Metabolic bone disease in HIV infection

AIDS

Volumn 23, Issue 11, 2009, Pages 1297-1310

  Borderi, Marco ^a   Gibellini, Davide ^a   Vescini, Fabio ^b   De Crignis, Elisa ^a   Cimatti, Laura ^a   Biagetti, Carlo ^a   Tampellini, Livia ^a   Re, Maria C ^a,c  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b Ospedale Civile di Gorizia   (Italy)

^c NATIONAL INSTITUTE OF BIOSTRUCTURES AND BIOSYSTEMS   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR; ALENDRONIC ACID; ALKALINE PHOSPHATASE BONE ISOENZYME; BISPHOSPHONIC ACID DERIVATIVE; CALCIUM CARBONATE; COLONY STIMULATING FACTOR 1; DENOSUMAB; DIDANOSINE; EMTRICITABINE; GLYCOPROTEIN GP 120; INDINAVIR; LAMIVUDINE; NELFINAVIR; NUCLEOSIDE ANALOG; PARATHYROID HORMONE; PARATHYROID HORMONE[1-34]; PROTEINASE INHIBITOR; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; SELECTIVE ESTROGEN RECEPTOR MODULATOR; STAVUDINE; STRONTIUM RANELATE; TENOFOVIR; TRANSCRIPTION FACTOR RUNX2; TUMOR NECROSIS FACTOR ALPHA; VITAMIN D; ZALCITABINE; ZIDOVUDINE; ZOLEDRONIC ACID;

APOPTOSIS; AUTOCRINE EFFECT; BONE DENSITY; BONE STRENGTH; CALCIUM INTAKE; CELL ACTIVITY; CELL DIFFERENTIATION; DIET SUPPLEMENTATION; EXERCISE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPOPHOSPHATEMIA; METABOLIC BONE DISEASE; MONITORING; MORBIDITY; MORTALITY; NOTE; OSTEOBLAST; OSTEOCLAST; OSTEOPENIA; OSTEOPOROSIS; PARACRINE SIGNALING; PATHOGENESIS; PRIORITY JOURNAL; RISK FACTOR; RISK REDUCTION; SCREENING; SMOKING CESSATION; VITAMIN D DEFICIENCY; WEIGHT CONTROL;

ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; BONE DISEASES, METABOLIC; EPIDEMIOLOGIC METHODS; HIV INFECTIONS; HUMANS;

EID: 68449100595     PISSN: 02699370     EISSN: 14735571     Source Type: Journal    
DOI: 10.1097/QAD.0b013e32832ce85a     Document Type: Note

References (137)

1. Levy JA. HIV pathogenesis: 25 years of progress and persistent challenges. AIDS 2009; 23:147-160.
2. Haggerty C, Pitt E, Siliciano R. The latent reservoir for HIV in resting cells and other viral reservoirs during chronic infection: insight from treatment and treatment-interruption trials. Curr Opin HIV AIDS 2006; 1:62-68.
3. Arnsten JH, Freeman R, Howard AA, Floris-Moore M, Lo Y, Klein RS. Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection. AIDS 2007; 21:617-623.
4. Allison GT, Bostrom MP, Glesby MJ. Osteonecrosis in HIV disease: epidemiology, etiologies, and clinical management. AIDS 2003; 17:1-9.
5. Serrano S, Marinoso ML, Soriano JC, Rubies-Prat J, Aubia J, Coll J, et al. Bone remodelling in human immunodeficiency virus-1-infected patients. A histomorphometric study. Bone 1995; 16:185-191.
6. Mondy K, Tebas P. Emerging bone problems in patients infected with human immunodeficiency virus. Clin Infect Dis 2003; 36:S101-S105.
7. Kanis JA, Johnell O, Oden A, Dawson A, De Laet C, Jonsson B. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int 2001; 12:989-995.
8. World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. WHO technical report series 843. Geneva: WHO, 1994.
9. Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ, Khaltaev N. A reference standard for the description of osteoporosis. Bone 2008; 42:467-475.
10. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285:785-795.
11. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS 2006; 20:2165-2174.
12. Tebas P, Powderly WG, Claxton S, Marin D, Tantisiriwat W, Teitelbaum SL, et al. Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS 2000; 14:F63-F67.
