Smith M, Roast J, Collins GS
… +2 more, Holt TA, Frighi V
Osteoporos Int
· 2026 Apr · PMID 42008168
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UNLABELLED: People with intellectual disability (ID) have a relatively high incidence of fractures, so current risk prediction models are not appropriate. A new prediction model for people with ID showed good calibration...UNLABELLED: People with intellectual disability (ID) have a relatively high incidence of fractures, so current risk prediction models are not appropriate. A new prediction model for people with ID showed good calibration and discrimination in external validation. This is the first such prediction model developed for people with ID. PURPOSE: Compared with the general population, people with intellectual disabilities (ID) have higher incidences of major osteoporotic fracture (MOF) and hip fracture (HF), and they develop osteoporosis at a younger age. The rate of HF in those aged 50 years and over is two times higher than that in women without ID and four times higher than that in men without ID. It is essential to identify people with ID who are at risk of such fractures so that a targeted fracture prevention strategy can be designed. However, current fracture prediction models are derived from the general population and may underestimate risk in the ID population. METHODS: Prediction models (IDFracture) for the 10-year risk of HF and MOF were developed and validated in populations of people with ID aged 30-79 years. Models were developed in the CPRD GOLD database and temporally validated in the Aurum database. The predictors included those in current fracture prediction models and ID-specific predictors such as Down syndrome. All the predictors were included in the Cox regression models. Bootstrapping was used to adjust for overfitting. RESULTS: The development cohort included 38,665 people with IDs, 1045 with MOFs and 360 with HFs within 10 years. The external validation cohort included 76,385 people, 2420 MOFs and 1001 HFs. Discrimination, as judged by the C statistic, was good: MOF 0.775 and HF 0.839. The calibration was also good but tended to overpredict at the highest predicted risks. CONCLUSION: IDFracture has potential as a screening tool in clinical practice to identify people with ID who are at increased risk of MOF and HF.
UNLABELLED: In Japan, a national reimbursement add-on for secondary fracture prevention after hip fracture surgery, implemented on April 1, 2022, was associated with lower 1-year refracture risk and higher early uptake o...UNLABELLED: In Japan, a national reimbursement add-on for secondary fracture prevention after hip fracture surgery, implemented on April 1, 2022, was associated with lower 1-year refracture risk and higher early uptake of post-fracture DXA assessment within 90 days and anti-osteoporosis medication initiation within 120 days, but not with improved 1-year post-fracture treatment persistence. PURPOSE: To assess whether the Japanese national reimbursement add-on policy for preventing secondary fracture after hip fracture surgery, introduced in April 2022, was associated with actual changes in refracture risk and key secondary fracture prevention care processes after hip fracture surgery. METHODS: We conducted a population-based interrupted time-series analysis using longitudinal health insurance claims data collected in Japan between 2019 and 2023. Participants were adults aged ≥ 50 years with newly identified and surgically treated hip fracture. The intervention was implementation of the policy on 1 April 2022. Outcome measures were absolute changes 12 months after policy implementation in the 1-year cumulative risk of first refracture, 90-day cumulative probability of receiving dual-energy X-ray absorptiometry (DXA) assessment, 120-day cumulative probability of initiating anti-osteoporosis medication, and 1-year post-fracture treatment persistence. RESULTS: Twelve months after policy implementation, the absolute effect on the 1-year cumulative risk of refracture in the hip fracture series was - 1.02 percentage points (95% confidence interval, - 1.44 to - 0.60). The absolute effects on early care processes were 41.37 percentage points (40.21 to 42.54) for DXA assessment and 22.83 percentage points (21.70 to 23.95) for the initiation of anti-osteoporosis medication. The absolute effect on 1-year post-fracture treatment persistence was - 6.76 percentage points (- 10.04 to - 3.49). CONCLUSIONS: The reimbursement add-on policy for secondary fracture prevention after hip fracture surgery was associated with a lower 1-year cumulative refracture risk and a higher cumulative probability of receiving DXA assessment and initiating anti-osteoporosis medication, but not with improved 1-year post-fracture treatment persistence. Strategies supporting sustained follow-up and reengagement may be needed.
