The Impact of Glucagon-Like Peptide 1 Receptor Agonists on Bone Metabolism and Its Possible Mechanisms in Osteoporosis Treatment.
Xie Baocheng,Chen Shichun,Xu Yongxiang,Han Weichao,Hu Runkai,Chen Minyi,Zhang Yusheng,Ding Shaobo
Frontiers in pharmacology
Diabetes mellitus and osteoporosis are closely related and have complex influencing factors. The impact of anti-diabetic drugs on bone metabolism has received more and more attention. Type 2 diabetes mellitus (T2DM) would lead to bone fragility, high risk of fracture, poor bone repair and other bone-related diseases. Furthermore, hypoglycemic drugs used to treat T2DM may have notable detrimental effects on bones. Thus, the clinically therapeutic strategy for T2DM should not only effectively control the patient's glucose levels, but also minimize the complications of bone metabolism diseases. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel and promising drug for the treatment of T2DM. Some studies have found that GLP-1RAs may play an anti-osteoporotic effect by controlling blood sugar levels, promoting bone formation and inhibiting bone resorption. However, in clinical practice, the specific effects of GLP-1RA on fracture risk and osteoporosis have not been clearly defined and evidenced. This review summarizes the current research findings by which GLP-1RAs treatment of diabetic osteoporosis, postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and describes possible mechanisms, such as GLP-1R/MAPK signaling pathway, GLP-1R/PI3K/AKT signaling pathway and Wnt/β-catenin pathway, that are associated with GLP-1RAs and osteoporosis. The specific role and related mechanisms of GLP-1RAs in the bone metabolism of patients with different types of osteoporosis need to be further explored and clarified.
10.3389/fphar.2021.697442
Trabecular bone score in adults with type 1 diabetes: a meta-analysis.
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
Type 1 diabetes mellitus (T1DM) is associated with a disproportionately high fracture rate despite a minimal decrease in bone mineral density. Though trabecular bone score (TBS), an indirect measure of bone architecture, is lower in adults with T1DM, the modest difference is unlikely to account for the large excess risk and calls for further exploration. INTRODUCTION:Fracture rates in type 1 diabetes mellitus (T1DM) are disproportionately high compared to the modestly low bone mineral density (BMD). Distortion of bone microarchitecture compromises bone quality in T1DM and is indirectly measured by trabecular bone score (TBS). TBS could potentially be used as a screening tool for skeletal assessment; however, there are inconsistencies in the studies evaluating TBS in T1DM. We performed this meta-analysis to address this knowledge gap. METHODS:An electronic literature search was conducted using PubMed, Scopus, and Web of Science resources (all-year time span) to identify studies relating to TBS in T1DM. Cross-sectional and retrospective studies in adults with T1DM were included. TBS and BMD data were extracted for pooled analysis. Fracture risk could not be analyzed as there were insufficient studies reporting it. RESULT:Data from six studies were included (T1DM: n = 378 and controls: n = 286). Pooled analysis showed a significantly lower TBS [standardized mean difference (SMD) = - 0.37, 95% CI - 0.52 to - 0.21; p < 0.00001] in T1DM compared to controls. There was no difference in the lumbar spine BMD (6 studies, SMD - 0.06, 95% CI - 0.22 to 0.09; p = 0.43) and total hip BMD (6 studies, SMD - 0.17, 95% CI - 0.35 to 0.01; p = 0.06) in the case and control groups. CONCLUSIONS:Adults with T1DM have a lower TBS but similar total hip and lumbar spine BMD compared to controls. The risk attributable to the significant but limited difference in TBS falls short of explaining the large excess propensity to fragility fracture in adults with T1DM. Further studies on clarification of the mechanism and whether TBS is suited to screen for fracture risk in adults with T1DM are necessary.
10.1007/s00198-023-06935-z
Association Between Abdominal Aortic Calcification, Bone Mineral Density, and Fracture in Older Women.
Lewis Joshua R,Eggermont Celeste J,Schousboe John T,Lim Wai H,Wong Germaine,Khoo Ben,Sim Marc,Yu MingXiang,Ueland Thor,Bollerslev Jens,Hodgson Jonathan M,Zhu Kun,Wilson Kevin E,Kiel Douglas P,Prince Richard L
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Although a relationship between vascular disease and osteoporosis has been recognized, its clinical importance for fracture risk evaluation remains uncertain. Abdominal aortic calcification (AAC), a recognized measure of vascular disease detected on single-energy images performed for vertebral fracture assessment, may also identify increased osteoporosis risk. In a prospective 10-year study of 1024 older predominantly white women (mean age 75.0 ± 2.6 years) from the Perth Longitudinal Study of Aging cohort, we evaluated the association between AAC, skeletal structure, and fractures. AAC and spine fracture were assessed at the time of hip densitometry and heel quantitative ultrasound. AAC was scored 0 to 24 (AAC24) and categorized into low AAC (score 0 and 1, n = 459), moderate AAC (score 2 to 5, n = 373), and severe AAC (score >6, n = 192). Prevalent vertebral fractures were calculated using the Genant semiquantitative method. AAC24 scores were inversely related to hip BMD ( r = -0.077, p = 0.013), heel broadband ultrasound attenuation ( r = -0.074, p = 0.020), and the Stiffness Index ( r = -0.073, p = 0.022). In cross-sectional analyses, women with moderate to severe AAC were more likely to have prevalent fracture and lumbar spine imaging-detected lumbar spine fractures, but not thoracic spine fractures (Mantel-Haenszel test of trend p < 0.05). For 10-year incident clinical fractures and fracture-related hospitalizations, women with moderate to severe AAC (AAC24 score >1) had increased fracture risk (HR 1.48; 95% CI, 1.15 to 1.91; p = 0.002; HR 1.46; 95% CI, 1.07 to 1.99; p = 0.019, respectively) compared with women with low AAC. This relationship remained significant after adjusting for age and hip BMD for clinical fractures (HR 1.40; 95% CI, 1.08 to 1.81; p = 0.010), but was attenuated for fracture-related hospitalizations (HR 1.33; 95% CI, 0.98 to 1.83; p = 0.073). In conclusion, older women with more marked AAC are at higher risk of fracture, not completely captured by bone structural predictors. These findings further support the concept that vascular calcification and bone pathology may share similar mechanisms of causation that remain to be fully elucidated © 2019 American Society for Bone and Mineral Research.
10.1002/jbmr.3830
Menopausal hormone therapy reduces the risk of fracture regardless of falls risk or baseline FRAX probability-results from the Women's Health Initiative hormone therapy trials.
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
In a combined analysis of 25,389 postmenopausal women aged 50-79 years, enrolled in the two Women's Health Initiative hormone therapy trials, menopausal hormone therapy vs. placebo reduced the risk of fracture regardless of baseline FRAX fracture probability and falls history. INTRODUCTION:The aim of this study was to determine if the anti-fracture efficacy of menopausal hormone therapy (MHT) differed by baseline falls history or fracture risk probability as estimated by FRAX, in a combined analysis of the two Women's Health Initiative (WHI) hormone therapy trials. METHODS:A total of 25,389 postmenopausal women aged 50-79 years were randomized to receive MHT (n = 12,739) or matching placebo (n = 12,650). At baseline, questionnaires were used to collect information on falls history, within the last 12 months, and clinical risk factors. FRAX 10-year probability of major osteoporotic fracture (MOF) was calculated without BMD. Incident clinical fractures were verified using medical records. An extension of Poisson regression was used to investigate the relationship between treatment and fractures in (1) the whole cohort; (2) those with prior falls; and (3) those without prior falls. The effect of baseline FRAX probability on efficacy was investigated in the whole cohort. RESULTS:Over 4.3 ± 2.1 years (mean ± SD), MHT (vs. placebo) significantly reduced the risk of any clinical fracture (hazard ratio [HR] 0.72 [95% CI, 0.65-0.78]), MOF (HR 0.60 [95% CI, 0.53-0.69]), and hip fracture (0.66 [95% CI, 0.45-0.96]). Treatment was effective in reducing the risk of any clinical fracture, MOF, and hip fracture in women regardless of baseline FRAX MOF probability, with no evidence of an interaction between MHT and FRAX (p > 0.30). Similarly, there was no interaction (p > 0.30) between MHT and prior falls. CONCLUSION:In the combined WHI trials, compared to placebo, MHT reduces fracture risk regardless of FRAX probability and falls history in postmenopausal women.
