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Androgen Deprivation Therapy (ADT) increases long-term fracture risk in prostate cancer. Our study showed a higher fracture risk within six months of ADT use, and current use was associated with a higher risk of fragility fractures. Attention is needed for the prevention of fragility fractures at the start of ADT., Purpose: Androgen Deprivation Therapy (ADT) is known to increase long-term fracture risk in men with prostate cancer (PCa), although the risk of fragility fractures remains unclear. This study aims to evaluate the risk of fragility and malignancy-related fractures in men with PCa treated with ADT., Methods: We conducted a retrospective cohort study of men with PCa. Follow-up time was divided into 30-day intervals and exposure (current, past, or no-ADT use). Current ADT use was stratified by duration of ADT use (≤ 182 days, 183-730 days, and > 730 days). Cause-specific Cox proportional hazard models were used to estimate the risk of fractures., Results: We included 471 patients (mean age 70.5 (± 8.3) years). The mean follow-up time was 5.0 (± 1.7) years in patients who never started ADT, 3.4 (± 2.3) years and 4.1 (± 2.0) years in patients who started ADT at baseline and during follow-up, respectively. In total, 60 patients had a fracture, 48 (80%) fragility, and 12 (20%) malignancy-related fractures. Current ADT use was associated with a higher risk of all fractures (HR 5.10, 95% CI 2.34-11.13) and fragility fractures (HR 3.61, 95% CI 1.57-8.30). The association with malignancy-related fractures could not be studied due to no events during no-ADT use. There was an increased risk of all fractures with longer duration of ADT use., Conclusions: Current ADT use was associated with a higher risk of fragility fractures than no-ADT use. A higher fracture risk was observed within the first six months of ADT use and persisted for longer durations., (© 2024. The Author(s).)

Introduction: Antidepressants and menopause are risk factors which are independently associated with an increased risk of fractures. This review aims to investigate the risk of fragility fractures in women aged 40 and older and prescribed antidepressants., Methods: A literature search was conducted using PubMed, Ovid Embase, Ovid PsychINFO, Web of Science, and Scopus from inception to 1 June 2024. Relevant citations were identified and screened against our inclusion/exclusion criteria. The study population comprised women over 40 years. The risk of fragility fractures was compared between users and non-users of antidepressants. Risk of bias assessment was carried out using the ROBINS-I tool. A meta-analysis of cohort studies was performed to assess fracture risk associated with prescribing of any antidepressant agents, and SSRIs specifically., Results: Of the 3,676 articles retrieved, five observational studies were found eligible for inclusion ( n  = 1,240,354). In a meta-analysis of 4 studies, an increased risk of fractures in women was associated with the prescribing of antidepressants (HR = 1.62, 95% CI: 1.15-2.28; I 2  = 96.50%) and SSRIs in particular (HR = 1.36, 95% CI: 1.20-1.55; I 2  = 40.32%)., Conclusions: Findings from this review suggest that prescribing of antidepressants is associated with an increased risk of fractures in women aged 40 and older. Substantial heterogeneity between studies may have affected the results of the meta-analysis.

Long-term glucocorticoids (GCs) treatment is associated with osteoporosis and fractures. We investigated whether low-dose GC treatment also increased the risk of osteoporotic fractures, and the results showed that even low-dose GC treatment increased the risk of osteoporotic fractures, especially spine fractures., Purpose: The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated., Methods: 119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6 months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up., Results: The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94])., Conclusion: Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Purpose: Skeletal fluorosis (SF) results from chronic exposure to fluoride (F-) causing excessive aberrantly mineralized brittle bone tissue, fractures, and exostoses. There is no established treatment other than avoiding the source of F-. Still, excess F- can persist in bone for decades after exposure ceases., Case Presentation: A 50-year-old woman presented with multiple, recurrent, low AQ2 trauma fractures yet high radiologic bone mineral density. Serum F- was elevated, and osteomalacia was documented by non-decalcified transiliac biopsy. She reported intermittently "huffing" a keyboard cleaner containing F- (difluoroethane) for years. Following cessation of her F- exposure, we evaluated the administration of the parathyroid hormone analog, abaloparatide, hoping to increase bone remodeling and diminish her skeletal F- burden., Conclusion: Due to the prolonged half-life of F- in bone, SF can cause fracturing long after F- exposure stops. Anabolic therapy approved for osteoporosis, such as abaloparatide, may induce mineralized bone turnover to replace the poorly mineralized osteomalacic bone characteristic of SF and thereby diminish fracture risk. Following abaloparatide treatment for our patient, there was a decrease in bone density as well as a reduction in F- levels., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

The widespread use of immune checkpoint inhibitors (ICIs) in clinical practice has broadened our understanding of their immune-related adverse events (irAEs). IrAEs, including musculoskeletal adverse events, remain a significant concern. While ICI-associated arthritis is a well-documented musculoskeletal side effect of ICI therapy, the direct effects of ICIs on bone in patients with cancer are poorly understood. There is emerging evidence to support the hypothesis that ICIs adversely impact bone turnover and can lead to osteoporosis and fragility fractures, which are not currently recognized as irAEs., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We investigated the relationship between sodium-glucose cotransporter-2 inhibitor (SGLT2i) and fracture in elderly women diagnosed with type 2 diabetes mellitus (T2DM) and newly prescribed antidiabetic medications (ADMs)., Material and Methods: We used the population-based cohort study data from the National Health Insurance Service of Korea (2013-2020). Women ≥65 years old with T2DM, who were newly prescribed ADMs other than glucagon-like peptide-1 receptor agonists and thiazolidinedione, and who had comprehensive health check-up data were included., Results: A total of 1,333 SGLT2i users were matched in a 1:2 ratio with 2,626 non-SGLT2i users. After propensity score matching, mean age, body mass index, number of ADMs, and other covariates were well-balanced between SGLT2i users and non-SGLT2i users. During the follow-up period, a higher incidence of vertebral fractures in SGLT2i users than in non-SGLT2i users (incidence rate 19.2 vs. 13.8 per 1,000 person-years; hazard ratio 1.40, 95 % confidence interval 1.00-1.96, p = 0.049). No significant difference was noted in other types of fracture., Conclusion: SGLT2i use showed an increased risk of vertebral fracture than non-SGLT2i use in elderly women. Although further validation is required, SGLT2i should be cautiously prescribed in older women due to the potential association with fracture risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Connections between long-term use of topical corticosteroids (TCSs) of varying potency and osteoporosis and major osteoporotic fracture (MOF) are unclear. Susceptibility to adverse bone effects of TCSs in different sex, age and ethnic groups is unknown too., Objectives: To demonstrate the association between cumulative dose of TCSs of varying potency and osteoporosis and MOF in Taiwanese population, with stratified analysis of sex and age., Methods: We conducted a nationwide case-control study and obtained data from Taiwan National Health Insurance Research Database. Cumulative TCS doses in different exposure periods were calculated, and the potency of TCSs was converted to prednisolone equivalent. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for osteoporosis and MOF associated with TCS use., Results: From 2017 to 2020, 129,682 osteoporosis cases and 34,999 MOF cases were selected and randomly matched with 518,728 and 139,996 controls by sex and age. We found clear dose-response relationships between long-term TCS exposure and osteoporosis and MOF. For example, compared to no TCS use, adjusted ORs of osteoporosis were 1.216 (95% CI 1.189-1.243), 1.260 (95% CI, 1.241-1.280) and 1.341 (95% CI, 1.314-1.369) for exposure to low, medium and high cumulative TCS doses, respectively, over 5 years. Adjusted ORs of MOF were 1.118 (95% CI 1.069-1.170), 1.191 (95% CI, 1.156-1.227) and 1.288 (95% CI, 1.238-1.340) for exposure to low, medium and high cumulative TCS doses, respectively, over 5 years. Stratified analysis showed women had higher ORs of osteoporosis and MOF compared to men. Younger people (<50 years) had highest OR of osteoporosis compared to other age groups., Conclusions: Higher cumulative TCS dose was associated with increased risk of osteoporosis and MOF. Long-term use of TCSs should be cautious, especially in susceptible populations such as women and young people., (© 2023 European Academy of Dermatology and Venereology.)

