Thursday, August 16, 2012

Odanacatib

It appears there may soon be a new medication available for the treatment of osteoporosis. In the most recent issue of the Journal of Bone and Mineral Research, two articles (Masarachia, P.J., et al. 2012 and Cusick T., et al. 2012) from researchers at Merck Research Laboratories report on the new antiresorptive compound odanacatib. The studies confirmed that this inhibitor of cathepsin K (an enzyme released by osteoclasts that breaks down bone) not only inhibits bone resorption but increases bone mass. What is truly interesting about these reports is that odanacatib increased bone mass in the outer cortex of bone because, unlike bisphosphonates, it does not harm the bone resorbing osteoclasts.

By simply inhibiting production of the bone resorbing enzyme cathepsin K by osteoclasts (instead of destroying these cells like the bisphosphonates), odanacatib may indeed be a step in the right direction for a safer and more effective medication for osteoporosis. The jury is, of course, still out but odanacatib does show promise. Unfortunately, it wasn't until many years after bisphosphonates came to market that the severity of their adverse effects were realized. Now with osteonecrosis of the jaw, atrial fibrilation, and increased brittleness of bones from long-term use of bisphosphonates becoming Merck's nightmare, who is to say what odanacatib might bring? But for the time being, I'm being positive and hopeful that this new medication will be of benefit to severely osteoporotic individuals.

The major simulators of cathepsin K release by the osteoclasts are proinflammatory cytokines. When the body is in a chronically inflamed state (a major contributor to osteoporosis), these cytokines cause all sorts of symptoms. (I explain this whole cytokine connection to disease and dysfunction in my book.) The great thing about antioxidants such as lipoic acid, N-acetyl cysteine, milk thistle, etc. that are found in OsteoNaturals' OsteoStim is that these help neutralize proinflammatory cytokine production all through-out the body, not just in the bone marrow. This is a much more sensible approach for reducing excessive cathepsin K production, and for improving bone health in the long run.

Odanacatib is currently in pre-marketing or phase 3 trials. Time will only tell if it is successful in improving the lives of osteoporosis sufferers or, over time, only lead to more problems.

Masarachia P.J., et al. 2012. Odanacatib reduces bone turnover and increases bone mass in the lumbar spine of skeletally mature ovariectomized rhesus monkeys. Journal of Bone and Mineral Research 27(3):509-523.

Cusick T., et al. 2012. Odanacatib treatment increases hip bone mass and cortical thickness by preserving endocortical bone formation and stimulating periosteal bone formation in the ovariectomized adult rhesus monkey. Journal of Bone and Mineral Research 27(3):524-537.
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