Fall 2015
Abstract: Bone disease has affected people with HIV since the early days of the epidemic. Over the years, low bone mineral density has proved frequent in HIV-positive people, who bear a high burden of traditional bone loss risk factors. Accumulated evidence from the United States, Canada, and Western Europe indicates that people with HIV run a higher risk of fracture than comparison groups. Five cross-sectional studies confirmed significantly higher fracture prevalence in people with HIV than in comparison groups. Ten longitudinal comparative studies all found higher fracture incidence in HIV populations, and the higher fracture rate with HIV proved significant in seven of these studies, independently of certain classical risk factors. In one U.S. study, fracture incidence rose steadily over the years in people with HIV but not in the general population. |
It all started with a bad tooth. A very bad tooth. In November 1989 -- a scant 5 years after researchers discovered the AIDS virus -- specialists in Copenhagen described what appears to be the first published case of bone disease in an HIV-positive person: tooth loss and necrosis of the alveolar (tooth socket) bone in a patient with trigeminal herpes zoster.1
Alveolar necrosis (bone death) did not emerge as a prominent complication of HIV infection, but over the next several years groups in the UK and France reported avascular necrosis of the hip2 and femoral head3 in people with HIV. In 1993 researchers in Spain compared 16 HIV-positive people with 27 healthy HIV-negatives and charted significantly lower levels of osteocalcin -- a bone formation marker -- in the HIV group.4 Bone mass also proved lower in the group with HIV. Although that difference lacked statistical significance, scores of later studies would confirm significantly lower bone mineral density (BMD) in people with HIV than in HIV-negative comparison groups.
BMD offers a convenient signal of bone health, but HIV clinicians and the people they see care more about the ultimate consequence of waning bone density: fractures. And plenty of research, detailed in this article, records higher fracture rates in people with than without HIV. The published history of broken bones in HIV-positive people dates back at least to 2001, when Italian clinicians reported fractures "after trivial trauma" in two men with AIDS -- one with osteopenia, the other with osteoporosis.5 One man was 49 and the other 51, and both had central and peripheral lipodystrophy. Both men had taken indinavir plus stavudine/lamivudine, both had well-controlled HIV infection, and neither had abnormal lipids.
Twelve years later meta-analysis of seven studies comparing fracture incidence in people with and without HIV calculated a 58% higher incidence of all fractures in the HIV group (pooled incidence rate ratio [IRR] 1.58, 95% confidence interval [CI] 1.25 to 2.00) and a 35% higher incidence of fragility fractures (pooled IRR 1.35, 95% CI 1.10 to 1.65).6 (Fragility fractures are those following minimal trauma and usually affecting the hip, spine, or wrist.7) Published from 2007 through 2012, these studies confirmed several traditional fracture risk factors in people with HIV -- older age, white race, low weight, alcohol or substance use, diabetes, and liver disease.6 Six of seven studies in the meta-analysis figured that hepatitis C virus (HCV) infection inflated fracture risk.
Researchers who ran the meta-analysis rate the 58% higher all-fracture risk and the 35% higher fragility-fracture risk "modest" surges in risk with HIV.6 A review of five cross-sectional studies (Table 1) and new longitudinal studies published since the meta-analysis (Table 2) add weight to the conclusion that HIV makes broken bones more likely.
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