13. Carr A, Miller J, Eisman JA, Cooper DA. Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight preanti-retroviral therapy. AIDS 2001; 15:703-709.
14. Moore AL, Vashisht A, Sabin CA, Mocroft A, Madge S, Phillips AN, et al. Reduced bone mineral density in HIV-positive individuals. AIDS 2001; 15:1731-1733.
15. Fernandez-Rivera J, Garcia R, Lozano F, Macias J, Garcia-Garcia JA, Mira JA, et al. Relationship between low bone mineral density and highly active antiretroviral therapy including protease inhibitors in HIV-infected patients. HIV Clin Trials 2003; 4:337-346.
16. Vescini F, Borderi M, Buffa A, Sinicropi G, Tampellini L, Chiodo F, et al. Bone mass in HIV-infected patients: focus on the role of therapy and sex. J Acquir Immune Defic Syndr 2003; 33:405-407.
17. Madeddu G, Spanu A, Solinas P, Calia GM, Lovigu C, Chessa F, et al. Bone mass loss and vitamin D metabolism impairment in HIV patients receiving highly active antiretroviral therapy. Q J Nucl Med Mol Imaging 2004; 48:39-48.
18. Bongiovanni M, Fausto A, Cicconi P, Menicagli L, Melzi S, Ligabo VE, et al. Osteoporosis in HIV-infected subjects: a combined effect of highly active antiretroviral therapy and HIV itself? J Acquir Immune Defic Syndr 2005; 40:503-504.
19. Lawal A, Engelson ES, Wang J, Heymsfield SB, Kotler DP. Equivalent osteopenia in HIV-infected individuals studied before and during the era of highly active antiretroviral therapy. AIDS 2001; 15:278-280.
20. Dubé MP, Qian D, Edmondson-Melançon H, Sattler FR, Goodwin D, Martinez C, et al. Prospective, intensive study of metabolic changes associated with 48 weeks of amprenavir-based antiretroviral therapy. Clin Infect Dis 2002; 35:475-481.
21. 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; 17:1917-1923.
22. Amiel C, Ostertag A, Slama L, Baudoin C, N'Guyen T, Lajeunie E, et al. BMD is reduced in HIV-infected men irrespective of treatment. J Bone Miner Res 2004; 19:402-409.
23. Landonio S, Quirino T, Bonfanti P, Gabris A, Boccassini L, Gulisano C, et al. Osteopenia and osteoporosis in HIV+ patients, untreated or receiving HAART. Biomedicine and Pharmacotherapy 2004; 58:505-508.
24. Cazanave C, Dupon M, Lavignolle-Aurillac V, Barthe N, Lawson-Ayayi S, Mehsen N, et al. Reduced bone mineral density in HIV-infected patients: prevalence and associated factors. AIDS 2008; 22:395-402.
25. Eriksen E, Axelrod D, Melsen F. Bone histomorphometry. New York: Raven Press; 1994.
26. Nolan D, Upton R, McKinnon E, John M, James I, Adler B, et al. Stable or increasing bone mineral density in HIV-infected patients treated with nelfinavir or indinavir. AIDS 2001; 15:1275-1280.
27. Mallon PW, Miller J, Cooper DA, Carr A. Prospective evaluation of the effects of antiretroviral therapy on body composition in HIV-1-infected men starting therapy. AIDS 2003; 17:971-979.
28. Sambrook P, Cooper C. Osteoporosis. Lancet 2006; 367: 2010-2018.
29. Kartsogiannis V, Ng KW. Cell lines and primary cell cultures in the study of bone cell biology. Mol Cell Endocrinol 2004; 228:79-102.
30. Marie PJ. Transcription factors controlling osteoblastogenesis. Arch Biochem Biophys 2008; 473:98-105.
31. Matsuo K, I rie N. Osteoclast-osteoblast communication. Arch Biochem Bioph 2008; 473:201-209.
32. Yellowley CE, Li Z, Zhou Z, Jacobs CR, Donahue HJ. Functional gap junctions between osteocytic and osteoblastic cells. J Bone Miner Res 2000; 15:209-217.
33. Taylor AF, Saunders MM, Shingle DL, Cimbala JM, Zhou Z, Donahue HJ. Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions. Am J Physiol Cell Physiol 2007; 292:545-552.