Background: The use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), has been linked to adverse effects on bone health, but findings are conflicting. This study aimed to quantify the associations between newer antidepressants and bone mineral density (BMD) and fracture risk through a comprehensive meta-analysis., Methods: Observational studies on the association between the use of novel antidepressants and BMD and hip fracture were systematically searched in PubMed, Embase, CINAHL, Cochrane Library, and Scopus. Random effects meta-analyses were conducted to pool results across the eligible studies. The heterogeneity, publication bias, and influence were assessed extensively., Results: 14 eligible studies with 1,417,134 participants were identified. Antidepressant use was associated with significantly lower BMD compared to non-use at all skeletal sites examined, with pooled standardized mean differences (SMD) ranging from -0.02 (total hip) to -0.04 (femoral neck). Importantly, antidepressant use was associated with a 2.5-fold increased risk of hip fracture (pooled odds ratio (OR) 2.50, 95% CI 2.26-2.76). While heterogeneity was detected, the overall findings were robust in sensitivity analyses., Conclusions: This meta-analysis provided strong evidence that novel antidepressants, especially widely used SSRIs, have detrimental impacts on bone health. The observed associations with decreased BMD and doubled hip fracture risk have important clinical implications.

Fractures often cause irreversible harm in Duchenne muscular dystrophy (DMD). This study investigated the trajectory of bone mineral density (BMD) using group-based trajectory modeling and identified that BMD acts as an early-stage indicator of clinically significant bone fragility. The greater the early-stage BMD, the better the 4-year bone health outcome., Purpose: Most Duchenne muscular dystrophy (DMD) children suffer bone loss after long-term glucocorticoid (GC) exposure, which induces scoliosis and fragility fractures. To assess the BMD progression pattern and individual medical risk markers for these phenotypes in young ambulatory boys with DMD, and provide evidence-based suggestions for clinical management of bone health., Methods: A retrospective longitudinal cohort study of 153 boys with DMD in West China Second University Hospital (2016-2023) was performed. Group-based trajectory modeling was used to study the BMD progression pattern, and potential predictors were further analyzed by logistic regression and survival analysis., Results: One hundred and fifty-three participants were included, 71 of which had more than 3 BMD records. Three BMD trajectories were identified. Baseline BMD and age-started GC and were independent predictors of trajectory attribution. The median survival time of the first observation of low BMD in GC-treated DMD boys was 5.32 (95% CI 4.05-6.59) years, and a significant difference was tested (P < 0.001) among the three trajectory groups., Conclusion: BMD may serve as a novel early indicating marker for monitoring bone fragility for DMD. We proposed a bone health risk stratification through BMD progression trajectory that allows us to adapt the osteoporosis warning sign in DMD from a fixed threshold approach to a more individualized strategy, where baseline BMD and age of glucocorticoid initiation can provide an earlier prediction of bone loss. Better management of primary BMD may be able to delay or avoid the onset of adverse bone health outcomes in the fifth year in children with DMD., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Importance: Corticosteroid injections (CSIs) are an important tool for pain relief in many musculoskeletal conditions, but the longitudinal effects of these treatments on bone health and fracture risk are unknown., Objective: To determine whether cumulative doses of corticosteroid injections are associated with higher risk of subsequent osteoporotic and nonosteoporotic fractures., Design, Setting, and Participants: This cohort study included adult patients receiving any CSI from May 1, 2018, through July 1, 2022. Eligible patients resided in Olmsted County, Minnesota, and were empaneled to receive primary care within the Mayo Clinic. Cox proportional hazards regression models were used to evaluate risk of fracture based on cumulative injected corticosteroid dose., Exposure: Receipt of any CSI during the study period., Main Outcomes and Measures: The primary outcome was risk of fracture by total triamcinolone equivalents received. Secondary outcomes consisted of risks of fracture based on triamcinolone equivalents received in subgroups of patients not at high risk for fracture and patients with osteoporosis., Results: A total of 7197 patients were included in the study (mean [SD] age, 64.4 [14.6] years; 4435 [61.6%] women; 183 [2.5%] Black and 6667 [92.6%] White), and 346 (4.8%) had a new fracture during the study period. Of these fractures, 149 (43.1%) were considered osteoporotic. In the adjusted Cox proportional hazards regression model, there was no association of higher fracture risk based on cumulative CSI dose (adjusted hazard ratio [HR], 1.04 [95% CI, 0.96-1.11]). There was also no associated higher risk of fracture in the non-high-risk (adjusted HR, 1.11 [95% CI, 0.98-1.26]) or osteoporosis (adjusted HR, 1.01 [95% CI, 0.90-1.11]) subgroups. Age, Charleson Comorbidity Index, and previous fracture were the only factors that were associated with higher fracture risk., Conclusions and Relevance: In this cohort study of cumulative injected corticosteroid dose and risk of subsequent fracture, no association was observed, including in patients with a preexisting diagnosis of osteoporosis. Treatment of painful conditions with CSI should not be withheld or delayed owing to concern about fracture risk.

Background: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high)., Objectives: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively., Search Methods: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023., Selection Criteria: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study., Main Results: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies., Authors' Conclusions: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Study Design: A retrospective study., Objective: The clinical efficacy of vertebroplasty and kyphoplasty treating osteoporotic vertebral compression fractures (OVCF) has been widely recognized in recent years. However, there are also disadvantages of bone cement leakage (BCL), limited correction of kyphosis and recovery of vertebral height. Nowadays, in view of these shortcomings, vesselplasty has been widely used in clinical practice. The objective of this study is to assess its clinical effect and application value for the treatment of OVCF with peripheral wall damage., Methods: 62 patients (70 vertebrae) treated for OVCF with peripheral wall damage using vesselplasty retrospectively reviewed. The data collection included operation time, volume of bone cement, relevant surgical complications, visual analog scale (VAS), Oswestry disability index (ODI), vertebral body height and kyphosis Cobb angle., Results: The volume of bone cement was 3-8 (5.3 ± 1.3) ml. There were 3 vertebrae of BCL (4.3%). VAS and ODI at different time points after operation were decreased compared with before operation (all p  < 0.05). There were no statistical differences between VAS or ODI at different postoperative time points ( p  > 0.05). Vertebral body height and Cobb angle at different time points after operation were improved compared with before operation (all p  < 0.05). There were no statistical differences between vertebral body height or Cobb angle at different postoperative time points (all p  > 0.05)., Conclusions: Vesselplasty may reduce the risk of BCL and better control the dispersion of bone cement in the treatment of OVCF. It relieves pain, restores vertebral body height and corrects kyphosis, especially in OVCF with peripheral wall damage. Therefore, vesselplasty is safe and worthy of clinical application.