10.1007/s00198-022-06483-y
Prevalence of thyroid dysfunction in older Chinese patients with type 2 diabetes-A multicenter cross-sectional observational study across China.
PloS one
Type 2 diabetes [T2D] and thyroid dysfunction [TD] often co-occur, have overlapping pathologies, and their risk increases with age. Since 1995, universal salt iodization has been implemented in China to prevent disorders caused by iodine deficiency. However, after two decades of implementation of universal salt iodization, the prevalence of TD in elderly Chinese patients with T2D is not well described and may have been underestimated. We conducted a questionnaire-based survey across 24 endocrinology centers in China between December 2015 and July 2016. Demographic and clinical data from 1677 patients with T2D were obtained and analyzed to examine the prevalence of TD along with T2D in these patients. We assessed TD prevalence according to the four TD subtypes [subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and clinical hyperthyroidism], TD history, gender, and age. The diagnosis rates were calculated for TD and also for the TD subtype. The number of patients reaching treatment goals for T2D [hemoglobin A1c <7%] and TD [normal free thyroxine and thyroid-stimulating hormone [TSH]] and the incidences of complications and comorbidities were recorded. Among the enrolled patients with T2D [N = 1677], TD was diagnosed in 23.79% [399/1677] out of which 61% (245/399) were previously diagnosed and 38.59% (154/399) were newly diagnosed cases. Subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and clinical hyperthyroidism were reported in 4.89%, 9.3%, 1.13%, and 3.16% of the total population, respectively. Among patients previously diagnosed with TD, the incidence in women [166/795; 20.88%] was higher than in men [79/882; 8.96%]. The treatment goals for TD and T2D were attained in 39.6% [97/245] and 34.41% [577/1677] of the cases, respectively. Diabetic complications and comorbidities were reported in 99.7% of patients, with peripheral neuropathy being the most common [43.46%] followed by cataract [24.73%]. We had found that the incidences of dyslipidemia, elevated LDL levels, and osteoporosis were significantly higher in patients with TD than those without TD. TD is underdiagnosed in elderly Chinese patients with T2D.
10.1371/journal.pone.0216151
Links between arterial stiffness and bone mineral density in middle-aged and elderly Chinese individuals: a cross-sectional study.
Zhang Meng,Bai Lijuan,Kang Jing,Ge Jing,Peng Wen
BMJ open
OBJECTIVES:To explore whether bone mineral density (BMD) is associated with arterial stiffness in middle-aged and elderly people with an advanced arterial stiffness index as indicated by the cardio-ankle vascular index (CAVI). DESIGN:A cross-sectional study. SETTING:This study was conducted from September 2015 to May 2017 at the geriatrics department of a provincial medical centre in China. PARTICIPANTS:A total of 580 patients aged 50 and over were enrolled in the study. The mean age of the group was 64.82±11.4 years, and 63.1% were male. PRIMARY OUTCOME MEASURES:Associations of age with CAVI values and BMD. Associations between BMD and CAVI values. RESULTS:With increasing age, CAVI values gradually increased (p<0.001) and the femoral neck (FN) and total hip (TH) BMD gradually decreased (p<0.001, all). In the bivariate correlation analyses between the covariates and CAVI values, age and CAVI values showed the greatest positive correlation (r=0.631, p<0.001), and CAVI values were negatively correlated with FN BMD (r=-0.229, p<0.001) and TH BMD (r=-0.218, p<0.001). In the linear regression analyses, TH BMD (B=-1.812 (95% CI -2.475 to -1.149), p<0.001) and FN BMD (B=-1.968 (95% CI -2.651 to -1.284), p<0.001) were negatively correlated with CAVI values. After adjusting for age, gender, body mass index, smoking, history of cardiovascular or cerebrovascular disease, history of diabetes mellitus, systolic blood pressure, high-density lipoprotein cholesterol, blood uric acid, fibrinogen and estimated glomerular filtration rate, only TH BMD was still negatively correlated with CAVI values (B=-0.843 (95%CI -1.454 to -0.232), p=0.007). However, there was no consistent and significant correlation between lumbar spine BMD and CAVI values. CONCLUSION:In this cross-sectional study, a significant correlation between TH BMD and CAVI values was observed in middle-aged and elderly Chinese inpatients. However, our cohort was a small sample of inpatients, and prospective studies from more centres are expected.
10.1136/bmjopen-2019-029946
Adherence to Daily, Weekly, and Monthly Dosing Regimens of Bisphosphonates for Osteoporosis Treatment in Postmenopausal Women in Japan: A Retrospective Study Using Claims Data.
Kosaka Yuki,Sugiyama Takehiro,Hara Konan,Kobayashi Yasuki
The Tohoku journal of experimental medicine
Poor medication adherence of osteoporosis patients is a major global medical problem because of its negative impact on health outcomes and quality of life. The aim of this study was to evaluate how differences in dosing regimens influence adherence to oral bisphosphonates using data from a large health insurance provider in Japan. This was a retrospective observational study using claims data obtained between October 2012 and January 2018, from the community-based National Health Insurance program of a large city in Japan. The data included in the analysis were obtained from women 60 to 74 years old whose oral bisphosphonate prescription was detected between April 2013 and February 2017. Treatment adherence was monitored from the initial prescription for one year, i.e., up to January 2018. Primary comparisons among the daily-dosing, weekly-dosing, and monthly-dosing groups were based on the mean medication possession ratio (MPR). Data from a total of 3,958 patients were analyzed. The numbers of patients aged 60-64, 65-69, and 70-74 were 425, 1,400, and 2,133, respectively. The highest mean MPR was 69.4% for the monthly-dosing of bisphosphonates, followed by the weekly-dosing at 63.5%, and daily-dosing at 57.2%. Using the Kruskal-Wallis test with Dunn-Bonferroni correction, there were significant differences in mean MPR for daily versus weekly (p < 0.01), daily versus monthly (p < 0.001), and weekly versus monthly dosing regimens (p < 0.05). These results suggest significantly more patients adhere to a monthly or weekly regimen of bisphosphonates in the treatment of osteoporosis than to a daily regimen.
10.1620/tjem.255.147
Bone Turnover Is Suppressed in Insulin Resistance, Independent of Adiposity.
Tonks Katherine T,White Christopher P,Center Jacqueline R,Samocha-Bonet Dorit,Greenfield Jerry R
The Journal of clinical endocrinology and metabolism
CONTEXT:The contribution of insulin resistance vs adiposity to bone mineral density (BMD), bone turnover, and fractures in humans remains unclear. OBJECTIVE:To evaluate BMD and bone turnover markers (BTMs) in lean (n = 18) and overweight/obese individuals with (n = 17) and without (n = 34, insulin-sensitive [Obsensitive, n=15] or insulin-resistant [Obresistant, n=19] by homeostasis model assessment insulin resistance) diabetes mellitus. DESIGN:Observational study. OUTCOME MEASURES:Insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp; whole body BMD and fat mass (FM) using dual energy X-ray absorptiometry; and by measurement of BTMs [osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), and collagen type 1 cross-linked C-terminal telopeptide (CTx)], with the patient fasting and during clamp hyperinsulinemia. RESULTS:Fasting BTMs correlated with glucose infusion rate/fat-free mass (GIR/FFM) and adiponectin and, inversely, with fasting insulin and visceral fat (P ≤ 0.04 for all). Obsensitive, Obresistant, and diabetic individuals were matched by their FM percentage. Clamp GIR/FFM was similar in the lean and Obsensitive subjects (P = 1) and approximately twofold greater (P < 0.001) than in the Obresistant and diabetic subjects. BMD was greater in Obresistant than in Obsensitive (P = 0.04) and lean (P = 0.001) subjects. At baseline, compared with Obsensitive and lean subjects, Obresistant and diabetic individuals had lower OC, P1NP, and CTx levels. This reached statistical significance for Obresistant vs lean and Obresistant vs Obsensitive for both OC and CTx and for diabetic vs lean for CTx (P ≤ 0.04 for all). During hyperinsulinemia, lean individuals suppressed CTx more than did diabetic individuals (P = 0.03). On multiple regression analysis, visceral adiposity explained 16.7% and 19.3% of the baseline OC and CTx variability, respectively. CONCLUSIONS:Increased visceral adiposity and higher fasting insulin in insulin-resistant states are associated with lower fasting OC and CTx and failure to further suppress with more insulin.
10.1210/jc.2016-3282
Association of serum uric acid levels with osteoporosis and bone turnover markers in a Chinese population.
