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Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40\u201360\u2009years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up. All women were staged as pre-, peri-, or postmenopausal at both time points. Multivariable linear regression assessed relationships and interactions between HIV infection, menopause, and change in BMD. At baseline, 450 women had mean age 49.5 (SD 5.7) years, 65 (14.4%) had HIV, and 140 (31.1%), 119 (26.4%), and 191 (42.4%) were pre-, peri-, and postmenopausal, respectively; 34\/205 (13.6%) women \u226550\u2009years had a total hip (TH) or lumbar spine (LS) T-score\u2009\u2264\u2009\u22122.5. At follow-up 38 (8.4%), 84 (18.7%), and 328 (72.9%) were pre-, peri-, and postmenopausal. Those with HIV at baseline lost more total body (TB) BMD (mean difference\u2009\u22120.013 [95% confidence interval \u22120.026, \u22120.001] g\/cm2, p\u00a0=\u00a00.040) and gained more weight 1.96 [0.32, 3.60] kg; p\u00a0=\u00a00.019 than HIV-uninfected women. After adjusting for age, baseline weight, weight change, and follow-up time, the transition from pre- to postmenopause was associated with greater TB BMD losses in women with HIV (\u22120.092 [\u22120.042, \u22120.142] g\/cm2; p\u00a0=\u00a00.001) than without HIV (\u22120.038 [\u22120.016, \u22120.060] g\/cm2, p\u00a0=\u00a00.001; interaction p\u00a0=\u00a00.034). Similarly, in women who were postmenopausal at both time points, those with HIV lost more TB BMD (\u22120.070 [\u22120.031, \u22120.108], p\u00a0=\u00a00.001) than women without HIV (\u22120.036 [\u22120.015, \u22120.057], p\u00a0=\u00a00.001, interaction p\u00a0=\u00a00.049). Findings were consistent but weaker at the LS and TH. Menopause-related bone loss is greater in women with HIV, suggesting women with HIV may be at greater risk of osteoporotic fractures. HIV services should consider routine bone health assessment in midlife women as part of long-term HIV care delivery. \u00a9 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4765","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:09:56Z","timestamp":1675296596000},"page":"619-630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Impact of Human Immunodeficiency Virus and Menopause on Bone Mineral Density: A Longitudinal Study of Urban-Dwelling South African Women"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2449-0027","authenticated-orcid":false,"given":"Tafadzwa MSc","family":"Madanhire","sequence":"first","affiliation":[{"name":"MRC International Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health London School of Hygiene and Tropical Medicine London UK"},{"name":"Biomedical Research and Training Institute Harare Zimbabwe"},{"name":"SAMRC\/Wits Developmental Pathways for Health Research Unit, School of Clinical Medicine, Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia H. PhD","family":"Goedecke","sequence":"additional","affiliation":[{"name":"Non-Communicable Diseases Research Unit South African Medical Research Council Cape Town South Africa"},{"name":"SAMRC\/Wits Developmental Pathways for Health Research Unit, School of Clinical Medicine, Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7034-6750","authenticated-orcid":false,"given":"Kate A. PhD","family":"Ward","sequence":"additional","affiliation":[{"name":"MRC Lifecourse Epidemiology Centre, School of Human Development and Health University of Southampton Southampton UK"},{"name":"SAMRC\/Wits Developmental Pathways for Health Research Unit, School of Clinical Medicine, Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole PhD","family":"Jaff","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel J. PhD","family":"Crowther","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology National Health Laboratory Service Johannesburg South Africa"},{"name":"Department of Chemical Pathology, Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane PhD","family":"Norris","sequence":"additional","affiliation":[{"name":"Global Health Research Institute, School of Human Development and Health University of Southampton Southampton UK"},{"name":"SAMRC\/Wits Developmental Pathways for Health Research Unit, School of Clinical Medicine, Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashida A. PhD","family":"Ferrand","sequence":"additional","affiliation":[{"name":"Clinical Research Department, Faculty of Infectious and Tropical Diseases London School of Hygiene and Tropical Medicine London UK"},{"name":"Biomedical Research and Training Institute Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9967-5822","authenticated-orcid":false,"given":"Andrea M. PhD","family":"Rehman","sequence":"additional","affiliation":[{"name":"MRC International Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health London School of Hygiene and Tropical Medicine London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa K. 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