The role of HIV and antiretroviral therapy in bone disease

AIDS Reviews

Volumn 13, Issue 2, 2011, Pages 109-118

  Gutiérrez, Félix ^a,b   Masiá, Mar ^a,b  

^a Hospital General Universitario   (Spain)

^b MIGUEL HERNÁNDEZ UNIVERSITY   (Spain)

Author keywords

AIDS; Antiretroviral therapy; Bone disease; Bone mineral density; HIV complications; Osteopenia; Osteoporosis; Tenofovir; Vitamin D

Indexed keywords

ABACAVIR PLUS LAMIVUDINE; ANTIRETROVIRUS AGENT; ATAZANAVIR PLUS RITONAVIR; CALCIUM; EFAVIRENZ; EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; HUMAN IMMUNODEFICIENCY VIRUS PROTEIN; INDINAVIR; LAMIVUDINE PLUS ZIDOVUDINE; LOPINAVIR PLUS RITONAVIR; NELFINAVIR; NEVIRAPINE; PARATHYROID HORMONE; PHOSPHATE; PROTEINASE INHIBITOR; RILPIVIRINE; RITONAVIR; STAVUDINE; TENOFOVIR; VITAMIN D; ZIDOVUDINE; ADENINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DRUG DERIVATIVE; PHOSPHONIC ACID DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

BONE DEMINERALIZATION; BONE DENSITY; BONE DISEASE; BONE MASS; BONE MINERAL; BONE REMODELING; CALCITRIOL DEGRADATION; CD4 LYMPHOCYTE COUNT; CELL COMPARTMENTALIZATION; CELL FUNCTION; CLINICAL PRACTICE; DRUG EFFECT; DUAL ENERGY X RAY ABSORPTIOMETRY; FRACTURE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HIP; HORMONE METABOLISM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPOPHOSPHATEMIA; IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME; LUMBAR SPINE; NEPHROTOXICITY; NONHUMAN; OSTEOBLAST; OSTEOCLAST; OSTEOLYSIS; OSTEOMALACIA; OSTEOPENIA; OSTEOPOROSIS; PARATHYROID HORMONE BLOOD LEVEL; PHOSPHATE BALANCE; REVIEW; SIDE EFFECT; VITAMIN D DEFICIENCY; VITAMIN D METABOLISM; ADULT; CLINICAL TRIAL (TOPIC); DRUG COMBINATION; METABOLIC BONE DISEASE; TREATMENT OUTCOME;

ADENINE; ADULT; ANTI-HIV AGENTS; BONE DISEASES, METABOLIC; CLINICAL TRIALS AS TOPIC; DRUG THERAPY, COMBINATION; HIV INFECTIONS; HUMANS; OSTEOPOROSIS; PHOSPHONIC ACIDS; REVERSE TRANSCRIPTASE INHIBITORS; TREATMENT OUTCOME;

EID: 80053091721     PISSN: 11396121     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (78)