UNLABELLED: This study investigated the link between the systemic inflammation response index (SIRI) and fracture risk in elderly women. Higher SIRI was associated with increased fracture risk, independent of clinical ri...UNLABELLED: This study investigated the link between the systemic inflammation response index (SIRI) and fracture risk in elderly women. Higher SIRI was associated with increased fracture risk, independent of clinical risk factors and bone mineral density, suggesting SIRI may be valuable for enhancing fracture risk assessment models. PURPOSE: The systemic inflammation response index (SIRI), including monocytes, neutrophils, and lymphocytes (SIRI = monocytes x neutrophils/lymphocytes), has been linked to various health outcomes, including osteoporosis. This study aimed to explore the association between SIRI and fracture risk in elderly women. METHODS: In a Swedish prospective cohort of 2965 women aged 75-80 years, baseline examinations included blood analyses, dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), physical function tests, and questionnaires. Cox proportional hazards regression models were used to assess associations between SIRI and incident fracture risk. RESULTS: The median follow-up time was 8 years (IQR 7.2-8.8), during which 230 hip fractures, 790 major osteoporotic fractures (MOF), and 1059 any type of fracture occurred. Higher SIRI was significantly linked to an increased risk of hip fracture (hazard ratio [HR] per 1 SD increase 1.18, 95% CI [1.07-1.32], p < 0.01), MOF (1.10 [1.03-1.18], p < 0.01), and any fracture (1.11 [1.05-1.17], p < 0.001) independent of age, BMI, clinical risk factors (CRFs), and femoral neck bone mineral density (FN BMD). SIRI was related to poorer physical function (timed up-and-go [TUG], 11.8%, p < 0.05, highest [Q5] compared to the lowest [Q1] quintile of SIRI) and lower activity levels (physical activity scale for the elderly [PASE], -28.8%, p < 0.05, Q5 vs. Q1). SIRI was positively associated with cortical porosity and trabecular number, but not with BMD measured by DXA. CONCLUSION: SIRI was positively and independently associated with incident fracture risk. Further studies are needed to establish whether SIRI provides additional value beyond existing risk factors.
UNLABELLED: Brief rationale: The impact of non-dialysis chronic kidney disease (CKD) on combined muscle and bone decline remains insufficiently described. MAIN RESULT: Patients with CKD showed markedly higher rates of sa...UNLABELLED: Brief rationale: The impact of non-dialysis chronic kidney disease (CKD) on combined muscle and bone decline remains insufficiently described. MAIN RESULT: Patients with CKD showed markedly higher rates of sarcopenia, osteoporosis, and osteosarcopenia than matched healthy controls. Significance of the paper: These findings support systematic evaluation of muscle and bone health in CKD management. PURPOSE: Chronic kidney disease (CKD) negatively affects bone and muscle quality. The combination of sarcopenia and osteoporosis, osteosarcopenia, is associated with an increased risk of fractures and mortality. Yet, little is known about osteosarcopenia in patients with non-dialysis-dependent CKD compared to healthy controls. We hypothesized that patients with CKD have a higher prevalence of osteosarcopenia than healthy adults. METHODS: In this cross-sectional study, 138 patients with CKD stages G4-5 were matched 1:1 on sex and age to healthy controls. We assessed appendicular lean mass and bone mineral density (BMD) at the hips and lumbar spine using dual-energy X-ray absorptiometry and evaluated muscle strength through handgrip strength, 30-s chair stands, and 10-m gait speed. Sarcopenia was defined using the criteria by the EWGSOP criteria, osteoporosis by the WHO criteria, and osteosarcopenia required the presence of both. RESULTS: CKD participants had weaker handgrip strength, poorer chair-stand performance, and slower gait speed compared to healthy controls. BMD was reduced in patients with CKD. The prevalence of sarcopenia (21.7% vs. 5.8%; OR 4.51 [1.91-11.8]), osteoporosis (21.7% vs. 10.1%; OR 2.44 [1.25-4.99]), and osteosarcopenia (8.7% vs 1.4%; OR 6.44 [1.39-60.4]) were higher in patients with CKD compared to controls. CONCLUSION: In this cross-sectional study, there was a higher prevalence of sarcopenia, osteoporosis, and osteosarcopenia in patients with CKD as compared to sex- and age-matched healthy controls. These findings indicate that it is relevant with a systematic assessment of muscle and bone health in CKD management.
