Lamivudine, Entecavir, or Tenofovir Treatment of Hepatitis B Infection: Effects on Calcium, Phosphate, FGF23 and Indicators of Bone Metabolism

Ann Hepatol. 2017 March-April;16(2):207-214. doi: 10.5604/16652681.1231577.

Abstract

Background: Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern.

Objective: To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients.

Material and methods: This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA.

Results: No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF-treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture.

Conclusion: Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.

Keywords: BMD; HBV; Vitamin D; fibroblast growth factor 23; hypophosphataemia.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Bone Density / drug effects
  • Bone Remodeling / drug effects
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Calcium / blood*
  • Cross-Sectional Studies
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Fractures, Bone / chemically induced
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / adverse effects
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Phosphates / blood*
  • Risk Factors
  • Tenofovir / adverse effects
  • Tenofovir / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Vitamin D Deficiency / chemically induced

Substances

  • Antiviral Agents
  • Biomarkers
  • FGF23 protein, human
  • Phosphates
  • Lamivudine
  • entecavir
  • Guanine
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Tenofovir
  • Calcium