Wednesday, November 22, 2017

Abnormal bone metabolism with tenofovir for HBV infection

March 21, 2017

Patients receiving long-term tenofovir therapy for hepatitis B virus (HBV) infection have an increased risk for abnormalities in bone metabolism, such as low serum phosphate, according to a study published in the Annals of Hepatology.1

Tenofovir, a first-line antiviral agent for HBV, is generally well-tolerated, although long-term tenofovir therapy has been linked to renal dysfunction and lower bone mineral density (BMD), which may result in hypophosphatemia and bone fractures.1

Osteocytes secrete fibroblast growth factor 23 (FGF23), a hormone that induces renal phosphate excretion. Elevated levels of FGF23 lead to renal phosphate wasting and subsequent hypophosphatemia, low serum calcitriol, and decreased bone mineralization.1 In a case report of a patient with human immunodeficiency virus (HIV) infection, tenofovir was associated with elevated FGF23 levels and phosphate wasting, which both of which normalized after tenofovir was discontinued.2

The long-term effects of tenofovir on various aspects of bone metabolism are unclear. Eric Yoshida, MD, Ramesh Saeedi, MD, PhD, and colleagues from the University of British Columbia in Vancouver, Canada, evaluated the effects of FGF23 on BMD, vitamin D metabolism, and renal phosphate handling in patients with HBV infection undergoing antiviral treatment.1

A total of 125 patients receiving tenofovir, entecavir, lamivudine, or no treatment for ≥1 year were enrolled in the study.1

Hypophosphatemia was common, occurring in nearly three-quarters of the study population. Patients treated with tenofovir accounted for the highest percentage of participants with hypophosphatemia (38.5%).1

Elevated FGF23 was observed in 4 patients (11.1%) receiving tenofovir therapy and in 1 patient (2.77%) receiving no treatment. Of these patients, however, only one in the tenofovir group had hypophosphatemia.1

In a subset of participants with abnormal serum levels of phosphate, serum calcium, or FGF23, two-thirds had insufficient levels of vitamin D, and one-third had increased urinary phosphate or calcium excretion. None of the patients with abnormal urinary excretion had high FGF23 levels. Rates of low dual-emission X-ray densitometry (DXA) Z-scores at the spine or hip were similar in all treatment groups.1

“The results of our study emphasize that patients on tenofovir should probably try to maximize the phosphorous in their diet. If they have low vitamin D levels, they probably need to go on vitamin D, such as the standard dose of 800 units per day,” Dr Yoshida said in an interview with Infectious Disease Advisor. “Clinicians need to be aware of these issues and give patients supplements as needed.”

By Crystal Wong

References

  1. Saeedi R, Mojebi-Mogharar A, Sandhu SK, et al. Lamivudine, entecavir, or tenofovir treatment of hepatitis B infection: effects on calcium, phosphate, FGF23 and indicators of bone metabolism. Ann Hepatol. 2017;16:207-214. doi:10.5604/16652681.1231577
  2. Saeedi R, Jiang SY, Holmes DT, Kendler DL. Fibroblast growth factor 23 is elevated in tenofovir-related hypophosphatemia. Calcif Tissue Int. 2014;94:665-668. doi:10.1007/s00223-014-9854-7

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