Osteoporosis International最新文献

Disability overcomes mortality burden in older adults with hip fracture, expanding unhealthy lifespan. Building comprehensive assessment, pre-fracture functional status and 30-day post-surgical recovery are the most powerful predictors of 5-years survival. A tool supporting estimation of long-term survival may optimize the appropriate delivery of targeted interventions.

Background: Older people with hip fractures are highly heterogeneous patients, impacting health and economic systems. The availability of tools to estimate survival may help optimize patients' outcomes and treatment management decisions.

Methods: A prospective observational study was conducted on older patients with hip fractures who received baseline and 30-day comprehensive assessment from discharge, focusing on functional status based on Basic Activity of Daily Living (BADL). The primary outcome was to identify predictors of 5-year survival and develop nomograms to be adopted at admission or 30 days after discharge.

Result: Among 231 hip fracture patients, 5-year survival was 38.3% in men and 61.9% in women; women experienced a 1.8 higher likelihood of survival than men. Pre-fracture functional status predicted mortality as a function of age. At hospital admission, pre-fracture BADL level was a protective factor (HR 0.742; 95% CI 0.668-0.825), while male gender (HR 1.840; 95% CI 1.192-2.841), age (HR 1.070; 95% CI 1.037-1.105), and multimorbidity (HR 1.096; 95% CI 1.007-1.193) were independent mortality risk factors. At the 30-day follow-up visit, the BADL recovery gap was an independent predictor of 5-year survival (HR 1.439; 95% CI 1.158-1.789), in addition to male gender (HR 1.773; 95% CI 1.146-2.744), age (HR 1.046; 95% CI 1.010-1.083), and pre-fracture BADL (HR 0.621; 95% CI 0.528-0.730), while comorbidity disappeared (HR 1.083; 95% CI 0.994-1.179).

Conclusion: More than half of hip fracture patients are still alive 5 years after surgical repair. Pre-fracture functional status and a 30-day functional recovery gap are the main predictors of survival. Nomograms may help to define prognosis and suitable interventions.

Osteoporosis is defined as a bone disease that is characterized by a reduction in bone mass and an elevated risk of fracture. Irisin, which is regulated by peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α), is a muscle-derived protein that is induced by exercise. A number of studies have indicated that irisin has the capacity to stimulate bone formation and decrease bone resorption, which plays a crucial role in bone metabolism. Regular exercise has been demonstrated to be an effective method for maintaining and enhancing bone health, with irisin emerging as a key regulatory molecule in this process. In light of these findings, irisin represents a promising approach for the treatment of osteoporosis. Animal studies are an essential part of the clinical trial process, as they are used to assess the efficacy and potential risks associated with proposed interventions. The objective of this review was to conduct a systematic review of animal studies and discuss the effects and mechanisms of irisin on bone in osteoporosis. A systematic search was conducted across eight databases, resulting in the identification, data extraction, and quality assessment of 27 articles. The results demonstrate that irisin can restore the steady state of bone homeostasis through the activation or inhibition of multiple pathways. It can ameliorate the microstructural damage and bone turnover caused by osteoporosis; improve the response to bone mechanical stress; promote the proliferation, differentiation, and mineralization of osteoblasts; and play an important role in exercise-based prevention and treatment of osteoporosis. Furthermore, irisin can attenuate inflammatory changes in bone and participate in the regulation of cell death. This review was registered at PROSPERO (CRD42024539678).

Objective: Vascular calcification shares many features with skeletal mineralisation and shares an inverse relationship with osteoporosis (skeletal de-mineralisation). However, medications that reduce bone loss (anti-resorptives) have had inconsistent effects on extra-skeletal mineralisation (i.e. vascular and valvular calcification). As such, this paper aims to synthesise existing literature examining the effect of anti-resorptive treatments on extra-skeletal (vascular and valvular) calcification across populations.

Methods: Medline and Embase were searched (inception to October 2024) for studies that assessed the association between anti-resorptive medication use and vascular/valvular calcification. Pooled standardised mean differences (SMDs) with 95% confidence intervals (CI) were calculated for all outcomes, using random-effects model. Leave-one-out sensitivity analyses were performed for internal validity.

Results: Of 4071 articles screened, 33 were included in the review, and 15 (2344 participants) had data available for meta-analysis. Anti-resorptive use was associated with non-significant, small magnitude improvements in abdominal aortic calcification (decreased value), coronary artery calcification (decreased value) and ejection fraction (increased value) but significant small reduction in aortic valve area (representing less calcification on the valve) with standardised mean difference of - 0.45 (95% confidence interval (CI) - 0.99; 0.08, I² = 84%), - 1.19 (95% CI - 2.92; 0.55, I² = 91%), - 0.67 (95% CI - 1.72; 0.38, I² = 94%), 0.26 (95% CI - 0.14; 0.66, I² = 62%) and 0.56 (95% CI 0.07; 1.06, I² = 76%), respectively.

