Antiretroviral Therapy and Bone Health

Open access


Objective: To determine the incidence of osteopenia and osteoporosis in Bulgarian human immunodeficiency virus (HIV)-infected patients.

Methods: Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry in 41 Bulgarian HIV-infected patients.

Results: Overall, 27% of patients had reduced BMD (7% osteoporosis and 20% osteopenia). There was a significant correlation between low BMD and increasing age and between low BMD and duration of antiretroviral therapy (ART) but no correlation with gender, therapy regimen or serum calcium or phosphate levels. Seventy-one percent had elevated serum cystatin C levels but there was no correlation between BMD and cystatin C levels. Serum calcium, phosphate, cystatin C and creatinine levels and the T- and Z-scores were tested for dependence on duration of therapy. Dependence was found for T- and Z-scores, (p = 0.048 and p = 0.038) but not for calcium, phosphate, cystatin C or creatinine levels. These variables were subsequently tested by means of cross-tabulation tables for correlations between pairs of parameters; no significant correlation was found between any pairs (R > 0.5 for all comparisons).

Conclusions: Significant correlations were observed between low BMD and increasing age and longer duration of ART but no relationship was observed with gender or therapy regimen.

1. Ando M, Yanagisawa N. Epidemiology, clinical characteristics, and management of chronic kidney disease in human immunodeficiency virus-infected patients. World J Nephrol 2015;4(3):388-95.

2. Borissova AM, Rashkov R, Boyanov M et al. Femoral neck bone mineral density and 10-year absolute fracture risk in a national representative sample of Bulgarian women aged 50 years and older. Arch Osteoporos 2011;6:189-95.

3. Bruera D, Luna N, David DO et al. Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy. AIDS 2003;17(13):1917-23.

4. Cazanave C, Dupon M, Lavignolle-Aurillac V et al. Reduced bone mineral density in HIV-infected patients: prevalence and associated factors. AIDS 2008;22(3):395-402.

5. Chitu-Tisu CE, Barbu EC, Lazar M et al. Body composition in HIV-infected patients receiving highly active antiretroviral therapy. Acta Clin Belg 2017;72(1):55-62.

6. Chitu-Tisu CE, Barbu EC, Lazar M et al. Low bone mineral density and associated risk factors in HIV-infected patients. Germs 2016;6(2):50-9.

7. Danjuma MI, Mohamad-Fadzillah NH, Khoo S. An investigation of the pattern of kidney injury in HIV-positive persons exposed to tenofovir disoproxil fumarate: an examination of a large population database (MHRA database). Int J STD AIDS 2014;25(4):273-9.

8. Deya-Martinez A, Fortuny C, Soler-Palacin P et al. Cystatin C: a marker for inflammation and renal function among HIV-infected children and adolescents. Pediatr Infect Dis J 2016;35(2):196-200.

9. Duvivier C, Kolta S, Assoumou L, Ghosn J, Rozenberg S, Murphy RL, et al. Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleo-side reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS 2009;23(7):817-24.

10. Ezinga M, Wetzels JF, Bosch ME et al. Long-term treatment with tenofovir: prevalence of kidney tubular dysfunction and its association with tenofovir plasma concentration. Antivir Ther 2014;19(8):765-71.

11. Gallant JE, Parish MA, Keruly JC, Moore RD. Changes in renal function associated with tenofovir disoproxil fumarate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment. Clin Infect Dis 2005;40(8):1194-8.

12. 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 2017. doi: 10.1007/s00198-017-4305-8.

13. Grant PM, Cotter AG. Tenofovir and bone health. Curr Opin HIV AIDS 2016;11(3):326-32.

14. Grigsby IF, Pham L, Mansky LM et al. Tenofovir-associated bone density loss. Ther Clin Risk Manag 2010;6:41-7.

15. Hall AM, Hendry BM, Nitsch D, Connolly JO. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis 2011;57(5):773-80.

16. Hileman CO, Eckard AR, McComsey GA. Bone loss in HIV: a contemporary review. Curr Opin Endocrinol Diabetes Obes 2015;22(6):446-51.

