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CATIE News - Heroin exposure linked to thinning bones

2010 Sept 1 - In high-income countries the widespread availability of anti-HIV therapy (commonly called ART or HAART) has led to tremendous improvement in the survival of HIV-positive people. Indeed, among HIV-positive people who are engaged in their care and treatment and who have minimal co-existing health issues researchers expect that survival will approach near-normal ranges.

However, over time the consequences of long-term HIV infection will intersect with those of an aging body. Already there are reports of some aging-related complications, such as cardiovascular disease, diabetes and kidney dysfunction, occurring earlier than normal in some HIV-positive people.

Another complication of aging is loss of bone mineral density (BMD). Thinner bones become weaker and can break when falls or accidents occur.

Substance use

A major risk factor for HIV infection is sharing of equipment for substance use. Researchers in the U.S. have found that a "relatively high proportion of middle-aged substance users with or at risk for HIV infection continue to use illicit drugs into their sixties." If this trend becomes widespread, more HIV-positive people will have to deal with ill health due to complications of aging and substance use.

Opioids

Analogues of opium are approved for the treatment of severe pain in many countries. However, many opioids, such as the following, have the potential for abuse:

  • morphine
  • codeine
  • heroin
  • oxycodone
  • tramadol

In general, people who are HIV positive and who also use opioids have many factors that increase their risk for thinning bones, including the following:

  • less-than-normal levels of testosterone
  • tobacco use
  • alcohol use
  • lack of exercise
  • below normal body weight
  • poor nutrition

Researchers in the Bronx, New York, undertook a multiyear study to assess changes in bone mineral density among men with or at risk for HIV infection. A large proportion of these men used opioids, especially heroin, and substances such as cocaine. The researchers found that exposure to opioids resulted in significant loss of BMD, particularly among HIV-positive men. Other findings appear later in this bulletin.

Study details

Researchers enrolled 230 HIV-positive men and for comparison 159 HIV-negative men. The average profile of these men at the start of the study was as follows:

  • age - 56 years
  • currently using methadone - 16%
  • use of heroin in the past five years - 24%
  • history of using cocaine or opioids - 85%
  • history of injection drug use - 57%
  • current or past use of cigarettes - 89%
  • diagnosed with alcoholism by researchers - 48%
  • positive for hepatitis C virus - 66%
  • diagnosed with depression by researchers - 42%
  • less-than-normal levels of testosterone - 46%
  • prior use of corticosteroids - 5%
  • CD4+ cell count - 400 cells
  • history of AIDS - 42%

In summary, this group of participants had many risk factors for developing thinning bones.

Participants received low-dose X-ray scans called DEXA at the start of the study and about three years later. They were regularly interviewed and had blood drawn for analysis.

Results-Changes in bone density

At the start of the study, DEXA scans revealed that HIV-positive men had significantly reduced bone mineral density at the hip and spine compared to HIV-negative men. When the second set of DEXA scans were taken nearly three years later, on average the bones of HIV-positive men had become thinner than in their initial scan and were also thinner than HIV-negative men. Overall, HIV-positive men were about three times more likely to have thinner bones than HIV-negative men.

Results-Factors linked to thinning bones

The researchers conducted a complex analysis to try to uncover which factors were linked to the men's loss of BMD. In their calculations they took into account such factors as age, race/ethnicity, use of corticosteroids, methadone use and so on. They made these critical findings:

  • The greatest degree of bone loss was seen in men who used heroin in the five years prior to entering the study and who had a diagnosis of AIDS.
  • Being infected with HCV infection, regardless of HIV status, was also associated with thinning bones.
  • Exposure to methadone approached but did not achieve statistical significance for a connection to bone loss.
  • Bone loss among HIV-positive men in the study was not linked to CD4+ cell count, duration of ART or use of any specific classes of anti-HIV drugs.
  • Although cigarette smoking is a well-established factor for thinning bones, it was not linked to decreased bone density in this study, perhaps because about 90% of participants were smokers.

Putting it all together

In this study of middle-aged men, use of heroin in the past five years and an AIDS diagnosis were strongly linked to what the research team called "a substantial decline in BMD." This decrease occurred at the hip and spine. To a lesser extent, being HCV positive or using methadone was also linked to decreased BMD.

Among healthy HIV-negative people, the risk of developing fractured bones at some point in their life is about 30%. Among HIV-positive people, emerging data suggests that this risk may be greater.

Why opioids?

Heroin, morphine, codeine, oxycodone, methadone, tramadol and related drugs have the potential to reduce BMD, perhaps by the following means:

  • They may directly interfere with the formation of bones. Since bones are hard and stiff, most people tend to think of them as static or fixed. In reality, at the cellular level, some bone cells are constantly being torn down and rebuilt. Opioids may interfere with this process, at least according to some laboratory experiments.
  • Prior studies suggest that heroin users, despite having high levels of calcium in their blood, tend to lose greater-than-normal levels of calcium in their urine.
  • Heroin, morphine and so on may reduce levels of testosterone, estrogen and other hormones that help preserve bone density.

The importance of methadone

Methadone is an important part of programs that help people break free from addiction to heroin, morphine and other opioids. Although the present study has found a statistical trend between methadone use and thinning bones, it cannot prove that exposure to methadone caused this problem.

Methadone users should not stop taking prescribed methadone because of the present study's findings. Instead, doctors caring for methadone users should consider assessments for factors linked to osteopenia and bone health, such as the following:

  • assessment of vitamin D and sex hormone levels in the blood
  • nutritional counseling to ensure sufficient calcium intake and good dietary habits
  • assessment for and counseling about ongoing addictions and support for quitting tobacco, alcohol and use of other substances if present
  • assessment of liver health and HCV infection
  • discussion and prioritizing HCV treatment if this infection is present
  • use of medicines to improve bone density

A possible alternative to methadone is buprenorphine. However, coverage of this drug is not available in all jurisdictions and it may not be suitable for every person.

Present and future research

The present study cannot definitively prove that exposure to opioids resulted in decreased bone density. A more sophisticated study focused on neuromuscular function, changes in sex hormones and rates of bone loss will be necessary to make a clear link between exposure to these drugs, changes in BMD and the impact of falls and accidents.

In the meantime, the present study is valuable, exposing some of the underlying conditions that position drug users for future ill health. More intensive programs are needed to help discourage substance use and help users to recover if they become addicted to opioids and other substances. Not only will such programs help the communities in which users live, but they also have the potential to reduce the long-term costs to society of addiction.

-Sean R. Hosein

REFERENCE:

  1. Sharma A, Flom PL, Weedon J, et al. Prospective study of bone mineral density changes in aging men with or at risk for HIV infection. AIDS . 2010; in press.

 

CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto.

From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca

Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE


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