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Context: Type 2 diabetes mellitus is associated with more rapid bone loss in women, but less evidence is available for men or those with prediabetes., Objective: To determine whether bone loss rate is affected by diabetes status in older men, we analyzed data from the Osteoporotic Fractures in Men (MrOS) study., Methods: The multisite MrOS study enrolled 5994 men aged ≥ 65 years. Diabetes status was defined by self-report, diabetes medication use, or elevated fasting serum glucose at baseline. Hip bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA) at baseline and a follow-up visit after 4.6 ± 0.4 years. This analysis included 4095 men, excluding those without follow-up DXA or with unknown diabetes status. Changes in hip BMD in participants with normoglycemia (NG), prediabetes, or type 2 diabetes, excluding thiazolidinedione (TZD) users, were evaluated using generalized linear models (GLM). Diabetes medication use and BMD loss among those with type 2 diabetes were also evaluated with GLM., Results: In adjusted models, hip BMD loss was greater in men with type 2 diabetes (- 2.23%; 95% CI: -2.54 to -1.91; P < .001) but not in men with prediabetes (-1.45%; 95% CI -1.63 to -1.26; P = .33) compared with NG (-1.57%; 95% CI -1.73 to -1.41). Among men with type 2 diabetes, TZD, insulin, and sulfonylurea use were associated with greater hip BMD loss., Conclusion: Men with type 2 diabetes, but not prediabetes, experienced accelerated bone loss compared to participants with normoglycemia. More rapid bone loss predicts increased risk of fractures and mortality in broader populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Bone health management in premenopausal women with breast cancer (BC) under hormone-deprivation therapies (HDTs) is often challenging, and the effectiveness of bone-active drugs is still unknown., Methods: This retrospective multicenter study included 306 premenopausal women with early BC undergoing HDTs. Bone mineral density (BMD) and morphometric vertebral fractures (VFs) were assessed 12 months after HDT initiation and then after at least 24 months., Results: After initial assessment, bone-active drugs were prescribed in 77.5% of women (151 denosumab 60 mg/6 months, 86 bisphosphonates). After 47.0 ± 20.1 months, new VFs were found in 16 women (5.2%). Vertebral fracture risk was significantly associated with obesity (odds ratio [OR] 3.87, P = .028), family history of hip fractures or VFs (OR 3.21, P = .040], chemotherapy-induced menopause (OR 6.48, P < .001), preexisting VFs (OR 25.36, P < .001), baseline T-score less than or equal to -2.5 standard deviation (SD) at any skeletal site (OR 4.14, P = .036), and changes at lumbar and total hip BMD (OR 0.94, P = .038 and OR 0.88, P < .001, respectively). New VFs occurred more frequently in women untreated compared to those treated with bone-active drugs (14/69, 20.8% vs 2/237, 0.8%; P < .001) and the anti-fracture effectiveness remained significant after correction for BMI (OR 0.03; P < .001), family history of fractures (OR 0.03; P < .001), chemotherapy-induced menopause (OR 0.04; P < .001), and preexisting VFs (OR 0.01; P < .001)., Conclusions: Premenopausal women under HDTs are at high risk of VFs in relationship with high BMI, densitometric diagnosis of osteoporosis, preexisting VFs, and family history of osteoporotic fractures. Vertebral fractures in this setting might be effectively prevented by bisphosphonates or denosumab., Competing Interests: Conflict of interest: R.P. received consultancy fees from Roche, Novartis, Eli Lilly, Daiichi Sankyo, Gilead, Eisai, and Accord, outside the submitted work. A.P. reports lecture fees from Amgen, Theramex, and UCB, outside the submitted work. A.N. reports lecture fees from Theramex, outside the submitted work. G.T. reports lectures fees from Theramex and Abiogen, outside the submitted work. R.T. received research grants from Pfizer, consultancy fees from MSD, and lecture fees from Pfizer, Eli Lilly, Eisai, and Genomic Health outside the submitted work. A.Z. received consultancy fees from Roche, Novartis, Pfizer, Eli Lilly & Co., AstraZeneca, and Genomic Health outside the submitted work. L.C. received consultancy fees from UCB and lecture fees from Abiogen Pharma and Bruno Farmaceutici, outside the submitted work. A.C. Bossi reports research grants from Bayer SA, Lilly Italia SpA, MSD USA, and Novo Nordisk Italia SpA and personal fees from Sanofi Italia SpA, Boehringer Ingelheim Italia SpA, and AstraZeneca Italia SpA, outside the submitted work. A.L. received grants from Pfizer and lecture fees from Recordati, outside the submitted work. A.B. reports receiving grants and personal fees from Janssen Cilag, grants and personal fees from Astellas, and personal fees from Bayer outside the submitted work. G.M. received consultancy fees and preceptorship from Amgen–UCB and Sanofi and lectures fees from Theramex and Recordati. The other authors have nothing to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Context: Male hypogonadism is associated with low bone mineral density (BMD) and increased fragility fracture risk. Patients with type 2 diabetes (T2D) have relatively higher BMD, but greater fracture risk., Objective: Evaluate the skeletal response to testosterone therapy in hypogonadal men with T2D compared with hypogonadal men without T2D., Methods: Single arm, open-label clinical trial (NCT01378299) involving 105 men (40-74 years old), with average morning testosterone <300 ng/dL. Subjects were injected intramuscularly with testosterone cypionate (200 mg) every 2 weeks for 18 months. Testosterone and estradiol were assessed by liquid chromatography/mass spectrometry; serum C-terminal telopeptide of type I collagen (CTX), osteocalcin and sclerostin by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) by high-performance liquid chromatography, areal BMD (aBMD) and body composition by dual-energy x-ray absorptiometry; tibial volumetric BMD (vBMD) and bone geometry by peripheral quantitative computed tomography., Results: Among our population of hypogonadal men, 49 had T2D and 56 were non-T2D. After 18 months of testosterone therapy, there were no differences in circulating testosterone and estradiol between the groups. Hypogonadal men with T2D had increased osteocalcin, reflecting increased osteoblast activity, compared with non-T2D men (P < .01). T2D men increased lumbar spine aBMD (P < .05), total area at 38% tibia (P < .01) and periosteal and endosteal circumferences at the same site (P < .01 for both). T2D men had reduced tibial vBMD (P < .01), but preserved bone mineral content (P = .01). Changes in HbA1c or body composition were similar between the 2 groups., Conclusion: Testosterone therapy results in greater improvements in the skeletal health of hypogonadal men with T2D than their nondiabetic counterparts., (Published by Oxford University Press on behalf of the Endocrine Society 2021.)