1. Brown T, Qaqish R. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS. 2006;20:2165-74. (Pubitemid 44684707)
2. Miller K, Masur H, Jones E, et al. High prevalence of osteonecrosis of the femoral head in HIV-infected adults. Ann Intern Med. 2002; 137:17-25.
3. Gutiérrez F, Padilla S, Ortega E, et al. Avascular necrosis of the bone in HIV-infected patients: incidence and associated factors. AIDS. 2002; 16:481-3. (Pubitemid 34165381)
4. Morse C; Mican J, Jones E, et al. The incidence and natural history of osteonecrosis in HIV-infected adults. Clin Infect Dis. 2007;44:739-48.
5. Gutierrez F, Padilla S, Masiá M, et al. Osteonecrosis in patients infected with HIV: clinical epidemiology and natural history in a large case series. J Acquir Immune Defic Syndr. 2006;42:286-92. (Pubitemid 44050005)
6. Triant V, Brown T, Lee H, Grinspoon S. Fracture prevalence among HIVinfected versus non HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab. 2008;93:3499-504.
7. Young B, Dao C, Buchacz K, et al. 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. 2011;52:1061-8.
8. Womack J, Goulet J, Gibert C, et al. Increased risk of fragility fractures among HIV infected compared to uninfected male veterans. PLoS One. 2011;6:e17217.
9. Tebas P, Powderly W, Claxton S, et al. Accelerated bone mineral loss in HIV-infected patients receiving antiretroviral therapy. AIDS. 2000; 14:F63-7. (Pubitemid 30182458)
10. McComsey G, Kitch D, Daar E, et al. Bone and limb fat outcomes of ACTG A5224s, a substudy of ACTG A5202: A prospective, randomized, partially blinded phase III trial of ABC/3TC or TDF/ FTC with EFV or ATV/r for initial treatment of HIV-1 infection. 17th CROI. 2010 San Francisco, USA [abstract 106LB].
11. Carr A, Miller J, Eisman J, Cooper D. Osteopenia in HIV-infected men: association with lactic acidemia and lower weight pre-antiretroviral therapy. AIDS. 2001;15:703-9. (Pubitemid 32423217)
12. Gallant J, Staszewski S, Pozniak A, et al. Efficacy and safety of tenofovir DF vs. stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. 903 Study Group. JAMA. 2004;292:191-201. (Pubitemid 38917996)
13. van Vonderen M, Lips P, van Agtmael M, et al. First line zidovudine/ lamivudine/lopinavir /ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir. AIDS. 2009;23:1367-76.
14. Madruga J, Cassetti I, Suleiman J, et al. Study 903E Team. The safety and efficacy of switching stavudine to tenofovir DF in combination with lamivudine and efavirenz in HIV-1-infected patients: three-year follow-up after switching therapy. HIV Clin Trials. 2007;8:381-90. (Pubitemid 350305212)
15. Stellbrink H, Orkin C, Arribas J, et al. 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. 2010;51:963-72.
16. Martin A, Bloch M, Amin J, et al. Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine: a randomized, 96- week trial. Clin Infect Dis. 2009;49:1591-601.
17. Overton T, Mondy K, Bush T, et al. Factors associated with low bone mineral density in a large cohort of HIV-infected US adults: baseline results from the SUN study. 14th CROI. 2007 Los Angeles, USA [abstract 836].
18. Mondy K, Yarasheski K, Powderly WG, et al. Longitudinal evolution of bone mineral density and bone markers in HIV-infected individuals. Clin Infect Dis. 2003;36:482-90. (Pubitemid 36241317)
19. Lo Re V, Guaraldi G, Leonard M, et al. Viral hepatitis is associated with reduced bone mineral density in HIV-infected women but not men. AIDS. 2009;23:2191-8.
20. Gibellini D, De Crignis E, Ponti C, et al. HIV-1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNFalpha activation. J Med Virol. 2008;80:1507-14.
21. Cotter E, Malizia A, Chew N, Powderly W, Doran P. 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 Retroviruses. 2007;23:1521-30.
22. Fakruddin J, Laurence J. 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. 2003;278:48251-8. (Pubitemid 37523280)
23. Cotter E, Mallon P, Doran P. Is PPARg a prospective player in HIV-1 associated bone disease? PPAR Res. 2009;2009:1-9.
24. Fakruddin J, Laurence J. HIV-1 Vpr enhances production of receptor of activated NF-kappaB ligand (RANKL) via potentiation of glucocorticoid receptor activity. Arch Virol. 2005;150:67-78. (Pubitemid 40171950)
25. Gruber M, Weih K, Boone E, Smith P, Clouse K. Endogenous macrophage CSF production is associated with viral replication in HIV-1- infected human monocyte derived macrophages. J Immunol. 1995; 154:5528-35.
26. Aukrust P, Haug C, Ueland T, et al. Decreased bone formative and enhanced resorptive markers in human immunodeficiency virus infection: indication of normalization of the bone-remodeling process during highly active antiretroviral therapy. J Clin Endocrinol Metab. 1999;84: 145-50. (Pubitemid 29036693)
27. Kong Y, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397:315-23.