34. Burger EH, Van der Meer JW, Van de Gevel JS, Gribnau JC, Thesingh GW, Van Furth R. In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes. J Exp Med 1982; 156:1604-1614.
35. Väänänem HK, Laitala-Leinonen T. Osteoclast lineage and function. Arch Biochem Biophys 2008; 473:132-138.
36. Bossard MJ, Tomaszek TA, Thompson SK, Amegadzie BY, Hanning CR, Jones C, et al. Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification. J Biol Chem 1996; 271:12517-12524.
37. Vääräniemi J, Halleen JM, Kaarlonen K, Ylipahkala H, Alatalo SL, Andersson G, et al. Intracellular machinery for matrix degradation in bone-resorbing osteoclasts. J Bone Miner Res 2004; 19:1432-1440.
38. Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Väänä nen H K. Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin Lab 2006; 52:499-509.
39. Murray AB, Schmidt J, Rieke L. Retrovirus-induced osteopetrosis in mice. Ultrastructural evidence of early virus production in osteoblasts and osteocytes. Am J Pathol 1986; 124:319-323.
40. Foster RG, Lian JB, Stein G, Robinson HL. Replication of an osteopetrosis-inducing avian leukosis virus in fibroblasts, osteoblasts, and osteopetrotic bone. Virology 1994; 205:179-187.
41. Labat ML. Retroviruses and bone diseases. Clin Orthopaed 1996; 326:287-308.
42. Centers for Disease Control. Transmission of HIV through bone transplantation. JAMA 1988; 260:2487-2488.
43. Roder W, Muller H, Muller WEG, Merz H. HIV infection in human bone. J Bone joint Surg Br 1992; 74:179-180.
44. Buck BE, Resnick L, Shah SM, Malinin TI. Human immunodeficiency virus cultured from bone. Implications for transplantation. Clin Orthop Relat Res 1990; 251:249-253.
45. Mellert W, Kleinschmidt A, Schmidt J, Festl H, Emler S, Roth WK, et al. Infection of human fibroblasts and osteoblast-like cells with HIV-1. AIDS 1990; 4:527-535.
46. Fessel WJ, Hurley LB. Is HIV sequestered in bone? Possible implications of virological and immunological findings in some HIV-infected patients with bone disease. AIDS 2003; 17:255-257.
47. Nacher M, Serrano S, Gonzalez A, Hernàndez A, Luisa Mariñoso M, Vilella R, et al. Osteoblasts in HIV-infected patients: HIV-1 infection and cell function. AIDS 2001; 15:2239-2243.
48. Gibellini D, DeCrignis E, Ponti C, Cimatti L, Borderi M, Tschon M, et al. HIV-1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNFalpha activation. J Med Virol 2008; 80:1507-1514.
49. Aiuti A, Turchetto L, Cota M, Cipponi A, Brambilla A, Arcelloni C, et al. Human CD34+ cells express CXCR4 and its ligand stromal cell derived factor-1. Implications for infection by T-cell tropic human immunodeficiency virus. Blood 1999; 94:62-73.
50. Perfettini JL, Castedo M, Roumier T, Andreau K, Nardacci R, Piacentini M, Kroemer G. Mechanisms of apoptosis induction by the HIV-1 envelope. Cell Death Differ 2005; 12:S916-923.
51. Herbeuval JP, Shearer GM. Are blockers of gp120/CD4 interaction effective inhibitors of HIV-1 immunopathogenesis? AIDS Rev 2006; 8:3-8.
52. Badley AD, Dockrell D, Simpson M, Schut R, Lynch DH, Leibson P, et al. Macrophage-dependent apoptosis of CD4+ T lymphocytes from HIV-infected individuals is mediated by FasL and tumor necrosis factor. J Exp Med 1997; 185:55-64.
53. Alirezaei M, Watry DD, Flynn CF, Kiosses WB, Masliah E, Williams BR, et al. Human immunodeficiency virus-1/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signaling in neurons. J Neurosci 2007; 27: 11047-11055.
54. Gibellini D, Vitone F, Buzzi M, Schiavone P, De Crignis E, Cicola R, et al. HIV-1 negatively affects the survival/maturation of cord blood CD34(+) hematopoietic progenitor cells differentiated towards megakaryocytic lineage by HIV-1 gp120/CD4 membrane interaction. J Cell Physiol 2007; 210:315-324.
