Agents That Impair Absorption of Vitamin D
Older Anticonvulsants: Older anticonvulsants, such as carbamazepine, phenobarbital and phenytoin, have been associated with drug-induced osteomalcia.It has been postulated that these agents increase the degradation of 25(OH)D3, the predominant circulating metabolite. However, many early studies were confounded because they were conducted on institutionalized patients who were predisposed to other risk factors, such as poor dietary vitamin D intake and/or reduced exposure to sunlight. Tolman and colleagues reported a positive correlation between the incidence of osteomalacia and the duration of anticonvulsant therapy; they documented the development of bone disease in over 75% of patients receiving anticonvulsant therapy for periods greater than 10 years. Hahn, et al. also reported that phenytoin reduced calcium absorption by directly inhibiting intestinal transport.
Chronic Laxative Use: Laxative abuse has also been implicated in compromised bone status. The overuse of cathartics has been associated with malabsorption of vitamin D and calcium. Use of irritant laxatives such as phenolphthalein and bisacodyl may damage the structural integrity of the intestinal mucosa and cause impaired colonic reabsorption, steatorrhea, and malabsorption of vitamin D and calcium. Orally ingested mineral oil can coat ingested food particles along with the surface of the intestines. It forms a mechanical barrier to the digestion and absorption of nutrients. Mineral oil also increases gastric motility, which reduces the time required to adequately absorb ingested nutrients. Moreover, studies have shown that mineral oil — especially if taken at mealtime or during the postprandial absorptive period, when nutrients are absorbed — can prevent the absorption of vitamin D.
Other Agents: Other agents that impair the absorption of vitamin D and have shown documented increased risk of deficiency include the absorbable and nonabsorbable types of hypo-lipidemic drugs. Similarly, cholestyramine, an anion-exchange resin, has been found to bind bile salts and interfere with the bioavailability of numerous fat-soluble nutrients, including vitamin D. Knodel and colleagues associated large doses of cholestyramine (>32 g/day) with the malabsorption of fat-soluble vitamins. They also observed cholestyramine-induced osteomalacia resulting from impaired absorption of vitamin D.
Agents That Cause Secondary Impairment of Vitamin D
Isoniazid/cimetidine: Medications that inhibit the hepatic and/or renal hydroxylation of vitamin D subject patients to increased development of bone disease due to the secondary impairment of calcium absorption. For example, drugs such as isoniazid and cimetidine inhibit the hepatic and renal hydroxylation of vitamin D. This results in a functional vitamin D deficiency — with a secondary impairment of calcium absorption. Odes, et al. concluded that even short-term therapy with cimetidine altered vitamin D metabolism in humans. The researchers concluded this after monitoring levels of 25(OH)D3 for 30 days in patients receiving treatment. Calcium channel blockers such as verapamil can also have a negative impact on vitamin D levels by decreasing its hydroxylation in the body.In addition, medications that promote the catabolism of vitamin D metabolites, such as phenytoin and phenobarbital, have the same effects.