Unfavorable Polygenic Risk Score in HIV Increases Risk for Osteoporosis

Osteoporosis is independently associated with bone mineral density (BMD)-associated polygenic risk score (PRS) among patients with HIV infection, according to results of a study published in The Journal of Infectious Diseases.

Researchers conducted a study among patients of European descent who were included in the Swiss HIV Cohort Study. Patients included in the analysis each had at least 2 per-protocol dual x-ray absorptiometry measurements, obtained at least 2 years apart. The researchers aimed to investigate whether an individual BMD-associated PRS was independently associated with osteoporosis risk among patients with HIV infection. Univariable and multivariable odds ratios (ORs) for the occurrence of DXA-defined osteoporosis were determined using traditional and HIV-related osteoporosis risk factors, as well as a genome-wide PRS made from 9413 single-nucleotide polymorphisms.

Clinical risk factors for osteoporosis included age, sex, menopausal status, smoking status, BMI, physical activity, HIV acquisition, injection drug use, diabetes history, hepatitis C virus (HCV) positivity, alcohol use, and parental history of hip fracture.

A total of 438 patients were included in the analysis, of whom 149 had osteoporosis and 289 had no history of osteoporosis (controls). Overall, the median patient age was 53 years, 82% were men, and 95% had virologically-suppressed HIV infection.

In the univariable analysis, the probability of osteoporosis was significantly associated with genetically predicted heel quantitative ultrasound speed of sound polygenic risk score (gSOS-PRS; P <.001) and combined clinical risk factors (P <.001). However, no significant associations were observed for parental history of hip fracture or longevity-PRS.

In the multivariable analysis, participants in the second, third, fourth, and fifth quintiles of gSOS-PRS were at increased risk for osteoporosis (ORs, 2.53, 2.88, 2.70, and 4.13, respectively). The analysis also showed that the occurrence of osteoporosis remained significantly associated with combined clinical risk factors. The likelihood of osteoporosis was linked with prolonged tenofovir disoproxil fumarate exposure (OR per 5 years, 1.65; 95% CI, 1.20-2.29), but not with extended boosted protease inhibitors exposure (OR per 5 years, 1.18, 95% CI, 0.92-1.50) or HCV seropositivity (OR, 0.98; 95% CI, 0.44-2.15).

This study was limited as only patients of European descent were included. Other limitations include the small sample size, the predominance of younger men, and the inability to assess potentially osteoporosis-related non-antiretroviral medication.

According to the researchers, “Knowledge of an unfavorable osteoporosis-PRS may provide an early opportunity to obtain DXA and suggest to HIV clinicians to pay even greater attention to the management of clinical risk factors…”

This article originally appeared on Infectious Disease Advisor