Comprehensive Evaluation of the Efficacy and Safety of Different Vitamin D Combination Regimens Based on Indirect Comparisons for Children with Rickets: A Network Meta-Analysis

Why It Matters

The study demonstrates that tailored vitamin D combination therapies can achieve superior biochemical correction of rickets without added safety concerns, guiding clinicians toward more effective, individualized treatment strategies.

Key Takeaways

• Vitamin D combos raise 25‑OH D by ~15 nmol/L vs monotherapy
• BALP reduced ~28 U/L with probiotic‑enhanced regimens
• Calcium and phosphate rise without added adverse events
• Term infants show markedly greater biochemical response than preterms
• Xinjia Yupingfeng decoction leads for 25‑OH D; probiotics lead for BALP

Pulse Analysis

Vitamin D deficiency remains a leading driver of pediatric rickets worldwide, affecting up to one‑quarter of children in low‑resource regions and increasingly common in high‑income nations. While vitamin D₃ monotherapy has been the standard of care, its modest impact on bone‑turnover markers and radiographic healing has prompted clinicians to explore adjunctive agents such as calcium, zinc, probiotics, and traditional herbal extracts. These combination approaches aim to address multiple pathways—enhancing mineral availability, modulating gut microbiota, and providing bioactive compounds that may synergize with vitamin D metabolism.

The network meta‑analysis published in Frontiers in Nutrition aggregates data from ten randomized controlled trials, revealing that combination regimens consistently outperform vitamin D₃ alone across key biochemical endpoints. Serum 25‑hydroxyvitamin D rose by roughly 15 nmol/L, bone‑specific alkaline phosphatase fell by about 28 U/L, and calcium and phosphate concentrations improved without a rise in adverse events. Notably, the Xinjia Yupingfeng decoction topped the ranking for 25‑OH D elevation, while probiotic Saccharomyces boulardii achieved the highest reduction in BALP. Term infants responded more robustly than preterm peers, underscoring the influence of developmental maturity on treatment efficacy.

For practitioners, these findings endorse a shift toward individualized, goal‑oriented combination therapy—selecting calcium‑rich herbal formulas when boosting vitamin D status is paramount, or adding probiotics to target bone‑remodeling markers. However, the evidence base is still limited by small sample sizes, geographic concentration in Chinese studies, and a focus on short‑term laboratory outcomes rather than functional growth or radiographic improvement. Future large‑scale, multicenter trials should prioritize preterm populations, long‑term safety of active vitamin D analogues, and clinically meaningful endpoints to refine guidelines and ensure that the most vulnerable children receive the optimal therapeutic mix.