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Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Research Article

The Prevalence and Associated Factors of Reduced Bone Mineral Density (BMD) Among Men with Suppressed Viral Load Taking Antiretroviral Therapy

Author(s): Safiye Nur Ozcan*, Dilek Yildiz Sevgi, Ahsen Oncul, Alper Gunduz, Ozgun Pehlivan, Rana Terlemez, Banu Kuran and Ilyas Dokmetas

Volume 20, Issue 1, 2022

Published on: 11 January, 2022

Page: [74 - 81] Pages: 8

DOI: 10.2174/1570162X19666211202100308

Price: $65

Abstract

Background: Reduced bone mineral density (BMD) is a frequent comorbidity observed in people living with HIV (PLHIV).

Objective: The aim of the study is to determine the prevalence and associated factors of reduced bone mineral density (BMD) among men with suppressed viral load taking antiretroviral therapy.

Methods: The study was conducted as a cross-sectional design between January to April 2019. 211 patients were included in the study. Z-score at either body site between -1.0 and -2.0 or -2 or less was defined as osteopenia or osteoporosis, respectively. Multivariate logistic regression analysis was used to evaluate the factors affecting the development of reduced BMD.

Results: The mean age of the patients involved in the study was 34.8 ± 7.6. Osteoporosis was detected in 21.4% and osteopenia in 44.5% of the patients. There was a significant relationship found between HIV diagnosis time, ART usage duration, tenofovir disoproxil fumarate (TDF) use, TDF use in the past, total TDF usage time and decreased BMD. Multivariate logistic regression analysis showed that the likelihood of reduced bone marrow density was 67% lower among those with regular milk or dairy product intake compared to those without (OR=0.330; 95% CI = 0.12-0.92, p=0.033).

Conclusion: There is a high prevalence of reduced BMD among PLHIV aged under 50, which is mainly confounded by HIV diagnosis time, ART usage duration and TDF usage. Although virological control has been achieved, these patients should be followed up, considering that they may have decreased BMD.

Keywords: HIV/AIDS, osteoporosis, risk factors, bone mineral density, TDF, PLHIV.

