CASE REPORTS Fibroblast Growth Factor 23 is Elevated in Tenofovir-Related Hypophosphatemia Ramesh Saeedi • Shi Yuan Jiang • Daniel T. Holmes • David L. Kendler Received: 9 January 2014 / Accepted: 18 March 2014 / Published online: 5 April 2014 Ó Springer Science+Business Media New York 2014 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 hypo- phosphatemia, Fanconi syndrome, osteomalacia, and bilateral hip fracture. Routine serum biochemistry was assessed by standard methods. The plasma FGF23 con- centration 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 refer- ence units (RU)/mL (15 times upper limit of normal; ref- erence interval [RI] B 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. Vita- min D 3 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. Keywords HIV Á Fibroblast growth factor 23 Á Bone mineral density Á Hypophosphatemia Á Tenofovir Introduction Tenofovir disoproxil fumarate (TDF), a nucleotide reverse transcriptase inhibitor widely used for the treatment of human immunodeficiency virus (HIV) infection, has been associated with nephrotoxicity and declining bone mineral density (BMD) [1, 2]. Nephrotoxicity has been reported in 22–53 % of patients receiving TDF, including proximal renal tubular dysfunction, Fanconi-like syndrome, and renal failure [1, 2]. Proximal renal tubular abnormalities leading to urinary phosphate wasting or impairment of renal 1a-hydroxylation of vitamin D and subsequent osteomalacia have been reported in 1.6–22 % of TDF- treated subjects [3]. Fibroblast growth factor 23 (FGF23), a phosphaturic hormone secreted by osteocytes, regulates phosphate and vitamin D metabolism [4]. Persistent elevation in FGF23 leads to increased renal phosphate wasting in the proximal tubules. Also, the formation of 1,25(OH) 2 vitamin D (cal- citriol) is inhibited by suppression of renal 1a-hydroxylase activity. The paraclinical picture of FGF23 excess is The authors declare that they have no conflict of interest. R. Saeedi Á D. T. Holmes Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada S. Y. Jiang Department of Medicine, University of British Columbia, Vancouver, BC, Canada D. L. Kendler (&) Department of Medicine, Endocrinology and Metabolism, University of British Columbia, Prohealth, 150-943 W Broadway, Vancouver, BC V5Z 4E1, Canada e-mail: davidkendler@gmail.com 123 Calcif Tissue Int (2014) 94:665–668 DOI 10.1007/s00223-014-9854-7