Skip to main content

Advertisement

SpringerLink
Log in

People living with HIV and fracture risk

  • Review
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary PLHIV have an increased risk of osteoporosis and fractures when compared with people of the same age and sex. In this review, we address the epidemiology and the pathophysiology of bone disease and fractures in PLHIV. The assessment of fracture risk and fracture prevention in these subjects is also discussed. The spectrum of HIV-associated disease has changed dramatically since the introduction of potent antiretroviral drugs. Today, the survival of people living with HIV (PLHIV) is close to that of the general population. However, the longer life-span in PLHIV is accompanied by an increased prevalence of chronic diseases. Detrimental effects on bone health are well recognised, with an increased risk of osteoporosis and fractures, including vertebral fractures, compared to the general population. The causes of bone disease in PLHIV are not fully understood, but include HIV-specific risk factors such as use of antiretrovirals and the presence of chronic inflammation, as well as traditional risk factors for fracture. Current guidelines recommend the use of FRAX to assess fracture probability in PLHIV age ≥ 40 years and measurement of bone mineral density in those at increased fracture risk. Vitamin D deficiency, if present, should be treated. Bisphosphonates have been shown to increase bone density in PLHIV although fracture outcomes are not available.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Pantaleo G, Graziosi C, Fauci AS (1993) The immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 328:327–335

    Article  CAS  PubMed  Google Scholar 

  2. Fang CT, Chang YY, Hsu HM, Twu SJ, Chen KT, Lin CC, Huang LY, Chen MY, Hwang JS, Wang JD, Chuang CY (2007) Life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy. QJM 100:97–105

    Article  CAS  PubMed  Google Scholar 

  3. van Sighem AI, Gras LA, Reiss P, Brinkman K, de Wolf F, study Anoc (2010) Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. AIDS 24:1527–1535

    Article  PubMed  Google Scholar 

  4. Collaboration of Observational HIVEREiE, Lewden C, Bouteloup V et al (2012) All-cause mortality in treated HIV-infected adults with CD4 >/=500/mm3 compared with the general population: evidence from a large European observational cohort collaboration. Int J Epidemiol 41:433–445

    Article  Google Scholar 

  5. Arnsten JH, Freeman R, Howard AA, Floris-Moore M, Lo Y, Klein RS (2007) Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection. AIDS (London, England) 21:617–623

    Article  Google Scholar 

  6. Prior J, Burdge D, Maan E, Milner R, Hankins C, Klein M, Walmsley S (2007) Fragility fractures and bone mineral density in HIV positive women: a case-control population-based study. Osteoporos Int 18:1345–1353

    Article  CAS  PubMed  Google Scholar 

  7. Gonciulea A, Wang R, Althoff KN, Palella FJ, Lake J, Kingsley LA, Brown TT (2017) An increased rate of fracture occurs a decade earlier in HIV+ compared with HIV- men. AIDS (London, England) 31:1435–1443

    Article  Google Scholar 

  8. Gedmintas L, Wright EA, Dong Y, Lehmann E, Katz JN, Solomon DH, Losina E (2017) Factors associated with fractures in HIV-infected persons: which factors matter? Osteoporos Int 28:239–244

    Article  CAS  PubMed  Google Scholar 

  9. Borges AH, Hoy J, Florence E, Sedlacek D, Stellbrink HJ, Uzdaviniene V, Tomazic J, Gargalianos-Kakolyris P, Schmid P, Orkin C, Pedersen C, Leen C, Pradier C, Mulcahy F, Ridolfo AL, Staub T, Maltez F, Weber R, Flamholc L, Kyselyova G, Lundgren JD, Mocroft A, for EuroSIDA (2017) Antiretrovirals, fractures, and osteonecrosis in a large international HIV cohort. Clin Infect Dis 64:1413–1421

    Article  CAS  PubMed  Google Scholar 

  10. Battalora L, Buchacz K, Armon C, Overton ET, Hammer J, Patel P, Chmiel JS, Wood K, Bush TJ, Spear JR, Brooks JT, Young B, HIV Outpatient Study (HOPS) and SUN Study Investigators (2016) Low bone mineral density and risk of incident fracture in HIV-infected adults. Antivir Ther 21:45–54

    Article  CAS  PubMed  Google Scholar 

  11. Sharma A, Shi Q, Hoover DR, Anastos K, Tien PC, Young MA, Cohen MH, Golub ET, Gustafson D, Yin MT (2015) Increased fracture incidence in middle-aged HIV-infected and HIV-uninfected women: updated results from the women's interagency HIV study. J Acquir Immune Defic Syndr 70:54–61

    Article  PubMed  PubMed Central  Google Scholar 

  12. Prieto-Alhambra D, Güerri-Fernández R, De Vries F, Lalmohamed A, Bazelier M, Starup-Linde J, Diez-Perez A, Cooper C, Vestergaard P (2014) HIV infection and its association with an excess risk of clinical fractures: a nationwide case-control study. J Acquir Immune Defic Syndr 66:90–95