55. Cotter EJ, Malizia AP, Chew N, Powderly WG, Doran PP. HIV roteins 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; 23:1521-1530.
56. Aukrust P, Haug CJ, Ueland T, Lien E, Müllier F, Espevik 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; 84:145-150.
57. Teichmann J, Stephan E, Discher T, Lange U, Federlin K, Stracke H, et al. Changes in calciotropic hormones and biochemical markers of bone metabolism in patients with human immunodeficiency virus infection. Metabolism 2000; 49:1134-1139.
58. Wang L, Mondai D, La Russa VF, Agrawal KC. Suppression of clonogenic potential of human bone marrow mesenchymal stem cells by HIV Type 1: putative role of HIV type 1 Tat protein and inflammatory cytokines. AIDS Res Hum Retroviruses 2002; 18:917-931.
59. Cotter EJ, Mallon PW, Doran PP. Is PPAR-γ a prsospective player in HIV-1 associated bone disease? PPAR Res 2009; 2009:1-9.
60. Gibellini D, Borderi M, De Crignis E, Cicola R, Vescini F, Caudarella R, et al. RANKL/OPG/TRAIL plasma levels and bone mass loss evaluation in antiretroviral naive HIV-1-positive men. J Med Virol 2007; 79:1446-1454.
61. Konishi M, Takahashi K, Yoshimoto E, Uno K, Kasahara K, Mikasa K. Association between osteopenia/osteoporosis and the serum RANKL in HIV-infected patients. AIDS 2005; 19:1240-1241.
62. Mora S, Zamproni I, Cafarelli L, Giacomet V, Erba P, Zuccotti G, et al. Alterations in circulating osteoimmune factors may be responsible for high bone resorption rate in HIV-infected children and adolescents. AIDS 2007; 21:1129-1135.
63. Fakruddin JM, Laurence J. HIV envelope gp120-mediated regulation of osteoclastogensis via receptor activator of nuclear factor κb ligand (RANKL) decretion and its modulation by certain HIV protease inhibitors through interferon-γ/RANKL cross-talk. J Biol Chem 2003; 278:48251-48258.
64. Fakruddin JM, Laurence J. HIV-1 Vpr enhances production of receptor of activated NF-κB ligand (RANKL) via potentiation of glucocorticoid receptor activity. Arch Virol 2005; 150:67-78.
65. Fakruddin JM, Laurence J. Interactions among HIV-1, interferon γ and receptor of activated NF-κB ligand (RANKL): implications for HIV pathogenesis. Clin Exp Immunol 2004; 137:538-545.
66. Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H, et al. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 1990; 345:442-444.
67. Dai XM, Ryan GR, Hapel AJ, Dominguez MG, Russell RG, Kapp S, et al. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood 2002; 99:1116-1202.
68. Gruber MF, Weih KA, Boone EJ, Smith PD, Clouse KA. Endogenous macrophage CSF production is associated with viral replication in HIV-1-infected human monocytederived macrophages. J Immunol 1995; 154:5528-5535.
69. Kalter DC, Nakamura M, Turpin JA, Baca LM, Hoover DL, Dieffenbach C, et al. Enhanced HIV replication in macrophage colony stimulating factor treated monocytes. J Immunol 1991; 146:298-306.
70. Bergamini A, Perno CF, Dini L, Capozzi M, Pesce CD, Ventura L, et al. Macrophage colony-stimulating factor enhances the susceptibility of macrophages to infection by HIVand reduces the activity of compounds that inhibit virus binding. Blood 1994; 84:3405-3412.
71. Wang J, Roderiquez G, Oravecz T, Norcross MA. Cytokine regulation of human immunodeficiency virus type 1 entry and replication in human monocytes/macrophages through modulation of CCR5 expression. J Virol 1998; 72:7642-7647.
72. Haine V, Fischer-Smith T, Rappaport J. M-CSF in the pathogenesis of HIV infection: potential target for therapeutical intervention. J Neuroimmune Pharmacol 2006; 1:32-40.
