Fibroblast growth factor 23 is elevated in tenofovir-related hypophosphatemia.
In human immunodeficiency virus (HIV)-infected patients, tenofovir disoproxil fumarate (TDF) may cause hypophosphatemia leading to osteomalacia due to renal phosphate wasting. Fibroblast growth factor 23 (FGF23) may play a role in this setting. We present an HIV-infected patient with TDF-induced profound hypophosphatemia, Fanconi syndrome, osteomalacia, and bilateral hip fracture. Routine serum biochemistry was assessed by standard methods. The plasma FGF23 concentration was measured at Mayo Laboratories (Scottsdale, AZ, USA). Bone mineral density (BMD) was measured using a Hologic Discovery densitometer. At presentation, the patient's plasma C-terminal FGF23 was 2,760 reference units (RU)/mL (15 times upper limit of normal; reference interval [RI] ≤ 180 RU/mL), serum phosphate was 0.58 (RI 0.8-1.6 mmol/L), and TmPO4/GFR was 95%. DXA at the lumbar spine showed a Z score of -4.0. Vitamin D3 and oral phosphate were administered, and TDF was discontinued. After 4 months off TDF, lumbar spine BMD significantly increased by 12% (Z score -3.5); by 6 months the plasma C-terminal FGF23 declined to 1.8 times the upper limit of normal, and both urine and serum phosphate levels normalized. By its marked elevation and subsequent near normalization, FGF23 may be responsible for a component of the phosphate wasting syndrome in these patients. The time course of resolution was 6 months. As expected, with calcium, vitamin D, and phosphate management, BMD significantly improved with resolution of osteomalacia. Clinicians should be aware of this side effect of TDF and the time course of its resolution.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Ramesh
R
Saeedi
Shi Yuan
SY
Jiang
Daniel T
DT
Holmes
David L
DL
Kendler
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D015519:Bone Density; D005198:Fanconi Syndrome / Q000139:chemically induced; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D017674:Hypophosphatemia / Q000139:chemically induced* / Q000150:complications; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects*; D010018:Osteomalacia / Q000139:chemically induced; D010024:Osteoporosis / Q000097:blood* / Q000209:etiology; D000068698:Tenofovir
D019380:Anti-HIV Agents; C000717427:FGF23 protein, human; D063065:Organophosphonates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000068698:Tenofovir; D000225:Adenine