Abstract: Background Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. Methods In a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of −2.0 or less at the lumbar spine, total hip, or femoral neck and −3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator — oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 μg daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage ch...

Abstract: Summary Osteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3 % (hip) or 20 % (major) 10-year fracture risk also confer an osteoporosis diagnosis.

Abstract: Several recent studies suggest that obesity may be a risk factor for fracture The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 22 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred Femoral neck BMD was measured in 108,267 of these women Obesity (BMI ≥ 30 kg/m(2) ) was present in 22% A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women Compared to a BMI of 25 kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m(2) was 087 (95% confidence interval [CI], 085-090) When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 116; 95% CI, 109-123) Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD At a population level, high BMI remains a protective factor for most sites of fragility fracture The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored

Abstract: The pediatrician plays a major role in helping optimize bone health in children and adolescents. This clinical report reviews normal bone acquisition in infants, children, and adolescents and discusses factors affecting bone health in this age group. Previous recommended daily allowances for calcium and vitamin D are updated, and clinical guidance is provided regarding weight-bearing activities and recommendations for calcium and vitamin D intake and supplementation. Routine calcium supplementation is not recommended for healthy children and adolescents, but increased dietary intake to meet daily requirements is encouraged. The American Academy of Pediatrics endorses the higher recommended dietary allowances for vitamin D advised by the Institute of Medicine and supports testing for vitamin D deficiency in children and adolescents with conditions associated with increased bone fragility. Universal screening for vitamin D deficiency is not routinely recommended in healthy children or in children with dark skin or obesity because there is insufficient evidence of the cost-benefit of such a practice in reducing fracture risk. The preferred test to assess bone health is dual-energy x-ray absorptiometry, but caution is advised when interpreting results in children and adolescents who may not yet have achieved peak bone mass. For analyses, z scores should be used instead of T scores, and corrections should be made for size. Office-based strategies for the pediatrician to optimize bone health are provided. This clinical report has been endorsed by American Bone Health.

Abstract: Bone fragility is a major health concern, as the increased risk of bone fractures has devastating outcomes in terms of mortality, decreased autonomy, and healthcare costs. Efforts made to address this problem have considerably increased our knowledge about the mechanisms that regulate bone formation and resorption. In particular, we now have a much better understanding of the cellular events that are triggered when bones are mechanically stimulated and how these events can lead to improvements in bone mass. Despite these findings at the molecular level, most exercise intervention studies reveal either no effects or only minor benefits of exercise programs in improving bone mineral density (BMD) in osteoporotic patients. Nevertheless, and despite that BMD is the gold standard for diagnosing osteoporosis, this measure is only able to provide insights regarding the quantity of bone tissue. In this article, we review the complex structure of bone tissue and highlight the concept that its mechanical strength stems from the interaction of several different features. We revisited the available data showing that bone mineralization degree, hydroxyapatite crystal size and heterogeneity, collagen properties, osteocyte density, trabecular and cortical microarchitecture, as well as whole bone geometry, are determinants of bone strength and that each one of these properties may independently contribute to the increased or decreased risk of fracture, even without meaningful changes in aBMD. Based on these findings, we emphasize that while osteoporosis (almost) always causes bone fragility, bone fragility is not always caused just by osteoporosis, as other important variables also play a major role in this etiology. Furthermore, the results of several studies showing compelling data that physical exercise has the potential to improve bone quality and to decrease fracture risk by influencing each one of these determinants are also reviewed. These findings have meaningful clinical repercussions as they emphasize the fact that, even without leading to improvements in BMD, exercise interventions in patients with osteoporosis may be beneficial by improving other determinants of bone strength.

Abstract: Context: Current osteoporosis medications increase bone mineral density (BMD) modestly and reduce, but do not eliminate, fracture risk. Attempts to improve efficacy by administering anabolic agents and bisphosphonates concomitantly have been unsuccessful. Conversely, 12 months of concomitant denosumab and teriparatide therapy increases BMD more than either drug alone. Objective: The purpose of this study was to determine whether 24 months of combined denosumab and teriparatide will increase hip and spine BMD more than either individual agent. Design: Preplanned continuation of the Denosumab and Teriparatide Administration (DATA) randomized controlled trial in which postmenopausal osteoporotic women received teriparatide (20 μg daily), denosumab (60 mg every 6 months), or both medications for 24 months. Participants: Participants were 94 postmenopausal women with osteoporosis. Outcome Measures: Lumbar spine, femoral neck, total hip, and distal radius BMD and serum markers of bone turnover were measured. Re...