Graphical Abstract
[2]
Brown T, Peerapatanapokin W. Evolving HIV epidemics: the urgent need to refocus on populations with risk. Curr Opin HIV AIDS 2019; 14(5): 337-53.
[http://dx.doi.org/10.1097/COH.0000000000000571] [PMID: 31368909]
[3]
Republic of turkey moh, general directorate of public health, hiv/aids statistics report 2019. Available from: https://hsgm.saglik.gov.tr/tr/bulasici-hastaliklar/hiv-aids/hiv-aids-liste/h%C4%B1v-aids-istatislik.htmlAccessed
[4]
Turkey HIV/AIDS Control Program (2019-2024). Ministry of health, publish number:1131. Available from: https://hsgm.saglik.gov.tr/depo/birimler/Bulasici-hastaliklar-db/hastaliklar/HIV-ADS/Tani-Tedavi_Rehberi/HIV_AIDS_Kontrol_Programi.pdf
[5]
Yemisen M, Aydın OA, Gunduz A, et al. Epidemiological profile of naive HIV-1/AIDS patients in Istanbul: the largest case series from Turkey. Curr HIV Res 2014; 12(1): 60-4.
[http://dx.doi.org/10.2174/1570162X12666140411111803] [PMID: 24725060]
[6]
Erdinc FS, Dokuzoguz B, Unal S, et al. Temporal trends in the epidemiology of HIV in turkey. Curr HIV Res 2020; 18(4): 258-66.
[http://dx.doi.org/10.2174/1570162X18666200427223823] [PMID: 32342820]
[7]
Tükenmez-Tigen E, Korten V. HIV infection and the effects of antiretroviral therapy on the development of osteopenia. Klimik Journal 2012; 25(2): 51-7.
[http://dx.doi.org/10.5152/kd.2012.16]
[8]
Borderi M, Gibellini D, Vescini F, et al. Metabolic bone disease in HIV infection. AIDS 2009; 23(11): 1297-310.
[http://dx.doi.org/10.1097/QAD.0b013e32832ce85a] [PMID: 19550284]
[9]
Weinberg M, Schambelan M. Bone and calcium disorders in patients with HIV [Internet]. 2020. Available from: http://www.uptodate.com/contents/bone- and-calcium-disorders-in-hiv-infected-patients
[10]
European AIDS Clinical Society (EACS) Guidelines. Bone disease: screening, DXA [Internet]. Available from: eacssociety.org/guidelines/eacs-guidelines/eacs-guidelines.html
[11]
Powderly WG. Osteoporosis and bone health in HIV. Curr HIV/AIDS Rep 2012; 9(3): 218-22.
[http://dx.doi.org/10.1007/s11904-012-0119-7] [PMID: 22581359]
[12]
Gutiérrez F, Masiá M. The role of HIV and antiretroviral therapy in bone disease. AIDS Rev 2011; 13(2): 109-18.
[PMID: 21587342]
[13]
Kwak MK, Lee EJ, Park JW, et al. CD4 T cell count is inversely associated with lumbar spine bone mass in HIV-infected men under the age of 50 years. Osteoporos Int 2019; 30(7): 1501-10.
[http://dx.doi.org/10.1007/s00198-019-04942-7] [PMID: 30915506]
[14]
Matovu FK, Wattanachanya L, Beksinska M, Pettifor JM, Ruxrungtham K. Bone health and HIV in resource-limited settings: a scoping review. Curr Opin HIV AIDS 2016; 11(3): 306-25.
[http://dx.doi.org/10.1097/COH.0000000000000274] [PMID: 27023284]
[15]
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.
[http://dx.doi.org/10.1097/QAD.0b013e3282f423dd] [PMID: 18195566]
[16]
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.
[http://dx.doi.org/10.1086/656412] [PMID: 20839968]
[17]
Shaiykova A, Pasquet A, Goujard C, et al. Reduced bone mineral density among HIV-infected, virologically controlled young men: prevalence and associated factors. AIDS 2018; 32(18): 2689-96.
[http://dx.doi.org/10.1097/QAD.0000000000002001] [PMID: 30234605]
[18]
Dao CN, Patel P, Overton ET, 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(3): 396-405.
[19]
Bang UC, Shakar SA, Hitz MF, et al. Deficiency of 25-hydroxyvitamin D in male HIV-positive patients: a descriptive cross-sectional study. Scand J Infect Dis 2010; 42(4): 306-10.
[http://dx.doi.org/10.3109/00365540903463981] [PMID: 20085419]
[20]
Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995; 332(5): 305-11.
[http://dx.doi.org/10.1056/NEJM199502023320506] [PMID: 7816067]
[21]
Titanji K, Vunnava A, Sheth AN, et al. Dysregulated B cell expression of RANKL and OPG correlates with loss of bone mineral density in HIV infection. PLoS Pathog 2014; 10(10): e1004497.
[http://dx.doi.org/10.1371/journal.ppat.1004497] [PMID: 25393853]
[22]
Kiebzak GM, Beinart GA, Perser K, Ambrose CG, Siff SJ, Heggeness MH. Undertreatment of osteoporosis in men with hip fracture. Arch Intern Med 2002; 162(19): 2217-22.
