Hypophosphataemic osteomalacia in patients on adefovir dipivoxil

Fanconi syndrome results from generalised renal tubular toxicity and, owing to phosphate wasting can cause hypophosphataemic osteomalacia. Large clinical trials advocated the safety of adefovir dipivoxil at a daily dose of 10 mg, the standard dose given to patients with hepatitis B. We diagnosed Fanconi syndrome in conjunction with severe osteomalacia in 2 hepatitis B-positive patients on standard-dose adefovir therapy. The first patient was a 40-year-old male with a 5 month history of bone pain involving his knees, ankles, and ribs. He had been receiving adefovir dipivoxil for 27 months before the development of hypophosphataemia, urinary phosphate wasting, and aminoaciduria. These abnormalities resolved within weeks of discontinuation of adefovir dipivoxil and supplementation with elemental phosphate, calcium carbonate, and cholecalciferol. The second patient was a 53-year-old female with a 6 month history of lethargy, cachexia, and generalized bone pain. She had been receiving adefovir for 64 months before the development of these symptoms. She had hypophosphataemia, hypocalcaemia, metabolic acidosis, and severe vitamin D deficiency, but initially no urinary phosphate wasting. Four months of high-dose cholecalciferol supplementation unmasked her Fanconi syndrome including significant urinary phosphate wasting. The patient improved within weeks of discontinuation of adefovir and supplementation with elemental phosphate, calcium carbonate, and calcitriol. Despite large clinical trials advocating the safety of adefovir dipivoxil at 10-mg daily, long-term use of this agent may be nephrotoxic and in rare cases, cause Fanconi syndrome and severe hypophosphataemic osteomalacia. Clinicians prescribing this drug should be aware of this potential complication.