Osteoporosis International最新文献

Designing appropriate diagnostic and treatment methods to reduce fall risk and improve quality of life, as well as reduce the cost of care in elderlies. Our findings have potential for early diagnosis of those with a high probability of falling based on fairly simple clinical measures of hyperkyphosis, forward head, and lordosis.

Introduction: Poor balance is an underlying cause of falling in the elderly, for which a change in the natural curvature of the spine plays a major role. Little is known about the relationship between spinal curvatures and fall incidence in this population. We primarily aimed to investigate the relationship between sagittal plane spinal curvatures and fall incidence over 1 year among nursing facility residents. Secondarily, we aim to determine associations of sagittal plane spinal curvatures with participants' perception of fall risk and balance capability.

Methods: Participants (100 residents mean age 70.17 ± 6.01 years) underwent standing measures of sagittal plane spinal curvatures (flexible ruler technique) and forward displacement of the head relative to the cervical spine. The Tinetti Performance Oriented Mobility Assessment (POMA) and Fall Efficacy Scale assessed participants' perception of balance and fear of falling. Incident falls were self-reported monthly and tracked across 1 year. Spearman's correlations and logistic regression evaluated associations between fall incidence and spinal curvature. Predictive performance of spinal curvature and fall risk was determined by the corresponding ROC for defining a cut-off for variables of spinal curvature and fall risk indicators.

Results: Predictive performance of spinal curvature and fall risk factors indicated 84% and 77% of participants were correctly classified using models of kyphosis and head angle, respectively.

Conclusions: Our study adds new data on spinal curvatures and incident falls among nursing facility residents. Efforts are needed to intervene to counter progression of spinal curvatures and improve fall prevention practices.

Objectives: Previous evidence suggests that bisphosphonates (BPs) may lower the risk of recurrent fractures and enhance functional recovery in patients with fractures. However, there has been controversy regarding the optimal timing of treatment initiation for patients with fragility fractures. We conducted a meta-analysis to evaluate the available evidence on the use of BPs during the perioperative period and compared it to both non-perioperative periods and non-usage.

Methods: Electronic searches were performed using PubMed, EMBASE, Web of Science and the Cochrane Library published before February 2023, without any language restrictions. The primary outcomes included fracture healing rate, healing time, and new fractures. We also examined a wide range of secondary outcomes. Random effects meta-analysis was used.

Results: A total of 19 clinical trials involving 2543 patients were included in this meta-analysis. When comparing patients with non-perioperative BPs use in 4-6 weeks and approximately 10-12 weeks post-surgically, the overall risk ratios (RRs) of perioperative BPs use for healing rate were 1.06 (95% CI: 0.81, 1.38, p=0.69) and 1.02 (95% CI: 0.94, 1.11, p=0.65), respectively, suggesting no difference in healing rate between perioperative and non-perioperative BP initiation. For healing time, the overall mean difference between perioperative and non-perioperative periods was -0.19 week (95% CI: -1.03, 0.64, p=0.65) at approximately 10-12 weeks, indicating no significant impact of perioperative BP initiation on healing time. In terms of new fractures, the overall RR with BP use was 0.35 (95% CI: 0.17-0.73, p=0.005), when compared to patients without BPs use. This suggests a protective impact of BP use against new fractures compared to patients without BP use. Perioperative BP use was associated with a markedly higher likelihood of having adverse experiences, including fever (RR: 23.78, 95% CI: 8.29, 68.21, p< 0.001), arthralgia (RR: 10.20, 95% CI: 2.41, 43.16, p=0.002), and myalgia (RR: 9.42, 95% CI: 2.54, 34.87, p< 0.001), compared with non-BPs use.

Conclusions: Treatment with BP during the perioperative period does not affect the healing process and has positive effects on therapy for patients with fragility fractures. These compelling findings underscore the potential efficacy of BP use during the perioperative period as a viable treatment option for patients with fragility fractures.

Identifying dysregulated plasma proteins in osteoporosis (OP) progression offers insights into prevention and treatment. This study found 8 such proteins associated with OP, suggesting them as therapy targets. This discovery may cut drug development costs and improve personalized treatments.