Abstract: Physical exercise is an important stimulus for osteoporosis prevention and treatment. However, it is not clear yet which modality would be better to stimulate bone metabolism and enhance physical function of postmenopausal women. This review paper aims to summarize and update present knowledge on the effects of different kinds of aquatic and ground physical exercises on bone metabolism and physical function of postmenopausal women. Moderate to intense exercises, performed in a high speed during short intervals of time, in water or on the ground, can be part of a program to prevent and treat postmenopausal osteoporosis. Mechanical vibration has proven to be beneficial for bone microarchitecture, improving bone density and bone strength, as well as increasing physical function. Although impact exercises are recognized as beneficial for the stimulation of bone tissue, other variables such as muscle strength, type of muscle contraction, duration and intensity of exercises are also determinants to induce changes in bone metabolism of postmenopausal women. Not only osteoanabolic exercises should be recommended; activities aimed to develop muscle strength and body balance and improve the proprioception should be encouraged to prevent falls and fractures.

Abstract: Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

Abstract: Background. Adults with osteogenesis imperfecta (OI) have a high risk of fracture. Currently, few treatment options are available, and bone anabolic therapies have not been tested in clinical trials for OI treatment. Methods. 79 adults with OI were randomized to receive 20 μg recombinant human parathyroid hormone (teriparatide) or placebo for 18 months in a double-blind, placebo-controlled trial. The primary endpoint was the percent change in areal bone mineral density (aBMD) of the lumbar spine (LS), as determined by dual-energy X-ray absorptiometry. Secondary endpoints included percent change in bone remodeling markers and vertebral volumetric BMD (vBMD) by quantitative computed tomography, estimated vertebral strength by finite element analysis, and self-reported fractures. Results. Compared with the placebo group, the teriparatide group showed increased LS aBMD (6.1% ± 1.0% vs. 2.8% ± 1.0% change from baseline; P < 0.05) and total hip aBMD (2.6% ± 1.0% vs. –2.4% ± 1.0% change; P < 0.001). Vertebral vBMD and strength improved with teriparatide therapy (18% ± 6% and 15% ± 3% change, respectively), but declined with placebo (–5.0% ± 6% and –2.0% ± 3% change; P < 0.05 for both comparisons). Serum procollagen type 1 N-terminal propeptide (P1NP) and urine collagen N-telopeptide (NTx) levels increased with teriparatide therapy (135% ± 14% and 64% ± 10% change, respectively). Teriparatide-induced elevation of P1NP levels was less pronounced in severe forms of OI (type III/IV) compared with the milder form (type I). Type I OI patients exhibited robust BMD increases with teriparatide; however, there was no observed benefit for those with type III/IV OI. There was no difference in self-reported fractures between the 2 groups. Conclusions. Adults with OI, particularly those with less severe disease (type I), displayed a teriparatide-induced anabolic response, as well as increased hip and spine aBMD, vertebral vBMD, and estimated vertebral strength. Trial registration. Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00131469","term_id":"NCT00131469"}}NCT00131469. Funding. The Osteoporosis Imperfecta Foundation, Eli Lilly and Co., the National Center for Advancing Translational Science (NCATS) at the NIH (grant no. UL1RR024140), and the Baylor College of Medicine General Clinical Research Center (grant no. RR00188).

Abstract: Bariatric surgery is a popular and effective treatment for severe obesity but may have negative effects on the skeleton. This review summarizes changes in bone density and bone metabolism from animal and clinical studies of bariatric surgery, with specific attention to Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), and sleeve gastrectomy (SG). Skeletal imaging artifacts from obesity and weight loss are also considered. Despite challenges in bone density imaging, the preponderance of evidence suggests that bariatric surgery procedures have negative skeletal effects that persist beyond the first year of surgery, and that these effects vary by surgical type. The long-term clinical implications and current clinical recommendations are presented. Further study is required to determine mechanisms of bone loss after bariatric surgery. Although early studies focused on calcium/vitamin D metabolism and mechanical unloading of the skeleton, it seems likely that surgically induced changes in the hormonal and metabolic profile may be responsible for the skeletal phenotypes observed after bariatric surgery.