Yan Dan-Dan,Wang Jie,Hou Xu-Hong,Bao Yu-Qian,Zhang Zhen-Lin,Hu Cheng,Jia Wei-Ping
Acta pharmacologica Sinica
Recent evidence shows that uric acid is protective against some neurological diseases, but can be detrimental in many metabolic and cardiovascular disorders. In this study, we examined the association between serum uric acid levels and bone metabolism in Chinese males and postmenopausal females. A total of 943 males and 4256 postmenopausal females were recruited in Shanghai. The levels of serum uric acid and bone turnover markers (BTMs) were detected along with other biochemical traits. In addition, the fat distribution was calculated through MRI and image analysis software, and bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry. For postmenopausal females, the prevalence of osteoporosis was significantly lower in the hyperuricemia group compared with the normouricemic group (P=4.65E-06). In females, serum uric acid level was significantly associated with osteoporosis, with odds ratio (OR) and 95% confidence interval (95% CI) of 0.844 [0.763; 0.933] (P=0.0009) after adjusting for age, body mass index, HbA1c, lean mass, visceral and subcutaneous fat areas, albumin, 25-hydroxyvitamin D3 [25(OH)D3], and parathyroid hormone (PTH). In females, serum uric acid level was positively correlated with the BMD of the femoral neck (β±SE: 0.0463±0.0161; P=0.0042), total hip (β±SE: 0.0433±0.0149; P=0.0038) and L1-4 (β±SE: 0.0628±0.0165; P=0.0001) after further adjusting for age, BMI, HbA1c, lean mass, VFA, SFA, albumin, 25(OH)D3 and PTH. Regarding BTMs, serum uric acid level was negatively correlated with N-terminal procollagen of type I collagen (PINP) in females (β±SE: -0.1311±0.0508; P=0.0100). In summary, our results suggest that uric acid has a protective effect on bone metabolism independent of body composition in Chinese postmenopausal females.
10.1038/aps.2017.165
Type 2 diabetes and risk of low-energy fractures in postmenopausal women: meta-analysis of observational studies.
Dytfeld Joanna,Michalak Michał
Aging clinical and experimental research
BACKGROUND:Observational studies on osteoporotic fractures in patients with type 2 diabetes indicate their increased incidence compared to those without diabetes, but results are inconsistent. Currently, type 2 diabetes is not considered as an independent risk factor for low-energy fractures in elder subjects. The aim of the study was to assess the association between type 2 diabetes and risk for hip and vertebral fractures in postmenopausal women. MATERIALS AND METHODS:We searched Medline, Web of Science and Cochrane databases for articles published before September 2013. Studies assessing fractures in women aged >50 diagnosed with type 2 diabetes, regardless of the diabetes treatment, were deemed eligible. To estimate fracture risk meta-analysis in a random effect model was performed. The results were shown by the odds ratio (OR) and 95 % confidence interval (CI). Heterogeneity was tested using a Q-Cochrane test (significance was analyzed with p < 0.10) and I measure. RESULTS:A total of 15 observational studies (11 cohort and 4 cross-sectional, 263.006 diabetics and 502.115 controls) were included. Thirteen papers provided information on the incidence of hip fractures, and seven on vertebral ones. The meta-analysis revealed type 2 diabetes was associated with higher risk for hip fracture (OR 1.296, 95 % CI (1.069-1.571), but not vertebral fracture (OR = 1.134, 95 % CI (0.936-1.374). There was significant heterogeneity between hip fracture studies. American origin was identified as a potential source of such heterogeneity. CONCLUSIONS:The results of our meta-analysis indicate there is an increased risk for hip fracture in postmenopausal women with type 2 diabetes.
10.1007/s40520-016-0562-1
Effects of glucagon-like peptide 1 receptor agonists on comorbidities in older patients with diabetes mellitus.
Onoviran Olusola F,Li Dongming,Toombs Smith Sarah,Raji Mukaila A
Therapeutic advances in chronic disease
Elderly patients with diabetes are at high risk of polypharmacy because of multiple coexisting diseases and syndromes. Polypharmacy increases the risk of drug-drug and drug-disease interactions in these patients, who may already have age-related sensory and cognitive deficits; such deficits may delay timely communication of early symptoms of adverse drug events. Several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved for diabetes: liraglutide, exenatide, lixisenatide, dulagluatide, semaglutide, and albiglutide. Some are also approved for treatment of obesity. The current review of literature along with clinical case discussion provides evidence supporting GLP-1 RAs as diabetes medications for polypharmacy reduction in older diabetes patients because of their multiple pleiotropic effects on comorbidities (e.g. hyperlipidemia, hypertension, and fatty liver) and syndromes (e.g. osteoporosis and sleep apnea) that commonly co-occur with diabetes. Using one medication (in this case, GLP-1 RAs) to address multiple conditions may help reduce costs, medication burden, adverse drug events, and medication nonadherence.
10.1177/2040622319862691
Relationship between carotid or coronary artery calcification and osteoporosis in the elderly.
Zhu Jie,Guo Feng,Zhang Jie,Mu Chunli
Minerva medica
BACKGROUND:The aim of this study was to investigate the correlation between senile osteoporosis and calcified plaques in the arteries and to study the common potential risk factors for loss of bone mass and calcified plaques in the arteries. METHODS:Eligible patients (≥60 years old) who received treatment in our hospital from January 2016 to December2016 were included in this study. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). Multivariate regression model was used to analyze the correlation of osteoporosis and loss of bone mass with the risk of calcified plaques in the carotid and coronary arteries. RESULTS:Compared with plaque-free group, patients in the group with calcified plaques were older with a lower BMD, more cases of hypertension, diabetes and hyperlipidemia, higher levels of osteoprotegerin and leptin in serum and lower levels of serum adiponectin and 25 (OH) D. Severe loss of bone mass, osteoporosis and decreased serum level of 25 (OH) D were correlated with the occurrence of calcified plaques in the arteries after confounding factors such as age were adjusted. Severe loss of bone mass was remarkably correlative with the risk of calcified plaques and coexisting calcified plaques in the carotid and coronary arteries after confounding factors such as age were adjusted. CONCLUSIONS:Osteoporosis and severe loss of bone mass are closely related to plaques in the carotid and coronary arteries. The elderly population with severe low bone mass is the key target population for the prevention of cardiovascular events.
10.23736/S0026-4806.18.05632-X
Advanced glycation end products in musculoskeletal system and disorders.
Methods (San Diego, Calif.)
The human population is ageing globally, and the number of old people is increasing yearly. Diabetes is common in the elderly, and the number of diabetic patients is also increasing. Elderly and diabetic patients often have musculoskeletal disorder, which are associated with advanced glycation end products (AGEs). AGEs are heterogeneous molecules derived from non-enzymatic products of the reaction of glucose or other sugar derivatives with proteins or lipids, and many different types of AGEs have been identified. AGEs are a biomarker for ageing and for evaluating disease conditions. Fluorescence, spectroscopy, mass spectrometry, chromatography, and immunological methods are commonly used to measure AGEs, but there is no standardized evaluation method because of the heterogeneity of AGEs. The formation of AGEs is irreversible, and they accumulate in tissue, eventually causing damage. AGE accumulation has been confirmed in neuromusculoskeletal tissues, including bones, cartilage, muscles, tendons, ligaments, and nerves, where they adversely affect biomechanical properties by causing charge changes and forming cross-linkages. AGEs also bind to receptors, such as the receptor for AGEs (RAGE), and induce inflammation by intracellular signal transduction. These mechanisms cause many varied aging and diabetes-related pathological conditions, such as osteoporosis, osteoarthritis, sarcopenia, tendinopathy, and neuropathy. Understanding of AGEs related pathomechanism may lead to develop novel methods for the prevention and therapy of such disorders which affect patients' quality of life. Herein, we critically review the current methodology used for detecting AGEs, and present potential mechanisms by which AGEs cause or exacerbate musculoskeletal disorders.
10.1016/j.ymeth.2020.09.012
Diabetes pharmacotherapy and effects on the musculoskeletal system.