Background/aims: Long-term use of acid suppressants such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonist (H2RA) has been associated with the risk of osteoporotic fracture. Acid suppressants and muco-protective agents (MPAs) are often used together as anti-ulcer agents. We evaluated the association between the risk of osteoporotic fracture and the combined use of these anti-peptic agents., Methods: A population-based case-control study was conducted by analyzing the Korean National Health Insurance Data from 2014 to 2020. Patients who had been prescribed anti-peptic agents, such as PPI, H2RA, or MPA, were included. Considering the incidence of osteoporotic fractures, the case group (n = 14,704) and control group (n = 58,816) were classified by 1:4 matching based on age and sex., Results: The use of all types of anti-peptic agents was associated with an increased risk of osteoporotic fractures (PPI: hazard osteoratio [HR], 1.31; H2RA: HR, 1.44; and MPA: HR, 1.33; all p < 0.001). Compared to PPI alone, the combined use of "PPI and H2RA" (HR, 1.58; p = 0.010) as well as "PPI, H2RA, and MPA" (HR, 1.71; p = 0.001) was associated with an increased risk of osteoporotic fracture. However, compared with PPI alone, "MPA and PPI or H2RA" was not associated with an increased risk of osteoporotic fracture., Conclusion: This study found that the combined use of "PPI and H2RA" was associated with a higher risk of osteoporotic fractures. In cases where deemed necessary, the physicians may initially consider prescribing the combination use of MPA.

Introduction: Androgen deprivation therapy (ADT) is widely used for the treatment of prostate cancer. ADT is associated with reduced bone density leading to an increased risk of osteoporotic fracture. The objective of this retrospective cohort study was to quantify fracture risk in men treated with ADT for prostate cancer in real-world practice in Japan., Materials and Methods: Data were extracted from the Japanese Medical Data Vision (MDV) database. Men initiating ADT for treatment of prostate cancer between April 2010 and March 2021 were identified and matched to a cohort of prostate cancer patients not taking ADT using a propensity score. Fracture rates were estimated by a cumulative incidence function and compared between cohorts using a Cox cause-specific hazard model. Information was extracted on demographics, comorbidities and bone densitometry., Results: 30,561 men with PC starting ADT were matched to 30,561 men with prostate cancer not treated with ADT. Following ADT initiation, <5% of men underwent bone densitometry. Prescription of ADT was associated with an increased fracture risk compared to not taking ADT (adjusted hazard ratio: 1.63 [95% CI 1.52-1.75])., Conclusion: ADT is associated with a 1.6-fold increase in the risk of osteoporotic fracture in men with prostate cancer. Densitometry in this population is infrequent and monitoring urgently needs to be improved in order to implement effective fracture prevention., (© 2024. The Author(s).)

Purpose: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome., Methods: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4)., Results: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001)., Conclusion: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hormone therapy with aromatase inhibitors (AIs) for estrogen receptor-dependent breast cancer may expose patients to an increased osteoporosis risk. This study was performed to estimate fracture risk in women with breast cancer to whom AIs were prescribed in Japan., Methods: This retrospective study used data from the Japanese Medical Data Vision database. Women with breast cancer prescribed AIs over a 12-month period were identified and matched to women not prescribed AIs using a propensity score. Fracture rates were estimated by a cumulative incidence function and compared using a cause-specific Cox hazard model. The proportion of women undergoing bone density tests was retrieved., Results: For all fractures sites combined, cumulative fracture incidence at 10 years was 0.19 [95%CI: 0.16-0.22] in women prescribed AIs and 0.18 [95%CI: 0.15-0.21] without AIs. AI prescription was not associated with any changes in risk (adjusted hazard ratio: 1.08 [95%CI: 0.99-1.17] p  = 0.08). Women prescribed AI more frequently underwent bone density testing (31.9% [95% CI: 31.2%; 32.6%] versus 2.2% [95% CI: 2.0%; 2.4%])., Conclusions: The anticipated association between AI exposure and osteoporotic fracture risk in Japanese women with breast cancer was not seen clearly.

Background: Several studies have shown associations between cadmium (Cd) exposure and an increased risk of fractures. However, the size of the risk is still unclear and proper adjustment for smoking is a challenge. The aim of this study was to quantify the association between dietary cadmium measured in blood and fracture risk in the general Swedish population through a large population-based case-control study in never-smokers., Methods: The study included 2113 incident cases with osteoporosis-related fractures and the same number of age- and sex-matched controls in never-smokers from the Swedish population-based Malmö Diet and Cancer study cohort. Cd in blood (B-Cd) was analyzed at baseline (1991-1996). Incident osteoporosis-related fractures (of the hip, distal radius, and proximal humerus) up to the year 2014 were identified using the National Patient Register. Associations between B-Cd and fractures were analyzed using logistic regression., Results: Median B-Cd was 0.22 μg/L (P25 = 0.16, P75 = 0.31) among 2103 cases and 0.21 (P25 = 0.15, P75 = 0.30) among 2105 controls. The risk of fracture was significantly increased (OR 1.58; 95 % confidence interval 1.08-2.31, per μg/L of B-Cd), after adjustment for age, sex, BMI, physical activity, and fiber consumption. In analyses by cadmium quartiles, the OR increased monotonically and was significant in the highest quartile of B-Cd (for B-Cd > 0.31 versus B-Cd < 0.15 μg/L; OR 1.21; 95 % confidence interval 1.01-1.45)., Conclusion: Even modestly increased blood cadmium in never-smokers is associated with increased risk of incident osteoporosis-related fractures., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