Purpose: This study aims to identify potential therapeutic targets for OP using summary data-based Mendelian randomization (SMR) and colocalization analysis methods. Furthermore, we seek to explore the biological significance and pharmacological value of these drug targets.

Methods: To identify potential therapeutic targets for OP, we conducted SMR and colocalization analysis. Plasma protein (pQTL, exposure) data were sourced from the study by Ferkingstad et al. (n = 35,559). Summary statistics for bone mineral density (BMD, outcome) were obtained from the GWAS Catalog (n = 56,284). Additionally, we utilized enrichment analysis, protein-protein interaction (PPI) network analysis, drug prediction, and molecular docking to further analyze the biological significance and pharmacological value of these drug targets.

Results: In the SMR analysis, while 20 proteins showed significance, only 8 potential drug targets (GCKR, ERBB3, CFHR1, GPN1, SDF2, VTN, BET1L, and SERPING1) received support from colocalization (PP.H4 > 0.8). These proteins are closely associated with immune function in terms of biological significance. Molecular docking also demonstrated favorable binding of drugs to proteins, consistent with existing structural data, further substantiating the pharmacological value of these targets.

Conclusions: The study identified 8 potential drug targets for OP. These prospective targets are believed to have a higher chance of success in clinical trials, thus aiding in prioritizing OP drug development and reducing development costs.

Is osteoporosis related to worst outcomes after fall accidents? After a fall accident, there were no differences in walking and balance between individuals with/without osteoporosis. Gains in fat tissue, higher pain, and difficulty to walk were related to previous falls, regardless of osteoporosis.

Purpose: Impairments are expected after an accidental fall in the older age; whoever, it is still unclear if patients suffering from osteoporosis are in higher risks of fall accidents and if such accidents would cause worst outcomes compared with older adults without osteoporosis. The objective of this study was to discriminate fallers and non-fallers via a combination of physical performance measurements of older adults (65 + years) with and without osteoporosis.

Methods: Older adults (n = 116) were screened for a previous fall accident and tested during (i) quiet stance; (ii) single- and dual-task walking; (iii) 8-Foot Up-and-Go; (iv) Mini BESTest; (v) 2-min step-in-place and (vi) 30-s chair stand. Evaluation of average daily pain intensity and total body fat% were obtained.

Results: Forty-four subjects (38%) reported a previous fall accident. There was, however, no association between osteoporosis and previous fall. Fallers had a higher daily pain intensity, higher body fat%, slower walking speed during a cognitive dual-task test and worse performance at the 8-Foot Up-and-Go test and the Mini BESTest compared to non-fallers.

Conclusions: Although the presence of osteoporosis might not increase the risk of fall accidents, healthcare professionals should expect that accidental falls in older adults are associated with higher body fat%, higher daily pain intensity and problems performing daily activities such as walking.

People with prior lean mass loss had a ~ 10% higher risk of MOF and ~ 22-26% higher risk of hip fracture, and the results were similar in people on anti-osteoporosis medications. Loss of lean mass is associated with increased fracture risk. Patients should be encouraged to pursue strategies to prevent loss of lean mass.

Background: Sarcopenia increases fracture risk. If the risk persists after starting osteoporosis medication, patients may need to be encouraged to pursue strategies to prevent loss of lean mass.

Objective: To estimate the effects of loss in appendicular lean mass (ALM) or total body lean mass (TBLM) on subsequent fracture risk and effect modification with anti-osteoporosis medication use.

Methods: We conducted a registry-based cohort study linked to population-based data. We identified individuals ≥ 40 years of age with two DXA assessments ≥ 1 year apart and minimum 0.5 years of observation. ALM and TBLM were estimated from weight, sex, and percent fat from DXA (R² = 0.91 and 0.84 vs total body DXA, respectively). We report hazard ratios (HR) from Cox regression models estimating time to first incident major osteoporotic fracture (MOF) and hip fracture, adjusted for fracture risk; osteoporosis medication was included as an interaction term and used to stratify analyses.

