Anticonvulsant Osteomalacia Determined by Quantitative Analysis of Bone Changes

Abstract

Material was obtained by biopsy from the right iliac crest of 60 adult epileptic out-patients receiving chronic anticonvulsant therapy with diphenylhydantoin (DPH), either in single-drug or combined-drug regime, and of 16 controls with the same distribution by sex and age. Four (7%) of the epileptics were hypocalcemic and 25 (42%) had elevated serum alkaline phosphatase values. A quantitative analysis of the morphological bone changes was performed on decalcified and undecalcified bone, using integrating filters and the point count principle. An increased amount of unmineralized bone was found in 32 (53%) of the epileptics. The trabecular osteoclastic resorption surfaces and the mean volume of periosteocytic lacunae were increased in 36 (69%) and 45 (75%) patients, respectively. The calcification rate was decreased in relation to what is referred to elsewhere as normal. The bone changes suggest a mineralization defect analogous to osteomalacia with secondary hyperparathyroidism. An increased osteoid volume or thickness and decreased calcification rate were correlated to low dietary vitamin D intake, low exposure to sunlight, high hepatic clearance rate of DPH, combined-drug treatment and the male sex. These parameters should be considered risk factors of anticonvulsant osteomalacia.