Context: The clinical and radiological aspects of normocalcemic hyperparathyroidism (NHPT) are confounded by the differing methods used to rule out secondary hyperparathyroidism and by the small sample size., Objective: To assess the clinical, biochemical, and radiological profile of NHPT compared with primary hyperparathyroidism (PHPT) and control subjects., Design: Multicentric cross-sectional study., Setting: Outpatient clinic., Patients: 47 NHPT, 41 PHPT, and 39 age- and sex-matched control subjects., Main Outcome Measures: Calcium metabolism and bone turnover markers (BTMs). Lumbar spine, total hip, femoral neck, one-third distal radius bone mineral density (BMD). Morphometric vertebral fracture (VF) assessed by dual-energy X-ray absorptiometry., Results: NHPT patients had significantly higher parathyroid hormone, 25(OH)-vitamin D levels and lower calcium × phosphorus product than controls (P < .001). Compared with PHPT, the NHPT group had significantly higher 25(OH) vitamin D levels (P = .016). NHPT had BTM levels similar to controls and PHPT. NHPT, PHPT, and controls have similar lumbar spine and femoral neck BMD. NHPT and controls had a similar radial BMD, while patients with PHPT had a lower radial BMD than both patients with NHPT (P = .031) and controls (P < .05). Using the control group as the reference, after adjustment for interacting factors, there was no increase in risk of moderate-severe VF in NHPT (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.25-4.55), while PHPT had an increased risk (OR 3.81,95% CI 1.15-15.12). Seventy-nine percent of NHPT and 59% of PHPT patients fulfilled the criteria for asymptomatic hyperparathyroidism., Conclusions: The biochemical phenotype of NHPT is intermediate between PHPT and controls. In contrast, the bone phenotype resembles controls with normal bone turnover, no significant BMD impairment, and no increased risk of VF., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Weight loss therapy of older adults with obesity is limited by weight loss-induced decrease in bone mineral density (BMD), which could exacerbate ongoing age-related bone loss and increase the risk for fractures. Therefore, it is recommended that weight loss therapy of older adults with obesity should include an intervention such as regular exercise to reduce the concomitant bone loss. However, the most appropriate exercise types to combine with weight loss therapy in this older population is unknown. In a randomized controlled trial, we performed a head-to-head comparison of aerobic or resistance exercise, or both, during matched ~10% weight loss in 160 older adults with obesity. We measured changes in BMD (total hip, femoral neck, trochanter, intertrochanter, one-third radius, lumbar spine) and bone markers. Changes between groups were analyzed using mixed-model repeated measures analyses of variance. After 6 months of intensive lifestyle interventions, BMD decreased less in the resistance group (-0.006 g/cm 2 [-0.7%]) and combination group (-0.012 g/cm 2 [-1.1%]) than in the aerobic group (-0.027 g/cm 2 [-2.6%]) (p = 0.001 for between-group comparisons). Serum C-telopeptide, procollagen type 1 N-propeptide, and osteocalcin concentrations increased more in the aerobic group (33%, 16%, and 16%, respectively) than in the resistance group (7%, 2%, and 0%, respectively) and combination group (11%, 2%, and 5%, respectively) (p = 0.004 to 0.048 for between-group comparisons). Multiple regression analyses revealed that the decline in whole body mass and serum leptin were the independent predictors of the decline in hip BMD (multiple R = 0.45 [p < .001]). These findings indicate that compared with aerobic exercise, resistance and combined aerobic and resistance exercise are associated with less weight loss-induced decrease in hip BMD and less weight loss-induced increase in bone turnover. Therefore, both resistance and combined aerobic and resistance exercise can be recommended to protect against bone loss during weight loss therapy of older adults with obesity. (LITOE ClinicalTrials.gov number NCT01065636.) © 2019 American Society for Bone and Mineral Research. Published 2019. This article is a U.S. Government work and is in the public domain in the USA., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Context: Adults with type 2 diabetes (T2D) have higher fracture risk compared with nondiabetics, despite having higher bone mineral density (BMD). Insulin resistance (IR) has been associated with increased BMD. It is not known if IR increases fracture risk., Objective: We investigated the relationship among IR HOMA-IR, BMD, and incident nonspine fractures in nondiabetic individuals., Design: Participants included 2398 community-dwelling, nondiabetic older adults (age 74 ± 3 years, 53% women, 38% black) in the Health, Aging and Body Composition Prospective Cohort Study [median follow-up: 12 (interquartile range: 6) years]., Results: The cut-off values for the HOMA-IR quartiles were 1.05, 1.54, and 2.33. Total hip BMD was 0.104 g/cm2 higher in the fourth vs the first HOMA-IR quartile (P < 0.001). This difference was attenuated after adjustment for BMI (adjusted mean difference 0.007 g/cm2; P = 0.371). In unadjusted models, fracture risk was lower in those with higher HOMA-IR [hazard ratio (HR) 0.86 (95% CI 0.73 to 1.01) and 0.65 (95% CI 0.47 to 0.89) for the third and fourth quartile, respectively, vs the first quartile]. However, after adjustment for BMD and BMI, fracture risk was significantly higher in the third quartile (HR 1.19, 95% CI 1.00 to 1.41) and tended to be increased in the fourth quartile (HR 1.12, 95% CI 0.87 to 1.46) vs the first quartile., Conclusions: Greater IR is associated with higher BMD in nondiabetic older adults. In contrast to the relationship between T2D and fracture risk, we did not find consistent evidence that greater IR is associated with increased fracture risk after adjustment for BMI and BMD., (Copyright © 2019 Endocrine Society.)

