenzene, and o-, m-, and p-Xylenes by the Newly Isolated Bacterium Comamonas sp. JB.
Jiang Bei,Zhou Zunchun,Dong Ying,Tao Wei,Wang Bai,Jiang Jingwei,Guan Xiaoyan
Applied biochemistry and biotechnology
A bacterium designated strain JB, able to degrade six benzene, toluene, ethylbenzene, and o-, m-, and p-xylene (BTEX) compounds, was isolated from petroleum-contaminated soil. Taxonomic analyses showed that the isolate belonged to Comamonas, and until now, the genus Comamonas has not included any known BTEX degraders. The BTEX biodegradation rate was slightly low on the mineral salt medium (MSM), but adding a small amount of yeast extract greatly enhanced the biodegradation. The relationship between specific degradation rate and individual BTEX was described well by Michaelis-Menten kinetics. The treatment of petrochemical wastewater containing BTEX mixture and phenol was shown to be highly efficient by BTEX-grown JB. In addition, toxicity assessment indicated the treatment of the petrochemical wastewater by BTEX-grown JB led to less toxicity than untreated wastewater.
MicroRNA-548-3p overexpression inhibits proliferation, migration and invasion in osteoblast-like cells by targeting STAT1 and MAFB.
Ramírez-Salazar Eric G,Almeraya Erika V,López-Perez Tania V,Patiño Nelly,Salmeron Jorge,Velázquez-Cruz Rafael
Journal of biochemistry
Osteoporosis is the most common bone disease and a public health issue with increasing prevalence in Mexico. This disease is caused by an imbalance in the bone remodelling process mediated by osteoclast and osteoblast. MicroRNAs have emerged as key players during the differentiation of both types of cells specialized involved in bone metabolism. We found high expression levels of miR-548x-3p in circulating monocytes derived from postmenopausal osteoporotic women. This study aimed to analyse the functional characterization of miR-548x-3p roles in the bone remodelling process. We validated by RT-qPCR, the elevated levels of miR-548x-3p in circulating monocytes derived from osteoporosis women. Through bioinformatics analysis, we identify MAFB and STAT1 as potential target genes for miR-548x-3p. Both genes showed low levels of expression in circulating monocytes derived from osteoporotic women. In addition, we demonstrated the binding of miR-548x-3p to the 3'-UTR of both mRNAs. MiR-548x-3p was overexpressed in osteoblasts-like cell lines decreasing the levels of MAFB and STAT1 mRNA and protein. We found that miR-548x-3p overexpression inhibits the proliferation, migration and invasion of the cell lines evaluated. Our results identified, by the first time, the potential role of miR-548x-3p as a modulator of the bone remodelling process by regulating the expression of MAFB and STAT1.
Effects of PTH and PTH Hypersecretion on Bone: a Clinical Perspective.
Rejnmark Lars,Ejlsmark-Svensson Henriette
Current osteoporosis reports
PURPOSE OF REVIEW:Hyperparathyroidism may be due to an autonomous hypersecretion of parathyroid hormone (PTH) or occurs in response to a number of physiological stimuli. A number of recent findings have provided new insights into the importance of the calcium-parathyroid-vitamin D axis to bone in normal physiology and pathological conditions. RECENT FINDINGS:PTH is known to affect bone microarchitecture with different effects on cortical and trabecular bone compartments. In trabecular bone, PTH may exert anabolic effects, whereas PTH promotes bone resorption in cortical bone. Vertebral fractures are prevalent in primary hyperparathyroidism (PHPT), and patients seem to fracture at higher values of bone mineral density (BMD) than patients with osteoporosis. This may be explained by changes in bone microarchitecture, which cannot be detected by measuring BMD. Even in mild PHPT, bone seems to benefit from parathyroidectomy. In secondary hyperparathyroidism, bone seems much more susceptible to fracture with insufficient levels of vitamin D compared with a replete vitamin status. If elevated PTH levels cannot be explained by conditions known to cause secondary hyperparathyroidism, the condition is termed normocalcemic PHPT, which also has been associated with an increased risk of fractures. Hyperparathyroidism is harmful to bone, which is why it is of importance to normalize PTH levels either by parathyroidectomy in PHPT or by counteracting conditions known to increase PTH in secondary hyperparathyroidism.
A Contemporary View of the Definition and Diagnosis of Osteoporosis in Children and Adolescents.
Ward Leanne M,Weber David R,Munns Craig F,Högler Wolfgang,Zemel Babette S
The Journal of clinical endocrinology and metabolism
The last 2 decades have seen growing recognition of the need to appropriately identify and treat children with osteoporotic fractures. This focus stems from important advances in our understanding of the genetic basis of bone fragility, the natural history and predictors of fractures in chronic conditions, the use of bone-active medications in children, and the inclusion of bone health screening into clinical guidelines for high-risk populations. Given the historic focus on bone densitometry in this setting, the International Society for Clinical Densitometry published revised criteria in 2013 to define osteoporosis in the young, oriented towards prevention of overdiagnosis given the high frequency of extremity fractures during the growing years. This definition has been successful in avoiding an inappropriate diagnosis of osteoporosis in healthy children who sustain long bone fractures during play. However, its emphasis on the number of long bone fractures plus a concomitant bone mineral density (BMD) threshold ≤ -2.0, without consideration for long bone fracture characteristics (eg, skeletal site, radiographic features) or the clinical context (eg, known fracture risk in serious illnesses or physical-radiographic stigmata of osteoporosis), inappropriately misses clinically relevant bone fragility in some children. In this perspective, we propose a new approach to the definition and diagnosis of osteoporosis in children, one that balances the role of BMD in the pediatric fracture assessment with other important clinical features, including fracture characteristics, the clinical context and, where appropriate, the need to define the underlying genetic etiology as far as possible.