Diabetes/metabolism research and reviews
Persons with type 1 or type 2 diabetes have a significantly higher fracture risk than age-matched persons without diabetes, attributed to disease-specific deficits in the microarchitecture and material properties of bone tissue. Therefore, independent effects of diabetes drugs on skeletal integrity are vitally important. Studies of incretin-based therapies have shown divergent effects of different agents on fracture risk, including detrimental, beneficial, and neutral effects. The sulfonylurea class of drugs, owing to its hypoglycemic potential, is thought to amplify the risk of fall-related fractures, particularly in the elderly. Other agents such as the biguanides may, in fact, be osteo-anabolic. In contrast, despite similarly expected anabolic properties of insulin, data suggests that insulin pharmacotherapy itself, particularly in type 2 diabetes, may be a risk factor for fracture, negatively associated with determinants of bone quality and bone strength. Finally, sodium-dependent glucose co-transporter 2 inhibitors have been associated with an increased risk of atypical fractures in select populations, and possibly with an increase in lower extremity amputation with specific SGLT2I drugs. The role of skeletal muscle, as a potential mediator and determinant of bone quality, is also a relevant area of exploration. Currently, data regarding the impact of glucose lowering medications on diabetes-related muscle atrophy is more limited, although preclinical studies suggest that various hypoglycemic agents may have either aggravating (sulfonylureas, glinides) or repairing (thiazolidinediones, biguanides, incretins) effects on skeletal muscle atrophy, thereby influencing bone quality. Hence, the therapeutic efficacy of each hypoglycemic agent must also be evaluated in light of its impact, alone or in combination, on musculoskeletal health, when determining an individualized treatment approach. Moreover, the effect of newer medications (potentially seeking expanded clinical indication into the pediatric age range) on the growing skeleton is largely unknown. Herein, we review the available literature regarding effects of diabetes pharmacotherapy, by drug class and/or by clinical indication, on the musculoskeletal health of persons with diabetes.
10.1002/dmrr.3100
Analyses of the relationship between hyperuricemia and osteoporosis.
Lee Jung Woo,Kwon Bong Cheol,Choi Hyo Geun
Scientific reports
The aim of the present study was to evaluate the association between hyperuricemia and osteoporosis in a Korean population. Data from participants of the Korean Genome and Epidemiology Study who were ≥ 40 years old were collected from 2004 to 2016. Among 173,209 participants, 11,781 with hyperuricemia (> 7.0 mg/dL in men and > 6.0 mg/dL in women) and 156,580 controls were selected based on serum measurements. Odds ratios (ORs) of osteoporosis between individuals with hyperuricemia and controls were analyzed using a logistic regression model. In the adjusted model, age, sex, income group, body mass index, smoking, alcohol consumption, hypertension, diabetes mellitus, hyperlipidemia history and nutritional intake were adjusted. The adjusted OR (aOR) of osteoporosis was 0.79 [95% confidence interval (CI) = 0.71-0.87, P < 0.001]. In subgroup analyses according to age and sex, statistical significance was observed in men > 60 years old and in women > 50 years old. In another subgroup analysis according to past medical history, significant differences were found according to hypertension (aOR = 0.83, 95% CI = 0.73-0.94, and 0.75, 95% CI = 0.64-0.87), diabetes mellitus (aOR = 0.77, 95% CI = 0.69-0.86), and hyperlipidemia (aOR = 0.74, 95% CI = 0.61-0.89, and 0.81, 95% CI = 0.72-0.91). This study demonstrated that hyperuricemia was associated with a decreased risk of osteoporosis.
10.1038/s41598-021-91570-z
Systematic Review: Are the Elderly With Diabetes Mellitus Type 2 Prone to Fragility Fractures?
Papaioannou Ioannis,Pantazidou Georgia,Kokkalis Zinon,Georgopoulos Neoklis,Jelastopulu Eleni
Cureus
Diabetes mellitus type 2 (T2DM) is an emerging public health issue with high prevalence rates among older adults while fragility fractures constitute a significant public health burden with a great impact. Osteoporosis is the most important metabolic bone disease in patients with diabetes mellitus. Based on current evidence, individuals with T2DM are more vulnerable to fragility fractures than their non-diabetic counterparts, although until now, there aren't any systematic reviews or meta-analyses concerning the impact of T2DM on the risk of fragility fractures in elderly patients. The aim of this study is to fill this gap in the current literature concerning this specific patient group. Literature in PubMed and Google Scholar was searched for relevant articles published up to January 2021. The keywords used were: elderly, diabetes mellitus type 2, and fragility fractures. Among the 180 articles retrieved, only four full-text articles were eligible and, finally, two studies (one population-based cohort study and one cross-sectional study) met the inclusion criteria for the review. Although we identified 15 records through the manual research, finally 17 records were included in the current review. The records retrieved from the manual research were 11 prospective cohort studies, two population-based studies, one prospective observational study, and one retrospective cohort study. The author's name, year of publication, country, type of study, and number of patients were reported. According to this systematic review, there is almost consensus about the increased prevalence of all kinds of fragility fractures and especially low-energy hip fractures among elderly patients with T2DM compared with their counterparts without T2DM while there is relative controversy concerning non-vertebral fractures. Vertebral fractures in the elderly with T2DM require further evaluation because the results from cohort studies are more conflicting. Finally, insulin usage can increase the possibility of fragility fractures and can even double this risk. Bone fragility should be recognized as a new complication of T2DM, especially in elderly patients, due to several additional aggravating factors such as senile osteoporosis, severe vitamin D deficiency, presence of many comorbidities, increased possibility of insulin usage, and the presence of diabetes-related complications (mainly neuropathy and retinopathy). Clinicians who treat these patients should be aware of the special diagnostic and therapeutic approaches concerning these patients.
10.7759/cureus.14514
Oxytocin and Bone: Review and Perspectives.
Breuil Véronique,Trojani Marie-Charlotte,Ez-Zoubir Amri
International journal of molecular sciences
Recent data demonstrate the anabolic effect of oxytocin on bone. Bone cells express oxytocin receptors. Oxytocin promotes osteoblasts differentiation and function, leading to an increased bone formation with no effect on bone resorption and an improvement of bone microarchitecture. Oxytocin is synthetized by osteoblasts, and this synthesis is stimulated by estrogen. Animal studies demonstrate a direct action of oxytocin on bone, as the systemic administration of oxytocin prevents and reverses the bone loss induced by estrogen deficiency. Although oxytocin is involved in bone formation in both sexes during development, oxytocin treatment has no effect on male osteoporosis, underlining the importance of estrogen that amplifies its local autocrine and paracrine secretion. There are few human data showing a decrease in the oxytocin serum level in anorexia nervosa independently of estrogen and in amenorrheic women associated with impaired bone microarchitecture; in post-menopausal women a higher oxytocin serum level is associated with higher bone density, but not in osteoporotic men. Oxytocin displays many effects that may be beneficial in the management of osteoporosis, cardiovascular diseases, cognitive disorders, breast cancer, diabetes and body fat gain, all age-related diseases affecting elderly women, opening exciting therapeutic perspectives, although the issue is to find a single route, dosage and schedule able to reach all these targets.
10.3390/ijms22168551
An update on therapies for the treatment of diabetes-induced osteoporosis.
Mohsin Sahar,Baniyas May Myh,AlDarmaki Reem Smh,Tekes Kornélia,Kalász Huba,Adeghate Ernest A
Expert opinion on biological therapy
: Currently, 424 million people aged between 20 and 79 years worldwide are diabetic. More than 25% of adults aged over 65 years in North America have Type 2 diabetes mellitus (DM). Diabetes-induced osteoporosis (DM-OS) is caused by chronic hyperglycemia, advanced glycated end products and oxidative stress. The increase in the prevalence of DM-OS has prompted researchers to develop new biological therapies for the management of DM-OS. : This review covered the current and novel biological agents used in the management of DM-OS. Data were retrieved from PubMed, Scopus, American Diabetes Association and International Osteoporosis Foundation websites, and ClinicalTrials.gov. The keywords for the search included: DM, osteoporosis, and management. : Several biological molecules have been examined in order to find efficient drugs for the treatment of DM-OS. These biological agents include anti-osteoporosis drugs: net anabolics (parathyroid hormone/analogs, androgens, calcilytics, anti-sclerostin antibody), net anti-resorptive osteoporosis drugs (calcitonin, estrogen, selective estrogen receptor modulators, bisphosphonates, RANKL antibody) and anti-diabetic drugs (alpha glucosidase inhibitors, sulfonylureas, biguanides, meglitinides, thiazolidinediones, GLP-1 receptor agonists, dipeptidylpeptidase-4 inhibitors, sodium glucose co-transporter-2 inhibitors, insulin). Biological medications that effectively decrease hyperglycemia and, at the same time, maintain bone health would be an ideal drug/drug combination for the treatment of DM-OS.