The ability of bone mineral density (BMD) and other risk factors to predict fracture risk is well-established for as long as 5 to 10 years. However, their value to predict risk over a longer term has not been directly studied. We investigated whether a single assessment of femoral neck BMD and fracture history can predict fracture risk over 20 to 25 years. We used data from the Study of Osteoporotic Fractures (SOF) that assessed BMD and risk factors in 7959 women age ≥67 (mean = 73.4) in 1988-1990. Follow-up for fractures continued for 25 years for hip fracture, and for 20 years for any nonvertebral fracture. Using age-adjusted proportional hazards models, we analyzed the relationships between a single baseline assessment of femoral neck BMD, fracture history and age, and 20-25-year fracture incidence. The 25-year cumulative incidence of hip fracture was 17.9%; 20-year incidence of any nonvertebral fracture was 46.2%. The 25-year hip fracture incidence was highest in those ≥80 years old (22.6%) compared to 13.9% in women aged <70 years. A single femoral neck BMD measurement strongly predicted long-term hip fracture risk to 25 years: 29.6% risk in the lowest BMD quartile versus 7.6% with the highest relative hazard (RH) = 4.9 (95% CI, 4.1 to 6.0). Femoral neck BMD predicted hip fracture with little degradation over time from RH/SD = 2.6 (2.2 to 3.0) for 0 to 5 years to RH/SD = 1.8 (1.4 to 2.4) for 20 to 25 years. Lifetime hip fracture risk was similar (∼30%) regardless of age from 67 to >80 years. History of hip fracture predicted hip fractures only slightly better than history of nonvertebral fracture (RH = 1.6 [95% CI, 1.1 to 2.2] versus RH = 1.4 [95% CI, 1.2 to 1.5], respectively). Fracture history remained strongly predictive up to 25 years. We conclude that a single BMD and fracture history assessment can predict fracture risk over 20 to 25 years. Long-term risk of hip fracture remains extremely high in the oldest age groups, supporting risk assessment and consideration of treatment even in the oldest, highest-risk women.© 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Aims: Few data regarding prevalence of and risk factors for poor bone health in aging individuals with long-standing T1D are available. In this study, we aim to describe the prevalence of bone fragility and to identify factors associated with low bone density in individuals with long-term T1D., Methods: We examined the prevalence of non-vertebral fractures in 985 subjects enrolled in the Joslin 50-Year Medalist Study and measured bone mineral density (BMD) by dual-energy X-ray absorptiometry at the femoral neck, lumbar spine and radius in a subset (65 subjects, mean age 62.6 years, duration 52.5 years, HbA1c 7.1%) with no significant clinical or demographic differences from the rest of the cohort., Results: Medalists have low prevalence of fractures (0.20% hip and 0.91% wrist) and normal Z-score values (spine +1.15, total hip +0.23, femoral neck -0.01, radius +0.26; p > 0.05 for differences vs. 0 at all sites). A significant relationship was found between lower BMD and higher total cholesterol, triglycerides and LDL levels, but not HbA1c. Low BMD at the femoral neck was associated with cardiovascular disease after adjustment for confounding factors: prevalence risk ratio of CVD [95% CI] 4.6 [1.2-18.1], p = 0.03. No other diabetic vascular complication was found to be associated with low BMD., Conclusions: These are the first data regarding bone health in aging individuals who have had diabetes for 50 or more years. The low rates of non-vertebral fractures and the normal Z-score suggest the long T1D diabetes duration did not increase the risk of bone fractures in Medalists compared to non-diabetic peers. Additionally, the association with cardiovascular disease demonstrates the BMD differences in groups are likely not due to glycemic control alone.

Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specifically, Visceral Adipose Tissue (VAT) may potentially prove detrimental. It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health. Although aging is largely known to decrease bone strength, little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage. Given the exponentially growing obesity rate in recent years and the increased life expectancy of western countries it appears of utmost importance to timely focus on this topic.

