High Rate of Bone Thinning in People With Long Antiretroviral Treatment

March 2011

Almost three quarters of HIV-positive people in a Spanish clinic had lower-than-normal bone mineral density (osteopenia or osteoporosis), and the rate of bone thinning increased with time.1 This 671-person study found a link between treatment with protease inhibitors (PIs) or Viread (tenofovir) and low bone mineral density. Certain traditional risk factors -- including low weight and older age -- made osteopenia or osteoporosis more likely.


Earlier studies found that people with HIV have about a 3 times higher rate of low bone mineral density than the general population.2-4 Low bone density raises the risk of broken bones (fractures), and other research found a higher fracture rate in HIV-positive people than in the general population.5,6 Some of these studies are relatively small or focus on a single point in time. In contrast, the new study is relatively large and assessed bone density for 5 years or more in many study participants.

Traditional risk factors for osteopenia and osteoporosis -- such as cigarette smoking and low weight -- contribute to the risk in people with HIV. The potential roles of HIV itself and treatment with antiretrovirals in low bone density are not as well understood. Researchers at a large HIV clinic in Barcelona, Spain, planned this study to determine the impact of traditional and HIV-related risk factors on bone density over an extended period.

  • How the study worked. In an HIV clinic population including about 2300 people seen from 2000 through 2009, the researchers focused on 671 people (29%) who had at least one DEXA scan measuring bone mineral density in the lumbar (lower) spine, femoral neck (thin part at top of thigh bone), and total body. The investigators used DEXA results to calculate t scores for all study participants; t scores compare bone mineral density in an individual with bone density in a young person. A t score of –1 to –2.5 indicates osteopenia (moderate bone thinning), while a t score below –2.5 indicates osteoporosis (severe bone thinning). For people with two or more DEXA scans, the researchers determined whether bone thinning got any worse from one scan to the next.

    The investigators recorded general factors that affect bone mineral density, such as age, body mass index (weight figured as kilograms divided by height in meters squared, or kg/m2), and smoking habits. They also recorded HIV-specific factors, such as duration of HIV infection, CD4 count, viral load, and treatment with various antiretrovirals, including PIs and Viread. Then the researchers used standard statistical methods to determine whether any of these factors affected the risk of low bone density independently of the other factors analyzed.

  • What the study found. In the study group of 671 HIVpositive people, 483 (72%) were men, 288 (43%) smoked, and 416 (62%) had adequate calcium intake (necessary for healthy bones). Median body mass index was 23 kg/ m2 (normal is 18.5 to 24.9 kg/m2), and median age was 42.1 years. This group had been infected with HIV for a median of 11.1 years, current median CD4 count was 496, and 61% had an undetectable viral load. Only 7 people (1%) had never taken antiretrovirals. While 53% of study participants were taking a PI at the time of their DEXA scan, 53% were taking Viread. Median time taking antiretrovirals was 7.4 years.

    Among all 671 study participants, 319 (47.5%) had osteopenia and 155 (23%) had osteoporosis. The proportion of people with osteoporosis was lower in those infected with HIV for under 2 years (16%) than in those infected more than 11 years (31%). And the proportion of people with osteoporosis was lower in those taking antiretrovirals for under 2 years (17%) than in those taking antiretrovirals more than 10 years (36%).

    The researchers conducted a statistical analysis to determine which factors affected the risk of low bone density regardless of what other risk factors a person might have. This analysis revealed four traditional risk factors: older age, male gender, lower body mass index (weight), and infection with hepatitis B or C virus in addition to HIV. Three antiretroviral-related risk factors also raised the risk of osteopenia or osteoporosis in this analysis: longer time taking a PI, taking a PI at the time of the last DEXA scan, and taking Viread at the last DEXA scan.

    The study group included 391 people (58% of 671) who had two or more DEXA scans. Median time between the first and last DEXA scan was 2.5 years, and 105 people (16% of 671) had their last scan 5 or more years after their first scan. In this 391-person subgroup, 49% had osteopenia at the first scan and 50% at the last scan last; 22% had osteoporosis at first scan and 27% at the last scan. In the 105 people with 5 or more years between their first and last scan, 18% with normal bone density at the first scan had osteopenia at the last scan, and 29% with osteopenia at the first scan had osteoporosis at the last scan. Overall, 12.5% of people with two or more DEXA scans went from a normal t score to osteopenia and 15.6% went from osteopenia to osteoporosis.

