PURPOSE: Information regarding mediators of differences in bone mineral density (BMD) among Asian ethnicities are limited. Since the majority of hip fractures are predicted to be from Asia, differences in BMD in Asian ethnicities require further exploration. We compared BMD among the Chinese, Malay, or Indian ethnicities in Singapore, aiming to identify potential mediators for the observed differences.

METHODS: BMD of 1201 women aged 45-69 years was measured by dual-energy X-ray absorptiometry. We examined the associations between ethnicity and BMD at both sites, before and after adjusting for potential mediators measured using standardized questionnaires and validated performance tests.

RESULTS: Chinese women had significantly lower femoral neck BMD than Malay and Indian women. Of the more than 20 variables examined, age, body mass index, and height accounted for almost all the observed ethnic differences in femoral neck BMD between Chinese and Malays. However, Indian women still retained 0.047 g/cm2 (95% CI, 0.024, 0.071) higher femoral neck BMD after adjustment, suggesting that additional factors may contribute to the increased BMD in Indians. Although no crude ethnic differences in lumbar spine BMD were observed, adjusted regression model unmasked ethnic differences, wherein Chinese women had 0.061(95% CI, - 0.095, 0.026) and 0.065 (95% CI, - 0.091, 0.038) g/cm2 higher lumbar spine BMD compared to Malay and Indian women, respectively.

METHODS: Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122.

FINDINGS: Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N(t)RTI group and 28·0% (37·6) in the raltegravir group (mean difference 10·2%, 95% CI 0·1-20·4; p=0·048). Mean absolute change was 1·04 kg (SD 2·29) in the N(t)RTI group and 1·81 kg (2·50) in the raltegravir group (mean difference 0·6, 95% CI -0·1 to 1·3; p=0·10).

INTERPRETATION: Our findings suggest that for people with virological failure of a first-line regimen containing efavirenz plus tenofovir and lamivudine or emtricitabine, the WHO-recommended switch to a ritonavir-boosted protease inhibitor plus zidovudine (a thymidine analogue nucleoside reverse transcriptase inhibitor) and lamivudine might come at the cost of peripheral lipoatrophy. Further study could help to define specific groups of people who might benefit from a switch to an N(t)RTI-sparing second-line ART regimen.