Electronic Health Records (EHRs) Can Identify Patients at High Risk of Fracture but Require Substantial Race Adjustments to Currently Available Fracture Risk Calculators.

BACKGROUND: Osteoporotic fracture prediction calculators are poorly utilized in primary care, leading to underdiagnosis and undertreatment of those at risk for fracture. The use of these calculators could be improved if predictions were automated using the electronic health record (EHR). However, this approach is not well validated in multi-ethnic populations, and it is not clear if the adjustments for race or ethnicity made by calculators are appropriate. OBJECTIVE: To investigate EHR-generated fracture predictions in a multi-ethnic population. DESIGN: Retrospective cohort study using data from the EHR. SETTING: An urban, academic medical center in Philadelphia, PA. PARTICIPANTS: 12,758 White, 7,844 Black, and 3,587 Hispanic patients seeking routine care from 2010 to 2018 with mean 3.8 years follow-up. INTERVENTIONS: None. MEASUREMENTS: FRAX and QFracture, two of the most used fracture prediction tools, were studied. Risk for major osteoporotic fracture (MOF) and hip fracture were calculated using data from the EHR at baseline and compared to the number of fractures that occurred during follow-up. RESULTS: MOF rates varied from 3.2 per 1000 patient-years in Black men to 7.6 in White women. FRAX and QFracture had similar discrimination for MOF prediction (area under the curve, AUC, 0.69 vs. 0.70, p=0.08) and for hip fracture prediction (AUC 0.77 vs 0.79, p=0.21) and were similar by race or ethnicity. FRAX had superior calibration than QFracture (calibration-in-the-large for FRAX 0.97 versus QFracture 2.02). The adjustment factors used in MOF prediction were generally accurate in Black women, but underestimated risk in Black men, Hispanic women, and Hispanic men. LIMITATIONS: Single center design. CONCLUSIONS: Fracture predictions using only EHR inputs can discriminate between high and low risk patients, even in Black and Hispanic patients, and could help primary care physicians identify patients who need screening or treatment. However, further refinements to the calculators may better adjust for race-ethnicity.

BMDs Derived From Total Body DXA are Strongly Correlated With Dedicated Hip and Spine BMD and are Associated With Prior Fractures in NHANES.

Dedicated dual energy X-ray absorptiometry (DXA) bone mineral density (BMD) of the hip and spine are strongly associated with fractures, but it is not clear whether total body (TB) DXA measures correlate with dedicated DXA or relate to fractures. Using National Health and Nutrition Examination Survey (NHANES) data from years 2013-2014 and 2017-2018, we assessed Pearson correlations between dedicated and TB DXA measures. Associations with fractures were examined using self-reported prior fractures or fractures found on vertebral fracture assessment (VFA) using logistic regression models while controlling for age, gender, race/ethnicity, and body mass index. Among 1418 subjects from NHANES 2013-2014, we found signification correlations between all dedicated DXA BMD and TB DXA BMD measures. For dedicated spine BMD, the TB site with the strongest correlation was TB lumbar spine (r = 0.87, p < 0.001), while for dedicated total hip and femoral neck BMD, total body, pelvis, leg, and trunk BMD had the strongest correlations (r = 0.67-0.75, p < 0.001 for all). There were relatively few differences by sex or race/ethnicity. Findings were similar in 481 subjects from NHANES 2017-2018. In NHANES 2013-2014, there were 438 prior fractures in 370 subjects (26.3%). When controlling for age, gender, race/ethnicity, and body mass index, the adjusted odds ratio for fracture per T-score decrease of BMD were similar for TB BMD measures as for dedicated BMD measures (OR 1.10-1.28). In conclusion, total body DXA measures are correlated with hip and spine DXA and are strongly associated with prior fracture. Our results suggest that total body DXA measures are valid alternative sites to study BMD and fracture risk.

The PARADIGHM (physicians advancing disease knowledge in hypoparathyroidism) registry for patients with chronic hypoparathyroidism: study protocol and interim baseline patient characteristics.