    Figure 1: Factors raising risk of loww bone density.

    Figure 1. Three antiretroviral-related factors (lower three bars) and three general factors (upper three bars) raised the risk of osteopenia or osteoporosis in 391 people with two or more DEXA scans of bone mineral density. PIs are protease inhibitors, a type of antiretroviral. DEXA is a scan that calculates bone mineral density.

    Statistical analysis that considered many risk factors for declining bone mineral density found six factors that affected the risk of osteopenia or osteoporosis regardless of what other risk factors a person had -- older age, male gender, low body mass index, time taking PI therapy, time taking Viread, and taking a PI at the time of DEXA scanning (Figure 1). Factors that did not affect bone density risk in this analysis included time since HIV infection diagnosis, current CD4 count, lowest-ever CD4 count, and viral load.

  • What the results mean for you. In this large study of people in an HIV clinic, about three quarters had moderately or severely low bone mineral density (osteopenia or osteoporosis). Among people with two or more scans to determine bone density over a span of several years, rates of osteopenia or osteoporosis rose over those years. Results of this study are important because it included almost 400 people with two or more bone mineral scans; that allowed the researchers to assess the impact of continuing antiretroviral therapy and other factors on bone density.

    Several factors raised the risk of osteopenia or osteoporosis independently of other risk factors studied: older age, male gender, lower body mass index, infection with hepatitis B or C virus, longer time taking a PI, and longer time taking Viread.

    This study has one possible limitation: The analysis included only people who had one or more DEXA scans, less than one third of the clinic population. Doctors might have ordered DEXA scans for these people because they suspected a high risk of bone thinning. As a result, the study group might include a higher-than-normal proportion of people with low bone density.

    However, the researchers point out that DEXA scanning is part of the routine checkup for all HIV-positive people in this clinic. The long duration of HIV infection and antiretroviral therapy could be the main reasons for high rates of osteopenia and osteoporosis in this study group. The researchers stress that the link between use of PIs and Viread does not mean antiretrovirals in general should be avoided because of a possible impact on bone health. Rather, they say, "continuous antiretroviral therapy is essential to prevent clinical progression to AIDS and non-AIDS-related diseases."

    These new findings add to earlier results showing high rates of osteopenia and osteoporosis in HIV-positive people. Because of these findings, people with HIV infection should know what lifestyle decisions and other factors raise the risk of low bone mineral density. A panel of US experts on bone disease in people with HIV underlines several such factors that may be more common in HIV-positive people (Table 1).7

    The Spanish researchers believe DEXA scanning for bone mineral density "should be a priority in HIV-infected patients, specifically in those at risk of fracture."1 They recommend prevention strategies such as lifestyle modifications, including adequate nutrition to prevent low weight and adequate intake of calcium and vitamin D. The US experts recommend DEXA scanning for (1) all HIV-positive men 50 years old or older, (2) all HIVpositive women past the menopause, and (3) possibly for HIV-positive people who have had a broken bone.7

Table 1. Conditions That May Raise Risk of Osteoporosis or Fracture With HIV

Lifestyle choices or habitsMore than 3 alcohol drinks daily, low dietary calcium, methadone/opiates, physical inactivity, tobacco use
Hypogonadal statesEarly menopause, low testosterone in men, premenopausal infrequent menstruation
Other endocrine disordersAdrenal insufficiency
Blood disordersHemophilia, sickle-cell disease
Lung diseasesEmphysema
MedicationsAntiretrovirals, glitazones, glucocorticoids, proton pump inhibitors, excess thyroxine
MiscellaneousChronic metabolic acidosis, chronic infection, chronic kidney disease, depression, vitamin D deficiency
Source: McComsey et al.7


  1. 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;24:2827-2833.
  2. Knobel H, Guelar A, Vallecillo G, Nogues X, Diez A. Osteopenia in HIV-infected patients: is it the disease or is it the treatment? AIDS. 2001;15:807-808.
  3. 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.
  4. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS. 2006;20:2165-2174.
  5. 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;93:3499-3504.
  6. Wormack J, Goulet J, Gibert C, et al. HIV infection and fragility fracture risk among male veterans. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 129.
  7. 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;51:937-946.

This article was provided by The Center for AIDS Information & Advocacy. It is a part of the publication HIV Treatment ALERTS!. Visit CFA's website to find out more about their activities and publications.

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