IMPORTANCE Despite advancements in the management of thalassemia major (TM), osteoporosis remains a significant concern among patients. However, there is a lack of quantitative network comparison between different interventions for managing osteoporosis in this population.

OBJECTIVE To compare the efficacy of different treatment options for osteoporosis in individuals with thalassemia through network meta-analysis.

DATA SOURCES PubMed/Medline, Cochrane library, and Scopus databases were searched for articles until March 2025.

STUDY SELECTION Studies evaluating interventions for osteoporosis management in individuals with thalassemia major were included.

DATA EXTRACTION AND SYNTHESIS Data extraction was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The network meta-analysis was carried out using a frequentist framework in the R programming language.

MAIN OUTCOMES AND MEASURES Bone mineral density (BMD) and changes in BMD at various skeletal sites, including the total hip/femoral neck, lumbar spine, and wrist, assessed using Z-scores and grams per cubic centimeter (g/cm).

RESULTS Thirteen studies involving a total of 942 participants and evaluating eight thalassemia induced osteoporosis treatments, were included in this network meta-analysis. Compared with control, significant improvement in BMD at Total Hip or Femoral Neck (Z-score) was observed in Zoledronic Acid [MD = 0.51; 95% CI: 0.27 to 0.75], Alendronate [MD = 0.37; 95% CI: 0.20 to 0.54], Pamidronate [MD = 0.27; 95% CI: 0.01 to 0.54], and Zinc [MD = 0.26; 95% CI: 0.09 to 0.43]. The P-score and SUCRA rankings indicated Zoledronic Acid as the most effective treatment for improving BMD at Total Hip or Femoral Neck, measured using both Z-Score and g/cm. Meanwhile, BMD at lumbar spine (Z-Score) displayed significant improvement in the Pamidronate [MD = 0.60; 95% CI: 0.38 to 0.82], Zinc [MD = 0.34; 95% CI: 0.28 to 0.40], Zoledronic Acid [MD = 0.25 95% CI: 0.08 to 0.43] and Alendronate [MD = 0.19; 95% CI: -0.10 to 0.27], compared to the control group.

CONCLUSIONS AND RELEVANCE This study unveils a spectrum of treatments for managing osteoporosis in individuals with thalassemia. It emphasizes the critical role of bisphosphonates, nutritional supplementation, and novel agents in enhancing bone health and overall quality of life for this patient population. These findings provide essential guidance for clinicians in optimizing osteoporosis management for individuals with thalassemia.

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2025
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