BACKGROUND: The PARADIGHM registry of adult and pediatric patients with chronic hypoparathyroidism evaluates the long-term safety and effectiveness of treatment with recombinant human parathyroid hormone, rhPTH(1-84), and describes the clinical disease course under conditions of routine clinical practice. In this first report, we detail the registry protocol and describe the baseline characteristics of two adult patient cohorts from an interim database analysis. One cohort after study entry were prescribed rhPTH(1-84), and the other cohort received conventional therapy of calcium and active vitamin D. METHODS: An observational study of patients with chronic hypoparathyroidism in North America and Europe, collecting data for ≥10 years per patient. Main outcome measures were baseline patient demographics, clinical characteristics, medications, and disease outcome variables of symptoms, biochemical parameters, and health assessments. Baseline is the enrollment assessment for all variables except biochemical measurements in patients treated with rhPTH(1-84); those measurements were the most recent value before the first rhPTH(1-84) dose. Exclusion criteria applied to the analysis of specified outcomes included pediatric patients, patients who initiated rhPTH(1-84) prior to enrollment, and those who received rhPTH(1-34). Clinically implausible biochemical outlier data were excluded. RESULTS: As of 30 June 2019, data of 737 patients were analyzed from 64 centers; 587 (80%) were women, mean ± SD age 49.1±16.45 years. At enrollment, symptoms reported for patients later prescribed rhPTH(1-84) (n=60) and those who received conventional therapy (n=571), respectively, included fatigue (51.7%, 40.1%), paresthesia (51.7%, 29.6%), muscle twitching (48.3%, 21.9%), and muscle cramping (41.7%, 33.8%). Mean serum total calcium, serum phosphate, creatinine, and estimated glomerular filtration rate were similar between cohorts. Health-related quality of life (HRQoL) 36-item Short Form Health Survey questionnaire scores for those later prescribed rhPTH(1-84) were generally lower than those for patients in the conventional therapy cohort. CONCLUSIONS: At enrollment, based on symptoms and HRQoL, a greater percentage of patients subsequently prescribed rhPTH(1-84) appeared to have an increased burden of disease than those who received conventional therapy despite having normal biochemistry measurements. PARADIGHM will provide valuable real-world insights on the clinical course of hypoparathyroidism in patients treated with rhPTH(1-84) or conventional therapy in routine clinical practice. TRIAL REGISTRATION: EUPAS16927, NCT01922440.

The Prediction of Body Composition in African Americans From Spine and Hip Dual-Energy Absorptiometry.

Body composition, the makeup of the body's fat and lean tissue, is associated with important health outcomes and provides useful clinical information. Although body composition can be measured with total body dual-energy X-ray absorptiometry (DXA), this is rarely performed. As an alternative to total body DXA measurement, methods for estimation of body composition have been developed. These methods use soft tissue measures from spine and hip DXA to predict body composition and include prediction equations previously published by Leslie and proprietary equations within General Electric densitometry software. However, these estimates have not been tested in African Americans (AA), an ethnicity with a different distribution of fat than Caucasians (CA). Therefore, we examined the performance of the existing models in 99 CA and 162 AA subjects over the age of 40 who had total body, spine, and hip DXA measurements. We observed that existing models estimated body composition well in CA but underestimated fat mass and overestimated lean mass in AA. AA subjects were then randomly divided into 2 equal-sized subgroups-the first to develop new prediction equations and the second to independently validate them. We found that body composition can be more accurately estimated using either a new model that we derived in AA subjects using backward stepwise elimination or by adding a fixed offset for AA to the previously published model. Our results demonstrate that body composition estimates from spine and hip DXA require consideration of race/ethnicity.

Dual-energy X-ray Absorptiometry.

Bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) is the most commonly used method to assess fracture risk. DXA utilizes two different energy X-rays to calculate BMD and, by comparison to a young normative database, the T-score. In 1994, the World Health Organization defined osteoporosis based on T-score, changing the paradigm of the field and forever placing DXA measurements in the center of osteoporosis diagnosis. Since then, many large studies have demonstrated the predictive value of BMD by DXA-for every standard deviation decline in BMD, there is a relative risk of 1.5-2.5 for fracture. This predictive ability is similar to how blood pressure can predict myocardial infarction. Limitations of DXA are also important to consider. While BMD by DXA can identify those at risk, there is a significant overlap in the BMD of patients who will and will not fracture. Special considerations are also needed in men and ethnic minority groups. These groups may have different bone size, thus affecting the normative range of BMD, and/or distinct bone structure that affect the association between BMD and fractures. Finally, BMD can be affected by positioning errors or artifacts, including osteoarthritis, fracture, and jewelry. Of course, DXA has tremendous strengths as well-namely its wide availability, its low radiation exposure, and a large body of evidence that relate DXA measurements to fracture risk. For these reasons, DXA remains the cornerstone of fracture assessment now and for the foreseeable future.

Ethnic Differences in Osteoporosis After Cardiac Transplantation.

