Drugs for Disorders of Bone: Pharmacological and Clinical Considerations

Gregory R. Mundy, Lawrence G. Raisz

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

The drug therapy of disorders of mineral metabolism has been a neglected field, partly because of a lack of understanding of the pathophysiology of metabolic bone disease. With the recent advances in knowledge of the physiological regulation of calcium metabolism and of the factors influencing bone resorption and bone formation, a number of new drugs are being developed for these disorders. The three major hormones that regulate calcium metabolism — parathyroid hormone, the active forms of vitamin D, and calcitonin — may all be used as therapeutic agents. In Paget’s disease of bone, calcitonin has been found effective and remarkably non-toxic. Calcitonin has been less useful in hypercalcaemia and ineffective in osteoporosis. The clinical use of parathyroid hormone preparations and active vitamin D metabolites is limited at present, but synthetic, biologically active parathyroid hormone fragments and active vitamin D metabolites have considerable potential as therapeutic agents. Steroid hormones are widely used in metabolic bone disease. Glucocorticosteroids are useful in some forms of hypercalcaemia, but the efficacy of sex hormones in osteoporosis has not been established, despite 30 years of use. Mithramycin is an antitumour antibiotic that inhibits DNA-directed RNA synthesis and causes a reduction in serum calcium in both normocalcaemic and hypercalcaemic patients. It is a toxic drug and is probably overused at present. Phosphate therapy is effective in hypercalcaemia, nephrolithiasis, and some phosphatelosing renal tubular disorders. Diphosphonates, which are pyrophosphate analogues, may be useful in the therapy of Paget’s disease, but their mode of action is unclear. Although fluoride may increase bone mass in osteoporosis, its efficacy has not been established. Similarly, calcium infusions, which in early studies seemed promising, are now considered of doubtful benefit in the treatment of osteoporosis. Nevertheless, patients with osteoporosis should receive an adequate intake of calcium, as well as vitamin D. The diuretics have differing effects on calcium metabolism which vary with their site of action on the renal tubules. Frusemide and ethacrynic acid, which produce hypercalciuria and a fall in serum calcium, are useful drugs in the emergency treatment of hypercalcaemia. The thiazide diuretics, on the other hand, lead to hypocalciuria and may potentiate hypercalcaemia in some patients, but they are effective drugs in idiopathic hypercalciuria.

Original languageEnglish (US)
Pages (from-to)250-289
Number of pages40
JournalDrugs
Volume8
Issue number4
DOIs
StatePublished - Oct 1974
Externally publishedYes

Keywords

  • Bone disease, metabolic: pharmacology
  • Bone disease, metabolic: treatment
  • Calcium metabolism: pharmacology
  • Hypercalcaemia
  • Hypercalciuria
  • Osteomalacia
  • Osteoporosis
  • Paget’s disease of bone

ASJC Scopus subject areas

  • Pharmacology (medical)

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