Bone mineral density measured by dual-energy X-ray absorptiometry and novel markers of bone formation and resorption in patients on antiepileptic drugs

Abstract

In patients on antiepileptic drugs, bone loss has been mainly demonstrated at radial sites using old technology and has been ascribed to drug-induced vitamin D deficiency rather than to any direct effects of the treatment on bone cells. We examined 38 epileptic patients (24 women and 14 men) aged 20–49 years who were using either carbamazepine or phenytoin or both. Bone mineral density (BMD) at the lumbar spine and three femoral sites was measured by dual-energy x-ray absorptiometry (DXA) and serum and urine markers of bone and mineral metabolism were determined. 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 collagen (ICTP), a novel serum marker of bone matrix degradation. In female patients on phenytoin, weight- and height-adjusted BMD was reduced at the femoral neck and the Ward's triangle (p < 0.05) but was at the control level in the other patient groups at all four measurement sites. Compared 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 genders the serum levels of vitamin D binding protein were normal. Both female and male patients had hypocalcemia, but women only showed hypocalciuria. The serum intact parathyroid hormone was 42% higher (p < 0.01) in women and 26% (p = 0.07) in men. The serum markers of bone formation, bone alkaline phosphatase, osteocalcin, and PICP, were higher for both 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 women (33%, p < 0.01; 13%, p = NS; and 27%, p < 0.05, respectively). Serum 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.