Cardiac transplantation is associated with a high risk of fracture. African Americans (AAs) are believed to have a lower risk of osteoporosis than Caucasians, but it is not clear whether they are also protected from osteoporosis resulting from the use of glucocorticoids and/or organ transplantation. We examined possible ethnic differences in 33 cardiac transplant recipients (16 AAs) in a cross-sectional analysis. In addition to bone mineral density and vertebral fracture assessment, we also compared biochemical variables, trabecular bone score, total body dual-energy X-ray absorptiometry, and disability. Overall fracture rates were low in both groups, with only 6 total subjects with fractures on vertebral fracture assessment or history of fracture. While T-scores were similar between groups, Z-scores were lower in AA with the difference reaching statistical significance when controlling for important covariates. The trabecular bone score was also lower in AAs than in Caucasians even when adjusting for age and tissue thickness (1.198 ± 0.140 vs 1.312 ± 0.140, p = 0.03). While AAs are generally thought to be protected from osteoporosis, our study instead suggests that AAs may be at higher risk of bone deterioration after cardiac transplantation and may need to be managed more aggressively than suggested by current guidelines.

Ethnic Differences in Trabecular Bone Score.

Trabecular bone score (TBS), a noninvasive textural analysis of the lumbar spine dual-energy X-ray absorptiometry (DXA) image, has been shown to predict fractures in Caucasian (CA) populations but has not been thoroughly studied in African-American (AA) populations. The aim of this study was to compare the TBS in AAs and CAs and to assess whether TBS can be used to refine fracture risk stratification in AA patients. Eight hundred twenty-five women (390 AAs, 435 CAs) referred for bone mineral density (BMD) as part of their clinical care had measurements of the TBS, the BMD of the lumbar spine, total hip, and femoral neck, and vertebral fracture assessment for detection of vertebral fractures. Unadjusted TBS was higher in CA than AA (1.275 vs 1.238, p < 0.001), but this was no longer true after adjusting for age and tissue thickness. Interestingly, differences in TBS were still highly significant in those under 60 yr of age even with adjustment for tissue thickness, but not in older subjects. There were 74 CAs and 56 AAs with vertebral fractures on vertebral fracture assessment (17% vs 14%, p = 0.30). In CA, the odds ratio (OR) for prevalent vertebral fracture per SD decrease in TBS was 2.33 (p < 0.001), whereas in AA, the OR was 1.43 (p = 0.02). In a multivariate logistic regression model that also included age, BMD T-score, and glucocorticoid use, the association between TBS and prevalent vertebral fractures was still highly significant in CAs (OR 1.54, p = 0.008) but not in AAs (OR 1.23, p = 0.21). Our results suggest that TBS may be less discriminatory in regard to fracture risk in AAs than in CAs and that TBS may need to be used differently in these 2 ethnic groups.

The ISCD and Vertebral Fractures.

Some 30 years ago the diagnosis of osteoporosis relied primarily on the measurement of bone mineral density by DXA. More recently, however, it was recognized that vertebral fractures are an important predictor of future fractures and that they reflect some aspect of bone fragility not captured by BMD measurement. In response to that, DXA manufacturers developed VFA, spine imaging on the densitometer, which allowed integration of BMD with information on vertebral fractures obtained at the same visit. ISCD has been instrumental in several aspects of VFA use such as developing and teaching courses for VFA or more broadly, for recognition of vertebral fractures; in developing guidelines for performance, interpretation and reporting of the VFA; and in advocating for reimbursement for VFA tests performed in the clinical practice. ISCD is poised to continue as a leader in vertebral fracture recognition and application of VFA to clinical practice and research.

Vertebral Morphometry.

There is as yet no agreement about the criteria by which to arrive at an imaging diagnosis of a vertebral fracture. Because high-grade fractures result in alterations in vertebral shape, 1 possible avenue of diagnosis has been to quantitate changes in vertebral shape. The result has been a variety of methods for the relative and absolute measurements of vertebral dimensions. Such measurements have also lent themselves to automated computed analysis. The number of techniques reflects the absence of any consensus about the best. The semiquantitative technique proposed by Genant has become the most widely used and has served the field well for comparative purposes. Its use in higher grade fractures has been widely endorsed, if some concepts (e.g., short vertebral height-vertebrae) are at variance with lower grades of fracturing. Vertebral morphometry may be the only recourse in high volume epidemiological and interventional studies.

Utility of heel dual-energy X-ray absorptiometry in diagnosing osteoporosis.

