Other possible risk factors

Despite these findings, there is still disagreement between studies as to the major risk factors for bone mineral loss in people with HIV.

Some studies suggest that the duration of HIV infection is the crucial factor in osteopenia.1 2 3 4 For example, a French study of 85 consecutive patients attending an HIV clinic found that 20% of treatment-naive patients had osteopenia, and 45% of PI-naive patients had osteopenia. Only the duration of HIV infection was significantly associated with osteopenia.5

Similarly, a study conducted by the Chelsea and Westminster Hospital, London, found no significant difference in BMD between 52 untreated HIV-positive patients, 22 men on PI therapy and ten men receiving NRTIs only. Indeed, antiretroviral therapy of any sort seemed to reduce the severity of bone mineral loss when patients were matched for duration since HIV diagnosis, and there was a trend towards reduced risk in those with lower viral load regardless of risk. These findings suggest that bone mineral loss may be a consequence of long-term HIV infection and immune activation.6

However, the SMART study, perhaps the most rigorous comparison of treated and untreated individuals, in that it compared individuals broadly within the CD4 range 200 to 500, found that individuals taking antiretroviral drugs experienced greater declines in BMD, most noticeably at the hip, and had a fivefold greater risk of serious fractures than untreated individuals.7

A number of factors, other than PI treatment, may be associated with reduced BMD:

  • More rapid loss of subcutaneous fat correlated with a greater reduction in BMD in 171 patients, regardless of PI therapy. However, indinavir (Crixivan) therapy was associated with increased BMD compared to nelfinavir.8 In addition, research to date has not shown a consistent association between lipodystrophy and bone thinning.9 10
  • Higher lactate levels in the blood. Lactic acidemia has been associated with current ddI or d4T treatment and the magnitude of CD4 cell count increases since starting treatment.11 The authors suggested that bone-derived calcium may be used to buffer high levels of acid in the blood. However, other research has failed to confirm this association.12
  • Lower weight prior to starting antiretroviral therapy and lower weight while taking antiretroviral therapy, particularly in women.13
  • Heroin use and advanced HIV disease were risk factors for loss of BMD in older HIV-positive men in the CHAMPS study.14
  • Hepatitis C infection is known to increase the risk of osteoporosis and bone fracture in HIV-negative individuals. Co-infection with HIV and hepatitis C was associated with increased risk of fracture in a retrospective US analysis15, and hepatitis B and C co-infection have been associated with lower BMD in women with HIV infection.16

References

  1. Knobel H et al. Osteopenia in HIV-infected patients: is it the disease or is it the treatment? AIDS 15(6): 807-808, 2001
  2. Lawal A et al. Equivalent osteopenia in HIV-infected individuals studied before and during the era of highly active antiretroviral therapy. AIDS 15(2): 278-280, 2001
  3. McGowan I et al. Assessment of bone mineral density (BMD) in HIV-infected antiretroviral-therapy-naive patients. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 628, 2001
  4. Negredo E et al. Bone mineral density in HIV-infected patients. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 626, 2001
  5. Allavena C et al. Osteopenia and osteoporosis in HIV-infected patients: role of antiretroviral therapy (ART)? 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, abstract 1304, 2000
  6. Moyle G et al. Osteopenia: a consequence of HIV not HAART? Antiviral Therapy 5 (Supp 5): 43, 2000
  7. Grund B et al. Continuous antiretroviral therapy decreases bone mineral density. AIDS 23:1519–1529, 2009
  8. Nolan D et al. Stable or increasing bone mineral density in HIV-infected patients treated with nelfinavir or indinavir. AIDS 15(10): 1275-1280, 2001
  9. Huang JS et al. Increased abdominal visceral fat is associated with reduced bone density in HIV-infected men with lipodystrophy. AIDS 15(8): 975-982, 2001
  10. Tebas P et al. Lack of association between visceral adiposity and osteopenia in HIV-infected individuals. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 633, 2001
  11. Carr A et al. Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight pre-antiretroviral therapy. AIDS 15: 703-709, 2001
  12. Claxton S et al. Circulating leptin and lactate levels are not associated with osteopenia in HIV-infected men. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 634, 2001
  13. Dolan SE at al. Effects of weight, body composition, and testosterone on bone mineral density in HIV-infected women. J Acquir Immune Defic Syndr 45: 161-67, 2007
  14. Sharma A et al. Prospective study of bone mineral density changes in aging men with or at risk of HIV infection. AIDS, 24: online edition, DOI: 10. 1097/QAD.0b013e32833d7da7, 2010
  15. Bedimo R et al. HCV co-infection is associated with a high risk of osteoporotic fractures among HIV-infected patients. Eighteenth International AIDS Conference, Vienna, abstract TUAB0104, 2010
  16. Lo Re V et al. Viral hepatitis is associated with reduced bone mineral density in HIV-infected women but not men. AIDS 23: 2191-98, 2009
This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.