    Article  PubMed  Google Scholar 

  13. Kurita T, Kitaichi T, Nagao T, Miura T, Kitazono Y (2014) Safety analysis of Epzicom® (lamivudine/abacavir sulfate) in post-marketing surveillance in Japan. Pharmacoepidemiol Drug Saf 23:372–381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Peters BS, Perry M, Wierzbicki AS, Wolber LE, Blake GM, Patel N, Hoile R, Duncan A, Kulasegaram R, Williams FM (2013) A cross-sectional randomised study of fracture risk in people with HIV infection in the probono 1 study. PLoS One 8:e78048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Güerri-Fernandez R, Vestergaard P, Carbonell C, Knobel H, Avilés FF, Castro AS, Nogués X, Prieto-Alhambra D, Diez-Perez A (2013) HIV infection is strongly associated with hip fracture risk, independently of age, gender, and comorbidities: a population-based cohort study. J Bone Miner Res 28:1259–1263

    Article  PubMed  Google Scholar 

  16. Yin MT, Kendall MA, Wu X, Tassiopoulos K, Hochberg M, Huang JS, Glesby MJ, Bolivar H, McComsey GA (2012) Fractures after antiretroviral initiation. AIDS (London, England) 26:2175–2184

    Article  CAS  Google Scholar 

  17. Hansen ABE, Gerstoft J, Kronborg G, Larsen CS, Pedersen C, Pedersen G, Obel N (2012) Incidence of low and high-energy fractures in persons with and without HIV infection: a Danish population-based cohort study. AIDS 26:285–293

    Article  PubMed  Google Scholar 

  18. Bedimo R, Maalouf NM, Zhang S, Drechsler H, Tebas P (2012) Osteoporotic fracture risk associated with cumulative exposure to tenofovir and other antiretroviral agents. AIDS (London, England) 26:825–831

    Article  CAS  Google Scholar 

  19. Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, Berti A, Rossi E, Roverato A, Palella F (2011) Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis 53:1120–1126

    Article  PubMed  Google Scholar 

  20. Young B, Dao CN, Buchacz K, Baker R, Brooks JT (2011) Increased rates of bone fracture among HIV-infected persons in the HIV outpatient study (HOPS) compared with the US general population, 2000-2006. Clin Infect Dis 52:1061–1068

    Article  PubMed  Google Scholar 

  21. Yong MK, Elliott JH, Woolley IJ, Hoy JF (2011) Low CD4 count is associated with an increased risk of fragility fracture in HIV-infected patients. J Acquir Immune Defic Syndr 57:205–210

    Article  PubMed  Google Scholar 

  22. Hasse B, Ledergerber B, Furrer H, Battegay M, Hirschel B, Cavassini M, Bertisch B, Bernasconi E, Weber R (2011) Morbidity and aging in HIV-infected persons: the swiss HIV cohort study. Clin Infect Dis 53:1130–1139

    Article  PubMed  Google Scholar 

  23. Yin MT, McMahon DJ, Ferris DC, Zhang CA, Shu A, Staron R, Colon I, Laurence J, Dobkin JF, Hammer SM, Shane E (2010) Low bone mass and high bone turnover in postmenopausal human immunodeficiency virus-infected women. J Clin Endocrinol Metab 95:620–629

    Article  CAS  PubMed  Google Scholar 

  24. Collin F, Duval X, Moing VL, Piroth L, Kaied FA, Massip P, Villes V, Raffi GCF (2009) Ten-year incidence and risk factors of bone fractures in a cohort of treated HIV1-infected adults. AIDS 23:1021–1024

    Article  PubMed  Google Scholar 

  25. Triant VA, Brown TT, Lee H, Grinspoon SK (2008) Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab 93:3499–3504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JMAH, Miller MD, Coakley DF, Lu B, Toole JJ, Cheng AK (2004) Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. J Am Med Assoc 292:191–201

    Article  CAS  Google Scholar 

  27. Shiau S, Broun EC, Arpadi SM, Yin MT (2013) Incident fractures in HIV-infected individuals: a systematic review and meta-analysis. AIDS (London, England) 27:1949–1957

    Article  Google Scholar 

  28. Premaor MO, Compston JE (2018) The hidden burden of fractures in people living with HIV. J Bone Min Res Plus WOA 2:247–256

    Google Scholar 

  29. Ilha T, Comim FV, Copes RM, Compston JE, Premaor MO (2018) HIV and vertebral fractures: a systematic review and Metanalysis. Sci Rep 8:7838

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Compston J (2016) HIV infection and bone disease. J Intern Med 280:350–358