Abstract: Anorexia nervosa (AN) is reported in 0.3% of young females 1. It is the third most common medical condition among adolescent girls based on one report, and the incidence of AN appears to be increasing in this population 2. Girls with AN are characterized by low weight and multiple hormonal abnormalities which impact bone metabolism. Some of these alterations include low levels of leptin, hypogonadism, relative IGF-1 deficiency, and hypercortisolism 3–6. Markers of bone turnover are suppressed in adolescent girls with AN 4,7,8, and bone mineral accrual is reduced 4,9,10. Girls with AN consequently have decreased areal bone mineral density (aBMD) compared to normal-weight individuals 11. Furthermore, cortical and trabecular microarchitecture is impaired in girls with AN, and finite element-derived estimates of stiffness and failure load are also lower than in controls 12,13. However, it is not known whether lower aBMD in adolescents with AN translates to an increased risk for fractures during childhood. The onset of AN occurs most commonly during adolescence 14. Adolescence is normally marked by rapid bone accumulation 15. Diseases, such as AN, which impair bone accrual during this period can adversely affect attainment of peak bone mass, and therefore BMD later in life. In patients with AN, disease onset prior to the attainment of peak bone mass results in more severe skeletal outcomes compared to disease onset in adulthood 16. Several studies have demonstrated an increased fracture risk in adults with AN. Fracture incidence increases soon after the diagnosis of AN and remains elevated many years later 17–19. However, no prior study has examined the prevalence of childhood and adolescent fracture before or after the diagnosis of AN in adolescents. In addition, although measurement of aBMD is a valuable tool to estimate fracture risk in postmenopausal women 20, data demonstrating its ability to predict fractures in children are limited 21. The relationship between aBMD and fracture prevalence has not been examined in adolescents with AN. We assessed fracture history and aBMD in a large group of adolescents females with AN and normal-weight controls. The study was conducted to determine whether the prevalence of childhood and adolescent fracture is increased in adolescent females with AN compared to normal-weight controls, and to examine whether reductions in aBMD predict fracture risk in females with AN. We hypothesized that the risk of fracture would be increased among adolescent females with AN compared to controls and that decreases in aBMD would be associated with a history of fracture.

Abstract: Summary The increased risk for fractures in type 2 diabetes mellitus (T2DM) despite higher average bone density is unexplained. This study assessed trabecular bone quality in T2DM using the trabecular bone score (TBS). The salient findings are that TBS is decreased in T2DM and low TBS associates with worse glycemic control.

Abstract: Bone strength is predominantly determined by bone density, but bone microarchitecture also plays an important role. We examined whether trabecular bone score (TBS) predicts the risk of vertebral fractures in a Japanese female cohort. Of 1950 randomly selected women aged 15 to 79 years, we analyzed data from 665 women aged 50 years and older, who completed the baseline study and at least one follow-up survey over 10 years, and who had no conditions affecting bone metabolism. Each survey included spinal imaging by dual-energy X-ray absorptiometry (DXA) for vertebral fracture assessment and spine areal bone mineral density (aBMD) measurement. TBS was obtained from spine DXA scans archived in the baseline study. Incident vertebral fracture was determined when vertebral height was reduced by 20% or more and satisfied McCloskey-Kanis criteria or Genant's grade 2 fracture at follow-up. Among eligible women (mean age 64.1 ± 8.1 years), 92 suffered incident vertebral fractures (16.7/103 person-years). These women were older with lower aBMD and TBS values relative to those without fractures. The unadjusted odds ratio of vertebral fractures for one standard deviation decrease in TBS was 1.98 (95% confidence interval [CI] 1.56, 2.51) and remained significant (1.64, 95% CI 1.25, 2.15) after adjusting for aBMD. The area under the receiver operating characteristic curve of TBS and aBMD combined was 0.700 for vertebral fracture prediction and was not significantly greater than that of aBMD alone (0.673). However, reclassification improvement measures indicated that TBS and aBMD combined significantly improved risk prediction accuracy compared with aBMD alone. Further inclusion of age and prevalent vertebral deformity in the model improved vertebral fracture prediction, and TBS remained significant in the model. Thus, lower TBS was associated with higher risk of vertebral fracture over 10 years independently of aBMD and clinical risk factors including prevalent vertebral deformity. TBS could effectively improve fracture risk assessment in clinical settings. © 2014 American Society for Bone and Mineral Research.

