Bone Complications of HIV

Module 13, Version 4


  • Arribas JR, Thompson M, Sax PE, et al. Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment: Week 144 Results. J Acquir Immune Defic Syndr. 2017;75(2):211-218.
  • Bolland MJ, Horne AM, Briggs SE, et al. Effects of Intravenous Zoledronate on Bone Turnover and Bone Density Persist for at Least 11 Years in HIV-Infected Men. J Bone Miner Res. 2019;34(7):1248-1253.
  • Bolland MJ, Wang TK, Gray A, et al. Stable bone density in HAART-treated individuals with HIV: a meta-analysis. J Clin Endocrinol Metab. 2011;96:2721-2731.
  • Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and management of bone disease in HIV. Clin Infect Dis. 2015;60:1242-1251.
  • Brown TT, Moser C, Currier J, et al. Changes in bone mineral density after initiation of antiretroviral treatment with tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir or raltegravir. J Infect Dis. 2015;212:1241-1249.
  • Carr A, Grund B, Schwartz AV, et al. The rate of bone loss slows after 1-2 years of initial antiretroviral therapy: final results of the Strategic Timing of Antiretroviral Therapy (START) bone mineral density substudy. HIV Med. 2020;21(1):64-70.
  • Castillo AB, Tarantal AF, Watnik MR, Martin RB. Tenofovir treatment at 30 mg/kg/day can inhibit cortical bone mineralization in growing rhesus monkeys (Macaca mulatta). J Orthop Res. 2002;20:1185-1189.
  • Conessa-Botella A, Florence E, Lynen L, et al. Decrease of vitamin D concentration in patients with HIV infection on a non nucleoside reverse transcriptase inhibitor-containing regimen. AIDS Res Ther. 2010;7:40.
  • Cosman F, de Beur SJ, LeBoff MS, et al. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014;25(10):2359-2381.
  • Desquilbet L, Jacobson LP, Fried LP, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. Journal of Gerontology: Medical Sciences. 2007;62A:(11)1279-1286.
  • Erlandson KM, Lake JE, Sim M, et al. Bone Mineral Density Declines Twice as Quickly Among HIV-Infected Women Compared with Men. JAIDS. 2018;77(3):288-294.
  • Eron JJ, Chloe C, Gallant JE, et al. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS. 2018;32(11):1431-1442.
  • Fox J, Peters B, Prakash M, et al. Improvement in vitamin D deficiency following antiretroviral regimen change: Results from the MONET trial. AIDS Res Hum Retrovir. 2011:27:29-34.
  • Gaksch M, Jorde R, Grimnes G, et al. Vitamin D and mortality: Individual participant data meta-analysis of standardized 25- hydroxyvitamin D in 26916 individuals from a European consortium. PLos ONE. 2017;12:e0170791.
  • Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naïve patients: a 3-year randomized trial. JAMA. 2004;292:191-201.
  • Goh SSL, Lai PSM, Tan ATB, Ponnampalavanar S. Reduced bone mineral density in human immunodeficiency virus-infected individuals: a meta-analysis of its prevalence and risk factors. Osteoporos Int. 2018;29(3):595-613.
  • Grant PM, Kitch D, McComsey GA, Collier AC, et al. Long-term Bone Mineral Density Changes in Antiretroviral-Treated HIV-Infected Individuals. J Infect Dis. 2016;214(4):607-611.
  • Grant PM, Kitch D, McComsey GA, et al. Low baseline CD4+ count is associated with greater bone mineral density loss after antiretroviral therapy initiation. Clin Infect Dis. 2013;57:1483-1488.
  • Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587-2599.
  • Grigsby IF, Pham L, Mansky LM, et al. Tenofovir-associated bone density loss. Ther Clin Risk Manag. 2010;6:41-47.
  • Gyllensten K, Josephson F, Lidman K, Sääf M. Severe vitamin D deficiency diagnosed after introduction of antiretroviral therapy including efavirenz in a patient living at latitude 59 degrees N. AIDS. 2006;20:1906-1907.
  • Hagins D, Orkin C, Daar ES, et al. Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96-week results from two randomized clinical trials. HIV Med. 2018;19(10):724-733.