Although peripheral dual-energy X-ray absorptiometry measurements have been found to predict fractures in population studies of white subjects, little is known about their utility in other races and in patients with greater risk of fracture. In a cross-sectional study of 874 women referred for bone mineral density (BMD) testing, we examined the utility of heel BMD in African-American (AA) compared with Caucasian (CA) women and in women using glucocorticoids. The ability of heel T-score to predict central osteoporosis was similar in AA and CA women (odds ratio [OR] per 1 unit decrease in T-score of 2.79 [95% confidence interval {CI} 2.16-3.60] and 3.15 [95% CI 2.53-3.92], respectively). The association between heel T-score and prevalent vertebral fractures was also similar in the 2 groups (OR 1.46 [95% CI 1.15-1.85] in AA and 1.42 [95% CI 1.16-1.74] in CA). In women using glucocorticoids heel T-score was better than central T-score in predicting vertebral fractures (OR 1.38 [95% CI 1.03-1.85] and 1.22 [95% CI 0.86-1.73], respectively). We conclude that in a multiracial referral population heel BMD predicts central osteoporosis and prevalent vertebral fractures equally well in AA as in CA women and may be better than central BMD in assessing fragility in glucocorticoid users.

Simplified criteria for selecting patients for vertebral fracture assessment.

The 2013 Position Development Conference of the International Society for Clinical Densitometry (ISCD) has adopted simplified indications for vertebral fracture assessment (VFA) based on an analysis of the Study of Osteoporotic Fractures (SOF). This showed that a simpler regression model, which included only age, bone mineral density (BMD), and height loss, was able to differentiate women with vertebral fractures from those without vertebral fractures almost as well as more complex models. We aimed to verify these findings in 1228 women referred for BMD testing and determine if the 2013 ISCD indications for VFA would perform as well the 2007 indications. The simple and complex SOF-based models were similar in terms of sensitivity (88.4% vs 89.4%), specificity (44.4% vs 45.5%), positive (25.9% vs 26.5%) and negative (94.5% vs 95.1%) predictive values, and area under the receiver operating characteristics curve (AUROC) (0.664 vs 0.674). The 2013 and 2007 ISCD VFA indications did not differ significantly in terms of sensitivity (88.2% vs 91.3%), specificity (41.3% vs 37.5%), positive (25.3% vs 22.9%) and negative (93.9% vs 95.5%) predictive values, and AUROC (0.648 vs 0.644). Our study provides support for the use of the simplified 2013 ISCD VFA indications as a practical approach to VFA testing.

Prediction models of prevalent radiographic vertebral fractures among older women.

It is unknown how well prediction models incorporating multiple risk factors identify women with radiographic prevalent vertebral fracture (PVFx) compared with simpler models and what their value might be in clinical practice to select older women for lateral spine imaging. We compared 4 regression models for predicting PVFx in women aged 68 y and older enrolled in the Study of Osteoporotic Fractures with a femoral neck T-score ≤ -1.0, using area under receiving operator characteristic curves (AUROC) and a net reclassification index. The AUROC for a model with age, femoral neck bone mineral density, historical height loss (HHL), prior nonspine fracture, body mass index, back pain, and grip strength was only minimally better than that of a more parsimonious model with age, femoral neck bone mineral density, and historical height loss (AUROC 0.689 vs 0.679, p values for difference in 5 bootstrapped samples <0.001-0.35). The prevalence of PVFx among this older population of Caucasian women remained more than 20% even when women with low probability of PVFx, as estimated by the prediction models, were included in the screened population. These results suggest that lateral spine imaging is appropriate to consider for all Caucasian women aged 70 y and older with low bone mass to identify those with PVFx.

Prediction models of prevalent radiographic vertebral fractures among older men.

No studies have compared how well different prediction models discriminate older men who have a radiographic prevalent vertebral fracture (PVFx) from those who do not. We used area under receiver operating characteristic curves and a net reclassification index to compare how well regression-derived prediction models and nonregression prediction tools identify PVFx among men age ≥65 yr with femoral neck T-score of -1.0 or less enrolled in the Osteoporotic Fractures in Men Study. The area under receiver operating characteristic for a model with age, bone mineral density, and historical height loss (HHL) was 0.682 compared with 0.692 for a complex model with age, bone mineral density, HHL, prior non-spine fracture, body mass index, back pain, grip strength, smoking, and glucocorticoid use (p values for difference in 5 bootstrapped samples 0.14-0.92). This complex model, using a cutpoint prevalence of 5%, correctly reclassified only a net 5.7% (p = 0.13) of men as having or not having a PVFx compared with a simple criteria list (age ≥ 80 yr, HHL >4 cm, or glucocorticoid use). In conclusion, simple criteria identify older men with PVFx and regression-based models. Future research to identify additional risk factors that more accurately identify older men with PVFx is needed.