73. Yamada N, Tsujimura T, Ueda H, Hayashi S, Ohyama H, Okamura H, et al. Down-regulation of osteoprotegerin production in bone marrow macrophages by macrophage colony-stimulating factor. Cytokine 2005; 31:288-297.
74. Palella FJ Jr, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr 2006; 43:27-34.
75. Martin JL, Brown CE, Matthews-Davis N, Reardon JE. Effects of antiviral nucleoside analogs on human DNA polymerases and mitochondrial DNA synthesis. Antimicrob Agents Chemother 1994; 38:2743-2749.
76. Lewis W, Dalakas MC. Mitochondrial toxicity of antiviral drugs. Nat Med 1995; 1:417-422.
77. Brinkman K, ter Hofstede HJ, Burger DM, Smeitink JA, Koopmans PP. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 1998; 12:1735-1744.
78. Walker UA, Setzer B, Venhoff N. Increased long-term mitochondrial toxicity in combinations of nucleoside analogue reverse-transcriptase inhibitors. AIDS 2002; 16:2165-2173.
79. Boubaker K, Flepp M, Sudre P, Furrer H, Haensel A, Hirschel B, et al. Hyperlactatemia and antiretroviral therapy: the Swiss HIV Cohort Study. Clin Infect Dis 2001; 33:1931-1937.
80. Moyle GJ, Datta D, Mandalia S, Morlese J, Asboe D, Gazzard BG. Hyperlactatemia and lactic acidosis during antiretroviral therapy: relevance, reproducibility and possible risk factors. AIDS 2002; 16:1341-1349.
81. Pan G, Wu X, McKenna MA, Feng X, Nagy TR, McDonald JM. AZT enhances osteoclastogenesis and bone loss. AIDS Res Hum Retroviruses 2004; 20:608-620.
82. Birkus G, Hitchcock MJ, Cihlar T. Assessment of mitochondrial toxicity in human cells treated with tenofovir: comparison with other nucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemoter 2002; 46:716-723.
83. Venhoff N, Setzer B, Melkaoui K, Walker UA. Mitochondrial toxicity of tenofovir, emtricitabine and abacavir alone and in combination with additional nucleoside reverse transcriptase inhibitors. Antivir Ther 2007; 12:1075-1085.
84. Tarantal AF, Marthas ML, Shaw JP, Cundy K, Bischofberger N. Administration of 9-(2-(R)-(phosphonomethoxy)propyl) adenine (PMPA) to gravid and infant Rhesus macaques (Macaca mulatta): safety and efficacy studies. J Acquir Immun Defic Syndr Hum Retrovirol 1999; 20:323-333.
85. Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS, Rodriguez RA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2005; 40:1559-1585.
86. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest 2006; 116:2062-2072.
87. Izzedine H, Hulot JS, Vittecoq D, Gallant JE, Staszewski S, Launay-Vacher V, et al. Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral naïve HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study. Nephrol Dial Transplant 2005; 20:743-746.
88. Peyrière H, Reynes J, Rouanet I, Daniel N, Merle de Boever C, Mauboussin JM, et al. Renal tubular dysfunction associated with tenofovir therapy report of 7 cases. J Acquir Immune Defic Syndr 2004; 35:269-273.
89. Barrios A, Garcia Benayas T, Gonzàlez-Lahoz J, Soriano V. Tenofovir-related nephrotoxicity in HIV-infected patients. AIDS 2004; 18:960-963.
90. Labarga P, Barreiro P, Martin-Carbonero L, Rodriguez-Novoa S, Solera C, Medrano J, et al. Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir. AIDS 2009; 23:689-696.
91. Parsonage MJ, Wilkins EG, Snowden N, Issa BG, Savage MW. The development of hypophosphataemic osteomalacia with myopathy in two patients with HIV infection receiving tenofovir therapy. HIV Med 2005; 6:341-346.
92. Brim NM, Cu-Uvin S, Hu SL, O'Bell JW. Bone disease and pathologic fractures in a patient with tenofovir-induced Fanconi syndrome. AIDS Read 2007; 17:322-328.
93. Callens S, De Roo A, Colebunders R. Fanconi-like syndrome and rhabdomyolysis in a person with HIV infection on highly active antiretroviral treatment including tenofovir. J Infect 2003; 47:262-263.
