Bone turnover elevated in HIV-positive patients and linked to duration of HAART
Simon Collins, HIV i-Base
Mondy and colleagues from the University of Washington reported results from a longitudinal study looking at prevalence of osteopenia or osteoporosis in HIV-infected persons and assessed bone mineralisation, metabolism, and histomorphometry over time.
128 patients were enrolled in an original cross-sectional study, 93 of whom were then followed for 72 weeks in a longitudinal study. Baseline data included sociodemographic and clinical data, dietary intake history (including vitamin D, calcium, caffeine, alcohol, and average energy intake) together with history of antiretroviral and other medication that may potentially alter bone metabolism. BMI, DEXA and serum and 24-h urine bone markers were taken every six months. Bone biopsy was performed for seven patients who consented to this procedure.
This group was largely a white male group (14% women, 16% non-white). Sixty-eight percent were using a protease-based treatment, 70% had an undetectable viral load and mean duration of treatment was over five years (76 months). Many patients had risks for low BMD such as history of significant weight loss (27%), current or past smokers (35%) low activity level (55%) and calcium intake below RDA (70%).
Almost half (46%) of the patients in the original cross-sectional study had either osteopenia or osteoporosis, confirming findings of previous reports that this is a widespread issue for HIV-positive patients. Osteopenia was more common in people with a history of smoking (44% vs 28%, p=0.06) or previous steroid use for longer than one month (10% vs 2.9%, p=0.08) or previous weight loss (37% vs 19%, p=0.04). Strong associations were found with low current weight, BMI, whole body fat mass, trunk fat mass and peripheral fat mass (all p <0.01). Duration of HIV therapy was the only other factor strongly associated with osteopenia (p=0.05).
The longitudinal follow up showed a small but significant increase in lumbar and hip BMD over 72 weeks (2.6±0.6% and 2.4%±0.4% respectively, both p<0.01). These mean percentage increases remained significant regardless of duration of HAART. Increases in lumbar BMD correlated with CD4 cell increases and baseline viral suppression. The majority of subjects also had high indices of bone metabolism that remained elevated but generally stable for all patients during the 72-week follow-up period, regardless of type of antiretroviral therapy, immune status, or bone mineral density. The authors also emphasised that traditional risk factors are likely to be more important contributory factors than HAART-related factors.
That no correlation was found between BMD and indices of bone turnover was explained by the results of the seven biopsies which showed that multiple mechanisms are likely to underlie the pathogenesis of HIV-related osteopenia.
Although no link to individual drugs or drug classes was found in this study, it was limited by the length of time people had been on treatment at baseline, and the many treatment changes made by patients prior to and during the study.
The authors conclude that higher markers for bone turnover in patients on HAART therapy is a serious concern and that prospective longitudinal studies from patients in early HIV disease and prior to commencing therapy are still required.
Mondy K, Yarasheski K, Tebas P et al. Longitudinal Evolution of Bone Mineral Density and Bone Markers in HIV–Infected Individuals. Clin Inf Dis 2003:36:482-90 (15 Feb03)
Pablo Tebas, one of the authors of this study, presented results at the Retrovirus conference from successful use of alendronate, vitamin D and calcium in HIV-patients with osteopenia and osteoporosis (Oral Abstract 134) – again to be covered in full in the next issue of HTB.
He also commented that although monitoring of BMD is not addressed in current guidelines for management of HIV, guidelines for rheumatic disease recommend routine monitoring for any patient group where incidence of osteopenia and osteoperosis rises to levels as high as 40-60% – the incidence currently reported in the HIV-positive population.