Antiresorptive Drugs and the Risk of Femoral Shaft Fracture in Men and Women With Osteoporosis: A Cohort Study Using the National Database of Health Insurance Claims of Japan.

BACKGROUND: This cohort study aimed to estimate incidence rates of femoral shaft fracture in patients who were treated with antiresorptive drugs. METHODS: We used data from the National Database of Health Insurance Claims of Japan from April 2009 and October 2016. All patients with new use of an antiresorptive drug, prescription-free period of ≥3 months, and no prior femoral fractures were included. Femoral shaft fractures were identified using a validated definition based on International Classification of Diseases, 10th revision (ICD-10) codes. Incidence rate ratios were estimated using Poisson regression, with adjustment for sex, age, and the Charlson Comorbidity Index. RESULTS: We identified 7,958,655 patients (women: 88.4%; age ≥75 years: 51.2%). Femoral shaft fractures were identified in 22,604 patients. Incidence rates per 100,000 person-years were 74.8 for women, 30.1 for men, 30.1 for patients aged ≤64 years, 47.7 for patients aged 65-74 years, and 99.0 for patients aged ≥75 years. Adjusted incidence rate ratios in patients taking versus not taking each type of antiresorptive drug were 1.00 (95% confidence interval [CI], 0.98-1.03) for bisphosphonates, 0.46 (95% CI, 0.44-0.48) for selective estrogen receptor modulators, 0.24 (95% CI, 0.18-0.32) for estrogens, 0.75 (95% CI, 0.71-0.79) for calcitonins, and 0.93 (95% CI, 0.84-1.03) for denosumab. The adjusted incidence rate ratio for alendronate was 1.18 (95% CI, 1.14-1.22). CONCLUSION: The incidence rates of femoral shaft fracture varied across patients treated with different antiresorptive drugs. Further research on a specific antiresorptive drug can increase understanding of the risk of femoral shaft fracture.

Decreased rate of hip fracture and consequent reduction in estimated medical costs in Japan.

The frequency of hip fractures associated with aging of the population is declining in many countries. Even in Japan, where this frequency has been increasing continually, a shift to decreasing frequency has been noted in recent reports. The objective of this study was to investigate the effects of this decrease and to estimate the number of hip fracture patients and the resulting reduction in national medical care expenditures. The differences in the number of patients were estimated by multiplying the population for each sex and each age group by the fracture rates before the decrease (2007) and after the decrease (2012). Total reduced cost was calculated by multiplying the treatment cost required for hip fracture and the annual medical cost of nursing care. The estimated number of hip fracture patients decreased by approximately 4000 in the elderly female population, and the resulting reduction in medical costs was approximately US$280 million. The number of patients with hip fractures has decreased in elderly Japanese women; as a result, the medical costs for treatment and nursing care might decrease.

The importance of absolute bone mineral density in the assessment of antiresorptive agents used for the prevention of osteoporotic fractures.

The usefulness of bone mineral density (BMD) monitoring during antiresorptive treatment is still controversial. This study aimed to determine which factors of change (absolute value or the percent change from the baseline) in BMD are associated with the risk of future fractures. A total of 565 postmenopausal osteoporosis who were treated antiresorptive drugs were included in this prospective observational study. Lumbar BMD (LBMD) was measured at baseline and 1-yr after the initial and subsequent incident fracture was observed. The percent changes in LBMD at 1 yr were 5.4 ± 6.4% and 118 (20.9%) achieved increased LBMD with change of classification to >-2.5 standard deviation (SD). After the initial 1-yr examination, incident fractures developed in 152 (26.9%). The incident fracture risk was significantly associated with the absolute value in LBMD, but not with the percent change. A Cox proportional hazard model demonstrated that increased LBMD with change of classification to >-2.5 SD was a significant predictor for a reduction in incident fractures (hazard ratio: 0.41, 95% confidence interval: 0.21-0.71). In conclusion, these results suggest that monitoring of the antifracture efficacy of antiresorptive treatments should be based on the absolute value of BMD. In particular, increased change to >-2.5 SD is important for reducing the future fracture risk.

Urinary pentosidine improves risk classification using fracture risk assessment tools for postmenopausal women.

We investigated whether measurement of pentosidine, in addition to the conventional risk assessment tool, the Fracture and Immobilization Score (FRISC), improves early identification of fracture cases. A total of 765 postmenopausal Japanese women with baseline measurement of urinary pentosidine were followed in a hospital-based cohort study. Endpoints were incidence of vertebral fracture, incidence of long bone fracture, and incidence of long bone and vertebral fracture. To assess the effect of pentosidine on fracture risk, we fitted multivariate Cox regression models adjusted for age, body weight, diabetes mellitus, lumbar BMD, prior fracture, and presence of back pain. To explore potential nonlinear relationships, we fitted a multivariate generalized additive model. To assess the discriminatory power of pentosidine, we performed receiver operating characteristic analysis. The hazard ratios for a 1 SD increase in pentosidine were 1.18 (95% CI 1.05-1.33, p < 0.01) for vertebral fracture and 1.20 (95% CI 1.07-1.33, p < 0.01) for long bone and vertebral fractures. The relationship was approximately linear, and there was no indication of the presence of a threshold. The C statistics were 0.732 (95% CI 0.686-0.778) for the model with both pentosidine and the 10-year risk and 0.702 (95% CI 0.654-0.750) for the 10-year risk alone. Eighty-three subjects (11%) in the whole cohort were in the highest quartile of pentosidine, although their 10-year risks were less than 15% and included 17 incident vertebral fracture cases. Urinary pentosidine improves risk classification using conventional risk assessment tools. Optimal clinical strategies of diagnosis and treatment remain uncertain and in need of additional investigation.

The Fracture and Immobilization Score (FRISC) for risk assessment of osteoporotic fracture and immobilization in postmenopausal women--A joint analysis of the Nagano, Miyama, and Taiji Cohorts.

INTRODUCTION: We aimed to (i) explore risk factors for major osteoporotic fracture or immobilization; (ii) develop a prediction model that can be used to assess the risk of fracture and immobilization; and (iii) assess external validity of the final model. METHODS: A total of 1787 postmenopausal Japanese women were followed in a hospital-based cohort study. Endpoints included the annual incidence of major osteoporotic fracture and immobilization. For each endpoint, multivariate Poisson regression models were fitted separately and risk factors were screened through backward variable selection. The predictive accuracy of the final model (FRISC) was evaluated in two independent community-based cohorts. RESULTS: Over a median follow-up of 5.3 years, a total of 383 major osteoporotic fractures (279 clinical vertebral, 44 hip, 60 distal forearm) and 83 immobilizations occurred in the developmental dataset. Backward variable selection confirmed that the following are risk factors for major osteoporotic fracture: age, weight, prior fracture, back pain, and lumbar bone mineral density (BMD). Age, prior fracture and dementia were significant risk factors for immobilization. Hosmer-Lemeshow tests did not indicate any significant deviation between the observed fracture frequency and prediction from the FRISC in the independent validation dataset. The C statistic for the FRISC was 0.727 (95% confidence interval: 0.660 to 0.794) and was higher than that for BMD alone significantly (p=0.03). CONCLUSIONS: We developed a novel prediction model for fracture and immobilization, FRISC, and the clinical risk factors in the FRISC allows better identification of populations at high risk of fracture than BMD alone. A web application is available at http://www.biostatistics.jp/prediction/frisc.