FRAX®在女性骨质疏松症诊疗中的应用研究进展

骨质疏松症是常见的骨骼疾病，绝经后女性为骨质疏松症的高危人群。骨折风险评价工具（fracture risk assessment tool，FRAX?）是一款研究、应用广泛的骨折风险评估工具。近年来研究表明，虽然FRAX?尚不完美，但对女性人群的骨折具有合理的预测能力，结合其他骨折危险因素对该工具进行调整、改进的研究也多见报道。设立符合本国国情的FRAX?阈值有助于医生更好地使用该工具和进行临床决策。美国设立了固定的FRAX?阈值，英国则是按年龄分层的阈值。国内对FRAX?的研究尚处于初级阶段，暂无特异的干预阈值，这在一定程度上阻碍了该工具在我国的推广使用。笔者回顾了国内外FRAX?对女性骨质疏松性骨折的预测能力、骨量异常的诊断能力、在合并其他疾病的女性人群中的应用和干预阈值的研究等最新成果，为临床医生了解FRAX?的研究进展、探索针对我国人群干预阈值奠定基础。     

Predictive Value of DXA Appendicular Lean Mass for Incident Fractures,Falls, and Mortality,Independent of Prior Falls,FRAX, and BMD: Findings from the Women's Health Initiative (WHI)

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX^®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height²) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height² (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height² was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height² and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height², depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height² and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX®, Falls,and BMD in the Osteoporotic Fractures in Men (MrOS) Study: A Meta-Analysis

Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height² (ALM/ht²) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX^®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht² only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht²), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Fracture experience among participants from the FROCAT study: what thresholding is appropriate using the FRAX tool?

ObjectiveTo perform an external validation of FRAX algorithm thresholds for reporting level of risk of fracture in Spanish women (low <5%; intermediate ≥5% and <7.5%; high ≥7.5%) taken from a prospective cohort “FRIDEX”.MethodsA retrospective study of 1090 women aged ≥40 and ≤90 years old obtained from the general population (FROCAT cohort). FRAX was calculated with data registered in 2002. All fractures were validated in 2012. Sensitivity analysis was performed.ResultsWhen analyzing the cohort (884) excluding current or past anti osteoporotic medication (AOM), using our nominated thresholds, among the 621 (70.2%) women at low risk of fracture, 5.2% [CI95%: 3.4–7.6] sustained a fragility fracture; among the 99 at intermediate risk, 12.1% [6.4–20.2]; and among the 164 defined as high risk, 15.9% [10.6–24.2]. Sensitivity analysis against model risk stratification FRIDEX of FRAX Spain shows no significant difference. By including 206 women with AOM, the sensitivity analysis shows no difference in the group of intermediate and high risk and minimal differences in the low risk group.ConclusionsOur findings support and validate the use of FRIDEX thresholds of FRAX when discussing the risk of fracture and the initiation of therapy with patients.     

FRAX评估江苏镇江地区中老年人群骨折风险的回顾性研究

目的评估FRAX■工具对江苏镇江地区中老年人骨质疏松性骨折的预测价值。方法对1070例江苏镇江地区中老年人群进行分组性研究,应用FRAX■工具计算未来10年主要骨质疏松性骨折(probability of major osteoporosis fracture,PMOF)和髋部骨折的概率(probability of hip fracture,PHF),分析年龄、体质量指数、有无骨质疏松性骨折史以及不同骨量对FRAX预测结果的影响。结果随着年龄的增长10年内PMOF和PHF同步增加;随着体重指数的增加,10年内PMOF和PHF同步下降;有骨质疏松性骨折史的人群10年内PMOF和PHF明显增加;随着骨量下降,10年内PMOF和PHF逐渐增加;不同骨量受人群在不同骨质疏松骨折风险组中的分布不同。在骨质疏松性骨折高风险人群中,骨质疏松者占78.1%,低骨量者占20.7%,正常骨量者占1.3%。结论FRAX■工具可用于江苏镇江地区中老年人群骨质疏松骨折风险的评估。FRAX■工具可能低估了低骨量人群的骨质疏松性骨折的风险,该工具对中老年低骨量人群的预测价值值得进一步研究。     

The Added Value of SARC-F to Prescreening Using FRAX for Hip Fracture Prevention in Older Community Adults

Objectives

To examine the potential added value of a simple 5-item questionnaire for sarcopenia screening (SARC-F) to the Fracture Risk Assessment Tool (FRAX) for hip fracture risk prediction, in order to identify at-risk older adults for screening with dual-energy x-ray absorptiometry (DXA).

Effects of FRAX Model Calibration on Intervention Rates: A Simulation Study

The WHO fracture risk assessment tool (FRAX^®) estimates an individual’s 10-yr major osteoporotic and hip fracture probabilities using a tool customized to the fracture epidemiology of a specific population. Incorrect model calibration could therefore affect performance of the model in clinical practice. The current analysis was undertaken to explore how simulated miscalibration in the FRAX^® tool would affect the numbers of individuals meeting specific intervention criteria (10-yr major osteoporotic fracture probability ≥20%, 10-yr hip fracture probability ≥3%). The study cohort included 36,730 women and 2873 men aged 50 yr and older with FRAX^® probability estimates using femoral neck bone mineral density. We simulated relative miscalibration error in 10% increments from −50% to +50% relative to a correctly calibrated FRAX^® model. We found that small changes in model calibration (even on the order of 10%) had large effects on the number of individuals qualifying for treatment. There was a steep gradient in the relationship between relative change in calibration and relative change in intervention rates: for every 1% change in calibration, there was a 2.5% change in intervention rates for women and 4.1% for men. For hip fracture probability, the gradient of the relationship was closer to unity. These results highlight the importance of FRAX^® model calibration, and speak to the importance of using high-quality fracture epidemiology in constructing FRAX^® tools.     

Limited Osteoporosis Screening Effectiveness Due to Low Treatment Rates in a National Sample of Older Men

Objective

To determine the association between dual-energy x-ray absorptiometry (DXA) testing for osteoporosis and subsequent fractures in US male veterans without a previous fracture.