We reviewed and meta-analyzed 20 observational studies to examine the relationship between sedative-hypnotic use and osteoporotic fractures. We searched PubMed, Embase, APA PsycINFO, and Web of Science™ for studies that used cohort, case-control, case-crossover, and self-controlled case series designs. We further assessed the quality of each study and performed meta-analyses of association estimates, e.g., odds ratios (ORs). The analysis included 6,084,083 participants and found a slight association between the use of sedative-hypnotics and osteoporotic fractures, with differing strength of associations between different classes of drugs and greater sedative-hypnotics exposure. The pooled estimates ORs for case-control studies were 1.33 (95% CI 0.98-1.80) with benzodiazepines (BZD) and any fractures, 1.32 (95% CI 1.05-1.66) with BZDs and hip fractures, and case-crossover studies were 1.15 (95% CI 0.95-1.41) with BZDs and any fractures, 1.41 (95% CI 1.08-1.85) with Z-drugs and any fractures. The study suggests that more research is needed to aid medical professionals in balancing this potential risk of osteoporotic fractures associated with sedative-hypnotic use against other reported adverse events and anticipated therapy outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs., Methods: 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs., Results: Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site., Conclusions: TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: The therapeutic efficacy of renin-angiotensin system inhibitors (RASi) in elderly patients with hypertension and at risk of fractures has been in the limelight because of accumulating evidence that localized RAS activation in bone tissue leads to osteoclastic bone resorption, resulting in osteoporosis. This study set out to investigate the association between RASi use and fracture incidence in a large cohort., Methods: We employed a nested case-control design to investigate the association between RASi use and newly developed fractures. A case was defined as a patient newly diagnosed with a fracture between January 2004 and December 2015. We selected 1,049 cases and controls using 1:1 propensity score matching. Conditional logistic regression analysis was conducted to estimate the association between RASi exposure and fracture incidence., Results: Overall, RASi usage was significantly associated with lower odds for fracture incidence (ever-users vs never-users: OR, 0.73; 95% CI, 0.59-0.91). We found that ARB-only users experienced fewer fractures than RASi-never users (OR, 0.65; 95% CI, 0.49-0.86), whereas ACEi-only users or ARB/ACEi-ever users did not. In subgroup analysis, RASi-ever users without cerebrovascular disease, those with a BMI exceeding 23, and statin exposure had significantly lower ORs., Conclusions: The present study established a significant association between RASi use and reduced fracture incidence, thus highlighting the potential clinical utility of RASi use as a preventive strategy in elderly patients at risk for osteoporotic fractures., (© 2023. The Author(s).)

Introduction: Osteoporotic fractures lead to significant decreases in the quality of life with increases in morbidity, mortality, and disability. Treatment with a variety of anti-epileptic drugs, such as phenytoin, has been understood to cause a decrease in bone mineral density., Materials and Methods: Cohort A was identified as patients that were 18-55 years old that had epilepsy and recurrent seizures that were also prescribed phenytoin. Cohort B was identified as patients that were 18-55 years old that had epilepsy and recurrent seizures but were not prescribed phenytoin or other anti-epileptic medications. Cohorts were matched for relevant confounding pathologies and demographic factors. Outcomes were evaluated from 1 day to 5 years after the indexed event., Results: A total of 35,936 patients with epilepsy that were prescribed phenytoin were matched with 109,335 patients with epilepsy that were not prescribed phenytoin. Patients on phenytoin therapy were at significantly higher risk for osteoporosis without pathological fracture, fracture of metatarsal bone, fracture of shoulder and upper arm, fracture of distal radius, fracture of thoracic vertebra, fracture of cervical vertebra, fracture of lumbar vertebra, fracture of femoral head or neck, pertrochanteric fracture, femoral shaft fracture, and distal tibia fracture (all outcomes p < 0.001)., Conclusion: Epileptic patients on phenytoin therapy that were 18-55 years old exhibited higher associated risk of osteoporosis and osteoporotic-fragility fractures of various regions. Patients that undergo phenytoin therapy for epilepsy treatment should be educated on the increased risk of bone fractures and have appropriate lifestyle and diet modifications., (© 2023. The Japanese Society Bone and Mineral Research.)

Context: Despite prevalent anti-osteoporosis medication (AOM) switching in real-world osteoporosis management, few studies have evaluated the impact of persistent AOM treatment, allowing for AOM switching, on the risk of subsequent fracture., Objective: We examined the association between persistence in AOM and subsequent fractures, allowing for medication switching among patients with osteoporotic fractures., Methods: This retrospective cohort study used Taiwan National Health Insurance claims data to select patients who initiated AOM between 2013 and 2016. Treatment persistence was defined as use of any AOM on a given day of interest with a 45-day grace period. Medication switch was allowed for persistence if remaining on treatment. AOMs with long-lasting inhibition of bone resorption (zoledronate and denosumab) were categorized as high-potency; others as low-potency. Multivariate Cox models were used to evaluate risk of subsequent fractures ≥3 months after initiating AOM., Results: A total of 119 473 patients were included (mean [SD] follow-up 46.4 [15.6] months), and 26.8% switched from the index AOM. Within 1 year, 52% remained persistent with AOM. Compared to patients with persistent AOM, those not persistent had higher risk of subsequent hip (adjusted hazard ratio [aHR] = 1.31; 95% CI, 1.21-1.42), vertebral (aHR = 1.17; 95% CI, 1.13-1.22), and radius fractures (aHR = 1.16; 95% CI, 1.08-1.25). Patients with persistent AOM who switched from high- to low-potency AOM had higher risk of subsequent vertebral fractures than those with persistent AOM and no potency switch (aHR = 1.28; 95% CI, 1.02-1.60)., Conclusion: Patients with non-persistent AOM had higher risk of subsequent fractures than persistent users when allowing AOM switch. Switching AOM potency may influence the risk of subsequent vertebral fractures and warrants further investigation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: As tenofovir disoproxil fumarate (TDF) requires long-term use, a reduction in bone density should be considered a possibility when treating patients with chronic hepatitis B (CHB) with aging and systemic diseases. Patients treated with tenofovir alafenamide (TAF) have improved bone mineral density loss compared to patients treated with TDF. Although improvements in bone density caused by TAF have been reported, studies on the actual reduction of fractures are insufficient., Aim: To evaluate the impact of TAF on the risk of osteoporotic fractures in comparison with that of TDF., Methods: Using the national claims data of the Health Insurance Review and Assessment Service, we conducted a retrospective cohort study of 32,582 patients with CHB who had been initially treated with TDF or TAF between November 2017 and December 2020. The numbers of patients treated with TDF and TAF were 20,877 and 11,705, respectively. The annual fracture rate per 100 patients in each group was calculated, and the Cox proportional hazard ratio (HR) was analysed after applying inverse probability treatment weights (IPTW) for both groups., Results: Among 32,582 patients, the average age was 47.8 ± 11.2 years, 64.5% were men, and the follow-up period was 24.4 ± 11.6 months. The incidence of osteoporotic fractures was 0.78 and 0.49 per 100 person-years in the TDF and TAF groups, respectively. After application of IPTW, the HR was 0.68 (95% confidence interval 0.55-0.85, p = 0.001)., Conclusion: TAF-treated patients with CHB had a significantly lower risk of osteoporotic fracture than TDF-treated patients., (© 2023 John Wiley & Sons Ltd.)

Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture; however, the mechanism is unclear. PPI users taking calcium supplements were more likely to have hyperparathyroidism compared to non-users (OR 1.56, CI 1.08-2.23, p = 0.018). This highlights the importance of monitoring PPI use, especially in older adults., Purpose: Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture. Hyperparathyroidism may be implicated, but few studies have considered this relationship. This study evaluated the relationship between PPI use and hyperparathyroidism in older adults., Methods: Participants were from the TUDA study, a large cross-sectional cohort of older Irish adults. Participants with an estimated glomerular filtration rate (eGFR) < 30 ml/min and serum calcium > 2.5 mmol/l were excluded to avoid hyperparathyroidism due to chronic renal disease and primary hyperparathyroidism. Hyperparathyroidism was defined as a parathyroid hormone (PTH) > 65 pg/ml. Multivariate regression models were used to analyse the relationship between PPI use and hyperparathyroidism., Results: A total of 4139 participants met the inclusion criteria, of whom 37.8% (n = 1563) were taking PPI medication. PPI use was identified in 41.4% of calcium supplement users and 35.4% of non-calcium supplement users. Overall, compared to non-users of PPIs, those taking PPIs were older (74.8 vs 72.9 years, p < 0.001) and had a higher prevalence of hyperparathyroidism (17.8 vs 11.0%, p < 0.001). In those taking calcium supplements (but not in non-users), PPI use was significantly associated with hyperparathyroidism (OR 1.56, CI 1.08-2.23, p = 0.018) after adjusting for age, sex, body mass index, serum vitamin D, eGFR, timed-up-and-go, dairy intake, medications, and comorbidities., Discussion: The results are consistent with the hypothesis of PPIs reducing calcium absorption, leading to a rise in PTH which could mediate increased fracture risk. No relationship of PPI use with hyperparathyroidism was observed in non-users of calcium supplements, possibly owing to lower dietary calcium intake. These results highlight the importance of monitoring PPI use, especially in older adults at risk of fracture., (© 2023. The Author(s).)

Proton pump inhibitors (PPIs) are commonly prescribed medications. The existing data suggest that individuals at a high risk of fractures have been exposed to high doses of PPIs for prolonged durations. CYP2C19 plays a pivotal role in metabolism of PPIs and thereby influences their pharmacokinetic profile. Hence, we hypothesize that CYP2C19 genotypes may be associated with fragility fracture among PPIs users due to PPI exposure. This study aimed to investigate the association between CYP2C19 genotypes, bone mineral density (BMD), and osteoporotic fracture in a hospital-based population. This retrospective cohort study enrolled patients who were prescribed long-term PPIs at Taichung Veterans General Hospital using data extracted from the Taiwan Precision Medicine Initiative between January 2010 and April 2021. Associations between CYP2C19 phenotypes, comorbidities, and fractures in PPI users were analyzed. We enrolled 1518 long-term PPI users; 571 (38%), 727 (48%), and 220 (14%) CYP2C19 normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs), respectively. Among them, 49 (3.2%) patients developed fractures within the 1-year follow-up period; 20 (3.5%) fractures in NMs, 24 (3.3%) in IMs, and 5 (2.3%) in PMs, respectively. No significant difference was observed among CYP2C19 genotypes and fracture. Additionally, BMD measurements during the 1-year follow-up period were made available among 75 participants. No significant difference in BMD between CYP2C19 PMs and non-PMs was found. This real-world, hospital-based study concludes that CYP2C19 PMs/IMs are not associated with an increased risk for fractures or reduced BMD in individuals on long-term PPI therapy., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: Second fractures at the cemented vertebrae (SFCV) are often seen after percutaneous kyphoplasty, especially at the thoracolumbar junction. Our study aimed to develop and validate a preoperative clinical prediction model for predicting SFCV., Methods: A cohort of 224 patients with single-level thoracolumbar osteoporotic vertebral fractures (T11-L2) from 3 medical centers was analyzed between January 2017 and June 2020 to derive a preoperative clinical prediction model for SFCV. Backward-stepwise selection was used to select preoperative predictors. We assigned a score to each selected variable and developed the SFCV scoring system. Internal validation and calibration were conducted for the SFCV score., Results: Among the 224 patients included, 58 had postoperative SFCV (25.9%). The following preoperative measures on multivariable analysis were summarized in the 5-point SFCV score: bone mineral density (≤-3.05), serum 25-hydroxy vitamin D3 (≤17.55 ng/mL), standardized signal intensity of fractured vertebra on T1-weighted images (≤59.52%), C7-S1 sagittal vertical axis (≥3.25 cm), and intravertebral cleft. Internal validation showed a corrected area under the curve of 0.794. A cutoff of ≤1 point was chosen to classify a low risk of SFCV, for which only 6 of 100 patients (6%) had SFCV. A cutoff of ≥4 points was chosen to classify a high risk of SFCV, for which 28 of 41 (68.3%) had SFCV., Conclusion: The SFCV score was found to be a simple preoperative method for identification of patients at low and high risk of postoperative SFCV. This model could be applied to individual patients and aid in the decision-making before percutaneous kyphoplasty., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The prevalence of glucocorticosteroid-induced osteoporosis (GIOP) is well established in higher income countries. There are limited studies showing a wide prevalence of GIOP in Africa. Prospective studies are needed on GIOP in African rheumatology patients to implement appropriate management algorithms., Purpose: The prevalence of glucocorticosteroid-induced osteoporosis (GIOP) is well established in developed countries, but little is known about GIOP in African adult patients with inflammatory rheumatic musculoskeletal diseases (RMDs). This study aimed to determine the prevalence of GIOP and osteoporotic fracture risk in African patients with inflammatory RMDs according to radiographic and bone mineral density (BMD) findings., Methods: PubMed, Google Scholar, Scopus, and African Index Medicus were searched up to 31 December 2020. Heterogeneity was assessed using I 2 statistic across the included studies. A random-effects model was applied to estimate the pooled effect size across studies. All statistical analyses were performed using STATA™ version 14 software. The study was registered with PROSPERO, number CRD42021256252., Results: In this meta-analysis, a total of 7 studies with 780 participants, stratified by geographical region were included. The pooled prevalence of GIOP based on BMD data was 47.7% (95% CI 32.9-62.8) with 52.2% (95% CI 36.5-67.6) in North African countries and 15.4% (95% 1.9-45.4%) in South Africa with a high heterogeneity (I 2  = 93.3%, p = 0.018). There was no data from the rest of African countries. We were unable to complete the meta-analysis of osteoporotic fractures due to the lack of available data., Conclusion: This study revealed that the prevalence of GIOP varies significantly in Africa. There is no information, however, for most of Africa, and further prospective studies are needed to develop context-specific GIOP preventive strategies in patients with RMDs., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: The fracture risks of non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin in patients with atrial fibrillation (AF) remain controversial., Methods: PubMed, Cochrane Library, EMBASE, Clinical Trials.gov databases for RCTs, and cohort studies were systematically searched from inception to 10 June 2021., Results: Twelve-two studies met the inclusion criteria and 477,821 patients were included. Warfarin increased the risk of fracture in AF patients compared with NOACs in overall any fracture (RR = 0.79; 95% CI = 0.70-10.88; p  = 0.00), osteoporotic fracture (RR = 0.746; 95% CI = 0.630-0.883; p  = 0.001). No significant difference was observed in the hip or pelvic fracture, vertebral fracture, extremity fracture, wrist fracture, femoral neck fracture, and ankle fracture. In subgroup analyses based on several aspects, NOACs were associated with a significant reduction in any fracture (standard dosage NOACs, cohort studies, elderly patients, rivaroxaban in RCTs, dabigatran, rivaroxaban, and apixaban in cohort studies), in the hip/pelvic fracture (follow-up time ≤1 year, cohort studies), and osteoporotic fracture (cohort studies)., Conclusion: NOACs were associated with a significantly lower risk of any fracture and osteoporotic fracture compared to warfarin. This benefit was also observed in specific NOACs types of dabigatran, rivaroxaban, and apixaban. However, whether NOACs had a less fracture risk than warfarin on the other risk of fractures was still uncertain.

