Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.
Division of Mechanical and Aerospace Engineering, Faculty of Engineering, Hokkaido University, Sapporo, Japan.
J Bone Miner Metab. 2022 Jul;40(4):613-622. doi: 10.1007/s00774-022-01323-9. Epub 2022 Mar 25.
Bisphosphonates (BPs) have been shown to reduce the incidence of vertebral fractures during the first year or two of glucocorticoid (GC) treatments and are therefore recommended as a first-line treatment for GC-induced osteoporosis (GIO). However, there are theoretical concerns about the long-term use of BPs in low-turnover osteoporosis caused by chronic GC therapy.
We analyzed the trabecular microarchitecture, bone metabolism, and material strength of iliac crest bone biopsy samples from 10 female patients with rheumatoid arthritis who received an average of 6.7 years of BP therapy for GIO (GIOBP group), compared with those of 10 age- and bone mineral density (BMD)-matched non-rheumatoid arthritis postmenopausal women (reference group).
Patients in the GIOBP group had a significantly greater fracture severity index, as calculated from the number and the extent of vertebral fractures compared with the reference patients. Micro-computed tomography analysis showed that the degree of mineralization and trabecular microarchitecture were significantly lower in the GIOBP group than in the reference patients. Patients in the GIOBP group exhibited lower bone contact stiffness, determined by micro-indentation testing, than in the reference group. The contact stiffness of the bone was negatively correlated with the fracture severity index and the daily prednisolone dosage. Immunohistochemistry and serum bone turnover markers showed decreased osteoclastic activity, impaired mineralization, and an increased fraction of empty lacunae in the GIOBP group.
Our findings indicate that patients receiving long-term BP for GIO are still at high risk for fragility fractures because of poor bone quality.
双膦酸盐(BPs)已被证明可降低糖皮质激素(GC)治疗最初一到两年内椎体骨折的发生率,因此被推荐作为 GC 诱导性骨质疏松症(GIO)的一线治疗药物。然而,长期使用 BPs 治疗慢性 GC 治疗引起的低转换型骨质疏松症存在理论上的担忧。
我们分析了 10 名接受 BP 治疗平均 6.7 年的 GIO 患者(GIOBP 组)和 10 名年龄和骨密度(BMD)匹配的非类风湿关节炎绝经后妇女(参考组)的髂嵴骨活检样本的小梁微结构、骨代谢和材料强度。
与参考患者相比,GIOBP 组患者的骨折严重程度指数显著更高,这是通过计算椎体骨折的数量和程度得出的。微计算机断层扫描分析显示,GIOBP 组患者的矿化程度和小梁微结构明显低于参考患者。通过微压痕测试,GIOBP 组患者的骨接触刚度明显低于参考组。骨接触刚度与骨折严重程度指数和每日泼尼松龙剂量呈负相关。免疫组织化学和血清骨转换标志物显示,GIOBP 组患者的破骨细胞活性降低、矿化受损以及空骨陷窝比例增加。
我们的研究结果表明,长期接受 BP 治疗 GIO 的患者仍存在脆性骨折的高风险,原因是骨质量较差。