Delayed Denosumab Injections and Bone Mineral Density Response: An Electronic Health Record-based Study.
Lyu Houchen,Zhao Sizheng S,Yoshida Kazuki,Tedeschi Sara K,Xu Chang,Nigwekar Sagar U,Leder Benjamin Z,Solomon Daniel H
The Journal of clinical endocrinology and metabolism
CONTEXT:Discontinuation of denosumab leads to a rapid reversal of its therapeutic effect. However, there are no data regarding how unintended delays or missed injections of denosumab impact bone mineral density (BMD) response. OBJECTIVE:We examined the association of delays in injections of denosumab with BMD change. DESIGN:We used electronic medical records from two academic hospitals from 2010 to 2017. PARTICIPANTS:Patients older than 45 years of age and used at least 2 doses of 60 mg denosumab. Denosumab adherence was evaluated by the medication coverage ratio (MCR). Good adherence corresponds to a dosing interval ≤7 months (defined by MCR ≥93%), moderate adherence corresponds to an interval of 7 to 10 months (MCR 75%-93%), and poor adherence corresponds to an interval ≥10 months (MCR ≤75%). OUTCOME MEASURES:Annualized percent BMD change from baseline at the lumbar spine, total hip, and femoral neck. RESULTS:We identified 938 denosumab injections among 151 patients; the mean (SD) age was 69 (10) years, and 95% were female. Patients with good adherence had an annualized BMD increase of 3.9% at the lumbar spine, compared with patients with moderate (3.0%) or poor adherence (1.4%, P for trend .002). Patients with good adherence had an annualized BMD increase of 2.1% at the total hip, compared with patients with moderate (1.3%) or poor adherence (0.6%, P for trend .002). CONCLUSIONS:A longer interval between denosumab injections is associated with suboptimal BMD response at both spine and total hip. Strategies to improve the timely administration of denosumab in real-world settings are needed.
[Pain management in osteoporosis].
Heuchemer L,Emmert D,Bender T,Rasche T,Marinova M,Kasapovic A,Conrad R,Mücke M
Osteoporosis is a very common disease all over the world, in which a reduction in bone density can lead to an increased risk of fractures and a diminished physical height. Osteoporosis is also associated with acute and chronic pain, which especially occurs in the back and can significantly reduce the quality of life. To provide sufficient care for affected patients, it is essential to know the particularities of pain management in osteoporosis, such as pharmacological and nonpharmacological treatment options. This article gives a comprehensive review of pain management in osteoporosis and also explains the underlying pathomechanisms, risk factors, and diagnostic procedures.
Awareness of osteoporosis among 368 residents in China: a cross-sectional study.
Oumer Kemal Sherefa,Liu Yawen,Yu Qiong,Wu Fan,Yang Shuman
BMC musculoskeletal disorders
BACKGROUND:Studies on osteoporosis awareness among the general population in China are still limited. We examined the level of osteoporosis awareness among residents in China, determined the risk factors associated with a lower level of osteoporosis awareness, and assessed the sources of their knowledge about osteoporosis. METHODS:We conducted a cross-sectional study among 368 general residents aged 30 years or older from 19 provinces during January-March 2018 in China. All participants were identified and interviewed face-to-face by medical students in Jilin University using a structured questionnaire. Osteoporosis awareness scores (percent of the correct answer) were determined across several domains, including definition, diagnosis, risk factors, and prevention of osteoporosis. We used multiple linear regression models to test the relationship between risk factors and overall awareness scores. RESULTS:The mean age of included participants was 52.9 ± 10.2 years, and 53% of them were male. Osteoporosis awareness score for definition was 77.7%, diagnosis 49.6%, risk factors 49.2%, treatment 60.5%, and prevention 69.9%. The overall awareness score was 67.8%. Lower family income and education level were significantly associated with lower overall awareness score (all p < 0.05). Television or radio health program was reported to be their main source of knowledge about osteoporosis. CONCLUSION:The awareness level for osteoporosis in our study is moderate; lower family income and education level were risk factors for lower awareness. Television or radio health programs had the greatest contribution to osteoporosis awareness.
Correlation Between Bone Density and Lumbar Compression Fractures.
Takahashi Toshihide,Takada Tomoya,Narushima Takeshi,Tsukada Atsuro,Ishikawa Eiichi,Matsumura Akira
Gerontology & geriatric medicine
Bone densitometry is widely used to evaluate osteoporosis; however, it is pointed out that bone density may be high in the case of fractures, deformities, and osteosclerotic changes. The present study evaluated bone density measured at our hospital and evaluated its correlation with the presence or absence of lumbar spine fractures. Bone density of the lumbar spine and femur was measured in 185 patients from July 2017 to June 2019 at our hospital, and the presence or absence of a lumbar spine compression fracture was evaluated on the basis of the image. Information regarding age, sex, lumbar bone density, presence or absence of lumbar fracture, number of lumbar fractures, and grade of lumbar fracture was also statistically evaluated. Analysis was performed for 185 patients (20 males and 165 females, average age 76.9 ± 7.5 years). The bone density was 0.830 ± 0.229 of compression fractured bodies (number of vertebral bodies were 132) and 0.765 ± 0.178 g/cm of noncompression fractured bodies (number of vertebral bodies was 608). The presence of lumbar fractures significantly increases bone density. For diagnosing osteoporosis, both bone density and the possibility of lumbar spine fractures must be considered.
