Abstract
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.
Reference
Hall AM (2013) Update on tenofovir toxicity in the kidney. Pediatr Nephrol 28(7):1011–1123
Woodward CL, Hall AM, Williams IG, Madge S, Copas A, Nair D, Edwards SG, Johnson MA, Connolly JO (2009) Tenofovir-associated renal and bone toxicity. HIV Med 10(8):482–487
Wanner DP, Tyndall A, Walker UA (2009) Tenofovir-induced osteomalacia. Clin Exp Rheumatol 27:1001–1003
Ramon I, Kleynen P, Body JJ, Karmali R (2010) Fibroblast growth factor 23 and its role in phosphate homeostasis. Eur J Endocrinol 162:1–10
Quarles L (2008) Endocrine functions of bone in mineral metabolism regulation. J Clin Invest 118:3820–3828
Walton RJ, Bijvoet OLM (1975) Nomogram for derivation of renal threshold phosphate concentration. Lancet 306(7929):309–310
Norden AG, Lapsley M, Lee PJ, Pusey CD, Scheinman SJ, Tam FW, Thakker RV, Unwin RJ, Wrong O (2001) Glomerular protein sieving and implications for renal failure in Fanconi syndrome. Kidney Int 60(5):1885–1892
Hall AM, Hendry BM, Nitsch D, Connolly JO (2011) Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis 57:773–780
Earle KE, Seneviratne T, Shaker J, Shoback D (2004) Fanconi’s syndrome in HIV+ adults: report of three cases and literature review. J Bone Miner Res 19:714–721
Rebolledo BJ, Unnanuntana A, Lane JM (2011) Bilateral pathologic hip fractures associated with antiretroviral therapy: a case report. J Bone Joint Surg Am 93(14):e78
Saidenberg-Kermanac’h Souabnib L, Prendkic V, Prie D, Boissier MC (2011) Normal plasma FGF23 levels kinetic in tenofovir-related hypophosphatemic osteomalacia in an HIV-infected patient with von Recklinghausen disease. Joint Bone Spine 78(3):306–308
Haverkort M, Van Der Serk BW, Lips P, Slieker WA, ter Heine R, Huitema AD, Bronsveld W (2011) Tenofovir-induced Fanconi syndrome and osteomalacia in two HIV-infected patients: role of intracellular tenofovir diphosphate levels and review of the literature. Scand J Infect Dis 43(10):821–826
Bech A, Van Bentum P, Nabbe K, Gisolf J, Richter C, De Boer H (2012) Fibroblast growth factor 23 in hypophosphataemic HIV-positive adults on tenofovir. HIV Med 13(9):558–563
Liao E (2013) FGF23 associated bone diseases. Front Med 7(1):65–80
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Saeedi, R., Jiang, S.Y., Holmes, D.T. et al. Fibroblast Growth Factor 23 is Elevated in Tenofovir-Related Hypophosphatemia. Calcif Tissue Int 94, 665–668 (2014). https://doi.org/10.1007/s00223-014-9854-7
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DOI: https://doi.org/10.1007/s00223-014-9854-7