28. Wei S, Kitaura H, Zhou P, Ross F, Teitelbaum S. IL-1 mediates TNF induced osteoclastogenesis. J Clin Invest. 2005;115:282-90. (Pubitemid 40385470)
29. Hittinger G, Poggi C, Delbeke E, Profizi N, Lafeuillade A. Correlation between plasma levels of cytokines and HIV-1 RNA copy number in HIV-infected patients. Infection. 1998;26:100-3. (Pubitemid 28142928)
30. Knobel H, Guelar A, Vallecillo G, Nogués X, Díez A. Osteopenia in HIVinfected patients: is it the disease or is it the treatment? AIDS. 2001;15:807-8. (Pubitemid 32423234)
31. Bruera D, Luna N, David DO, Bergoglio LM, Zamudio J. Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy. AIDS. 2003;17:1917-23. (Pubitemid 37070277)
32. Powderly W, Cohen C, Gallant J, Lu B, Enejosa J, Cheng A. Similar incidence of osteopenia and osteoporosis in ART-naive patients treated with tenofovir DF or stavudine in combination with lamivudine and efavirenz over 144 weeks. 903 Study Group. 12th CROI. 2005 Boston, USA [abstract 823].
33. Gutiérrez Rodero F, Padilla Urrea S. [Bone metabolism disorders and avascular bone necrosis: a further problem in HIV-infected patients?] Med Clin (Barc). 2002;119:103-8.
34. Rivas P, Gorgolas M, Garcia-Delgado R, Diaz-Curiel M, Goyenechea A, Fernandez-Guerrero M. Evolution of bone mineral density in AIDS patients on treatment with zidovudine/lamivudine plus abacavir or lopinavir/ ritonavir. HIV Med. 2008;9:89-95. (Pubitemid 351228131)
35. Brown T, McComsey G, King M, Qaqish R, Bernstein B, da Silva B. Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen. J Acquir Immune Defic Syndr. 2009; 51:554-61.
36. Huang J, Hughes M, Riddler S, Haubrich R, AIDS Clinical Trials Group 5142 Study Team. Effects of randomized regimen and nucleoside reverse transcriptase inhibitor (NRTI) selection on 96 week bone mineral density (BMD): results from ACTG 5142. 18th IAC; 2010, Vienna, Austria [abstract WEAB0304].
37. Grund B, Peng G, Gibert C, et al. INSIGHT SMART Body Composition Substudy Group. Continuous antiretroviral therapy decreases bone mineral density. AIDS. 2009;23:1519-29.
38. Mulligan K, Glidden D, Gonzales P, et al. Effects of FTC/TDF on bone mineral density in seronegative men from 4 continents: DEXA results of the global iPrEx Study. 18th CROI. 2011 Boston, USA [abstract 94LB].
39. Dolan S, Kanter J, Grinspoon S. Longitudinal analysis of bone density in human immunodeficiency virus-infected women. J Clin Endocrinol Metab. 2006;91:2938-45. (Pubitemid 44271739)
40. Duvivier C, Kolta S, Assoumou L, et al. ANRS 121 Hippocampe study group. Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS. 2009;23:817-24.
41. Dubé M, Qian D, Edmondson-Melançon H, et al. Prospective, intensive study of metabolic changes associated with 48 weeks of amprenavirbased antiretroviral therapy. Clin Infect Dis. 2002;35:475-81. (Pubitemid 34852578)
42. Tebas P, Zhang J, Yarasheski K, et al. Switching to a protease inhibitorcontaining/ nucleoside-sparing regimen increases limb fat but raises serum lipid levels: results of a prospective randomized trial, ACTG 5125s. J Acquir Immune Defic Syndr. 2007;45:193-200. (Pubitemid 46869812)
43. Tebas P, Yarasheski K, Henry K, et al. Evaluation of the virological and metabolic effects of switching protease inhibitor combination antiretroviral therapy to nevirapine-based therapy for the treatment of HIV infection. AIDS Res Hum Retroviruses. 2004;20:589-94. (Pubitemid 38813655)
44. Madruga J, Cassetti I, Suleiman J, et al. Study 903E Team. The safety and efficacy of switching stavudine to tenofovir DF in combination with lamivudine and efavirenz in HIV-1-infected patients: three-year follow-up after switching therapy. HIV Clin Trials. 2007;8:381-90. (Pubitemid 350305212)
45. th CROI. 2010 San Francisco, USA [abstract 747].
46. Bonjoch A, Figueras M, Estany C, et al. High prevalence of and progression to low bone mineral density in HIV-infected patients: a longitudinal cohort study. AIDS. 2010;24:2827-33.
47. Jain R, Lenhard J. Select HIV protease inhibitors alter bone and fat metabolism ex vivo. J Biol Chem. 2002;277:19247-50. (Pubitemid 34967427)
48. Wang M, Wei S, Faccio R, et al. The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling. J Clin Invest. 2004;114:206-13. (Pubitemid 39071625)
49. Pan G, Kilby M, McDonald J. Modulation of osteoclastogenesis induced by nucleoside reverse transcriptase inhibitors. AIDS Res Hum Retroviruses. 2006;22:1131-41. (Pubitemid 44904264)
50. Holick M. Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs Aging. 2007;24:1017-29. (Pubitemid 350145410)
51. Bang U, Shakar S, Hitz M, et al. Deficiency of 25-hydroxyvitamin D in male HIV-positive patients: a descriptive cross-sectional study. Scand J Infect Dis. 2010;42:306-10.
