Proteinuria Is Associated With Increased Risk of Fragility Fracture in Men With or at Risk of HIV Infection

Abstract

Background: Proteinuria has been associated with bone loss and fractures in general population but data in HIV-infected population is lacking. Setting: Prospective, multicenter cohort study of men with or at risk for HIV infection. Methods: Between 2006 and 2015, urine protein measurements and bone fracture histories were ascertained semi-annually in 947 HIV-infected (HIV+) and 969 HIV-uninfected (HIV-) men ≥ age 40. Proteinuria was defined as protein-to-creatinine ratio ≥ 200 mg/g at ≥ 2 consecutive visits. Outcome measures: 1) all fractures (excluding fractures of skull, face, digits) 2) fragility fractures (fractures of vertebral column, femur, wrist, humerus). Multivariable Cox proportional hazards models assessed the association between proteinuria and fracture after adjusting for additional risk factors. Results: The overall period prevalence of proteinuria was higher among HIV+ than HIV-(29% vs 6%, p<0.001). Men with proteinuria had a significantly higher risk of fragility fracture compared to men without proteinuria (aHR=2.29 [1.12-4.66]), and did not differ by HIVserostatus (p-interaction=0.83). The risk of all fractures was not statistically different between men with or without proteinuria (aHR=1.31 [0.84-2.05]). Among HIV+ men, the association between confirmed proteinuria and fragility fracture was attenuated (aHR=2.12 [0.95-4.73]) after additional adjustment for CD4 + T cell count/mm 3 , history of AIDS, the presence of detectable plasma HIV-1 RNA, and cumulative exposure to tenofovir disoproxil fumarate.

What's new in bone disease and fractures in HIV?

“…The Multicentre AIDS Cohort Study (MACS), a prospective cohort study of men with and without HIV, has explored associations between frailty, fractures and biomarkers related to bone and renal function. An analysis of 947 PWH and 969 subjects without HIV revealed associations between higher urine protein/creatinine ratio (>200 mg/L), a marker of renal tubular function, and fragility fracture (OR 2.29 (95% CI 1.12, 4.66) [20]. Another marker of interest is fibroblast growth factor 23 (FGF23), a bone-derived factor that is a key modifier of the axis linking renal and bone metabolism.…”

Changing trends in lipid profile and biomarkers of renal function and bone metabolism before and after switching from tenofovir disoproxil fumarate to tenofovir alafenamide: a prospective observational study

“…Because the patients in our study were not older age and have already acquired high CD4 + T-cell counts by treatment including TDF on enrollment, major reason of the improvement of proteinuria might be discontinuation of TDF exposure. As Proteinuria itself is one of risk factors for CKD [ 19 ] and fragility fracture [ 17 ] in HIV-infected patients, early detection of proteinuria could motivate switching ARVs.…”

Risk of Fractures in Older Adults Living with HIV

“…Some of the drugs that are used such as Efavirenz are related to a decrease of the 25-hydroxyvitamin D; Tenofovir is associated to secondary hyperparathyroidism, leading to an elevated bone turnover [21]; keeping in mind that these are fi rst line drugs, this creates a complicated outlook on the early management of infected patients. The side eff ects of some of the antiretroviral therapy, as protease inhibitors, and the main pathogenesis of the illness, cause kidney failure that is associated with proteinuria, leading to a low bone mineral density and elevated risk of fracture [22].…”