The effect of pulse steroid therapy on bone density and turnover: A systematic review and meta-analysis

Chronic exposure to glucocorticoids (GC) is a leading cause of secondary osteoporosis and fractures. While the skeletal effects of long-term oral GC are wellestablished, the bone effects of intermittent high-dose intravenous pulse methylprednisolone therapy remain less clearly defined. This study aimed to evaluate its impact on skeletal health in adults not receiving antiosteoporosis treatment.

This meta-analysis was conducted according to PRISMA guidelines and prospectively registered. PubMed, Scopus, Embase, and Google Scholar were searched up to September 2025. Studies included longitudinal cohort and case-control studies with appropriate comparators and randomised controlled trials reporting pre- and post-intravenous methylprednisolone bone outcomes.

Eight studies (n=192, 72% females) were included. Pulse intravenous methylprednisolone did not significantly reduce bone mineral density (BMD) at the lumbar spine (mean difference [MD] 0.01 g/cm2; 95% confidence interval [CI] -0.02 to 0.03), femoral neck (MD -0.01 g/cm2; 95% CI -0.03 to 0.01), or total hip (MD -0.03 g/cm2; 95% CI -0.06 to 0.01) over a mean followup period of 5.5 months. Trabecular bone score showed no significant pooled change (MD -0.01 g/cm2). In contrast, procollagen type-1 N-terminal propeptide (MD -36.95 ng/mL; 95% CI -56.86 to -17.03) and C-terminal telopeptide (MD -0.19 ng/dL; 95% CI -0.32 to -0.07) significantly decreased. Serum 25-hydroxyvitamin D increased modestly, while serum calcium and parathyroid hormone remained unchanged.

Pulse intravenous methylprednisolone does not cause short-term BMD loss, though it is associated with measurable suppression of bone turnover markers. Larger controlled studies with standardised sampling, peripheral site assessment, and fracture outcomes are needed to determine long-term skeletal risk from pulse regimens.