94. Creput C, Gonzalez-Canali G, Hill G, Piketty C, Kazatchkine M, Nochy D. Renal lesions in HIV-1-positive patient treated with tenofovir. AIDS 2003; 17:935-937.
95. Rollot F, Nazal EM, Chauvelot-Moachon L, Kelaidi C, Daniel N, Saba M, et al. Tenofovir-related Fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiency syndrome: the role of lopinavir-ritona-vir-didanosine. Clin Infect Dis 2003; 37:e174-e176.
96. Karras A, Lafaurie M, Furco A, Bourgarit A, Droz D, Seren D, et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi Syndrome, and Nephrogenic Diabetes Insipidus. Clin Infect Dis 2003; 36:1070-1073.
97. Hazra R, Gafni RI, Maldarelli F, Balis FM, Tullio An, DeCarlo E, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatrie HIV infection. Pediatrics 2005; 116:e846-e854.
98. Jones S, Restrepo D, Kasowitz A, Korenstein D, Wallenstein S, Schneider A, et al. Risk factors for decreased bone density and effects of HIV on bone in the elderly. Osteoporos Int 2008; 19:913-918.
99. Calmy A, Norris R, Fux C, Vallier N, Samaras K, Hesse K. Osteopenia and proximal renal tubular disease are independently associated with tenofovir therapy. Abstract at XVII IAS International Conference. Mexico City 2008.
100. Guillemi S, Ng F, Zhang W, Lima V, Rocha C, Harris M, et al. Risk factors for reduced bone mineral density in HIV-infected individuals in the modern HAART era, Abtract poster # 969 at 15th CROI 2008.
101. Buchacz K, Brooks JT, Tong T, Moorman AC, Baker RK, Holmberg SD, et al. The HIV Outpatient Study (HOPS) Investigators Evaluation of hypophosphataemia in tenofovir disoproxil fumarate (TDF)-exposed and TDF-unexposed HIV-infected out-patients receiving highly active antiretroviral therapy. HIV Medicine 2006; 7:451-456.
102. Schooley RT, Ruane P, Myers RA, Beall G, Lampiris H, Berger D, et al. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS 2002; 16:1257-1263.
103. Squires K, Pozniak AL, Pierone JG, Steinhart CR, Berger D, Bellos NC, et al. Tenofovir Disoproxil Fumarate in Nucleo-side-Resistant HIV-1 Infection A Randomized Trial. Ann Intern Med 2003; 139:313-320.
104. Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JM, et al., 903 Study Group. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004; 292:191-201.
105. Izzedine H, Isnard-Bagnis C, Hulot JS, Vittecoq D, Cheng A, Jais CK, et al. Renal safety of tenofovir in HIV treatment experienced patients. AIDS 2004; 18:1074-1076.
106. Jain RG, Lenhard JM. Select HIV protease inhibitors alter bone and fat metabolism exvivo. J Biol Chem 2002; 277:19247-19250.
107. Wong BR, Besser D, Kim N, Arron JR, Vologodskaia M, Hanafusa H, et al. RANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell 1999; 4:1041-1049.
108. Wang MW, Wei S, Faccio R, Takeshita S, Tebas P, Powderly WG, et al. The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling. J Clin Invest 2004; 114:206-213.
109. Malizia A, Cotter E, Chew N, Powderly WG, Doran PP. HIV protease inhibitors selectively induce gene expression alterations associated with reduced calcium deposition in primary human osteoblasts. AIDS Res Hum Retroviruses 2007; 23:243-250.
110. Holick MF. Vitamin D and bone health. J Nutr 1996; 126: 1159S-1164S.
111. Whitfield GK, Hsieh JC, Jurutka PW, Selznick SH, Haussier CA, MacDonald PN, et al. Genomic actions of 1,25-dihydroxyvitamin D3. J Nutr 1995; 125:1690S-1694S.
112. Holick MF. Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs Aging 2007; 24:1017-1029.
113. Eagling VA, Back DJ, Barry MG. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol 1997; 44:190-194.
114. Von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Duan SX, Fogelman SM, et al. Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharmacol 1998; 38:106-111.
115. 2-vitamin D. Antiviral Therapy 2000; 6:10-18.