[http://dx.doi.org/10.1001/archinte.162.19.2217] [PMID: 12390065]
[23]
Martin K, Lawson-Ayayi S, Miremont-Salamé G, et al. Symptomatic bone disorders in HIV-infected patients: incidence in the Aquitaine cohort (1999-2002). HIV Med 2004; 5(6): 421-6.
[http://dx.doi.org/10.1111/j.1468-1293.2004.00247.x] [PMID: 15544694]
[24]
Young B, Dao CN, Buchacz K, Baker R, Brooks JT. 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(8): 1061-8.
[http://dx.doi.org/10.1093/cid/ciq242] [PMID: 21398272]
[25]
Cotter AG, Sabin CA, Simelane S, et al. Relative contribution of HIV infection, demographics and body mass index to bone mineral density. AIDS 2014; 28(14): 2051-60.
[http://dx.doi.org/10.1097/QAD.0000000000000353] [PMID: 25265073]
[26]
Gutiérrez F, Masiá M. The role of HIV and antiretroviral therapy in bone disease. AIDS Rev 2011; 13(2): 109-8.
[PMID: 21587342]
[27]
Duvivier C, Kolta S, Assoumou L, et al. 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(7): 817-24.
[http://dx.doi.org/10.1097/QAD.0b013e328328f789] [PMID: 19363330]
[28]
Brown TT, McComsey GA, King MS, Qaqish RB, Bernstein BM, da Silva BA. Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen. J Acquir Immune Defic Syndr 2009; 51(5): 554-61.
[http://dx.doi.org/10.1097/QAI.0b013e3181adce44] [PMID: 19512937]
[29]
Stellbrink H, Orkin C, Arribas JR, 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(8): 963-72.
[30]
Tsai MS, Hung CC, Liu WC, et al. Reduced bone mineral density among HIV-infected patients in Taiwan: prevalence and associated factors. J Microbiol Immunol Infect 2014; 47(2): 109-15.
[http://dx.doi.org/10.1016/j.jmii.2012.08.026] [PMID: 23073318]
[31]
Aydın OA, Karaosmanoglu HK, Karahasanoglu R, Tahmaz M, Nazlıcan O. Prevalence and risk factors of osteopenia/osteoporosis in Turkish HIV/AIDS patients. Braz J Infect Dis 2013; 17(6): 707-11.
[http://dx.doi.org/10.1016/j.bjid.2013.05.009] [PMID: 24076108]
[32]
Üstündağ N, Korkmaz M, Öksüzkaya A, Balbaloğlu Ö, Eray İ. Osteoporozun sınıflandırılması, risk faktörlerinin belirlenmesi ve bir dakikalık osteoporoz risk testi. Euros J Fam Med 2013; 2(3): 107-14.
[34]
Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis - 2016. Endocr Pract 2016; 22(Suppl. 4): 1-42.
[http://dx.doi.org/10.4158/EP161435.GL] [PMID: 27662240]
[35]
Kirazlı Y, Atamaz Çalış F, El Ö, et al. Updated approach for the management of osteoporosis in Turkey: a consensus report. Arch Osteoporos 2020; 15(1): 137.
[http://dx.doi.org/10.1007/s11657-020-00799-0] [PMID: 32860546]
[36]
Lewiecki EM, Gordon CM, Baim S, et al. International society for clinical densitometry 2007 adult and pediatric official positions. Bone 2008; 43(6): 1115-21.
[http://dx.doi.org/10.1016/j.bone.2008.08.106] [PMID: 18793764]
[37]
Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet 2002; 359(9321): 1929-36.
[http://dx.doi.org/10.1016/S0140-6736(02)08761-5] [PMID: 12057569]
[38]
Triant VA, Brown TT, Lee H, Grinspoon SK. Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab 2008; 93(9): 3499-504.
[http://dx.doi.org/10.1210/jc.2008-0828] [PMID: 18593764]
[39]
Stone B, Dockrell D, Bowman C, McCloskey E. HIV and bone disease. Arch Biochem Biophys 2010; 503(1): 66-77.
[http://dx.doi.org/10.1016/j.abb.2010.07.029] [PMID: 20682280]
[40]
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(18): 2827-33.
[http://dx.doi.org/10.1097/QAD.0b013e328340a28d] [PMID: 21045635]
[41]
Ceballos ME, Carvajal C, Jaramillo J, Dominguez A, González G. Vitamin d and bone mineral density in HIV newly diagnosed therapy-naive patients without any secondary causes of osteoporosis. Calcif Tissue Int 2019; 104(1): 42-9.
[http://dx.doi.org/10.1007/s00223-018-0474-5] [PMID: 30209528]
[42]
Compston J. HIV infection and osteoporosis. Bonekey Rep 2015; 4: 636.
[http://dx.doi.org/10.1038/bonekey.2015.3] [PMID: 25709813]
[43]
Cervero M, Torres R, Agud JL, et al. Prevalence of and risk factors for low bone mineral density in Spanish treated HIV-infected patients. PLoS One 2018; 13(4): e0196201.
