Archives of Osteoporosis

, 13:56 | Cite as

Increased prevalence of asymptomatic vertebral fractures in HIV-infected patients over 50 years of age

  • Maria LlopEmail author
  • W. A. Sifuentes
  • S. Bañón
  • C. Macia-Villa
  • M. J. Perez-Elías
  • M. Rosillo
  • S. Moreno
  • M. Vázquez
  • J. L. Casado
Original Article



The prevalence of asymptomatic vertebral fracture in HIV-infected patients over 50 was 20%, associated with older age, male sex, longer time since HIV diagnosis, and tubular renal alterations. Vertebral fractures were independent of osteoporosis at lumbar spine, and were not predicted by the use of the FRAX equation.


Vertebral fractures (VF) are the hallmark of osteoporotic fractures. Our objective was to determine the prevalence of asymptomatic VF and associated factors in HIV-infected patients over 50 years, and the role of FRAX equation.


In a cross-sectional study, a diagnosis of VF was established by the semiquantitative method of Genant in thoracic and lumbar radiographs. Simultaneously, a dual X-ray absorptiometry (DXA), bone and kidney-related analytical, calcium intake, physical exercise, HIV-related factors, and FRAX estimation were evaluated.


Overall, 128 patients (35 women, 27%) were included. Mean age was 57 years. Hypophosphatemia and tubular renal dysfunction were observed in 13 and 21%. DXA scan showed osteopenia and osteoporosis at hip in 65 and 7% of patients, and in spine in 39 and 34%, respectively. VF were observed in 26 patients (20%), with a trend to be associated with lower serum phosphate, increased alkaline phosphatase, and with lower daily calcium intake. In a multivariate analysis, older age (OR 1.2 per year; 14% of VF at 50–55; 44% at 65–70), male sex (26 vs 6%), longer time since HIV diagnosis, and renal and tubular dysfunction were the associated factors. VF were not related with osteoporosis at lumbar spine, and could not be predicted by the FRAX equation.


The prevalence of asymptomatic vertebral fractures is high in HIV-infected patients older than 50 years, and is not identified by the presence of osteoporosis in spine neither predicted by the FRAX equation. Spine and lumbar X-rays should be routinely performed in this aging population.


Vertebral fractures Bone HIV Antiretroviral treatment DXA FRAX equation 



We would like to thank Ana Abad for their important contribution in database management.

Author contribution

JLC, MLL, and CM conceived and designed the study and were responsible for patient enrollment, follow-up, and data analysis and drafted and finalized the article; MR conceived and performed analytical evaluations, and WAS, SB, MJPE, MV, and SM were responsible for patient enrollment, clinically followed up patients, and helped to write the work. All coauthors revised the manuscript and approved the final version.

