Performance of FRAX in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study

FRAX was developed to predict 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Aromatase inhibitors (AI) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. AI exposure is not a direct input to FRAX but is captured under “secondary osteoporosis”. To inform use of FRAX in women treated with AI, we used a population-based registry for the Province of Manitoba, Canada, to identify women aged ≥40 years initiating AI for breast cancer with at least 12 months’ AI exposure (n = 1775), women with breast cancer not receiving AI (n = 1016), and women from the general population (n = 34,205). Among AI users, fracture probability estimated without BMD (AI use coded as secondary osteoporosis) significantly overestimated risk (10-year observed/predicted ratio 0.56, 95% confidence interval [CI] 0.45–0.68; 10-year hip fracture observed/predicted ratio 0.33, 95% CI 0.18–0.49). However, when BMD was included in the fracture probability, there was no significant difference between observed and predicted fracture risk. In Cox proportional hazards models, FRAX stratified risk of MOF, hip, and any fracture equally well in all subgroups (p-interaction >0.1). When adjusted for FRAX score without BMD, with AI use coded as secondary osteoporosis, AI users were at significantly lower risk for MOF (hazard ratio [HR] = 0.78, 95% CI 0.64–0.95), hip fracture (HR = 0.46, 95% CI 0.29–0.73) and any fracture (HR = 0.75, 95% CI 0.63–0.89). AI use was no longer significantly associated with fractures when AI use was not entered as secondary osteoporosis in FRAX without BMD or when BMD was included in the FRAX calculation. In conclusion, FRAX scores stratify fracture risk equally well in women receiving AI therapy as in non-users, but including secondary osteoporosis as a risk factor for AI users overestimates fracture risk. Our results call this practice into question. © 2019 American Society for Bone and Mineral Research.     

2型糖尿病患者FRAX评分与年龄、体质指数及股骨颈骨密度相关性的Meta分析

目的 评定FRAX评分工具中个别危险因素对评估2型糖尿病(T2DM)患者骨折风险的应用价值。方法 通过使用关键词计算机网络检索并收录PubMed、FMRS、中国知网、万方等文献数据库自创建入库以来到2020年10月关于技术应用FRAX对评估2型糖尿病患者早期骨折发生风险的相关病例文献进行数据对照分析研究,严格选取根据目前纳入临床标准与患者骨折发生风险因素进行数据筛选分析相关联的文献并分析提取计算出与其病例相关的文献数据,应用NOS量表进行文献质量分析评价,采用review manager 5.3.0进行Meta质量分析,比较了患者年龄、体质指数、股骨颈骨密度3个最重要危险影响因素在2型糖尿病患者和非2型糖尿病人群类型中的明显差异。结果 共有12篇文献纳入研究,均为随机对照研究,合计5 059例2型糖尿病患者和49 535例非2型糖尿病人群纳入研究。合并数据分析显示年龄和股骨颈骨密度差异均无统计学意义(P>0.05),体质指数BMI[SMD=0.37,95%CI(0.22～0.53),P<0.000 01],差异有明显统计学意义。结论 2型糖尿病患者的体质指数(BMI)对使用...     

Appropriate Osteoporosis Treatment by Family Physicians in Response to FRAX vs CAROC Reporting: Results From a Randomized Controlled Trial

Canadian guidelines recommend either the FRAX or the Canadian Association of Radiologists and Osteoporosis Canada (CAROC) fracture risk assessment tools to report 10-yr fracture risk as low (<10%), moderate (10%–20%) or high (>20%). It is unknown whether one reporting system is more effective in helping family physicians (FPs) identify individuals who require treatment. Individuals ≥50 yr old with a distal radius fracture and no previous osteoporosis diagnosis or treatment were recruited. Participants underwent a dual-energy x-ray absorptiometry scan and answered questions about fracture risk factors. Participants' FPs were randomized to receive either a FRAX report or the standard CAROC-derived bone mineral density report currently used by the institution. Only the FRAX report included statements regarding treatment recommendations. Within 3 mo, all participants were asked about follow-up care by their FP, and treatment recommendations were compared with an osteoporosis specialist. Sixty participants were enrolled (31 to FRAX and 29 to CAROC). Kappa statistics of agreement in treatment recommendation were 0.64 for FRAX and 0.32 for bone mineral density. The FRAX report was preferred by FPs and resulted in better postfracture follow-up and treatment that agreed more closely with a specialist. Either the clear statement of fracture risk or the specific statement of treatment recommendations on the FRAX report may have supported FPs to make better treatment decisions.     

