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.     

应用FRAX评估中老年男性人群骨折风险的多中心研究

目的探讨分别按照不同地区及人群、不同骨密度测量方法计算骨折风险评估工具(FRAX~)的多中心研究在评价男性中老年人骨折风险的预测价值。方法分别搜集中国医科大学航空总医院(本文简称HK)、北京密云区中医医院(本文简称MY)、山东省医学科学院颈肩腰腿痛医院(本文简称SD)行双能X线骨密度检查的中老年人男性病例共7095例,输入相关资料,应用FRAX~中国模式计算各研究对象10年内主要部位骨质疏松性骨折及髋部骨折的概率,应用统计学对比分析根据上述研究资料得到的FRAX值。结果三个中心研究对象10年内主要部位骨质疏松性骨折概率及髋部骨折概率分别行两两Mann-Whitney U检验,P0.05,差异均有统计学意义,分别对三个中心男性人群进行年龄分组,并进行两两对比,其中MY-SD对比组中50～59岁组及80～89组,P0.05,差异无统计学意义,其余MY-HK,HK-SD对比组P0.05,差异具有统计学意义。结论前臂骨密度及髋部骨密度代入FRAX后均能较好的预测未来10年男性人群骨折的风险概率;即使是不同地区人群及应用不同检测设备得到的前臂骨密度值代入FRAX后仍能较好的预测未来10年男性人群的骨折风险概率,且差异在某些年龄组无显著性,FRAX~工具对男性中老年人骨折风险预测极具价值。     

2018 update of French recommendations on the management of postmenopausal osteoporosis

Objectives

To update the 2012 recommendations on pharmacotherapy for postmenopausal osteoporosis, under the aegis of the Bone Task Force of the French Society for Rheumatology (SFR) and of the Osteoporosis Research and Information Group (GRIO), in collaboration with scientific societies (Collège national des généralistes enseignants, Collège national des gynécologues et obstétriciens français, Fédération nationale des collèges de gynécologie médicale, Groupe d’étude de la ménopause et du vieillissement hormonal, Société française de chirurgie orthopédique, Société française d’endocrinologie, and Société française de gériatrie et de gérontologie).

New treatment approach for osteopenia

Nearly 44 million persons in the United States have osteoporosis or osteopenia, most of whom are osteopenic. Because of sheer numbers, an increased number of fractures occur in the osteopenic group. Bone mineral density alone, based on dual energy X-ray absorptiometry scan results, is not enough to identify persons at increased risk for fracture. The World Health Organization (WHO) Working Group On Osteoporosis has developed an online tool, known as FRAX, to calculate future hip fracture probability based on individual clinical risk factors. Determining the risk of hip fracture is critical because it is the most devastating osteoporosis complication. The FRAX model was developed from population-based cohort studies in Europe, North America, Asia, and Australia. In 2008, the National Osteoporosis Foundation (NOF) adopted the WHO approach in the treatment of osteopenia. This article presents a clinical scenario to demonstrate the application of the WHO FRAX tool and the new NOF guidelines.     

FRAX评估类风湿关节炎患者骨质疏松性骨折风险的临床应用

目的探讨骨折危险性评估工具(FRAX)评估类风湿关节炎(RA)患者骨质疏松性骨折风险的临床应用。方法选择本院就诊RA患者54例,采集患者骨折危险因素等临床资料,应用FRAX,使用或不使用骨密度(BMD)分别计算出未来10年髋部骨折及主要骨质疏松性骨折的概率,对结果进行分析比较。结果 54例RA患者,未使用BMD未来10年髋部骨折概率0~20%,主要骨质疏松性骨折概率2.5%~24%;使用BMD计算的骨折概率高于未使用BMD计算的骨折概率,差异有统计学意义(P<0.01);糖皮质激素疗程≥1年的患者使用BMD计算的骨折概率高于未使用BMD计算的骨折概率,差异有统计学意义(P<0.01);按骨折风险分组,中高危组与低危组在类风湿因子、抗ccp、c反应蛋白水平方面的差异有统计学意义(P<0.01)。结论 FRAX可作为评估RA患者骨质疏松性骨折风险的一种切实可行的方法,若联合BMD可更准确地评估骨折风险。类风湿因子、抗ccp、C反应蛋白高水平的RA患者更应注重骨质疏松的防治。     

Performance of FRAX and FRAX-Based Treatment Thresholds in Women Aged 40 Years and Older: The Manitoba BMD Registry

We examined among women aged ≥40 years the performance of the Fracture Risk Assessment Tool (FRAX) and FRAX-based osteoporosis treatment thresholds under the US National Osteoporosis Foundation (NOF) and UK National Osteoporosis Guideline Group (NOGG) guidelines. We used registry data for all women aged ≥40 years in Manitoba, Canada, with baseline bone mineral density (BMD) testing (n = 54,459). Incident major osteoporotic fracture (MOF), hip fracture, and clinical fracture were assessed from population-based health services data (mean follow-up 10.5 years). Age-stratified hazard ratios (HR) were estimated from Cox regression models. We assessed the sensitivity, specificity, positive predictive value (PPV), number needed to screen (NNS), and number needed to treat (NNT) to prevent a fracture (assuming 20% relative risk reduction on treatment) for osteoporosis treatment thresholds under the NOF and NOGG guidelines. Femoral neck T-score and FRAX (with and without BMD) predicted all fracture outcomes at all ages. There was good calibration in FRAX-predicted versus observed 10-year MOF and hip fracture probability. Overall sensitivity (PPV) for incident MOF was 25.7% (24.0%) for femoral neck T-score ≤ –2.5; 20.3% (26.3%) for FRAX (with BMD)-predicted 10-year MOF risk ≥20% (NOF threshold); 27.3% (22.0%) for FRAX-predicted 10-year MOF risk ≥ age-dependent cut-off (NOGG threshold), 59.4% (19.0%) for the NOF treatment algorithm; and 28.5% (18.4%) for the NOGG treatment algorithm. Sensitivity for identifying incident MOF varied by age, ranging from 0.0% to 26.3% in women 40 to 49 years old and from 49.0% to 93.3% in women aged 80+ years. The gradient of risk for fracture prediction from femoral neck T-score and FRAX (with and without BMD) as continuous measures was strong across the age spectrum. The sensitivity and PPV of the strategies based on dichotomous cut-offs are low, especially among women aged 40 to 49 years (who have lowest incidence rates). Threshold-based approaches should be reassessed, particularly in younger women. © 2019 American Society for Bone and Mineral Research.     

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.     

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。     

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).