Since high levels of lactic acid — a condition called lactic acidosis — have previously been linked to the use of nukes, these drugs may play a critical role in the loss of bone. Readers should be aware that there are likely other factors involved in the loss of bone in PHAs who were not in this study (for a list of risk factors for bone loss, see the next story).

Why do bones shrink?

It is important to note that bones are living tissue. Bone cells therefore need energy just like other cells in the body. The Australian researchers think that the energy-producing parts of bone cells — mitochondria — get damaged by the use of nukes. Damaged cells in the bone and elsewhere in the body produce high levels of lactic acid. To neutralize this acid, the body uses calcium. If it is not getting enough calcium from food, the body may take calcium from bones. Over the long term, this loss of calcium from bones could lead to osteoporosis.

Study details

Researchers analysed data collected from 221 male HIV positive subjects who were divided into the following groups:

• 32 subjects not taking anti-HIV treatment who did not have lipodystrophy (body-shape changes)
• 14 subjects who used nukes and who had lipodystrophy
• 28 subjects who used nukes and who did not have lipodystrophy
• 103 subjects who used protease inhibitors and nukes and who had lipodystrophy
• 44 subjects who used protease inhibitors and nukes and who did not have lipodystrophy

All subjects received special X-ray scans, called DEXA (dual-energy X-ray absorptiometry), of their bodies as well as various blood tests. DEXA scans are particularly useful when trying to find out the thickness of bones. High levels of lactic acid were defined as any readings greater than 2.0 mmol/Litre. The basic profile of subjects at the start of the study was as follows:

• average age – 43 years
• average CD4+ count – 485 cells
• average viral load – about 1,500 copies
• average length of HIV infection – 7½ years
• 20% of subjects had AIDS
• 52% had lipodystrophy
• 20% had high levels of lactic acid in their blood
• 14% had symptoms of lactic acidosis

Results — thinning bones

According to the results of the DEXA scans, a total of 51 subjects, or 23%, had bones that had shrunk. The subjects were grouped in the following manner:

• 44 had lost calcium and other minerals in their bones
• 7 had lost so many minerals that their bones were thin and porous

Loss of calcium and other minerals from the bone occurred in the following groups of people:

• 2 subjects who had never used anti-HIV drugs
• 11 subjects who had used nukes
• 36 subjects who had used nukes and protease inhibitors

When the researchers compared data from HIV negative, healthy Australian men, the proportion of HIV positive subjects with thinning bones was 50% higher.

Factors linked to bone loss

Subjects who lost bone mass during the study were more likely than others to have the following:

• lactic acid levels greater than 2 mmol/L
• lower muscle mass
• older age
• longer use of d4T

Factors not linked to bone loss

The researchers found that the following factors were not associated with the loss of bone in this study:

• smoking tobacco
• exercise
• the type of protease inhibitor used
• the type of non-nuke used
• levels of fatty substances — cholesterol and triglycerides — in the blood

What's next?

The findings reported by the Australian researchers are certainly important because they help narrow the focus on the possible drug-related causes of osteoporosis in HAART users. These findings need confirmation because doctors don't know if switching nukes, particularly from d4T to other nukes, will reduce the risk of developing thinning bones.

The research team also suggests that regular testing for lactic acid levels should be considered only in PHAs who use nukes who also have fractures, osteoporosis or other risk factors for bone disease.

The people who may be at high risk for osteoporosis include PHAs with the following factors:

• women who have gone through menopause
• men with lower-than-normal levels of testosterone
• little physical exercise or excessive bed rest
• low levels of calcium in the diet
• use of corticosteroids

REFERENCE

Carr A, Miller J, Eisman JA and Cooper DA. Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight pre-antiretroviral therapy. AIDS 2001;15:703-709.

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Copyright © 2001 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca.

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