An insight into the implications of estrogen deficiency and transforming growth factor β in antiepileptic drugs-induced bone loss.

There have been a number of reports that chronic antiepileptic drug (AEDs) therapy is associated with abnormal bone and calcium metabolism, osteoporosis/osteomalacia, and increased risk of fractures. Bony adverse effects of long term antiepileptic drug therapy have been reported for more than four decades but the exact molecular mechanism is still lacking. Several mechanisms have been proposed regarding AEDs induced bone loss; Hypovitaminosis D, hyperparathyroidism, estrogen deficiency, calcitonin deficiency. Transforming growth factor-β (TGF- β) is abundant in bone matrix and has been shown to regulate the activity of osteoblasts and osteoclasts in vitro. All isoforms of TGF- β are expressed in bone and intricately play role in bone homeostasis by modulating estrogen level. Ovariectomised animal have shown down regulation of TGF- β in bone that could also be a probable target of AEDs therapy associated bone loss. One of the widely accepted hypotheses regarding the conventional drugs induced bone loss is hypovitaminosis D which is by virtue of their microsomal enzyme inducing effect. However, despite of the lack of enzyme inducing effect of certain newer antiepileptic drugs, reduced bone mineral density with these drugs have also been reported. Thus an understanding of bone biology, pathophysiology of AEDs induced bone loss at molecular level can aid in the better management of bone loss in patients on chronic AEDs therapy. This review focuses mainly on certain new molecular targets of AEDs induced bone loss.