Comparative Efficacy and Safety of Anti-Osteoporotic Therapies for Kidney Transplant Recipients: A Systematic Review and Network Meta-Analysis

Xiaopei Liu¹Xingyao Li¹Yanhong Zhao¹Qi Gao¹Yuan Xue¹Zhongheng Wu¹Xingmin Shi^2,3Xili Wu^1*

• ¹Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
• ²Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi'an, China
• ³Xi'an Jiaotong University, Xi'an, China

Background: Kidney transplant recipients (KTRs) are at an increased risk of osteoporosis, which negatively impacts their quality of life and transplant outcomes. However, the efficacy and safety of anti-osteoporosis treatments in this group remain uncertain. Methods: We conducted a systematic search of PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials up to August 1, 2024. Randomized controlled trials (RCTs) examining anti-osteoporotic medications in KTRs were included. Primary outcomes were changes in bone mineral density (BMD) at femoral neck and lumbar spine, and adverse events. We performed a frequentist network meta-analysis using random-effects models. Evidence certainty was assessed using the GRADE approach. Results: Twenty-one RCTs involving 1,066 participants were included, published between 2000 and 2021. For femoral neck BMD, bisphosphonates significantly improved BMD compared to control (MD=0.04, 95%CI=0.00-0.09, p<0.05) based on low certainty evidence, while calcitonin was significantly superior to calcium (MD=-0.14, 95%CI=-0.28 to -0.01). Most other comparisons showed no statistically significant differences based on very low to moderate certainty evidence. For lumbar spine BMD, bisphosphonates, calcitonin, and calcium demonstrated statistically significant inferiority compared to denosumab, with bisphosphonates showing MD=-4.98 (95%CI=-6.84 to -3.13), calcitonin showing MD=-4.35 (95%CI=-6.24 to -2.47), and calcium showing MD=-5.85 (95%CI=-7.72 to -3.98), while denosumab was superior to control (MD=5.10, 95%CI=3.25-6.95), based on low to very low certainty evidence from one RCT. Calcitonin was also significantly superior to calcium (MD=0.60, 95%CI=0.07-1.12). For safety outcomes, no statistically significant differences were observed between interventions based on low to moderate certainty evidence. Conclusion: Denosumab appears most effective for improving lumbar spine BMD in KTRs, while calcitonin shows promise for femoral neck BMD improvement. However, the low to moderate certainty of evidence necessitates individualized treatment approaches considering patient-specific factors including renal function and safety profiles. These findings suggest current guidelines emphasizing bisphosphonates as first-line therapy may require revision, though larger long-term studies with fracture endpoints are needed to confirm these results.