All of these factors work toward decreasing bone formation and increasing osteoclastic activities (bone resorption) [67] Studies on HIV-transgenic rats, an animal model of HIV infection that lacks many of the confounding influences on bone that are associated with human HIV patients revealed a significant 75% decline in expression of bone marrow OPG due to defective B cell OPG production [67] This loss of OPG, coupled with a dramatic five-fold increase in receptor RANKL production by B-cells, accounted for a significant increase in osteoclast differentiation [67]. This evidence concerns the gene TNFRSF11B and HIV infectious disease.