  • Hamzah L, Tiraboschi JM, Iveson H, et al. Effects on vitamin D, bone and the kidney of switching from fixed-dose tenofovir disoproxil fumarate/emtricitabine/efavirenz to darunavir/ritonavir monotherapy: a randomized, controlled trial (MIDAS). Antivir Ther. 2016;21:287-296.
  • Havens PL, Long D, Schuster GU, et al. Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 117 and 109 study teams. Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone. Antivir Ther. 2018;23(7):623-628.
  • Havens PL, Perumean-Chaney SE, Patki A, et al. Changes in bone mass after discontinuation of preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine in young men who have sex with men: extension phase results of Adolescent Trials Network Protocols 110 and 113. Clin Infect Dis. 2020;70(4):687-691.
  • Hernlund E, Svedbom A, Ivergård M, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. Arch Osteoporos. 2013;8:136.
  • Hodder S, Squires K, Kityo C, et al. Brief Report: Efficacy and Safety of Switching to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide (E/C/F/TAF) in Virologically Suppressed Women. J Acquir Immune Defic Syndr. 2018;78(2):209-213.
  • Holick MF, Binkley NC, Heike A. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911-1930.
  • Hosek S, Rudy B, Landowitz R, et al. An HIV preexposure prophylaxis demonstration project and safety study for young MSM. J Acquir Immune Defic Syndr. 2017 Jan 1;74(1):21-29.
  • Hoy JF, Richardson R, Ebeling PR, et al. Zoledronic acid is superior to tenofovir disoproxil fumarate-switching for low bone mineral density in adults with HIV. AIDS. 2018 Sep 10;32(14):1967-1975.
  • Kalayjian RC, Albert JM, Cremers S, et al. Women have enhanced bone loss associated with phosphaturia and CD4+ cell restoration during initial antiretroviral therapy. AIDS. 2018;32(17):2517-2524.
  • Kanis J. Diagnosis of osteoporosis and assessment of fracture risk. Lancet. 2002;359:1929-1936.
  • Keily M, Cashman KD. Summary outcomes of the ODIN project on food fortification for Vitamin D Deficiency prevention. Int J of Environ. Res. Public Health. 2018 Oct 24;15(11):2342.
  • Khosla S. Pathogenesis of age-related bone loss in humans. J Gerontol A Biol Med Sci. 2013;68:1226-1235.
  • Lin, KW. Vitamin D Screening and Supplementation in Primary Care: Time to Curb Our Enthusiasm. Am Fam Physician. 2018 Feb 15;97(4):226-227.
  • Llop M, Sifuentes WA, Bañón S, et al. Increased prevalence of asymptomatic vertebral fractures in HIV-infected patients over 50 years of age. Arch Osteoporos. 2018 May 8;13(1):56. PMID: 29736771.
  • McComsey GA, Kendall MA, Tebas P, et al. Alendronate with calcium and vitamin D supplementation is safe and effective for treatment of decreased bone mineral density in HIV. AIDS. 2007;21:2473-2482.
  • McComsey GA, Kitch D, Daar ES, et. al. Bone mineral density and fractures in antiretroviral-naïve persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: AIDS Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011;203:1791-1801.
  • McComsey GA, Tebas P, Shane E, et al. Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis. 2010;51:937-946.
  • McComsey G, Lupo S, Parks D, et al. Switch from tenofovir disoproxil fumarate combination to dolutegravir with rilpivirine improves parameters of bone health. AIDS. 2018. 32:477-485.
  • Mulligan K, Glidden DV, Anderson PL, et al. Effects of emtricitabine/tenofovir on bone mineral density in HIV-negative persons in a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2015;61:572-580.
  • Ofotokun I, Titanji K, Lahiri C, et al. A single-dose zoledronic acid infusion prevents antiretroviral therapy-induced bone loss in treatment naïve HIV-infected patients: A phase 2b trial. Clin Inf Dis. 2016;63(5):663–71.
  • Overton ET, Chan ES, Brown TT, et al. Vitamin D and calcium attenuate bone loss with antiretroviral therapy initiation: a randomized trial. Ann Intern Med. 2015:162:815-824.
  • Pinzone MR, Moreno S, Cacopardo B, Nunnari G. Is there enough evidence to use bisphosphonates in HIV‐infected patients? A systematic review and meta‐analysis. AIDS Rev. 2014;16(4):213-22.
