Denosumab

Current choices in therapy for osteoporosis are something short of satisfactory. Estrogen works well but many women are reluctant or unwilling to take it for long due to its association with increased risk for breast cancer when used over a period of years. The bisphosphonates-- Boniva, Actonel, Reclast, and Fosamax-- are a good, non-hormonal choice if you don't mind taking a pill on an empty stomach 1/2 hr. before eating in the a.m. then sitting bolt upright 'til breakfast so the drug won't cause acid reflux and heartburn. Evista works but may give you blood clots or hot flashes, and Forteo is a dandy boost for way low bone density if you're o.k. with a daily shot.

Thank heavens, a new choice is moving through phase 3 studies on its way to the old gal market (guys can get osteoporosis too, but their major problem now is that no one thinks to check them for it). This medication, denosumab, is a selective inhibitor of receptor activator of nuclear factor-B ligand (RANKL). No surprise that a ligand know as RANKL is the cause of our skeletal woes joining the ranks of other things that rankle in our golden years--thinning hair, receding gums, falling arches, and teen-aged boys.

Here's the scoop. RANKL is a protein made by osteoblasts or those cells in charge of making new bone cells. RANKL hooks up with RANK to activate the RANKL-RANK pathway which then activates osteoclasts or the cells that break down bone. This whole bone thing is a regular Ecclesiastesian cycle, all this building up and breaking down at the right time and right place. When your season turns to menopause, however, the balance shifts, and suddenly you're breaking down via osteoclasts more than you're building up via osteoblasts.

Enter denosumab, a human monoclonal antibody that grabs the RANKL before it can grab the RANK. In doing so, the drug acts like osteoprotegerin(OPG) which was the normal RANKL inhibitor back in the day when you didn't need to worry about the state of your bone density. Apparently, both estrogen and Evista increase levels of OPG whereas denosumab has a biological activity equivalent to it.

So what do you have to do to be on denosumab? Get up early, stand up straight, endure hot flashes, worry about your breasts? No, none of that. Denosumab is administered as a shot twice a year, a shot under the skin no less, not like one of those stingy tetanus jabs into your deltoid muscle. Here's what lead investigator Steven Cummings, MD had to say about that: "it's a whole lot easier . . . to give what is essentially [like a] flu shot."