Context: Although obesity is associated with high bone mass, recent reports suggest an increase in the incidence of fractures in obese patients., Objectives: The objectives of the study were to evaluate the influence of increasing body fat on bone mineral density (BMD) and to determine the influence of the different adipokines on BMD in frail obese elderly patients., Design and Setting: This is a cross-sectional study of baseline characteristics of elderly obese patients participating in a lifestyle therapy with diet with or without exercise and conducted in a university setting., Patients: One hundred seventy-three, elderly (≥65 y old), obese (body mass index of ≥30 kg/m(2)) who were mostly frail participated in the study., Outcome Measures: BMD, percentage of total body fat, percentage of fat-free mass, percentage of lean mass, body mass index, adiponectin, leptin, IL-6, bone turnover markers (osteocalcin and C-telopeptide), high-sensitivity C-reactive protein, free estradiol, and 25-hydroxyvitamin D were measured., Results: Higher tertiles of percentage body fat and lower lean mass were associated with a lower BMD. High-sensitivity C-reactive protein levels were highest in the highest fat tertile (third, 5.5 ± 5.4 vs first, 1.5 ± 1.3 mg/L, P < .05) for women, whereas IL-6 levels were highest in the highest tertile in men (third, 3.5 ± 3.1 vs first, 1.7 ± 0.8 pg/mL, P < .05). Leptin increased with increasing fat tertiles in both genders (P < .05), whereas adiponectin increased with increasing fat tertiles only in men (P < .05). A multivariate analysis revealed adiponectin as an important mediator of the effect of fat mass on BMD. Osteocalcin levels were highest in the highest fat tertile in women but not in men. Physical function test scores decreased with increasing fat tertiles in women (P < .05) but not in men., Conclusions: Increasing adiposity together with decreasing lean mass is associated with lower BMD, higher adipokine levels, and worsening frailty in elderly obese adults.

Unlabelled: We studied the relationships among strength, muscle mass, and bone mineral density (BMD) with lifestyle change. Lifestyle therapy consisted of exercise, diet, and diet plus exercise. Diet was by caloric restriction to induce and maintain a weight loss of 10 % from baseline body weight. Exercise attenuated weight loss-induced muscle and bone losses. Exercise improved strength despite muscle loss in patients on diet and exercise. Changes in strength did not correlate with changes in BMD. However, changes in thigh muscle volume correlated with, and predicted changes in hip BMD., Introduction: Losses of hip BMD and lean body mass are major complications of lifestyle therapy in frail, obese older adults; however, the contribution of mechanical strain loss from muscle loss is poorly defined. We determined the effect of changes in thigh muscle volume and muscle strength on BMD in frail, obese older adults undergoing lifestyle therapy aimed at intentional weight loss with or without exercise., Methods: One hundred seven obese older adults were randomized to control, diet, exercise, and diet-exercise groups for 1 year. Thigh muscle volume was measured by magnetic resonance imaging, BMD by DXA, knee strength by dynamometry, total strength by one-repetition maximum (1-RM), and bone markers by immunoassay., Results: Thigh muscle volume decreased in the diet group (-6.2 ± 4.8 %) and increased in the exercise group (2.7 ± 3.1 %), while it was not significantly different from the control in the diet-exercise group. Changes in hip BMD followed similar pattern as those in thigh muscle volume. Knee extension and flexion increased in the exercise group (23 ± 20 %; 25 ± 19 %) and diet-exercise group (20 ± 19 %; 20.6 ± 27 %) but were unchanged in the control and diet groups. Changes in thigh muscle volume correlated with changes in hip BMD (r = 0.55, P = <0.001) and were an independent predictor of changes in hip BMD (β = 0.12, P = 0.03) in the multiple regression analyses after accounting for demographic factors and changes in weight and physical activity. There were no correlations between BMD changes and knee strength, 1-RM, and sclerostin changes., Conclusions: Changes in thigh muscle volume predict hip BMD changes in obese older patients undergoing lifestyle therapy. The effect of exercise in attenuating thigh muscle loss when added to diet may in part account for the reduction in weight loss-induced bone loss in the diet-exercise group.

Context: Femoral shaft cortical thickening has been mentioned in reports of atypical subtrochanteric and diaphyseal (S/D) femur fractures, but it is unclear whether thickening precedes fracture or results from a preceding stress fracture and what role bisphosphonates might play in cortical thickening., Objective: Our objective was to examine the relationship of cortical thickness to S/D fracture risk as well as establish normal reference values for femoral cortical thickness in a large population-based cohort of older women., Design: Using pelvic radiographs obtained in 1986-1988, we measured femoral shaft cortical thickness 3 cm below the lesser trochanter in women in the Study of Osteoporotic Fractures. We measured this in a random sample and in those with S/D fractures and femoral neck and intertrochanteric fractures. Low-energy S/D fractures were identified from review of radiographic reports obtained between 1986 and 2010. Radiographs to evaluate atypia were not available. Analysis used case-cohort, proportional hazards models., Outcomes: Cortical thickness as a risk factor for low-energy S/D femur fractures as well as femoral neck and intertrochanteric fractures in the Study of Osteoporotic Fractures, adjusting for age and bone mineral density in proportional hazards models., Results: After age adjustment, women with thinner medial cortices were at a higher risk of S/D femur fracture, with a relative hazard of 3.94 (95% confidence interval = 1.23-12.6) in the lowest vs. highest quartile. Similar hazard ratios were seen for femoral neck and intertrochanteric fractures. Medial or total cortical thickness was more strongly related to fracture risk than lateral cortical thickness., Conclusions: In primarily bisphosphonate-naive women, we found no evidence that thick femoral cortices placed women at higher risk for low-energy S/D femur fractures; in fact, the opposite was true. Women with thin cortices were also at a higher risk for femoral neck and intertrochanteric fractures. Whether cortical thickness among bisphosphonate users plays a role in atypical S/D fractures remains to be determined.