Long-term or supra-physiological dose of glucocorticoid (GC) application in clinic can lead to impaired bone growth and osteoporosis. The side effects of GC on the skeletal system are particularly serious in growing children, potentially causing growth retardation or even osteoporotic fractures. Children's bone growth is dependent on endochondral ossification of growth plate chondrocytes, and excessive GC can hinder the development of growth plate and longitudinal bone growth. Despite the availability of drugs for treating osteoporosis, they have failed to effectively prevent or treat longitudinal bone growth and development disorders caused by GCs. As of now, there is no specific drug to mitigate these severe side effects. Traditional Chinese Medicine shows potential as an alternative to the current treatments by eliminating the side effects of GC. In summary, this article comprehensively reviews the research frontiers concerning growth and development disorders resulting from supra-physiological levels of GC and discusses the future research and treatment directions for optimizing steroid therapy. This article may also provide theoretical and experimental insight into the research and development of novel drugs to prevent GC-related side effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hua, Huang, Li, Lin and Cui.)

Background: The prevalence of osteoporosis and osteoporotic fractures is expected to increase with the aging of the population in the coming decades. In this study, we systematically reviewed the evidence on the association between exposure to air pollution and osteoporosis-related outcomes., Methods: We systematically searched evidence according to the PRISMA on PubMed, Scopus, and Web of Science (until August 2022). The risk of bias (RoB) was assessed using the Risk of Bias in the Non-randomized Studies of Exposures (ROBINS-E) tool. Random effects meta-analysis was applied to calculate combined estimates. We evaluated the heterogeneity using Cochran's Q test and quantified it by I 2 and tau 2 statistics. The overall body of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) tool., Results: Out of 5254 retrieved articles, 19 studies (11 cross-sectional, seven cohorts, and one case-control) met our inclusion criteria. Most of the studies had a high probability of RoB (n = 17), and only two had a moderate RoB. Different outcomes including bone mineral density, bone mineral content, osteoporotic fracture, osteoporosis, and osteopenia were reported across the studies. The associations were reported for different air pollutants including PM2.5, PM10, nitrogen oxides, nitrogen dioxide, ozone, black carbon, carbon monoxide, sulfur dioxide, nitrogen oxide, and coarse particulate matter. Evidence was suggestive of the negative role of PM10, PM2.5, and nitrogen dioxide (e.g. bone mineral density pooled estimate: -0.02, 95%CI: -0.03: -0.01). The overall body of evidence for most of the exposure-outcome pairs was low and very low., Conclusions: The evidence on the association between air pollution exposure and osteoporosis-related outcomes is heterogenic. However, the evidence suggests an increased risk of osteoporotic fracture and osteoporosis in outdoor air pollutants. Due to the small number of studies in each group, also observed heterogeneity, and publication bias, the results should be interpreted with caution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Rheumatoid arthritis (RA) has been linked to an increased risk of osteoporosis as well as fractures. Patients diagnosed with RA had a 25% increased risk of osteoporotic fracture, according to a recent population-based cohort study that compared them to people without RA. Several studies have found a correlation between osteoporosis and the presence of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and 6. These cytokines play a crucial part in the process of bone resorption by boosting osteoclast activation and encouraging osteoclast differentiation. Based on the correlation between RA, osteoporosis, and inflammation, it is possible that systemic immunosuppression with disease-modifying antirheumatic drugs (DMARDs) can help individuals with RA have a lower chance of developing osteoporosis and osteoporotic fractures. There is little information on how different DMARDs, biologic or non-biologic, affect RA patients' bone metabolism. In this study, we present an overview of the influence that targeted therapies, such as biologics, non-biologics, and small molecule inhibitors, have on bone homeostasis in RA patients., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Bone modifying agents (BMAs) prevent skeletal related events among patients with metastatic, castration-resistant prostate cancer (mCRPC) involving bone and prevent osteoporotic fractures among patients at high risk. BMA utilization for patients with mCRPC has not been well quantified., Methods: We used linked SEER registry and Medicare claims data. We included men diagnosed with stage IV prostate adenocarcinoma during 2007-2015, aged > = 66 at diagnosis, with sufficient continuous enrollment in Medicare Parts A, B, and D, who received androgen deprivation therapy. We limited to those who subsequently received a CRPC-defining treatment (CDT). We identified patients with evidence of bone metastasis using claims. Our primary outcome was receipt of a BMA (zoledronic acid or denosumab) within 180 days of initiating CDT., Results: Among 1292 included patients, 1034 (80%) had bone metastasis. BMA use within 180 days of initiating CDT was higher among patients with bone metastases than those without (705/1034 [68%] vs 56/258 [22%]). Among patients without bone metastasis, those with high osteoporotic fracture risk were more likely than those without to receive a BMA (OR = 2.48, 95% CI: 1.17, 5.29); however, only 26% of patients with high fracture risk received a BMA. Among patients who received BMAs, most (62%) first initiated them >90 days before initiating CDT., Conclusions: Two-thirds of patients with mCRPC and bone metastases received BMAs within 180 days after initiating CDT. A greater proportion of patients without bone metastasis may warrant BMA therapy for osteoporotic fracture prevention. Some patients with bone metastasis may be able to delay BMA initiation until CRPC., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: To evaluate major osteoporotic fracture (MOF) risk among type 2 diabetes patients treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) across eGFR and albuminuria categories., Methods: A population-based cohort of type 2 diabetes patients started on SGLT2i or dipeptidyl peptidase-4 inhibitors (DPP4i) during 2007-2020 was identified from Hong Kong Hospital Authority database. One-to-one propensity score matching was applied to match each SGLT2i user with one DPP4i user. The primary outcomes were 180- and 365-day risks of MOF. Cox proportional hazard regression models were used to estimate hazard ratios (HR)., Results: A total of 28,696 patients (14,348 in each group) were included. Over 180-day follow-up, MOF occurred in 25 (0.17 %) SGLT2i users and 24 (0.17 %) DPP4i users (incidence of 4.07 and 3.63/1,000 person-years, respectively). At 365 days, MOF occurred in 43 (0.30 %) SGLT2i users and 44 (0.31 %) DPP4i users (incidence of 4.16 and 3.64/1,000 person-years, respectively). Risks of MOF were comparable between two groups at both 180 days (HR = 1.13, 95 %CI 0.65-1.98, P = 0.67) and 365 days (HR = 1.15, 95 %CI 0.75-1.75, P = 0.52). Subgroup analyses were consistent across age, sex, eGFR, albuminuria, or KDIGO categories., Conclusions: Our study did not reveal a statistically significant increase in fracture risk with SGLT2i use compared with DPP4i among type 2 diabetes patients, across eGFR and albuminuria categories., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown., Methods: We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture., Results: Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37)., Conclusions: Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy., Implications for Cancer Survivors: Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Perfluoroalkyl substances (PFAS) have been reported to be related to decreased bone mineral density, but the relationship with osteoporosis and fractures is less studied. This study aimed to investigate the risks of osteoporotic fractures in a Swedish population with long-term exposure to PFAS through drinking water., Methods: The Ronneby Register Cohort, including 61,504 individuals who had ever lived in Ronneby during 1985-2013, was used. Exposure to PFAS was assessed according to the yearly residential address with or without highly contaminated water supply and was categorized as 'never-high' and 'ever-high' exposure. The 'ever-high' exposure was further divided into 'early-high' and 'late-high' depending on if the exposure was before or after 2005. Inpatient and outpatient hospital diagnoses of fractures were retrieved from the National Patient Register. Major osteoporotic fractures (MOF, i.e., hip, vertebrae, proximal humerus and distal forearm fractures), and hip fractures were considered as the primary outcomes. Cox proportional hazard models with time-varying exposure were used to estimate the hazard ratios (HRs). Stratified analyses were performed in each sex and age group (<50 yrs and ≥ 50 yrs)., Results: Elevated risks of MOF (HR 1.11, 95% CI 1.03-1.19) and hip fractures (1.12, 1.00-1.24) were observed when comparing 'ever-high' to 'never-high' exposure. The HRs were even higher for 'late-high' exposure (MOF: 1.29, 1.16-1.44; hip fractures: 1.22, 1.01-1.47). Further adjustment for highest achieved education slightly attenuated the estimates. Individuals above 50 years old showed even higher HR estimates. Similar patterns were found for all fractures., Conclusion: Our results provide further evidence supporting the adverse effects of PFAS on osteoporosis. A better understanding of dose-response relationships as a basis for risk assessment is warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In this randomized, controlled trial, sequential therapy with once-weekly subcutaneous injection of teriparatide for 72 weeks, followed by alendronate for 48 weeks resulted in a significantly lower incidence of morphometric vertebral fracture than monotherapy with alendronate for 120 weeks in women with osteoporosis at high risk of fracture., Purpose: To determine whether the anti-fracture efficacy of sequential therapy with teriparatide, followed by alendronate is superior to that of monotherapy with alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed., Methods: Japanese women aged at least 75 years were eligible for the study, if they had primary osteoporosis and if they were at high risk of fracture. Patients were randomly assigned (1:1) to receive the sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 μg for 72 weeks, followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint in the final analysis was the incidence of morphometric vertebral fracture during the 120-week follow-up period., Results: Between October 2014 and June 2020, 505 patients in the sequential therapy group and 506 in the monotherapy group were enrolled. Of these, 489 and 496, respectively, were included in the main analysis. The incidence of morphometric vertebral fracture during the 120-week follow-up period in the sequential therapy group (64 per 627.5 person-years, annual incidence rate 0.1020) was significantly lower than that in the monotherapy group (126 per 844.2 person-years, annual incidence rate 0.1492), with a rate ratio of 0.69 (95% confidence interval 0.54 to 0.88, P < 0.01). After 72 weeks, no patient had a severe adverse event that was considered related to the study drug., Conclusion: Once-weekly injection of teriparatide, followed by alendronate resulted in a significantly lower incidence of morphometric vertebral fracture than alendronate monotherapy in women with osteoporosis who were at high risk of fracture. TRIAL REGISTRATION NUMBER, DATE OF REGISTRATION: jRCTs031180235 and UMIN000015573, March 12, 2019., (© 2022. The Author(s).)

