Osteoporosis (OP) is a prevalent and serious comorbidity in rheumatoid arthritis (RA), significantly increasing the fracture burden. Although early detection is crucial, OP screening in RA is often delayed, representing...Osteoporosis (OP) is a prevalent and serious comorbidity in rheumatoid arthritis (RA), significantly increasing the fracture burden. Although early detection is crucial, OP screening in RA is often delayed, representing an unmet clinical need. Clinical prediction models (CPMs) offer a solution for early risk stratification, yet a synthesis that integrates RA-OP risk factors and evaluates existing CPMs is lacking. This review addresses this gap by delineating the multidimensional risk network for RA-OP and evaluating the development, performance, and applicability of current CPMs. We find that despite evolution from basic to sophisticated biomarker-integrated algorithms, most CPMs are constrained by modest sample sizes, insufficient external validation, and suboptimal clinical translatability. The current paradigm focuses predominantly on diagnosis rather than prognosis. To address these limitations, future research should aim to enhance the methodological rigor and generalizability of models, expand their predictive scope to encompass future risk of OP and fractures, and develop RA-specific fracture prediction tools that incorporate disease-specific pathophysiology, with performance rigorously benchmarked against established tools such as the fracture risk assessment tool (FRAX). Progress along these lines may help shift the management paradigm toward more proactive and personalized prevention, with the potential to improve long-term skeletal health outcomes in RA.
UNLABELLED: Patients with rheumatoid arthritis have higher fracture risks than those without RA, particularly in seropositive cases. The risk of fractures remained elevated regardless of bDMARD or tsDMARD use, warranting...UNLABELLED: Patients with rheumatoid arthritis have higher fracture risks than those without RA, particularly in seropositive cases. The risk of fractures remained elevated regardless of bDMARD or tsDMARD use, warranting further large-scale studies. Our findings highlight the need for active surveillance and timely intervention in RA patients, particularly those with SPRA and regardless of bDMARD or tsDMARD use. OBJECTIVES: Evidence of the association between the serological status and the risk of fracture among patients with rheumatoid arthritis (RA) considering exposure to disease-modifying antirheumatic drugs (DMARDs) is scarce. We investigated the risk of fracture among patients with RA according to the serological status considering exposures to biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs). METHODS: We conducted a population-based retrospective cohort study using the Korean National Health Insurance Service database including patients who were diagnosed with RA between 2010 and 2017 (n = 43,677) and controls matched according to age and sex (n = 131,031). RESULTS: Patients with RA had a higher risk of any fractures compared to matched controls (adjusted hazard ratio [aHR] 1.68, 95% confidence interval [CI] 1.62‒1.75). Patients with seropositive RA (SPRA) had an increased risk of fracture (aHR 1.19, 95% CI 1.11‒1.28 for any fractures; aHR 1.40, 95% CI 1.26‒1.55 for vertebral fractures; aHR 1.55, 95% CI 1.19‒2.02 for hip fractures) compared to those with seronegative RA. Compared to matched controls, RA patients showed higher fracture risk regardless of bDMARDs (exposed: 2.28-fold; unexposed: 1.64-fold) or tsDMARDs (exposed: 1.91-fold; unexposed: 1.68-fold). CONCLUSION: Patients with RA were at higher risk of fractures compared to those without RA, with even higher risk among those with SPRA. The risk of fractures remained elevated regardless of bDMARD or tsDMARD use, warranting further studies to explore the impact of bDMARDs and tsDMARDs on fracture risk in patients with RA.
