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Vertebral fracture assessment (VFA) is a new method for imaging thoracolumbar spine on bone densitometer. Among patients referred for bone densitometry, the selection of patients for VFA testing can be optimized using an index derived from clinical risk factors and bone density measurement.VFA, a method for imaging thoracolumbar spine on bone densitometer, was developed because vertebral fractures, although common and predictive of future fractures, are often not clinically diagnosed. The study objective was to develop a strategy for selecting patients for VFA.A convenience sample from a university hospital bone densitometry center included 892 subjects (795 women) referred for bone mineral density (BMD) testing. We used questionnaires to capture clinical risk factors and dual-energy X-ray absorptiometry to obtain BMD and VFA.Prevalence of vertebral fractures was 18% in women and 31% in men (p = 0.003 for gender difference). In women, age, height loss, glucocorticoid use, history of vertebral and other fractures, and BMD T-score were significantly and independently associated with vertebral fractures. A multivariate model which included above predictors had an area under the receiver operating curve of 0.85 with 95% confidence interval (CI) of 0.81 to 0.89. A risk factor index was derived from the above multivariate model. Using a level of 2 as a cut-off yielded 93% sensitivity (95% CI 87, 96) and 48% specificity (95% CI 69, 83). Assuming a 15% prevalence of vertebral fractures, this cut-off value had a 24% positive and 97% negative predictive value and required VFA scanning of three women at a cost of $60 (assuming a $20 cost/VFA scan) to detect one with vertebral fracture(s).Selecting patients for VFA can be optimized using an index derived from BMD measurement and easily obtained clinical risk factors.

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.)

Importance: Deficient (ie, <20 ng/mL) or insufficient (ie, 20 to <30 ng/mL) 25-hydroxyvitamin D (also known as calcifediol) levels are more common in Black individuals than White individuals and are associated with increased coronavirus disease 2019 (COVID-19) risk. Whether COVID-19 risk is associated with differences in vitamin D levels of 30 ng/mL or greater is not known., Objective: To examine whether COVID-19 test results are associated with differences in vitamin D levels of 30 ng/mL or greater, including for White individuals and for Black individuals., Design, Setting, and Participants: This retrospective cohort study was conducted at an academic medical center in Chicago, Illinois. Participants included individuals with data on vitamin D level within 365 days before COVID-19 testing, which was conducted from March 3 to December 30, 2020. Data were analyzed from September 11, 2020, to February 5, 2021., Exposures: The last vitamin D level before COVID-19 testing was categorized as less than 20 ng/mL (ie, deficient), 20 to less than 30 ng/mL (ie, insufficient), 30 to less than 40 ng/mL, or 40 ng/mL or greater. Treatment was defined by vitamin D type and dose 14 days before COVID-19 testing and treatment changes after last vitamin D level., Main Outcomes and Measures: The main outcome was a positive result for COVID-19 in polymerase chain reaction testing. Multivariable analyses tested whether previously measured vitamin D level was associated with having test results positive for COVID-19 in White individuals and in Black individuals, controlling for months and treatment changes since the vitamin D level was measured, as well as demographic characteristics and comorbidity indicators., Results: A total of 4638 individuals (mean [SD] age 52.8 [19.5] years; 3205 [69%] women) had data for a vitamin D level within 1 year before COVID-19 testing, including 2288 (49%) Black individuals, 1999 (43%) White individuals, and 351 individuals (8%) who were another race/ethnicity (eg, Asian, Mideast Indian, >1 race). Stratified by vitamin D level, 1251 individuals (27%) had less than 20 ng/mL, 1267 individuals (27%) had 20 to less than 30 ng/mL, 1023 individuals (22%) had 30 to less than 40 ng/mL, and 1097 individuals (24%) had 40 ng/mL or greater. Lower vitamin D levels were more common in Black individuals (<20 ng/mL: 829 of 2288 Black individuals [36%]) than White individuals (<20 ng/mL: 315 of 1999 White individuals [16%]). A total of 333 individuals (7%) had test results positive for COVID-19, including 102 White individuals (5%) and 211 Black individuals (9%). Multivariate analysis controlling for time since last vitamin D level measurement was used to estimate the outcomes associated with levels 14 days before COVID-19 testing. A positive test result for COVID-19 was not significantly associated with vitamin D levels in White individuals but was associated with vitamin D levels in Black individuals (compared with ≥40 ng/mL: <20 ng/mL incidence rate ratio [IRR], 2.55 [95% CI, 1.26-5.15]; P = .009; 20 to <30 ng/mL IRR, 1.69 [95% CI, 0.75-3.84]; P = .21; 30 to <40 ng/mL IRR, 2.64 [95% CI, 1.24-5.66]; P = .01). Stratified by vitamin D level, estimated COVID-19 positivity rates in Black individuals were 9.72% (95% CI, 6.74%-13.41%) for individuals with a vitamin D level less than 20 ng/mL, 6.47% (95% CI, 3.33%-10.28%) for individuals with a vitamin D level of 20 to less than 30 ng/mL, 10.10% (95% CI, 6.00%-15.47%) for individuals with a vitamin D level of 30 to less than 40 ng/mL, and 3.82% (95% CI, 1.78%-6.68%) for individuals with a vitamin D level of 40 ng/mL or higher. Multivariate analysis in individuals with a vitamin D level of 30 ng/mL or greater found that the IRR of a positive COVID-19 test result was 0.97 (95% CI, 0.94-0.99; P = .008) per 1-ng/mL increase in vitamin D overall and 0.95 (95% CI, 0.91-0.98; P = .003) per 1-ng/mL increase in vitamin D in Black individuals., Conclusions and Relevance: In this single-center retrospective cohort study, COVID-19 risk increased among Black individuals with vitamin D level less than 40 ng/mL compared with those with 40 ng/mL or greater and decreased with increasing levels among individuals with levels greater than 30 ng/mL. No significant associations were noted for White individuals. Randomized clinical trials should examine whether increasing vitamin D level to greater than 40 ng/mL affects COVID-19 risk.