In this post hoc analysis, we assessed romosozumab efficacy and safety in European patients enrolled in FRAME. Romosozumab treatment through 12 months, followed by denosumab for a further 24 months, resulted in early and sustained risk reduction for major fracture categories, associated with large gains in bone mineral density., Introduction: In the multinational FRAME phase 3 trial of romosozumab in postmenopausal women with osteoporosis, marked differences between clinical and non-vertebral fracture outcomes were observed among patients from Central and Southern America versus rest of world. This post hoc analysis assessed romosozumab efficacy and safety in European patients enrolled in the FRAME trial and extension study., Methods: In FRAME (NCT01575834), patients were randomised 1:1 to romosozumab 210 mg or placebo monthly (QM) for 12 months, followed by open-label denosumab 60 mg Q6M to month 36, including a 12-month extension study. We report incidence of major fracture outcomes, bone mineral density (BMD) change from baseline and safety for European patients enrolled in FRAME., Results: In FRAME, 3013/7180 (41.96%) patients were European; 1494 received romosozumab and 1519 received placebo. Through 12 months, romosozumab reduced fracture risk versus placebo for non-vertebral fracture (1.4% versus 3.0%; p = 0.004), clinical fracture (1.4% versus 3.6%; p &lt; 0.001), new vertebral fracture (0.4% versus 2.1%; p &lt; 0.001) and major osteoporotic fracture (0.9% versus 2.8%; p &lt; 0.001), with results sustained through 36 months following transition to denosumab. Hip fractures were numerically reduced with romosozumab at month 12 (0.2% versus 0.6%; p = 0.092). Romosozumab increased BMD versus placebo at month 12; all patients in the romosozumab and placebo groups experienced further increases by month 36 after transition to denosumab. Adverse events were balanced between groups., Conclusions: Among European patients in FRAME, romosozumab resulted in early and sustained risk reduction for all major fracture categories, associated with large BMD gains that continued after transition to denosumab., (© 2022. The Author(s).)

Androgen deprivation therapy for prostate cancer can lead to osteoporosis and increased fracture risk. The Fracture Risk Assessment Tool (FRAX®) questionnaire can be used for risk stratification, and our study has demonstrated that the majority of men (91%) in our cohort commencing ADT for prostate cancer were considered low risk for future osteoporotic fracture., Purpose/introduction: Long-term use of androgen deprivation therapy (ADT) in prostate cancer patients results in increased bone turnover and decreased bone mineral density (BMD). Proper assessment of any existing osteoporotic fracture risk is crucial prior to starting treatment. However, this risk assessment is poorly performed in these patients in spite of available validated tools including the Fracture Risk Assessment Tool (FRAX®). The objective of this study was to assess the distribution of osteoporotic fracture risk in a cohort of men commencing ADT for prostate cancer using the FRAX® algorithm., Methods: Between July 2020 and May 2022, 200 men filled in the FRAX® questionnaire just before ADT. They were stratified into the high-risk (> 20% probability of a MOF over the next 10 years), intermediate-, and low-risk categories for fragility fractures. We also measured their serum vitamin D and calcium levels., Results: The average age was 73.5 years (54-89). It took less than 10 min to complete the assessment. Only six patients were at high-risk, were started on bisphosphonates immediately, and referred for a dual energy X-ray absorptiometry (DEXA) scan. Twelve patients in the intermediate-risk category were referred for DEXA scans for bone mineral density measurements. A total of 182 patients (91%), were in the low-risk category and given lifestyle advice only. All had normal calcium levels but 134 (67%) patients, mostly in the low-risk category, had reduced vitamin D levels (< 50 nmol/L)., Conclusion: The FRAX® questionnaire is simple and immediately identifies patients who are at risk of fragility fractures. Our study has demonstrated that the majority of men (91%) in our cohort commencing ADT for prostate cancer were considered low risk for future osteoporotic fracture. We were surprised that more than half of our patients had low vitamin D levels., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