10.1080/14712598.2019.1618266
Osteoporosis and risk of fracture in patients with diabetes: an update.
Montagnani Andrea,Gonnelli Stefano,Alessandri Massimo,Nuti Ranuccio
Aging clinical and experimental research
Diabetes mellitus (DM) and osteoporotic fractures are two of the most important causes of mortality and morbidity in older subjects. Recent data report a close association between fragility fracture risk and DM of both type 1 (DM1) and type 2 (DM2). However, DM1 is associated with reduced bone mineral density (BMD), whereas patients with DM2 generally have normal or increased BMD. This apparent paradox may be explained by the fact that, at a given level of BMD, diabetic patients present lower bone quality with respect to non-diabetics, as shown by several studies reporting that diabetes may affect bone tissue by means of various mechanisms, including hyperinsulinemia, deposition of advanced glycosylation endproducts (AGEs) in collagen, reduced serum levels of IGF-1, hypercalciuria, renal failure, microangiopathy and inflammation. In addition, the propensity to fall and several comorbidities may further explain the higher fracture incidence in DM patients with respect to the general population. It is reasonable to expect that close metabolic control of diabetes may improve bone status, although its effect on reduction of fracture risk has not yet been demonstrated. However, metformin has a direct effect on bone tissue by reducing AGE accumulation, whereas insulin acts directly on osteoclast activity, and thiazolidinediones (TZD) may have a negative effect by switching mesenchymal progenitor cells to adipose rather than bone tissue. New prospects include the incretins, a class of antidiabetic drugs which may play a role linking nutrition and bone metabolism. Better knowledge on how diabetes and its treatments influence bone tissue may lie at the basis of effective prevention of bone fracture in diabetic patients. Thus, close glycemic control, adequate intake of calcium and vitamin D, screening for low BMD, and prevention and treatment of diabetic complications are key elements in the management of osteoporosis in both DM1 and DM2. Attention should be paid to treating diabetes with TZD in women with DM2, particularly if elderly. Lastly, patients with osteoporosis and diabetes should be offered the same pharmacological treatments as non-diabetics, although specific trials on the effects of anti-osteoporotic drugs in the diabetic population are lacking.
10.1007/bf03351073
Osteoporosis and Osteopenia Among Patients With Type 2 Diabetes Aged ≥50: Role of Sex and Clinical Characteristics.
Xu Hui,Wang Zhida,Li Xuerui,Fan Meijuan,Bao Cuiping,Yang Rongrong,Song Fei,Xu Weili,Qi Xiuying
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry
INTRODUCTION/BACKGROUND:Although some studies have explored the association of adiposity and life habits (such as smoking) with osteoporosis and osteopenia among type 2 diabetes mellitus (T2DM) patients, the association between diabetic clinical characteristics (especially hypoglycemic drug use) and osteoporosis/osteopenia remains unclear. This study aimed to investigate the relationship of clinical characteristics with osteoporosis and osteopenia among T2DM patients by sex. METHODS:A total of 1222 T2DM patients aged ≥50 were included in the present study. Information on demographic, anthropometric and clinical characteristics was collected from medical records. Bone mineral density was assessed by dual-energy X-ray absorptiometry densitometer. Multiple adjusted logistic regression analyses were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of osteoporosis and osteopenia related to clinical characteristics. RESULTS:Of all participants, the prevalence of osteoporosis and osteopenia was 9.2% and 41.3%, respectively, and they were higher in females (14.7% and 48.5%) than in males (2.8% and 33%). After adjustment for potential confounders, the results showed that overweight (OR = 0.59; 95% CI, 0.42-0.81) and obesity (OR = 0.35; 95% CI, 0.24-0.50) were related to decreased odds of osteoporosis and osteopenia in both male and female T2DM patients, poor glycemic control (OR = 1.63; 95% CI, 1.08-2.47) was associated with increased odds of osteoporosis and osteopenia in males, and metformin treatment (OR = 0.65; 95% CI, 0.43-0.99) was associated with decreased odds of osteoporosis and osteopenia in females. CONCLUSIONS:Better glycemic management and rational choice of antidiabetic medication might be promising to prevent osteoporosis in T2DM patients. Further longitudinal studies are warranted to explore the association between antidiabetic treatment and osteoporosis.
10.1016/j.jocd.2019.04.004
Lipid Levels Related to Osteoporosis in Patients with Type 2 Diabetes.
Wu Yujie,Xing Xuenong,Ye Shandong,Chen Chao,Wang Jumei
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
OBJECTIVE:Osteoporosis is a systemic skeletal disorder characterizedby reduced bone mass, deteriorated bone structure. Various studies have tried to evaluate the association between lipid level and osteoporosis, but the results were proved to be controversial. The objectives of this study are to assess the correlation between BMD and serum lipid levels, to determine independent variables associated with osteoporosis and osteopenia in men and postmenopausal women with type 2 diabetes (T2D). MATERIALS AND METHODS:All participants of the study were carried out biochemical analysis of blood and the analysis of the lipid profile that included total cholesterol (TC) and triglyceride (TG). Physical examination and dual-energy X-ray absorptiometry examination were performed. Multiple linear regression and multivariate logistic regression were used to evaluate associations between serum TC and TG levels and the osteoporosis or osteopenia. RESULTS:The level of serum TG was directly correlated with BMD at the lumbar spine in all patients in multiple linear regression models. After adjusting for potential confounding factors, decreased level of serum TG was independent risk factor for osteoporosis(p=0.022) in T2D patients. It also showed that a greater BMI was protective factor for osteoporosis (p=0.019) and lower level of β-CTX was an independent risk factor for osteopenia (p=0.008) and osteoporosis (p=0.001) in T2D patients. CONCLUSION:Among Chinese patients with type 2 diabetes, the decreased level of serum TG might indicate a risk of osteoporosis. Further research is needed to confirm the finding and to clarify the contradictions identified.
10.1055/a-0735-9361
Association of inflammatory markers with all-cause mortality and cardiovascular mortality in postmenopausal women with osteoporosis or osteopenia.
BMC women's health
BACKGROUND:The objective of the present study was to investigate whether associations exist between inflammatory biomarkers and all-cause mortality and cardiovascular disease (CVD) mortality in women with postmenopausal osteoporosis (PMOP) or osteopenia. METHODS:In this retrospective cohort study, data were obtained from the National Health and Nutrition Examination Survey database from the years 2007 to 2010, 2013 to 2014, and 2017 to 2018. The inflammatory biomarkers including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), neutrophil × platelet/lymphocyte (SII), neutrophil × monocyte/lymphocyte (SIRI), and neutrophil × monocyte × platelet/lymphocyte ratio (AISI) were calculated. RESULTS:A total of 2,834 women were included, with a median survival of 113.51 (3.15) months. During follow-up, 602 women died of all-cause mortality and 185 women died of CVD. NLR, MLR, SIRI, and AISI were significantly associated with all-cause mortality in postmenopausal women with osteoporosis or osteopenia. NLR, MLR, SIRI, and AISI were related to CVD mortality in postmenopausal women with osteoporosis or osteopenia (All P < 0.05). Based on the results of the subgroup analysis, AISI, SIRI, and MLR were associated with all-cause mortality and CVD mortality in postmenopausal women with PMOP or osteopenia who had a history of CVD and diabetes. AISI, SII, MLR, and NLR were associated with all-cause mortality and CVD mortality in PMOP or osteopenia women with a body mass index (BMI) > 25 kg/m. PLR was associated with all-cause mortality in PMOP or osteopenia women aged ≥ 65 years. CONCLUSION:Inflammatory biomarkers were correlated with mortality risk in the PMOP or osteopenia population. This finding may be helpful for the prognosis management of PMOP or osteopenia in postmenopausal women.
10.1186/s12905-023-02631-6
Plasma periostin as a biomarker of osteoporosis in postmenopausal women with type 2 diabetes.
