Bone Density Risk Factors in People With HIV: A Long, Familiar List

Fall 2015

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Substance Use, Old Age, Young Age

Apart from drinking too much alcohol and smoking, substance use -- particularly with opioids or opioid substitutes -- figures prominently in bone-risk research but has not earned a place on the 69-item National Osteoporosis Foundation risk list. Here's some of the evidence:

A prospective study of 245 middle-aged women with HIV and 219 women without HIV -- about half of them opioid or cocaine users -- determined that methadone therapy independently predicted waning BMD at the femoral neck.5 Current methadone use also predicted falling BMD (at the total hip) in a study of 230 men with HIV and 159 without HIV, all of them 49 or older and nearly all of them opioid or cocaine users.31 This prospective study linked heroin use plus AIDS to falling BMD at the total hip or femoral neck. Two other studies tied methadone treatment to lower spine BMD in 495 middle-aged women with or without HIV2 and 559 men 49 or older and with or without HIV.3

Incidence of diverse major chronic diseases ratchets relentlessly upward with age, and osteoporosis is no exception. As prevalence of predisposing comorbid diseases climbs and bone mass dwindles with age, risk of osteoporosis and osteoporotic fracture grows apace. And fracture risk with age appears to climb faster with age in people with HIV than in HIV-negative people, suggest results of a large cross-sectional study at Boston's Partners HealthCare System.32 The analysis compared 8525 HIV-positive adults with 2.2 million HIV-negative people in the same system, all of them seen at some point between October 1996 and March 2008. Fragility fracture prevalence rose steeply starting at age 40 in both the HIV-positive and negative groups, but the climb was steeper among both women and men with HIV than in their HIV-negative counterparts (Figure 2).

Difference in Fragility Fracture Prevalence With Age in HIV+ vs HIV- Women and Men

Difference in Fragility Fracture Prevalence With Age in HIV+ vs HIV- Women and Men

Figure 2. Fragility fracture prevalence in a Boston healthcare system rose faster with age in women and men with HIV than in those without HIV.32

The risk imbalance between people with and without HIV may begin early in life -- even before people reach peak bone mass in their early 20s -- if children are infected at birth or in adolescence. The impact of early HIV infection came clear in a three-way comparison involving perinatally and behaviorally HIV-infected young men and healthy controls.33

The researchers cited five previous studies that recorded lower BMD in perinatally and behaviorally infected children and adolescents than in HIV-negative controls, even after adjustment for sexual maturation stage, height, and weight. But they noted that DXA has limitations in growing children that may make comparisons between HIV-positive and negative youngsters unreliable. Thus they used both DXA and high-resolution peripheral quantitative CT (HR-pQCT) to measure BMD in this cross-sectional study of 15 perinatally HIV-infected men, 15 men infected during adolescence, and 15 healthy HIV-negative controls.33 Everyone was between 20 and 25 years old, everyone had reached Tanner stage 5, and all HIV-positive men were on antiretroviral therapy. People usually attain peak bone mass by age 20. Among men with HIV, 60% were black and 40% Hispanic. Among controls, 20% were black and 80% Hispanic. Height, weight, body mass index, smoking status, and alcohol use did not differ significantly between study participants with and without HIV.

Men with and without HIV had similar bone size, but DXA-derived BMD Z scores proved significantly lower in HIV-positive men than in healthy controls at the spine, hip, and radius. HR-pQCT showed significantly lower total and trabecular volumetric BMD at the radius (forearm) and tibia (shin) in men with HIV. Cortical and trabecular thickness were also significantly lower in men with HIV at the radius and tibia. Other bone measures also favored men without HIV. No DXA or HR-pQCT results differed significantly between perinatally and behaviorally infected men with HIV.

The investigators believe their data "suggest that men infected with HIV early in life have lower peak bone mass, a thinner cortical shell, markedly abnormal trabecular bone microstructure with deficiencies in trabecular plates and axial bone volume fraction, and reduced bone strength."33 They proposed that "these deficits may place them at higher risk of fractures as they age than uninfected individuals and HIV-infected individuals who were infected later in life, after acquisition of peak bone mass."

Osteoporosis Risk Pieces Not So Puzzling

With the National Osteoporosis Foundation 69-item risk lists (Table 1, 2, and 3) as a starting point, findings outlined in this article suggest a simpler schema for judging and lowering risk in people with HIV. The blueprint hinges on six immutable risk factors (Figure 3, center), with the understanding that low weight can be improved if its cause is poor nutrition or eating disorders. Six lifestyle changes (Figure 3, left) can lower chances of poor bone health regardless of fixed risk factors. Six comorbidities prevalent in people with HIV (Figure 3, top right) add to the risk of osteoporosis, but all these diseases can be prevented or treated. Five types of nonantiretroviral medications often taken by people with HIV (Figure 3, bottom right) can hike the risk of bone disease and should be considered in the risk equation.

Figure 3

Figure 3. A simplified osteoporosis risk schema for people with HIV considers fixed risk factors (center), lifestyle changes that can lower risk (left), and diseases and medications common in many HIV populations (right). PPIs, proton pump inhibitors; SSRIs, selective serotonin reuptake inhibitors. (Based mainly on National Osteoporosis Foundation risk lists,

The Figure 3 framework abridges the National Osteoporosis Foundation risk factor list by focusing on those most often pinpointed in studies of people with HIV. Still, it remains too lengthy for most to memorize. But anyone can keep in mind the three prime risk factors HIV bone guidelines list for fragility fracture:15

  1. History of fragility fracture
  2. Glucocorticoids for more than 3 months (≥5 mg of prednisone daily or equivalent)
  3. High risk for falls

The following article in this issue covers fragility fracture risk assessment according to the new guidelines.15

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

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