Despite the availability of various osteoporosis treatments, adherence remains suboptimal. One contributing factor may be patient experience with therapy. This US, multicenter, combined retrospective chart review and patient questionnaire study included postmenopausal women at high risk for fracture and is the first study to describe real-world patient experience with abaloparatide (ABL) injection. Eight geographically diverse secondary care sites in the United States participated ( n = 193). Mean ± SD age was 67.4 ±8.62 years. Most patients (86%) were satisfied with the ABL regimen, especially with ease of preparation (82%), ease of storage (87%), and storage convenience (89%), an attribute 83% of the patients thought was important. The majority of patients reported complete satisfaction with the ABL regimen allowing for their ability to conduct daily activities (85%) and convenience to fit into their daily schedule (84%). All reported taking ABL as directed, by injection in the lower abdomen, and 83% of patients reported medium or high adherence. Patients were satisfied with the needle size (76% completely satisfied), and 93% reported never deliberately missing a dose. Although injecting medication (18%) and higher out-of-pocket costs (17%) were deemed the most bothersome attributes, the majority (69%) noted their healthcare team understands how osteoporosis impacts their lives. In multivariable analyses, ease of preparation (OR = 2.62; 95% CI, 1.01-6.81; p = 0.048) and fracture history (OR = 1.72; 95% CI, 1.03-2.86; p = 0.037) were significantly associated with overall satisfaction. Ease of preparation was a predictor of higher satisfaction with treatment convenience (coefficient = 13.60; 95% CI, 8.08-19.12; p = 0.00). Remembering to take the medication was a significant predictor of self-reported adherence (OR = 16.66; 95% CI, 3.30-84.24; p = 0.001). In conclusion, the majority of patients were satisfied with ABL and found it convenient/easy to prepare and store. High self-reported adherence may be associated with positive patient experience including ease of use and adequate support from healthcare providers. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research., (© 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.)