Abstract: Osteoporosis and related fractures cause significant morbidity and mortality worldwide and result in enormous costs to affected individuals and society. Lifestyle choices across the lifespan impact osteoporosis and fracture risk. Physical activity is a viable strategy for the prevention and treatment of low bone mass.

Abstract: Literature has been conflicting as to whether obesity is protective against osteoporosis. Understanding the relationship is particularly important in light of the increasing prevalence of obesity among older adults. Study results confirm a protective association between obesity and osteoporosis in a recent, nationally representative sample of US older adults. Currently, the majority of US older adults are either overweight or obese. Evidence regarding the relationship between body composition measures and bone mass is conflicting, possibly because different measures of obesity reflect multiple mechanisms. Additionally, there are important age, gender, and racial differences in a risk of osteoporosis and fat mass composition. The objective of this study was to examine the association between body mass index (BMI) and bone mineral density (BMD) in a recent, nationally representative sample of US older adults as well as to see if this relationship differs by age, sex, and race. Data for this study were obtained from the National Health and Nutrition Examination Survey (2005–2008) for adults ages 50 and older (n = 3,296). Linear regression models were used to predict BMD of the femoral neck (measured by dual-energy X-ray absorptiometry (DXA)) as a function of BMI (measured height and weight) and a range of study covariates. Every unit increase in BMI was associated with an increase of 0.0082 g/cm2 in BMD (p < 0.001). Interaction terms for BMI and age (p = 0.345), BMI and sex (p = 0.413), and BMI and race (p = 0.725) were not statistically significant. Study results confirm the positive association between BMI and BMD, and this relationship does not differ by age, sex, or race. A 10-unit increase in BMI (e.g., from normal BMI to obese) would result in moving an individual from an osteoporotic BMD level to a normal BMD level. Results demonstrate a protective, cross-sectional association between obesity and osteoporosis in a recent sample of US older adults.

Abstract: Purpose of reviewApart from the well known effects of vitamin D on maintaining calcium homeostasis and promoting bone mineralization, there is some evidence suggesting that vitamin D also modulates human reproductive processes. We will review the most interesting and relevant studies on vitamin D an

Abstract: Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5.0 × 10(-8)) level: 14q24.2 (rs227425, P-value 3.98 × 10(-13), SMOC1) in the combined sample of males and females and 21q22.13 (rs170183, P-value 4.15 × 10(-9), CLDN14) in the female-specific sample. The two newly identified SNPs were also significant in the GEnetic Factors for OSteoporosis consortium (GEFOS, n = 32 960) summary results. We have also independently confirmed 13 previously reported loci at the GWS level: 1p36.12 (ZBTB40), 1p31.3 (GPR177), 4p16.3 (FGFRL1), 4q22.1 (MEPE), 5q14.3 (MEF2C), 6q25.1 (C6orf97, ESR1), 7q21.3 (FLJ42280, SHFM1), 7q31.31 (FAM3C, WNT16), 8q24.12 (TNFRSF11B), 11p15.3 (SOX6), 11q13.4 (LRP5), 13q14.11 (AKAP11) and 16q24 (FOXL1). Gene expression analysis in osteogenic cells implied potential functional association of the two candidate genes (SMOC1 and CLDN14) in bone metabolism. Our findings independently confirm previously identified biological pathways underlying bone metabolism and contribute to the discovery of novel pathways, thus providing valuable insights into the intervention and treatment of osteoporosis.

