Abstract
Understanding bone accrual in adolescents may inform approaches to improve skeletal health and reduce adult fracture risk. We investigated the effect of HIV on bone mineral accrual assessed by peripheral quantitative computed tomography (pQCT). Children with HIV (CWH) on ART for ≥2 years, and children without HIV (CWOH), aged 8-16 years (n = 609), had tibial pQCT scans at 0 and 12 months. Linear regression estimated sex-stratified differences in change (∆) and mean pQCT bone density (trabecular and cortical), size (total cross-sectional area [CSA]), and strength (SSI) between CWH and CWOH, adjusting for socio-economic status (SES) and orphanhood and incorporating an interaction term for baseline pubertal status (Tanner 1-2[pre/early] vs 3-5[mid/late]). Structural equation modeling tested whether baseline height-for-age-Z-scores (HAZ) mediate the effect of HIV on ∆bone outcomes. CWH were more likely than CWOH to be orphans (44% vs 7%), of lower SES (43% vs 27%), and be stunted (30% vs 8%); but similar in age. At baseline and follow-up, CWH had lower trabecular density, CSA, and SSI than CWOH. After adjustment, bone density and strength increased similarly in CWH and CWOH. CWH in mid/late puberty at baseline had greater 12 months increases in CSA than CWOH, particularly males (mean difference [31.3(95%CI:-3.1, 65.6) mm2 in mid/late puberty vs -2.04(-23.8, 19.7) mm2 in pre/early puberty; interaction p-value = 0.013]). HAZ mediated the effect of HIV on ∆bone outcomes only in females. as follows: indirect pathways from HIV to ∆trabecular density [-2.47 (-4.4, -0.5) mg/cm3], ∆cortical density [-3.26 (-5.5, -0.9) mg/cm3], and ∆SSI [-15.76 (-27.3, -4.2) mm3]. In conclusion, CWH show bone deficits at follow-up. Investigations of bone mineral accrual earlier in life and post-puberty to peak bone mass are needed.