Making Bone: Novel form of vitamin D builds up rat skeleton

Calcium is indispensable for bone growth, and vitamin D is needed to maintain proper amounts of calcium in the body. But as people age, they lose bone mass, often despite taking supplements of calcium and vitamin D.

Now, lab tests show that a newly synthesized form of vitamin D, called 2MD, induces bone-making cells to capture calcium and fortify bone mass. When given to rats, 2MD significantly increases the animals’ bone density, researchers report in the Oct. 15 Proceedings of the National Academy of Sciences.

The findings appear so promising that study coauthor Hector F. DeLuca, a biochemist at the University of Wisconsin–Madison, is planning to seek regulatory approval to test 2MD in people by the end of the year. The drug’s full name is

2-methylene-19-nor-(205)-1a,25(OH)2D3.

DeLuca and his colleagues synthesized 2MD by tinkering with a part of the vitamin D molecule that binds to a molecular receptor on the surface of cells. When normal vitamin D locks onto this receptor, it acts like a hormone and orchestrates the release of other chemicals that balance blood concentrations of calcium and phosphates.

The researchers found that 2MD also binds to the vitamin D receptor–but with vastly different results. In lab-dish experiments with cells called osteoblasts, 2MD boosted the mineralization that’s normally part of bone manufacture to at least five times that of osteoblasts exposed to vitamin D, and to about 20 times that of osteoblasts not exposed to any form of the vitamin.

Next, DeLuca and his team gave 2MD to mature female rats whose ovaries had been removed. This animal model approximates human menopause, in which women stop producing the bone-preserving hormone estrogen. The treated rats’ overall bone density over 23 weeks grew by 9 percent, while similar rats not getting 2MD saw no improvement. In the 2MD-treated rats, vertebral bone density rose 25 percent, far more than the average.

The drug is given orally, and the studies have found no toxicity.

It appears that 2MD “is an extremely potent molecule,” says biochemist Glenville Jones of Queen’s University in Kingston, Ontario. He notes that the Japanese company Chugai Pharmaceuticals in Tokyo has developed a drug called ED-71–another vitamin D analog–that also shows promise in spurring osteoblasts to form bone.

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