Table 2.

Summary of Studies Reporting Sex Differences for Bone Disease Among People With HIV

Author, Year [Ref]	Study Design Study Size (% PWH) No. of Men and Women	Study Population (Location, Race/Ethnicity, Age)	Outcomes Measured	Key Findings	Limitations
Bone mineral density
Kalayjian et al, 2018 [25]	Longitudinal N = 499 (100% PWH) 438 men, 61 women	• PWH from US enrolled in 2 ACTG studies (A5224 & A5303) • 46% White, 32% Black, 19% Hispanic • Mean age: 37 y (women), 40 y (men)	BMD at left hip & lumbar spine at baseline (ART-naive) and 48wk post–ART initiation	• WWH vs MWH had lower adjusted baseline BMD at spine (–0.39g/cm2, P<.05) and hip (–0.05g/cm2, P<.05) • WWH vs MWH had 1.7% greater adjusted BMD decline at hip (P<.05) • WWH vs MWH had 0.6% greater BMD decline at hip per 100 CD4+ cells/µL increase (P<.05)	WWH were underrepresented, older, and more often Black compared with MWH. Did not control for substance use or capture menopause status. Did not include persons without HIV for comparison.
Negredo et al, 2018 [30]	Longitudinal N = 875 (100% PWH) 659 men, 216 women	• PWH cared for at single HIV unit in Barcelona, Spain • Racial/ethnic data not available • Median age: 42 y	• Risk of progression to different BMD category after age 45 stratified by ART regimen: PI and/or TDF (primary) • Probability of progression to different BMD category over 10 y (secondary)	• WWH vs MWH had higher risk of progression from osteopenia to osteoporosis after age 45 y on a PI regimen: HR, 5.9 (95% CI, 1.2–27.6) vs 1.8 (95% CI, .9–3.4), respectively • WWH vs MWH had higher risk of progression from osteopenia to osteoporosis after age 45 on combined PI + TDF regimen: HR, 6.9 (95% CI, 1.4–34.4) vs 1.2 (95% CI, .6–2.6), respectively • Probability of progression to lower BMD over 10 y was greater among MWH vs WWH up to age 50; however, greater among WWH vs MWH after age 50	WWH were underrepresented. Did not control for BMD loss risk factors including menopause status. Did not report statistical significance of sex differences. Did not include persons without HIV for comparison.
Han et al, 2020 [31]	Prospective longitudinal cohort N = 172 (62% PWH) 88 men, 84 women	• ART-naive PWH and adults enrolled in TNT-HIV 003 bone substudy from Thai Red Cross AIDS Research Centre, Bangkok • Median age: 38 y	BMD loss (≥5%) at total hip, lumbar spine, and femoral neck at baseline, 1, 2, and 5 y post–ART initiation	• WWH vs MWH had higher adjusted odds of BMD loss at lumbar spine over 5 y (aOR, 3.0 [95% CI, 1.0–8.8], P=.05) but not at total hip (P=.2) or femoral neck (P=.8)	High rates of loss to follow-up among PWH. Did not capture menopause status.
Fracture
Komatsu et al, 2018 [32]	Longitudinal N = 3251 (100% PWH) 3040 men, 211 women	• PWH cared for at 35 healthcare facilities across Japan • Mean age: 41 y (women), 40 y (men)	Cumulative risk of osteoporosis-related fracture after initiating TDF-containing regimen	• WWH vs MWH had higher fracture rate (42.2 vs 13.5 per 10 000 PY) • WWH vs MWH were older at time of first fracture (66 vs 43 y) • WWH vs MWH had shorter average time to first fracture post–TDF initiation (123 vs 1438 d)	WWH were underrepresented. Few total fractures reported over follow-up period. Did not report statistical significance of sex differences. Did not control for many fracture risk factors including menopause status. Did not include persons without HIV for comparison.
Gedmintas et al, 2014 [33]	Longitudinal N = 3161 (100% PWH) 2292 men, 869 women	• PWH cared for at 2 Boston hospitals • Racial/ethnic data not available • Mean age: 41 y (women), 44 y (men)	Incident fracture rate at osteoporotic sites and nonosteoporotic sites overall and across 5 age strata	• No significant sex differences in fracture rates within any age stratum • MWH vs WWH had a higher osteoporotic fracture risk across most age strata (IRR range, 1.07–1.54) except for those aged 46–55 (IRR, 0.88) • MWH vs WWH had similar risk of lifetime osteoporotic fractures (IRR, 1.26 [95% CI, .90–1.75]) • MWH vs WWH had similar lifetime IR of fracture at any site (IRR, 1.00 [95% CI, .83–1.19])	Not powered to detect sex differences between age strata. Did not control for many fracture risk factors including menopause status. Did not include persons without HIV for comparison.

Abbreviations: ACTG, AIDS Clinical Trial Group; aOR, adjusted odds ratio; ART, antiretroviral therapy; BMD, bone mineral density; CI, confidence interval; HR, hazard ratio; IR, incidence rate; IRR, incidence rate ratio; MWH, men with HIV; PI, protease inhibitor; PWH, persons with HIV; PY, person-years; TDF, tenofovir disoproxil fumarate; WWH, women with HIV.