    Article  CAS  PubMed  Google Scholar 

  31. Rochira V, Zirilli L, Orlando G, Santi D, Brigante G, Diazzi C, Carli F, Carani C, Guaraldi G (2011) Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One 6:e28512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Samad F, Harris M, Puskas CM, Ye M, Chia J, Chacko S, Bondy GP, Lima VD, Montaner JS, Guillemi SA (2017) Incidence of diabetes mellitus and factors associated with its development in HIV-positive patients over the age of 50. BMJ Open Diabetes Res Care 5:e000457

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hernandez-Romieu AC, Garg S, Rosenberg ES, Thompson-Paul AM, Skarbinski J (2017) Is diabetes prevalence higher among HIV-infected individuals compared with the general population? Evidence from MMP and NHANES 2009-2010. BMJ Open Diabetes Res Care 5:e000304

    Article  PubMed  PubMed Central  Google Scholar 

  34. Echeverria P, Bonjoch A, Puig J, Estany C, Ornelas A, Clotet B, Negredo E (2018) High prevalence of sarcopenia in HIV-infected individuals. Biomed Res Int 2018:5074923

    Article  PubMed  PubMed Central  Google Scholar 

  35. Hawkins KL, Zhang L, Ng DK et al (2018) Abdominal obesity, sarcopenia, and osteoporosis are associated with frailty in men living with and without HIV. AIDS (London, England) 32:1257–1266

    Article  Google Scholar 

  36. Pinto Neto LF, Sales MC, Scaramussa ES, da Paz CJ, Morelato RL (2016) Human immunodeficiency virus infection and its association with sarcopenia. Braz J Infect Dis 20:99–102

    Article  PubMed  Google Scholar 

  37. Wasserman P, Segal-Maurer S, Rubin DS (2014) High prevalence of low skeletal muscle mass associated with male gender in midlife and older HIV-infected persons despite CD4 cell reconstitution and viral suppression. J Int Assoc Provid AIDS Care 13:145–152

    Article  PubMed  Google Scholar 

  38. Abdul Aziz SA, McStea M, Ahmad Bashah NS et al (2018) Assessment of sarcopenia in virally suppressed HIV-infected Asians receiving treatment. AIDS 32:1025–1034

    Article  PubMed  Google Scholar 

  39. Stone B, Dockrell D, Bowman C, McCloskey E (2010) HIV and bone disease. Arch Biochem Biophys 503:66–77

    Article  CAS  PubMed  Google Scholar 

  40. Hileman CO, Eckard AR, McComsey GA (2015) Bone loss in HIV: a contemporary review. Curr Opin Endocrinol Diabetes Obes 22:446–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Dong HV, Cortes YI, Shiau S, Yin MT (2014) Osteoporosis and fractures in HIV/hepatitis C virus coinfection: a systematic review and meta-analysis. AIDS (London, England) 28:2119–2131

    Article  Google Scholar 

  42. Byrne DD, Newcomb CW, Carbonari DM et al (2015) Increased risk of hip fracture associated with dually treated HIV/hepatitis B virus coinfection. J Viral Hepat 22:936–947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Titanji K (2017) Beyond antibodies: B cells and the OPG/RANK-RANKL pathway in health, non-HIV disease and HIV-induced bone loss. Front Immunol 8:1851

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Ofotokun I, Titanji K, Vunnava A et al (2016) Antiretroviral therapy induces a rapid increase in bone resorption that is positively associated with the magnitude of immune reconstitution in HIV infection. AIDS (London, England) 30:405–414

    Article  CAS  Google Scholar 

  45. Peyriere H, Reynes J, Rouanet I, Daniel N, de Boever CM, Mauboussin JM, Leray H, Moachon L, Vincent D, Salmon-Ceron D (2004) Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases. J Acquir Immune Defic Syndr 35:269–273

    Article  PubMed  Google Scholar 

  46. Labarga P, Barreiro P, Martin-Carbonero L, Rodriguez-Novoa S, Solera C, Medrano J, Rivas P, Albalater M, Blanco F, Moreno V, Vispo E, Soriano V (2009) Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir. AIDS 23:689–696

    Article  CAS  PubMed  Google Scholar 

  47. Woodward CL, Hall AM, Williams IG, Madge S, Copas A, Nair D, Edwards SG, Johnson MA, Connolly JO (2009) Tenofovir-associated renal and bone toxicity. HIV Med 10:482–487

    Article  CAS  PubMed  Google Scholar 

  48. Gupta SK (2008) Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system. AIDS Patient Care STDs 22:99–103

    Article  PubMed  Google Scholar 

  49. Conesa-Buendia FM, Llamas-Granda P, Larranaga-Vera A, Wilder T, Largo R, Herrero-Beaumont G, Cronstein B, Mediero A (2019) Tenofovir causes bone loss via decreased bone formation and increased bone Resorption, which can be counteracted by dipyridamole in mice. J Bone Miner Res 34:923–938