Importance: Vitamin D treatment has been found to decrease the incidence of viral respiratory tract infection, especially in patients with vitamin D deficiency. Whether vitamin D is associated with coronavirus disease 2019 (COVID-19) incidence is unknown., Objective: To examine whether the last vitamin D status before COVID-19 testing is associated with COVID-19 test results., Design, Setting, and Participants: This retrospective cohort study at an urban academic medical center included patients with a 25-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol level measured within 1 year before being tested for COVID-19 from March 3 to April 10, 2020., Exposures: Vitamin D deficiency was defined by the last measurement of 25-hydroxycholecalciferol less than 20 ng/mL or 1,25-dihydroxycholecalciferol less than 18 pg/mL before COVID-19 testing. Treatment changes were defined by changes in vitamin D type and dose between the date of the last vitamin D level measurement and the date of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize the most recent vitamin D status before COVID-19 testing as likely deficient (last level deficient and treatment not increased), likely sufficient (last level not deficient and treatment not decreased), and 2 groups with uncertain deficiency (last level deficient and treatment increased, and last level not deficient and treatment decreased)., Main Outcomes and Measures: The outcome was a positive COVID-19 polymerase chain reaction test result. Multivariable analysis tested whether vitamin D status before COVID-19 testing was associated with testing positive for COVID-19, controlling for demographic and comorbidity indicators., Results: A total of 489 patients (mean [SD] age, 49.2 [18.4] years; 366 [75%] women; and 331 [68%] race other than White) had a vitamin D level measured in the year before COVID-19 testing. Vitamin D status before COVID-19 testing was categorized as likely deficient for 124 participants (25%), likely sufficient for 287 (59%), and uncertain for 78 (16%). Overall, 71 participants (15%) tested positive for COVID-19. In multivariate analysis, testing positive for COVID-19 was associated with increasing age up to age 50 years (relative risk, 1.06; 95% CI, 1.01-1.09; P = .02); non-White race (relative risk, 2.54; 95% CI, 1.26-5.12; P = .009), and likely deficient vitamin D status (relative risk, 1.77; 95% CI, 1.12-2.81; P = .02) compared with likely sufficient vitamin D status. Predicted COVID-19 rates in the deficient group were 21.6% (95% CI, 14.0%-29.2%) vs 12.2%(95% CI, 8.9%-15.4%) in the sufficient group., Conclusions and Relevance: In this single-center, retrospective cohort study, likely deficient vitamin D status was associated with increased COVID-19 risk, a finding that suggests that randomized trials may be needed to determine whether vitamin D affects COVID-19 risk.

Context: Diabetes mellitus (DM) is associated with an increased risk of fracture, but it is not clear which diabetes and nondiabetes risk factors may be most important., Objective: The aim of the study was to evaluate risk factors for incident major osteoporotic fractures (MOFs) of the hip, wrist, and humerus in African American (AA), Hispanic (HIS), and Caucasian (CA) subjects with DM., Methods: This was a retrospective cohort study of 18 210 subjects with DM (7298 CA, 7009 AA and 3903 HIS) at least 40 years of age, being followed at a large healthcare system in Philadelphia, Pennsylvania., Results: In a global model in CA with DM, MOF were associated with dementia (HR 4.16; 95% CI, 2.13-8.12), OSA (HR 3.35; 95% CI, 1.78-6.29), COPD (HR 2.43; 95% CI, 1.51-3.92), and diabetic neuropathy (HR 2.52; 95% CI, 1.41-4.50). In AA, MOF were associated with prior MOF (HR 13.67; 95% CI, 5.48-34.1), dementia (HR 3.10; 95% CI, 1.07-8.98), glomerular filtration rate (GFR) less than 45 (HR 2.05; 95% CI, 1.11-3.79), thiazide use (HR 0.54; 95% CI, 0.31-0.93), metformin use (HR 0.59; 95% CI, 0.36-0.97), and chronic steroid use (HR 5.03; 95% CI, 1.51-16.7). In HIS, liver disease (HR 3.06; 95% CI, 1.38-6.79) and insulin use (HR 2.93; 95% CI, 1.76-4.87) were associated with MOF., Conclusion: In patients with diabetes, the risk of fracture is related to both diabetes-specific variables and comorbid conditions, but these relationships vary by race/ethnicity., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Diabetes mellitus (DM) has been associated with a 60% to 90% increased risk of fracture but few studies have been performed in African American and Hispanic subjects., Objective: The aim of the present study was to quantify the risk of incident major osteoporotic fractures (MOFs) of the hip, wrist, and humerus in African Americans, Hispanics, and Caucasians with DM compared with those with hypertension (HTN)., Methods: We performed a retrospective cohort study of 19,153 subjects with DM (7618 Caucasians, 7456 African Americans, and 4079 Hispanics) and 26,217 with HTN (15,138 Caucasians, 8301 African Americans, and 2778 Hispanics) aged ≥40 years, treated at a large health care system in Philadelphia, Pennsylvania. All information about the subjects was obtained from electronic health records., Results: The unadjusted MOF rates for each race/ethnicity were similar among those with DM and those with HTN (Caucasians, 1.85% vs 1.84%; African Americans, 1.07% vs 1.29%; and Hispanics, 1.69% vs 1.33%; P = NS for all). However, the MOF rates were higher for Caucasians and Hispanics with DM than for African Americans with DM (P < 0.01). In a multivariable model controlled for age, body mass index, sex, and previous MOF, DM was a statistically significant predictor of MOFs only for Caucasians and Hispanics [hazard ratio (HR), 1.23; 95% CI, 1.02 to 1.48; P = 0.026] but not for African Americans (HR, 0.92; 95% CI, 0.68 to 1.23; P = 0.56)., Conclusions: Hispanics had a DM-related fracture risk similar to that of Caucasians, but AAs did not have an additional fracture risk conferred by DM., (Copyright © 2019 Endocrine Society.)