UNLABELLED: This target-trial emulation study sought to assess the association between romosozumab and incident dementia. We analyzed longitudinal claims data from 69,543 Japanese individuals with osteoporosis (using ter...UNLABELLED: This target-trial emulation study sought to assess the association between romosozumab and incident dementia. We analyzed longitudinal claims data from 69,543 Japanese individuals with osteoporosis (using teriparatide as an active comparator), finding that romosozumab initiation among individuals with osteoporosis may correlate with a lower dementia risk than teriparatide initiation. PURPOSE: The neurocognitive benefits of osteoporosis treatments remain underexplored despite growing interest in the bone-brain connection. We aimed to analyze the association between romosozumab and incident dementia, using teriparatide as the active comparator. METHODS: We emulated a target trial using longitudinal commercial claims data from Japan. We identified individuals aged ≥ 50 years with osteoporosis who newly initiated either romosozumab or teriparatide between 2019 and 2023. The primary outcome was incident dementia, and the secondary outcome was Alzheimer's disease. We estimated the absolute risk reduction (ARR) and relative risk (RR) using a weighted Kaplan-Meier estimator, conducting both intention-to-treat and per-protocol analyses. RESULTS: A total of 69,543 individuals were included in the study (90% female; mean age, 81 years). In the 2-year intention-to-treat analyses, the ARR was 0.7% (95% confidence interval, - 0.1 to 1.3%), with a RR of 0.91 (95% confidence interval, 0.84 to 1.01). For Alzheimer's disease specifically, the ARR was 0.6% (95% confidence interval, 0.0 to 1.1%), with an RR of 0.88 (95% confidence interval, 0.79 to 1.00). In the 1-year per-protocol analyses, the ARR was 1.0% (95% confidence interval, 0.7 to 1.4%), with a RR of 0.76 (95% confidence interval, 0.69 to 0.82). For Alzheimer's disease specifically, the ARR was 0.6% (95% confidence interval, 0.3 to 0.9%), with an RR of 0.77 (95% confidence interval, 0.65 to 0.86). CONCLUSIONS: In this target trial emulation study, romosozumab initiation among individuals with osteoporosis may be associated with a lower risk of dementia, particularly Alzheimer's disease, than teriparatide initiation.
UNLABELLED: Contemporary IBD care lacks precise osteoporosis risk estimates and data on comparative therapy. In U.S., IBD patients had a 56% higher 5-year risk of a new osteoporosis diagnosis (highest in Crohn's disease)...UNLABELLED: Contemporary IBD care lacks precise osteoporosis risk estimates and data on comparative therapy. In U.S., IBD patients had a 56% higher 5-year risk of a new osteoporosis diagnosis (highest in Crohn's disease); denosumab matched bisphosphonates for 1-2-year fracture prevention in this population. Our study prioritizes early screening, steroid-sparing strategies, and individualized antiresorptive therapy. BACKGROUND: Osteoporosis is a frequent extra-intestinal complication of inflammatory bowel disease (IBD), yet its current burden and the comparative efficacy of available anti-resorptive therapies remain uncertain. METHODS: Using the US TriNetX network we formed two retrospective cohorts. (1) Adults with IBD (2013-2023) were 1:1 propensity-matched to non-IBD controls to estimate 5-year risk of new osteoporosis diagnosis and identify determinants. (2) IBD patients with osteoporosis initiating denosumab or bisphosphonates (2013-2022) were matched for demographics, comorbidities, and IBD phenotype; spine/hip fractures and risk for incident onset fractures were calculated for both the cohorts. RESULTS: Among 143,248 patients with IBD (mean age 44.2 y; 51.8% female), risk of new osteoporosis diagnosis exceeded controls by 58% at 1 year (adjusted odds ratio [aOR] 1.58, 95% CI 1.51-1.65) and was highest in Crohn's disease (CD) (aOR 1.79, 95% CI 1.68-1.90); ulcerative colitis (UC) also demonstrated increased 1-year risk (aOR 1.47, 95% CI 1.39-1.56). Subgroup analysis showed increased risk in patients age > 65, female sex and Asian race for UC. For CD, age > 65, female sex, nicotine dependence and alcohol use were associated with increased risk. The osteoporosis treatment cohort included 2,423 patients (520 denosumab and 1,903 bisphosphonates). After matching, denosumab produced similar 1-year (2.33% vs 3.49%, aOR 0.65 CI 0.31-1.38) and 2-year (4.65% vs 6.78%; aOR 0.67, CI: 0.39-1.14) fracture rates compared to bisphosphonates. CONCLUSION: IBD confers a substantially higher and multifactorial osteoporosis risk. Denosumab showed similar observed short-term fracture rates to bisphosphonates, although clinically meaningful differences could not be excluded. Early bone-health screening, steroid-sparing therapy, and individualized antiresorptive treatment remain essential.
