BONE-MINERAL DENSITY MEASURED BY DUAL-ENERGY X-RAY ABSORPTIOMETRY ANDNOVEL MARKERS OF BONE-FORMATION AND RESORPTION IN PATIENTS ON ANTIEPILEPTIC DRUGS

In patients on antiepileptic drugs, bone loss has been mainly demonstr ated at radial sites using old technology and has been ascribed to dru g-induced vitamin D deficiency rather than to any direct effects of th e treatment on bone cells. We examined 38 epileptic patients (24 women and 14 men) aged 20-49 Sears who were using either carbamazepine or p henytoin or both. Bone mineral density (BMD) at the lumbar spine and t hree femoral sites was measured by dual-energy x-ray absorptiometry (D XA) and serum and urine markers of bone and mineral metabolism were de termined. The latter included the C-terminal extension peptide of type I procollagen (PICP), a putative serum marker of bone formation, and the cross-linked carboxyl-terminal telopeptide of human type I collage n (ICTP), a novel serum marker of bone matrix degradation. In female p atients on phenytoin, weight- and height-adjusted BMD was reduced at t he femoral neck and the Ward's triangle (p < 0.05) but was at the cont rol level in the other patient groups at all four measurement sites. C ompared with controls, the serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were reduced by 26% (p < 0.01) and by 27% (p < 0.001) in female patients. These changes were independent of the therapy used. They were not present in male patients. For both gender s the serum levels of vitamin D binding protein were normal. Both fema le and male patients had hypocalcemia, but women only showed hypocalci uria. The serum intact parathyroid hormone was 42% higher (p < 0.01) i n women and 26% (p = 0.07) in men. The serum markers of bone formation , bone alkaline phosphatase, osteocalcin, and PICP, were higher for bo th sexes, the percentage elevations being more striking in men (104% p < 0.001; 66%, p < 0.001; and 63%; p < 0.001, respectively) than in wo men (33%, p < 0.01; 13%, p = NS; and 27%, p < 0.05, respectively). Ser um ICTP was 46% higher (p < 0.001) in women and 22% (p < 0.05) in men. We conclude that in patients on antiepileptic drugs, bone turnover is accelerated independently of the presence of hypovitaminosis D. Such biochemical alterations do not necessarily lead to reduced bone mass, however.