Vitamin D metabolism

Primary hyperparathyroidism occurs as a result of hyperplasia or the occurrence of adenoma. Secondary hyperparathyroidism may result from renal failure because of the associated phosphate retention, resistance to the metabolic actions of PTH, or impaired vitamin D metabolism. The last-mentioned factor is primarily responsible for the development of osteomalacia. Muscle symptoms are much more common in patients with osteomalacia than in primary hyperparathyroidism. Muscle biopsy has revealed disseminated atrophy, sometimes confined to type 2 fibers, but in other cases involving both fiber types. Clinical features of osteomalacic myopathy are proximal limb weakness and associated bone pain the condition responds well to treatment with vitamin D. 

Vitamin D Metabolism Both Regulates Is Regulated by Calcium Homeostasis... 

The main function of vitamin D is in the control of calcium homeostasis, and in mrn vitamin D metabolism is... 

NS (chronic) (general population) Other No effect on vitamin D metabolism in children 5-24 (levels measured) Koo et al. 1991... 

Effects on Vitamin D Metabolism. Lead interferes with the conversion of vitamin D to its hormonal form, 1,25-dihydroxyvitamin D. This conversion takes place via hydroxylation to 25-hydroxyvitamin D in the liver followed by 1-hydroxylation in the mitochondria of the renal tubule by a complex cytochrome P-450 system (Mahaffey et al. 1982 Rosen and Chesney 1983). Evidence for this effect comes primarily from studies of children with high lead exposure. 

However, results obtained by Koo et al. (1991) indicate that low to moderate lead exposure (average lifetime PbB level range of 4.9-23.6 pg/dL, geometric mean of 9.8 pg/dL, n=105) in young children with adequate nutritional status, particularly with respect to calcium, phosphorus, and vitamin D, has no effect on vitamin D metabolism, calcium and phosphorus homeostasis, or bone mineral content. The authors attribute the difference in results from those other studies to the fact that the children in their study had lower PbB levels (only 5 children had PbB levels >60 pg/dL and all 105 children had average lifetime PbB levels <45 pg/dL at the time of assessment) and had adequate dietary intakes of calcium, phosphorus, and vitamin D. They concluded that the effects of lead on vitamin D metabolism observed in previous studies may, therefore, only be apparent in children with chronic nutritional deficiency and chronically elevated PbB levels. Similar conclusions were reached by IPCS (1995) after review of the epidemiological data. 

The possible mechanism kidney-induced hypertension is discussed in Section 2.4.2, Mechanisms of Toxicity. Lead appears to affect vitamin D metabolism in renal tubule cells, such that circulating levels of the vitamin D hormone, 1,25-dihydroxyvitamin D, are reduced. This effect is discussed later in this section under Other Systemic Effects. 

It is possible that lead s interference with heme synthesis may underlie the effects on vitamin D metabolism. Evidence that lead affects heme synthesis in the kidney was presented in the section on hematological effects. In addition, apparent thresholds for the effects of lead on renal vitamin D metabolism and for erythrocyte protoporphyrin accumulation are similar. 

Acute-Duration Exposure. There are few data available for acute exposures in humans. This may be a function of the time required for the expression of effects (decreased heme synthesis, neurobehavioral changes, increased blood pressure, and interference with vitamin D metabolism) and the usual modes of exposure in humans, which are repeated ingestion of lead-containing dirt or lead-based paint chips in... 

Might antagonize verapamil Might induce hypercalcemia with thiazide diuretics Fiber laxatives (variable), oxalates, phytates, and sulfates can decrease calcium absorption if given concomitantiy Phenytoin, barbiturates, carbamazepine, rifampin increase vitamin D metabolism... 

Phenytoin, carbamazepine, phenobarbital, oxcarbazepine, and valproic acid may interfere with vitamin D metabolism, causing asymptomatic high-turnover bone disease with normal bone density or decreased bone mineral... 

Enzyme induction properties Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D. Rifampin and isoniazid have been reported to alter vitamin D metabolism. In some cases, reduced levels of circulating 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D have been accompanied by reduced serum calcium and phosphate, and elevated parathyroid hormone. 

Spontaneous reports of osteoporosis, osteopenia, bone fractures, and delayed healing of bone fractures have been seen in the isotretinoin population. While causality to isotretinoin has not been established, an effect cannot be ruled out. Physicians should use caution when prescribing isotretinoin to patients with a genetic predisposition for age-related osteoporosis, a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism. This would include patients diagnosed with anorexia nervosa and those who are on chronic drug therapy that causes drug-induced osteoporosis/osteomalacia and/or affects vitamin D metabolism, such as systemic corticosteroids and any anticonvulsants. 

Blood dyscrasias, lymphadenopathy, and osteomalacia, caused by interference of vitamin D metabolism, may occur... 

Patients with nephrotic syndrome can lose vitamin D metabolites in the urine, presumably by loss of the vitamin D-binding protein. Such patients may have very low 25(OH)D levels. Some of them develop bone disease. It is not yet clear what value vitamin D therapy has in such patients, because therapeutic trials with vitamin D (or any other vitamin D metabolite) have not yet been carried out. Because the problem is not related to vitamin D metabolism, one would not anticipate any advantage in using the more expensive vitamin D metabolites in place of vitamin D itself. 

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