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Arnsten JH, Freeman R, Howard AA, Floris-Moore M, Santoro N, Schoenbaum EE (2006) HIV infection and bone mineral density in middle-aged women. Clin Infect Dis Off Publ Infect Dis Soc Am 42(7):1014–1020CrossRefGoogle Scholar
  2. 2.
    Porcelli T, Gotti D, Cristiano A, Maffezzoni F, Mazziotti G, Focà E, Castelli F, Giustina A, Quiros-Roldan E (2014) Role of bone mineral density in predicting morphometric vertebral fractures in patients with HIV infection. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 25(9):2263–2269CrossRefGoogle Scholar
  3. 3.
    Amiel C, Ostertag A, Slama L, Baudoin C, N’Guyen T, Lajeunie E et al (2004) BMD is reduced in HIV-infected men irrespective of treatment. J Bone Miner Res Off J Am Soc Bone Miner Res 19(3):402–409CrossRefGoogle Scholar
  4. 4.
    Brown TT, Qaqish RB (2006) Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS Lond Engl. 20(17):2165–2174CrossRefGoogle Scholar
  5. 5.
    Walker Harris V, Brown TT (2012 Jun) Bone loss in the HIV-infected patient: evidence, clinical implications, and treatment strategies. J Infect Dis 205(Suppl 3):S391–S398CrossRefGoogle Scholar
  6. 6.
    Casado JL, Bañon S, Andrés R, Perez-Elías MJ, Moreno A, Moreno S (2014) Prevalence of causes of secondary osteoporosis and contribution to lower bone mineral density in HIV-infected patients. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 25(3):1071–1079CrossRefGoogle Scholar
  7. 7.
    Castronuovo D, Cacopardo B, Pinzone MR, Di Rosa M, Martellotta F, Schioppa O et al (2013) Bone disease in the setting of HIV infection: update and review of the literature. Eur Rev Med Pharmacol Sci 17(18):2413–2419PubMedGoogle Scholar
  8. 8.
    Torti C, Mazziotti G, Soldini PA, Focà E, Maroldi R, Gotti D, Carosi G, Giustina A (2012) High prevalence of radiological vertebral fractures in HIV-infected males. Endocrine 41(3):512–517CrossRefGoogle Scholar
  9. 9.
    Borderi M, Calza L, Colangeli V, Vanino E, Viale P, Gibellini D, Re MC (2014) Prevalence of sub-clinical vertebral fractures in HIV-infected patients. New Microbiol 37(1):25–32PubMedGoogle Scholar
  10. 10.
    Gazzola L, Savoldi A, Bai F, Magenta A, Dziubak M, Pietrogrande L, Tagliabue L, del Sole A, Bini T, Marchetti G, d’Arminio Monforte A (2015) Assessment of radiological vertebral fractures in HIV-infected patients: clinical implications and predictive factors. HIV Med 16(9):563–571CrossRefGoogle Scholar
  11. 11.
    Hansen A-BE, 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 Lond Engl 26(3):285–293CrossRefGoogle Scholar
  12. 12.
    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(9):3499–3504CrossRefGoogle Scholar
  13. 13.
    Womack JA, Goulet JL, Gibert C, Brandt C, Chang CC, Gulanski B, Fraenkel L, Mattocks K, Rimland D, Rodriguez-Barradas MC, Tate J, Yin MT, Justice AC, for the Veterans Aging Cohort Study Project Team (2011) Increased risk of fragility fractures among HIV infected compared to uninfected male veterans. PLoS One 6(2):e17217CrossRefGoogle Scholar
  14. 14.
    Prieto-Alhambra D, Güerri-Fernández R, De Vries F, Lalmohamed A, Bazelier M, Starup-Linde J et al (2014) HIV infection and its association with an excess risk of clinical fractures: a nationwide case-control study. J Acquir Immune Defic Syndr 1999 66(1):90–95CrossRefGoogle Scholar
  15. 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(6):1259–1263CrossRefGoogle Scholar
  16. 16.
    Cauley JA, Hochberg MC, Lui L-Y, Palermo L, Ensrud KE, Hillier TA, Nevitt MC, Cummings SR (2007) Long-term risk of incident vertebral fractures. JAMA 298(23):2761–2767CrossRefGoogle Scholar
  17. 17.
    Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB, Licata A, Benhamou L, Geusens P, Flowers K, Stracke H, Seeman E (2001) Risk of new vertebral fracture in the year following a fracture. JAMA 285(3):320–323CrossRefGoogle Scholar
  18. 18.