  • Pozniak A, Arribas JR, Gathe J, et al. Switching to tenofovir alafenamide, coformulated with elvitegravir, cobicistat, and emtricitabine, in HIV-infected patients with renal impairment: 48-week results from a single-arm, multicenter, open-label phase 3 Study. J Acquir Immune Defic Syndr. 2016;71:530-537.
  • Premaor MO, Compston JE. The Hidden Burden of Fractures in People Living With HIV. JBMR Plus. 2018;2(5):247-256. PMID: 30283906
  • Qaseem A, Forciea MA, McLean RM, et al. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guidelines Update from the American College of Physicians. Ann Intern Med. 2017; 166(11):818 839.
  • Rashbaum B, Spinner CD, McDonald C, et al. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve patients with HIV-1: subgroup analyses of the phase 3 AMBER study. HIV Res Clin Pract. 2019;20(1):24-33.
  • Sax PE, Wohl D, Yin M, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015;385:2606-2615.
  • Schwartz JB, Moore KL, Yin M, et al. Relationship of vitamin D, HIV, HIV treatment, and lipid levels in the Women's Interagency HIV Study of HIV-infected and uninfected women in the United States. J Int Assoc Provid AIDS Care. 2014;13:250-259.
  • Sharma A, Ma Y, Tien PC, et al. HIV Infection Is Associated With Abnormal Bone Microarchitecture: Measurement of Trabecular Bone Score in the Women's Interagency HIV Study. J Acquir Immune Defic Syndr. 2018;78(4):441-449.
  • Spector SA. Vitamin D and HIV: letting the sun shine in. Top Antivir Med. 2011;19:6-10.
  • Tebas P, Powderly WG, Claxton S, et. al. Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS. 2000;14:F63-F67.
  • Thomsen MT, Wiegandt YL, Gelpi M, et al. Prevalence of and Risk Factors for Low Bone Mineral Density Assessed by Quantitative Computed Tomography in People Living With HIV and Uninfected Controls. J Acquir Immune Defic Syndr. 2020;83(2):165-172.
  • Wohl DA, Ruane PJ, Hosek S, et al. Bone Safety Outcomes With F/TAF vs F/TDF for PrEP in the DISCOVER Trial. Open Forum Infect Dis. 2019;6(2):S464.
  • Womack JA, Goulet JL, Gilbert C, et al. Increased risk of fragility fractures among HIV-infected compared to uninfected male veterans. PLoS ONE. 2011;6:e17217.
  • Young B, Dao CN, Buchacz K. Increased rates of bone fracture among HIV-infected persons in the HIV outpatient study (HOPS) compared with the US general population, 2000-2006. Clin Infec Dis. 2011;52:1061-1068.
  • European AIDS Clinical Society. Guidelines 10.0. November 2019. Available at: Accessed August 31, 2020.
  • ODIN: Food-based solutions for optimal Vitamin D nutrition and health through the lifecycle. Available at: Accessed August 31, 2020.
  • UNAIDS. AIDSinfo. People living with HIV – People aged 50 and over. 2019. Available at Accessed August 5, 2020.
  • World Health Organization. Assessment of fracture risk and its implication to screening for postmenopausal osteoporosis: Technical report series 843. Geneva: WHO,1994.
  • Battalora L, Armon C, Palella FJ, et al. Breaking bones is bad: incident fracture and mortality in the HIV Outpatient Study. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 30.
  • Brown T, Yin MT, Gupta S, et al. Switching from TDF to TAF in HIV-infected adults with low BMD: a pooled analysis. Program and abstracts of the 2017 Conference on Retroviruses and Opportunistic Infections; February 13-16, 2017; Seattle, Washington. Abstract 683.
  • McAllister J, Morris D, Holliday S, Carr A. Substantial loss of bone mineral density in some patients receiving tenofovir-emtricitabine as HIV pre-exposure prophylaxis. Program and abstracts of the 18th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV; September 12-13, 2016; New York, New York. Abstract O02.
  • Ritchie AM, Katzman WB, Ma Y, et al. Hyperkyphosis and aging in the Women's Interagency HIV Study. 25th Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018. Boston. Abstract 727.

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