Safety of Romosozumab in Osteoporotic Men and Postmenopausal Women: A Meta-Analysis and Systematic Review.
Mariscal Gonzalo,Nuñez Jorge H,Bhatia Sanjay,Barrios Carlos,Domenech-Fernández Pedro
Monoclonal antibodies in immunodiagnosis and immunotherapy
Sclerostin is a protein synthesized mainly by osteocytes whose function is to inhibit bone formation. A recent monoclonal antibody, Romosozumab, is able to block sclerostin. The aim of this meta-analysis is to compare the safety of Romosozumab with placebo and alendronate. Five randomized controlled trials that described the safety of Romosozumab in healthy men and postmenopausal women were analyzed. The measures to be compared were the number of adverse events and the number of serious adverse events. Specific results included injection site reaction, arthralgia, nasopharyngitis, and back pain. A total of 11,741 patients were included in this meta-analysis, in three different groups: Romosozumab, alendronate, and placebo. Significant differences were seen between the groups with regard to injection site reaction: 5.88% in the Romosozumab group versus 3.62% in the placebo group (Mantel-Haenszel [M-H] 1.54, confidence interval [95% CI] 1.22-1.96; < 0.001) and 2.62% in the alendronate group (M-H 1.8, 95% CI 1.32-2.60; < 0.001). In addition, patients treated with Romosozumab had significantly fewer total adverse events than the alendronate group (M-H 0.85, 95% CI 0.74-0.98; < 0.05). In conclusion, Romosozumab may have lower adverse effects compared to alendronate and comparable to a placebo, except injection site reactions. Injection site reactions were more with romosozumab compared to alendronate and compared to the placebo as well. Romosozumab appears to have a similar safety profile to bisphosphonates.
Oolong tea drinking boosts calcaneus bone mineral density in postmenopausal women: a population-based study in southern China.
Duan Pengfei,Zhang Jiahong,Chen Jialian,Liu Zhixi,Guo Pi,Li Xiaolian,Li Linfen,Zhang Qingying
Archives of osteoporosis
INTRODUCTION:Observational studies have shown that tea consumption has a potentially beneficial effect on bone health. However, few studies have assessed the effects of types of tea consumed on bone health. We aimed to investigate whether drinking oolong tea is associated with increased calcaneus bone mineral density (BMD) in postmenopausal women. METHODS:From an epidemiological survey in Shantou, 476 postmenopausal women aged 40 to 88 years were enrolled in the study. All women were questioned about their demographic features, lifestyle, health status, types of tea consumed, habit of tea consumption, and habitual dietary intake by use of a structured questionnaire. Estimated areal BMD was measured by calcaneal quantitative ultrasound (QUS). RESULTS:As compared with non-tea drinkers, oolong tea drinkers had higher calcaneus BMD (β 34.70 [95% CI 10.38, 59.03]). In addition, calcaneus BMD was significantly increased for those drinking 1-5 cups/day (β 27.43 [95% CI 3.70, 51.16]) but not > 5 cups/day. We observed no linear increase in calcaneus BMD with increasing years of tea consumption and local polynomial regression fitting showed a parabola-shaped association between years of tea consumption and calcaneus BMD. However, symptoms of osteoporosis did not differ by types of tea consumed. CONCLUSION:Long-term moderate oolong tea consumption may have beneficial effects on bone health in postmenopausal women in Shantou of southern China.
Urban-Rural Differences in Bone Mineral Density and its Association with Reproductive and Menstrual Factors Among Older Women.
Wang Jing,Zhang Weiqiang,Wang Xiaoyun,Li Chenguang,Li Jinlong,Zhao Yongjian,Chen Lin,Qi Xiaofeng,Qiao Liang,Da Weiwei,Liu Li,Xu Chongqing,Zhu Sen,Li Yimian,Zhang Hao,Sha Nannan,Wang Qiang,Zhu Yin,Luo Jianxing,Cui Xuejun,Liang Qianqian,Lu Sheng,Shi Qi,Wang Yongjun,Shu Bing
Calcified tissue international
PURPOSE:This study aimed to compare the bone mineral density (BMD) of older women living in rural and urban areas, and evaluate the potential factors affecting the risk of osteoporosis. METHODS:We recruited 574 women aged 65 years or older from rural areas and 496 from urban areas in Shanghai, China. The BMD values of the lumbar vertebrae and total left hip were measured by a dual energy X-ray absorptiometry densitometer. We also recorded information about education level, family income, medications, reproductive and menstrual history, diet, smoking, and alcohol consumption. RESULTS:Women in urban areas had significantly higher BMD in their lumbar spine, and there was a dramatic increase in the proportion of women with osteoporosis in rural areas. The age at menarche was significantly higher among women living in rural areas, and there were more years from menarche to menopause among urban women. Rural women had significantly higher numbers of both pregnancies and parity, and a significantly lower age at first parity. In multiple linear regression analyses, years from menarche to menopause was independently related to high lumbar spine BMD, while age at menarche and parity was independently related to low lumbar spine BMD. CONCLUSION:More older women in rural areas had osteoporosis. Later menarche, less years from menarche to menopause and higher parity might partially contribute to decreased BMD among women in rural areas. More attention should be paid to women in rural areas to prevent bone loss and further bone and health impairment.
