Antiepileptic Drugs
Certain anticonvulsants may cause bone loss.7 The medications most commonly associated with osteoporosis include phenytoin, phenobarbital, carbamazepine, and primidone. 3,7,8 These antiepileptic drugs (AEDs) are all potent inducers of CYP-450 isoenzymes. In one study of community-dwelling elderly women, bone loss nearly doubled in those receiving AEDs, compared to the general population.8
There are several known and proposed mechanisms for bone loss with AEDs. As mentioned previously, all of these medications induce hepatic CYP-450 enzymes, leading to rapid metabolism of vitamin D, and possibly, estrogen. AEDs are also associated with decreased fractional calcium absorption, secondary hyperparathyroidism, and increased bone turnover. 3,7,8 At therapeutic levels, phenytoin and carbamazepine have exhibited direct effects on the bone by inhibiting osteoblast cells.8 A mechanism that may be solely linked to phenytoin is the inhibition of osteocalcin secretion--a hormone that regulates calcium in the bone.7 AEDs may exhibit any combination of these effects, and the impact on bone loss can be additive if a combination regimen is used.
To combat the loss of bone mass associated with traditional AEDs, it may be advisable to use a newer AED with a lower incidence of hepatic induction.3 Long-term studies still need to be conducted to evaluate if the newer agents cause bone loss, but to date, results appear promising. Supplementation with vitamin D and calcium is essential for the prevention of bone loss in patients who may be stabilized on an older medication. Preventive doses of at least 400 international units (IU) of vitamin D and 1,000 to 1,500 mg of calcium are recommended for those at risk.3,7