ANAHEIM, Calif., March 21 -- New chemicals that, if successful, could become the first osteoporosis treatment to stimulate new bone growth -- rather than merely retard bone loss -- were described here today at a national meeting of the American Chemical Society, the world's largest scientific society. Researchers from the Seattle biotechnology company ZymoGenetics Incorporated said their new compounds are showing positive results in animals and, unlike other bone-growth candidates, can be put in a pill.
In humans, bone undergoes continuous remodeling, with cells called osteoclasts "eating up"old bone as osteoblast cells replace it with new bone. Osteoporosis, which affects some 15-20 million Americans, is caused by increased bone breakdown without new bone formation. The result is a loss of bone mass and increased susceptibility to fractures, most commonly in those age 45 and older. The cost of treatments associated with osteoporosis in the U.S. has been estimated at $3.8 billion annually.
Current treatments, including estrogens, all act to decrease bone loss. They can't do anything about bone that is already gone and, therefore, are not helpful to everyone. "Our new bone forming agents may have better and more widespread utility for treatment of osteoporosis," said ZymoGenetics senior scientist Nand Baindur, Ph.D.
There are currently no drugs available to help grow bone. Researchers have tried giving patients proteins that the body naturally uses to stimulate osteoblasts, such as parathyroid hormone and bone morphogenic proteins (BMPs). But, according to Dr. Baindur, those clinical trials have been mostly unsuccessful or inconclusive. Furthermore, he explains that proteins are big molecules which can usually be given only by injection and don't hold up well in the body. Even if such treatments worked, he adds, the proteins are generally difficult to formulate and manufacture, tending to eventually make them expensive.
Instead of using the proteins themselves, Dr. Baindur's laboratory screened tens of thousands of compounds for the ability to stimulate BMPs. They have selected three -- two synthetic chemicals and one natural product -- for pre-clinical development, and early indications look promising. "This is the first report of small molecule drug-like compounds which have been shown to stimulate the formation of new bone in animals," says Dr. Baindur.
Such small molecule compounds are not only relatively inexpensive and easily made, but usually quite stable. Dr. Baindur adds that they can also be easily modified or formulated as the need arises. The new compounds should be able to be put into pill form. While no human tests have yet been conducted, Dr. Baindur says "these compounds are predicted to be useful in the clinical treatment of osteoporosis and related bone-deficit conditions, including bone fractures. As bone formation agents, they can potentially be given alone or in combination with agents which decrease bone loss."
While bone regenerating pills are probably years away from the market, there is the possibility that one of the new compounds might have a head start in clinical trials. The natural product candidate is part of a chemical class called statins, some of which are already in use for the treatment of heart disease.
Dr. Baindur will present this poster, MEDI 76, on Sunday, March 21, at 7:30 p.m., at the Convention Center A1.
A nonprofit organization with a membership of nearly 159,000 chemists and chemical engineers, the American Chemical Society publishes scientific journals and databases, convenes major research conferences, and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.