The effect of calcium and vitamin D compounds on bone mineral density in patients undergoing glucocorticoid therapies: a network meta-analysis.

INTRODUCTION/OBJECTIVES: The objective of our systematic review and network meta-analysis (NMA) is to investigate which vitamin D and/or calcium regimen would yield the greatest increase in lumbar spine, femoral neck, and total hip bone mineral density (BMD) in adult patients undergoing glucocorticoid therapy. METHOD: We performed NMAs based on a prospectively developed protocol. A database search of MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL and Chinese databases were conducted for relevant randomized controlled trials (RCTs). Outcomes were percentage change in lumbar spine, femoral neck, and total hip BMD from baseline. RESULTS: We included 16 RCTs containing 1073 eligible patients in our analysis. We found alfacalcidol+calcium to yield the greatest percentage increase in lumbar spine BMD (MD 6.05, 95% credible interval [CrI] - 4.18 to 16.18) compared to no treatment, and calcitriol+calcium to yield the greatest percentage increase in femoral neck BMD (MD 8.46, 95% CrI - 4.74 to 21.51) compared to no treatment. Cholecalciferol+calcium ranked first in terms of its ability to increase total hip BMD; however this finding needs to be interpreted with caution due to low sample sizes in the cholecalciferol+calcium treatment arm. None of the treatment arms ruled out the possibility of no effect for any outcome. CONCLUSIONS: Alfacalcidol and calcitriol were the most efficacious treatment arms for increasing lumbar spine and femoral neck BMD, respectively. Our findings need to be validated by further investigations using larger, better-designed RCTs. Key Points •The efficacy of calcium/vitamin D compounds was examined using network meta-analyses. •Alfacalcidol + calcium yielded the greatest increase in lumbar spine BMD, calcitriol + calcium yielded the greatest increase in femoral neck BMD. •Future guidelines should place greater emphasis on the efficacy of different vitamin D compounds.

Pharmacological prevention of fractures in patients undergoing glucocorticoid therapies: a systematic review and network meta-analysis.

OBJECTIVE: To perform a network meta-analysis (NMA) on the efficacy of antiosteoporotic interventions in the prevention of vertebral and non-vertebral fractures in adult patients taking glucocorticoids (GCs). METHODS: We performed NMAs based on a prospectively developed protocol. A librarian-assisted database search of MEDLINE, EMBASE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), the Cochrane Central Register of Controlled Trials (CENTRAL) and Chinese databases was conducted for randomized controlled trials (RCTs) comparing antiosteoporotic interventions in adult patients taking GCs. Outcomes were vertebral and non-vertebral fracture incidences. RESULTS: We included 56 RCTs containing 6479 eligible patients in our analysis. We found that alendronate and teriparatide were associated with decreased odds of both vertebral and non-vertebral fractures. Denosumab and risedronate were associated with decreased odds of vertebral fractures, while etidronate, ibandronate and alfacalcidol were associated with decreased odds of non-vertebral fractures. We observed low network heterogeneity as indicated by the I2 statistic, and we did not detect evidence of publication bias. All outcomes were based on a moderate quality of evidence according to GRADE. CONCLUSION: Bisphosphonates, teriparatide and denosumab are associated with decreased odds of fracture in patients undergoing GC therapy. Vitamin D metabolites and analogues (e.g. alfacalcidol) may have greater anti-fracture efficacy compared with plain vitamin D. SYSTEMATIC REVIEW REGISTRATION: The International Prospective Register of Systematic Reviews (PROSPERO)-CRD42019127073.