Osteoporosis International最新文献

This study compared the effectiveness and cardiovascular safety of romosozumab and teriparatide. The main finding was that there were no significant differences between the two drugs in fracture prevention and risk of major adverse cardiac events. This suggests that romosozumab and teriparatide are comparable options for treating osteoporosis.

Purpose: This study aimed to determine the preventive effects of romosozumab versus teriparatide on fractures and the risk of cardiovascular events in patients initiating these drugs.

Methods: We conducted an active comparator, a new user cohort design, with confounding controlled by inverse probability of treatment weighting using a Japanese administrative claims database (March 2019 to October 2022). This cohort study included 49,104 patients aged 50 years or older who initiated romosozumab (n = 16,125) or teriparatide (n = 32,979) for osteoporosis. The study exposure was the initiation of romosozumab or teriparatide. Effectiveness outcomes were nonvertebral fracture and hip fracture. The safety outcome was major adverse cardiac events (MACE). Follow-up period was 365 days.

Results: The weighted incidence rate difference (IRD) for nonvertebral fracture between romosozumab versus teriparatide was -0.08 (95% confidence interval [CI], -0.34 to 0.17) events per 100 person-years (weighted hazard ratio [HR], 0.95 [95% CI, 0.81 to 1.12]); weighted IRD for hip fracture was 0.00 (95% CI, -0.16 to 0.16) events per 100 person-years (weighted HR, 0.99 [95% CI, 0.76 to 1.29]); and weighted IRD for MACE was -0.06 (95% CI, -0.20 to 0.09) events per 100 person-years (weighted HR, 0.90 [95% CI, 0.68 to 1.19]).

Conclusion: In patients with osteoporosis, there was no significant difference in the prevention of nonvertebral fracture and hip fracture between romosozumab and teriparatide. In addition, the risk of MACE was comparable between the two drugs.

Osteoporotic fracture has been understudied in men. In US male veterans aged 50 years and older between 2002 and 2019, hip fracture incidence increased between 2006 and 2019, fewer than 6% of men underwent DXA, and fewer than 0.5% of men were treated. Investigation of low screening and treatment rates is warranted.

Purpose: In the United States, the annual incidence of osteoporotic hip fracture is estimated to be 250,000 to 300,000; the one-year mortality in some studies has been as high as 32%. Reports that hip fracture rates in US women 65 years and older may no longer be declining led to this investigation of hip fracture in men, a less studied population. We assessed the trends in the incidence of hip fracture in US male veterans 50 years and older of age as well as the rates of diagnosis and treatment in such men.

Methods: We assessed the recent trends of hip fracture incidence in a nation-wide male veteran population 50 years and older of age. Using data from the US Veterans Affairs Informatics and Computing Infrastructure (VINCI) 2002-2019, we calculated the annual age-standardized hip fracture incidence. Secondary objectives included evaluating the annual proportion of hip fracture patients who underwent dual-energy X-ray absorptiometry (DXA) before or after the fracture and/or received osteoporosis medication after the hip fracture over the study period.

Results: Hip fracture incidence increased in male veterans from 2006 to 2019. Fewer than 6% of men underwent a DXA scan and fewer than 0.5% received osteoporosis medications up to two years after a hip fracture.

Conclusions: Despite available screening methods such as DXAs and medications for primary and secondary prevention of osteoporotic fractures, hip fracture incidence is not decreasing in older male veterans. Our study highlights a need for closer attention to fracture risk in men.

We utilized data from the NHANES to investigate the impact of physical activity on mortality in osteoporotic patients. Our study suggests that osteoporotic patients may require higher volumes of physical activity to reduce mortality risk compared to the general population. In osteoporotic patients, the dose-response relationships between physical activity volumes and both all-cause and cardiovascular mortality were linear. In contrast, these relationships were non-linear in participants without osteoporosis.

Purpose: To determine the impact of physical activity on mortality in osteoporotic patients.

Methods: A total of 5606 participants were included in this study, including 716 osteoporosis patients. Physical activity was assessed using standardized questionnaire. Participants were categorized into four groups: inactive (no physical activity), low active (physical activity volumes < 150 min/week), moderate active (≥ 150 min/week but < 300 min/week), and high active (≥ 300 min/week). Multivariable Cox regression models, using the inactive group as the reference and adjusted for potential confounders, were performed to estimate the hazard ratio (HR) and 95% confidence interval (CI).

