What the Research Shows: Bone Health

Long term use of anticonvulsant drugs — which is the way most people must take them, since they are prescribed to treat chronic conditions — has been linked to thinning of the bones (osteopenia) and brittle bones (osteoporosis). The culprit appears to be the effect of the medication on bone metabolism and increased bone turnover (the rate at which bones replace the minerals that give them strength). This finding has special significance for women who, after menopause, are typically at increased risk for bone loss and osteoporosis. Reduced height has also been reported in women who took anticonvulsants during childhood.

Several drugs have been implicated in bone loss. Phenytoin, phenobarbital, and primidone appear to have the most impact on reducing bone density and increasing bone turnover. Carbamazepine and valproate have been associated with lower concentrations of serum calcium, a key factor in bone health. For the newer anticonvulsant drugs, less is known about their effects on bone health as they have often been studied in patients on polytherapy with the older drugs or in small numbers of patients on monotherapy. Lamotrigine has not been linked to similar markers for risks to bone health. Actetazolamide, a potent carbonic anhydrase inhibitor, has been associated with bone loss in some older studies. Zonisamide, a partial carbonic anhydrase inhibitor, has been cited in a case report in a patient with multiple fractures. Since zonisamide and topiramate are both partial carbonic anhydrase inhibitors, caution would indicate that prophylaxis against bone loss should be advocated for patients on these as well as the other new anticonvulsant drugs until firm long-term bone health data is available.