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Information in the electronic health record (EHR), such as diagnoses, vital signs, utilization, medications, and laboratory values, may predict fractures well without the need to verbally ascertain risk factors. In our study, as a proof of concept, we developed and internally validated a fracture risk calculator using only information in the EHR., Purpose: Fracture risk calculators, such as the Fracture Risk Assessment Tool, or FRAX, typically lie outside the clinician workflow. Conversely, the electronic health record (EHR) is at the center of the clinical workflow, and many variables in the EHR could predict fractures without having to verbally ascertain FRAX risk factors. We sought to evaluate the utility of EHR variables to predict fractures and, as a proof of concept, to create an EHR-based fracture risk model., Methods: Routine clinical data from 24,189 subjects presenting to primary care from 2010 to 2018 was utilized. Major osteoporotic fractures (MOFs) were captured by physician diagnosis codes. Data was split into training (n = 18,141) and test sets (n = 6048). We fit Cox regression models for candidate risk factors in the training set, and then created a global model using a backward stepwise approach. We then applied the model to the test set and compared the discrimination and calibration to FRAX., Results: We found variables related to vital signs, utilization, diagnoses, medications, and laboratory values to be associated with incident MOF. Our final model included 19 variables, including age, BMI, Parkinson's disease, chronic kidney disease, and albumin levels. When applied to the test set, we found the discrimination (AUC 0.73 vs. 0.70, p = 0.08) and calibration were comparable to FRAX., Conclusion: Routinely collected data in EHR systems can generate adequate fracture predictions without the need to verbally ascertain fracture risk factors. In the future, this could allow for automated fracture prediction at the point of care to improve osteoporosis screening and treatment rates., Competing Interests: Declarations. Conflicts of interest: None., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objective: Black patients fracture less often than White patients at any given bone mineral density (BMD). This may be related to superior bone structure; however, bone structure is challenging to measure in clinical practice. Advances in 3-dimensional (3D) modeling have allowed for the measurement of trabecular and cortical parameters from dual-energy x-ray absorptiometry (DXA). This technology, known as 3D-DXA, may provide a way to assess hitherto unexplained differences in bone structure between Black and White patients., Methods: This is a secondary analysis of 775 women (368 Black and 407 White) previously recruited from an osteoporosis clinic. All women had undergone DXA and vertebral fracture assessment, and 3D-DXA was run retrospectively on the proximal femur BMD scan. Participants were classified as having a prior fracture if there was a fracture on vertebral fracture assessment or a self-reported history of fragility fracture., Results: Black women had generally superior 3D-DXA parameters, with the largest differences in cortical thickness of the femoral neck (FN) and buckling ratio of the FN. There were substantial differences in associations between fracture and 3D-DXA parameters in Black women compared with White women. After adjusting for age, glucocorticoids, and areal BMD T-score, cortical thickness of the FN was significantly associated with prior fracture (odds ratio, 1.4 per standard deviation decline; 95% CI, 1.0-1.9; P = .04) in Black women but not White women., Conclusion: 3D-DXA parameters were superior in Black women than in White women, and cortical thickness of the FN was associated with fractures only in Black women. 3D-DXA may improve fracture risk assessment in Black patients., Competing Interests: Disclosure R.K.J. has received research support from the Amgen Foundation. M.L.P. is an employee of 3D-Shaper Medical. L.H. is an employee of 3D-Shaper Medical. The other authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Context: Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels., Objective: Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism., Design: Phase 3 trial with a 26-week double-blind, placebo-controlled period followed by a 156-week open-label extension (OLE)., Setting: 21 sites across North America and Europe., Participants: 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52., Intervention(s): All OLE participants received TransCon PTH administered once daily., Main Outcome Measure(s): Multi-component efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes (PROs) and bone mineral density (BMD). Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events (TEAEs)., Results: At week 52, 81% (63/78) met the multi-component efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. PROs showed sustained improvements in quality of life, physical functioning, and well-being. Mean BMD Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most TEAEs were mild or moderate and none led to trial discontinuation during the OLE., Conclusions: At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

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., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

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)., (© 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).)