Results: We included 21,249 individuals (mean 67 [SD 10] years, 95% female, 37% on osteoporosis medication). The mean follow-up was 7 years (SD 4). A total of 1868 and 548 people had incident MOF and hip fracture, respectively. People with prior ALM loss (HR per SD 1.09, 95% CI 1.04-1.15) or TBLM loss (HR per SD 1.09, 95% CI 1.42-1.14) had a higher risk of MOF. Hip fracture risk was greater in people with prior ALM loss (HR per SD 1.22, 95% CI 1.12-1.33) and TBLM loss (HR per SD 1.26, 95% CI 1.16-1.38). There were no interactions with anti-osteoporosis medication use (all p > 0.3). When restricted to people on anti-osteoporosis medication, each SD in ALM or TBLM loss was associated with 8-9% increased MOF risk and 18-23% increased hip fracture risk.

Conclusions: Loss of lean mass is associated with increased fracture risk among individuals on anti-osteoporosis medication. Patients should be encouraged to pursue strategies to prevent sarcopenia.

We studied factors affecting osteoporotic hip fracture mortality in Hawai'i, a region with unique geography and racial composition. Men, older adults, higher ASA score, lower BMI, and NHPI race were associated with higher mortality. This is the first study demonstrating increased mortality risk after hip fracture in NHPI patients.

Purpose: To estimate mortality rates and identify specific risk factors associated with 1-year mortality after osteoporotic hip fracture in Hawai'i.

Methods: A retrospective review of adults (≥ 50 years) hospitalized with an osteoporotic hip fracture at a large multicenter healthcare system in Hawai'i from 2011 to 2019. The Kaplan-Meier curves and log-rank tests examined survival probability by sex, age group, race/ethnicity, primary insurance, body mass index (BMI), and American Society of Anesthesiologists (ASA) physical status classification. After accounting for potential confounders, adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were obtained from Cox proportional hazards regression models.

Results: We identified 1755 cases of osteoporotic hip fracture. The cumulative mortality rate 1 year after fracture was 14.4%. Older age (aHR 3.50; 95% CI 2.13-5.76 for ≥ 90 vs 50-69), higher ASA score (aHR 5.21; 95% CI 3.09-8.77 for ASA 4-5 vs 1-2), and Native Hawaiian/Pacific Islander (NHPI) race (aHR 1.84; 95% CI 1.10-3.07 vs. White) were independently associated with higher mortality risk. Female sex (aHR 0.64; 95% CI 0.49-0.84 vs male sex) and higher BMI (aHR 0.35; 95% CI 0.18-0.68 for obese vs underweight) were associated with lower mortality risk.

Conclusion: In our study, men, older adults, higher ASA score, lower BMI, and NHPI race were associated with significantly higher mortality risk after osteoporotic hip fracture. NHPIs are an especially vulnerable group and comprise a significant portion of Hawai'i's population. Further research is needed to address the causes of higher mortality and interventions to reduce hip fractures and associated mortality.

Examining fracture dynamics by socioeconomic status may inform healthcare and prevention. We found a higher risk of hip fracture in men and women with lower educational level in Norway. However, by age 90 + years, the cumulative incidence was higher in those with higher education, due to their higher life expectancy.

Purpose: Socioeconomic gradients are seen for several health outcomes in high-income countries. We aimed to examine possible educational gradients in risk of hip fracture in Norway and to describe the cumulative incidence of hip fracture by educational level.

Methods: In a population-wide cohort of Norwegians aged ≥ 50 years, information on attained education from Statistics Norway was linked to hospital-treated hip fractures and deaths during 2002-2019. We estimated relative fracture risk by educational level (primary, secondary or tertiary) in Cox proportional hazards regression. We also examined the cumulative incidence over attained age by gender and educational level in competing risk regression.

Results: The population included N = 1,389,858 individuals with 135,938 incident hip fractures. Compared with men who had attained tertiary education, hazard ratios (95% confidence intervals) for hip fracture were 1.44 (1.40, 1.49) in men with primary education only and 1.26 (1.22, 1.29) in men with secondary education. In women, the corresponding estimates were 1.28 (1.25, 1.31) and 1.16 (1.13, 1.19). In the age range 50 to 90 years, the highest cumulative incidence of hip fracture was seen in those with primary education. The gradient gradually diminished with advancing age and was reversed in the oldest (> 90 years) in both genders.

