UNLABELLED: We evaluated hypophosphatasia diagnostic criteria in adults with low alkaline phosphatase levels and a positive versus negative ALPL genetic test. Performance was optimal with biochemical and genetic data. Wi...UNLABELLED: We evaluated hypophosphatasia diagnostic criteria in adults with low alkaline phosphatase levels and a positive versus negative ALPL genetic test. Performance was optimal with biochemical and genetic data. Without them, sensitivity decreased, though specificity remained. Clinical features alone showed limited discriminative value. PURPOSE: To facilitate early diagnosis of hypophosphatasia (HPP), an international expert group recently proposed standardized diagnostic criteria. This study evaluated the validity and diagnostic utility of the proposed criteria in adults, including scenarios with limited access to tissue-non-specific alkaline phosphatase (TNSALP) substrates and/or genetic assessment. METHODS: Criteria were applied in adults with persistently low alkaline phosphatase levels (ALP) and a positive genetic test (+ GT) confirming HPP versus those with a negative test (-GT). Diagnostic performance was evaluated by sensitivity, specificity, predictive values and area under the ROC curve (AUC). RESULTS: Eighty-three adults were included (47 + GT, 36 -GT). Among + GT individuals, 97.9% met the diagnostic criteria (95.7%, two major; 44.7%, one major and two minor criteria) versus 2.8% of -GT. The two-major criteria arm showed sensitivity of 95.7% and specificity of 100%. The one-major plus two-minor arm had lower sensitivity (44.7%) but high specificity (97.2%). Most discriminative variables were chronic musculoskeletal pain, early tooth loss, and chondrocalcinosis. The criterion based on elevated substrates showed high sensitivity (97.9%) but low specificity (33.3%). In the + GT group, without genetic testing, 51.1% met the criteria (AUC 0.741); without substrate data, 44.7% (AUC 0.71), and with only clinical features, 6.4% (AUC 0.532). CONCLUSION: HPP criteria show high sensitivity and specificity, supporting their clinical utility. Diagnostic performance is optimal when biochemical and genetic data are available. In settings lacking access to genetic testing or substrates, sensitivity is notably reduced despite preserved specificity, and clinical features alone provide limited discriminative value.
UNLABELLED: In this global real-world study, psychotropic medications, particularly analgesics, were associated with increased risks of fractures (HR, 2.41; P < 0.001) and disease relapse (HR, 3.63; P < 0.001) in patient...UNLABELLED: In this global real-world study, psychotropic medications, particularly analgesics, were associated with increased risks of fractures (HR, 2.41; P < 0.001) and disease relapse (HR, 3.63; P < 0.001) in patients with multiple sclerosis. Interaction analyses further indicated a higher fracture risk among opioid users (HR, 3.83; P < 0.001). PURPOSE: Patients with multiple sclerosis (MS) frequently require psychotropic medications, yet their effects on fracture risk and disease activity remain unclear. This study evaluated the risks of fractures, MS relapse, and mortality associated with psychotropic medication use in patients with MS. METHODS: We conducted a global, retrospective cohort study using the TriNetX Research Network. Adult patients with MS were categorized into a psychotropics group and a control group. Propensity score matching in a 1:1 ratio was performed to balance baseline covariates. Primary outcomes included risks of all fractures (hip, vertebral, and extremity), MS relapse, and mortality assessed over a 5-year follow-up. Interaction analyses were performed to determine the differential effects of medication classes. RESULTS: After matching, 117,534 patients (58,777 per group) were included. At the 5-year follow-up, the psychotropic users exhibited significantly higher risks of all fractures (HR, 2.41; 95% CI 2.22-2.63; NNH, 49) and MS relapse (HR, 3.63; 95% CI 3.51-3.75; NNH, 6). No significant difference was observed in mortality. Interaction testing revealed that analgesic use was the primary contributor to fracture risk. Subgroup analysis further identified opioids as the high-risk agent (HR, 3.83; 95% CI 3.45-4.25; NNH, 24), whereas non-opioid analgesics showed no significant association with overall fracture risk. CONCLUSIONS: Psychotropic medication use was associated with increased fracture and relapse risk in multiple sclerosis, driven primarily by opioid analgesics, without an effect on mortality. Bone-conscious pain management and fall prevention should be prioritized.
