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Firstline HAART Causes Bone Loss
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This was the initial publication in AIDS reporting bone loss immediately after starting HAART which was the basis for the poster at CROI by Paddy Mallon where he reported the changes in bone cytokines/metabolism occurring in these very same patients., the loss remains but stabilizes in one measure but continued down out to 24 months in another measure.
First line AZT/3TC/lopinavir/ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir - (07/02/09) pdf attached
AIDS:
17 July 2009
van Vonderen, Marit GAa,*; Lips, Paula; van Agtmael, Michiel Aa; Hassink, Elly AMb; Brinkman, Keesc; Geerlings, Suzanne Ed; Sutinen, Jussie; Ristola, Mattie; Danner, Sven Aa; Reiss, Peterd
Metabolic bone disease in HIV infection: HIV, ART Implicated EDITORIAL - (07/02/09)
"we demonstrated a rapid BMD decrease in both femoral neck and lumbar spine after initiation of cART, in parallel to an increase in bone turnover. The loss of BMD was significantly greater in the ZDV/3TC/LPV/r group compared to the NVP/LPV/r group, suggesting that ZDV/3TC contributes to this process, the mechanism of which remains to be elucidated.....lactic acidemia due to NRTI-related mitochondrial dysfunction has also been suggested to play a role in reduced (total body) BMD in HIV-infected patients."
"BMD decreased rapidly in both femoral neck and lumbar spine after cART initiation. BMD loss during 24 months measured by DXA, but not by QCT, was greater in the ZDV/3TC/LPV/r group compared to the NVP/LPV/r group [femoral neck: -6.3% ± 1.0% (P < 0.0001) compared to -2.3% ± 0.9% (P = 0.01), between-group P = 0.0006); lumbar spine: -5.1% ± 0.8% (P < 0.0001) compared to -2.6% ± 0.7% (P = 0.0006), between-group P = 0.07]."
"Our finding that patients treated with ZDV/3TC/LPV/r had significantly greater bone loss compared to those using NVP/LPV/r suggests that ZDV/3TC contributes to bone loss in patients initiating cART. This result is somewhat consistent with another study in which patients using ZDV-containing regimens or stavudine-containing regimens had a small but significant total body BMD decrease during 104 weeks follow-up, whereas those switching to abacavir had stable BMD [21]. Both zidovudine and lamivudine have been shown to enhance osteoclastogenesis [17], potentially leading to bone loss. Lactic acidemia due to NRTI-related mitochondrial dysfunction has also been suggested to play a role in reduced (total body) BMD in HIV-infected patients [22]'
"this is the first prospective study comparing a ZDV/3TC-containing with a ZDV/3TC-sparing regimen investigating changes in BMD and bone turnover after treatment initiation in cART-naive HIV-infected patients. Our findings confirm the high prevalence of osteopenia [1], already present prior to start of cART. We observed a rapid BMD decrease in both femoral neck and lumbar spine after initiation of cART. The BMD loss measured by DXA was significantly greater in patients randomized to ZDV/3TC/LPV/r compared to those using NVP/LPV/r. In both groups, lumbar spine bone loss appeared to stabilize in the second year of treatment, whereas in the femoral neck progressive bone loss was observed in the second year in the ZDV/3TC/LPV/r group only. Furthermore, markers of bone formation (osteocalcin), and bone resorption (urine DPD/creatinine ratio) increased significantly after cART initiation in all patients, indicating an increase in bone turnover."
"Three patients, two in the ZDV/3TC/LPV/r group and one in the NVP/ LPV/r group, developed lumbar spine osteoporosis over 24 months; two patients with osteoporosis at baseline dropped out of the study."
'A greater decrease in lumbar spine BMD by DEXA was significantly correlated with a decrease in serum 25-hydroxy-vitamin D (correlation coefficient 0.43, P =0.009), and a greater decrease in lumbar spine BMD by QCT was significantly correlated with an increase in parathyroid hormone (correlation coefficients 0.42 (P = 0.017) and 0.42 (P = 0.018) for levels L2 and L3, respectively).'
"In addition to direct effects of HIV proteins on osteoblasts and osteoclasts, chronic inflammation may play a role, and various cytokines are known to increase osteoclast activity [31,32] and inhibit bone formation [33,34]. Suppression of HIV and the accompanying chronic inflammatory response may reverse or ameliorate some of these processes."
"the 0.5 SD BMD loss in the lumbar spine in the ZDV/3TC/LPV/r group can be calculated to correspond to an approximately 50-60% greater relative fracture risk, whereas in the NVP/LPV/r arm this risk would be around 30% greater. As the absolute fracture risk is low in this age category, a clinically significant difference may only become apparent after longer follow-up with older age. Previous studies have shown that the relative risk of fracture for a BMD decrease of one standard deviation below age-adjusted mean (Z-score) is approximately 2-2.5 [36,37]. Although these studies were performed in a different population, these results suggest that the observed BMD changes in our study may eventually increase the risk of osteoporotic fractures."
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