17. Hojs R, Bevc S, Ekart R et al. Serum cystatin C-based equation compared to serum creatinine-based equations for estimation of glomerular filtration rate in patients with chronic kidney disease. Clin Nephrol 2008;70(1):10-7.

18. Hudec SM, Camacho PM. Secondary causes of osteoporosis. Endocr Pract 2013;19(1):120-8.

19. International Society for Clinical Densitometry (ISCD). 2017. Available from: [Accessed 22 November 2017].

20. Joffe I, Epstein S. Osteoporosis associated with rheumatoid arthritis: pathogenesis and management. Semin Arthritis Rheum 1991;20(4):256-72.

21. Kirilov G. Laboratory diagnosis of parathyroid gland diseases and bone mineral metabolism. In: Paradigm, editor. Hormonal and Functional Diagnosis of Endocrine Diseases; 2012.

22. Kohlmeier L, Gasner C, Bachrach LK, Marcus R. The bone mineral status of patients with Marfan syndrome. J Bone Miner Res 1995;10(10):1550-5.

23. Lucas K, Behrens BA, Nolte I et al. Comparative investigation of bone mineral density using CT and DEXA in a canine femoral model. J Orthop Res 2017. doi: 10.1002/jor.23574.

24. McComsey GA, Kitch D, Daar ES et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarateemtricitabine along with efavirenz or atazanavir-ritonavir: AIDS Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis 2011;203(12):1791-801.

25. 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(8):937-46.

26. Moran CA, Weitzmann MN, Ofotokun I. Bone loss in HIV infection. Curr Treat Options Infect Dis 2017;9(1):52-67.

27. Pan G, Yang Z, Ballinger SW, McDonald JM. Pathogenesis of osteopenia/osteoporosis induced by highly active anti-retroviral therapy for AIDS. Ann N Y Acad Sci 2006;1068:297-308.

28. Powderly WG. Osteoporosis and bone health in HIV. Curr HIV/AIDS Rep 2012;9(3):218-22.

29. Rosen CJ. The epidemiology and pathogenesis of osteoporosis. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A et al. Endotext. South Dartmouth (MA): MDText. com, Inc.; 2000.

30. Sandhu SK, Hampson G. The pathogenesis, diagnosis, investigation and management of osteoporosis. J Clin Pathol 2011;64(12):1042-50.

31. Shlipak MG, Mattes MD, Peralta CA. Update on cystatin C: incorporation into clinical practice. Am J Kidney Dis 2013;62(3):595-603.

32. Streinu-Cercel A, Sandulescu O, Ceapraga G, et al. Prevalence of osteo-renal impairment in the Romanian HIV cohort. BMC Infect Dis 2016;16 Suppl 1:93.

33. Van Dijk FS. Genetics of osteoporosis in children. Endocr Dev 2015;28:196-209.

34. Wasserman P, Rubin DS. Highly prevalent vitamin D deficiency and insufficiency in an urban cohort of HIV-infected men under care. AIDS Patient Care STDS 2010;24(4):223-7.

35. Welz T, Childs K, Ibrahim F et al. Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase. Aids 2010;24(12):1923-8.

36. Woodward CL, Hall AM, Williams IG et al. Tenofovir-associated renal and bone toxicity. HIV Med 2009;10(8):482-7.

37. World Health Organization. WHO scientific group on the assessment of osteoporosis at primary health care level 2007. Available from: [Accessed 22 November 2017].

38. Yancheva N. Complications of antiretroviral therapy in HIV-infected patients. Vitamin D deficiency. PhD Thesis.

39. Yancheva N, Nikolova M, Alexandrova M et al. Deficiency of vitamin D in HIV infected patients and its effect on some of the immunological parameters. World J AIDS 2015;5(3):182-8.

40. Yancheva N, Tchervenyakova T, Gabarska I, Elenkov I. De-ficiency of vitamin D in HIV infected patients and its effect on some of the biochemical parameters. Indian J Pharm Sci 2016;3(2):57-64.

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