The Effect of Fracture Recency on Observed 10-Year Fracture Probability: A Registry-Based Cohort Study

FRAX estimates 10-year fracture major osteoporotic fracture (MOF) and hip fracture probability from multiple risk factors. FRAX does not consider prior fracture site or time since fracture. Fracture risk is greater in the initial 2-year post-fracture period (imminent risk), implying that FRAX may underestimate risk in this setting. We used the population-based Manitoba Bone Mineral Density (BMD) Program registry to examine the effect of fracture recency and site on incident fracture risk predictions using FRAX. We identified women aged 40 years or older with baseline BMD and FRAX scores. Observed fracture outcomes to 10 years were compared with predicted 10-year fracture probability stratified by prior fracture status: none, recent (<2 years [median 0.3 years]), and remote (≥2 years [median 10.6 years]). For women with recent fractures, we also examined proposed multipliers to adjust FRAX for the effect of fracture recency and site. The cohort comprised 33,465 women aged 40 to 64 years (1897 recent fracture, 2120 remote fracture) and 33,806 women aged ≥65 years (2365 fracture, 4135 remote fracture). Observed fracture probability was consistent with predicted probability in most analyses. In women aged 40 to 64 years, there was a significant effect of recent vertebral and humerus fracture on MOF (observed to predicted 1.61 and 1.48, respectively), but these effects were still lower than the proposed multipliers (2.32 and 1.67, respectively). No significant effect of fracture recency was found after hip or forearm fracture in either age group. Our findings contribute to accumulating evidence of the importance of recent fracture. The effect of fracture recency was not consistent across fracture sites and with a lower magnitude than previously reported. Further quantification of effect size and specificity in additional independent cohorts is warranted to validate and refine recent-fracture multipliers in fracture risk assessment. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Absolute fracture risk assessment using lumbar spine and femoral neck bone density measurements: Derivation and validation of a hybrid system

The World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) computes 10‐year probability of major osteoporotic fracture from multiple risk factors, including femoral neck (FN) T‐scores. Lumbar spine (LS) measurements are not currently part of the FRAX formulation but are used widely in clinical practice, and this creates confusion when there is spine‐hip discordance. Our objective was to develop a hybrid 10‐year absolute fracture risk assessment system in which nonvertebral (NV) fracture risk was assessed from the FN and clinical vertebral (V) fracture risk was assessed from the LS. We identified 37,032 women age 45 years and older undergoing baseline FN and LS dual‐energy X‐ray absorptiometry (DXA; 1990–2005) from a population database that contains all clinical DXA results for the Province of Manitoba, Canada. Results were linked to longitudinal health service records for physician billings and hospitalizations to identify nontrauma vertebral and nonvertebral fracture codes after bone mineral density (BMD) testing. The population was randomly divided into equal‐sized derivation and validation cohorts. Using the derivation cohort, three fracture risk prediction systems were created from Cox proportional hazards models (adjusted for age and multiple FRAX risk factors): FN to predict combined all fractures, FN to predict nonvertebral fractures, and LS to predict vertebral (without nonvertebral) fractures. The hybrid system was the sum of nonvertebral risk from the FN model and vertebral risk from the LS model. The FN and hybrid systems were both strongly predictive of overall fracture risk (p < .001). In the validation cohort, ROC analysis showed marginally better performance of the hybrid system versus the FN system for overall fracture prediction (p = .24) and significantly better performance for vertebral fracture prediction (p < .001). In a discordance subgroup with FN and LS T‐score differences greater than 1 SD, there was a significant improvement in overall fracture prediction with the hybrid method (p = .025). Risk reclassification under the hybrid system showed better alignment with observed fracture risk, with 6.4% of the women reclassified to a different risk category. In conclusion, a hybrid 10‐year absolute fracture risk assessment system based on combining FN and LS information is feasible. The improvement in fracture risk prediction is small but supports clinical interest in a system that integrates LS in fracture risk assessment. © 2011 American Society for Bone and Mineral Research.     

