Contents

Reduced bone density and HIV

Many studies have found that some HIV-positive people tend to have bones that are not as thick or dense as they ought to be. Such bones have reduced bone mineral density, as minerals such as calcium have been removed, rendering the bones more porous and weak.

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Osteopenia is a relatively mild form of reduced bone mineral density and osteoporosis is the more severe form. People with osteopenia or osteoporosis are at heightened risk for breaking bones when they have accidents or fall. Osteopenia and osteoporosis can even lead to damage in the absence of accidents as the spine and hips slowly degrade under the burden of bearing the body’s weight.

There are many risk factors for developing reduced bone mineral density among HIV-negative people and these same factors are at play among HIV-positive people. While some of these factors can be changed, some cannot, as the following lists show:

Risk factors that cannot be changed:

  • history of fractures among parents, brothers or sisters
  • personal history of fractures
  • being a woman – bone density decreases during the transition to menopause
  • being elderly

Risk factors that can be changed:

  • use of corticosteroids
  • excess intake of alcohol
  • smoking tobacco
  • use of street drugs such as crystal meth, heroin and related substances
  • deficiency of the hormone estrogen in women
  • insufficient exercise
  • less-than-ideal body weight
  • insufficient intake of calcium

Some HIV-positive people may have additional risk factors, including:

  • deficiency of vitamin D (needed to absorb calcium and other minerals used for bone building)
  • being depressed
  • deficiency of the hormone testosterone in men
  • chronic inflammation
  • co-infection with hepatitis C virus (HCV)

Chronic inflammation is a consequence of HIV infection. Although use of potent combination anti-HIV therapy (commonly called ART or HAART) can greatly reduce inflammation, because ART does not cure HIV infection some residual inflammation remains.

Impact of ART

In general, after a person begins to take ART bone density may continue to decrease by 1% to 4% for several years, then stabilize and even increase.

Tenofovir and bones

Several studies have found that the use of the drug tenofovir (Viread, and in Truvada, Atripla and Complera) as part of ART may temporarily accelerate bone thinning in a minority of HIV-positive people. However, in such studies the loss of bone mineral density associated with the use of this drug tends to stabilize over time in most people. Moreover, results from randomized clinical trials comparing different treatments have not found an increased risk for fractures among people who use tenofovir or tenofovir-containing drugs.

Reports have emerged from studies of a different design, specifically observational or cohort studies, of an increased risk of either kidney dysfunction or an increased risk for fractures among some participants who used tenofovir. A future issue of TreatmentUpdate will review and explain those findings.

Tenofovir may cause kidney dysfunction in a small proportion of participants in randomized clinical trials, and this dysfunction may affect the kidneys’ ability to regulate calcium or phosphorus levels. These minerals are used to maintain bone mineral density. In most cases when kidney dysfunction has occurred in tenofovir users in randomized clinical trials it was usually temporary.

Tenofovir has been widely used for the past decade in high-income countries. For the vast majority of tenofovir users, the drug is safe and effective when used as directed.

Concern about efavirenz

Use of efavirenz (Sustiva, Stocrin and in Atripla) is associated with having lower-than-normal levels of vitamin D in the blood of some HIV-positive people. This vitamin helps to absorb calcium and phosphorus from food, and reduced levels of vitamin D may affect the ability to maintain bone mineral density.

Other drugs

Drugs that have the potential to affect kidney health, impact the functioning of bone cells or interfere with the body’s processing of vitamin D, if taken over the long term or frequently, may also have the potential to affect bone mineral density. Such drugs can include the following:

  • antibiotics – Bactrim/Septra (trimethoprim-sulfamethoxazole)
  • antiviral agents – acyclovir (Zovirax) and valacyclovir (Valtrex), foscarnet (Foscavir), cidofovir (Vistide)
  • antifungal agents – amphotericin B
  • antiseizure drugs – phenytoin, carbamazepine, valproic acid
  • antidepressants – lithium
  • anti-inflammatory drugs – ibuprofen (Advil, Motrin), naproxen (Naprosyn), acetaminophen (Tylenol), indomethacin (Indocid)
  • opiates – codeine, morphine, methadone and related substances

— Sean R. Hosein

REFERENCES:

  1. Lindsay R, Cosman F. Chapter 354. Osteoporosis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
  2. Curran A, Martinez E, Podzamczer D, et al. Changes in body composition and mitochondrial DNA in HIV-1-infected patients switching to fixed-dose abacavir/lamivudine or tenofovir/emtricitabine: a substudy of the BICOMBO Trial. Antiviral Therapy. 2012; in press.
  3. Cotter AG, Powderly WG. Endocrine complications of human immunodeficiency virus infection: hypogonadism, bone disease and tenofovir-related toxicity. Best Practice & Research. Clinical Endocrinology & Metabolism. 2011 Jun;25(3):501-15.
  4. Langsetmo L, Hitchcock CL, Kingwell EJ, et al. Physical activity, body mass index and bone mineral density—associations in a prospective population-based cohort of women and men: the Canadian Multicentre Osteoporosis Study (CaMos). Bone. 2012 Jan;50(1):401-8.
  5. Szulc P, Debiesse E, Boutroy S, et al. Poor trabecular microarchitecture in male current smokers: the cross-sectional STRAMBO study. Calcified Tissue International. 2011 Oct;89(4):303-11.
  6. Milos G, Gallo LM, Sosic B, et al. Bone mineral density in young women on methadone substitution. Calcified Tissue International. 2011 Sep;89(3):228-33.
  7. Bleicher K, Cumming RG, Naganathan V, et al. Lifestyle factors, medications, and disease influence bone mineral density in older men: findings from the CHAMP study. Osteoporosis International. 2011 Sep;22(9):2421-37.
  8. Diem SJ, Harrison SL, Haney E, et al. Depressive symptoms and rates of bone loss at the hip in older men. Osteoporosis International. 2012; in press.
  9. Cizza G, Ronsaville DS, Kleitz H, et al. Clinical subtypes of depression are associated with specific metabolic parameters and circadian endocrine profiles in women: the power study. PLoS One. 2012;7(1):e28912.
  10. Wu Q, Bencaz AF, Hentz JG, et al. Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies. Osteoporosis International. 2012 Jan;23(1):365-75.
  11. Walker Harris V, Sutcliffe CG, et al. Hip bone geometry in HIV/HCV-co-infected men and healthy controls. Osteoporosis International. 2012; in press.
  12. Sharma A, Cohen HW, Freeman R, et al. Prospective evaluation of bone mineral density among middle-aged HIV-infected and uninfected women: Association between methadone use and bone loss. Maturitas. 2011 Nov;70(3):295-301.
  13. Vestergaard P, Hermann P, Jensen JE, et al. Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention Study (DOPS). Osteoporosis International. 2012 Apr;23(4):1255-65.
  14. Estrella MM, Kirk GD, Mehta SH, et al. Vitamin D deficiency and persistent proteinuria among HIV-infected and uninfected injection drug users. AIDS. 2012 Jan 28;26(3):295-302.
  15. Grey A, Rix-Trott K, Horne A, et al. Decreased bone density in men on methadone maintenance therapy. Addiction. 2011 Feb;106(2):349-54.
  16. Lapi F, Simonetti M, Michieli R, et al. Assessing 5-year incidence rates and determinants of osteoporotic fractures in primary care. Bone. 2012 Jan;50(1):85-90.
  17. Svalheim S, Røste LS, Nakken KO, et al. Bone health in adults with epilepsy. Acta neurologica Scandinavica. Supplementum. 2011;(191):89-95.
  18. Pack AM, Morrell MJ, McMahon DJ, et al. Normal vitamin D and low free estradiol levels in women on enzyme-inducing antiepileptic drugs. Epilepsy & Behavior. 2011 Aug;21(4):453-8.
  19. Holick MF, Binkley NC, Hike A, et al. Evaluation, treatment and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism. 2011 Jul;96(7):1911-30.
  20. Mazziotti G, Canalis E, Giustina A. Drug-induced osteoporosis: mechanisms and clinical implications. American Journal of Medicine. 2010 Oct;123(10):877-84.
  21. Vrzal R, Doricakova A, Novotna A, et al. Valproic acid augments vitamin D receptor-mediated induction of CYP24 by vitamin D3: a possible cause of valproic acid-induced osteomalacia? Toxicology Letters. 2011 Feb 5;200(3):146-53.
  22. Yong MK, Elliott JH, Woolley IJ, et al. Low CD4 count is associated with an increased risk of fragility fracture in HIV-infected patients. Journal of Acquired Immune Deficiency Syndromes. 2011 Jul 1;57(3):205-10.
  23. Kim EY, Kwon do H, Lee BD, et al. Frequency of osteoporosis in 46 men with methamphetamine abuse hospitalized in a National Hospital. Forensic Science International. 2009 Jul 1;188(1-3):75-80.
  24. Welz T, Childs K, Ibrahim F, et al. Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase. AIDS. 2010 Jul 31;24(12):1923-8.
  25. Liu AY, Vittinghoff E, Sellmeyer DE, et al. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS One. 2011;6(8):e23688.
  26. Ofotokun I, McIntosh E, Weitzmann MN. HIV: inflammation and bone. Current HIV/AIDS Reports. 2012 Mar;9(1):16-25.
  27. Bolland MJ, Wang TK, Grey A, et al. Stable bone density in HAART-treated individuals with HIV: a meta-analysis. Journal of Clinical Endocrinology & Metabolism. 2011 Sep;96(9):2721-31.
  28. 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 fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. Journal of Infectious Diseases. 2011 Jun 15;203(12):1791-801.
  29. Yin MT, Overton ET. Increasing clarity on bone loss associated with antiretroviral initiation. Journal of Infectious Diseases. 2011 Jun 15;203(12):1705-7.
  30. Bech A, Van Bentum P, Nabbe K, et al. Fibroblast growth factor 23 in hypophosphataemic HIV-positive adults on tenofovir. HIV Medicine. 2012; in press.
  31. Grigsby IF, Pham L, Mansky LM, et al. Tenofovir treatment of primary osteoblasts alters gene expression profiles: implications for bone mineral density loss. Biochemical and Biophysical Research Communications. 2010 Mar 26;394(1):48-53.
  32. Havens PL, Stephensen CB, Hazra R, et al. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial. Clinical Infectious Diseases. 2012 Apr;54(7):1013-1025.
  33. Martin A, Bloch M, Amin J, et al. Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-Lamivudine: a randomized, 96-week trial. Clinical Infectious Diseases. 2009 Nov 15;49(10):1591-601.
  34. Yin MT, Zhang CA, McMahon DJ, et al. Higher rates of bone loss in postmenopausal HIV-infected women: a longitudinal study. Journal of Clinical Endocrinology and Metabolism. 2012 Feb;97(2):554-62.