The long-term residual effects of low-magnitude mechanical stimulation therapy on skeletal health.
Journal of biological engineering
BACKGROUND:Low-magnitude mechanical stimulation (LMMS) may improve skeletal health. The objective of this research was to investigate the long-term residual effects of LMMS on bone health. 10-week old female mice were given LMMS for 8 weeks; SHAM did not receive LMMS. Some groups remained on study for an additional 8 or 16 weeks post treatment ( = 17). RESULTS:Epiphyseal trabecular mineralizing surface to bone surface ratio (MS/BS) and bone formation rate (BFR/BS) were significantly greater in the LMMS group compared to the SHAM group at 8 weeks by 92 and 128% respectively. Mineral apposition rate (MAR) was significantly greater in the LMMS group 16 weeks post treatment by 14%.Metaphyseal trabecular bone mineral density (BMD) increased by 18%, bone volume tissue volume ratio (BV/TV) increased by 37%, and trabecular thickness (Tb.Th.) increased by 10% with LMMS at 8 weeks post treatment. Significant effects 16 weeks post treatment were maintained for BV/TV and Tb.Th. The middle-cortical region bone volume (BV) increased by 4% and cortical thickness increased by 3% with 8-week LMMS. CONCLUSIONS:LMMS improves bone morphological parameters immediately after and in some cases long-term post LMMS. Results from this work will be helpful in developing treatment strategies to increase bone health in younger individuals.
Fumitremorgin C Attenuates Osteoclast Formation and Function Suppressing RANKL-Induced Signaling Pathways.
Yuan Yu,Chen Kai,Chen Xi,Wang Chao,Qiu Heng,Cao Zhen,Song Dezhi,Sun Youqiang,Guo Jianmin,Tickner Jennifer,Xu Jiake,Zou Jun
Frontiers in pharmacology
Excessive bone resorption conducted by osteoclasts is considered as the main cause of osteoclast-related bone diseases such as osteoporosis. Therefore, the suppression of excessive osteoclast formation and function is one of the strategies to treat osteoclast-related bone diseases. Fumitremorgin C (Fum) is a mycotoxin extracted from . It has been shown to have extensive pharmacological properties, but its role in the treatment of osteoclast-related bone diseases remains unclear. In this study, we aim to find out whether Fum can inhibit the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and function. The results showed that Fum could significantly attenuate osteoclast formation and function at concentrations from 2.5 to 10 µM. The protein expression of bone resorption factors such as NFATc1, cathepsin K, V-ATPase-d2, and c-Fos was suppressed with the treatment of Fum at a concentration of 10 µM. In addition, Fum was also shown to suppress the activity of NF-κB, intracellular reactive oxygen species level, and MAPK pathway. Taken together, the present study showed that Fum could attenuate the formation and function of osteoclast suppressing RANKL-induced signaling pathways, suggesting that Fum might be a potential novel drug in the treatment of osteoclast-related bone diseases.
Evolutionary Perspectives on the Developing Skeleton and Implications for Lifelong Health.
Kralick Alexandra E,Zemel Babette S
Frontiers in endocrinology
Osteoporosis is a significant cause of morbidity and mortality in contemporary populations. This common disease of aging results from a state of bone fragility that occurs with low bone mass and loss of bone quality. Osteoporosis is thought to have origins in childhood. During growth and development, there are rapid gains in bone dimensions, mass, and strength. Peak bone mass is attained in young adulthood, well after the cessation of linear growth, and is a major determinant of osteoporosis later in life. Here we discuss the evolutionary implications of osteoporosis as a disease with developmental origins that is shaped by the interaction among genes, behavior, health status, and the environment during the attainment of peak bone mass. Studies of contemporary populations show that growth, body composition, sexual maturation, physical activity, nutritional status, and dietary intake are determinants of childhood bone accretion, and provide context for interpreting bone strength and osteoporosis in skeletal populations. Studies of skeletal populations demonstrate the role of subsistence strategies, social context, and occupation in the development of skeletal strength. Comparisons of contemporary living populations and archeological skeletal populations suggest declines in bone density and strength that have been occurring since the Pleistocene. Aspects of western lifestyles carry implications for optimal peak bone mass attainment and lifelong skeletal health, from increased longevity to circumstances during development such as obesity and sedentism. In light of these considerations, osteoporosis is a disease of contemporary human evolution and evolutionary perspectives provide a key lens for interpreting the changing global patterns of osteoporosis in human health.
Friend or Foe? Essential Roles of Osteoclast in Maintaining Skeletal Health.
Wang Haixing,Yang Guangpu,Xiao Yinbo,Luo Guotian,Li Gang,Li Ziqing
BioMed research international
Heightened activity of osteoclast is considered to be the culprit in breaking the balance during bone remodeling in pathological conditions, such as osteoporosis. As a "foe" of skeletal health, many antiosteoporosis therapies aim to inhibit osteoclastogenesis. However, bone remodeling is a dynamic process that requires the subtle coordination of osteoclasts and osteoblasts. Severe suppression of osteoclast differentiation will impair bone formation because of the coupling effect. Thus, understanding the complex roles of osteoclast in maintaining proper bone remodeling is highly warranted to develop better management of osteoporosis. This review aimed to determine the varied roles of osteoclasts in maintaining skeletal health and to highlight the positive roles of osteoclasts in maintaining normal bone remodeling. Generally, osteoclasts interact with osteocytes to initiate targeted bone remodeling and have crosstalk with mesenchymal stem cells and osteoblasts via secreted factors or cell-cell contact to promote bone formation. We believe that a better outcome of bone remodeling disorders will be achieved when proper strategies are made to coordinate osteoclasts and osteoblasts in managing such disorders.