Conclusions: There was a clear educational gradient in hip fracture incidence in both men and women in Norway, with a higher risk in people with lower education. Despite this, the cumulative incidence of hip fracture in old age was highest among people with higher education, due to their higher life expectancy.

We assessed multiple components of muscle function in ten adults with X-linked hypophosphatemia (XLH) receiving burosumab treatment. Lower limb power (+ 9%), short physical performance battery (SPPB) score (+ 1.2 points), and physical activity (+ 65%) increased following 6 months of treatment, and hand grip increased (+ 10%) between 6 and 12 months of treatment.

Purpose: X-linked hypophosphatemia (XLH) is a rare genetic disorder of phosphate metabolism. Burosumab is a monoclonal antibody treatment shown to improve phosphate homeostasis and improve symptoms as well as fracture healing when used as a therapy for XLH in adults. However, little is known about its effects on the large deficits in multiple components of physical function previously reported in XLH.

Methods: Ten adults (6 females, age 41.1 ± 15.7 y) were recruited from specialist centres in London and Bristol. During clinical visits for initial burosumab treatment and at 6-month and 12-month follow-up, physical function, and physical activity (PA) assessments were performed. In detail, lower limb power was assessed by mechanography via a countermovement jump, mobility by short physical performance battery (SPPB), functional capacity by 6-min walk test (6MWT), upper limb strength by hand grip dynamometry, and PA via an International Physical Activity Questionnaire (IPAQ). Differences between baseline and 6-month follow-up, and in a subset of 5 patients between 6- and 12-month follow-up, were assessed.

Results: Lower limb power increased by 9% (P = 0.049) from baseline to 6 months, as did SPPB score (+ 1.2 points, P = 0.033) and total PA (+ 65%, P = 0.046) although hand grip and 6MWT did not differ. Only for hand grip was a significant improvement (+ 10%, P = 0.023) seen between 6 and 12 months.

Conclusions: Burosumab treatment is associated with improved lower limb function and mobility at 6 months, with improvement in hand grip strength at 12 months. Future studies should explore the underlying mechanisms and describe on function and other patient outcomes.

This 78-week (18-month) study conducted in 479 postmenopausal women with osteoporosis evaluated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P41 relative to US reference denosumab. CT-P41 had equivalent efficacy and pharmacodynamics to US-denosumab, with similar pharmacokinetics and comparable safety and immunogenicity profiles.

Purpose: To demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis.

Methods: This 78-week (18-month), double-blind, randomized, active-controlled Phase 3 study (NCT04757376) comprised two treatment periods (TPs). In TPI, patients (N = 479) were randomized 1:1 to 60 mg subcutaneous CT-P41 or US-denosumab. At Week 52, those who had received CT-P41 in TPI continued to do so. Those who had received US-denosumab were randomized (1:1) to continue treatment or switch to CT-P41 in TPII. The primary efficacy endpoint was percent change from baseline in lumbar spine bone mineral density at Week 52. Efficacy equivalence was concluded if associated 95% confidence intervals (CI) for least squares (LS) mean group differences fell within ± 1.503%. The primary pharmacodynamic (PD) endpoint was area under the effect curve for serum carboxy-terminal cross-linking telopeptide of type I collagen through the first 26 weeks, with an equivalence margin of 80-125% (for 95% CIs associated with geometric LS mean ratios).

Results: Equivalence was demonstrated for CT-P41 and US-denosumab with respect to primary efficacy (LS mean difference [95% CI]: - 0.139 [- 0.826, 0.548] in the full analysis set and - 0.280 [- 0.973, 0.414] in the per-protocol set) and PD (geometric LS mean ratio [95% CI]: 94.94 [90.75, 99.32]) endpoints. Secondary efficacy, PD, pharmacokinetics, and safety results were comparable among all groups up to Week 78, including after transitioning to CT-P41 from US-denosumab.

Conclusions: CT-P41 was equivalent to US-denosumab in women with postmenopausal osteoporosis, with respect to primary efficacy and PD endpoints.