Tenofovir therapy is associated with increased urinary phosphate excretion and decreased bone mineral density in patients with chronic hepatitis B.

Abstract

Introduction: The bone disease associated with chronic liver disease is common and poorly characterised in patients with chronic viral hepatitis. Tenofovir is recommended as first line therapy for chronic hepatitis B (CHB); however, an association with increased bone loss and kidney toxicity in HIV lead us to investigate bone mineral density (BMD) and renal tubular function in hepatitis B patients. Method(s): We conducted a cross-sectional single-centre study of CHB patients treated with tenofovir compared to untreated CHB patients. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the hip and lumbar spine and expressed as a Z score (age and gender adjusted). Testosterone, oestradiol, calcium, phosphate, PTH, 25(OH)VitD and biochemical markers of bone turnover (C-telopeptide of type I collagen (CTX), N-terminal propeptide of type I collagen (P1NP)) were measured. Urine testing for phosphate, amino acid, B2-microglobulin and glucose excretion was performed. Mann Whitney U was used to compare baseline characteristics and multivariate logistic regression to adjust for cirrhosis status, age, gender and weight. Result(s): 10 untreated CHB controls and 22 patients treated with tenofovir (mean treatment duration 2.6 +/- 1.4 years) were enrolled. The mean age was 44.1 +/- 8.7 and 52% were female (11.8% post-menopausal) and 48% were male (6.2% hypogonadal). Cirrhosis was present in 16% (5 patients on tenofovir; no patients in the control group). BMD at the lumbar spine as measured by Z score was lower in the tenofovir treated group compared to controls in the univariate analysis (-1.14 +/- 1.18 vs -0.2 +/- 1.3, P = 0.02) and remained significant in the multivariate analysis (P = 0.03) after adjusting for cirrhosis, age, gender and weight. There was no significant difference in serum calcium, phosphate, P1NP, CTX, 25(OH)VitD between the tenofovir and control group. Increased duration of tenofovir use was correlated with increased urinary excretion of phosphate (r = 0.567, P = 0.034). Conclusion(s): Tenofovir is significantly associated with reduced BMD at the lumbar spine. Increased duration of tenofovir use is associated with increased urine phosphate loss through which accelerated bone loss may occur. Routine monitoring of BMD with 2 yearly DXA and and urine phosphate should be considered in CHB patients on tenofovir to screen for potential accelerated bone loss.