    Article  CAS  PubMed  Google Scholar 

  50. Ramalho J, Martins CSW, Galvao J et al (2019) Treatment of human immunodeficiency virus infection with tenofovir disoproxil fumarate-containing antiretrovirals maintains low bone formation rate, but increases osteoid volume on bone histomorphometry. J Bone Miner Res 34:1574–1584

    Article  CAS  PubMed  Google Scholar 

  51. De Clercq E (2016) Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF). Biochem Pharmacol 119:1–7

    Article  PubMed  CAS  Google Scholar 

  52. Sax PE, Wohl D, Yin MT et al (2015) 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 385:2606–2615

    Article  CAS  PubMed  Google Scholar 

  53. Sax PE, Zolopa A, Brar I et al (2014) Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. Journal of Acquired Immune Deficiency Syndromes (1999) 67:52–58

    Article  CAS  Google Scholar 

  54. Maggiolo F, Rizzardini G, Raffi F, Pulido F, Mateo-Garcia MG, Molina JM, Ong E, Shao Y, Piontkowsky D, Das M, McNicholl I, Haubrich R (2019) Bone mineral density in virologically suppressed people aged 60 years or older with HIV-1 switching from a regimen containing tenofovir disoproxil fumarate to an elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide single-tablet regimen: a multicentre, open-label, phase 3b, randomised trial. Lancet HIV 6:e655–e666

    Article  PubMed  Google Scholar 

  55. Gutierrez F, Masia M (2011) The role of HIV and antiretroviral therapy in bone disease. AIDS Rev 13:109–118

    PubMed  Google Scholar 

  56. Mouly S, Lown KS, Kornhauser D, Joseph JL, Fiske WD, Benedek IH, Watkins PB (2002) Hepatic but not intestinal CYP3A4 displays dose-dependent induction by efavirenz in humans. Clin Pharmacol Ther 72:1–9

    Article  CAS  PubMed  Google Scholar 

  57. Brown TT, McComsey GA (2010) Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hydroxyvitamin D. Antivir Ther 15:425–429

    Article  CAS  PubMed  Google Scholar 

  58. Cozzolino M, Vidal M, Arcidiacono MV, Tebas P, Yarasheski KE, Dusso AS (2003) HIV-protease inhibitors impair vitamin D bioactivation to 1,25-dihydroxyvitamin D. AIDS (London, England) 17:513–520

    Article  CAS  Google Scholar 

  59. Stellbrink HJ, Orkin C, Arribas JR, Compston J, Gerstoft J, van Wijngaerden E, Lazzarin A, Rizzardini G, Sprenger HG, Lambert J, Sture G, Leather D, Hughes S, Zucchi P, Pearce H, ASSERT Study Group (2010) Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis 51:963–972

    Article  PubMed  Google Scholar 

  60. Brown TT, Moser C, Currier JS, Ribaudo HJ, Rothenberg J, Kelesidis T, Yang O, Dubé MP, Murphy RL, Stein JH, McComsey G (2015) 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 212:1241–1249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Haskelberg H, Hoy JF, Amin J, Ebeling PR, Emery S, Carr A, Group SS (2012) Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. PLoS One 7:e38377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Grund B, Peng G, Gibert CL, Hoy JF, Isaksson RL, Shlay JC, Martinez E, Reiss P, Visnegarwala F, Carr AD (2009) Continuous antiretroviral therapy decreases bone mineral density. AIDS (London, England) 23:1519–1529

    Article  CAS  PubMed Central  Google Scholar 

  63. Assoumou L, Katlama C, Viard JP, Bentata M, Simon A, Roux C, Kolta S, Costagliola D, Rozenberg S (2013) Changes in bone mineral density over a 2-year period in HIV-1-infected men under combined antiretroviral therapy with osteopenia. AIDS (London, England) 27:2425–2430

    Article  CAS  Google Scholar 

  64. McComsey GA, Kitch D, Daar ES, Tierney C, Jahed NC, Tebas P, Myers L, Melbourne K, Ha B, Sax PE (2011) Bone mineral density and fractures in antiretroviral-naive 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 203:1791–1801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Bedimo RJ, Drechsler H, Jain M, Cutrell J, Zhang S, Li X, Farukhi I, Castanon R, Tebas P, Maalouf NM (2014) The RADAR study: week 48 safety and efficacy of RAltegravir combined with boosted DARunavir compared to tenofovir/emtricitabine combined with boosted darunavir in antiretroviral-naive patients. Impact on bone health. PLoS One 9:e106221

    Article  PubMed  PubMed Central  Google Scholar 

  66. Bernardino JI, Mocroft A, Mallon PW, Wallet C, Gerstoft J, Russell C, Reiss P, Katlama C, de Wit S, Richert L, Babiker A, Buño A, Castagna A, Girard PM, Chene G, Raffi F, Arribas JR, NEAT001/ANRS143 Study Group (2015) Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial. Lancet HIV 2:e464–e473