MicroRNA Alterations for Diagnosis, Prognosis, and Treatment of Osteoporosis: A Comprehensive Review and Computational Functional Survey.
Hu Hai,He Xiaodi,Zhang Yazhong,Wu Rongrong,Chen Jiajia,Lin Yuxin,Shen Bairong
Frontiers in genetics
Osteoporosis (OP) is a systemic bone disease with a series of clinical symptoms. The use of screening biomarkers in OP management is therefore of clinical significance, especially in the era of precision medicine and intelligent healthcare. MicroRNAs (miRNAs) are small, non-coding RNAs with the potential to regulate gene expression at the post-transcriptional level. Accumulating evidence indicates that miRNAs may serve as biomarkers for OP prediction and prevention. However, few studies have emphasized the role of miRNAs in systems-level pathogenesis during OP development. In this article, literature-reported OP miRNAs were manually collected and analyzed based on a systems biology paradigm. Functional enrichment studies were performed to decode the underlying mechanisms of miRNAs in OP etiology and therapeutics in three-dimensional space, i.e., integrated miRNA-gene-pathway analysis. In particular, interactions between miRNAs and three well-known OP pathways, i.e., estrogen-endocrine, WNT/β-catenin signaling, and RANKL/RANK/OPG, were systematically investigated, and the effects of non-genetic factors on personalized OP prevention and therapy were discussed. This article is a comprehensive review of OP miRNAs, and bridges the gap between an understanding of OP pathogenesis and clinical translation.
miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway.
Meng Yi-Chen,Lin Tao,Jiang Heng,Zhang Zheng,Shu Lun,Yin Jia,Ma Xiao,Wang Ce,Gao Rui,Zhou Xu-Hui
Molecular therapy. Nucleic acids
Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could regulate osteoblast differentiation in ovariectomized rats with osteoporosis. miR-122 was upregulated and Purkinje cell protein 4 (PCP4) was downregulated in ovariectomized rats. PCP4 was identified as a target of miR-122 by dual-luciferase reporter gene assay. We transfected isolated osteoblasts from ovariectomized rats with miR-122 mimic or inhibitor or PCP4 overexpression vectors. Proliferation and differentiation of osteoblasts were repressed by the overexpression of miR-122 but enhanced by overexpression of PCP4. miR-122 could induce the activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, while PCP4 blocked this pathway. Rescue experiments further demonstrated that the inhibiting effects of miR-122 on osteoblast differentiation could be compensated by activation of the PCP4 or inhibition of JNK signaling pathway. Collectively, our data imply that miR-122 inhibits osteoblast proliferation and differentiation in rats with osteoporosis, highlighting a novel therapeutic target for osteoporotic patients.
Executive summary of the European guidance for the diagnosis and management of osteoporosis in postmenopausal women.
Kanis J A,Cooper C,Rizzoli R,Reginster J-Y,
Calcified tissue international
A guidance on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis was recently published in Osteoporosis International as a joint effort of the International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (Kanis et al. in Osteoporos Int https://doi.org/10.1007/s00198-018-4704-5 , 2018). This manuscript updates the previous guidelines document, published in 2013 (Kanis et al. in Osteoporos Int 24:23-57, 2013) and is written in a European perspective. The present article reports and summarizes the main recommendations included in this 2018 guidance document.
Postmenopausal osteoporosis: Assessment and management.
Best practice & research. Clinical endocrinology & metabolism
Osteoporosis increases the risk of fractures, which are associated with increased mortality and lower quality of life. Patients with prevalent fracture are at high risk to of sustaining another one. Optimal protein and calcium intakes, and vitamin D supplies, together with regular weight bearing physical exercise are the corner stones of fracture prevention. Evidence for anti-fracture efficacy of pharmacological interventions relies on results from randomised controlled trials in postmenopausal women with fractures as the primary outcome. Treatments with bone resorption inhibitors, like bisphosphonates or denosumab, and bone formation stimulator like teriparatide, reduce vertebral and non-vertebral fracture risk. A reduction in vertebral fracture risk can already be detected within a year after starting therapy.
Fruit and vegetable consumption and the risk of postmenopausal osteoporosis: a meta-analysis of observational studies.