Abaloparatide significantly increased bone mineral density (BMD) in women with postmenopausal osteoporosis and decreased risk of vertebral, nonvertebral, and clinical fractures compared with placebo. The Abaloparatide for the Treatment of Men with Osteoporosis (ATOM; NCT03512262) study evaluated the efficacy and safety of abaloparatide compared with placebo in men. Eligible men aged 40 to 85 years with osteoporosis were randomized 2:1 to daily subcutaneous injections of abaloparatide 80 μg or placebo for 12 months. The primary endpoint was change from baseline in lumbar spine BMD. Key secondary endpoints included BMD change from baseline at the total hip and femoral neck. A total of 228 men were randomized (abaloparatide, n = 149; placebo, n = 79). Baseline characteristics were similar across treatment groups (mean age, 68.3 years; mean lumbar spine BMD T-score, -2.1). At 12 months, BMD gains were greater with abaloparatide compared with placebo at the lumbar spine (least squares mean percentage change [standard error]: 8.48 [0.54] versus 1.17 [0.72]), total hip (2.14 [0.27] versus 0.01 [0.35]), and femoral neck (2.98 [0.34] versus 0.15 [0.45]) (all p < 0.0001). The most common (≥5%) treatment-emergent adverse events were injection site reaction, dizziness, nasopharyngitis, arthralgia, bronchitis, hypertension, and headache. During 12 months of abaloparatide treatment, men with osteoporosis exhibited rapid and significant improvements in BMD with a safety profile consistent with previous studies. These results suggest abaloparatide can be considered as an effective anabolic treatment option for men with osteoporosis. © 2022 Radius Health Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 Radius Health Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Chronic hypoparathyroidism (HypoPT) is associated with significant morbidity and impaired quality of life (QoL). The goals of management for chronic HypoPT include improvement in QoL and the prevention of both hypo- and hypercalcemia symptoms and long-term complications. Several groups have provided consensus statements and guidelines on the management of HypoPT; however, due to limited evidence, these recommendations have largely been based on literature reviews, expert opinion, and consensus statements. The objective of this study was to use a systematic approach to describe current practice for the initial assessment and follow-up of patients with chronic HypoPT. We developed a survey asking experts in the field to select the responses that best reflect their current practice. The survey found no differences in responses between nonsurgical and postsurgical patient assessment. For new patients, respondents usually performed an assessment of serum lab profile (calcium [either albumin-adjusted or ionized], magnesium, creatinine, phosphate, 25-hydroxyvitamin D), 24-hour urine (creatinine, calcium), and a renal ultrasound to evaluate for the presence of nephrocalcinosis or nephrolithiasis. For follow-up patients, most respondents perform blood tests and urine tests every 6 months or less frequently. The reported clinical practice patterns for monitoring for complications of chronic HypoPT vary considerably among respondents. Based on the responses in this systematic expert practice survey, we provide practice suggestions for initial assessment and follow-up of patients with chronic HypoPT. In addition, we highlight areas with significant variation in practice and identify important areas for future research. © 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)., (© 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).)

Hypoparathyroidism (HypoPT) is a rare disorder characterized by hypocalcemia in the presence of a low or inappropriately normal parathyroid hormone level. HypoPT is most commonly seen after neck surgery, which accounts for approximately 75% of cases, whereas approximately 25% have HypoPT due to nonsurgical causes. In both groups of patients, conventional therapy includes calcium and active vitamin D analogue therapy aiming to maintain serum calcium concentration in the low normal or just below the normal reference range and normalize serum phosphorus, magnesium concentrations, and urine calcium levels. The limitations of conventional therapy include wide fluctuations in serum calcium, high pill burden, poor quality of life, and renal complications. Parathyroid hormone (PTH) replacement therapy may improve the biochemical profile in those in whom conventional therapy proves unsatisfactory. Based on a systematic review and meta-analysis of the literature, the panel made a graded recommendation suggesting conventional therapy as first line therapy rather than administration of PTH (weak recommendation, low quality evidence). When conventional therapy is deemed unsatisfactory, the panel considers use of PTH. Because pregnancy and lactation are associated with changes in calcium homeostasis, close monitoring is required during these periods with appropriate adjustment of calcium and active vitamin D analogue therapy to ensure that serum calcium remains in the mid to low normal reference range in order to avoid maternal and fetal complications. Emerging therapies include molecules with prolonged PTH action as well as different mechanisms of action that may significantly enhance drug efficacy and safety. © 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)., (© 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).)

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., (Copyright © 2021 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Hypoparathyroidism is characterized by insufficient levels of parathyroid hormone (PTH). TransCon PTH is an investigational long-acting prodrug of PTH(1-34) for the treatment of hypoparathyroidism., Objective: This work aimed to investigate the safety, tolerability, and efficacy of daily TransCon PTH in adults with hypoparathyroidism., Methods: This phase 2, randomized, double-blind, placebo-controlled 4-week trial with open-label extension enrolled 59 individuals with hypoparathyroidism. Interventions included TransCon PTH 15, 18, or 21 µg PTH(1-34)/day or placebo for 4 weeks, followed by a 22-week extension during which TransCon PTH dose was titrated (6-60 µg PTH[1-34]/day)., Results: By Week 26, 91% of participants treated with TransCon PTH achieved independence from standard of care (SoC, defined as active vitamin D = 0 μg/day and calcium [Ca] ≤ 500 mg/day). Mean 24-hour urine Ca (uCa) decreased from a baseline mean of 415 mg/24h to 178 mg/24h by Week 26 (n = 44) while normal serum Ca (sCa) was maintained and serum phosphate and serum calcium-phosphate product fell within the normal range. By Week 26, mean scores on the generic 36-Item Short Form Health Survey domains increased from below normal at baseline to within the normal range. The Hypoparathyroidism Patient Experience Scale symptom and impact scores improved through 26 weeks. TransCon PTH was well tolerated with no treatment-related serious or severe adverse events., Conclusion: TransCon PTH enabled independence from oral active vitamin D and reduced Ca supplements (≤ 500 mg/day) for most participants, achieving normal sCa, serum phosphate, uCa, serum calcium-phosphate product, and demonstrating improved health-related quality of life. These results support TransCon PTH as a potential hormone replacement therapy for adults with hypoparathyroidism., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)