Conclusion: The significance of small positive effect of anti-resorptives on aortic stenosis is clinically uncertain. Despite strong biological links between vascular calcification and skeletal mineralisation, anti-resorptives do not appear to have a strong favourable influence on extra-skeletal mineralisation. This suggests that mechanisms that link vascular calcification with osteoporosis may be acting in pathways not influenced by anti-resorptives. This systematic review and meta-analysis summarises the effect of anti-resorptives on vascular and valvular calcification. There is a small, positive effect of anti-resorptives on aortic stenosis, though this is of uncertain clinical importance.

This study investigated simulated tube current reduction and sparse sampling for low-dose computed tomography (CT) regarding volumetric bone mineral density (vBMD) and cortical bone thickness (Ct.Th) of the proximal femur. Sparse sampling with dose reductions of up to 90% may still allow extraction of bone strength parameters with clinically acceptable accuracy.

Introduction: We aimed to investigate effects of CT with simulated lowered tube current and sparse sampling on trabecular and cortical vBMD as well as Ct.Th of the entire proximal femur, its subregions, and with detailed spatial assessments.

Methods: Clinical routine multi-detector CT (MDCT) scans covering the hips from 40 patients were used for simulations of low-dose imaging with 50% and 10% of the original tube current (D50, D10) or projections (P50, P10) combined with statistical iterative reconstruction (SIR), which were then compared against original data with full dose (D100 P100) regarding trabecular vBMD, cortical vBMD, and Ct.Th. An automated framework for multi-parametric assessments was used. Relative errors by comparing measures from original data and simulated low-dose data, regression analyses, Bland-Altman analyses, and statistical parametric mapping (SPM, to assess the spatial distribution of accuracy) were computed.

Results: Sparse sampling enabled drastic reductions of radiation exposure (down to 10% of original imaging) while still producing determinants of bone strength with clinically acceptable relative changes. Lower biases according to Bland-Altman analyses were observed for sparse sampling compared to imaging with virtually lowered tube currents (D10 P100 versus D100 P10) regarding trabecular vBMD, cortical vBMD, as well as Ct.Th. Better accuracy across the whole proximal femur for D100 P50 than for D50 P100 and for D100 P10 than for D10 P100 was observed.

Conclusions: Sparse sampling with SIR may enable drastic reductions of radiation exposure (up to 90% of original doses) for opportunistically measuring image-based surrogate parameters of bone strength.

This study investigated whether osteoporosis impacts reoperation or periprosthetic fracture after total ankle arthroplasty. Findings showed no significant difference in reoperation or fracture rates between patients with or without osteoporosis, suggesting osteoporosis may not be a major risk factor for these outcomes.

Background: This study examines the association between osteoporosis and postoperative periprosthetic fracture or reoperation after primary total ankle arthroplasty (TAA) to guide surgical decision-making.

Methods: The United States TriNetX network identified adults undergoing primary TAA. Patients were split per the presence or absence of osteoporosis. The primary outcome was the risk ratio (RR) with 95% confidence intervals (CI) of reoperation within 3 years of primary TAA. Secondary outcome included the RR with 95% CI for postoperative periprosthetic fractures after primary TAA.

Results: There were 270 patients per cohort. There was no statistically significant difference in the likelihood of reoperation in the osteoporosis cohort as compared to the non-osteoporosis cohort through 3 years (5.9% versus 5.6%; p = 0.853). There was also no statistically significant difference in the likelihood of postoperative periprosthetic fractures in the osteoporosis cohort as compared to the non-osteoporosis cohort (6.3% versus 4.1%; p = 0.244).

Conclusion: These findings suggest that osteoporosis may not be a meaningful risk factor for reoperation or postoperative periprosthetic fracture after primary TAA.

Background: Studies have shown that beta-antagonists, an antihypertensive drug, may be associated with fracture risk in adult users. However, this conclusion remains controversial. This meta-analysis was used to explore the association between beta-receptor antagonist use and fracture risk in adult patients.

Methods: We searched Embase, Medline, PubMed, and Web of Science; finally, 16 articles were identified, and the extracted odds ratio (OR), hazard ratio (HR), and 95% confidence interval (95% CI) were used to estimate the association between beta-blockers and the risk of fracture in adult patients. All the results are adjusted. Sensitivity analysis and Egger's test were employed to assess the stability of the results and potential publication bias.

