The Effect of Anticonvulsant Therapy on Serum Levels of 25-Hydroxy-Vitamin D, Calcium, and Parathyroid Hormone

Abstract

In 20 female patients treated for 2 to 37 years (mean :12) with anticonvulsant drugs, low serum levels of 25-hydroxy-vitamin D (25-OH-D; 6.4 +/- 3.2 ng/ml M +/- SD), relative hypocalcemia (9.2 +/- 0.4 mg/100 ml) and high levels of parathyroid hormone (PTH 277 +/- 165 pg/ml) were found compared to an age-matched control group (respectively 8.6 +/- 3.2 ng/ml, 9.6 +/- 0.3 mg/100 ml and 183 +/- 95 pg/ml) living in the same psychiatric clinic. A significant negative correlation was found between total duration of treatment and either serum 25-OH-D or serum calcium. After treatment with an oral vitamin D3 supplement (2000 IU/day) for 3 weeks, the serum 25-OH-D levels, although increased, remained lower than normal in the epileptic group and neither hypocalcemia nor their secondary hyperparathyroidism were corrected. These data confirm the occurrence of vitamin D deficiency in patients treated with anticonvulsant drugs resulting in hypocalcemia and secondary hyperparathyroidism.

Phenobarbital-induced Alterations in the Metabolism of [3H]Vitamin D3 by the Perfused Rachitic Rat Liver In Vitro

“…These decreased concentrations have been thought to be secondary to increased hepatic degradation of the 25-hydroxy metabolite to more polar by-products with resultant increased biliary excretion of the vitamin (8)(9)(10). However, using a recycling in vitro hepatic perfusion system, we have shown that phenobarbital treatment of rats for 5 (24). These results are similar to our values of 19.5 and 20.5 nM/g liver per min in phenobarbital-treated and control rachitic perfused livers, where only a loading dose was administered.…”

“…The hypocalcemia, elevated levels of circulating immunoreactive parathyroid hormone, and increased amounts ofunmineralized bone or osteoid attending anticonvulsant therapy (1)(2)(3)(4)(5)(6)(7) have been attributed to derangements in vitamin D metabolism resulting in decreased serum concentrations of 25-hydroxyvitamin D3 (2-4). These decreased concentrations have been thought to be secondary to increased hepatic degradation of the 25-hydroxy metabolite to more polar by-products with resultant increased biliary excretion of the vitamin (8)(9)(10).…”

“…Invest. C) The American Society for unmineralized bone or osteoid are frequent complications attending anticonvulsant therapy of seizure disorders in man (1)(2)(3)(4)(5)(6)(7). This disordered bone and mineral metabolism resulting from chronic phenobarbital and dilantin treatment has been attributed to decreased circulating levels of 25-hydroxyvitamin D3 (2-4) and increased metabolism of vitamin D3 to more polar degradation products by the liver (8)(9)(10).…”

Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs

“…Drugs such as CBZ, PB, PRM and DPH are known to induce hepatic mixed function oxidase activity throughout the microsomal enzymes (P450) in the liver. They are thought to affect bone and mineral metabolism indirectly by increasing the metabolism of vitamin D, thereby causing vitamin D insufficiency or deficiency 2,3,6,10 . The other mechanism of the AEDs involves a direct action on bone cells, increasing bone resorption and formation.…”

“…The most common laboratory abnormalities described in relation to AED are hypocalcaemia, hypophosphatemia, elevated levels of alkaline phosphatase (AP), reduced levels of 25-hydroxy vitamin D (25OHD) and increased serum parathyroid hormone (PTH) 3,4,10 . The chronic use of AED is a well-known cause of secondary osteoporosis 14,15 .…”