    Article  PubMed  Google Scholar 

  67. Tebas P, Kumar P, Hicks C, Granier C, Wynne B, Min S, Pappa K (2015) Greater change in bone turnover markers for efavirenz/emtricitabine/tenofovir disoproxil fumarate versus dolutegravir + abacavir/lamivudine in antiretroviral therapy-naive adults over 144 weeks. AIDS (London, England) 29:2459–2464

    Article  CAS  Google Scholar 

  68. Carr A, Grund B, Schwartz AV, Avihingsanon A, Badal-Faesen S, Bernadino JI, Estrada V, la Rosa A, Mallon P, Pujari S, White D, Wyman Engen N, Ensrud K, Hoy JF, International Network for Strategic Initiatives in Global HIV Trials START bone mineral density substudy group (2020) 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 21:64–70

    Article  CAS  PubMed  Google Scholar 

  69. Glidden DV, Mulligan K, McMahan V et al (2017) Brief report: Recovery of bone mineral density after discontinuation of tenofovir-based HIV pre-exposure prophylaxis. Journal of Acquired Immune Deficiency Syndromes (1999) 76:177–182

    Article  Google Scholar 

  70. Mirembe BG, Kelly CW, Mgodi N et al (2016) Bone mineral density changes among young, healthy African women receiving oral tenofovir for HIV preexposure prophylaxis. Journal of Acquired Immune Deficiency Syndromes (1999) 71:287–294

    Article  CAS  Google Scholar 

  71. Spinelli MA, Glidden DV, Anderson PL, Gandhi M, McMahan V, Defechereux P, Schechter M, Veloso VG, Chariyalertsak S, Guanira JV, Bekker LG, Buchbinder SP, Grant RM (2019) Impact of estimated pre-exposure prophylaxis (PrEP) adherence patterns on bone mineral density in a large PrEP demonstration project. AIDS Res Hum Retrovir 35:788–793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Desai M, Field N, Grant R, McCormack S (2017) Recent advances in pre-exposure prophylaxis for HIV. BMJ (Clin Res ed) 359:j5011

    Article  Google Scholar 

  73. Goh SSL, Lai PSM, Tan ATB, Ponnampalavanar S (2017) Reduced bone mineral density in human immunodeficiency virus-infected individuals: a meta-analysis of its prevalence and risk factors. Osteoporos Int

  74. Yin MT, Lund E, Shah J et al (2014) Lower peak bone mass and abnormal trabecular and cortical microarchitecture in young men infected with HIV early in life. AIDS (London, England) 28:345–353

    Article  Google Scholar 

  75. Tan DH, Raboud J, Szadkowski L, Szabo E, Hu H, Wong Q, Cheung AM, Walmsley SL (2017) Novel imaging modalities for the comparison of bone microarchitecture among HIV+ patients with and without fractures: a pilot study. HIV Clin Trials 18:28–38

    Article  PubMed  Google Scholar 

  76. Kazakia GJ, Carballido-Gamio J, Lai A, Nardo L, Facchetti L, Pasco C, Zhang CA, Han M, Parrott AH, Tien P, Krug R (2018) Trabecular bone microstructure is impaired in the proximal femur of human immunodeficiency virus-infected men with normal bone mineral density. Quant Imaging Med Surg 8:5–13

    Article  PubMed  PubMed Central  Google Scholar 

  77. Calmy A, Chevalley T, Delhumeau C, Toutous-Trellu L, Spycher-Elbes R, Ratib O, Zawadynski S, Rizzoli R (2013) Long-term HIV infection and antiretroviral therapy are associated with bone microstructure alterations in premenopausal women. Osteoporos Int 24:1843–1852

    Article  CAS  PubMed  Google Scholar 

  78. Yin MT, Shu A, Zhang CA, Boutroy S, McMahon DJ, Ferris DC, Colon I, Shane E (2013) Trabecular and cortical microarchitecture in postmenopausal HIV-infected women. Calcif Tissue Int 92:557–565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Guerri-Fernandez R, Molina D, Villar-Garcia J et al (2016) Brief report: HIV infection is associated with worse bone material properties, independently of bone mineral density. Journal of Acquired Immune Deficiency Syndromes (1999) 72:314–318

    Article  Google Scholar 

  80. Marques de Menezes EG, de Paula FJ, Machado AA, de Assis Pereira F, Barbosa Junior F, Navarro AM (2013) Impact of antiretroviral therapy on bone metabolism markers in HIV-seropositive patients. Bone 57:62–67

