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Bone Mass in HIV-Infected Patients: Focus on the Role of Therapy and Sex
  JAIDS Journal of Acquired Immune Deficiency Syndromes 2003; 33(3):405-407
To the Editor:
In the past decade, many studies have shown that osteoporosis can be a complication of HIV infection. The use of new drugs for the treatment of HIV infection has led not only to a higher survival rate of the patients but also to the onset of severe adverse effects such as diabetes, insulin resistance, lipodystrophy, hyperlipidemia, lactic acidosis, and bone mass loss. Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, with a consequent increase in bone fragility with susceptibility to fracture. In 1994, the World Health Organization established classification criteria based on bone mineral density (BMD) T-score; T-score indicates the number of standard deviations (SD) below the average peak bone mass (PBM) in young adults, whereas BMD Z-score indicates the number of SD below the mean BMD of an age-matched and sex-matched population. PBM is usually reached at the age of 25 to 30 years; after this period, all people begin to lose bone mass at a rate of 0.5% to 1% per year. No differences are seen in the rate of bone mass loss between males and females until the onset of menopause, when women show a fast and pronounced reduction of BMD because of the lack of estrogens.14 In the past decade, some cross-sectional studies showed a high prevalence of both osteopenia and high bone turnover rates among HIV-infected patients. The aim of this study was the evaluation of osteopenia and osteoporosis rates in a population of HIV-infected patients and the investigation of antiretroviral therapy action on bone mass. Moreover, we tried to discover whether any differences in BMD exist between males and females.
We recruited 70 consecutive subjects from an outpatient HIV clinic (34 males and 36 females) with a mean age of 41 7 years. All the females but one had regular menstrual cycles. Anthropometric characteristics of the patients were evaluated. On the basis of highly active antiretroviral therapy (HAART), we identified three different groups: group A = untreated patients or "naive" (5.7%); group B = HIV-infected patients using HAART (two nucleoside reverse transcriptase inhibitors [NRTI] plus one non-nucleoside reverse transcriptase inhibitor [NNRTI]) not receiving protease inhibitors (PIs) (44.3%); and group C = HIV-infected patients using HAART and receiving PIs (50%). Patients were also characterized on the basis of CDC 1993 Classification.15 All the patients underwent BMD measurements of the spine and the hip by means of dual X-ray absorptiometry (DXA) (Hologic 4500 QDR Elite, Bedford, Massachussets). This machine contains a database for normal men, derived from NHANES study, which can be used for the diagnosis of osteoporosis in men, according to Looker et al.16 We therefore decided to calculate osteopenia and osteoporosis rates on the basis of T-score values, according to the WHO Clinical Classification.13 The same cutoff values were arbitrarily used when osteoporosis classification was calculated on the basis of Z-Score.
Patient anthropometric and densitometric values were grouped according to the sex or to the therapeutic group. The mean and 95% confidence interval for each group and variable were calculated. Parametric data of the two groups were compared with unpaired t test. The prevalence of nonparametric data was tested for significance with [chi]2 when appropriate. Values of p [le] 0.05 were considered statistically significant.
In our whole population, osteopenia and osteoporosis rates were 40% and 8.6%, respectively, according to lumbar T-score, whereas they were 33% and 5.7%, respectively, according to lumbar Z-score. Hip T-score showed an osteopenia rate of 45.7% and an osteoporosis rate of 10%; according to hip Z-score, osteopenia and osteoporosis rates were 35.8% and 7.1%, respectively. Age, gender, and antiretroviral regimen group did not show any difference among these classes. "Naive" patients were excluded from statistical analysis because of their small number. No differences in osteopenia and osteoporosis rates were found between groups B and C, either on lumbar spine or on proximal femur. Also, gender and age distribution were similar in groups B and C. When patients were grouped according to sex, males and females did not show any differences in the prevalence of osteopenia. However, males showed significantly higher rates of osteoporosis than females both on the spine and hip, using both T-scores and Z-scores.
Finally, men had a higher body mass index (BMI), weight, and height than women (p = 0.0001), whereas age did not show any statistical difference. Many authors have observed a reduction of bone mass in HIV-infected patients, but whether it depends on therapy, on virus infection itself, or on both is still controversial. Not all the studies agreed on a negative effect of HAART on bone metabolism. In fact, Moyle et al. observed that the patients treated with NNRTI showed higher BMD than those treated with NRTI or PIs. Other authors described PIs as the "guilty" drug, whereas others could not find any difference among the various drugs used in HAART. We did not find any differences between treatment groups. In fact, group B (patients on HAART without PIs) and group C (patients on HAART plus PIs) had similar BMD. Because of their very small number, "naive" patients could not be compared with other groups, thus preventing a deeper comprehension of the specific action of HIV on bone mass. However, our patients showed a higher prevalence of osteopenia and osteoporosis than that which could be expected in age-matched and sex-matched subjects (in fact, the mean age was 41 7 years, and all the females but one had regular menstrual cycles).
Therefore, our results confirm the majority of observations in the literature, which describes a high rate of reduced bone mass among HIV-infected patients. Surprisingly, we found a higher rate of osteoporosis in males than in females, although the two groups had a similar age range and the males had a significantly higher BMI. A low BMI and aging are well-established risk factors for osteoporosis in the general population, but these important parameters could not account for the higher osteoporosis rate in our male patients, especially because females were the group with the highest theoretical risk, due to their significantly lower BMI. To our knowledge, this is the first observation of such a difference between men and women and, on the basis of our data, we cannot explain it as of yet. Some differences may exist in sex hormone concentrations, with particular regard to circulating estrogens. We may hypothesize that HIV or HAART are somehow involved in the regulation of aromatase activity and, therefore, on estrogen concentration inside the bone microenvironment, but this hypothesis needs confirmation. In conclusion, our results showed a very high prevalence of bone mass reduction in HIV-infected patients, and no differences were found among different drug regimens. Moreover, we found a higher prevalence of osteoporosis in men than in women, which needs further study to be confirmed. Finally, further investigations are also necessary to understand its etiopathogenesis.
Fabio Vescini; *Marco Borderi; Angela Buffa; Giuseppe Sinicropi; *Livia Tampellini; *Francesco Chiodo; Renata Caudarella Department of Internal Medicine and Applied Biotechnology
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