[http://dx.doi.org/10.1371/journal.pone.0196201] [PMID: 29709013]
[44]
Post FA. Bone mineral density decline in patients on stable antiretroviral therapy. AIDS 2017; 31(5): 727-9.
[http://dx.doi.org/10.1097/QAD.0000000000001396] [PMID: 28225451]
[45]
Grijsen ML, Vrouenraets SME, Steingrover R, et al. High prevalence of reduced bone mineral density in primary HIV-1-infected men. AIDS 2010; 24(14): 2233-8.
[http://dx.doi.org/10.1097/QAD.0b013e32833c93fe] [PMID: 20616695]
[46]
Wang Q, Liu J, Ding H, et al. Reduced bone mineral density among ART-naive male patients with HIV in China. Future Virol 2015; 10(7): 827-33.
[http://dx.doi.org/10.2217/fvl.15.51]
[47]
Kooij KW, Wit FWNM, Bisschop PH, et al. Low bone mineral density in patients with well-suppressed HIV infection: association with body weight, smoking, and prior advanced HIV disease. J Infect Dis 2015; 211(4): 539-48.
[http://dx.doi.org/10.1093/infdis/jiu499] [PMID: 25180239]
[48]
Battalora L, Buchacz K, Armon C, et al. Low bone mineral density and risk of incident fracture in HIV-infected adults. Antivir Ther 2016; 21(1): 45-54.
[http://dx.doi.org/10.3851/IMP2979] [PMID: 26194468]
[49]
Bolland MJ, Grey AB, Gamble GD, Reid IR. CLINICAL Review # : low body weight mediates the relationship between HIV infection and low bone mineral density: a meta-analysis. J Clin Endocrinol Metab 2007; 92(12): 4522-8.
[http://dx.doi.org/10.1210/jc.2007-1660] [PMID: 17925333]
[50]
Mondy K, Yarasheski K, Powderly WG, et al. Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals. Clin Infect Dis 2003; 36(4): 482-90.
[http://dx.doi.org/10.1086/367569] [PMID: 12567307]
[51]
Grund B, Peng G, Gibert CL, et al. Continuous antiretroviral therapy decreases bone mineral density. AIDS 2009; 23(12): 1519-29.
[http://dx.doi.org/10.1097/QAD.0b013e32832c1792] [PMID: 19531929]
[52]
Arnsten JH, Freeman R, Howard AA, Floris-Moore M, Santoro N, Schoenbaum EE. HIV infection and bone mineral density in middle-aged women. Clin Infect Dis 2006; 42(7): 1014-20.
[http://dx.doi.org/10.1086/501015] [PMID: 16511769]
[53]
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(5): 617-23.
[http://dx.doi.org/10.1097/QAD.0b013e3280148c05] [PMID: 17314524]
[54]
Atencio P, Cabello A, Conesa-Buendía FM, et al. Increased risk factors associated with lower BMD in antiretroviral-therapy-naïve HIV-infected adult male. BMC Infect Dis 2021; 21(1): 542.
[http://dx.doi.org/10.1186/s12879-021-06263-9] [PMID: 34107907]
[55]
Starup-Linde J, Rosendahl SB, Storgaard M, Langdahl B. Management of osteoporosis in patients living with HIV-A systematic review and meta-analysis. J Acquir Immune Defic Syndr 2020; 83(1): 1-8.
[http://dx.doi.org/10.1097/QAI.0000000000002207] [PMID: 31809356]
[56]
Avihingsanon A, Kerr SJ, Ramautarsing RA, et al. The association of gender, age, efavirenz use, and hypovitaminosis d among HIV-infected adults living in the tropics. AIDS Res Hum Retroviruses 2016; 32(4): 317-24.
[http://dx.doi.org/10.1089/aid.2015.0069] [PMID: 26413903]
[57]
Abraham AG, Zhang L, Calkins K, et al. Vitamin D status and immune function reconstitution in HIV-infected men initiating therapy. AIDS 2018; 32(8): 1069-76.
[http://dx.doi.org/10.1097/QAD.0000000000001782] [PMID: 29547433]
[58]
Reyes-Garcia R, Mendoza N, Palacios S, et al. Effects of daily intake of calcium and vitamin d-enriched milk in healthy postmenopausal women: a randomized, controlled, double-blind nutritional study. J Womens Health (Larchmt) 2018; 27(5): 561-8.
[http://dx.doi.org/10.1089/jwh.2017.6655] [PMID: 29676968]
[59]
Cumming RG, Nevitt MC. Calcium for prevention of osteoporotic fractures in postmenopausal women. J Bone Miner Res 1997; 12(9): 1321-9.
[http://dx.doi.org/10.1359/jbmr.1997.12.9.1321] [PMID: 9286747]
[60]
Fabiani R, Naldini G, Chiavarini M. Dietary patterns in relation to low bone mineral density and fracture risk: a systematic review and meta-analysis. Adv Nutr 2019; 10(2): 219-36.
[http://dx.doi.org/10.1093/advances/nmy073] [PMID: 30657847]
[61]