    Article  PubMed  CAS  Google Scholar 

  81. Raynaud-Messina B, Bracq L, Dupont M, Souriant S, Usmani SM, Proag A, Pingris K, Soldan V, Thibault C, Capilla F, al Saati T, Gennero I, Jurdic P, Jolicoeur P, Davignon JL, Mempel TR, Benichou S, Maridonneau-Parini I, Vérollet C (2018) Bone degradation machinery of osteoclasts: an HIV-1 target that contributes to bone loss. Proc Natl Acad Sci U S A 115:E2556–E2565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Lee JW, Hoshino A, Inoue K et al (2017) The HIV co-receptor CCR5 regulates osteoclast function. Nat Commun 8:2226

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Raynaud-Messina B, Verollet C, Maridonneau-Parini I (2019) The osteoclast, a target cell for microorganisms. Bone 127:315–323

    Article  CAS  PubMed  Google Scholar 

  84. Gibellini D, Borderi M, De Crignis E, Cicola R, Vescini F, Caudarella R, Chiodo F, Re MC (2007) RANKL/OPG/TRAIL plasma levels and bone mass loss evaluation in antiretroviral naive HIV-1-positive men. J Med Virol 79:1446–1454

    Article  CAS  PubMed  Google Scholar 

  85. Cotter EJ, Malizia AP, Chew N, Powderly WG, Doran PP (2007) HIV proteins regulate bone marker secretion and transcription factor activity in cultured human osteoblasts with consequent potential implications for osteoblast function and development. AIDS Res Hum Retrovir 23:1521–1530

    Article  CAS  PubMed  Google Scholar 

  86. Fakruddin JM, Laurence J (2003) HIV envelope gp120-mediated regulation of osteoclastogenesis via receptor activator of nuclear factor kappa B ligand (RANKL) secretion and its modulation by certain HIV protease inhibitors through interferon-gamma/RANKL cross-talk. J Biol Chem 278:48251–48258

    Article  CAS  PubMed  Google Scholar 

  87. Beaupere C, Garcia M, Larghero J, Feve B, Capeau J, Lagathu C (2015) The HIV proteins Tat and Nef promote human bone marrow mesenchymal stem cell senescence and alter osteoblastic differentiation. Aging Cell 14:534–546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Chew N, Tan E, Li L, Lim R (2014) HIV-1 tat and rev upregulates osteoclast bone resorption. J Int AIDS Soc 17:19724

    Article  PubMed  PubMed Central  Google Scholar 

  89. Hoy J, Grund B, Roediger M, Ensrud KE, Brar I, Colebunders R, Castro ND, Johnson M, Sharma A, Carr A (2013) Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: the SMART body composition substudy. J Bone Miner Res 28:1264–1274

    Article  CAS  PubMed  Google Scholar 

  90. Haskelberg H, Carr A, Emery S (2011) Bone turnover markers in HIV disease. AIDS Rev 13:240–250

    PubMed  Google Scholar 

  91. Yin MT, Shiau S, Rimland D, Gibert CL, Bedimo RJ, Rodriguez-Barradas MC, Harwood K, Aschheim J, Justice AC, Womack JA (2016) Fracture prediction with modified-FRAX in older HIV-infected and uninfected men. J Acquir Immune Defic Syndr 72:513–520

    Article  PubMed  PubMed Central  Google Scholar 

  92. Yang J, Sharma A, Shi Q, Anastos K, Cohen MH, Golub ET, Gustafson D, Merenstein D, Mack WJ, Tien PC, Nieves JW, Yin MT (2018) Improved fracture prediction using different fracture risk assessment tool adjustments in HIV-infected women. AIDS 32:1699–1706

    Article  CAS  PubMed  Google Scholar 

  93. Sharma A, Ma Y, Tien PC, Scherzer R, Anastos K, Cohen MH, Hans D, Yin MT (2018) 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 78:441–449

    Article  PubMed  PubMed Central  Google Scholar 

  94. McGinty T, Cotter AG, Sabin CA, Macken A, Kavanagh E, Compston J, Sheehan G, Lambert J, Mallon PWG, Group HUS (2019) Assessment of trabecular bone score, an index of bone microarchitecture, in HIV positive and HIV negative persons within the HIV UPBEAT cohort. PLoS One 14:e0213440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Ciullini L, Pennica A, Argento G, Novarini D, Teti E, Pugliese G, Aceti A, Conti FG (2018) Trabecular bone score (TBS) is associated with sub-clinical vertebral fractures in HIV-infected patients. J Bone Miner Metab 36:111–118

    Article  PubMed  Google Scholar 

  96. EACS (2018) European guidelines for treatment of HIV-positive adults in Europe 2018. http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html. European AIDS clinical society http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html 2019

  97. Brown TT, Hoy J, Borderi M, Guaraldi G, Renjifo B, Vescini F, Yin MT, Powderly WG (2015) Recommendations for evaluation and management of bone disease in HIV. Clin Infect Dis 60:1242–1251

