Break No Bones About It
HIV Itself -- As Well As Medications and Traditional Causes -- May Increase the Risk of Fracture
Everyone's heard about elderly people falling and breaking their hips, but for a while, there were stories about much younger HIV-positive people with brittle, breaking bones. Some were even having hip replacements (see "I couldn't cross at the light"). What was going on?
As suspected, the life-saving HIV medications that were still relatively new at that time played a role -- but they were only partially to blame, it turned out.
Providing an overview on the matter at this year's CROI was Todd T. Brown, M.D., Ph.D., of Johns Hopkins University. Yes, HIV medications may negatively affect bone health, but there is also the effect of HIV itself, as well as the usual suspects like cigarettes and alcohol. (See the half-hour presentation at retroconference.org, Wednesday sessions, "Long-term Non-AIDS Complications," 4-6 p.m.)
In 2006, Brown and colleagues published a report in the medical journal AIDS showing that a large number of people with HIV (15%) had osteoporosis. Osteoporosis is a loss of bone tissue that makes fractures more likely. They found that compared to HIV-negative control groups, people with HIV were three-and-a-half times more likely to have osteoporosis. They gathered those numbers after analyzing 11 HIV studies that included data on bone mineral density (BMD).
But if HIV and the medications used to treat it combine with traditional risk factors to make for brittle bones, the Titans clash over what to do about it. As with many conditions, you can decide to be aggressive with screening and treatment, or not.
Several studies have clarified the role of HIV medications. (See sidebar.)
Many other things, however, affect people with HIV and the chance to keep their bones intact. First there's HIV itself. Later on, the role of HIV came to light. The virus has proteins that, in a variety of ways, weaken bone mass.
Then there's the immune system. "Many cross-sectional studies have shown an association between low CD4 cell counts and lower bone mineral density," Brown said, adding that this information is still being investigated "to figure out what exactly is going on."
Other personal attributes are "very important to pathogenesis [the cause of disease]," said Brown. "We know that there are a variety of traditional osteoporosis risk factors that may be higher in prevalence in our HIV patient population," Brown said. He listed the following:
The use of steroids, often prescribed in the treatment of disease, can also negatively affect bones. Brown suggested that patients with reduced bone mineral density be checked for the following secondary causes of BMD, as a "minimal work-up":
To help prevent bone loss, patients have several options. First are calcium and vitamin D supplements. Then there's weight-bearing exercise; smoking cessation and alcohol reduction; and treatment of secondary causes of reduced BMD.
Brown noted that the level of vitamin D deficiency in the general U.S. population is "exceedingly high" and suggested supplementation of 1,000 to 1,200 IU vitamin D for everyone, no matter their level of bone mineral density. During the question-and-answer section, however, he admitted that's a standard recommendation that he, like many providers in the audience, thinks is too low. He said he usually recommends 50,000 IU of herbal calciferol twice a week for eight to 12 weeks in patients with low levels of vitamin D.
There are also the common sense measures doctors tell their patients who are at risk for falling or breaking a bone. This includes the many people with HIV suffering from the nerve damage of peripheral neuropathy, making them unsteady on their feet. Take care of loose rugs and clutter on the floor. Keep wires behind furniture. Add night lights to help you watch your step. Avoid slippery or uneven surfaces. Beware of drinking excess alcohol. Wear sturdy shoes.
Also at higher risk are those people with HIV who have lipoatrophy, or fat loss and thinning. Hips with less fat cushioning them are at greater risk of breaking in a fall.
Cognitive or visual impairment, sedative use, and muscle weakness resulting from hypogonadism are also osteoporosis risk factors.
Boys with HIV seem to be another group at risk. At the lipodystrophy conference in London in November, the Pediatric ACTG (AIDS Clinical Trials Group) reported that of children with HIV, boys failed to reach peak bone mineral mass, while girls didn't. This puts those boys at greater risk of fracture.
Brown said the development of bone mineral mass peaks around age 30 and goes downhill from there. For anyone to be osteoporatic at 65, Brown said, means that they lost bone mineral density quickly after 30, or they failed to reach peak bone mineral density in the first place, or a combination of the two. "[This report] suggests that, at least in males, there's failure to reach bone mineral mass and there are obvious ramifications later on in life."
"We talk about BMD in HIV, but what we really want to know is about fractures," Brown said. "This data is beginning to emerge. The risk of fracture is higher in HIV patients, particularly as age advances. So, we know that osteoporosis is common. We know that there's an increased risk of fracture in HIV-infected patients. We also know that the etiology is multifactorial. So the issue that comes up is what to do about it, how to screen for it, and how to treat it."
Brown concluded that although osteporosis is common in HIV, he doesn't recommend universal screening, but that aggressive screening and treatment in people over the age of 50 would be good.
Daniel S. Berger, M.D., of Northstar Medical Clinic in Chicago, said, "I take issue with screening [only] for people over 50. [There should be a] bone DEXA [scan] for everyone diagnosed with HIV." Brown said he agrees with a universal DEXA in "a world of endless resources." He called the relative risk of fracture high, but the actual risk very low, and he would rather put a patient on biphosphonate therapy for osteoporosis when the patient is 55 and best able to benefit from treatment. Otherwise, patients with low bone mineral density who are in their 30s or 40s should start taking calcium supplements, cut down on their drinking, stop smoking, and take other steps to improve their bone status.
In response to another question from the audience, he said he thinks HIV-positive women on Depoprovera should definitely take calcium and vitamin D.
Even though the virus and its medications may be attacking your bones, Brown said you may not want to rush to take bone meds. He said there is a theoretical concern with bisphosphonates, which make up first-line treatment of osteoporosis. "[There is a] question on whether this very potent effect on bone turnover is actually a good thing. We require bone turnover to repair micro-fractures that occur all the time with regular wear and tear." It's unknown what effect this would have on younger patients taking the medications for a longer period of time. Currently, he said, doctors recommend a holiday from the treatment every five or 10 years. These medications include Actonel (risedronate), Fosamax (alendronate), ibandronate, and zolendronic acid.
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