title: Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients.
abstract: Tenofovir disoproxil fumarate (TDF) is an adenine analogue reverse transcription inhibitor widely used in first-line treatment of human immunodeficiency virus (HIV) infection and also in hepatitis B virus infection. Its use has been linked to sporadic Fanconi syndrome, renal failure and bone disease. We present the clinical characteristics of tenofovir-induced osteomalacia, discuss bone biopsy findings, describe predisposing factors and compare our results with other reported cases. We describe five cases of hypophosphatemic osteomalacia induced by TDF and recorded at the rheumatology service of a university hospital between 2010 and 2014. We also report the characteristics of bone biopsies of this pathology, which have not been previously described. We include a review of published cases of proximal renal tubulopathy (PRT) and osteomalacia induced by TDF (PubMed 1995-2014; keywords: osteomalacia, tenofovir, Fanconi syndrome, hypophosphatemic osteomalacia, proximal renal tubulopathy, bone biopsy). Five HIV patients who developed hypophosphatemic osteomalacia under TDF treatment (>5 years) presented increasing bone pain and a progressive inability to walk without assistance as a result of multiple insufficiency fractures. Bone biopsy performed in three patients after tetracycline labelling showed increased osteoid thickness, confirming osteomalacia. A literature review retrieved 17 publications on this condition, including 53 cases: 26 patients developed isolated PRT, 25 presented PRT and with multiple insufficiency fractures and two presented isolated bone disease, including osteomalacia and osteoporosis. Rheumatologists should be alert to this complication in patients receiving tenofovir. The main complaint reported by these patients is diffuse pain, predominantly in the lower limbs, indicating multiple stress fractures. Serum phosphate and appropriate screening for abnormal proximal tubule function should be monitored. Bone scintigraphy should be carried out in cases of limb pain before the occurrence of more severe complications.
authors.affiliation: Rheumatology Service, University Hospital Germans Trias i Pujol, Carretera del Canyet s/n, Badalona, Barcelona, 08916, Spain. 23769lms@comb.es.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Mateo
authors.affiliation: Rheumatology Service, University Hospital Germans Trias i Pujol, Carretera del Canyet s/n, Badalona, Barcelona, 08916, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Holgado
authors.affiliation: Pathology Service, Hospital del Mar, Barcelona, Spain.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mariñoso
authors.affiliation: Radiology Service, University Hospital Germans Trias i Pujol, Carretera del Canyet s/n, Badalona, Barcelona, 08916, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Pérez-Andrés
authors.affiliation: Lluita Contra la SIDA Foundation, University Hospital Germans Trias i Pujol, Carretera del Canyet s/n, Badalona, Barcelona, 08916, Spain.|Internal Medicine Department, University Hospital Germans Trias i Pujol, Carretera del Canyet s/n, Badalona, Barcelona, 08916, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Bonjoch
authors.affiliation: Internal Medicine Department, University Hospital Germans Trias i Pujol, Carretera del Canyet s/n, Badalona, Barcelona, 08916, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Romeu
authors.affiliation: Rheumatology Service, University Hospital Germans Trias i Pujol, Carretera del Canyet s/n, Badalona, Barcelona, 08916, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Olivé
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001842:Bone and Bones / Q000000981:diagnostic imaging; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D017674:Hypophosphatemia / Q000139:chemically induced* / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010018:Osteomalacia / Q000139:chemically induced* / Q000000981:diagnostic imaging; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir
keywords: Fanconi syndrome; HIV; Hypophosphatemic osteomalacia; Osteomalacia; Proximal renal tubulopathy; Tenofovir