FRAX在绝经后骨质疏松症中骨折风险评估的Meta分析

目的 系统评价未使用骨密度检测时,通过FRAX工具评估绝经后骨质疏松症(PMOP)中骨折发生概率的应用准确性。方法 系统检索CNKI、CBM、VIP、WanFang、PubMed、Embase、Cochrane 图书馆,开展方法学质量评估,同时借助软件Stata16.0和Metadisc实施Meta分析。所纳入文献合计12篇,涉及研究为14个。结果 Meta分析结果表明,FRAX敏感度为84.68%,特异性为63.18%。合并SROC曲线绘制,最终得到诊断的准确率为85%,P<0.05,准确率接近骨密度检测方法。其中,髋部骨折概率对于骨密度评估方法的敏感度为81.9%,特异性为65.02%。使用FRAX评估时,诊断的准确率为83%,P<0.05;主要部位骨折概率对于骨密度评估方法的敏感度为73.5%;特异性为72.71%,使用FRAX评估时得到诊断的准确率为81%,P<0.05。 结论 FRAX工具是一种可靠的应用于绝经后骨质疏松症中的骨折评估方法。     

Imputation of 10‐year osteoporotic fracture rates from hip fractures: A clinical validation study

The World Health Organization (WHO) fracture risk assessment system (FRAX) allows for calibration from country‐specific fracture data. The objective of this study was to evaluate the method for imputation of osteoporotic fracture rates from hip fractures alone. A total of 38,784 women aged 47.5 years or older at the time of baseline femoral neck bone mineral density (BMD) measurement were identified in a database containing all clinical dual energy X‐ray absorptiometry (DXA) results for the Province of Manitoba, Canada. Health service records were assessed for the presence of nontrauma osteoporotic fracture codes after BMD testing (431 hip, 787 forearm, 336 clinical vertebral, and 431 humerus fractures). Ten‐year hip and osteoporotic fracture rates were estimated by the Kaplan‐Meier method. The population was stratified by age (50 to 90 years, 5‐year width strata) and again by femoral neck T‐scores (?4.0 to 0.0, 0.5 SD width strata). Within each stratum, the ratio of hip to osteoporotic fractures was calculated and compared with the predicted ratio from FRAX. Increasing age was associated with greater predicted hip‐to‐osteoporotic ratios (youngest 0.07 versua oldest 0.41) and observed ratios (youngest 0.10 versus oldest 0.48). Lower T‐scores were associated with greater predicted (highest 0.04 versus lowest 0.71) and observed ratios (highest 0.06 versus lowest 0.44). There was a strong positive correlation between predicted and observed ratios (Spearman r = 0.90–0.97, p < .001). For 14 of the 18 strata, the predicted ratio was within the observed 95% confidence interval (CI). Since collection of population‐based hip fracture data is considerably easier than collection of non–hip fracture data, this study supports the current emphasis on using hip fractures as the preferred site for FRAX model calibration. © 2010 American Society for Bone and Mineral Research     

应用FRAX工具评估系统性红斑狼疮患者骨折风险及相关因素分析

目的 探讨骨折危险性评估工具(FRAX)评估系统性红斑狼疮(SLE)患者骨质疏松性骨折风险并进行相关因素分析.方法 纳入2018年1月至2019年6月我院治疗的90例SLE患者以及60例正常体检人员,分别设为研究组与对照组.采用双能X线骨密度仪测定骨密度,比较两组骨密度差异;采用FRAX评估SLE患者骨质疏松性骨折风险...     

