Osteomalacia in an HIV-infected man receiving rifabutin, a cytochrome P450 enzyme inducer: a case report

Mark J Bolland¹ , Andrew Grey¹ , Anne M Horne¹ and Mark G Thomas²

¹Department of Medicine, University of Auckland, Private Bag 92 019, Auckland 1020, New Zealand

²Department of Infectious Diseases, Auckland City Hospital, and Department of Molecular Medicine and Pathology, University of Auckland, Private Bag 92 019, Auckland 1020, New Zealand

author email corresponding author email

Annals of Clinical Microbiology and Antimicrobials 2008, 7:3doi:10.1186/1476-0711-7-3


Published:	28 January 2008

Abstract

Introduction

People infected with human immunodeficiency virus are frequently treated with medications that can induce or inhibit cytochrome P450 enzymes.

Case presentation

A 59 year old man treated with zidovudine, lamivudine, indinavir, and ritonavir for infection with human immunodeficiency virus volunteered to take part in a study of bone loss. He was found to have vitamin D insufficiency with secondary hyperparathyroidism and received vitamin D and calcium supplementation. He suffered a recurrence of infection with Mycobacterium avium intracellulare for which he received treatment with ciprofloxacin, rifabutin, and ethambutol. Subsequently, he developed worsening vitamin D deficiency with hypocalcaemia, secondary hyperparathyroidism and elevated markers of bone turnover culminating in an osteomalacic vertebral fracture. Correction of the vitamin D deficiency required 100,000 IU of cholecalciferol monthly.

Rifabutin is a cytochrome P450 inducer, and vitamin D and its metabolites are catabolised by cytochrome P450 enzymes. We therefore propose that treatment with rifabutin led to the induction of cytochrome P450 enzymes catabolising vitamin D, thereby causing vitamin D deficiency and osteomalacia. This process might be mediated through the steroid and xenobiotic receptor (SXR).

Conclusion

Treatment with rifabutin induces the cytochrome P450 enzymes that metabolise vitamin D and patients treated with rifabutin might be at increased risk of vitamin D deficiency. In complex medication regimens involving agents that induce or inhibit cytochrome P450 enzmyes, consultation with a clinical pharmacist or pharmacologist may be helpful in predicting and/or preventing potentially harmful interactions.