Effect of theophylline on calcium metabolism and circulating vitamin D metabolites

Theophylline has been shown to induce the hepatic microsomal enzyme system. These same enzymes increase the metabolism of vitamin D and 25-hydroxyvitamin D when induced by chronic barbiturate or phenytoin administration. To assess the long-term effects of theophylline on vitamin D and calcium metabolism, young rats were treated for 4 weeks with constant subcutaneous theophylline infusions. Theophylline-treated animals had a significantly increased urinary calcium excretion (p less than 0.0001), a significantly decreased total body calcium per gram body weight (p less than 0.05), and significantly decreased serum 25-hydroxy-vitamin D concentrations (p less than 0.002) when compared to control animals. These alterations in the concentration of 25-hydroxyvitamin D may impair the ability to increase 1,25-dihydroxyvitamin D-dependent intestinal calcium absorption to compensate for excessive urinary calcium losses. These data suggest that theophylline promotes skeletal calcium loss, and its use may be a risk factor for the development of osteopenia in humans.