BACKGROUND: Hypophosphatasia (HPP) is a rare metabolic bone disorder that can present with a wide spectrum of skeletal and extraskeletal signs and symptoms. Biochemically, HPP is characterized by a decreased activity of...BACKGROUND: Hypophosphatasia (HPP) is a rare metabolic bone disorder that can present with a wide spectrum of skeletal and extraskeletal signs and symptoms. Biochemically, HPP is characterized by a decreased activity of the tissue nonspecific alkaline phosphatase (TNSALP) and subsequent accumulation of inorganic pyrophosphate (PPi). Fractures in patients with HPP can show delayed healing or even progress to nonunion. In pediatric patients, fractures can be particularly debilitating, as children usually engage in high levels of physical activity. CASE PRESENTATION: The 16-year-old girl, carrying a pathogenic variant in the ALPL gene, presented 17 weeks (4 months) after the initial diagnosis of a fracture at the base of the fifth metatarsal (MT-V). The patient was still symptomatic, and magnetic resonance imaging and cone beam computed tomography (CBCT) showed no radiological signs of healing despite immobilization. Given the prolonged absence of fracture consolidation, TNSALP enzyme replacement therapy with asfotase alfa (AA) was initiated and dosed according to body weight, in line with approved pediatric regimens. Thirteen weeks after initiation of AA, CBCT demonstrated full radiological consolidation. Furthermore, bone mineral density (BMD) in the fracture gap increased by 36%, returning to the average BMD level of the MT-V. CONCLUSION: Here we present, to the best of our knowledge, the first pediatric case in which treatment with AA supported healing of a delayed union stress fracture in the context of clinically diagnosed and genetically supported HPP. Our findings support considering AA initiation in pediatric patients diagnosed with HPP who present delayed fracture healing despite standard conservative management.
PURPOSE: Proximal humerus fractures (PHFs) often lead to significant morbidity and are associated with an increased risk of mortality. The aim of this study was to assess the mortality rate in patients ≥ 65 years with PH...PURPOSE: Proximal humerus fractures (PHFs) often lead to significant morbidity and are associated with an increased risk of mortality. The aim of this study was to assess the mortality rate in patients ≥ 65 years with PHFs. Mortality risk was assessed for 30-day/in-hospital, 1-year, and 5-year follow-up, and was compared based on treatment type. METHODS: A systematic review and meta-analysis was performed in accordance with PRISMA guidelines. Studies were included if they reported mortality rates at 30-day/in-hospital, 1-year, or 5-year in patients ≥ 65 years with PHFs. Data were analysed using a random-effects model to account for anticipated heterogeneity. Subgroup analysis was performed by treatment type (operative vs non-operative). RESULTS: Seventeen studies including 414,379 shoulders (82% female) with a mean age of 78.8 ± 2.5 reported 1-year mortality. Meta-analysis yielded a pooled 1-year mortality rate of 10% (95% CI 8.97-11.20%). Pooled 30-day/in-hospital mortality was 1.74% (95% CI 1.39-2.10%), and 5-year mortality was 36.10% (95% CI 34.50-37.70%). Mortality was lower in the operative group (7.92%, 95% CI 6.98-8.86%) compared to non-operative group (10.80%, 95% CI 9.44-12.17%), with a difference of - 2.89% (95% CI - 4.54 to - 1.23%). However, this finding should be interpreted with caution due to likely confounding by indication inherent in observational studies. CONCLUSION: For patients ≥ 65 years, PHFs are associated with high rates of mortality in the short-to-medium-term: 10.1% at 1 year and 36.1% at 5-year follow-up. These high mortality rates in patients ≥ 65 years support that PHFs are fragility fractures, and these patients could benefit from comprehensive geriatric assessment in defined orthogeriatric pathways.
UNLABELLED: The relationship between bone mineral density (BMD) at the forearm and fracture risk was determined in a meta-analysis of primary data from 11 cohort studies of 35,121 men and women. Low forearm BMD was a sig...UNLABELLED: The relationship between bone mineral density (BMD) at the forearm and fracture risk was determined in a meta-analysis of primary data from 11 cohort studies of 35,121 men and women. Low forearm BMD was a significant predictor of fracture risk, independently of FRAX®. INTRODUCTION: The aim of this study was to quantify the relationship between forearm BMD, FRAX and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value on fracture risk. METHODS: We studied 35,121 men and women from 11 predominantly population-based cohorts followed for an average of 11.1 years and a total of 388,654 person-years. The association between forearm BMD, FRAX probabilities (calculated without femoral neck BMD), and the risk of fracture was examined using an extension of the Poisson regression model in each cohort by sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD difference in BMD). The different studies were merged using weighted coefficients. RESULTS: The GR of forearm BMD for major osteoporotic fracture was 1.41 (95% confidence interval [CI] 1.31-1.51) when adjusted for age and time since baseline and was similar in men and women (p > 0.20). GRs decreased significantly with age. When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, forearm BMD remained a significant, independent predictor for fracture (GR = 1.34, 95% CI 1.26-1.44). A similar GR was noted for hip fracture (GR = 1.48; 95% CI 1.35-1.62) that persisted after adjustment for FRAX (GR = 1.39; 95% CI 1.27-1.52). Adjustments to FRAX probabilities based on forearm BMD varied by age and Z-score. CONCLUSIONS: Forearm BMD is a risk factor for MOF and hip fracture risk beyond the risk attributable to FRAX. Its validation on an international basis permits its use in case finding with FRAX.