    Melton LJ, Atkinson EJ, Cooper C, O’Fallon WM, Riggs BL (1999) Vertebral fractures predict subsequent fractures. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 10(3):214–221CrossRefGoogle Scholar
  19. 19.
    Crans GG, Genant HK, Krege JH (2005) Prognostic utility of a semiquantitative spinal deformity index. Bone 37(2):175–179CrossRefGoogle Scholar
  20. 20.
    Fink HA, Milavetz DL, Palermo L, Nevitt MC, Cauley JA, Genant HK, Black DM, Ensrud KE, Fracture Intervention Trial Research Group (2005) What proportion of incident radiographic vertebral deformities is clinically diagnosed and vice versa? J Bone Miner Res Off J Am Soc Bone Miner Res 20(7):1216–1222CrossRefGoogle Scholar
  21. 21.
    Gehlbach SH, Bigelow C, Heimisdottir M, May S, Walker M, Kirkwood JR (2000) Recognition of vertebral fracture in a clinical setting. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 11(7):577–582CrossRefGoogle Scholar
  22. 22.
    Ross PD (1997) Clinical consequences of vertebral fractures. Am J Med 103(2A):30S–42S discussion 42S–43SCrossRefGoogle Scholar
  23. 23.
    Bañón S, Rosillo M, Gómez A, Pérez-Elias MJ, Moreno S, Casado JL (2015 Jun) Effect of a monthly dose of calcidiol in improving vitamin D deficiency and secondary hyperparathyroidism in HIV-infected patients. Endocrine 49(2):528–537CrossRefGoogle Scholar
  24. 24.
    Mondy K, Yarasheski K, Powderly WG, Whyte M, Claxton S, DeMarco D, Hoffmann M, Tebas P (2003) Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals. Clin Infect Dis Off Publ Infect Dis Soc Am 36(4):482–490CrossRefGoogle Scholar
  25. 25.
    Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary reference Intakes for calcium and vitamin D [Internet]. Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Washington (DC): National Academies Press (US); 2011 [cited 2017 May 21]. (The National Academies Collection: Reports funded by National Institutes of Health). Available from:
  26. 26.
    Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE et al (2003) International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 35(8):1381–1395CrossRefGoogle Scholar
  27. 27.
    Del Palacio M, Romero S, Casado JL (2012) Proximal tubular renal dysfunction or damage in HIV-infected patients. AIDS Rev 14(3):179–187PubMedGoogle Scholar
  28. 28.
    Yin MT, Shiau S, Rimland D, Gibert CL, Bedimo RJ, Rodriguez-Barradas MC et al (2016) Fracture prediction with modified-FRAX in older HIV-infected and uninfected men. J Acquir Immune Defic Syndr 1999 72(5):513–520Google Scholar
  29. 29.
    Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group (2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl (113):S1–S130Google Scholar
  30. 30.
    Kanis JA (2002) Diagnosis of osteoporosis and assessment of fracture risk. Lancet Lond Engl 359(9321):1929–1936CrossRefGoogle Scholar
  31. 31.
    Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res Off J Am Soc Bone Miner Res 8(9):1137–1148CrossRefGoogle Scholar
  32. 32.
    Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D et al (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis: the Study of Osteoporotic Fractures Research Group. J Bone Miner Res Off J Am Soc Bone Miner Res 11(7):984–996CrossRefGoogle Scholar
  33. 33.
    Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 19(4):385–397CrossRefGoogle Scholar
  34. 34.
    Martínez E, Jódar Gimeno E, Reyes García R, Carpintero P, Casado JL, Del Pino Montes J et al (2014) Consensus statement: recommendations for the management of metabolic bone disease in human immunodeficiency virus patients. Enferm Infecc Microbiol Clin 32(4):250–258CrossRefGoogle Scholar
  35. 35.
    Sözen T, Özışık L, Başaran NÇ (2017) An overview and management of osteoporosis. Eur J Rheumatol 4(1):46–56CrossRefGoogle Scholar
  36. 36.
    Greendale GA, Wilhalme H, Huang M-H, Cauley JA, Karlamangla AS (2016) Prevalent and incident vertebral deformities in midlife women: results from the Study of Women’s Health Across the Nation (SWAN). PLoS One 11(9):e0162664CrossRefGoogle Scholar