Quinn MJ, Williams B, Crotti TN
… +1 more, Bowen JM
Osteoporos Int
· 2026 Apr · PMID 41697310
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Cancer treatment-induced bone loss (CTIBL) and skeletal fractures are potential consequences of anticancer therapies used in the treatment of non-metastatic breast cancer (BC). This systematic review and meta-analysis ai...Cancer treatment-induced bone loss (CTIBL) and skeletal fractures are potential consequences of anticancer therapies used in the treatment of non-metastatic breast cancer (BC). This systematic review and meta-analysis aim to synthesise the available evidence regarding the effectiveness and safety of bone protective interventions in the mitigation of CTIBL and skeletal fractures. Multiple databases including MEDLINE/PubMed, Embase and Cochrane, clinical trial registries and grey literature were systematically searched for experimental and observational studies, investigating the use of bisphosphonates, denosumab, calcium or vitamin D supplementation. Outcomes of interest were change in bone mineral density (BMD), the incidence of skeletal fractures, change in bone turnover markers, the incidence of adverse events (AEs), the presence of aromatase inhibitor musculoskeletal symptoms and quality of life. A total of 88 studies were included in our systematic review and meta-analysis, with sample sizes ranging from 11 to 4819 participants. For change in BMD outcomes able to be meta-analysed, bisphosphonates demonstrated a significant benefit compared to controls (pooled mean difference estimate; lumbar spine: 4.17, p = 0.0; total hip: 1.81, p = 0.034; femoral neck: 2.35, p = 0.001). Incidence of skeletal fractures significantly decreased with bisphosphonates compared to controls (pooled relative risk estimate; 0.77, p < 0.001). Denosumab demonstrated similar effects on BMD and skeletal fracture incidence; however, meta-analysis was not possible due to the lack of randomised controlled trials. Osteonecrosis of the jaw represents the most concerning AE with bisphosphonates. Considering the effectiveness and safety, and the level of evidence available, bisphosphonates present as the preferred bone protective intervention for the management of bone health in patients with non-metastatic BC.
UNLABELLED: The Build Better Bones website was developed using a robust stakeholder-engaged approach to be a self-management resource for people with osteoporosis and for care partners of people with osteoporosis. The we...UNLABELLED: The Build Better Bones website was developed using a robust stakeholder-engaged approach to be a self-management resource for people with osteoporosis and for care partners of people with osteoporosis. The website focuses on providing education and resources for exercise, nutrition, home safety, and advice for care partners. INTRODUCTION: Osteoporosis is a common chronic disease that requires effective self-management, including optimal diet, exercise, and home safety practices. The COVID-19 pandemic disrupted traditional outpatient care and increased the need for remote resources. In response, the International Osteoporosis Foundation (IOF) Rehabilitation Working Group developed a web-based platform "Build Better Bones" to support individuals with osteoporosis and their care providers. METHODS: The website's development followed a design thinking, iterative process informed by input from diverse stakeholders, including patients, healthcare professionals, and design experts. Qualitative feedback from 24 stakeholders across three countries shaped the platform's usability and content. Key features include an evidence-based exercise library, practical nutritional guidance, and home safety recommendations. To ensure inclusivity, the site was designed to accommodate a global audience through translation into five languages and culturally diverse animated characters. RESULTS: Stakeholders emphasized the primacy of site navigation and readability, empowering and inclusive images, and compassionate language. The website provides exercises tailored to the management of osteoporosis, focusing on exercise and nutrition with an emphasis on home safety to minimize the risk of fracture. The inclusion of interactive elements, multilingual support, and visually appealing content was guided by stakeholder input. Patients identified the accordion-style presentation and focus on empowering self-management, while clinicians valued the evidence-based exercise recommendations. Qualitative input highlighted the need for inclusive language, accessibility improvements, and practical guidance for safe practice at home. CONCLUSION: The "Build Better Bones" platform bridges a gap in osteoporosis care by providing evidence-based resources tailored to both clinicians and patients that can be disseminated to a global audience. Iterative stakeholder feedback has ensured that the platform is aligned with user needs, making it scalable and adaptable to real-world conditions. Future efforts will focus on expanding content, improving tailored features, and integrating additional languages to serve a global audience.
Dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing osteoporosis, but degenerative spinal changes and vascular calcifications can result in artefactual overestimation of bone mineral density (BMD)...Dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing osteoporosis, but degenerative spinal changes and vascular calcifications can result in artefactual overestimation of bone mineral density (BMD) (3-5). Extreme elevations in T-scores in the absence of metabolic bone disease are exceptionally uncommon. We report a 95-year-old male with multiple chronic comorbidities who presented with poor oral intake and a urinary tract infection. DXA revealed a lumbar spine T-score of + 11.0. Laboratory and imaging evaluation showed no evidence of osteopetrosis, Paget's disease, secondary hyperparathyroidism, hematologic malignancy, or other metabolic bone disorders. Computed tomography demonstrated extensive abdominal aortic and iliac artery calcifications, vertebral deformities, endplate sclerosis, and severe degenerative changes. The extreme lumbar T-score was determined to be artefactual, caused by a combination of advanced vertebral degeneration and vascular calcification. This appears to be the first reported case of a lumbar spine T-score exceeding + 10 in a nonagenarian without metabolic bone disease. Clinicians should correlate DXA findings with clinical, laboratory, and imaging data to avoid misdiagnosis.
Savaré L, Porcu G, Tratsevich A
… +3 more, Ronco R, Ieva F, Corrao G
Osteoporos Int
· 2026 Feb · PMID 41622332
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UNLABELLED: We compared two methods to describe adherence to osteoporotic drugs after fragility fractures. While both similarly predicted refracture risk, a novel approach using sequence analysis provided a clearer pictu...UNLABELLED: We compared two methods to describe adherence to osteoporotic drugs after fragility fractures. While both similarly predicted refracture risk, a novel approach using sequence analysis provided a clearer picture of patient behavior, helping clinicians better understand and address adherence issues in osteoporosis care. BACKGROUND: Fragility fractures are common among individuals with osteoporosis, causing significant morbidity, mortality, and healthcare costs. Although effective pharmacological treatments exist, underdiagnosis and poor treatment adherence remain pervasive in clinical practice. METHODS: In order to select an effective methodology to describe and visually represent treatment adherence and correctly stratify patients with fragility fractures according to their adherence patterns, a conventional method using average PDC was compared to an alternative method, given by the state sequence analysis (SSA) and clustering procedure. Data on patients aged 50 or older who experienced fragility fractures between 2012 and 2017 were retrieved from healthcare utilization databases in Lombardy, Italy. Fine and Gray's model was employed to analyze the association between adherence (calculated by conventional and alternative methods) and refracture risk. Finally, the discriminatory power to predict outcomes was calculated for each approach. RESULTS: Out of the 8976 patients included in this observational study, four different adherence groups were considered using the conventional method (very poor, poor, intermediate, and optimal), while three clusters (non-adherence, short-term adherence, and long-term adherence) were obtained from the SSA. Compared with non-adherent patients, those with long-term adherence were found to have a significantly reduced risk of combined death and refracture with both methods. Regarding discriminatory performance, the two approaches showed similar AUC, 0.646 and 0.644 for conventional and alternative methods, respectively. CONCLUSIONS: Based on the SSA and cluster analysis, the alternative method does not significantly modify the prediction of the refracture risk but enhances the description and visualization of the adherence patterns.
Osteoporos Int
· 2026 Apr · PMID 41622331
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UNLABELLED: Bone loss accelerates in early menopause, increasing fracture risk. In 223 women followed for 2 years, higher fiber and energy intake were linked to better bone structure, while higher fat intake and some phy...UNLABELLED: Bone loss accelerates in early menopause, increasing fracture risk. In 223 women followed for 2 years, higher fiber and energy intake were linked to better bone structure, while higher fat intake and some physical activity domains were inversely associated. Specific short-chain fatty acids showed positive associations, highlighting diet-microbiome interactions in bone health. BACKGROUND: The early postmenopausal period is characterized by accelerated loss of bone mineral density (BMD), underscoring the importance of modifiable lifestyle factors as potential targets for prevention. METHODS: This study is a secondary analysis of the ELBOW trial, a 2-year longitudinal study of early postmenopausal Swedish women. We investigated the association between dietary intake, physical activity, and short-chain fatty acids (SCFAs) with bone outcomes in 223 early postmenopausal Swedish women aged 50-60 years. Assessments were conducted at baseline, 1 year, and 2 years. Diet and physical activity were assessed using validated questionnaires, and SCFAs were measured in plasma. Bone parameters, including total hip BMD, tibial volumetric BMD (vBMD), and bone microarchitecture, were evaluated using dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). Associations were analyzed using linear mixed models for repeated measures. RESULTS: Higher baseline fiber intake was positively associated with trabecular bone volume fraction, while total fat was inversely associated with total hip BMD, total vBMD, and cortical area. Greater energy intake during follow-up was positively associated with cortical area. No associations were observed between bone characteristics and calcium or vitamin D intake. Baseline transport-related and changes in domestic/gardening activity were inversely associated with bone measurements. Among SCFAs, baseline levels of acetic acid, formic acid, and isovaleric acid were positively associated with bone outcomes, while changes in caproic acid levels were negatively associated. CONCLUSION: These findings suggest that specific dietary components and gut microbiota-derived metabolites may play a role in maintaining bone health during early postmenopause and highlight the need for further investigation into their preventive and therapeutic potential.