UNLABELLED: We developed a revised FRAX® model for Sweden, derived from recent incidence data on fractures, mortality, and origin of birth, and defined age-dependent intervention thresholds. PURPOSE: Since the developmen...UNLABELLED: We developed a revised FRAX® model for Sweden, derived from recent incidence data on fractures, mortality, and origin of birth, and defined age-dependent intervention thresholds. PURPOSE: Since the development of the Swedish FRAX model in 2008, fracture incidence patterns have changed. The primary aim of this study was to develop a revised FRAX model, based on region of birth, and updated incidences for death and fracture for Sweden. A secondary aim was to define age-dependent intervention thresholds. METHODS: Based on national registries, all persons from the age of 40 years living in Sweden between 2005 and 2021 were included. Yearly age- and sex-standardized incidences of hip fracture and major osteoporotic fracture (MOF) were calculated and presented per geographic region of birth. Hip fracture and MOF incidences from 2019 to 2021 were used to create a revised FRAX model for Sweden. Two models, one for Swedish/Nordic-born individuals and one for non-Nordic-born, were developed. The revised FRAX models were compared with the previous FRAX model. Age-specific intervention thresholds were calculated and presented. RESULTS: Compared with the previous FRAX model, the revised model yielded lower 10-year probabilities of both hip fracture and MOF in men and women. The non-Nordic models showed substantially lower probabilities across all age groups and sexes. Intervention thresholds for MOF without BMD ranged from a 10-year probability of 4.5% at age 40 years to 21.5% at age 70 years and older. CONCLUSION: The revised FRAX models provide more accurate fracture prediction in Sweden, with lower risk estimates for older people, but due to the introduction of age-dependent intervention thresholds, it is likely that more younger patients will become eligible for treatment in Sweden.
UNLABELLED: We studied over 45,000 Danish adults with non-dialysis-dependent chronic kidney disease to assess whether parathyroid hormone (PTH) and alkaline phosphatase (ALP) were associated with fracture risk. Elevated...UNLABELLED: We studied over 45,000 Danish adults with non-dialysis-dependent chronic kidney disease to assess whether parathyroid hormone (PTH) and alkaline phosphatase (ALP) were associated with fracture risk. Elevated PTH (over twice normal) and ALP (above 70 U/L) were linked to higher fracture rates, suggesting these markers may help identify high-risk patients. PURPOSE: Patients with chronic kidney disease (CKD) have an increased risk of bone fracture. We aimed to examine the association between parathyroid hormone (PTH), alkaline phosphatase (ALP), and fracture risk in non-dialysis-dependent CKDG3-5. METHODS: Danish adults with eGFR < 60 ml/min/1.73 m and measured PTH were identified from nationwide healthcare registers between 2010 and 2022. PTH was standardized to the assay-specified upper normal limit (UNL) and stratified as normal, slightly elevated (1.1-2.0 × UNL), high (2.1-4.0 × UNL), and very high (≥ 4.0 × UNL). ALP was stratified as low to low-normal (< 70 U/L), upper-normal (70-105 U/L), slightly elevated (106-125 U/L), and high (> 125 U/L). Rates of major osteoporotic fracture (MOF; hip, vertebra, wrist, and humerus fracture) and any fracture were estimated in multiple Cox regression models adjusted for relevant confounders. RESULTS: Among 45,611 included individuals adjusted rates of MOF were increased in patients with high PTH (hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04-1.26, p = 0.005) and very high PTH (HR 1.23, 95% CI 1.04-1.46, p = 0.012), compared to patients with normal PTH. Patients with ALP levels in the upper-normal (HR 1.11, CI 1.02-1.20, p = 0.01), slightly elevated (HR 1.29 CI 1.13-1.47, p < 0.001), and high (HR 1.59, CI 1.39-1.75, p < 0.001) categories showed significantly higher rates of MOF compared to low to low-normal ALP. We found similar HRs of any fracture event stratified by ALP- and PTH levels. CONCLUSION: Our nationwide observational cohort study demonstrates that PTH and ALP were positively associated with fracture risk in non-dialysis-dependent CKDG3-5.