Hu Danqing,Cheng Lixiao,Jiang Wenjie
Food & function
The association of the consumption of fruit and vegetables (FV) and the risk of postmenopausal osteoporosis (PMOP) has been a controversial subject. Thus, we carried out a meta-analysis to evaluate the association of FV consumption and the risk of PMOP. PubMed, Web of Science and Wan Fang were searched for relevant articles published up to March 2018. To evaluate the association of FV intake and PMOP risk, combined odds ratio (OR) and 95% confidence intervals (CIs) were calculated with the fixed or random effects model. Eighteen studies involving 12 643 participants were included in this meta-analysis. When comparing the highest with the lowest consumption, the pooled OR of PMOP was 0.68 (95% CI, 0.56-0.83; I2 = 57.3%; REM) for fruit and 0.87 (95% CI, 0.65-1.16; I2 = 68.9%; REM) for vegetables. For the intake of fruit and the risk of PMOP, subgroup analysis showed a significant association in case-control studies (OR, 0.52; 95% CI, 0.35-0.77; I2 = 3.1%; FEM) and cross-sectional studies (OR, 0.73; 95% CI, 0.59-0.89; I2 = 61.1%; REM). For the intake of vegetables and the risk of PMOP, subgroup analysis showed a significant association in case-control studies (OR, 0.62; 95% CI, 0.42-0.90; I2 = 0.0%; FEM) but not in cross-sectional studies (OR, 0.95; 95% CI, 0.69-1.29; I2 = 68.9%; REM). This meta-analysis indicates that fruit intake might be beneficial for the prevention of osteoporosis in postmenopausal women. The findings need to be confirmed by further investigations.
Calcium in the prevention of postmenopausal osteoporosis: EMAS clinical guide.
Cano Antonio,Chedraui Peter,Goulis Dimitrios G,Lopes Patrice,Mishra Gita,Mueck Alfred,Senturk Levent M,Simoncini Tommaso,Stevenson John C,Stute Petra,Tuomikoski Pauliina,Rees Margaret,Lambrinoudaki Irene
INTRODUCTION:Postmenopausal osteoporosis is a highly prevalent disease. Prevention through lifestyle measures includes an adequate calcium intake. Despite the guidance provided by scientific societies and governmental bodies worldwide, many issues remain unresolved. AIMS:To provide evidence regarding the impact of calcium intake on the prevention of postmenopausal osteoporosis and critically appraise current guidelines. MATERIALS AND METHODS:Literature review and consensus of expert opinion. RESULTS AND CONCLUSION:The recommended daily intake of calcium varies between 700 and 1200mg of elemental calcium, depending on the endorsing source. Although calcium can be derived either from the diet or supplements, the former source is preferred. Intake below the recommended amount may increase fragility fracture risk; however, there is no consistent evidence that calcium supplementation at, or above, recommended levels reduces risk. The addition of vitamin D may minimally reduce fractures, mainly among institutionalised people. Excessive intake of calcium, defined as higher than 2000mg/day, can be potentially harmful. Some studies demonstrated harm even at lower dosages. An increased risk for cardiovascular events, urolithiasis and even fractures has been found in association with excessive calcium intake, but this issue remains unresolved. In conclusion, an adequate intake of calcium is recommended for general bone health. Excessive calcium intake seems of no benefit, and could possibly be harmful.
Brazilian guidelines for the diagnosis and treatment of postmenopausal osteoporosis.
Radominski Sebastião Cézar,Bernardo Wanderley,Paula Ana Patrícia de,Albergaria Ben-Hur,Moreira Caio,Fernandes Cesar Eduardo,Castro Charlles H M,Zerbini Cristiano Augusto de Freitas,Domiciano Diogo S,Mendonça Laura M C,Pompei Luciano de Melo,Bezerra Mailze Campos,Loures Marco Antônio R,Wender Maria Celeste Osório,Lazaretti-Castro Marise,Pereira Rosa M R,Maeda Sergio Setsuo,Szejnfeld Vera Lúcia,Borba Victoria Z C
Revista brasileira de reumatologia
Osteoporosis is the leading cause of fractures in the population older than 50 years. This silent disease affects primarily postmenopausal women and the elderly, and the morbidity and mortality rates are high. The main goal of treating osteoporosis is the prevention of fractures. The identification of populations at risk through early diagnosis and treatment is essential. The last Brazilian guideline for the treatment of postmenopausal osteoporosis was elaborated in 2002. Since then, new strategies for diagnosis and risk stratification have been developed, and drugs with novel action mechanisms have been added to the therapeutic arsenal. The Osteoporosis and Osteometabolic Diseases Committee of the Brazilian Society of Rheumatology, in conjunction with the Brazilian Medical Association and other Societies, has developed this update of the guidelines for the treatment of postmenopausal osteoporosis according to the best scientific evidence available. This update is intended for professionals in many medical and health specialties involved in the treatment of osteoporosis, for physicians in general and for health-related organizations.
Cost-effectiveness of Virtual Bone Strength Testing in Osteoporosis Screening Programs for Postmenopausal Women in the United States.
