Imanishi Yasuo, Furukubo Taku, Shoji Shigeichi
Department of Vascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Department of Pharmacy, Shirasagi Hospital, Osaka, Japan.
Endocr J. 2025 Aug 1;72(8):847-862. doi: 10.1507/endocrj.EJ24-0271. Epub 2025 Apr 23.
Chronic kidney disease (CKD) induces secondary osteoporosis, characterized by an imbalance between bone formation and resorption due to kidney dysfunction; the result is a reduction in both bone mineral density and quality. This condition is compounded by disruption of bone metabolic turnover, abnormalities in bone microstructure and collagen cross-linking, and compromised bone quality, all of which contribute to increased bone fragility. Reduced kidney function is complicated by secondary hyperparathyroidism, which exacerbates bone fragility. Managing osteoporosis in patients with CKD is challenging because drugs may be contraindicated or require cautious administration, particularly those with high urinary excretion rates. In addition, severe hypercalcemia or hypocalcemia may develop in these patients following administration of active vitamin D or denosumab, respectively. The choice of pharmacotherapy depends on the stage of CKD; however, evidence for the safety and efficacy of osteoporosis drugs in moderate to severe cases of CKD, particularly stages G4, G5, and G5D (i.e., dialysis patients), is limited. This article focuses on the pathophysiology of CKD-associated osteoporosis, as well as the increased fracture risk, and provides a concise overview of safety considerations regarding administration of osteoporosis drugs in Japan. The data presented highlight the complexities associated with drug use in patients with CKD.
慢性肾脏病(CKD)会引发继发性骨质疏松症,其特征是由于肾功能障碍导致骨形成与骨吸收失衡;结果是骨矿物质密度和质量均降低。这种情况因骨代谢周转紊乱、骨微结构和胶原交联异常以及骨质量受损而更加复杂,所有这些因素都会导致骨脆性增加。肾功能减退会并发继发性甲状旁腺功能亢进,这会加剧骨脆性。对CKD患者的骨质疏松症进行管理具有挑战性,因为药物可能禁忌使用或需要谨慎给药,尤其是那些经尿排泄率高的药物。此外,这些患者在分别使用活性维生素D或地诺单抗后可能会出现严重高钙血症或低钙血症。药物治疗的选择取决于CKD的阶段;然而,骨质疏松症药物在中度至重度CKD病例,特别是G4、G5和G5D期(即透析患者)中的安全性和有效性证据有限。本文重点关注CKD相关性骨质疏松症的病理生理学以及骨折风险增加,并简要概述了日本在骨质疏松症药物给药方面的安全性考虑因素。所呈现的数据凸显了CKD患者用药的复杂性。