Fragile bones linked to vitamin D gene.

Vitamin D does build strong bones, but perhaps not exactly in the way scientists had envisioned. Australian researchers have linked a single gene-one that codes for vitamin D's receptor, or cellular docking site -to the tendency of people to lose bone mass as they age and to develop osteoporosis.

Despite all the environmental factors, such as dietary calcium, exercise, and smoking, known to influence the thinning of bones (SN: 12/26/91, p.262), genetics still plays a key role in determining who will suffer fractures late in life, says John A. Eisman of the Garvan Institute of Medical Research in Sydney, Scientists had thought that many genes set the stage for osteoporosis.

After examining the results of earlier studies, however, Eisman focused on the gene that codes for the vitamin D receptor. Once activated in the body, vitamin D becomes a key hormone that alters a cell's absorption of calcium.

The Sydney group determined the distribution of the two forms, or alleles, of this gene in 250 fraternal and identical twins. The researchers also measured the density of several bones, including the spine, in each person. A twin with one or two copies of one allele had denser bones than the sibling with one or two copies of the other allele, Eisman, Nigel A. Morrison, and their colleagues report in the Jan. 20 NATURE. When the scientists evaluated 311 middle-aged women, they found they could predict bone density on the basis of the women's genetic makeup.

They suspect that the vitamin D receptor helps control how fast bone builds up and disintegrates. During the first 20 years of life, bone thickens. Decades later, it begins to thin. The twin studies suggest that one form of the receptor leads to less thickening; such bone then has less to lose before becoming fragile.

The researchers calculate that people with two copies of the allele that leads to weaker bones should develop osteoporosis by age 65; those with one copy, by age 69; and those with none, by age 76.

"What is surprising is that [the researchers] made the association with one particular gene," comments Gregory R. Mundy, an endocrinologist at the University of Texas Health Science Center in San Antonio. "I think [the finding] is going to make people sit up and take notice."

However, "it still needs to be confirmed in other groups; Mundy cautions. If the result holds up, then a simple genetic test may help identify people particularly susceptible to developing weak bones, he adds. Moreover, Eisman thinks the finding will speed the development of more effective treatments for osteoporosis.