Weight loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight loss therapy should include an intervention such as exercise training (ET) to minimize bone loss. The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 years) obese (body mass index [BMI] ≥ 30  kg/m(2) ) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (-9.6%) and diet-exercise (-9.4%) groups, not in the exercise (-1%) and control (-0.2%) groups (between-group p  <  0.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (-1.1%) than in the diet group (-2.6%), whereas BMD increased in the exercise group (1.5%) (between-group p  <  0.001). Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%, respectively), whereas they decreased in the exercise group (-13% and -15%, respectively) (between-group p  <  0.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (-15%) compared with the diet group (9%) (p  =  0.04). Serum leptin and estradiol concentrations decreased in the diet (-25% and -15%, respectively) and diet-exercise (-38% and -13%, respectively) groups, not in the exercise and control groups (between-group p  =  0.001). Multivariate analyses revealed that changes in lean body mass (β  =  0.33), serum osteocalcin (β  = -0.24), and one-repetition maximum (1-RM) strength (β  =  0.23) were independent predictors of changes in hip BMD (all p  <  0.05). In conclusion, the addition of ET to weight loss therapy among obese older adults prevents weight loss-induced increase in bone turnover and attenuates weight loss-induced reduction in hip BMD despite weight loss-induced decrease in bone-active hormones., (Copyright © 2011 American Society for Bone and Mineral Research.)

Introduction: Ghrelin is a stomach secreted hormone, believed to play an important role in energy balance and in food intake. Experimental studies have shown a positive effect of ghrelin on bone metabolism, but both in vivo and clinical findings have been contradictory. We aimed to investigate the effect of ghrelin on volumetric BMD in a large cohort of elderly subjects., Methods: We have studied 401 women (mean age 75.1years, range 65-94) and 306 men (mean age 73.9years, range 65-94) from the InChianti study, which included measurements of BMD using quantitative CT of the tibia and of body composition using bio impedancemetry. Serum ghrelin was measured using ELISA. We excluded participants with diabetes, hyperthyroidism, using hormone replacement or glucocorticoid therapy. We evaluated the correlation of ghrelin with total, trabecular, and cortical BMD using Pearson's coefficient, and linear regression models to estimate the association between ghrelin and BMD controlling for potential confounders., Results: In women, after correction for potential confounders, ghrelin was associated with trabecular BMD (β=7.08, P<0.02), but not with total or cortical BMD. In men, adjusted multivariable models showed a nearly significant association between serum ghrelin and trabecular BMD (β=4.99, P=0.069) and no association with either cortical or total BMD., Conclusions: Serum ghrelin is positively correlated with trabecular BMD in a cohort of elderly healthy Italian women. The fact that trabecular is more metabolically active than cortical bone and the larger number of females might explain this selective association., Competing Interests: Authors declare they have no conflict of interest that would prejudice the impartiality of this scientific work., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Few data are available on the effect of the diet in general on bone health. The objective of this study was to identify dietary patterns and to evaluate the association between such patterns and bone mineral density (BMD) changes over time., Methods: We analyzed a sample of women aged ≥65 years participating in the InCHIANTI Study. BMD was evaluated using computed tomography of the tibia and nutritional intake using the EPIC questionnaire. We used a cluster analysis to identify patterns of dietary intake. The clusters were compared with respect to nutritional intake; risk factors for osteoporosis; comorbidity; total, trabecular, and cortical BMD; and BMD changes over 6 years., Results: The sample size was 434, with a mean age of 75.2 years (SD, 7.01 years; range, 65-94 years). Based on dietary variables, 2 clusters were identified with a marked difference in energy intake (30 kcal/kg of ideal body weight [IBW] in cluster 1 vs 44 kcal/kg IBW in cluster 2). We found no meaningful differences between clusters with regard to nondietary risk factors for osteoporosis, BMD measured at baseline, and changes in BMD over the 6-year follow-up; cluster 2 showed a greater increase in cortical BMD (+30.2 mg/cm(3) vs +16.7 mg/cm(3)). Members of cluster 2 were less likely to have a lower cortical BMD increase (adjusted odds ratio, 0.452; 95% confidence interval, 0.215-0.950)., Conclusions: Cortical BMD increases more in participants eating a diet exceeding the RDA for macronutrients. Cortical BMD may be more sensitive to diet and dietary interventions than trabecular bone.

Background: Adipose tissue has been suggested to influence bone density and metabolism through the effect of some adipokines. However, whether adiponectin and visfatin may correlate with bone metabolism is still unclear., Aim: The aim of this study was to investigate the relationship of adiponectin and visfatin with bone density in patients with metabolic syndrome (MS)., Subjects: We enroled 72 consecutive patients with MS (25 males, 47 females; mean age 58.14±11 yr) and 40 control subjects., Methods: Plasma adiponectin and visfatin levels were measured. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) at the level of lumbar spine L2-L4 (BMD L2-L4) and femoral neck (BMD-Fn)., Results: MS patients had higher plasma visfatin and lower adiponectin levels than controls, (p<0.01 for both). Adiponectin was negatively correlated with BMD-Fn and BMD L2-L4 (r=-0.20, r=-0.24, respectively; p<0.05 for both) whereas plasma visfatin levels were positively correlated to BMD L2-L4 only in men (r=0.44; p<0.05)., Conclusions: Our study shows that adiponectin and visfatin are oppositely associated with BMD. Although the mechanisms behind these correlations are unclear, a modulation of bone metabolism by these adipokines can be suggested.