Capasso A, Arpaia C, Panicucci C
… +21 more, Gulli C, Villa M, Repetto A, Coratti G, Morando S, Cicala G, Oliva A, Milardi D, Cipolla C, Catapano G, Marzoli A, Damasio MB, Brogna C, Palermo C, Di Iorgi N, Bruno C, Ficociello L, Gaudino S, Pane M, Ward LM, Mercuri E
UNLABELLED: Brief rationale: To investigate vertebral fracture and risk factors in DMD. MAIN RESULTS: Vertebral fractures were found in 42% of subjects with an increased risk associated with low TB BMD, early steroid exp...UNLABELLED: Brief rationale: To investigate vertebral fracture and risk factors in DMD. MAIN RESULTS: Vertebral fractures were found in 42% of subjects with an increased risk associated with low TB BMD, early steroid exposure and low BMI. Significance of the paper: Bone health monitoring should start early, regardless of functional status. PURPOSE: To describe the prevalence of vertebral fractures (VFs) in Duchenne Muscular Dystrophy (DMD) and to establish the role of several risk factors, focusing on ambulatory status and functional motor scores (Performance Upper Limb, North Star Ambulatory Assessment) not previously assessed. METHODS: We recorded the number and site of fractures together with anthropometric, radiological (total body bone mineral density (TB BMD) Z-scores measured by Dual Energy X-ray Absorptiometry (DXA)), and functional scales. Logistic and linear regression analyses were conducted to identify factors associated with prevalent VFs and predictors of Spinal Deformity Index (SDI). RESULTS: Of the 149 individuals (7-26 years) studied, 62 (42%) had VFs. These were equally present in ambulant and non-ambulant individuals (41 vs 42%) and were not associated with functional scores. The TB BMD Z-score was a protective factor both in non-ambulant and ambulant subgroups. Lower TB BMD Z-scores were also predictive of a greater SDI. In the ambulant subgroup a lower BMI reduced the risk of VF. In the overall cohort, each one-year delay in starting glucocorticoids reduced the risk of VFs by 27% (p = 0.007), and each additional unit in TB BMD Z-score reduced the risk of VFs by 54% (p = 0.0007). CONCLUSION: Our results suggest that ambulatory status and functional scores alone may not be reliable predictors for developing VFs and confirm the association with known risk factors, such as early initiation of glucocorticoid therapy and low BMD Z-scores, highlighting the need to guarantee a careful surveillance of possible VFs from the time of glucocorticoid initiation.
UNLABELLED: Chronic kidney disease patients face increased osteoporosis and fracture risk. High-potency statins were associated with lower osteoporosis incidence but also with higher long-term fracture incidence in this...UNLABELLED: Chronic kidney disease patients face increased osteoporosis and fracture risk. High-potency statins were associated with lower osteoporosis incidence but also with higher long-term fracture incidence in this observational study. These findings highlight the need for tailored statin use and proactive fracture monitoring in CKD populations for optimal bone health management. PURPOSE: Chronic kidney disease (CKD) affects approximately 850 million people worldwide and is associated with increased risks of cardiovascular events and fractures. The differential effects of statin potency on bone health in CKD patients remain incompletely understood. METHODS: This retrospective cohort study used the TriNetX US Collaborative Network to identify adults with CKD stages 3 or 4 initiating statin therapy, categorized into high-potency (atorvastatin 40-80 mg, rosuvastatin 20-40 mg) and low-potency groups. After 1:1 propensity score matching, three primary outcomes were evaluated: new osteoporosis diagnosis, anti-osteoporotic medication initiation, and incident fractures, assessed at 3-12 months and beyond 12 months. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox and competing risk regression models. RESULTS: Among 873,180 matched patients, high-potency statins were associated with a 20.0% reduction in osteoporosis diagnosis (HR 0.80; 95% CI 0.78-0.82) and 24.9% fewer anti-osteoporotic medication prescriptions (HR 0.75; 95% CI 0.73-0.78) during 3-12 months, with associations persisting beyond 12 months. Fracture risk did not differ at 3-12 months (HR 0.99; 95% CI 0.96-1.02); but increased beyond 12 months (HR 1.13; 95% CI 1.11-1.15). CONCLUSIONS: High-potency statins are associated with lower osteoporosis diagnosis rates and fewer anti-osteoporotic medication prescriptions in CKD stages 3 and 4. The increased long-term fracture risk may reflect a diagnostic gap wherein lower osteoporosis detection contributes to under-treatment of bone fragility. Prospective randomized controlled trials with bone-specific endpoints are warranted to confirm these findings.
