Effects of renal tubular dysfunction on bone in tenofovir-exposed HIV-positive patients

Tenofovir disoproxil fumarate (TDF) may cause renal tubular dysfunction (RTD) and reduce bone mineral density (BMD). We examined the relationship between RTD and BMD in TDF-exposed HIV-positive men. We analysed urinary retinol-binding protein/creatinine ratio (RBPCR) and fractional excretion of phosphate (FEPO4) to quantify RTD in a cross-sectional sample of randomly selected HIV-positive men at a single tertiary outpatient clinic. BMD at the lumbar spine and hip was measured by dual-energy X-ray absorptiometry. Multivariate logistic regression was used to analyse factors associated with RTD, and linear regression to examine the relationship between RTD and BMD. Of 293 men (mean age 48 years, 94% White ethnicity, median TDF exposure 2.1 years), 22.5% had RBPCR-defined RTD and 12.3% had FEPO4-defined RTD. We observed a negative correlation between RBPCR and BMD at the spine (β -0.2, P = 0.002) and hip (total: β -0.1, P = 0.02; femoral neck: β -0.1, P = 0.02), but not between FePO4 and BMD. In multivariable analyses, RTD defined by more than five-fold elevations in RBPCR was associated with significantly lower BMD of the spine. In HIV-positive patients receiving TDF-containing antiretroviral therapy, RTD was associated with lower BMD of the spine in HIV-positive men. RBPCR quantification may identify patients at increased risk of TDF-associated BMD loss.