Results: Osteoporotic patients demonstrated higher mortality rates attributed to various causes compared to non-osteoporosis participants. Physical activity was associated with lower mortality regardless of osteoporosis status. However, Multivariable Cox regression analysis indicated that among osteoporosis patients, only those engaging in ≥ 300 min/week physical activity experienced a significant decrease in mortality (all-cause mortality, HR (95% CI) 0.453 (0.268, 0.767) and cardiovascular mortality, HR (95% CI) 0.521 (0.259, 1.049)), surpassing the threshold of 150 min observed in non-osteoporosis patients. In sensitivity analysis, or when the proportion of vigorous physical activity was included as a confounder in the multivariate Cox regression analysis, only the high active group still showed a significant reduction in mortality. No significant interactions were observed when the analysis was stratified according to age, sex, and body mass index (P for interaction > 0.05). Restricted cubic spline analysis revealed a linear relationship between physical activity volume and all-cause mortality (P < 0.01 [overall] and P = 0.470 [non-linearity]) and cardiovascular-specific mortality (P = 0.003 [overall] and P = 0.610 [non-linearity]) in patients with osteoporosis. In contrast, these relationships were non-linear in participants without osteoporosis.

Conclusion: Patients with osteoporosis need to engage in ≥ 300 min/week physical activity to significantly reduce their mortality risk. And the higher the volume of physical activity, the lower the risk of death.

This study, using Mendelian randomization, reveals a causal link between nitrogen oxides and PM2.5 exposure and reduced total-body bone mineral density, highlighting a potential risk factor for osteoporosis. The findings emphasize the importance of targeted interventions in populations exposed to higher air pollution.

Introduction: With the aging of the population, the prevalence of osteoporosis is escalating. Observational studies suggest that air pollution might diminish bone mineral density (BMD), contributing to elevating the likelihood of developing osteoporosis.

Methods: Employing a two-sample Mendelian randomization (MR) analysis, our study aimed to explore the potential causal effect of air pollution on total-body BMD. We utilized extensive publicly available data from genome-wide association studies (GWAS) in this research. Inverse variance weighting was selected for the primary effect estimation, complemented by additional approaches such as the weighted median, MR-Egger, simple mode, and weighted mode. Sensitivity analyses were then conducted to evaluate heterogeneity, pleiotropy, and the presence of outliers.

Results: In the MR analysis, our findings revealed causal associations between nitrogen oxides (β =  - 0.55, 95% CI - 0.90 to - 0.21, P = 0.002) and particulate matter (PM) 2.5 (β =  - 0.33, 95% CI - 0.59 to - 0.08, P = 0.010) and a reduction in total-body BMD. No significant associations were detected between PM2.5-10, PM10, nitrogen dioxide, and total-body BMD (P > 0.05). Rigorous sensitivity analyses verified the stability of these significant results.

Conclusions: Our study illustrates that exposure to nitrogen oxides and PM2.5 may lead to a decrease in total-body BMD, increasing the risk of osteoporosis. This evidence holds crucial implications for policymakers and healthcare providers, as it can provide targeted interventions for the prevention of osteoporosis.

We report two cases of symptomatic severe hypophosphatemia requiring hospitalization and intravenous phosphate supplementation following denosumab therapy for osteoporosis. The two patients had normal kidney function and no previously reported risk factors for hypophosphatemia, both presented neurological symptoms and severe fatigue. After hospital admission, they were treated with intravenous phosphate: serum phosphate improved to normal levels and the patients were discharged with oral phosphate supplements and-in one patient-with oral calcitriol therapy. As prescription rates of denosumab therapy increase, attention should be paid to the risk of developing hypophosphatemia: the risk of such complication may be lower by early and regular monitoring of Ca, Pi, and PTH, as well as early supplementation of phosphate and/or vitamin D as needed. Whenever a patient receiving denosumab therapy complains otherwise unexplained fatigue, exercise intolerance, muscle pain, cramping, and paresthesias, we suggest hypophosphatemia as a potential complication to be ruled out.

Fragility fractures are a major problem in our aging society leading to early death and loss of independence for activities of daily living. Physical activity in a long-term follow-up of Portuguese women over 50 years with a fragility fracture was associated with better physical function and quality of life.

Purpose: To evaluate the long-term impact of physical activity on physical function and health-related quality of life (HRQoL) in women ≥ 50 years old who suffered a fragility fracture.

Methods: We evaluated the association of physical activity with physical function and HRQoL in women ≥ 50 years old who self-reported at least one low-impact fracture ≥ 40 years old from the EpiDoC cohort, a population-based cohort. Self-reported data regarding sociodemographics, clinical, and lifestyle behaviors were collected through a semi-structured questionnaire at baseline during a face-to-face clinical interview. During a long-term follow-up, a phone interview was conducted to evaluate physical activity (using a non-validated scale developed for the EpiDoC study), physical function (Health Assessment Questionnaire), and HRQoL (European Quality of Life - 5 Dimension). Women were divided into three groups according to the frequency of physical activity (non-frequent = 0 times/week, frequent = 1-2 times/week, or very frequent =  ≥ 3 times/week). The association of physical activity frequency (non-frequent, frequent, and very frequent) with physical function and HRQoL over time was assessed through linear mixed models considering varying intercepts for each woman.