Ghielmetti A, Grassi G, Carrara S
… +16 more, Palermo A, Naciu A, Sargentini E, Salcuni A, Vescini F, Zampogna M, Atlasova A, Rondinella S, Cosso R, Chiodini I, Favero V, Mazza M, Frara S, Mantovani G, Corbetta S, Eller-Vainicher C
UNLABELLED: Limited data on romosozumab super-responders. In 149 Italian women with severe osteoporosis, mean LS BMD gain was + 13.7%; 18% were super-responders (≥ 20%). PREDICTORS: high CTX/age/low Z-score for LS; prior...UNLABELLED: Limited data on romosozumab super-responders. In 149 Italian women with severe osteoporosis, mean LS BMD gain was + 13.7%; 18% were super-responders (≥ 20%). PREDICTORS: high CTX/age/low Z-score for LS; prior femoral fracture for FN. Highlights site-specific response drivers in real-world setting. PURPOSE: To evaluate romosozumab effectiveness in a large Italian multicentre cohort of women with severe postmenopausal osteoporosis and identify predictors of high-magnitude densitometric response. Real-world evidence on romosozumab is expanding, yet data on high-magnitude response variability and clinical determinants of "super-responder" phenotypes remain limited. METHODS: Retrospective analysis of postmenopausal women who completed 12 months of romosozumab across five Italian centers. DXA scans were performed at baseline and after treatment. Data included clinical history, morphometric and clinical fractures, and prior anti-osteoporotic therapies. "Very good responders" were defined as ≥ 10% BMD gain; "super-responders" as ≥ 20%. Multivariate logistic regression identified independent predictors. RESULTS: 149 women (mean age 69.4 ± 9.9 years) were included. Prevalent vertebral (85.2%), femoral (30.9%), and non-vertebral (49.0%) fractures were common; 82% had prior therapy. Mean BMD gains were + 13.7% at lumbar spine (LS), + 5.9% at femoral neck (FN), and + 4.4% at total hip (TH). Very good responders (≥ 10%) occurred in 65.2% at LS, 17.8% at FN, and 13.3% at TH; super-responders (≥ 20%) in 17.8% at LS and 5.9% at FN. LS super-response was independently associated with higher baseline CTX (OR 1.42; p = 0.018), older age (OR 1.10 per year; p = 0.036), and lower baseline LS Z-score (OR 0.29; p = 0.003). FN super-response linked to prior femoral fracture (OR 14.6; p = 0.020). CONCLUSION: Romosozumab demonstrated high effectiveness in this real-world cohort, with a substantial proportion achieving high-magnitude BMD responses despite extensive prior treatment. Distinct site-specific predictors emerged: bone turnover and age/Z-score for LS, prior femoral fracture for FN.