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., (Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

In an analysis of NHANES 2005-2006, older, but not younger, women and men with higher levels of physical activity had higher TBS, total hip T-score, and femoral neck T-score. Even modest levels of physical activity may be a crucial component of bone health maintenance., Purpose: Physical activity is associated with improved bone parameters in adolescence, but it is not clear if this persists into adulthood. Further, it is unclear how low levels of physical activity as measured by accelerometer may impact bone parameters., Methods: We analyzed data from subjects from NHANES 2005-2006 over the age of 20 who had accelerometry and bone mineral density (BMD) testing. We analyzed women and men separately and grouped by over or under 50 years of age: 484 younger women, 486 older women, 604 younger men, and 609 older men. Moderate-to-vigorous physical activity (MVPA) was categorized as low (less than 5 min daily), intermediate (5-20 min daily), or high (at least 20 min daily)., Results: Among younger women and men, there was no significant relationship between MVPA and BMD or trabecular bone score (TBS). Conversely, older women with intermediate and high MVPA had higher TBS (1.360 ± 0.008 and 1.377 ± 0.009 vs 1.298 ± 0.010, p < 0.001), total hip T-score (- 1.02 ± 0.13 and - 0.90 ± 0.09 vs. - 1.51 ± 0.08, p < 0.01), and femoral neck T-score than women with low MVPA, respectively. Similarly, older men with high MVPA had higher TBS, total hip T-score, and femoral neck T-score than men with intermediate and low MVPA., Conclusions: Older, but not younger, women and men with higher levels of activity had higher BMD and TBS. Benefits were noted with as little as 5-20 min of daily physical activity. Our results suggest that physical activity is a crucial component of bone health maintenance.

Hypoparathyroidism is a rare endocrine disorder where deficiency (or lack of effect) of parathyroid hormone results in disordered mineral metabolism leading to hypocalcemia and hyperphosphatemia. Many patients with this disorder have physical, emotional and cognitive complaints suggestive of impaired quality of life (QOL). Several recent studies have demonstrated that hypoparathyroid patients treated with calcium and vitamin D (conventional therapy) have reduced QOL compared to either suitable controls or general population. QOL has also been studied during treatment with PTH1-84, which has been FDA approved in the USA as an adjunct to calcium and vitamin D in patients not adequately controlled on conventional therapy. In open label studies, PTH therapy has resulted in dramatic improvements in SF-36 scores. In placebo-controlled, double-blinded studies the effect of PTH on QOL has been less striking. In one such study there was no improvement, possibly due to high incidence of hypercalcemia in the PTH-treated group. In contrast, in the pivotal trial leading to PTH1-84 approval, were hypercalcemia was less common, SF36 scores improved in the PTH-treated but not in the placebo group although between-group differences were not statistically significant. In the same study, patients who started with lower baseline QOL scores had greater improvements, suggesting that patients with poor wellbeing may be particularly suitable for this new therapy. In the future, it will be necessary to develop disease specific instruments to better define the nature of QOL impairments in this disease. In addition, further studies should focus on the possible relationship between biochemical variables and QOL parameters during treatment with different regimens., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The present study examined the efficacy and safety of a lower rhPTH(1-84) dose., Methods: RELAY was a dose-blinded, multicenter, 8-week study of patients with hypoparathyroidism randomized to fixed 25- or 50-μg/d doses of subcutaneous rhPTH(1-84). The primary end point was the percentage of patients at week 8 with supplement reductions in calcium to ≤500 mg/d and in calcitriol to ≤0.25 μg/d, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal. The secondary end point was the percentage of patients at week 8 with a ≥50% reduction in calcium and calcitriol doses, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal., Findings: Forty-two patients were randomized (25-μg group, n = 19; 50-μg group, n = 23). At week 8, the primary end point was achieved by 4 (21%; 95% CI, 6%-46%) and 6 (26%; 95% CI, 10%-48%) of the patients receiving 25 and 50 μg/d of rhPTH(1-84), respectively. The secondary end point was achieved by 2 (11%; 95% CI, 1%-33%) and 6 (26%; 95% CI, 10%-48%) of the patients receiving 25 and 50 μg/d of rhPTH(1-84), respectively. Treatment-emergent adverse events were reported by 11 (58%) patients in the 25-μg group and 17 (74%) patients in the 50-μg group., Implications: Doses as low as 25 µg/d of rhPTH(1-84) are well tolerated and may be effective for a subset of patients. ClinicalTrials.gov identifier: NCT01268098., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016. Published by Elsevier Inc.)

