Phenobarbital osteomalacia with

Long-term anticonvulsive therapy with diphenylhydantoin or phenobarbital is known to cause osteomalacia by influencing calcium metabolism (24,25). Alteration in the metabolism of vitamin D, presumably secondary to induction of hepatic microsomal enzymes, leads to the calcium and bone abnormalities (26). Patients on anticonvulsive therapy with phenytoin exhibit a decrease in serum 25-hydroxyvitamin D (27). Adequate dietary amounts of vitamin precursors or microsomal enzyme stimulators might prevent these effects of long-term therapy. 

In addition to the classical environmental or nutritional cause of these diseases, both osteomalacia and rickets can have a pharmacological origin via chronic treatment with anticonvulsants (phenobarbital and phenytoin) or glucocorticoids. These agents interfere with intestinal absorption of calcium and, thereby, cause pseudohyperparathyroidism. As a result, an increase in bone turnover and a decrease in the formation of appropriately mineralized bone is observed. In these patients, treatment with vitamin D improves calcium absorption, ultimately enhancing mineralization of the bone. 

Severe osteomalacia and rickets have been seen in a few patients taking phenytoin, phenobarbital, or primidone with acetazola-mide. A marked reduction in serum primidone levels with a loss in seizure controi, rises in serum carbamazepine levels with toxicity, and rises in phenytoin levels have also been described in a veiy small number of patients given acetazolamide. 

Severe osteomalacia developed in 2 women taking phenytoin or primidone and phenobarbital when they were given acetazolamide 750 mg daily, despite a normal intake of calcium. When the acetazolamide was withdrawn, the hyperchloraemic acidosis that had been seen in both patients abated and their high urinary excretion of calcium fell by 50%. Similar cases have been described in 3 children given acetazolamide, phenytoin and primidone, with phenobarbital and/or metharbital, who developed rickets. 

Other reports describe patients whose response to usual doses of vitamin D was poor, because of concurrent anticonvulsant treatment with pheny-toin and phenobarbital or primidone. " Other reports clearly show low serum calcium levels,low serum vitamin D levels, osteomalacia, and bone structure alterations in the presence of phenytoin. 

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