Clinicians who treat AIDS patients may be able to use the HIV protease inhibitor ritonavir to reduce bone loss, University scientists recently reported in The Journal of Clinical Investigation.
Bone researchers studied the effects of three HAART drugs on osteoclasts — cells that dismantle bones, and osteoblasts — cells that build bone. In healthy people, the skeleton is regularly renewed about once every decade mainly via the work of these two cell types.
In test-tube experiments, researchers found that one drug, indinavir, inhibited the activity of osteoblasts.
Another drug, ritonavir, blocked the formation of bone-dismantling osteoclasts.
Scientists also found evidence that ritonavir can suppress the activity of osteoclasts created prior to the introduction of the drug. A third drug had no effect on either cell type.
“Confirming these effects in humans may mean we have a drug that is effective not only in preventing HIV replication but also in arresting the development of osteoporosis,” said senior investigator F. Patrick Ross, Ph.D., research professor of pathology and immunology.
Clinicians first noted problematic weakening of bone in young male HIV patients several years ago. HIV’s effects on the body are thought to contribute to the problem, but scientists suspect some of the drugs in the HAART cocktail may be exacerbating bone loss.
In the new study, Ross’s postdoctoral fellow, Michael W.-H. Wang, M.D., and his colleagues reveal evidence that ritonavir is blocking a signaling pathway that fuses together simpler cells to make the more complex osteoclasts.
Scientists confirmed the effect in mice injected with parathyroid hormone, which stimulates osteoclast activity. Mice who received only the hormone had higher numbers of osteoclasts, but mice given both the hormone and ritonavir had unchanged osteoclast levels.
In additional test-tube studies, scientists found that suppression of the creation of new osteoclasts was reversible, with osteoclasts starting to develop again two to four days after scientists stopped adding the drug.