HIV-infected women demonstrate reduced bone mineral density and may benefit from bone density testing, researchers from Massachusetts General Hospital reported in the February 20th 2004 issue of AIDS.
Although there have been several studies of bone density in HIV-infected men (some showing low bone mass in men receiving HAART), bone density problems in HIV-positive women have been little studied. However, it is known that women in the general population are more likely than men to develop osteopenia (reduced bone mineral density) and osteoporosis (more severe bone loss), especially after menopause.
The Massachusetts General Hospital study included 84 HIV-infected women and 63 HIV-negative controls recruited between March 2000 and April 2003. Baseline characteristics were similar in the two groups. The average age was 41. In both groups, about one-third of the women were Caucasian and 14% were Hispanic, but there were more African-Americans in the HIV-positive group (36% vs 27%). The average body mass index (BMI) was 26-27 kg/m2 (range 20-35), but the HIV-infected women had significantly less body fat and had a history of lower weight as adults. The HIV-positive women had been infected for a mean duration of about eight years, and most (93%) had used antiretroviral therapy; at the time of the study, 80% were taking nucleoside reverse transcriptase inhibitors (NRTIs), 42% were on protease inhibitors (PIs), and 27% were on non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Women who had recently used hormone replacement therapy, growth hormone, steroids, hormonal contraceptives, megestrol acetate (Megace), and certain drugs known to affect bone density were excluded, as were those who had been pregnant in the past year. Subjects were classified as having either normal menstruation or oligomenorrhoea (less than three menstrual periods in the prior three months); 29% of the HIV-positive women and 19% of the controls were oligomenorrheic (a non-significant difference). Based on hormone level tests, 18% of the HIV-positive women and 13% of the controls were post-menopausal. More HIV-positive women than controls (44% vs 26%) smoked tobacco, a known risk factor for osteopenia.
Bone density was measured using dual-energy X-ray absorptiometry (DEXA) scans of the lumbar spine, neck of the femur (thigh bone), total hip, and total body. Measurements were expressed in terms of T-scores, which describe how an individual’s bone density compares to the average peak bone mass in a sex-matched population of healthy young adults. According to World Health Organization criteria, osteopenia is defined as a T-score between -1.0 and -2.5, and osteoporosis is defined as a T-score below -2.5. Blood and urine samples were assessed for levels of several endocrine and bone metabolism markers including estradiol, follicle-stimulating hormone, osteocalcin, osteoprotegerin, vitamin D, calcium, and N-telopeptides of type 1 collagen (a marker of bone resorption).
Results
HIV-infected women had lower bone density in the lumbar spine (1.02 vs 1.07 g/cm2, or T-scores of -0.62 vs -0.13; p=0.03), femoral neck (0.82 vs 0.87 g/cm2, or T-scores of -0.56 vs -0.12; p=0.01), and total hip (0.93 vs 0.99 g/cm2, or T-score of -0.33 vs 0.15; p=0.004) compared with HIV-negative women. The rate of spine or hip osteopenia was 54% among the HIV-positive women versus 30% among the controls; the respective rates of frank osteoporosis were 10% and 5%. Using a model that accounted for age, race, BMI, and menstrual status, the researchers determined that HIV-infected women were 2.5 times more likely to have low bone mineral density.
Among the HIV-positive women, current BMI, history of low weight, and lower body fat percentage were significantly associated with bone loss. Bone density was lower in women with oligomenorrhea, suggesting that abnormal menstrual function may contribute to bone loss in some women with HIV. As expected, bone mass was reduced in women whose hormone levels indicated menopause. But the researchers noted that based on levels of bone metabolism markers, the pattern of bone loss observed in the HIV-infected women differed from that seen in HIV-negative post-menopausal women with low oestrogen levels, suggesting an “uncoupling” of bone formation and resorption.
In this study, bone density did not differ based on current or past use of any class of antiretroviral therapy.
The authors concluded that, “Altered nutritional status, hormonal function and body composition may contribute to lower bone density in HIV-infected women.” This reduced bone mass may lead to higher rates of frank osteoporosis and fractures as these women age. The researchers suggested that, “Consideration should be given to testing bone density in HIV-infected women with risk factors for osteopenia,” including post-menopausal women and those with a history of wasting and fat loss. For those with bone loss, bisphosphonate drugs such as alendronate (Fosamax) may be of use, but further study of their safety and efficacy in HIV-positive women is needed.
Reference
Dolan S et al. Reduced bone density in HIV-infected women. AIDS 18(3): 475-483. 2004