    Article  PubMed  PubMed Central  Google Scholar 

  98. Wunder DM, Bersinger NA, Fux CA, Mueller NJ, Hirschel B, Cavassini M, Elzi L, Schmid P, Bernasconi E, Mueller B, Furrer H, Swiss HIV Cohort Study (2007) Hypogonadism in HIV-1-infected men is common and does not resolve during antiretroviral therapy. Antivir Ther 12:261–265

    Article  CAS  PubMed  Google Scholar 

  99. Rietschel P, Corcoran C, Stanley T, Basgoz N, Klibanski A, Grinspoon S (2000) Prevalence of hypogonadism among men with weight loss related to human immunodeficiency virus infection who were receiving highly active antiretroviral therapy. Clin Infect Dis 31:1240–1244

    Article  CAS  PubMed  Google Scholar 

  100. Womack JA, Murphy TE, Rentsch CT et al (2019) Polypharmacy, hazardous alcohol and illicit substance use, and serious falls among PLWH and uninfected comparators. Journal of Acquired Immune Deficiency Syndromes (1999) 82:305–313

    Article  CAS  Google Scholar 

  101. Collin F, Duval X, Le Moing V, Piroth L, Al Kaied F, Massip P, Villes V, Chene G, Raffi F (2009) Ten-year incidence and risk factors of bone fractures in a cohort of treated HIV1-infected adults. AIDS (London, England) 23:1021–1024

    Article  Google Scholar 

  102. Sharma A, Hoover DR, Shi Q, Holman S, Plankey MW, Tien PC, Weber KM, Floris-Moore M, Bolivar HH, Vance DE, Golub ET, Holstad MM, Yin MT (2018) Longitudinal study of falls among HIV-infected and uninfected women: the role of cognition. Antivir Ther 23:179–190

    Article  PubMed  PubMed Central  Google Scholar 

  103. Erlandson KM, Zhang L, Ng DK, Althoff KN, Palella FJ Jr, Kingsley LA, Jacobson LP, Margolick JB, Lake JE, Brown TT (2019) Risk factors for falls, falls with injury, and falls with fracture among older men with or at risk of HIV infection. J Acquir Immune Defic Syndr 81:e117–e126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Santos WR, Santos WR, Paes PP, Ferreira-Silva IA, Santos AP, Vercese N, Machado DR, de Paula FJ, Donadi EA, Navarro AM, Fernandes AP (2015) Impact of strength training on bone mineral density in patients infected with HIV exhibiting lipodystrophy. J Strength Cond Res 29:3466–3471

    Article  PubMed  Google Scholar 

  105. Perazzo JD, Webel AR, Alam SMK, Sattar A, McComsey GA (2018) Relationships between physical activity and bone density in people living with HIV: results from the SATURN-HIV study. J Assoc Nurse AIDS Care 29:528–537

    Article  Google Scholar 

  106. Yin MT, RoyChoudhury A, Bucovsky M et al (2019) A randomized placebo-controlled trial of low- versus moderate-dose vitamin D3 supplementation on bone mineral density in postmenopausal women with HIV. J Acquir Immune Defic Syndr 80:342–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Gregson CL, Hartley A, Majonga E, McHugh G, Crabtree N, Rukuni R, Bandason T, Mukwasi-Kahari C, Ward KA, Mujuru H, Ferrand RA (2019) Older age at initiation of antiretroviral therapy predicts low bone mineral density in children with perinatally-infected HIV in Zimbabwe. Bone 125:96–102

    Article  PubMed  PubMed Central  Google Scholar 

  108. Biver E, Calmy A, Aubry-Rozier B et al (2019) Diagnosis, prevention, and treatment of bone fragility in people living with HIV: a position statement from the Swiss Association against Osteoporosis. Osteoporos Int 30:1125–1135

    Article  CAS  PubMed  Google Scholar 

  109. Ciccullo A, D'Avino A, Lassandro AP et al (2018) Changes in bone mineral density in HIV-positive, virologically suppressed patients switching to lamivudine/dolutegravir dual therapy: preliminary results from clinical practice. Infez Med 26:336–340

    PubMed  Google Scholar 

  110. Ofotokun I, Collins LF, Titanji K, Foster A, Moran CA, Sheth AN, Lahiri CD, Lennox JL, Ward L, Easley KA, Weitzmann MN (2019) Antiretroviral therapy-induced bone loss is durably suppressed by a single dose of zoledronic acid in treatment-naïve persons with HIV infection: a Phase IIB Trial. Clin Infect Dis. pii: ciz1027. https://doi.org/10.1093/cid/ciz1027

  111. Bolland MJ, Grey A, Horne AM, Briggs SE, Thomas MG, Ellis-Pegler RB, Gamble GD, Reid IR (2012) Effects of intravenous zoledronate on bone turnover and bone density persist for at least five years in HIV-infected men. J Clin Endocrinol Metab 97:1922–1928

