Bisphosphonates bone

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promote the renal tubular reabsorption of calcium and phosphate. The plasma calcium concentration rises. After a dose of D2 or D3 there is a lag of about 21 h before the intestinal effect begins and this is probably due to the time needed for its metabolic conversion to the more active forms. But with the biologically active calcitriol the lag is only 2 h.

A large single dose of vitamin D has biological effects for as long as 6 months (because of metabolism and storage). Thus the agent is cumulative and overdose by a mother anxious that her child shall have strong bones can cause serious toxicity.

Indications for vitamin D are the prevention and cure of rickets of all kinds and osteomalacia, and the symptomatic treatment of some cases of hypoparathyroidism; also psoriasis.

Calcitriol is licensed for the management of postmenopausal osteoporosis.

In osteomalacia secondary to steatorrhoea or renal disease there is defective absorption of calcium from the gut and large amounts of vitamin D are often needed to enhance absorption.

Use of vitamin D as pharmacotherapy should in general be accompanied by monitoring of plasma calcium.

Dose and preparations (1.0 microgram = 40 units). Simple vitamin D deficiency can be prevented by taking an oral supplement of only 10 micrograms (400 units) of ergocalciferol daily. Vitamin D deficiency is not uncommon in Asians consuming unleavened bread and in the elderly living alone; it can be prevented by taking an oral supplement of ergocalciferol 20 micrograms (800 units) daily. Vitamin D in deficiency caused by intestinal malabsorption or chronic liver disease usually requires vitamin D in pharmacological doses, such as ergocalciferol tablets up to 1 mg (40 000 units) daily. The maximum antirachitic effect of vitamin D is delayed for 1-2 months and the plasma calcium concentration reflects the dosage given days or weeks before. Frequent changes of dose are therefore not required.

The hypocalcaemia of hypoparathyroidism may require ergocalciferol in doses up to 2.5 mg (100 000 units) daily to achieve normocalcaemia but the dose is difficult to titrate and hypercalcaemia from overdose may take weeks to resolve. The synthetic vitamin D derivatives, alfacalcidol and calcitriol, are therefore preferred as their rapid onset and offset of action makes for easier control of plasma calcium. Supplementary calcium by mouth may also be needed.

Alfacalcidol or calcitriol, but not ergocalciferol, should be prescribed if patients with severe renal impairment require vitamin D therapy (see above).

Calcipotriol and tacalcitol are vitamin D analogues available as creams or ointments for the treatment of psoriasis (p. 313).

Symptoms of overdose are due mainly to excessive rise in plasma calcium. General effects include: malaise, drowsiness, nausea, abdominal pain, thirst, constipation and loss of appetite. Other long-term effects include ectopic calcification almost anywhere in the body, renal damage and an increased calcium output in the urine; renal calculi may be formed. It is dangerous to exceed 10 000 units daily of vitamin D in an adult for more than about 12 weeks.

Vitamin D toxicity may arise from well-meaning, but needless, administration by parents. The US Food and Drug Administration warns that intake of fortified diet supplements should not exceed 400 units a day.

Patients with sarcoidosis are intolerant of vitamin D possibly even to the tiny amount present in a normal diet, and to that synthesised in their skin by sunlight. The intolerance may be due to overproduction of calcitriol (see above) by macrophages activated by interferon; the overproduction is reversed by corticosteroid, which is also used in the treatment of severe hypervitaminosis D (see below).

Epileptic patients taking drugs that are enzyme inducers can develop osteomalacia (adults) or rickets (children). This may be due to enzyme induction increasing vitamin D metabolism and causing deficiency, or there may be inhibition of one of the hydroxylations that increase biological activity.

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