UNLABELLED: Calcium isotope fractionation (δ⁴⁴⁴²Ca) was evaluated as a biomarker of bone metabolism in 301 patients. δ⁴⁴⁴²Ca correlated with urinary calcium excretion but not with bone mineral density or fracture status....UNLABELLED: Calcium isotope fractionation (δ⁴⁴⁴²Ca) was evaluated as a biomarker of bone metabolism in 301 patients. δ⁴⁴⁴²Ca correlated with urinary calcium excretion but not with bone mineral density or fracture status. Age, kidney function, and calcium intake influenced results, limiting its diagnostic utility for osteoporosis in clinical practice. Data on Calcium isotope fractions (δCa) in isolated bone diseases are limited. Previously proposed as a diagnostic marker in metabolic bone disorders, we now extend our findings from monogenic bone diseases to patients with osteoporosis and osteopenia. METHODS: In 301 patients (43 controls), serum and urine δCa were analyzed alongside bone (such as bone density) and treatment parameters. RESULTS: Age, kidney function, and calcium intake significantly affected δCa and must be considered in interpretation. δCa correlated strongly with urinary calcium excretion (serum: r²=0.55, urine: r²=0.20; p<0.0001) but not with bone turnover markers or BMD. Higher β-CTX were associated with low δCa levels (p<0.05). Osteoanabolic therapy increased δCa (p<0.05), whereas antiresorptive treatment had no effect. No differences in δCa appeared by fracture or BMD stratification, but age-adjusted δCa stratification showed higher urinary calcium and PTH (both p<0.0001) in individuals above the threshold, a pattern consistent with neutral or positive bone mineral balance. CONCLUSION: While δCa reflects aspects of calcium metabolism, such as nutritional calcium supply, in this real-world setting, it failed to predict fractures or distinguish osteoporosis from healthy controls or osteopenia and vice versa, indicating limited clinical use. Thus, although δCa is a parameter of interest for calcium metabolism, it does not substitute established bone diagnostics such as BMD or laboratory assessments. Future studies are needed to determine if and how δCa can contribute to individualized diagnostics and treatment monitoring in bone disease.
UNLABELLED: This study compared romosozumab and teriparatide for osteoporosis treatment using real-world data. Romosozumab was linked to significantly lower mortality, especially in older adults, without added cardiovasc...UNLABELLED: This study compared romosozumab and teriparatide for osteoporosis treatment using real-world data. Romosozumab was linked to significantly lower mortality, especially in older adults, without added cardiovascular risk. These findings highlight romosozumab as a potentially safer and more effective option for reducing death risk in patients with osteoporosis. BACKGROUND: Osteoporosis is a prevalent condition among older adults and significantly increases the risk of fragility fractures, particularly affecting the hip and vertebrae. Pharmacologic therapy remains central to osteoporosis management, with anabolic agents such as romosozumab and teriparatide demonstrating efficacy in increasing bone mineral density and reducing fracture risk. However, direct comparative evidence regarding their impact on mortality is limited. This study aimed to evaluate the differences in all-cause mortality between romosozumab and teriparatide in patients with osteoporosis, utilizing a large real-world dataset. METHODS: We conducted a retrospective cohort study using electronic medical records from the TriNetX US Collaborative Network, comprising data from over 120 healthcare organizations. Patients aged ≥ 20 years diagnosed with osteoporosis between January 1, 2016, and December 31, 2023, initiating either romosozumab or teriparatide were included. Individuals with malignancies, bone neoplasms, multiple myeloma, parathyroid disorders, or cerebrovascular accidents were excluded. Propensity score matching (1:1) balanced demographic, clinical, and laboratory characteristics between cohorts. The primary outcome was all-cause mortality, with subgroup analyses performed based on age, sex, comorbidities, and treatment settings. RESULTS: Each treatment group included 2470 matched patients. Over the follow-up period, romosozumab was associated with significantly lower all-cause mortality compared to teriparatide (hazard ratio [HR] 0.68, 95% CI 0.49-0.94). This survival advantage was particularly evident in patients aged ≥ 60 years (HR 0.65, 95% CI 0.47-0.88). Subgroup analyses consistently favored romosozumab across multiple comorbid conditions, including diabetes mellitus and chronic kidney disease, although these subgroup results did not reach statistical significance. Importantly, no increased mortality risk was observed in patients with hypertension or coronary heart disease, indicating a favorable cardiovascular safety profile in these populations. CONCLUSION: In this real-world analysis, romosozumab was associated with a significantly lower risk of all-cause mortality compared to teriparatide among patients with osteoporosis. These findings may support the preferential consideration of romosozumab, particularly for older adults and patients at elevated fracture risk, given the inherent limitations of the study design, while highlighting the necessity of careful cardiovascular risk assessment.