UNLABELLED: Veterans who choose to receive bone densitometry from a community clinic had less travel burden but may have experienced a longer time from referral to DXA. Ensuring access to DXA for accurate, timely diagnos...UNLABELLED: Veterans who choose to receive bone densitometry from a community clinic had less travel burden but may have experienced a longer time from referral to DXA. Ensuring access to DXA for accurate, timely diagnosis and to guide osteoporosis screening remains an important priority. PURPOSE: The Veterans Access, Choice, and Accountability Act (2014) expanded access to community-based dual-energy X-ray absorptiometry (DXA) for eligible veterans facing substantial travel burden or delays in VA access. We examined differences in travel burden, time from referral to DXA, and sociodemographic factors associated with receipt of VA-based DXA (VA-DXA) versus community DXA (CC-DXA) to understand the impact of this policy on veteran access to care. METHODS: We used mixed-effects logistic regression to estimate odds of receiving VA-DXA versus CC-DXA, from October 1, 2019-July 1, 2023, adjusting for clinical and demographic factors related to osteoporosis and access barriers. RESULTS: For veterans living < 40 miles from a VA DXA site, CC-DXA recipients traveled shorter distances than VA-DXA recipients (median 6.6 vs. 13.8 miles); this difference widened for those > 40 miles away from a VHA facility (7.0 vs. 60.7 miles). Conversely, VA-DXA had shorter elapsed time from referral to DXA regardless of proximity (e.g., < 40 miles: 24 vs. 39 days from referral). In adjusted models, living > 40 miles from a tertiary VA facility was the strongest predictor of CC-DXA (aOR 4.86). CC-DXA use was more likely among female (aOR 1.60) and rural veterans (aOR 2.01) and among those with low/moderate frailty, and less likely among Black (aOR 0.50) and Asian veterans (aOR 0.57) compared with White veterans, and among Hispanic versus non-Hispanic veterans (aOR 0.84). CONCLUSIONS: CC-DXA reduced travel burden but was associated with longer referral-to-DXA time. Ongoing monitoring is warranted to ensure equitable, timely DXA access.
UNLABELLED: Pediatric fracture epidemiology in Asian countries is limited. Using a nationwide claims database (2018-2024), we demonstrated lower fracture incidence in Thai vs. Western children. Incidence was higher in ma...UNLABELLED: Pediatric fracture epidemiology in Asian countries is limited. Using a nationwide claims database (2018-2024), we demonstrated lower fracture incidence in Thai vs. Western children. Incidence was higher in males and adolescents. Incidence fell during COVID-19 then rebounded, resulting in non-significant overall change. Forearm fractures and traffic injuries were prominent. PURPOSE: Data on pediatric fracture epidemiology in Thailand remain limited. We aimed to examine 7-year trends in fracture incidence among Thai children and adolescents. METHODS: Fractures recorded in the National Health Security Office (NHSO) claims database from 2018 to 2024 were identified using ICD-10 codes. Fracture incidence in individuals aged < 20 years was calculated per 10,000 person-years among NHSO-insured population. Temporal trends were summarized using annual percent change (APC). RESULTS: We identified 787,866 fractures among 569,819 individuals. The median annual age-standardized incidence rate (ASIR) was 88.1 per 10,000 person-years (range, 76.5-90.6), with a median (Q1-Q3) male-to-female incidence rate ratio (IRR) of 2.6 (2.5-2.6). Forearm fractures were the most common (31%). Incidence increased gradually with age in females but rose sharply in males, with the greatest sex difference during adolescence (IRR, 3.35 [95% CI: 3.32-3.38]). Transportation injuries (37%) and falls (35%) were the leading causes of fractures. ASIR declined during 2018-2022 (APC -4.2%/year, 95% CI: -6.5% to -2.0%) and increased during 2022-2024 (APC 9.6%/year, 95% CI: 4.5%-14.9%), resulting in an overall stable trend (average APC 0.15%/year, 95% CI: -1.27%-1.59%). CONCLUSIONS: Fracture incidence among the Thai pediatric population was lower than that reported from Western countries and remained relatively constant during 2018-2024. Incidence was highest in male adolescents, with traffic accident being the major contributor. Strengthening targeted prevention, particularly traffic-safety interventions, should be a national priority to reduce pediatric fracture burden in Thailand.