Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, 2500 N. State St, Jackson, MS, 39216, USA.
Arch Osteoporos. 2019 Mar 9;14(1):35. doi: 10.1007/s11657-019-0587-0.
The use of immunosuppressive agents, especially glucocorticoids, are associated with increased risks of bone loss in kidney transplant patients. Denosumab, a potent antiresorptive agent, has been shown to increase bone mineral density (BMD) in patients with CKD. However, its effects on bone metabolism and BMD in kidney transplant patients remain unclear.
A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2018 to identify studies evaluating denosumab's effect on changes in bone metabolism and BMD from baseline to post-treatment course in kidney transplant patients. Study results were pooled and analyzed utilizing random-effects model. The protocol for this systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095055).
Five studies (a clinical trial and four cohort studies) with a total of 162 kidney transplant patients were identified. The majority of patients had a baseline eGFR ≥ 30 mL/min/1.73 m. After treatment (≥ 6 to 12 months), there were significant increases in BMD with standardized mean differences (SMDs) of 3.26 (95% CI 0.88-5.64) and 1.83 (95% CI 0.43 to 3.22) for lumbar spine and femoral neck, respectively. There were also significant increases in T scores with SMDs of 0.92 (95% CI 0.58 to 1.25) and 1.14 (95% CI 0.17 to 2.10) for lumbar spine and femoral neck, respectively. After treatment, there were no significant changes in serum calcium (Ca) or parathyroid hormone (PTH) from baseline to post-treatment course (≥ 6 months) with mean differences (MDs) of 0.52 (95% CI, - 0.13 to 1.16) mmol/L and - 13.24 (95% CI, - 43.85 to 17.37) ng/L, respectively. The clinical trial data demonstrated more asymptomatic hypocalcemia in the denosumab (12 episodes in 39 patients) than in the control (1 episode in 42 patients) group. From the cohort studies, the pooled incidence of hypocalcemia following denosumab treatment was 1.7% (95% CI 0.4 to 6.6%). All reported hypocalcemic episodes were mild and asymptomatic, but the majority of patients required Ca and vitamin D supplements.
Among kidney transplant patients with good allograft function, denosumab effectively increases BMD and T scores in the lumbar spine and femur neck. From baseline to post-treatment, there are no differences in serum Ca and PTH. However, mild hypocalcemia can occur following denosumab treatment, requiring monitoring and titration of Ca and vitamin D supplements.
免疫抑制剂的使用，特别是糖皮质激素，与肾移植患者骨丢失风险增加有关。地舒单抗是一种有效的抗吸收剂，已被证明可增加 CKD 患者的骨矿物质密度（BMD）。然而，其对肾移植患者骨代谢和 BMD 的影响仍不清楚。
通过 MEDLINE、EMBASE 和 Cochrane 数据库从成立到 2018 年 4 月进行文献检索，以确定评估地舒单抗在基线至治疗后（≥6-12 个月）过程中对骨代谢和 BMD 变化影响的研究。利用随机效应模型对研究结果进行汇总和分析。本系统评价的方案已在 PROSPERO（国际前瞻性系统评价注册中心；编号：CRD42018095055）中注册。
共确定了 5 项研究（一项临床试验和四项队列研究），共纳入 162 例肾移植患者。大多数患者的基线 eGFR≥30ml/min/1.73m。治疗后（≥6-12 个月），腰椎和股骨颈的 BMD 分别有显著增加，标准化均数差（SMD）分别为 3.26（95%置信区间 0.88-5.64）和 1.83（95%置信区间 0.43-3.22）。腰椎和股骨颈的 T 评分也有显著增加，SMD 分别为 0.92（95%置信区间 0.58-1.25）和 1.14（95%置信区间 0.17-2.10）。治疗后，血清钙（Ca）或甲状旁腺激素（PTH）从基线到治疗后（≥6 个月）没有显著变化，平均差值（MD）分别为 0.52（95%置信区间，-0.13-1.16）mmol/L 和-13.24（95%置信区间，-43.85-17.37）ng/L。临床试验数据显示，地舒单抗组（39 例患者中有 12 例）无症状低钙血症的发生率高于对照组（42 例患者中有 1 例）。来自队列研究的数据显示，地舒单抗治疗后低钙血症的总发生率为 1.7%（95%置信区间 0.4-6.6%）。所有报告的低钙血症发作均为轻度和无症状，但大多数患者需要补充钙和维生素 D。
在具有良好同种异体移植功能的肾移植患者中，地舒单抗可有效增加腰椎和股骨颈的 BMD 和 T 评分。从基线到治疗后，血清 Ca 和 PTH 无差异。然而，地舒单抗治疗后可能会出现轻度低钙血症，需要监测并调整钙和维生素 D 的补充剂。