Journal of bone and mineral metabolism
INTRODUCTION:Periostin, as an emerging biomarker, is involved in multiple steps in bone metabolism. This study aimed to investigate the correlation between periostin levels and bone mineral density as well as bone turnover markers in postmenopausal women with type 2 diabetes (T2DM). MATERIALS AND METHODS:This study was a cross-sectional study that included 164 postmenopausal women with T2DM as study subjects and 32 age-matched nondiabetic postmenopausal women with normal bone mineral density (BMD) as healthy control subjects. A total of 164 subjects with T2DM were then divided into three groups according to BMD: the normal BMD group (n = 29), the osteopenia group (n = 70), and the osteoporosis group (n = 65). The clinical data of all subjects along with the relevant biochemical parameter data were collected. Plasma periostin was detected using an enzyme-linked immunosorbent assay (ELISA). RESULTS:Plasma periostin levels were significantly increased in T2DM patients with normal BMD compared with healthy controls (p < 0.05). In the diabetic group, plasma periostin levels were significantly elevated with decreased BMD, were positively correlated with osteocalcin levels (r = 0.162, p = 0.039) and were inversely associated with femoral neck BMD (r = - 0.308, p < 0.001) and total femur BMD (r = - 0.295, p < 0.001). In the case of chronic complications, periostin levels were slightly increased in individuals with complications of diabetic retinopathy, diabetic nephropathy and fracture (p > 0.05). CONCLUSIONS:The current study demonstrated that plasma periostin levels were significantly associated with BMD in patients with T2DM, and periostin might act as a novel biochemical marker of osteoporosis in postmenopausal women with type 2 diabetes.
10.1007/s00774-020-01200-3
Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation.
Weaver C M,Alexander D D,Boushey C J,Dawson-Hughes B,Lappe J M,LeBoff M S,Liu S,Looker A C,Wallace T C,Wang D D
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
UNLABELLED:The aim was to meta-analyze randomized controlled trials of calcium plus vitamin D supplementation and fracture prevention. Meta-analysis showed a significant 15 % reduced risk of total fractures (summary relative risk estimate [SRRE], 0.85; 95 % confidence interval [CI], 0.73-0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56-0.87). INTRODUCTION:Calcium plus vitamin D supplementation has been widely recommended to prevent osteoporosis and subsequent fractures; however, considerable controversy exists regarding the association of such supplementation and fracture risk. The aim was to conduct a meta-analysis of randomized controlled trials [RCTs] of calcium plus vitamin D supplementation and fracture prevention in adults. METHODS:A PubMed literature search was conducted for the period from July 1, 2011 through July 31, 2015. RCTs reporting the effect of calcium plus vitamin D supplementation on fracture incidence were selected from English-language studies. Qualitative and quantitative information was extracted; random-effects meta-analyses were conducted to generate summary relative risk estimates (SRREs) for total and hip fractures. Statistical heterogeneity was assessed using Cochran's Q test and the I (2) statistic, and potential for publication bias was assessed. RESULTS:Of the citations retrieved, eight studies including 30,970 participants met criteria for inclusion in the primary analysis, reporting 195 hip fractures and 2231 total fractures. Meta-analysis of all studies showed that calcium plus vitamin D supplementation produced a statistically significant 15 % reduced risk of total fractures (SRRE, 0.85; 95 % confidence interval [CI], 0.73-0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56-0.87). Numerous sensitivity and subgroup analyses produced similar summary associations. A limitation is that this study utilized data from subgroup analysis of the Women's Health Initiative. CONCLUSIONS:This meta-analysis of RCTs supports the use of calcium plus vitamin D supplements as an intervention for fracture risk reduction in both community-dwelling and institutionalized middle-aged to older adults.
10.1007/s00198-015-3386-5
Metabolic and Nutritional Characteristics in Middle-Aged and Elderly Sarcopenia Patients with Type 2 Diabetes.
He Qinghua,Wang Xiuzhi,Yang Caizhe,Zhuang Xiaoming,Yue Yanfen,Jing Hongjiang,Hu Jing,Sun Mingxiao,Guo Lixin
Journal of diabetes research
Sarcopenia is considered to be a new complication of type 2 diabetes (T2DM) leading to increased risk of adverse outcome. We performed a survey to evaluate glucose metabolism and nutritional status in sarcopenia patients with T2DM. Diabetic participants aged ≥50 years were grouped into a probable sarcopenia group with low muscle strength ( = 405) and a nonsarcopenia group with normal muscle strength ( = 720) according to the revised recommendations from EWGSOP2 (2018). Compared to the controls, the probable sarcopenia participants were older and had lower waist-to-hip ratio and BMI, longer diabetes duration, higher fasting plasma glucose level and glycosylated hemoglobin (HbA1c), decreased estimated glomerular filtration rate and lower bone mineral content, lower fatless upper arm circumference, lower appendicular skeletal muscle mass index (ASMI), and muscle quality in both genders. Multivariable logistic regression analysis showed increased age, male, low BMI, and increased HbA1c, combined with diabetic nephropathy and decreased serum albumin levels, were risk factors associated with low muscle strength in diabetes patients. In conclusion, diabetic patients with sarcopenia had worse glucose metabolism and nutritional status, decreased renal function and reduced muscle quality ,and muscle mass with a greater likelihood of osteoporosis, who need an overall health management to improve outcomes. This clinical trial registration is registered with the Chinese Clinical Trial Registry, ChiCTR-EOC-15006901.
10.1155/2020/6973469
Sexual dimorphism in the relation between sex hormones and osteoporosis in patients with type 2 diabetes mellitus.
Journal of bone and mineral metabolism
INTRODUCTION:To investigate the association between sex hormones and osteoporosis in type 2 diabetic mellitus (T2DM) patients. MATERIALS AND METHODS:We performed a retrospective study in patients with T2DM. The patients were assigned into three groups (normal bone mineral density, osteopenia, and osteoporosis) in both sexes. The clinical characteristics, bone metabolic markers, and sex hormones were compared. The relationship between the sex hormones and osteoporosis was analyzed by ordinary regression analysis. Statistical analysis was performed using SPSS 26.0. RESULTS:A total of 795 T2DM patients (446 men ≥ 50 years old and 349 postmenopausal women) were identified and analyzed. The osteoporosis group had the lowest estradiol level in men (P = 0.013) and the highest follicle-stimulating hormone (FSH) level in women (P = 0.042). In the multivariate analysis, men with lower estradiol levels (< 87.96 pmol/L) had a nearly 1.6-fold increased risk for osteoporosis than those with the higher estradiol levels (> 122.82 pmol/L). In addition, women with lower FSH (< 41.17 IU/L) had nearly 0.6-fold for osteoporosis compared to those with higher FSH (> 60.83 IU/L) after adjusting for age, duration of T2DM, body mass index, pulse pressure, creatinine clearance, glycosylated hemoglobin, fasting C-peptide, and estradiol (in FSH) or FSH (in estradiol). CONCLUSION:In T2DM, the estrogen level was negatively correlated with osteoporosis in men, and the FSH level was positively correlated with the osteoporosis in women.
10.1007/s00774-021-01291-6
Prevalence and Risk Factors of Osteoporosis in Postmenopausal Women with Type 2 Diabetes Mellitus.
Raška Ivan,Rašková Mária,Zikán Vít,Škrha Jan
Central European journal of public health
OBJECTIVE:Patients with type 2 diabetes (T2DM) are at increased risk of fractures. The aim of this study is to analyze the prevalence and risk factors of osteoporosis and osteoporosis related fractures in postmenopausal women with T2DM. METHODS:A total of 112 postmenopausal women with T2DM and 171 control nondiabetic women received a standardized questionnaire on osteoporosis risk factors, and were evaluated for bone mineral density (BMD, by using a dual energy X-ray absorptiometry), biochemical markers of bone and glucose metabolism, soluble receptor for advanced glycation end products (sRAGE) and its gene polymorphisms (rs1800625 or rs2070600). RESULTS:In T2DM patients the prevalence of osteoporosis was 25% and low trauma vertebral (Vfx) and non-vertebral fractures were found in 8% and 19% women, respectively. When compared between subjects with and without fractures, there were no significant differences in BMD at any site between the groups, except for distal radius, which was significantly lower in T2DM women with Vfx (p<0.05 vs.non-fractured without osteoporosis). We found no associations between bone and glucose metabolism variables, sRAGE and BMD. No significant differences were observed in sRAGE levels according to their rs1800625, rs 2070600 genotype or fracture prevalence. Serum osteocalcin was significantly lower in T2DM women (p<0.01 vs. controls) and in T2DM women with Vfx (p<0.05) vs. non-fractured without osteoporosis. T2DM women with low daily walking activity (< 2 h daily) had significantly higher serum sclerostin levels (p<0.05 vs. those who were walking > 2 h daily). CONCLUSION:Diabetes-specific parameters as well as RAGE polymorphisms did not associate with BMD or fractures in T2DM postmenopausal women. Lower levels of osteocalcin, namely in those with Vfx and higher sclerostin levels in those with low daily walking activity suggest lower bone remodeling and/or decreased bone quality in T2DM.