Introduction: Adiponectin serum concentration has been reported to be inversely correlated with bone mineral density (BMD) in humans. The data on this issue, however, are biased by small study sample size and lack of controlling for body composition., Methods: We used data from the third follow-up of the InCHIANTI study, which included measurements of BMD using quantitative CT of the tibia and of body composition using bioimpedenziometry. Serum adiponectin was measured using radioimmunoassay. We excluded participants with diabetes, hyperthyroidism, using hormone replacement or corticosteroid therapy. We evaluated the correlation of adiponectin with total, trabecular, and cortical BMD using Pearson's coefficient, and linear regression models to estimate the association between adiponectin and BMD controlling for potential confounders (age, body mass index, alcohol intake, fat mass, smoking)., Results: Our sample was made up of 320 men (mean age: 67 years, SD: 15.8, range: 29-97 years) and 271 postmenopausal women (mean age: 76 years, SD: 8.2, range: 42-97 years). In men, serum adiponectin was not independently associated with BMD. In women, after correction for potential confounders, adiponectin was associated with total (β=-0.626, P<0.001), trabecular (β=-0.696, P<0.001), and cortical (β=-1.076, P=0.001) BMD., Conclusion: Our results show that adiponectin is inversely associated with bone mass in women. Further studies are needed to confirm these findings prospectively and then to clarify the explanatory mechanisms., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Bone mineral density (BMD) may be influenced by the general dietary pattern and the potential renal acid load (PRAL)., Methods: We compared the dietary intake (estimated using the European Prospective Investigation into Cancer and nutrition questionnaire) of 497 community-living women (60 years of age and older) grouped according to tertiles of baseline total, trabecular and cortical BMD estimated using tibial peripheral quantitative computed tomography (pQCT), and of BMD variation over 6 years., Results: None of the nutrients taken into account nor PRAL was associated with total BMD, with the exception that the intake of polyunsaturated fatty acids (PUFA) was slightly higher among women with the highest total BMD. Similar results were found for trabecular BMD. Cortical BMD was associated with serum 25-OH vitamin D (38.8, 43.2, and 49.5 nmol/L in the first, second, and third tertiles, respectively; P=0.042). In the longitudinal analysis, a lower BMI was associated with greater loss of total BMD, while lower serum 25-OH vitamin D at baseline was associated with smaller loss of cortical BMD., Conclusions: We found no relationship between dietary acid load and BMD. We also confirmed the role of well-recognized risk factor for osteoporosis., (Copyright 2009 Elsevier Inc. All rights reserved.)

Background: Polymorphisms of the sex hormone-binding globulin (SHBG) gene are associated with differences in SHBG levels, influencing the risk for breast cancer and polycystic ovarian syndrome, but no association has been reported for osteoporosis in postmenopausal women., Objective: To determine the effect of G to A substitution in the 5'UTR (rs1799941) and the Asp356Asn (rs6259) polymorphisms of the SHBG gene on bone mineral density (BMD)., Methods: This is a cross-sectional study in a university-based research center from May, 2002 to December, 2007. A total of two hundred and thirteen healthy postmenopausal Caucasian women > or = 1 year from last menstrual period participated to this study. Serum estradiol by ultrasensitive radioimmnunoassay, serum sex hormone-binding globulin by immunoradiometric assay, and urinary NTx by enzyme-linked immunoassay were measured. BMD measurements were performed by dual energy X-ray absorptiometry and genotyping by Pyrosequencing., Results: There were no significant differences in SHBG levels associated with either rs1799941 or rs6259. Using a p value of <0.00625 for significance, we found that subjects with the A allele (GA+AA) for the rs1799941, had a trend for lower free estradiol index (FEI) compared to the GG genotype (p=0.04). They also had significantly lower BMD at the intertrochanter (p=0.003) and trend for lower BMD at the total hip (p=0.02). There was no significant difference in FEI levels between the genotypes for the rs6259 polymorphism, but women with the Asn allele (Asp/Asn+Asn/Asn), had significantly lower BMD in the total femur (p=0.004) and intertrochanter (0.002) compared to those with the Asp/Asp genotype., Conclusions: Our data suggest that polymorphisms of the SHBG gene are associated with significant differences in BMD at the proximal femur sites. Thus, genetic variations in the SHBG gene may influence BMD at the hip in postmenopausal women.