In this retrospective study, the effectiveness of short-term teriparatide with denosumab in reducing fragility fracture risk was determined in comparison with denosumab monotherapy. Administration of sequential teriparatide with denosumab showed excellent outcomes in suppressing the risk for fragility fractures compared with denosumab monotherapy., Introduction: To determine the effectiveness of short-term teriparatide with denosumab in reducing the risk of fragility fractures in comparison to denosumab monotherapy., Methods: The data of postmenopausal patients treated with denosumab for > 2 years between August 2015 and October 2020 were retrospectively analyzed. One hundred sixty four postmenopausal women of a total 615 were excluded, since they did not undergo > 2 bone mineral density (BMD) tests, were lost to follow-up, or received long-term teriparatide therapy. Total 320 patients received denosumab monotherapy and 131 patients received teriparatide for ≥ 3 months followed by denosumab. The number of osteoporotic fractures, presence of back pain before and after treatment, and annual BMD during treatment were comparatively assessed using t-test, Chi-square test, and linear mixed model analysis., Results: Before treatment, the denosumab monotherapy group had fewer osteoporotic fractures (mean ± standard deviation; 0.459 ± 0.689) than the sequential therapy group had (1.037 ± 0.871; p < 0.001). After treatment, the sequential therapy group had fewer osteoporotic fractures than the denosumab monotherapy group had (0.119 ± 0.348 versus 0.144 ± 0.385; p < 0.001). At 1 and 2 years after treatment, the increase in lumbar spine BMD was greater in the sequential therapy group than in the denosumab monotherapy group (p = 0.08, group × time). The difference between post and pre-treatment back pain visual analog scale score was significantly lower in the sequential therapy group than in the monotherapy group (3.246 ± 3.426 versus 1.734 ± 3.049; p < 0.001)., Conclusion: Short-term teriparatide use before denosumab showed excellent outcomes in suppressing the risk of fragility fractures compared with denosumab monotherapy., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Purposes: To identify the characteristics of the vertebral HU in the elderly patient with new osteoporosis vertebral compression fractures (OVCF) after treatment of percutaneous kyphoplasty (PKP), which may help us to preliminarily evaluate the risk of a new OVCF after the treatment of PKP., Methods: We retrospectively analyzed the patients who received PKP treatments in our hospital to find out the patients suffered new OVCFs after the treatment of PKP and set an age-, sex-, first fracture vertebrae-, surgical segment-, and comorbidity-matched control group without new fractures. We measured the axial and sagittal L1-HU values to compare their differences., Results: There were 32 patients who suffered new OVCFs and received another PKP surgery in our department. In the study group, the average L1 sagittal and axial HU values were 46.17 ± 21.31 HU and 47.77 ± 22.38 HU, and they had no statistical difference (P &gt; 0.05). For the control group, the average L1 sagittal and axial HU values were 75.69 ± 29.72 HU and 80.23 ± 30.26 HU, and their difference was not significant (P &gt; 0.05). No matter from the axial or sagittal evaluation, the L1 HU value in the study group was significantly lower than that in the control group (P &lt; 0.001). The AUC of using the L1 axial HU value to differentiate patients with new fractures from controls was 0.85 while the sagittal one was 0.82. In axial (and sagittal) evaluation, the cutoff value (adjusted to the multiple of five) had high specificity of 90% or high sensitivity of 90% to identify patients with new fractures of 45 HU and 75 HU (50 HU and 75 HU), respectively., Conclusions: The lower the vertebral HU value is, the more likely the patients suffer new OVCFs after PKP treatment., (© 2022. The Author(s).)

Thyroid-stimulating hormone (TSH) suppression therapy is one of the common treatments for most patients with differentiated thyroid cancer (DTC). Unfortunately, its detrimental effects on bone health are receiving increasing attention. It may increase the risk of osteoporosis and osteoporotic fractures. The trabecular bone score (TBS) is a relatively new gray-scale texture measurement parameter that reflects bone microarchitecture and bone strength and has been shown to independently predict fracture risk. We reviewed for the first time the scientific literature on the use of TBS in DTC patients on TSH suppression therapy and aim to analyze and compare the utility of TBS with bone mass strength (BMD) in the management of skeletal health and prediction of fracture risk. We screened a total of seven relevant publications, four of which were for postmenopausal female patients and three for all female patients. Overall, postmenopausal female patients with DTC had lower TBS and a significant reduction in TBS after receiving TSH suppression therapy, but their BMD did not appear to change significantly. In addition, TBS was also found to be an independent predictor of osteoporotic fracture risk in postmenopausal women with DTC receiving TSH suppression therapy. However, due to limitations in the number of studies and study populations, this evidence is not sufficient to fully demonstrate the adverse effects of TSH suppression therapy on patients' TBS or BMD and the efficacy of TBS, and subsequent larger and more case-cohort studies are needed to further investigate the relationship and application of TBS to TSH suppression therapy in terms of skeletal health impairment and fracture risk in DTC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ran, Wei, Gong and Xu.)

Glucocorticoids (GCs) are among the most widely prescribed medications in dermatologic practice. Although considered generally safe and efficacious, prolonged use and high dosing regimens may precipitate GC-induced osteoporosis, which contributes to an increased risk for fragility fractures. Dermatologists using and prescribing GCs must be aware of the risk for GC-induced osteoporosis. This review details the risks for osteoporosis and osteoporotic (OP) fractures in the setting of topical, intralesional, intramuscular, and systemic GC treatment, as well as nutritional supplementation recommendations that may reduce the risk of these adverse effects.

Background: Acrylamide, a component of fried foods, has been associated with several negative health outcomes. However, the relationship between dietary acrylamide and osteoporotic fractures has been explored by a few cross-sectional studies., Aims: To investigate if dietary acrylamide is associated with the onset of fractures in North American participants at high risk/having knee osteoarthritis (OA), over 8 years of follow-up., Methods: A Cox's regression analysis, adjusted for baseline confounders was run and the data were reported as hazard ratios (HRs) and 95% confidence intervals (CIs). Dietary acrylamide intake was assessed at the baseline using a food frequency questionnaire and categorized in tertiles (T), whilst fractures' history was recorded using self-reported information., Results: Altogether, 4,436 participants were included. Compared to participants with lower acrylamide intake (T1; < 3,313 μg), those with a higher acrylamide intake (T3; > 10,180 μg) reported a significantly higher risk of any fracture (HR = 1.37; 95% CI 1.12-1.68; p for trend = 0.009), forearm (HR = 1.73; 95% CI 1.09-2.77; p for trend = 0.04), spine (HR = 2.21; 95% CI 1.14-4.31; p for trend = 0.04), and hip fracture (HR = 4.09; 95% CI 1.29-12.96; p for trend = 0.046)., Conclusions: Our study is the first to report that high dietary acrylamide may be associated with an increased risk of osteoporotic fractures., (© 2022. The Author(s).)