    Article  CAS  PubMed  Google Scholar 

  112. Bolland MJ, Grey AB, Horne AM, Briggs SE, Thomas MG, Ellis-Pegler RB, Woodhouse AF, Gamble GD, Reid IR (2007) Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial. J Clin Endocrinol Metab 92:1283–1288

    Article  CAS  PubMed  Google Scholar 

  113. Guaraldi G, Orlando G, Madeddu G, Vescini F, Ventura P, Campostrini S, Mura MS, Parise N, Caudarella R, Esposito R (2004) Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis. HIV Clin Trials 5:269–277

    Article  CAS  PubMed  Google Scholar 

  114. Huang J, Meixner L, Fernandez S, McCutchan JA (2009) A double-blinded, randomized controlled trial of zoledronate therapy for HIV-associated osteopenia and osteoporosis. AIDS (London, England) 23:51–57

    Article  CAS  Google Scholar 

  115. Mondy K, Powderly WG, Claxton SA, Yarasheski KH, Royal M, Stoneman JS, Hoffmann ME, Tebas P (2005) Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection. J Acquir Immune Defic Syndr 38:426–431

    Article  CAS  PubMed  Google Scholar 

  116. Negredo E, Bonjoch A, Perez-Alvarez N et al (2015) Comparison of two different strategies of treatment with zoledronate in HIV-infected patients with low bone mineral density: single dose versus two doses in 2 years. HIV Med 16:441–448

    Article  CAS  PubMed  Google Scholar 

  117. Negredo E, Martinez-Lopez E, Paredes R et al (2005) Reversal of HIV-1-associated osteoporosis with once-weekly alendronate. AIDS (London, England) 19:343–345

    CAS  Google Scholar 

  118. Sahni S, Mangano KM, McLean RR, Hannan MT, Kiel DP (2015) Dietary approaches for bone health: lessons from the Framingham osteoporosis study. Curr Osteoporos Rep 13:245–255

    Article  PubMed  PubMed Central  Google Scholar 

  119. Hoy JF, Richardson R, Ebeling PR, Rojas J, Pocock N, Kerr SJ, Martinez E, Carr A, Investigators ZS (2018) Zoledronic acid is superior to tenofovir disoproxil fumarate-switching for low bone mineral density in adults with HIV. AIDS 32:1967–1975

    Article  CAS  PubMed  Google Scholar 

  120. Pinzone MR, Moreno S, Cacopardo B, Nunnari G (2014) Is there enough evidence to use bisphosphonates in HIV-infected patients? A systematic review and meta-analysis. AIDS Rev 16:213–222

    PubMed  Google Scholar 

  121. Landfeldt E, Strom O, Robbins S, Borgstrom F (2012) Adherence to treatment of primary osteoporosis and its association to fractures--the Swedish Adherence Register Analysis (SARA). Osteoporos Int 23:433–443

    Article  CAS  PubMed  Google Scholar 

  122. Bolland MJ, Horne AM, Briggs SE, Thomas MG, Reid I, Gamble GD, Grey A (2019) Effects of intravenous zoledronate on bone turnover and bone density persist for at least 11 years in HIV-infected men. J Bone Miner Res 34:1248–1253

    Article  CAS  PubMed  Google Scholar 

  123. Negredo E, Warriner AH (2016) Pharmacologic approaches to the prevention and management of low bone mineral density in HIV-infected patients. Curr Opin HIV AIDS 11:351–357

    Article  CAS  PubMed  Google Scholar 

  124. Papapoulos S, Lippuner K, Roux C, Lin CJ, Kendler DL, Lewiecki EM, Brandi ML, Czerwiński E, Franek E, Lakatos P, Mautalen C, Minisola S, Reginster JY, Jensen S, Daizadeh NS, Wang A, Gavin M, Libanati C, Wagman RB, Bone HG (2015) The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporos Int 26:2773–2783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Stopeck AT, Fizazi K, Body JJ, Brown JE, Carducci M, Diel I, Fujiwara Y, Martín M, Paterson A, Tonkin K, Shore N, Sieber P, Kueppers F, Karsh L, Yardley D, Wang H, Maniar T, Arellano J, Braun A (2016) Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer. Support Care Cancer 24:447–455

    Article  PubMed  Google Scholar 

  126. Wheeler AL, Tien PC, Grunfeld C, Schafer AL (2015) Teriparatide treatment of osteoporosis in an HIV-infected man: a case report and literature review. AIDS (London, England) 29:245–246

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

    M.O. Premaor

  2. Department of Medicine, Cambridge Biomedical Campus, Cambridge, UK

    J.E. Compston

Authors
  1. M.O. Premaor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J.E. Compston
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M.O. Premaor.

Ethics declarations

Conflicts of interest

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Premaor, M., Compston, J. People living with HIV and fracture risk. Osteoporos Int 31, 1633–1644 (2020). https://doi.org/10.1007/s00198-020-05350-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-020-05350-y

Keywords

Search

Navigation