IRCCS San Raffaele Scientific Institute, Nephrology and Dialysis Unit, Milan, Italy.
Università Vita Salute San Raffaele, Milan, Italy.
Int Urol Nephrol. 2024 Oct;56(10):3285-3293. doi: 10.1007/s11255-024-04110-9. Epub 2024 Jun 10.
In patients with chronic kidney disease (CKD), renal osteodystrophy may be associated with a progressive bone mass loss that increases fracture risk. Denosumab, a monoclonal antibody inhibiting osteoclast activity, is an antiresorptive medication used for the treatment osteoporosis.
Its efficacy and safety were initially established in the FREEDOM study, showing a significant reduction in incident fractures in osteoporotic women treated with denosumab. Subsequent post hoc analyses showed its efficacy in patients stratified by kidney function, but these analyses did not include patients with advanced stages of CKD. The capability of denosumab in improving bone mineral density in uremic patients was evaluated in 12 studies including 461 dialysis patients with low bone mineral density. The improvement of bone mineral density was the final end point in these studies assessed during a follow-up of 6-60 months. Nine of these studies did not have hyperparathyroidism among criteria for patient inclusion and their participants may have low-turnover bone disease. Despite current recommendations, no patients underwent bone biopsy before denosumab therapy.
Overall, findings in these studies suggest that denosumab is a viable option for promoting bone mass recovery in patients with advanced stages of CKD having either high or low serum levels of PTH. However, the increase of bone mineral density was lower in patients with low serum markers of bone turnover at baseline. These studies also highlighted the need for calcium and vitamin D supplementation to prevent hypocalcemia that remains a serious concern.
Denosumab emerges as a potentially safe and effective option for enhancing bone health in CKD patients.
在慢性肾脏病（CKD）患者中，肾性骨营养不良可能与进行性骨量丢失有关，从而增加骨折风险。地舒单抗是一种抑制破骨细胞活性的单克隆抗体，是一种用于治疗骨质疏松症的抗吸收药物。
其疗效和安全性最初在 FREEDOM 研究中得到证实，接受地舒单抗治疗的骨质疏松症女性骨折发生率显著降低。随后的事后分析显示，其在肾功能分层患者中有效，但这些分析不包括 CKD 晚期患者。在包括 461 名低骨密度透析患者的 12 项研究中评估了地舒单抗改善尿毒症患者骨密度的能力。这些研究的最终终点是在 6-60 个月的随访期间评估骨密度的改善。其中 9 项研究在纳入标准中没有甲状旁腺功能亢进症，其参与者可能患有低转换骨疾病。尽管有目前的建议，但在接受地舒单抗治疗之前，没有患者进行骨活检。
总体而言，这些研究的结果表明，地舒单抗是一种可行的选择，可促进 CKD 晚期患者骨量恢复，无论其 PTH 血清水平高低。然而，在基线时骨转换血清标志物较低的患者中，骨密度的增加较低。这些研究还强调了补充钙和维生素 D 的必要性，以防止低钙血症，这仍然是一个严重的问题。
地舒单抗作为一种潜在安全有效的增强 CKD 患者骨骼健康的选择出现。
