CATIE News

• People living with HIV are at greater risk of bone thinning, which can lead to fractures
• A study suggests this may be due to higher rates of smoking in some people with HIV
• Bone thinning can be prevented by addressing risk factors, and can be reversed

Studies have generally found that HIV-positive people are at heightened risk for reduced bone density—osteopenia (moderately thin bones) and osteoporosis (very thin bones). Thinner bones are weaker and susceptible to fractures during falls or accidents. In turn, fractures can lead to pain, reduced movement and quality of life, and, in some cases, disability.

The precise cause(s) of the reduced bone density in HIV-positive people is not clear. Many studies of bone thinning in HIV-positive people have not taken into account traditional risk factors.

Scientists in Denmark have published the results of a well-designed study comparing health-related information from HIV-negative and HIV-positive people of similar age. All participants underwent CT scans that produced a three-dimensional image of their bones.

After taking into account factors such as smoking, alcohol consumption, physical activity and so on, the scientists found that HIV infection was generally not a risk factor for reduced bone density. Instead, traditional risk factors—particularly smoking—played an important role in the loss of bone density.

The Danish scientists encouraged healthcare professionals to help HIV-positive patients limit or eliminate risk factors for bone loss.

Study details

The Danish scientists compared health-related information from 718 HIV-positive people and 718 HIV-negative people. Data from each HIV-positive person was matched to an HIV-negative person of the same gender and similar age.

The average profile of the HIV-positive participants upon entering the study was as follows:

• age – 52 years
• 86% men, 14% women
• smoking status: current smoker – 26%; former smoker – 40%; never smoker – 34%
• physical activity: inactive – 9%; slightly active – 36%; moderately active – 43%; very active – 12%
• CD4+ cell count – 75% of participants had more than 500 cells/mm³
• viral load – 96% of participants had an undetectable viral load (less than 50 copies/mL)
• past AIDS-related infection/cancer – 20%
• years on HIV treatment (ART) – 13
• detectable hepatitis C viral load – 6%

Most participants had adequate consumption of calcium.

Data were captured between March 2015 and December 2016.

Results

The distribution of very low bone density (indicating osteopenia) was more likely in HIV-positive people (17%) than in HIV-negative people (11%).

Very low bone density in HIV-positive people was linked to the following factors:

• older age
• being male
• years of smoking

HIV-positive people who engaged in physical activity and who were not thin tended to have thicker bones.

Focus on HIV and medicines

People who had AIDS-related infections/cancers in the past were more likely to have reduced bone density.

There was no link in the study between the use of tenofovir DF (the older form of tenofovir) or protease inhibitors and reduced bone density. This finding is important because some previous studies had found such a link.

Bear in mind

This is at least the second well-designed study from a high-income country in the current era that has found that traditional risk factors were very likely the cause of reduced bone density in HIV-positive people. 

Studies done 10, 15 or 20 years ago may have recruited participants who likely would have been exposed to earlier, toxic forms of ART; who delayed initiation of ART until serious immunological dysfunction had occurred; and who may have more likely been exposed to systemic corticosteroids. All of these factors could have contributed to reduced bone density.

Furthermore, these earlier studies did not usually collect detailed information about smoking, exercise and calcium intake as the present Danish study did.

Risk factors

Surveys have found that, in general, HIV-positive people tend to have higher rates of smoking than HIV-negative people. This was seen in the present Danish study, with rates of current smokers distributed as follows:

• HIV positive – 26%
• HIV negative – 13%

Certain health conditions and life stages can potentially contribute to bone loss, such as the following:

• anorexia
• amenorrhea
• Cushing’s syndrome
• chronic obstructive pulmonary disease
• diabetes (type 1 and type 2)
• malnutrition
• menopause
• severe liver disease
• some cancers
• testosterone deficiency

Some medicines are also associated with an increased risk for thinning bones, as follows:

• corticosteroids
• some anti-cancer drugs
• anti-seizure drugs
• some antidepressants
• excessive doses of the hormone thyroxine
• lithium
• proton pump inhibitors
• the transplant drug cyclosporine

Notes on ART, AIDS, young men and bones

ART

A decrease in bone density occurs in the first year after initiation of ART. This happens regardless of the combination of drugs that are taken. The reason(s) for this decline in bone density are not clear. However, within a couple of years of initiating ART, bone thinning significantly falls to levels seen in healthy HIV-negative people. A randomized placebo-controlled trial has found that supplementation with vitamin D₃ and calcium can significantly lessen the rate of bone thinning when ART is initiated.

AIDS

People who experience AIDS-related infections tend to have intense inflammation-related complications that affect vital organs and/or systems. To reduce injury from such complications, doctors may prescribe short-term courses of an anti-inflammatory medicine such as prednisone. This drug belongs to a class of drugs called corticosteroids; such drugs, if used for a long period, can reduce bone density. When someone develops AIDS, this indicates that severe immunological dysfunction has occurred because they did not initiate ART early enough. Untreated HIV infection is associated with high levels of chronic inflammation and malabsorption. These issues could, in theory, contribute to bone thinning before the initiation of ART.

Young men

Several years ago, a study in the Netherlands found that some young gay and bisexual men had thinner-than-normal bones, regardless of their HIV status. The scientists involved with that study were not certain why these otherwise-healthy young men had thin bones. But this finding may be something to bear in mind when trying to find potential causes of bone thinning. It suggests that, in some men, bone thinning can occur before HIV infection or the use of ART.

Back to the Danish study on bones

The Danish study focused on data captured at one point in time. A good next step would be for the scientists to receive additional funding for long-term research on bone density in HIV-positive people. A strength of this study is that it had a control (or comparison) group of people of similar age to the HIV-positive people. Another strength is the quality and depth of information in the database. The Danish scientists encouraged healthcare professionals to help their HIV-positive patients reduce their risk factors for bone loss.

Bone thinning can be reversed

At the microscopic level, bones are dynamic. Tiny portions are constantly being torn down and rebuilt. This is needed to help repair wear and tear on bones from everyday activities and injuries. In cases of osteopenia and osteoporosis, there is an imbalance that favours the breaking down rather than the building up of bone.

Due to the dynamic nature of bones, loss of bone density can be reversed with guidance from physicians, nurses and pharmacists who can give individualized advice about which of the following steps are needed:

• prescription medicine to normalize the imbalance in bone turnover
• vitamin D₃ supplementation if laboratory testing finds that levels are too low
• adequate consumption of calcium-rich foods
• weight-bearing exercise
• treating, reducing or eliminating risk factors for thinning bones

Resources

About osteoporosis – Osteoporosis Canada

Calcium calculator – Osteoporosis Canada

Treatments for osteoporosis – Osteoporosis Canada

Exercises for healthy bones – Osteoporosis Canada

B.C. study finds that HIV-positive women are likely to have other health conditions – CATIE News

The puzzle of thin bones in young MSM – CATIE News

Large study looks at risk factors for bone problems in HIV – TreatmentUpdate 214

Zoledronic acid maintains bone density in ART users – TreatmentUpdate 214

—Sean R. Hosein

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