  37. 37.
    Pitukcheewanont P, Safani D, Church J, Gilsanz V (2005) Bone measures in HIV-1 infected children and adolescents: disparity between quantitative computed tomography and dual-energy X-ray absorptiometry measurements. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 16(11):1393–1396CrossRefGoogle Scholar
  38. 38.
    Yin MT, Lund E, Shah J, Zhang CA, Foca M, Neu N, Nishiyama KK, Zhou B, Guo XE, Nelson J, Bell DL, Shane E, Arpadi SM (2014) Lower peak bone mass and abnormal trabecular and cortical microarchitecture in young men infected with HIV early in life. AIDS Lond Engl 28(3):345–353CrossRefGoogle Scholar
  39. 39.
    Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD (2007) Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res Off J Am Soc Bone Miner Res 22(3):425–433CrossRefGoogle Scholar
  40. 40.
    Genant HK, Delmas PD, Chen P, Jiang Y, Eriksen EF, Dalsky GP, Marcus R, San Martin J (2007) Severity of vertebral fracture reflects deterioration of bone microarchitecture. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 18(1):69–76CrossRefGoogle Scholar
  41. 41.
    Naves Díaz M (2006) Fracturas por osteoporosis en la mujer española. Med Clínica 127(11):413–414CrossRefGoogle Scholar
  42. 42.
    Grados F, Marcelli C, Dargent-Molina P, Roux C, Vergnol JF, Meunier PJ, Fardellone P (2004) Prevalence of vertebral fractures in French women older than 75 years from the EPIDOS study. Bone 34(2):362–367CrossRefGoogle Scholar
  43. 43.
    O’Neill TW, Felsenberg D, Varlow J, Cooper C, Kanis JA, Silman AJ (1996) The prevalence of vertebral deformity in European men and women: the European Vertebral Osteoporosis Study. J Bone Miner Res Off J Am Soc Bone Miner Res 11(7):1010–1018CrossRefGoogle Scholar
  44. 44.
    Zeytinoglu M, Jain RK, Vokes TJ (2017) Vertebral fracture assessment: enhancing the diagnosis, prevention, and treatment of osteoporosis. Bone 104:54–65CrossRefGoogle Scholar
  45. 45.
    Naylor KL, McArthur E, Leslie WD, Fraser L-A, Jamal SA, Cadarette SM, Pouget JG, Lok CE, Hodsman AB, Adachi JD, Garg AX (2014) The three-year incidence of fracture in chronic kidney disease. Kidney Int 86(4):810–818CrossRefGoogle Scholar
  46. 46.
    Casado JL (2016) Renal and bone toxicity with the use of tenofovir: understanding at the end. AIDS Rev 18(2):59–68PubMedGoogle Scholar
  47. 47.
    Bedimo R, Rosenblatt L, Myers J (2016) Systematic review of renal and bone safety of the antiretroviral regimen efavirenz, emtricitabine, and tenofovir disoproxil fumarate in patients with HIV infection. HIV Clin Trials 17(6):246–266CrossRefGoogle Scholar
  48. 48.
    Vannucci L, Masi L, Gronchi G, Fossi C, Carossino AM, Brandi ML (2017) Calcium intake, bone mineral density, and fragility fractures: evidence from an Italian outpatient population. Arch Osteoporos 12(1):40CrossRefGoogle Scholar
  49. 49.
    Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster J-Y et al (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 24(1):23–57CrossRefGoogle Scholar
  50. 50.
    Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA, Infectious Diseases Society of America (2014) Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am 58(1):e1–e34Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  • Maria Llop
    • 1
    Email author
  • W. A. Sifuentes
    • 1
  • S. Bañón
    • 2
  • C. Macia-Villa
    • 3
  • M. J. Perez-Elías
    • 2
  • M. Rosillo
    • 4
  • S. Moreno
    • 2
  • M. Vázquez
    • 1
  • J. L. Casado
    • 2
  1. 1.Department of RheumatologyRamon y Cajal HospitalMadridSpain
  2. 2.Department of Infectious DiseasesRamon y Cajal HospitalMadridSpain
  3. 3.Department of RheumatologySevero Ochoa HospitalMadridSpain
  4. 4.Department of BiochemistryRamon y Cajal HospitalMadridSpain

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