52. Rodriguez M, Daniels B, Gunawardene S, Robbins G. High frequency of vitamin D deficiency in ambulatory HIV-Positive patients. AIDS Res Hum Retroviruses. 2009;25:9-14.
53. Van Den Bout-Van Den Beukel C, Fievez L, Michels M, et al. Vitamin D deficiency among HIV type 1-infected individuals in the Netherlands: effects of antiretroviral therapy. AIDS Res Hum Retroviruses. 2008;24:1375-82.
54. Wasserman P, Rubin D. Highly prevalent vitamin D deficiency and insufficiency in an urban cohort of HIV-infected men under care. AIDS Patient Care STDS. 2010;24:223-7.
55. Stephensen C, Marquis G, Kruzich L, Douglas S, Aldrovandi G, Wilson C. Vitamin D status in adolescents and young adults with HIV infection. Am J Clin Nutr. 2006;83:1135-41. (Pubitemid 44713115)
56. Mueller N, Fux C, Ledergerber B, et al. High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients. AIDS. 2010;24:1127-34.
57. Dao C, Patel P, Overton E, et al. Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D Levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the US general population. Clin Infect Dis. 2011;52:396-405.
58. th CROI. 2010 San Francisco, USA [abstract 751].
59. Mouly S, Lown KS, Kornhauser D, et al. Hepatic but not intestinal CYP3A4 displays dose-dependent induction by efavirenz in humans. Clin Pharmacol Ther. 2002;72:1-9. (Pubitemid 34833182)
60. Brown T, McComsey G. Association between initiation of antiretroviral therapy with efavirenz and decreases in 25 hydroxyvitamin D. Antivir Ther. 2010;15:425-9.
61. Fox J, Peters B, Prakash M, Arribas J, Hill A, Moecklinghoff C. Improvement in vitamin D deficiency following antiretroviral regime change: Results from the MONET trial. AIDS Res Hum Retroviruses. 2011;27:29-34.
62. th CROI. 2011 Boston, USA [abstract 79LB].
63. Gupta S. Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system. AIDS Patient Care STDS. 2008; 22:99-103. (Pubitemid 351252586)
64. Castillo A, Tarantal A, Watnik M, et al. Tenofovir treatment at 30 mg/kg/ day can inhibit cortical bone mineralization in growing rhesus monkeys (Macaca mulatta). J Orthop Res. 2002;20:1185-9. (Pubitemid 35363975)
65. Peyriere H, Reynes J, Rouanet I, et al. Renal tubular dysfunction associated with tenofovir therapy report of 7 cases. J Acquir Immune Defic Syndr. 2004;35:269-73. (Pubitemid 38280652)
66. Labarga P, Barreiro P, Martin-Carbonero L, et al. Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir. AIDS 2009; 23:689-96.
67. Truvada. Product information 20/01/2010 -EMEA/H/C/000594 -R/0062. Availableat:http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/ human/medicines/000594/human-med-001113.jsp&murl=menus/ medicines/medicines. jsp&mid=WC0b01ac058001d124. Accessed September 11, 2010.
68. Woodward C, Hall A, Williams I, et al. Tenofovir-associated renal and bone toxicity. HIV Med. 2009;10:482-7.
69. Perrot S, Aslangul E, Szwebel T, Caillat-Vigneron N, Le Jeunne C. Bone pain due to fractures revealing osteomalacia related to tenofovir-induced proximal renal tubular dysfunction in a human immunodeficiency virusinfected patient. J Clin Rheumatol. 2009;15:72-4.
70. Rosenvinge M, Gedela K, Copas A, et al. Tenofovir-linked hyperparathyroidism is independently associated with the presence of vitamin D deficiency. J Acquir Immune Defic Syndr. 2010;54:496-9.
71. Childs K, Fishman S, Constable C, et al. Short communication: Inadequate vitamin D exacerbates parathyroid hormone elevations in tenofovir users. AIDS Res Hum Retroviruses. 2010;26:855-9.
72. Masiá M, Padilla S, Robledano C, López N, Ramos JM, Gutiérrez F. Longitudinal changes in parathyroid hormone concentrations in patients initiating antiretroviral therapy with tenofovir. AIDS Res Hum Retroviruses. 2011 [In press].
73. Cozzolino M, Vidal M, Arcidiacono M, Tebas P, Yarasheski K, Dusso A. HIV-protease inhibitors impair vitamin D bioactivation to 1,25-dihydroxyvitamin D. AIDS. 2003;17:513-20. (Pubitemid 36293104)
74. Van Den Bout-Van Den Beukel C, Fievez L, Michels M, et al. Vitamin D deficiency among HIV Type 1-infected individuals in the Netherlands: effects of antiretroviral therapy. AIDS Res Hum Retroviruses. 2008;24:1375-82.
75. Ofotokun I, Weitzmann N, Vunnava A, et al. HAART-induced immune reconstitution: A driving force behind bone resorption in HIV/AIDS. 18th CROI. 2011 Boston, USA [abstract 78].
76. European AIDS Clinical Society Guidelines. Prevention and management of non-infectious co-morbidities in HIV. Available at http://www. europeanaidsclinicalsociety. org/guidelinespdf/2-Non-Infectious-Co-Morbidities- in-HIV.pdf. [Accessed September 11, 2010].
77. Tang B, Eslick G, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a metaanalysis. Lancet. 2007;370:657-66. (Pubitemid 47285316)
78. th CROI. 2011 Boston, USA [abstract 80].