北京地区中老年人FRAX骨折风险评估与BMD、骨代谢相关生化指标间的相关回归研究

目的探讨北京南郊地区中老年人FRAX评估未来10年全身骨折风险PMOF、骨密度BMD、骨代谢相关指标指标25(OH)D3、PTH、N-MID等在年龄、性别、体质指数之间的差异及变化趋势,研究PMOF、骨密度与各骨代谢相关生化指标之间的相关性。方法收集接受DXA桡骨远端骨密度(BMD)检查的体检人群1133例,代入FRAX骨折风险评估工具计算全身主要部位骨折概率(PMOF),收集相应骨代谢生化指标:25-羟维生素D3[25(OH)D_3],血清骨钙素N端中分子片段(N-MID),甲状旁腺素(PTH)、血钙(Ca)、血磷(P)、血清碱性磷酸酶(ALP)等。分析比较各指标随年龄的变化趋势,比较各年龄组各指标性别间差异;分析比较不同性别、各年龄组中各指标在不同体质指数之间的差异及其变化趋势;采用多元逐步回归法分别分析未来10年骨折风险概率(PMOF)、BMD与各因素、各生化指标之间的相关回归关系。结果非优势手臂桡骨远端1/3处骨密度BMD随年龄增长而降低,各年龄组男性BMD值均大于女性,PMOF随年龄增长而增加,各年龄组男性PMOF均小于女性,差异有统计学意义(P0.05);各年龄组25(OH)D_3水平男性均大于女性,50岁以上年龄组N-MID男性均小于女性,差异有统计学意义(P0.05);多元逐步回归分析中BMD与年龄、N-MID呈负相关,与BMI为正相关,男性大于女性;PMOF与BMD、年龄呈负相关,与BMI、N-MID呈正相关,男性小于女性;在不同性别、各年龄组中BMI正常组的PMOF最低,超重组最高,差异有统计学意义。其他生化指标与BMD、PMOF之间的相关关系不显著(P0.05)。结论 BMD、PMOF与性别、年龄、BMI、骨钙素均相关,其中女性OF的风险均高于男性;BMD随年龄增长而降低,骨折风险增加;BMD与BMI呈正相关,但PMOF表现为超重人群骨折风险最高,故超重亦是使骨折风险增加的危险因素。随血清骨钙素增高,BMD降低,骨折风险增高,可在一定程度上反映骨组织的新陈代谢情况。关注骨代谢生化指标变化可在一定程度上预判骨密度及PMOF水平,对骨质疏松及其骨折的的早发现、早诊断、早预防和早治疗提供一定参考及理论依据。     

Probability of fractures predicted by FRAX® and observed incidence in the Spanish ECOSAP Study cohort

Purpose

To assess the ability of the Spanish version of the WHO fracture risk assessment tool (FRAX®) to predict the observed incident fractures in the ECOSAP Study cohort.

Methods

5201 women, aged 65 or older, were enrolled in a three-year, prospective study by a non-randomized sampling of consecutive cases in 58 primary care centers in Spain. Participants completed an osteoporosis and fracture risk questionnaire and attended follow-up visits every 6 months. All radiologically or surgically confirmed low-trauma, non-spinal fractures were collected. The individual 10-year absolute risks of hip and major osteoporotic fractures were calculated with the FRAX® algorithms for Spain without the inclusion of the bone mineral density (BMD) measurements. Calibration was evaluated by comparing the three-year estimated (E) fractures predicted with FRAX® with the number of observed (O) fractures, and their discriminative ability for the probability of new fractures with the area under the receiving operating characteristic (ROC) curves.

Results

Fifty (0.96%) women sustained an incident hip fracture, and 201 (3.81%) women presented with major osteoporotic fractures (hip, forearm or humerus). The E/O ratios for hip and major osteoporotic fractures were 1.10 and 0.66 respectively. Clinical vertebral fractures were not collected; therefore, the E/O ratio for major fractures should be expected to be lower. The difference between E and O cases reached statistical significance (χ², p < 0.001). Areas under the ROC curves were 0.640 and 0.615 for hip and major osteoporotic fractures respectively.

Conclusions

The Spanish FRAX® underestimates the risk for major osteoporotic fractures. The estimated risk for hip fractures was similar to the observed fractures; however the algorithm had only modest discriminative ability. These results should be interpreted in the context of the relatively low number of observed fractures, especially at the hip.