Polymorphisms of the CYP450 genes that encode for the enzymes that metabolize estrogen are linked to hormone-related cancers. We investigated the impact of two polymorphisms of the CYP1B1 gene previously reported to be associated with hormone-related disorders on estrogen metabolism and bone mineral density (BMD), another hormone-dependent condition, in women from different ethnic backgrounds. Four hundred sixty-eight postmenopausal Caucasian women, 220 from St. Louis, MO, USA (mean age=63.5+/-0.53 years) and 248 from Palermo, Italy (mean age=72.9+/-0.44 years) participated in the study. Measurements of urinary estrogen metabolites by enzyme-linked immunoassay, serum estradiol by ultrasensitive radioimmnunoassay, and serum sex hormone-binding globulin by immunoradiometric assay were performed only in the American women, while BMD by dual energy X-ray absorptiometry and genotyping by pyrosequencing were performed in both American and Italian women. Differences in the levels of metabolites, free estradiol index and BMD were analyzed by analysis of covariance. Analysis among the American participants for the Valine432Leucine polymorphism showed that, compared to women with the Val/Val genotype, women with the Leu allele (Val/Leu and Leu/Leu) had significantly higher log-transformed values of total urinary estrogen metabolite (ng/mg-creatinine) levels (1.23+/-0.04, 1.35+/-0.02, and 1.34+/-0.03; p=0.03), and significantly lower BMD (gm/cm(2)) in the lumbar spine (1.009+/-0.02, 0.955+/-0.01 and 0.931+/-0.02; p=0.03) and the femoral neck (0.748+/-0.02, 0.717+/-0.01 and 0.693+/-001, p=0.03) for the Val/Val, Val/Leu and Leu/Leu genotypes respectively. There were no significant differences in the urinary metabolites and BMD in the different genotypes for the Alanine119Serine polymorphism among the American women. Meanwhile, a separate analysis among the Italian women revealed no significant differences in BMD among the different genotypes for the two polymorphisms investigated. In conclusion, women with the Leu allele for the CYP1B1 Val432polymorphism have increased estrogen catabolism, as indicated by higher urinary estrogen metabolites, compared to those with Val/Val genotype. This may lead to relative hypoestrogenism and lower BMD in the lumbar spine and femoral neck in these women. Our data suggest that through its effect on the rate of estrogen catabolism, the Val432Leu polymorphism of the CYP1B1 gene may represent as a possible genetic risk factor for osteoporosis in American women.

Background: High calcium intake has been associated with both high bone mineral density (BMD) and high urinary estrogen metabolites. However, the role of dietary calcium and calcium supplements on estrogen metabolism and BMD remains unknown., Objective: The objective was to investigate the importance of the source of calcium intake on estrogen metabolism and BMD., Design: The average total daily calcium intake from supplements and diet, urinary estrogen metabolites, and spine and proximal femur BMD were studied in 168 healthy postmenopausal white women., Results: Women who obtained calcium primarily from the diet or from both the diet and supplements had significantly (P=0.03) lower ratios of nonestrogenic to estrogenic metabolites (2-hydroxyestrone 1/16 alpha-hydroxyestrone) than did those who obtained calcium primarily from supplements. Adjusted BMD z scores were significantly greater in the subjects who obtained calcium primarily from the diet or from both the diet and supplements than in those who obtained calcium primarily from calcium supplements at the spine (P=0.012), femoral neck (P=0.02), total femur (P=0.003), and intertrochanter (P=0.005). This difference was evident especially in those who obtained calcium primarily from the diet, whose total calcium intake was lower than that in those who obtained calcium primarily from supplements., Conclusion: Calcium from dietary sources is associated with a shift in estrogen metabolism toward the active 16 alpha-hydroxyl metabolic pathway and with greater BMD and thus may produce more favorable effects in bone health in postmenopausal women than will calcium from supplements.

Estrogen is a critical hormone for bone homeostasis in men, but no information is available on the role of estrogen metabolism among men. The aim of this study was to evaluate the effect of estrogen hydroxylation on male bone mineral density (BMD). Participants consisted of 61 healthy Caucasian males (mean age 66.6 +/- 1.0 years). Urinary estrogen metabolites were measured by enzyme-linked immunosorbent assay, serum estradiol by ultrasensitive radioimmunoassay, sex hormone binding globulin by radioimmunoassay, and BMD of the lumbar spine and the proximal femur by dual-energy X-ray absorptiometry. Active estrogen metabolites, 16alpha-hydroxyestrone (16alphaOHE(1)) and estriol (E(3)), positively correlated with adjusted BMD in all regions of the proximal femur (all P < 0.05) but not at the lumbar spine, and those in the highest tertile of urinary 16alphaOHE(1 )had the highest BMD. Free estradiol index (FEI) also positively correlated with BMD of the total hip, femoral neck, and intertrochanter (all P < 0.05), while there was no correlation between BMD with inactive metabolites (2-hydroxyestrone and 2-methoxyestrone) and serum testosterone. Multiple regression analysis showed 16alphaOHE(1), FEI, and body mass index are important independent predictors of BMD in all regions of the proximal femur. Estrogen metabolism may modulate BMD in men. Increased urinary 16alphaOHE(1) and E(3) levels are associated with high BMD at the proximal femur, and 16alphaOHE(1) appears to be a major determinant of BMD among the metabolites evaluated.

One of the most promising genetic approaches to dissecting a multifactorial disease is represented by genetically isolated population studies. We studied a genetic marker in a cohort of women living on the Mediterranean island of Lampedusa, a geographically isolated population. Lampedusa, located between the African coast and Sicily, consists of a young genetic isolate (<20 generations) with an exponential growth in the last generations. We analyzed the association between the FokI vitamin D receptor (VDR) gene polymorphism, previously proposed as a predictor of bone mass, with parameters of bone mass and turnover in a cohort of pre- and postmenopausal women living on Lampedusa. In 424 women (277 postmenopausal and 147 premenopausal), allelic frequencies were 49% for the F allele and 51% for the f allele. Using analysis of covariance, we found that subjects with ff genotype exhibited a significantly (P < 0.001) lower lumbar spine bone mass, by dual-energy X-ray absorptiometry, and lower values of bone ultrasonographic parameters (speed of sound and broadband ultrasound attenuation) relative to those with Ff and FF genotypes. Conversely, osteocalcin and serum cross-laps were significantly higher in ff and Ff compared to FF genotype. Our data suggest that FokI VDR polymorphism may contribute to the determination of bone mass and turnover in both pre- and postmenopausal women in this geographically isolated population.