Abstract: The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric α1(I) collagen. At the molecular level, we attribute the loss in toughness to a decrease in the stabilizing enzymatic cross-links and an increase in nonenzymatic cross-links, which may break prematurely, inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack-deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales.

Abstract: Context: Metabolic syndrome (MetS) is associated with low-grade inflammation, which may harmfully affect bone. Resveratrol (RSV) possesses anti-inflammatory properties, and rodent studies suggest bone protective effects. Objective: This study sought to evaluate effects of RSV treatment on bone in men with MetS. Setting and Design: The study was conducted at Aarhus University Hospital as a randomized, double-blinded, placebo-controlled trial assessing changes in bone turnover markers, bone mineral density (BMD), and geometry. Participants: The study population comprised 74 middle-aged obese men with MetS recruited from the general community, of which 66 completed all visits. Mean age of participants was 49.3 ± 6.3 years and mean body mass index was 33.7 ± 3.6 kg/m2. Intervention: Oral treatment with 1.000 mg RSV (RSVhigh), 150mg RSV (RSVlow), or placebo daily for 16 weeks. Main Outcome Measure: Prespecified primary endpoint was change in bone alkaline phosphatase (BAP). Results: BAP increased dose dependen...

Abstract: Importance Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established. Objective To test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years. Design, Setting, and Participants The prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003; the present analysis includes only the placebo group. Hip and spine dual-energy x-ray absorptiometry (DXA) were measured when placebo was begun (FLEX baseline) and after 1 to 3 years of follow-up. Two biochemical markers of bone turnover, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP), were measured at FLEX baseline and after 1 and 3 years. Main Outcomes and Measures Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover. Results During 5 years of placebo, 94 of 437 women (22%) experienced 1 or more symptomatic fractures; 82 had fractures after 1 year. One-year changes in hip DXA, NTX, and BAP were not related to subsequent fracture risk, but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk (lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio, 2.17 [95% CI, 1.38-3.41]; total hip DXA relative hazard ratio, 1.87 [95% CI, 1.20-2.92]). Conclusions and Relevance Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years, age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years. Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and cannot be recommended. Trial Registration clinicaltrials.gov Identifier:NCT00398931

Abstract: Background: Increased risk of osteoporosis and its clinical significance in patients with diabetes is controversial. We analyze osteoporosis prevalence and determinants of bone mineral density (BMD) in patients with type 1 and 2 diabetes. Methods: Three hundred and ninety-eight consecutive diabetic patients from a single outpatient clinic received a standardized questionnaire on osteoporosis risk factors, and were evaluated for diabetes-related complications, HbA1c levels, and lumbar spine (LS) and femoral neck (FN) BMD. Of these, 139 (71 men, 68 women) type 1 and 243 (115 men, 128 women) type 2 diabetes patients were included in the study. BMD (T-scores and values adjusted for age, BMI and duration of disease) was compared between patient groups and between patients with type 2 diabetes and population-based controls (255 men, 249 women). Results: For both genders, adjusted BMD was not different between the type 1 and type 2 diabetes groups but was higher in the type 2 group compared with controls (p < 0.0001). Osteoporosis prevalence (BMD T-score <�2.5 SD) at FN and LS was equivalent in the type 1 and type 2 diabetes groups, but lower in type 2 patients compared with controls (FN: 13.0% vs 21.2%, LS: 6.1% vs 14.9% men; FN: 21.9% vs 32.1%, LS: 9.4% vs 26.9% women). Osteoporosis prevalence was higher at FN-BMD than at LS-BMD. BMD was positively correlated with BMI and negatively correlated with age, but not correlated with diabetes-specific parameters (therapy, HbBA1c, micro- and macrovascular complications) in all subgroups. Fragility fracture prevalence was low (5.2%) and not different between diabetes groups. Fracture patients had lower BMDs compared with those without fractures; however, BMD T-score was above �2.5 SD in most patients. Conclusions: Diabetes-specific parameters did not predict BMD. Fracture occurrence was similar in both diabetes groups and related to lower BMD, but seems unrelated to the threshold T-score, <�2.5 SD. These results suggest that osteoporosis, and related fractures, is a clinically significant and commonly underestimated problem in diabetes patients.

Abstract: Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as salt-and-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT.