PAIN JOINTS SPINE · Jul 6, 2026
Impact of Anti-epileptic Drugs on Bone Health – A Prospective Observational Study
By Sheshi M, Konga J, Banoth P et al.
Background: Long-term antiepileptic drug (AED) therapy adversely affects bone metabolism, yet prospective comparative data from Indian adult populations remain limited. This study evaluated the differential effects of levetiracetam, phenytoin, carbamazepine, and valproate on bone mineral density (BMD), bone metabolic markers, and physical activity over six months. Methods: A prospective observational study was conducted at a tertiary care hospital in Hanamkonda, Telangana, India (January–June 2025). Of 156 patients screened, 132 were enrolled and 126 completed follow-up (levetiracetam n=46, phenytoin n=36, carbamazepine n=21, valproate n=23). DEXA was performed at baseline and six months; serum 25-hydroxyvitamin D, calcium, phosphorus, and PTH were measured at both time points. Statistical analyses included paired t-tests, one-way ANOVA with Bonferroni correction, ANCOVA (sensitivity analysis), McNemar-Bowker test, and Pearson's correlation. Results: Carbamazepine produced the most pronounced bone loss: lumbar spine T-score declined significantly (-1.88 to -2.05; Cohen's d=0.61; p=0.011) with the highest absolute osteoporosis burden (42.9% baseline, 47.6% follow-up). Phenytoin showed significant femoral neck decline (d=0.37; p=0.033) and significant rise in osteoporosis prevalence (22.2% to 38.9%; p=0.044), accompanied by falling vitamin D and rising PTH consistent with secondary hyperparathyroidism. Levetiracetam showed the smallest, non-significant changes across all parameters. Between-group ANOVA identified significant differences in Δ vitamin D (p=0.012) and Δ femoral neck T-score (p=0.035), both remaining significant after adjustment for therapy duration (p=0.019 and p=0.041, respectively). Conclusion: AED class significantly influences bone health. Enzyme-inducing AEDs, particularly carbamazepine, caused the greatest BMD loss through vitamin D depletion and secondary hyperparathyroidism. Levetiracetam demonstrated the most favourable bone safety profile. Routine DEXA monitoring and prophylactic calcium and vitamin D supplementation are recommended for patients on enzyme-inducing AED therapy.