Vitamin D Analogues and Fracture Risk in Chronic Kidney Disease: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Abstract

Vitamin D receptor agonists (VDRAs) are commonly prescribed in chronic kidney disease (CKD). However, their protective effects on bone remain controversial. We performed a systematic review and meta‐analysis of randomized controlled trials (RCTs) to evaluate the effect of VDRAs on fracture risk and bone mineral density (BMD) in adult patients with CKD. We searched MEDLINE, EMBASE, CENTRAL, http://clinicaltrials.gov, and the WHO's International Clinical Trials Registry Platform databases from inception to June 19, 2021. We included RCTs comparing VDRAs, to placebo or another medication, in adults with CKD requiring or not dialysis. Conference abstracts and trials involving kidney transplant recipients and/or comparing VDRAs to antiresorptive or anabolic bone therapy were excluded. Primary outcome was fracture at any anatomical site. Secondary outcomes were BMD at femoral neck, lumbar spine, and/or total hip. Prespecified subgroup analyses were conducted according to baseline demographics, overall risk of bias, and follow‐up time. From 6868 references retrieved, eight RCTs were eligible: five reported fracture, two reported BMD, and one reported both outcomes. As comparator, one study used no VDRAs, one used nutritional intervention and no medication, and six used placebo. In meta‐analysis, VDRAs were not associated with a significant reduction in total fractures in overall (risk ratio = 0.79, 95% confidence interval 0.38–1.65, I2 = 0%, six trials, 1507 participants, 27 fractures) or in prespecified subgroup analyses. Three trials reported BMD at different sites and with different BMD measurements; thus, a meta‐analysis could not be performed. Two RCTs were at high risk of bias, notably because of deviations from the intended interventions. As limitation, we have to mention the low total number of fractures included in our meta‐analysis. In conclusion, current evidence from RCTs is insufficient to associate VDRAs with bone protection in CKD. Further large and long‐term studies specifically designed to evaluate the efficacy of VDRAs on bone outcomes are thus required. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Active Vitamin D Use and Fractures in Hemodialysis Patients: Results from the International DOPPS

“…It is well recognized that active vitamin D improves high-turnover bone disease through suppression of PTH, [10,11] which would theoretically improve bone strength, although direct evidence is limited. [35] Our results do not negate such potential benefits of lowering PTH with active vitamin D, and it would be inappropriate to cite this study as evidence against the role of active vitamin D in the treatment of SHPT in HD patients.…”

Programa de resistência muscular para membros inferiores melhora sarcopenia urêmica

“…25 A vitamina D é responsável por promover a absorção de cálcio, mineralização da formação de tecido ósseo e manutenção da função muscular. Seu déficit no organismo, promove alterações como a redução da massa óssea e disfunções musculares, 26 Kaczor, 27 que indica que a diminuição da vitamina D pode causar atrofia muscular, principalmente das fibras de contração rápida e anormalidades no metabolismo do cálcio, impactando na diminuição da força muscular. Nos pacientes estudados, observou-se que a vitamina D não estava abaixo dos valores mínimos de referência, entretanto, é fato pontuar que os pacientes já em TRS realizam de forma rotineira a suplementação de vitamina D prescrita pelo médico, para prevenir os efeitos no sistema ósseo e muscular.…”

Development of free 25-hydroxyvitamin D3 assay method using liquid chromatography-tandem mass spectrometry

“…The total and free 25(OH)D 3 levels in serum were measured for 60 subjects included in the NOR ( n =15), CKD ( n =15), HC ( n =15), and PRG ( n =15) groups since the latter three conditions are thought to be associated with vitamin D levels in plasma [ 20–22 ]. The total 25(OH)D 3 levels (median: 14.30, IQR: 10.47–19.79) were consistent with that of a previous report (median = 11.88 ng/ml, IQR: 7.68–17.68 ng/ml), in which the total 25(OH)D 3 levels were also measured using the LC-MS/MS [ 24 ].…”

“…To address these limitations, in the present study, we developed a novel method based on LC-MS/MS in combination with ultrafiltration of serum samples, to quantitate and determine free 25(OH)D 3 as a dominant free vitamin D metabolite. We also compared free and total 25(OH)D 3 levels in the serum of healthy volunteers (NOR) with that of patients with chronic kidney disease (CKD), hepatic cirrhosis (HC), and pregnant (PRG) women, as the measurement of free 25(OH)D 3 is useful in understanding the pathophysiology of these conditions [ 20–22 ].…”