The effects of antiepileptic drugs on bone health: A systematic review

• Published in: Epilepsy research Vol. 173; p. 106619
• Main Authors: Griepp, Daniel W., Kim, David J., Ganz, Marc, Dolphin, Eugene J., Sotudeh, Nadia, Burekhovich, Steven A., Naziri, Qais
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2021
• Subjects: Anticonvulsants - adverse effects; Antiepileptic; Bone Density; Bone mineral density; Carbamazepine - adverse effects; Epilepsy; Epilepsy - drug therapy; Humans; Lamotrigine - pharmacology; Lamotrigine - therapeutic use; Long-term therapy; Osteopenia; Osteoporosis; NEIAEDs; VPA; Epilepsy; LS; FN; AEDs; TPM; CLZ; Osteoporosis; GBP; EIAEDs; BMD; CBZ; PHT; ESM; Osteopenia; MP; Antiepileptic; VGB; PB; DEXA; Long-term therapy; Bone mineral density; OXC; LEV; LTG
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2021.106619

•There is little compelling evidence supporting that enzyme-inducers are more harmful to bone than non-enzyme inducers.•Biochemical serum markers of bone turnover do not reliably correlate with changes in bone density.•Bone loss is less likely to be observed during initial years of antiepileptic drug therapy Epilepsy may be treated with antiepileptic drugs (AEDs), which have been reported to decrease bone mineral density (BMD). Current data is conflicting and variable, and little is known with regard to how duration of AED use or specific AEDs, such as CYP-450 enzyme-inducing (EIAEDs) versus non-enzyme inducing (NEIAEDs) drugs affect BMD. We sought to systematically review BMD changes due to AED use to identify trends in reporting. A literature search via Medline (PubMed), EMBASE, and Cochrane databases was performed. Peer-reviewed articles were identified that reported on BMD measurements in conjunction with AEDs. Twenty-six studies met inclusion criteria. Long-term therapy was shown across multiple, well-controlled studies to have the most significant BMD loss. Carbamazepine had the most frequent reporting of unfavorable effects on bone health and Lamotrigine seemed to show the most bone-protective qualities. Serum biochemical markers of bone turnover did not significantly correlate with measured BMD changes. The present study provides evidence that long-term AED therapy is the most significant risk factor for BMD loss. Furthermore, there was little compelling evidence to support that EIAEDs, as a class, were more harmful to bone than NEIAEDs, which has been previously suggested in multiple studies. Early clinical concern for significant loss of BMD may not be warranted as lower BMD was less likely to be observed during the initial years of AED therapy. Furthermore, serum markers of bone turnover are not clinically reliable in assessing BMD changes in patients taking AEDs.