Results: We included eight cohort studies, one of which was only used for subgroup analysis because it only discussed the male and female groups separately and did not discuss the combined population. Thus, we included seven studies in which cohort studies did not find an association between beta-receptor antagonists and fracture risk, the HR is 0.96 (95% CI: 0.88-1.05; P = 0.41). Nine case-control studies included 156,437 beta-blockers users and 432,288 non-users for analysis showed that beta-receptor antagonists would reduce the risk of fracture in middle-aged and elderly users, the OR is 0.86 (95% CI: 0.77-0.95; P < 0.0001). In the subgroup analysis by the sites of fracture, no association was found between beta-receptor antagonists and fracture risk. However, in analyzing groups stratified by gender, beta-receptor antagonists reduce the fracture risk.

Conclusion: In cohort studies, no association was found between beta-receptor antagonists and fracture risk. However, beta-receptor antagonists have been shown to reduce the risk of fractures in adult users in case-control studies. The results of this study need careful interpretation for the reason that case-control studies are inferior to cohort studies in determining cause and effect and the lack of enough randomized controlled trials (RCTs).

Over 12 years in the US and 26 years in Ontario, Canada, we found major differences in osteoporosis medications used. In both countries, osteoporosis medication initiation has not returned to pre-2008 levels; however, denosumab use is increasing. Future work should determine whether targeted screening or undertreatment drives these trends.

Purpose: Concerns about adverse events caused a rapid decline in osteoporosis medication use globally between 2008 and 2012. Trends in use in recent years have not been described. We aimed to describe and compare trends over time in the initiation and overall use of osteoporosis medications among older adults in the US and Ontario, Canada.

Methods: We conducted a serial cross-sectional study leveraging two data sources: healthcare administrative data for all older adult residents of Ontario, Canada (ON) and Medicare claims and enrollment data for a 20% random sample of beneficiaries (US). We included community-dwelling older adults aged ≥ 66 years at their first dispensing of an osteoporosis medication between 05/01/1996-12/31/2022 in ON and 01/01/2008-12/31/2020 in the US. We described and compared the number of incident and prevalent users of osteoporosis medications annually.

Results: We identified 771,025 (average age = 75.2 years; 78% female) individuals in ON and 424,995 (average age = 75.3 years; 85% female) in the US initiating osteoporosis medications. In the US, alendronate and denosumab were the most common therapies, while in ON, risedronate and denosumab were most common. New use of osteoporosis medications dropped more between 2008 and 2011 in the US versus ON (58% vs. 29% relative decrease). Initiation of osteoporosis medications did not rebound to pre-2008 levels.

Conclusion: New use of osteoporosis medications remains below pre-2008 levels, and differs between the US and Canada. Future research should aim to understand drivers of decreased use, like changes in the screening strategy used for initial treatment or persisting concerns about adverse effects.

Purpose: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis.

Methods: Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined.

Results: Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications.

Conclusion: We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis.

Osteoporosis poses a significant concern for childhood cancer survivors (CCS). While recommendations for surveillance and management of bone mineral density (BMD) exist, no systematic review and meta-analysis has been undertaken to quantify BMD Z-scores in childhood cancer patients undergoing cancer treatment and survivors who have completed treatments. Accordingly, we conducted a systematic review with a 3-level mixed-effects meta-analysis to examine the course of BMD Z-scores in childhood cancer patients and survivors and identified possible moderators using meta-regression models. A systematic search was conducted in CINAHL, Embase, PubMed, SPORTDiscus, and Web of Science databases from inception to November 2023. We included studies that involved children and adolescents diagnosed with cancer before the age of 18 who were undergoing cancer treatment or had completed treatments and reported lumbar spine, hip/femoral neck, or total body BMD Z-scores derived from dual-energy x-ray absorptiometry. Forty-nine studies (4547 participants) were included in the meta-analysis. BMD Z-scores across different sites decreased with respect to baseline in children undergoing cancer treatment (mean difference: - 0.36, 95% CI - 0.62 to - 0.11; p = .01) and remained low following treatment in child and adolescent CCS (lumbar spine: - 0.85 SD, 95% CI - 1.17 to - 0.54; p < .001; hip/femoral neck: - 1.03 SD, 95% CI - 1.38 to - 0.68; p < .001), and adult CCS (lumbar spine: - 0.46 SD, 95% CI - 0.67 to - 0.26; p < .001; hip/femoral neck: - 0.36 SD, 95% CI - 0.57 to - 0.16; p < .001). Hip/femoral neck BMD Z-scores were moderated by age at assessment (p = .006), time from diagnosis (p = .004), sex (p = .037), and height (p = .026). Lumbar spine BMD Z-scores were moderated by age at assessment (p = .018), and sex (p = .015). In conclusion, childhood cancer patients and survivors experience reductions in BMD. Future research should evaluate the implications of regular physical activity, targeted exercise medicine, and nutrition therapy as first-line countermeasures to mitigate the declines in bone health.