Indications of DXA in women younger than 65 yr and men younger than 70 yr: the 2013 Official Positions.

Dual-energy X-ray absorptiometry (DXA) is the method of choice to assess fracture risk for women 65 yr and older and men 70 yr and older. The 2007 International Society for Clinical Densitometry Official Positions had developed guidelines for assessing bone density in younger women during and after the menopausal transition and in men 50-69 yr and the 2008 National Osteoporosis Foundation (NOF) guidelines recommended testing in postmenopausal women younger than 65 yr and men 50-69 yr only in the presence of clinical risk factors. The purpose of the 2013 DXA Task Force was to reassess the NOF guidelines for ordering DXA in postmenopausal women younger than 65 yr and men 50-69 yr. The Task Force reviewed the literature published since the 2007 Position Development Conference and 2008 NOF, reviewing clinical decision rules such as the Osteoporosis Screening Tool and FRAX and sought to keep recommendations simple to remember and implement. Based on this assessment, the NOF guidelines were endorsed; DXA was recommended in those postmenopausal women younger than 65 yr and men 50-69 yr only in the presence of clinical risk factors for low bone mass, such as low body weight, prior fracture, high-risk medication use, or a disease or condition associated with bone loss.

The Official Positions of the International Society for Clinical Densitometry: vertebral fracture assessment.

Vertebral fracture assessment (VFA) is a low-cost method of accurately identifying individuals who have clinically unrecognized or undocumented vertebral fractures at the time of bone density test. Because prevalent vertebral fractures predict subsequent fractures independent of bone mineral density and other clinical risk factors, their recognition is an important part of strategies to identify those who are at high risk of fracture, so that prevention therapies for those individuals can be implemented. The 2007 Position Development Conference developed detailed guidelines regarding the indications for acquisition of, and interpretation and reporting of densitometric VFA tests. The purpose of the 2013 VFA Task Force was to simplify the indications for VFA yet keep them evidence based. The Task Force reviewed the literature published since the 2007 Position Development Conference and developed prediction models based on 2 large cohort studies (the Study of Osteoporotic Fractures and the Osteoporotic Fractures in Men Study) and the densitometry database of the University of Chicago. Based on these prediction models, indications for VFA were reduced to a simplified set of criteria based on age, historical height loss, use of systemic glucocorticoid therapy, and self-reported but undocumented prior vertebral fracture.

Visceral Adipose Tissue is Negatively Associated With Bone Mineral Density in NHANES 2011-2018.

Context: The relationship of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with bone mineral density (BMD) is not well established. Objective: To examine the associations of VAT and SAT with total body BMD in a large, nationally representative population with a wide range of adiposity. Methods: We analyzed 10 641 subjects aged 20 to 59 years in National Health and Nutrition Examination Survey 2011-2018 who had undergone total body BMD and had VAT and SAT measured by dual-energy X-ray absorptiometry. Linear regression models were fitted while controlling for age, sex, race or ethnicity, smoking status, height, and lean mass index. Results: In a fully adjusted model, each higher quartile of VAT was associated with an average of 0.22 lower T-score (95% CI, -0.26 to -0.17, P < 0.001), whereas SAT had a weak association with BMD but only in men (-0.10; 95% CI, -0.17 to -0.04, P = 0.002). However, the association of SAT to BMD in men was no longer significant after controlling for bioavailable sex hormones. In subgroup analysis, we also found differences in the relationship of VAT to BMD in Black and Asian subjects, but these differences were eliminated after accounting for racial and ethnic differences in VAT norms. Conclusions: VAT has a negative association with BMD. Further research is needed to better understand the mechanism of action and, more generally, to develop strategies for optimizing bone health in obese subjects.

Long-Term Safety and Efficacy of Recombinant Human Parathyroid Hormone (1-84) in Adults With Chronic Hypoparathyroidism.