Agten Christoph A,Ramme Austin J,Kang Stella,Honig Stephen,Chang Gregory
Purpose To investigate whether assessment of bone strength with quantitative computed tomography (CT) in combination with dual-energy x-ray absorptiometry (DXA) is cost-effective as a screening tool for osteoporosis in postmenopausal women. Materials and Methods A state-transition microsimulation model of osteoporosis for postmenopausal women aged 55 years or older was developed with a lifetime horizon and U.S. societal perspective. All model inputs were derived from published literature. Three strategies were compared: no screening, DXA with T score-dependent rescreening intervals, and a combination of DXA and quantitative CT with different intervals (3, 5, and 10 years) at different screening initiation ages (55-65 years). Oral bisphosphonate therapy was started if DXA hip T scores were less than or equal to -2.5, 10-year risk for hip fracture was greater than 3% (World Health Organization Fracture Risk Assessment Tool score, or FRAX), 10-year risk for major osteoporotic fracture was greater than 20% (FRAX), quantitative CT femur bone strength was less than 3000 N, or occurrence of first fracture (eg, hip, vertebral body, wrist). Outcome measures were incremental cost-effectiveness ratios (ICERs) in 2015 U.S. dollars per quality-adjusted life year (QALY) gained and number of fragility fractures. Probabilistic sensitivity analysis was also performed. Results The most cost-effective strategy was combined DXA and quantitative CT screening starting at age 55 with quantitative CT screening every 5 years (ICER, $2000 per QALY). With this strategy, 12.8% of postmenopausal women sustained hip fractures in their remaining life (no screening, 18.7%; DXA screening, 15.8%). The corresponding percentages of vertebral fractures for DXA and quantitative CT with a 5-year interval, was 7.5%; no screening, 11.1%; DXA screening, 9%; for wrist fractures, 14%, 17.8%, and 16.4%, respectively; for other fractures, 22.6%, 30.8%, and 27.3%, respectively. In probabilistic sensitivity analysis, DXA and quantitative CT at age 55 years with quantitative CT screening every 5 years was the best strategy in more than 90% of all 1000 simulations (for thresholds of $50 000 per QALY and $100 000 per QALY). Conclusion Combined assessment of bone strength and bone mineral density is a cost-effective strategy for osteoporosis screening in postmenopausal women and has the potential to prevent a substantial number of fragility fractures. RSNA, 2017 Online supplemental material is available for this article.
Two-year persistence and compliance with osteoporosis therapies among postmenopausal women in a commercially insured population in the United States.
Durden Emily,Pinto Lionel,Lopez-Gonzalez Lorena,Juneau Paul,Barron Richard
Archives of osteoporosis
This retrospective, observational study assessed 2-year persistence and compliance by treatment, route of administration, and dosing frequency in postmenopausal women initiating a new osteoporosis therapy. Two-year persistence and compliance rates were higher in women receiving injectables compared with oral agents. PURPOSE:This study extends previous studies limited to 1-year follow-up by examining persistence with osteoporosis therapies over a 2-year period and compares short- and long-term trends in persistence and compliance among postmenopausal women with commercial or Medicare supplemental insurance in the USA. METHODS:This retrospective, observational cohort study enrolled women ≥50 years newly initiating osteoporosis therapy between January 1 and December 31, 2012 (i.e., the index date), with continuous enrollment ≥14 months before and ≥24 months after their index date. Persistence (continuous therapy without a >60-day gap) and compliance with the index therapy were evaluated at 2 years of follow-up. Multivariable logistic regression was used to compare the odds of persistence and compliance across treatment and dosing regimens. RESULTS:This study included 43,543 patients with mean (standard deviation) age 65 (10) years. At 2 years of follow-up, persistence and compliance were higher for patients treated with injectable agents (ranging from 34 to 41%, excluding an every-3-month injection) than those treated with oral agents (ranging from 20 to 31%). Additionally, patients initiating oral bisphosphonates (except risedronate once daily), raloxifene (daily), or zoledronic acid (annually) had significantly lower odds of persistence compared with denosumab (every 6 months). CONCLUSIONS:Patients initiating injectable therapies had greater persistence and compliance at 2 years than those initiating oral therapies. Patients initiating an every-6-month injection had significantly higher persistence compared with those initiating more frequently dosed (e.g., daily and weekly) oral or injectable agents.
Expert Consensus on the Management of Patients with Postmenopausal Osteoporosis in the Spanish Healthcare System.
Del Pino-Montes Javier,Blanch Josep,Nogués Xavier,Moro María Jesús,Valero María Del Carmen,Canals Laura,Lizán Luis
Advances in therapy
INTRODUCTION:The management of postmenopausal osteoporosis (PMO) in routine clinical practice differs considerably from guideline recommendations. The objective of our study was to reach a consensus on the management of PMO, considering prevention, diagnosis, treatment and follow-up, according to expert opinion in Spain. METHODS:A two-round Delphi technique was conducted, including 38 experts. The questionnaire contained 35 sections, each one including 1-10 questions (n = 308) based on a literature review and contributions from the scientific steering committee. Each question was scored by experts from the current (1 = no occurrence, 9 = occurrence in all cases), wish (1 = total rejection; 9 = wish) and prediction (1 = no occurrence at all; 9 = occurs with maximum probability) perspectives. Consensus (wish and prediction perspectives) was considered when ≥75% of experts scored 7-9 (agreement) or 1-3 (disagreement). RESULTS:Overall, consensus was achieved on 75% of questions. While protocols of clinical management and consultation/referral should be followed, their implementation is unlikely. Furthermore, the medical specialties currently involved in PMO management are poorly defined. PMO patients without fracture should be managed (prevention, diagnosis, treatment and follow-up) in both primary care and rheumatology settings; however, experts predicted that only treatment and follow-up will be assumed by these specialties. A multidisciplinary team should be involved in patients with fracture. No assessment tools are usually applied, and prediction indicated that they will not be used. CONCLUSION:Efforts should be focused on questions with high divergence between wishes and predictions, defining actions that will improve PMO management. Collaboration between scientific societies and health authorities to address the identified opportunities of improvement is proposed. FUNDING:Amgen S.A.
Clinical Practice. Postmenopausal Osteoporosis.
