School of Health Science, Faculty of Medicine, Tottori University, Tottori, Japan.
Biostatistics Section, Department of Data Science, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
J Bone Miner Metab. 2021 Jul;39(4):668-677. doi: 10.1007/s00774-021-01208-3. Epub 2021 Mar 18.
To identify predictors for incident fractures in patients on pharmaceutical treatment for osteoporosis by a secondary analysis of the Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-04), which was a 2-year, randomized, parallel-group, controlled trial of minodronate and raloxifene in women with primary osteoporosis.
This was a prospective, observational study using JOINT-04 data, in which biomarkers, such as undercarboxylated osteocalcin (ucOC), N-telopeptide of type 1 collagen, tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase, homocysteine, and pentosidine in blood, and physical functions, such as the timed up and go test and one-leg standing test with eyes open (OLST), and the fall risk index, were measured. The relationships of incident morphometric vertebral fractures during the treatment period, as well as prevalent vertebral fractures, and baseline data were analyzed.
The full analysis set of the JOINT-04 included 3247 patients (1623 in the minodronate group and 1624 in the raloxifene group). The hazard ratio (95% confidence interval) for incident vertebral fractures over 2 years of pharmacotherapy, adjusted for confounders, was 0.93 (0.90-0.96) for ucOC, 1.15 (1.08-1.23) for TRACP-5b, 1.02 (1.01-1.03) for pentosidine, 0.91 (0.88-0.94) for the OLST, and 1.27 (1.01-1.60) for the fall risk index, which were all independent predictors.
Evaluating fracture risk for patients with osteoporosis considering these potential risk factors for fracture in addition to the established risk factors may be useful when starting pharmaceutical treatment.
通过对日本骨质疏松症干预试验方案 4（JOINT-04）的二次分析，确定接受骨质疏松症药物治疗的患者发生骨折的预测因素。JOINT-04 是一项为期 2 年、随机、平行分组、对照的密固达和雷洛昔芬治疗原发性骨质疏松症女性的试验。
这是一项使用 JOINT-04 数据的前瞻性观察性研究，其中包括生物标志物，如非羧化骨钙素（ucOC）、I 型胶原 N 端肽、抗酒石酸酸性磷酸酶 5b（TRACP-5b）、骨碱性磷酸酶、同型半胱氨酸和戊糖，以及身体功能，如计时起立行走测试和睁眼单腿站立测试（OLST）和跌倒风险指数，进行了测量。分析了治疗期间发生的形态计量性椎体骨折、现患椎体骨折以及基线数据的关系。
JOINT-04 的全分析集包括 3247 名患者（密固达组 1623 名，雷洛昔芬组 1624 名）。经过混杂因素调整，2 年药物治疗期间发生椎体骨折的风险比（95%置信区间），ucOC 为 0.93（0.90-0.96），TRACP-5b 为 1.15（1.08-1.23），戊糖为 1.02（1.01-1.03），OLST 为 0.91（0.88-0.94），跌倒风险指数为 1.27（1.01-1.60），均为独立预测因素。
在开始药物治疗时，除了已确定的骨折风险因素外，考虑这些骨折潜在风险因素评估骨质疏松症患者的骨折风险可能会有所帮助。