Context: Chronic hypoparathyroidism is conventionally treated with oral calcium and active vitamin D to reach and maintain targeted serum calcium and phosphorus levels, but some patients remain inadequately controlled. Objective: To assess long-term safety and efficacy of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) treatment. Methods: This was an open-label extension study at 12 US centers. Adults (n = 49) with chronic hypoparathyroidism were included. The intervention was rhPTH(1-84) for 6 years. The main outcome measures were safety, biochemical measures, oral supplement doses, bone indices. Results: Thirty-eight patients (77.6%) completed the study. Throughout 72 months, mean albumin-adjusted serum calcium was within 2.00 to 2.25 mmol/L (8.0-9.0 mg/dL). At baseline, 65% of patients with measurements (n = 24/37) were hypercalciuric; of these, 54% (n = 13/24) were normocalciuric at month 72. Mean serum phosphorus declined from 1.6 ± 0.19 mmol/L at baseline (n = 49) to 1.3 ± 0.20 mmol/L at month 72 (n = 36). Mean estimated glomerular filtration rate was stable. rhPTH(1-84)-related adverse events were reported in 51.0% of patients (n = 25/49); all but 1 event were mild/moderate in severity. Mean oral calcium supplementation reduced by 45% ± 113.6% and calcitriol by 74% ± 39.3%. Bone turnover markers declined by month 32 to a plateau above pretreatment values; only aminoterminal propeptide of type 1 collagen remained outside the reference range. Mean bone mineral density z score fell at one-third radius and was stable at other sites. Conclusion: 6 years of rhPTH(1-84) treatment was associated with sustained improvements in biochemical parameters, a reduction in the percentage of patients with hypercalciuria, stable renal function, and decreased supplement requirements. rhPTH(1-84) was well tolerated; no new safety signals were identified.

Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial.

Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double-blind, placebo-controlled, 26-week, phase 3 PaTHway trial assessed the efficacy and safety of PTH replacement therapy for hypoparathyroidism individuals with the investigational drug TransCon PTH (palopegteriparatide). Participants (n = 84) were randomized 3:1 to once-daily TransCon PTH (initially 18 µg/d) or placebo, both co-administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin-adjusted serum calcium levels (8.3-10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. Other outcomes of interest included health-related quality of life measured by the 36-Item Short Form Survey (SF-36), hypoparathyroidism-related symptoms, functioning, and well-being measured by the Hypoparathyroidism Patient Experience Scale (HPES), and urinary calcium excretion. At week 26, 79% (48/61) of participants treated with TransCon PTH versus 5% (1/21) wiplacebo met the composite primary efficacy endpoint (p < 0.0001). TransCon PTH treatment demonstrated a significant improvement in all key secondary endpoint HPES domain scores (all p < 0.01) and the SF-36 Physical Functioning subscale score (p = 0.0347) compared with placebo. Additionally, 93% (57/61) of participants treated with TransCon PTH achieved independence from conventional therapy. TransCon PTH treatment normalized mean 24-hour urine calcium. Overall, 82% (50/61) treated with TransCon PTH and 100% (21/21) wiplacebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred. In conclusion, TransCon PTH maintained normocalcemia while permitting independence from conventional therapy and was well-tolerated in individuals with hypoparathyroidism. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Fat Mass Has Negative Effects on Bone, Especially in Men: A Cross-sectional Analysis of NHANES 2011-2018.

CONTEXT: The effect of high levels of obesity on bone health are not clear. OBJECTIVE: We aimed to examine the associations of body composition and bone mineral density (BMD) in a large, nationally representative population with a wide range of body mass index. METHODS: We analyzed 10 814 subjects aged 20-59 from NHANES 2011-2018 who had total body BMD and body composition data. Body composition was examined as lean mass index (LMI) and fat mass index (FMI). Linear regression models were created with BMD as the outcome, while examining LMI and FMI and controlling for age, gender, race/ethnicity, height, and smoking status. RESULTS: In multivariable modeling, every 1 kg/m2 additional LMI was associated with 0.19 higher T-score, while every additional 1 kg/m2 in FMI was associated with 0.10 lower T-score (P < .001 for both). The negative association of FMI with BMD was mainly seen when adjusting for LMI. Effects of LMI were similar in men and women, but the effect of FMI was more negative in men (0.13 lower T-score per additional 1 kg/m2 of FMI in men vs 0.08 lower BMD T-score in women, P for interaction < .001). CONCLUSION: In subjects under 60 years old, lean mass had a strong positive association with BMD. Conversely, fat mass had a moderate, negative association with BMD that was most notable in men at high levels of fat. Our results emphasize the importance of bone health in obesity and may explain site-specific increases in fracture rates in some studies of obese subjects.