Results: This study followed 323 post-fracture women, during a mean follow-up of 3.9 ± 3.5 years. Frequent (β =  - 0.1419 [- 0.2783, - 0.0064]) and very frequent (β =  - 0.1908 [- 0.2944, - 0.0881]) physical exercise were associated with improvements in physical function relative to non-frequent physical exercise adjusted for BMI, multimorbidity, hospitalizations, alcohol and smoking habits, and the number of fragility fractures at baseline. As for HRQoL, a positive association was found for exercise frequency, specifically frequent (β = 0.1305 [0.0646, 0.1958]) and very frequent (β = 0.1354 [0.0856, 0.1859]) suggesting improvements for HRQoL, in this follow-up period.

Conclusions: These findings based on longitudinal data with long-term follow-up suggest that regular physical activity is associated with better function and HRQol among middle-aged and older post-fracture osteoporotic Portuguese women.

Sequential romosozumab-to-alendronate or sequential teriparatide-to-alendronate can be a cost-effective treatment option for postmenopausal women at very high risk of fracture.

Purpose: To estimate the 10-year probability of a major osteoporotic fracture (MOF) at which sequential treatment with romosozumab or teriparatide followed by alendronate, compared with alendronate alone, becomes cost-effective in a UK setting.

Methods: A microsimulation model with a Markov structure was used to simulate fractures, costs, and quality-adjusted life years (QALYs), in women receiving sequential treatment with either romosozumab or teriparatide followed by alendronate, compared with alendronate alone. Patients aged 50 to 90 years with a recent MOF, hip or spine fracture were followed from the start of a 5-year treatment until the age of 100 years or death. The analysis had a healthcare perspective. Efficacy of romosozumab, teriparatide and alendronate was derived from phase III randomised controlled trials. Resource use and unit costs were derived from the literature. Cost-effectiveness intervention threshold (CEIT), defined as the 10-year probability of a major osteoporotic fracture at which treatment becomes cost-effective, was compared with clinically appropriate intervention thresholds for bone-forming treatment in women with very high fracture risk as recommended by the UK National Osteoporosis Guideline Group (NOGG).

Results: The base case analysis showed that sequential romosozumab-to-alendronate treatment was cost-effective from a 10-year MOF probability of 18-35% and above depending on age and site of sentinel fracture at a willingness to pay (WTP) of £30,000. For teriparatide-to-alendronate, treatment was cost-effective at a 10-year MOF probability of 27-57%. The results were sensitive to pricing of the drugs but relatively insensitive to treatment duration, romosozumab persistence assumptions, and site of sentinel fracture. The CEITs for romosozumab-to-alendronate treatment were lower than the clinical thresholds from the age of 70 years meaning that treatment could be considered both cost-effective and aligned with the NOGG treatment guidelines. By contrast, for teriparatide-to-alendronate the CEITs were higher than the clinical thresholds irrespective of age. However, cost-effective scenarios were found in the presence of strong clinical risk factors in addition to a recent sentinel fracture.

Conclusion: The results of this study indicate that sequential romosozumab-to-alendronate or teriparatide-to-alendronate treatment can be a cost-effective treatment option for postmenopausal women at very high risk of fracture.

Denosumab initiation is related to a lower risk of type 2 diabetes than alendronate in anti-osteoporotic treatment-naïve users in primary care practices.

Purpose: Links have been suggested between bone metabolism and glucose tolerance. Downregulation of the receptor activator of nuclear factor κ B ligand (RANKL) signaling improves glucose metabolism. Denosumab, a human monoclonal antibody against RANKL, may be associated with a lower risk of type 2 diabetes (T2D). The aim was to compare incidence rates of T2DM in primary care patients initiating denosumab or alendronate, which is a first-line therapy of osteoporosis. Alendronate as comparator enhances comparability of the two cohorts.

Method: The IQVIA Disease Analyzer comprises a representative panel of general and specialist practices (Germany). A new-user comparative study was conducted among patients with denosumab or alendronate treatment (2010-2021) without history of diabetes and age ≥ 45 years. Incidence rates (per 1,000 person-years) and Cox proportional hazard ratios (HR; 95%CI) for T2DM were estimated.

Results: The cohorts consisted of 3,354 denosumab (age: 75 years; women: 87%) and 27,068 alendronate (76 years; 86%) users. Overall, 1,038 persons developed T2D during 54,916 person-years. T2DM incidence rates per 1,000 person-years were 11.9 (9.5-14.4) for denosumab and 20.1 (18.8-21.3) for alendronate users, respectively. Denosumab was associated with a reduced risk of T2DM compared to alendronate, adjusting for age, sex, index year, visits, obesity, comorbidities and statins (HR: 0.73; 0.58-0.89).

Conclusion: In this comparative study of older patients seen in routine practices, denosumab was associated with a lower risk of developing T2DM than alendronate.