Cowan Andrea C, Solo Karla, Lebedeva Victoria, Mohammadi Kamalabadi Yasaman, El-Shimy Maha, Joshi Aayushi, Olalike Edith Ginika, Tanaka Misa, Klotz Adam G R, Elazhary Hatoun Wahid, Zhu Antonia, Forster Adam, Veettil Shafaz, Nair Sachin G, Servin Martinez Maria Fernanda, Nayak Dweeti, Priya V Nikhila, Wellan Catherine, Cespedes Arcani Diana Maria, Roshanov Pavel S
Department of Medicine, Western University, London, ON, Canada.
Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
Can J Kidney Health Dis. 2024 Dec 23;11:20543581241306799. doi: 10.1177/20543581241306799. eCollection 2024.
Kidney transplant recipients are uniquely exposed to the disordered bone metabolism associated with chronic kidney disease beginning before transplantation followed by chronic corticosteroid use after transplantation. Previous efforts to synthesize the rapidly accruing evidence regarding estimation and management of fracture risk in kidney transplant recipients are outdated and incomplete.
To synthesize the evidence informing the overall incidence, patient-specific risk prediction, and methods of prevention of fractures in patient living with a kidney transplant.
Three systematic reviews will address the following questions: What is the overall incidence of skeletal fracture after kidney transplantation (review 1)? Which prediction models and individual prognostic factors predict fracture in kidney transplant recipients (review 2)? and How effective are different antifracture interventions at preventing fracture or improving surrogate markers of bone health in kidney transplant recipients (review 3)?
Cohort studies (reviews 1 and 2) and randomized trials (review 2) with a mean/median follow-up ≥12 months beginning after transplant. Review 3: randomized trials or new-user cohort studies with concurrent controls evaluating the effect of antifracture interventions including bisphosphonates, calcium supplementation, cinacalcet, denosumab, parathyroid hormone analogues, parathyroidectomy, raloxifene, romosozumab, steroid withdrawal or minimization protocols after kidney transplant, vitamin D (both active and nutritional), other antifracture interventions.
Adult kidney transplant recipients in studies published after the year 2000.
Review 1: incidence rate or cumulative risk of fracture. Review 2: For prediction models, measures of discrimination (eg, c-statistic), calibration (calibration curves, observed:expected ratios), and net benefit (ie, from decision curve analysis); for individual prognostic factors, relative measures of association with fractures. Review 3: measures of treatment effect on fractures and on surrogate markers of bone health (eg, bone mineral density, trabecular bone score).
We searched MEDLINE, Embase, and the Cochrane Library using subject headings and keywords related to kidney transplant and fractures. Pairs of reviewers will screen records independently in duplicate to identify studies relevant to one or more of the 3 reviews and categorize each study accordingly. Single reviewers will extract data and evaluate risk of bias for each included study using one of the following tools as appropriate: the Quality of Prognostic Studies tool, the Prediction model Risk Of Bias ASsessment tool, the Risk Of Bias In Non-randomised Studies-of Interventions tool, and the Cochrane Risk of Bias 2.0 tool. A second reviewer will independently verify. We will synthesize study-level summary estimates by random-effects meta-analysis for review 1, by vote counting and random-effects meta-analysis in review 2, and by random effects pairwise and, if feasible, network meta-analysis in review 3. We will summarize findings according to latest guidance of the Grading of Recommendations Assessment, Development, and Evaluation Working Group applicable to each review.
Reliance on published studies is susceptible to publication bias, particularly in studies of prediction (review 2) and of treatment effects (review 3).
This review will provide an evidence update on 3 topics of relevance to patients, clinicians, guideline developers, and researchers.
肾移植受者在移植前就开始独特地暴露于与慢性肾脏病相关的骨代谢紊乱中，移植后还会长期使用皮质类固醇。先前综合有关肾移植受者骨折风险评估和管理的快速积累证据的努力已过时且不完整。
综合有关肾移植患者骨折的总体发生率、患者特异性风险预测及预防方法的证据。
三项系统评价将解决以下问题：肾移植后骨骼骨折的总体发生率是多少（评价1）？哪些预测模型和个体预后因素可预测肾移植受者的骨折（评价2）？不同的抗骨折干预措施在预防肾移植受者骨折或改善骨健康替代指标方面的效果如何（评价3）？
队列研究（评价1和2）和随机试验（评价2），移植后开始的平均/中位随访时间≥12个月。评价3：随机试验或新使用者队列研究，有同期对照，评估抗骨折干预措施的效果，包括双膦酸盐、补钙、西那卡塞、地诺单抗、甲状旁腺激素类似物、甲状旁腺切除术、雷洛昔芬、罗莫佐单抗、肾移植后停用或减少类固醇方案、维生素D（活性和营养型）及其他抗骨折干预措施。
2000年后发表的研究中的成年肾移植受者。
评价1：骨折发生率或累积风险。评价2：对于预测模型，区分度测量指标（如c统计量）、校准指标（校准曲线、观察值：预期比值）和净效益（即来自决策曲线分析）；对于个体预后因素，与骨折相关的相对关联度测量指标。评价3：对骨折及骨健康替代指标（如骨密度、小梁骨评分）的治疗效果测量指标。
我们使用与肾移植和骨折相关的主题词和关键词检索MEDLINE、Embase和Cochrane图书馆。成对的评审人员将独立进行重复筛选记录，以识别与三项评价中的一项或多项相关的研究，并相应地对每项研究进行分类。单个评审人员将提取数据，并根据适用情况使用以下工具之一评估每项纳入研究的偏倚风险：预后研究质量工具、预测模型偏倚风险评估工具、非随机干预研究中的偏倚风险工具和Cochrane偏倚风险2.0工具。另一名评审人员将独立进行核实。我们将通过随机效应荟萃分析对评价1进行研究水平的汇总估计，通过投票计数和随机效应荟萃分析对评价2进行汇总估计，通过随机效应成对分析，并在可行的情况下对评价3进行网络荟萃分析。我们将根据适用于每项评价的推荐分级评估、制定和评价工作组的最新指南总结研究结果。
依赖已发表研究易受发表偏倚影响，尤其是在预测研究（评价2）和治疗效果研究（评价3）中。
本综述将提供与患者、临床医生、指南制定者和研究人员相关的三个主题的证据更新。
