HIV-positive pubescent boys have significantly lower bone mineral content and density than their HIV-negative peers, US investigators report in the online edition of AIDS. The researchers also found that treatment with Kaletra was associated with reduced bone mineral content and density.
“We evaluated bone mass across stages of puberty in a randomly selected group of perinatally HIV-infected compared to uninfected children/youth of similar Tanner stage and sociodemographic status”, write the investigators, “our most striking finding was that HIV-infected boys had significantly lower spinal and total bone mineral mass relative to uninfected boys”.
Several studies have found that bone mass is lower in children with HIV than HIV-negative children of the same sex and age. The reasons for this, and its association with the long-term fracture risk, are not yet fully understood.
Full bone density is achieved by the age of 30, but approximately 80% of this is attained by the age of 18.
The greatest gains in bone in the hip and spine occur in puberty: between the ages of 11 and 14 (Tanner stage 2-4) for girls and the ages of 13 to 17 (Tanner stage 4) for boys.
HIV treatment has significantly improved the prognosis of children infected with HIV at birth. In the US and similar countries, many of these children are now pubescent. Therefore to gain a better understanding of the impact of HIV infection on bone mass development, investigators from the Pediatric AIDS Clinical Trials Group P1045 team designed a cross-sectional study comparing bone mineral content and bone mineral density between HIV-positive individuals aged between 7 and 24 years olds and a group of age and sex matched HIV-negative controls.
A total of 236 HIV-positive patients and 143 HIV-negative controls were included in the analysis. All the HIV-positive individuals had been infected with the virus since birth
Height and weight were measured and stage of puberty (Tanner stage 1 - 5) was determined after a physical examination.
Information was obtained on factors known to affect bone metabolism including nutritional intake, vitamin D and calcium supplementation, exercise frequency, cigarette smoking and hours of television viewing (a marker for a sedentary lifestyle).
For the patients with HIV, data were obtained on CD4 cell, viral load, and medical history, including the use of antiretroviral therapy.
Dual-energy X-ray absorptiometry (DEXA) scans were performed on the whole body to assess whole bone mineral content, bone mineral density, and lean body mass.
There were no significant differences between the HIV-positive patients and the controls in terms of race and stage of puberty.
However, those with HIV had significantly lower age-adjusted height, weight, and body mass index (BMI) Z-scores. Dietary intake did not differ between the two groups, but the HIV-positive individuals were more likely to be taking vitamin D and calcium supplements (p < 0.001).
Almost three-quarter of the HIV-positive children had a CD4 cell count above 500 cells/mm3 and a CD4 cell percentage above 25%. Viral load was below 400 copies/ml in 56%.
All the HIV-positive children were taking nucleoside reverse transcriptase inhibitors (NRTIs), 56% had ever received a non-nucleoside reverse transcriptase inhibitor (NNRTI) and 67% had taken a protease inhibitor at some point.
For boys who were either pre-pubescent or in the very early stage of puberty (Tanner stages 1 and 2), bone density was similar between those who were HIV-positive and the HIV-negative controls.
However, by mid-puberty (Tanner stages 3 and 4), the HIV-positive boys had significantly lower bone mineral content than their HIV-negative peers. By the final stage of puberty (Tanner stage 5), total body and spinal bone mineral density were lower in boys with HIV-positive patients compared to the HIV-negative male controls (all p < 0.011).
When the investigators compared bone density in HIV-positive and HIV-negative females, they found no significant differences.
Next the investigators analysed the impact of antiretroviral drug use on bone density.
They found that individuals who took an NNRTI had significantly higher bone mineral content (p = 0.047) and higher spinal bone mineral density (p = 0.021) than patients who did not take this class of drug.
Next, the impact of individual antiretroviral drugs was examined. The investigators found that therapy with lopinavir/ritonavir (Kaletra) was associated with both significantly lower bone mineral content (p = 0.008) and total bone mineral density (p = 0.004).
By contrast, treatment with nevirapine (Viramune) was associated with significantly higher spinal bone mineral density (p = 0.039). AZT (zidovudine, Retrovir) was associated with a non-significant reduction in bone mineral content.
The investigators conclude, “longitudinal studies that examine changes within individuals will help to clarify the effect of puberty and sex on bone acquisition and inform the design and interventions to improve bone accrual and prevent skeletal losses in HIV-infected patients.”