10.21101/cejph.a4717
Does obesity mediate the relationship between diabetes and osteoporosis in Chinese elderly population?
He Pei,Zhong Jiao,Zhu Dong-Cheng,Ge Bing,Lei Shu-Feng,Deng Fei-Yan
American journal of human biology : the official journal of the Human Biology Council
OBJECTIVES:Diabetes mellitus (DM), osteoporosis (OP), and obesity (OB) are three complex diseases. OB is associated with both DM and OP, but it is unclear whether OB mediates association between DM and OP. The study aimed to investigate the potential mediation effects of OB on association between DM and bone mineral density (BMD) by the causal inference tests (CIT). METHODS:A total of 5682 Chinese aged over 65 years were enrolled in an ongoing cohort: Osteoporosis Preventive Project (OPP). Obesity-related indexes, including body mass index (BMI), waist circumference, and waist circumference-hip circumference-ratio (WHR), and BMD at total hip (TH) and femur neck (FN) were measured. RESULTS:Subjects with DM had significant greater values of age, weight, BMI, waist circumference, WHR, and BMD than non-DM subjects. BMD at TH and FN was significantly associated with DM (p < 0.05) with adjustment of age both in males and females. Further CIT showed that OB-related indexes (BMI, waist circumference, and WHR) are significantly mediators in the associations between DM and BMD in females, but not in males. Furthermore, the mediation effects of waist circumference were detected on DM and TH BMD in the females of normal-weight group. CONCLUSIONS:Obesity-related indexes, especially waist circumference, serve as significant mediator(s) between DM and OP in Chinese female elderly. Diabetes increases BMD by increasing obesity-related indexes. The findings established the intermediate role of OB underlying the association between DM and OP in human population.
10.1002/ajhb.23630
Menopause, hormone therapy and diabetes.
Stuenkel C A
Climacteric : the journal of the International Menopause Society
Over the past three decades, the prevalence of diabetes has increased four-fold. Coupled with the global obesity epidemic and aging of the world's population, a perfect metabolic storm is brewing. The influence of menopause and exogenous estrogen and progestogens must be included in this equation. In this review, criteria for diagnosing diabetes and recommendations for screening are described. The reported effects of menopause on diabetes risk in healthy women are reviewed as well as the relationship between established diabetes and the timing of menopause. The effects of menopausal hormone therapies (MHT) on glucose control in women with diabetes and the effect of MHT on diabetes risk in menopausal women without diabetes are described. Evidence-based strategies to prevent diabetes in midlife women are highlighted. The augmenting effect of diabetes on chronic health concerns of aging women, such as cardiovascular disease, osteoporosis, and cancer, along with current recommendations for screening and prevention are presented. Given the current demographics of today's world, the content of this review may apply to as many as one-third of the average practitioner's postmenopausal patient population.
10.1080/13697137.2016.1267723
Diabetes Is Associated with Musculoskeletal Pain, Osteoarthritis, Osteoporosis, and Rheumatoid Arthritis.
Journal of diabetes research
AIM:To investigate the associations between diabetes and musculoskeletal pain, osteoarthritis, osteoporosis, and rheumatoid arthritis. METHODS:Self-reported data were provided by the nationwide Danish National Health Survey 2013. Inclusion criteria were age ≥ 40 years and known diabetes status. The exposure variable was diabetes, and the outcome variables included musculoskeletal pain during the last 14 days in three body sites (back/lower back, limbs, and shoulder/neck), osteoarthritis, osteoporosis, and rheumatoid arthritis. Logistic regression analyses adjusted for age, gender, BMI, education, marital status, and physical activity were performed. RESULTS:9,238 participants with diabetes were 65.6 ± 11.0 (mean ± SD) years old; 55.6% were males. 99,980 participants without diabetes were 59.2 ± 11.8 years old; 46.7% were males. Diabetes was associated with back/lower back pain (OR 1.2 (CI 95% 1.1-1.2), < 0.001), pain in the limbs (1.4 (1.3-1.4), < 0.001), shoulder/neck pain (1.2 (1.1-1.3), < 0.001), osteoarthritis (1.3 (1.2-1.4), < 0.001), osteoporosis (1.2 (1.1-1.4), = 0.010), and rheumatoid arthritis (1.6 (1.4-1.7), < 0.001). In participants with diabetes, physical activity was associated with reduced pain (e.g., back/lower back pain (0.7 (0.6-0.7), < 0.001)). CONCLUSION:Diabetes was associated with elevated odds of having musculoskeletal pain. Diabetes was also associated with elevated odds of having osteoarthritis, osteoporosis, and rheumatoid arthritis. The most frequent disease in individuals with diabetes was osteoarthritis. The reported pain may have negative impacts on the level of physical activity. Health-care professionals should remember to inform patients with diabetes that musculoskeletal pain, osteoarthritis, osteoporosis, and rheumatoid arthritis are not contraindications to exercise training.
10.1155/2019/6324348
Hemoglobin level and osteoporosis in Chinese elders with type 2 diabetes mellitus.
Nutrition & diabetes
OBJECTIVES:Several studies demonstrated a positive relationship between hemoglobin level and bone mineral density (BMD). Thus, the association between hemoglobin concentration and osteoporosis in elders with type 2 diabetes mellitus (T2DM) was explored in this study. METHODS:Totally, 573 elders with T2DM were included in the study. BMD was measured by dual-energy X-ray absorptiometry. Hemoglobin levels were tested. The association between the hemoglobin level and osteoporosis was subjected to logistic regression analysis. RESULTS:For men, the hemoglobin levels were significantly lower in osteoporosis group than that in non-osteoporosis group (135.98 ± 16.20 vs. 142.84 ± 13.78 g/L, P = 0.002). Hemoglobin levels were positively related with BMD of total hip and femoral neck in men (r = 0.170, P = 0.004; r = 0.148, P = 0.012, respectively). After adjusting for age, body mass index (BMI), hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR) and 25-hydroxyvitamin D [25(OH) D], the hemoglobin level was related with a 0.97-fold lower risk of osteoporosis (odds ratio (OR): 0.97; 95% confidence interval (CI): 0.95-0.99; P = 0.004) in men, but no such association was found in women. CONCLUSION:Higher levels of hemoglobin play a protective role against osteoporosis in older men with T2DM.
10.1038/s41387-022-00198-z
Oxidative stress: A common pathological state in a high-risk population for osteoporosis.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Osteoporosis is becoming a major concern in the field of public health. The process of bone loss is insidious and does not directly induce obvious symptoms. Complications indicate an irreversible decrease in bone mass. The high-risk populations of osteoporosis, including postmenopausal women, elderly men, diabetic patients and obese individuals need regular bone mineral density testing and appropriate preventive treatment. However, the primary changes in these populations are different, increasing the difficulty of effective treatment of osteoporosis. Determining the core pathogenesis of osteoporosis helps improve the efficiency and efficacy of treatment among these populations. Oxidative stress is a common pathological state secondary to estrogen deficiency, aging, hyperglycemia and hyperlipemia. In this review, we divided oxidative stress into the direct effect of reactive oxygen species (ROS) and the reduction of antioxidant enzyme activity to discuss their roles in the development of osteoporosis. ROS initiated mitochondrial apoptotic signaling and suppressed osteogenic marker expression to weaken osteogenesis. MAPK and NF-κB signaling pathways mediated the positive effect of ROS on osteoclast differentiation. Antioxidant enzymes not only eliminate the negative effects of ROS, but also directly participate in the regulation of bone metabolism. Additionally, we also described the roles of proinflammatory factors and HIF-1α under the pathophysiological changes of inflammation and hypoxia, which provided a supplement of oxidative stress-induced osteoporosis. In conclusion, our review showed that oxidative stress was a common pathological state in a high-risk population for osteoporosis. Targeted oxidative stress treatment would greatly optimize the therapeutic schedule of various osteoporosis treatments.
10.1016/j.biopha.2023.114834
Predictors of osteoporotic fracture in postmenopausal women: a meta-analysis.