Chiţu-Tișu CE, Barbu EC, Lazăr M, Ion DA, Bădărău IA. Low bone mineral density and associated risk factors in HIV-infected patients. Germs 2016; 6(2): 50-9.
[http://dx.doi.org/10.11599/germs.2016.1089] [PMID: 27482514]
[62]
Dolan SE, Huang JS, Killilea KM, Sullivan MP, Aliabadi N, Grinspoon S. Reduced bone density in HIV-infected women. AIDS 2004; 18(3): 475-83.
[http://dx.doi.org/10.1097/00002030-200402200-00014] [PMID: 15090800]
[63]
Kelley CF, Barbour JD, Hecht FM. The relation between symptoms, viral load, and viral load set point in primary HIV infection. J Acquir Immune Defic Syndr 2007; 45(4): 445-8.
[http://dx.doi.org/10.1097/QAI.0b013e318074ef6e] [PMID: 17514014]
[64]
Walker Harris V, Brown TT. Bone loss in the HIV-infected patient: evidence, clinical implications, and treatment strategies. J Infect Dis 2012; 205(Suppl. 3): S391-8.
[http://dx.doi.org/10.1093/infdis/jis199] [PMID: 22577213]
[65]
Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: A 3-year randomized trial. JAMA 2004; 292(2): 191-201.
[http://dx.doi.org/10.1001/jama.292.2.191] [PMID: 15249568]
[66]
Taiwo BO, Chan ES, Fichtenbaum CJ, et al. AIDS Clinical Trials Group A5303 Study Team. Less bone loss with maraviroc- versus tenofovir-containing antiretroviral therapy in the AIDS clinical trials group A5303 study. Clin Infect Dis 2015; 61(7): 1179-88.
[http://dx.doi.org/10.1093/cid/civ455] [PMID: 26060295]
[67]
Wohl D, Oka S, Clumeck N, et al. A randomized, double-blind comparison of tenofovir alafenamide versus tenofovir disoproxil fumarate, each coformulated with elvitegravir, cobicistat, and emtricitabine for initial HIV-1 treatment: Week 96 results. J Acquir Immune Defic Syndr 2016; 72(1): 58-64.
[http://dx.doi.org/10.1097/QAI.0000000000000940] [PMID: 26829661]
[68]
Mills A, Arribas JR, Andrade-Villanueva J, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis 2016; 16(1): 43-52.
[http://dx.doi.org/10.1016/S1473-3099(15)00348-5] [PMID: 26538525]
[69]
Pozniak A, Arribas JR, Gathe J, et al. Switching to tenofovir alafenamide, coformulated with elvitegravir, cobicistat, and emtricitabine, in HIV-infected patients with renal impairment: 48-week results from a single-arm, multicenter, open-label phase 3 study. J Acquir Immune Defic Syndr 2016; 71(5): 530-7.
[http://dx.doi.org/10.1097/QAI.0000000000000908] [PMID: 26627107]
[70]
Jain RG, Lenhard JM. Select HIV protease inhibitors alter bone and fat metabolism ex vivo. J Biol Chem 2002; 277(22): 19247-50.
[http://dx.doi.org/10.1074/jbc.C200069200] [PMID: 11937496]
[71]
Kinai E, Nishijima T, Mizushima D, et al. Long-term use of protease inhibitors is associated with bone mineral density loss. AIDS Res Hum Retroviruses 2014; 30(6): 553-9.
[http://dx.doi.org/10.1089/aid.2013.0252] [PMID: 24494779]
[72]
Borges ÁH, Hoy J, Florence E, et al. Antiretrovirals, fractures, and osteonecrosis in a large International HIV cohort. Clin Infect Dis 2017; 64(10): 1413-21.
[http://dx.doi.org/10.1093/cid/cix167] [PMID: 28329090]
[73]
Baranek B, Wang S, Cheung AM, Mishra S, Tan DH. The effect of tenofovir disoproxil fumarate on bone mineral density: A systematic review and meta-analysis. Antivir Ther 2020; 25(1): 21-32.
[http://dx.doi.org/10.3851/IMP3346] [PMID: 32077867]
[74]
Noe S, Jaeger H, Wolf E. Antiretroviral therapy options in people living with HIV at risk of or with osteoporosis: Comment on “Diagnosis, prevention, and treatment of bone fragility in people living with HIV: a position statement from the Swiss Association against Osteoporosis”. Osteoporos Int 2019; 30(8): 1705-6.
[http://dx.doi.org/10.1007/s00198-019-05024-4] [PMID: 31143992]
[75]
Boontanondha P, Nimitphong H, Musikarat S, Ragkho A, Kiertiburanakul S. Vitamin D and calcium supplement attenuate bone loss among hivinfected patients receiving tenofovir disoproxil fumarate/emtricitabine/ efavirenz: An open-label, randomized controlled trial. Curr HIV Res 2020; 18(1): 52-62.
[http://dx.doi.org/10.2174/1570162X18666200106150806] [PMID: 31906840]

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