UNLABELLED: Denosumab-associated hypocalcemia is common in real-world settings. In this Saudi cohort, 21.1% developed hypocalcemia, with diuretic use and vitamin D deficiency as key predictors. Findings highlight that in...UNLABELLED: Denosumab-associated hypocalcemia is common in real-world settings. In this Saudi cohort, 21.1% developed hypocalcemia, with diuretic use and vitamin D deficiency as key predictors. Findings highlight that individualized risk assessment and monitoring may enhance the safety of osteoporosis treatment. BACKGROUND: Denosumab, a widely used antiresorptive agent for osteoporosis, has demonstrated significant benefits in reducing fracture risk. However, hypocalcemia is a recognized adverse effect, with real-world data suggesting higher incidence rates than those reported in clinical trials. This study explores the incidence, severity, and predictors of denosumab-associated hypocalcemia in a Saudi cohort. METHODS: A retrospective analysis was conducted at a tertiary care hospital, involving 303 Saudi adults with osteoporosis who received denosumab. The study evaluated changes in calcium levels, incidence of hypocalcemia, and potential risk factors, including vitamin D status, renal function, and medication use. Multivariate logistic regression identified predictors of hypocalcemia. RESULTS: Hypocalcemia occurred in 21.1% of patients, with 71.9% experiencing mild (grade 1) hypocalcemia. Most cases were asymptomatic (73.4%), with tingling and muscle aches reported in a minority of patients. Diuretic use emerged as a significant predictor (aOR 3.44, p = 0.008). Vitamin D deficiency was strongly associated with severe hypocalcemia (grade 3). Despite adherence to standard calcium and vitamin D supplementation, a substantial proportion of patients developed hypocalcemia, underscoring the need for individualized monitoring. CONCLUSION: Hypocalcemia following denosumab is common in real-world practice, particularly in patients on diuretics or with low vitamin D levels. Clinicians should consider comprehensive pre-treatment risk assessment and tailored monitoring strategies to mitigate adverse outcomes in osteoporosis management.
Park SS, Jeong H, Ahn CH
… +7 more, Park MJ, Kong SH, Kim SW, Shin CS, Kim YH, Kim K, Kim JH
Osteoporos Int
· 2026 Mar · PMID 41603925
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UNLABELLED: Arginine vasopressin deficiency (AVP-D) might increase fracture risk. This nationwide cohort study found a significantly increased hip fracture risk in female AVP-D patients ≥ 50 years, but not in males. Thes...UNLABELLED: Arginine vasopressin deficiency (AVP-D) might increase fracture risk. This nationwide cohort study found a significantly increased hip fracture risk in female AVP-D patients ≥ 50 years, but not in males. These findings highlight sex-specific vulnerability, urging focused fracture prevention in female AVP-D patients. PURPOSE: Arginine vasopressin deficiency (AVP-D) is associated with various complications and increased mortality. However, its association with long-term fracture risk remains unclear. We aimed to assess fracture risks in patients aged 50 years or older with AVP-D. METHODS: We used data from the Korea National Health Insurance Service database (2003-2020). A total of 3,497 patients aged ≥ 50 years diagnosed with AVP-D (2,111 men and 1,386 women) were included, along with 1:1 matched controls, based on age, sex, index year, and key comorbidities, including diabetes mellitus, hypertension, cardiovascular disease, and cerebrovascular disease. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of major osteoporotic fractures (MOFs), vertebral fractures (VFs), non-vertebral fractures (non-VFs), and hip fractures (HFs). RESULTS: After adjusting for confounding factors, including income status, steroid use, and prior fracture history, the risk for MOFs, VFs, non-VFs, and HFs in male patients with AVP-D were comparable to those in controls. In women with AVP-D, the risk of MOFs, VFs, or non-VFs was not different from controls, but the risk of HFs was significantly higher (HR 1.83; 95% CI, 1.06-3.17). Age, female, previous history of fracture, and steroid use contributed to high risk for fracture in patients with AVP-D. CONCLUSION: Compared with controls, only female patients with AVP-D demonstrated a significantly increased risk of HFs. These findings highlight the need for long-term follow-up, targeted screening, and proactive management of HF risk in female patients with AVP-D.