Journal of orthopaedic surgery and research
Osteoporosis affects more than 200 million women worldwide, with postmenopausal women being particularly susceptible to this condition and its severe sequelae disproportionately, such as osteoporotic fractures. To date, the current focus has been more on symptomatic treatment, rather than preventive measures. To address this, we performed a meta-analysis aiming to identify potential predictors of osteoporotic fractures in postmenopausal women, with the ultimate goal of identifying high-risk patients and exploring potential therapeutic approaches. We searched Embase, MEDLINE and Cochrane with search terms (postmenopausal AND fracture) AND ("risk factor" OR "predictive factor") in May 2022 for cohort and case-control studies on the predictors of osteoporotic fracture in postmenopausal women. Ten studies with 1,287,021 postmenopausal women were found eligible for analyses, in which the sample size ranged from 311 to 1,272,115. The surveyed date spanned from 1993 to 2021. Our results suggested that age, BMI, senior high school and above, parity ≥ 3, history of hypertension, history of diabetes mellitus, history of alcohol intake, age at menarche ≥ 15, age at menopause < 40, age at menopause > 50, estrogen use and vitamin D supplements were significantly associated with osteoporotic fracture in postmenopausal women. Our findings facilitate the early prediction of osteoporotic fracture in postmenopausal women and may contribute to potential therapeutic approaches. By focusing on preventive strategies and identifying high-risk individuals, we can work toward reducing the burden of osteoporosis-related fractures in this vulnerable population.
10.1186/s13018-023-04051-6
Diabetes and bone.
Archives of endocrinology and metabolism
Globally, one in 11 adults has diabetes mellitus of which 90% have type 2 diabetes. The numbers for osteoporosis are no less staggering: 1 in 3 women has a fracture after menopause, and the same is true for 1 in 5 men after the age of 50 years. Aging is associated with several physiological changes that cause insulin resistance and impaired insulin secretion, which in turn lead to hyperglycemia. The negative balance between bone resorption and formation is a natural process that appears after the fourth decade of life and lasts for the following decades, eroding the bone structure and increasing the risk of fractures. Not incidentally, it has been acknowledged that diabetes mellitus, regardless of whether type 1 or 2, is associated with an increased risk of fracture. The nuances that differentiate bone damage in the two main forms of diabetes are part of the intrinsic heterogeneity of diabetes, which is enhanced when associated with a condition as complex as osteoporosis. This narrative review addresses the main parameters related to the increased risk of fractures in individuals with diabetes, and the mutual factors affecting the treatment of diabetes mellitus and osteoporosis.
10.20945/2359-3997000000552
Hormones and Aging: An Endocrine Society Scientific Statement.
The Journal of clinical endocrinology and metabolism
Multiple changes occur across various endocrine systems as an individual ages. The understanding of the factors that cause age-related changes and how they should be managed clinically is evolving. This statement reviews the current state of research in the growth hormone, adrenal, ovarian, testicular, and thyroid axes, as well as in osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism, with a specific focus on older individuals. Each section describes the natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, key points, and scientific gaps. The goal of this statement is to inform future research that refines prevention and treatment strategies in age-associated endocrine conditions, with the goal of improving the health of older individuals.
10.1210/clinem/dgad225
The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity.
Frontiers in endocrinology
Osteoporosis is defined as a systemic skeletal disease characterized by decreased bone mass and micro-architectural deterioration leading to increased fracture risk. Osteoporosis incidence increases with age in both post-menopausal women and aging men. Among other important contributing factors to bone fragility observed in osteoporosis, that also affect the elderly population, are metabolic disturbances observed in obesity and Type 2 Diabetes (T2D). These metabolic complications are associated with impaired bone homeostasis and a higher fracture risk. Expansion of the Bone Marrow Adipose Tissue (BMAT), at the expense of decreased bone formation, is thought to be one of the key pathogenic mechanisms underlying osteoporosis and bone fragility in obesity and T2D. Our review provides a summary of mechanisms behind increased Bone Marrow Adiposity (BMA) during aging and highlights the pre-clinical and clinical studies connecting obesity and T2D, to BMA and bone fragility in aging osteoporotic women and men.
10.3389/fendo.2022.981487
Risk Factors for Osteoporosis in Postmenopausal Women.
Medical archives (Sarajevo, Bosnia and Herzegovina)
INTRODUCTION:Scientific studies show that many factors related to lifestyles affect the reduction of bone mineral density and osteoporosis in postmenopausal women. GOAL:The goal of this study was to determine whether smoking, drinking coffee and alcohol in menopausal women contribute to the reduction of bone mass and osteoporosis, as well as the impact of physical activity on bone mass. MATERIAL AND METHODS:The study was carried out as case study and matched controls. The group of cases consisted of 100 females in postmenopausal age, in which by the DEXA method was newly diagnosed osteoporosis at the Clinic of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center of RS during 2015-2016, while the control group consisted of 100 females in a postmenopausal age without diagnosed osteoporosis. The groups were matched by age (±2 years). In order to collect demographic data and information on risk factors for osteoporosis and lifestyle of patients was used the questionnaire Bone Mineral Density Questionnaire- Female of the Irish Association for osteoporosis. RESULTS:Testing the significance of differences in terms of smoking showed that the studied groups are statistically significantly different in terms of smoking (χ=24.025, p=0.000). In terms of consumption of coffee, a statistically significant difference was found between the group of cases and control group (χ=0.615, p=0.735). When observing the obtained information about the consumption of alcohol, we find that this preventable risk factor in the present study did not show as significant for osteoporosis in postmenopausal women (χ=4.35, p=0.114). Statistical analysis shows that there are significant differences between the group of cases and control group in terms of physical activity (χ=7.30, p=0.026). Analysis of the data of our study by univariate logistic regressions showed that smoking (p=0.000) was statistically significantly associated with osteoporosis, while physical activity is a protective factor for bone mass (p=0.036). Results of multivariate logistic regression showed that the independent risk factors for osteoporosis in postmenopausal women is smoking (OR=1.665; p=0.006). CONCLUSION:The results of our study show that smoking is an independent risk factor for osteoporosis in postmenopausal women, and physical activity is a protective factor for bone mass retention. Through education and certain preventive measures should be stressed the importance of these factors on bone health from the earliest period.
10.5455/medarh.2017.71.25-28
How to manage osteoporosis before the age of 50.
Rozenberg S,Bruyère O,Bergmann P,Cavalier E,Gielen E,Goemaere S,Kaufman J M,Lapauw B,Laurent M R,De Schepper J,Body J J
Maturitas
This narrative review discusses several aspects of the management of osteoporosis in patients under 50 years of age. Peak bone mass is genetically determined but can also be affected by lifestyle factors. Puberty constitutes a vulnerable period. Idiopathic osteoporosis is a rare, heterogeneous condition in young adults due in part to decreased osteoblast function and deficient bone acquisition. There are no evidence-based treatment recommendations. Drugs use can be proposed to elderly patients at very high risk. Diagnosis and management of osteoporosis in the young can be challenging, in particular in the absence of a manifest secondary cause. Young adults with low bone mineral density (BMD) do not necessarily have osteoporosis and it is important to avoid unnecessary treatment. A determination of BMD is recommended for premenopausal women who have had a fragility fracture or who have secondary causes of osteoporosis: secondary causes of excessive bone loss need to be excluded and treatment should be targeted. Adequate calcium, vitamin D, and a healthy lifestyle should be recommended. In the absence of fractures, conservative management is generally sufficient, but in rare cases, such as chemotherapy-induced osteoporosis, antiresorptive medication can be used. Osteoporosis in young men is most often of secondary origin and hypogonadism is a major cause; testosterone replacement therapy will improve BMD in these patients. Diabetes is characterized by major alterations in bone quality, implying that medical therapy should be started sooner than for other causes of osteoporosis. Primary hyperparathyroidism, hyperthyroidism, Cushing's syndrome and growth hormone deficiency or excess affect cortical bone more often than trabecular bone.
10.1016/j.maturitas.2020.05.004
The effects of vegetarian diets on bone health: A literature review.
Frontiers in endocrinology
In these recent years many people are adopting a vegetarian type diet due to the numerous positive health effects of this regimen such as the reduction of the incidence of many chronic disorders like diabetes, hypertension, obesity and cancer. However this diet is quite restrictive and so it could be possible to have a deficiency in some specific nutrients, increasing the risk of osteoporosis and fractures. Although there are conflicting results on the effects of the vegetarian diet on bone health and fracture incidence, it is always recommendable in vegetarian people to have an adequate intake of calcium and vitamin D, through an increased intake of supplements, natural and fortified foods, an adequate intake of protein, fruit, vegetables, as well as vitamin B12. The aim of this literature review is to revise the actual knowledge of the effect of some nutrients and vegetarian diets on bone health.
10.3389/fendo.2022.899375