Association of a Polygenic Risk Score With Osteoporosis in People Living With HIV: The Swiss HIV Cohort Study

J Infect Dis. 2023 Sep 15;228(6):742-750. doi: 10.1093/infdis/jiad179.

Abstract

Background: Bone mineral density (BMD) loss may be accelerated in people with HIV (PLWH). It is unknown whether a polygenic risk score (PRS) is associated with low BMD in PLWH.

Methods: Swiss HIV Cohort Study participants of self-reported European descent underwent ≥2 per-protocol dual x-ray absorptiometry (DXA) measurements ≥2 years apart (2011-2020). Univariable and multivariable odds ratios (ORs) for DXA-defined osteoporosis were based on traditional and HIV-related risk factors and a genome-wide PRS built from 9413 single-nucleotide polymorphisms associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements.

Results: We included 438 participants: 149 with osteoporosis and 289 controls (median age, 53 years; 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis PRS (top vs bottom quintile) had univariable and multivariable-adjusted osteoporosis ORs of 4.76 (95% CI, 2.34-9.67) and 4.13 (1.86-9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture yielded univariable osteoporosis ORs of 2.26 (1.37-3.74), 1.84 (1.40-2.43), and 1.54 (0.82-2.9).

Conclusions: In PLWH in Switzerland, osteoporosis was independently associated with a BMD-associated PRS after adjustment for established risk factors, including exposure to tenofovir disoproxil fumarate.

Keywords: HIV infection; aging; low bone mineral density; osteoporosis; polygenic risk score.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Density / genetics
  • Bone Diseases, Metabolic* / chemically induced
  • Bone Diseases, Metabolic* / complications
  • Bone Diseases, Metabolic* / epidemiology
  • Cohort Studies
  • Female
  • HIV
  • HIV Infections* / complications
  • HIV Infections* / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Osteoporosis* / chemically induced
  • Osteoporosis* / epidemiology
  • Osteoporosis* / genetics
  • Risk Factors
  • Switzerland / epidemiology
  • Tenofovir / adverse effects

Substances

  • Tenofovir