We studied bone mass and metabolism in 30 adult women (age 28.5 +/- 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine -1.29 +/- 0.31; femoral neck -0.60+/-0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar spine -2.35 +/- 0.2, femoral neck -1.83 +/- 0.2) and increased bone turnover relative to eugonadal women. Of the hypogonadal patients, 13 had taken HRT since age 15 +/- 1 years, but their bone mass and turnover markers were not different than untreated hypogonadal patients. In conclusion, while hypogonadism negatively affects bone mass acquisition in adult TM women, HRT at the standard replacement doses is not sufficient to secure optimal bone accrual.

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk. [ABSTRACT FROM AUTHOR]

Summary: Diabetes and osteoporosis are rapidly growing diseases. The link between the high fracture incidence in diabetes as compared with the non-diabetic state has recently been recognized. While this review cannot cover every aspect of diabetic osteodystrophy, it attempts to incorporate current information from the First International Symposium on Diabetes and Bone presentations in Rome in 2014. Diabetes and osteoporosis are fast-growing diseases in the western world and are becoming a major problem in the emerging economic nations. Aging of populations worldwide will be responsible for an increased risk in the incidence of osteoporosis and diabetes. Furthermore, the economic burden due to complications of these diseases is enormous and will continue to increase unless public awareness of these diseases, the curbing of obesity, and cost-effective measures are instituted. The link between diabetes and fractures being more common in diabetics than non-diabetics has been widely recognized. At the same time, many questions remain regarding the underlying mechanisms for greater bone fragility in diabetic patients and the best approach to risk assessment and treatment to prevent fractures. Although it cannot cover every aspect of diabetic osteodystrophy, this review will attempt to incorporate current information particularly from the First International Symposium on Diabetes and Bone presentations in Rome in November 2014. [ABSTRACT FROM AUTHOR]

Summary: Human chitotriosidase (Chit) increases during the osteoclast differentiation and their activity. We demonstrated that serum Chit was significantly higher in osteoporotic subjects than in healthy control ones and revealed a negative correlation between Chit and bone mineral density (BMD). This is the first study showing a correlation between Chit and severe postmenopausal osteoporosis. Introduction: Mammalian chitinases exert important biological roles in the monocyte lineage and chronic inflammatory diseases. In particular, Chit seems to promote bone resorption in vitro. No in vivo studies have been performed to confirm this finding. We aim to evaluate Chit activity in postmenopausal women affected by severe osteoporosis. Methods: In this cross-sectional study, 91 postmenopausal women affected by osteoporosis and 61 with either osteopenia or normal BMD were screened. All subjects were assessed by dual-energy X-ray absorptiometry (DXA) and X-ray vertebral morphometry. Osteoporotic subjects were considered eligible if they were affected by at least one vertebral osteoporotic fracture (group A = 57 subjects). Osteopenic or healthy subjects were free from osteoporotic fractures (group B = 51 subjects). Enzymatic Chit and serum β-CrossLaps (CTX) were measured in the whole population. Results: Group A showed higher serum levels of beta-CTX compared to group B (0.40 ± 0.26 ng/mL vs 0.29 ± 0.2 ng/mL, p = 0.022). Chit was significantly higher in group A than in group B (1042 ± 613 nmol/mL/h vs 472 ± 313 nmol/mL/h, p < 0.001, respectively) even after adjustment for age ( p < 0.001). Spearman correlation test revealed a negative correlation between Chit and BMD at each site (lumbar spine: r = −0.38, p = 0.001, femoral neck: r = −0.35, p = 0.001, total femur: r = −0.39, p < 0.001). Furthermore, a positive correlation between Chit and PTH was observed (r = 0.26, p = 0.013). No significant correlation was found between Chit and beta-CTX (r = 0.12, p = 0.229). After a multivariate analysis, a positive correlation between severe osteoporosis and Chit ( p < 0.001), beta-CTX ( p = 0.013), and age ( p < 0.001) was observed. Conclusion: This is the first clinical study showing a correlation between Chit and severe postmenopausal osteoporosis. Larger and prospective studies are needed to evaluate if Chit may be a promising clinical biomarker and/or therapeutic monitor in subjects with osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: This paper provides a framework for the development of national guidelines for the management of glucocorticoid-induced osteoporosis in men and women aged 18 years and over in whom oral glucocorticoid therapy is considered for 3 months or longer. Introduction: The need for updated guidelines for Europe and other parts of the world was recognised by the International Osteoporosis Foundation and the European Calcified Tissue Society, which set up a joint Guideline Working Group at the end of 2010. Methods and results: The epidemiology of GIO is reviewed. Assessment of risk used a fracture probability-based approach, and intervention thresholds were based on 10-year probabilities using FRAX. The efficacy of intervention was assessed by a systematic review. Conclusions: Guidance for glucocorticoid-induced osteoporosis is updated in the light of new treatments and methods of assessment. National guidelines derived from this resource need to be tailored within the national healthcare framework of each country. [ABSTRACT FROM AUTHOR]