Black Dennis M,Rosen Clifford J
The New England journal of medicine
Key Clinical Points Postmenopausal Osteoporosis Fractures and osteoporosis are common, particularly among older women, and hip fractures can be devastating. Treatment is generally recommended in postmenopausal women who have a bone mineral density T score of -2.5 or less, a history of spine or hip fracture, or a Fracture Risk Assessment Tool (FRAX) score indicating increased fracture risk. Bisphosphonates (generic) and denosumab reduce the risk of hip, nonvertebral, and vertebral fractures; bisphosphonates are commonly used as first-line treatment in women who do not have contraindications. Teriparatide reduces the risk of nonvertebral and vertebral fractures. Osteonecrosis of the jaw and atypical femur fractures have been reported with treatment but are rare. The benefit-to-risk ratio for osteoporosis treatment is strongly positive for most women with osteoporosis. Because benefits are retained after discontinuation of alendronate or zoledronic acid, drug holidays after 5 years of alendronate therapy or 3 years of zoledronic acid therapy may be considered for patients at lower risk for fracture.
Prevention and rehabilitation of osteoporosis.
Wiener medizinische Wochenschrift (1946)
Osteoporosis is a frequent disease in postmenopausal women. Despite the fact that fragility fractures cause many problems, osteoporosis is still underdiagnosed and undertreated. This manuscript outlines the topics diagnosis of osteoporosis, fracture risk prevention, and therapy after fracture. Regular physical activities, a sufficient intake of calcium, and a normal vitamin D level are important for bone health. Depending on the personal fracture risk, the patient may also be prescribed bone-specific medication to prevent fragility fractures. In case of a prevalent osteoporotic fracture, the initiation or adaptation of bone-specific therapy is indispensable. Since most osteoporotic fractures occur during a fall, fall risk reduction is an important measure to inhibit a new fracture. Rehabilitation of patients with fragility fractures varies with different localizations of the fracture and should be performed by a multidisciplinary team.
The safety and tolerability profile of therapies for the prevention and treatment of osteoporosis in postmenopausal women.
Komm Barry S,Morgenstern Diana,A Yamamoto Luis,Jenkins Simon N
Expert review of clinical pharmacology
At a time when the prevalence of osteoporosis and related fractures is increasing, initiation and continuation of pharmacologic therapies for prevention and treatment of postmenopausal osteoporosis have declined. This decline has been at least in part attributable to concerns about safety of these agents, such as atypical fractures with bisphosphonates and breast cancer with estrogen/progestin therapy, particularly when they are used long term by older women. However, in many cases, absolute risk of serious adverse effects is small and should be balanced against the larger potential for fracture reduction. Here, we review the safety and tolerability of available therapies for postmenopausal osteoporosis. Taking into consideration their relative efficacy, we also provide strategies for optimization of the risk:benefit ratio.
Impact of Dietary Habits and Physical Activity on Bone Health among 40 to 60 Year Old Females at Risk of Osteoporosis in India.
Munshi Rafiya,Kochhar Anita,Garg Vishal
Ecology of food and nutrition
Osteoporosis is a disorder of bones with increasing risk among women. However, a number of modifiable factors can help in combating this disorder. Present study examined the relationship of diet and physical activity and risk of osteoporosis through biochemical tests, bone mass density (BMD) scores, and standard questionnaires. Genetic risk for osteoporosis, presence of osteoarthritis, and thyroid problems were found among 8%, 7%, and 3% of participants, respectively; and 78% had onset of menopause between 47 to 55 years of age. Results revealed that less intake of proteins, minerals, and diverse fruit and vegetable consumption was significantly (p≤0.05; 0.01) correlated with decreased BMD score and serum calcium. It was concluded that adequate intake of varied fruits and vegetables, good protein, habit of daily physical activity, adequate sun exposure, and dietary calcium, may play a promising role in decreasing the risk of osteoporosis among women of this age group.
Adiponectin stimulates Rho-mediated actin cytoskeleton remodeling and glucose uptake via APPL1 in primary cardiomyocytes.
Palanivel Rengasamy,Ganguly Riya,Turdi Subat,Xu Aimin,Sweeney Gary
Metabolism: clinical and experimental
OBJECTIVE:Adiponectin is known to confer its cardioprotective effects in obesity and type 2 diabetes, mainly by regulating glucose and fatty acid metabolism in cardiomyocytes. Dynamic actin cytoskeleton remodeling is involved in regulation of multiple biological functions, including glucose uptake. Here we investigated in neonatal cardiomyocytes whether adiponectin induced actin cytoskeleton remodeling and if this played a role in adiponectin-stimulated glucose uptake. MATERIALS/METHODS:Primary cardiomyocytes were treated with full-length and globular adiponectin (fAd and gAd, respectively). RESULTS:Both fAd and gAd increased RhoA activity, phosphorylation of the Rho/ROCK signaling target cofilin and actin polymerization to form filamentous actin as determined by rhodamine-phallodin immunofluorescence and quantitative analysis of filamentous to globular actin ratio. Scanning electron microscopy also demonstrated structural remodeling. Adiponectin stimulated glucose uptake, was significantly abrogated in the presence of inhibitors of actin cytoskeleton remodeling (cytochalasin D) and Rho/ROCK signaling (C3 transferase, Y27632). We showed that adiponectin increased colocalization of actin and APPL1 and that actin remodeling, phosphorylation of AMPK, p38MAPK and cofilin, glucose uptake and oxidation were all attenuated after siRNA-mediated knockdown of APPL1. CONCLUSION:We show that adiponectin mediates Rho/ROCK-dependent actin cytoskeleton remodeling to increase glucose uptake and metabolism via APPL1 signaling.