116. Cozzolino M, Vidal M, Arcidiacono MV, Tebas P, Yarasheski KE, Dusso A. HIV-protease inhibitors impair vitamin D bioactivationto 1,25- dihydroxyvitamin D.AIDS 2003; 17:513-520.
117. Haug CJ, Aukrust P, Haug E, Mørkrid L, Müller F, Frøland SS. Severe deficiency of 1,25-dihydroxyvitamin D3 in human immunodeficiency virus infection: association with immunological hyperactivity and only minor changes in calcium homeostasis. J Clin Endocrinol Metab 1998; 83:3832-3838.
118. Ramayo E, González-Moreno MP, Macías J, Cruz-Ruíz M, Mira JA, Villar-Rueda AM, et al. Relationship between osteopenia, free testosterone, and vitamin D metabolite levels in HIV-infected patients with and without highly active antiretroviral therapy. AIDS Res Hum Retroviruses 2005; 21:915-921.
119. Tomazic J, Ul K, Volcansek G, Gorensek S, Pfeifer M, Karner P, Prezelj J, et al. Prevalence and risk factors for osteopenia/osteoporosis in an HIV-infected male population. Wien Klin Wochenschr 2007; 119:639-646.
120. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312:1254-1259.
121. Hans DB, Shepherd JA, Schwartz EN, Reid DM, Blake GM, Fordham JN, et al. Peripheral dual-energy X-ray absorptio-metry in the management of osteoporosis: the 2007 ISCD Official Positions. J Clin Densitom 2008; 11:188-206.
122. Vieth R. Vitamin D Toxicity, Policy, and Science. J Bone Min Res 2007; 22:V64-V68.
123. Welten DC, Kemper HC, Post GB, van Staveren WA. A meta-analysis of the effect of calcium intake on bone mass in young and middle aged females and males. J Nutr 1995; 125:2802-2813.
124. Cumming RG, Nevitt MC. Calcium for prevention of osteoporotic fractures in postmenopausal women. J Bone Miner Res 1997; 12:1321-1329.
125. Prentice A. Diet, nutrition and the prevention of osteoporosis. Public Health Nutr 2004; 7:227-243.
126. Guaraldi G, Orlando G, Madeddu G, Vescini F, Ventura P, Campostrini S, et al. Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis. HIV Clin Trials 2004; 5:269-277.
127. Mondy K, Powderly WG, Claxton SA, Yarasheski KH, Royal M, Stoneman JS, et al. Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection. J Acquir Immune Defic Syndr 2005; 38:426-431.
128. Negredo E, Martínez-López E, Paredes R, Rosales J, Pérez-Alvarez N, Holgado S, et al. Reversal of HIV-1-associated osteoporosis with once-weekly alendronate. AIDS 2005; 19:343-345.
129. McComsey GA, Kendall MA, Tebas P, Swindells S, Hogg E, Alston-Smith B, et al. Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS 2007; 21:2473-2482.
130. Bolland MJ, Grey AB, Home AM, Briggs SE, Thomas MG, Ellis-Pegler RB, et al. Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial. J Clin Endocrinol Metab 2007; 92:1283-1288.
131. Huang J, Meixner L, Fernandez S, McCutchan JA. A doubleblinded, randomized controlled trial of zoledronate therapy for HIV-associated osteopenia and osteoporosis. AIDS 2009; 23:51-57.
132. Ott S. Long-term safety of biphosphonates. J Clin Endocrinol Metab 2005; 90:1897-1899.
133. Roux S. RANKL inhibitors: a bright future? Joint Bone Spine 2006; 73:129-131.
134. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, et al., AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006; 354:821-831.
135. De Crignis E, Cimatti L, Borderi M, Gibellini D, Re MC. Bone alterations during HIV infection. New Microbiol 2008; 31:155-164.
136. Cummings SR, Black DM, Rubin SM. Lifetime risks of hip, Colles', or vertebral fracture and coronary heart disease among white postmenopausal women. Arch Intern Med 1989; 149:2445-2448.
137. Meunier PJ, Delmas PD, Eastell R, McClung MR, Papapoulos S, Rizzoli R, et al. Diagnosis and management of osteoporosis in postmenopausal women: clinical guidelines. International Committee for Osteoporosis Clinical Guidelines. Clin Ther 1999; 21:1025-1044.