Background: Normohormonal primary hyperparathyroidism presents diagnostic and intraoperative challenges, and current literature is conflicting about management. We aim to better define normohormonal primary hyperparathyroidism in order to improve the care for these patients., Methods: In the study, 516 consecutive patients undergoing parathyroidectomy for primary hyperparathyroidism were divided into 2 groups: classic primary hyperparathyroidism (classic primary hyperparathyroidism, increased serum levels of calcium, and parathyroid hormone) and normohormonal primary hyperparathyroidism (hypercalcemia, normal serum levels of parathyroid hormone). We evaluated inter-group differences in presentation, gland weight, pathology, and complications., Results: The normohormonal primary hyperparathyroidism group was comprised of 116 (22.5%) patients. Mean serum levels of parathyroid hormone and calcium were 62.1 pg/mL ± 10.1 and 10.6 mg/dL ± 0.63 in normohormonal primary hyperparathyroidism, and 142 ± 89.0pg/mL and 11.0 ± 0.88 (both P < .01) for classic primary hyperparathyroidism. Nephrolithiasis was more common in normohormonal primary hyperparathyroidism. Multigland hyperplasia was more common in normohormonal primary hyperparathyroidism 23 (19.8%) vs 44 (11%; P = .04). Concordant imaging studies were less likely in normohormonal primary hyperparathyroidism (82 [73.2%] vs 337 [87.1%; P < .01]), had a lesser total gland weight (531.8 mg ± 680.0 vs 1,039.6 mg ± 1,237.3; P < .01), and lesser 2-week parathyroid hormone (32.5 pg/mL ± 18.95 vs 41.0 pg/mL ± 27.8; P = .01). There was no difference in hypoparathyroidism (parathyroid hormone <15 pg/mL; P = .93) at 2 weeks postoperatively., Conclusion: Normohormonal primary hyperparathyroidism represents 22.5% of our primary hyperparathyroidism population, which is greater than reported previously. It is a distinct disease process from classic primary hyperparathyroidism in presentation, imaging, and operative findings. More hyperplasia and a lesser gland weight make it challenging to resect the ideal amount of tissue. Studies with long-term follow-up are needed to determine optimal operative management., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Context: Understanding the etiology, diagnosis, and symptoms of hypoparathyroidism may help to improve quality of life and long-term disease outcomes. This paper summarizes the results of the findings and recommendations of the Working Group on Presentation of Hypoparathyroidism., Evidence Acquisition: Experts convened in Florence, Italy, in May 2015 and evaluated the literature and recent data on the presentation and long-term outcomes of patients with hypoparathyroidism., Evidence Synthesis: The most frequent etiology is surgical removal or loss of viability of parathyroid glands. Despite precautions and expertise, about 20-30% of patients develop transient and 1-7% develop permanent postsurgical hypoparathyroidism after total thyroidectomy. Autoimmune destruction is the main reason for nonsurgical hypoparathyroidism. Severe magnesium deficiency is an uncommon but correctable cause of hypoparathyroidism. Several genetic etiologies can result in the loss of parathyroid function or action causing isolated hypoparathyroidism or a complex syndrome with other symptoms apart from those of hypoparathyroidism or pseudohypoparathyroidism. Neuromuscular signs or symptoms due to hypocalcemia are the main characteristics of the disease. Hyperphosphatemia can contribute to major long-term complications such as ectopic calcifications in the kidney, brain, eye, or vasculature. Bone turnover is decreased, and bone mass is increased. Reduced quality of life and higher risk of renal stones, renal calcifications, and renal failure are seen. The risk of seizures and silent or symptomatic calcifications of basal ganglia is also increased., Conclusions: Increased awareness of the etiology and presentation of the disease and new research efforts addressing specific questions formulated during the meeting should improve the diagnosis, care, and long-term outcome for patients.

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., (Copyright © 2016. Published by Elsevier Inc.)