Alpha Omega Alpha Honor Medical Society

2012 Research Abstract

Raltegravir, a Potent Inhibitor of Bone Formation

Investigator: Emily McIntosh, Emory University School of Medicine

Mentors: Igho Ofotokun, MD, MSc, and M. Neale Weitzmann, PhD, Emory University School of Medicine

Background: Close to 6% loss in bone mineral density (BMD) is observed early on (1-2 years) with antiretroviral therapy (ART) – a loss that has recently been proposed to stem from ART-induced disease reversal and immune reconstitution. It has recently been shown that a switch to a raltegravir (RAL) containing regimen in the later phase of therapy cauesd a decrease in bone formation. In this study, we investigated the direct actions on the skeleton of RAL in a murine model.

Methods: C57BL6 female mice were randomized to treatment with RAL or control group. BMD was measured every 4 weeks for 12 weeks at which time the mice were sacrificed for plasma CTx and OCN quantitation using ELISA.

Results: When RAL was administered to mice (n=15/group), BMD was markedly reduced by week 8 (5.3%↓ lumbar spine, p=0.040; 2.6%↓ femur, p=0.0002). These differences were consistent with a decline in bone formation (OCN 82%↓, p=0.001) and no significant change in bone resorption. Conclusions: RAL has a direct suppresssive effect on bone formation in C57Bl6 mice. This result suggest that the decrease in bone formation seen in the previously completed human study may be due to the RAL component of the switch regimen. Further corroborative studies in human are warranted.

Updated on May 16, 2013.

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