Bad Break: Homocysteine may weaken bones

In the 1960s, scientists discovered that people with a gene mutation that leads to extremely high concentrations of the amino acid homocysteine in their blood are prone to heart problems and bone deformities. Since then, physicians have found that even moderately elevated homocysteine readings increase people’s risk of heart disease.

Now, two groups of researchers poring over medical data find that elderly people with excess homocysteine fracture their bones more readily than do those with low amounts of the compound in their blood.

In one study, scientists analyzed blood samples obtained and stored from 1,999 men and women between 1979 and 1982 as part of the long-term Framingham Study. The team found that the quarter of men whose homocysteine concentrations were highest were nearly four times as likely to later break a hip as were the quarter of men with lowest blood homocysteine, says Robert R. McLean of the Hebrew Rehabilitation Center for Aged Research and Training Institute in Boston. Women with the most homocysteine were about twice as likely to break a hip as were women with the least. The study recorded bone breaks in men for an average of 12 years and in women for an average of 15 years.

In a similar study, Dutch researchers analyzed blood samples and health data from 2,406 people. Men and women with the highest homocysteine concentrations were roughly twice as likely to have broken a hip or other bone frequently fractured in elderly people as were those with lower homocysteine, says Joyce B.J. van Meurs of the Erasmus Medical Center in Rotterdam. The study checked for bone breaks for periods ranging from about 3 to 8 years.

The studies appear in the May 13 New England Journal of Medicine.

Curiously, the Dutch team found that people with the highest and lowest homocysteine readings didn’t have appreciably different bone densities, even though the high-homocysteine group had more fractures.

There’s no consensus that homocysteine concentrations in the body influence bone strength, but both groups of researchers point to the compound’s effect on collagen as a possible explanation for their findings. Collagen is the chief protein in bone, ligaments, tendons, skin, and other connective tissues. Test-tube studies have indicated that homocysteine interferes with the cross-linking between collagen fibers that reinforce those tissues.

The collagen fibers in skin samples of people with a genetic defect that causes extreme homocysteine overload aren’t tightly linked, van Meurs notes.

“Cross-linking is important for the strength of the collagen network,” van Meurs says. “If it’s disturbed, you will have less stability” and possibly more fractures.

Vitamin supplements could counter homocysteine’s effect on collagen, since both folate and vitamin B12 lower homocysteine concentrations in the blood, says Sally P. Stabler of the University of Colorado Health Sciences Center in Denver. U.S. food processors began fortifying flour with folate in the late 1990s, but there is no similar vitamin B12 program. Since elderly people often absorb vitamin B12 inefficiently from foods, the new study adds another reason for them to take multivitamin supplements containing B12, says Stabler.

Irwin H. Rosenberg of Tufts University in Boston agrees, particularly because vitamins represent a “relatively inexpensive intervention.” If people need further incentive to take multivitamins, he says, they should note that high homocysteine concentrations also have been correlated with Alzheimer’s disease (SN: 3/2/02, p. 141: Available to subscribers at High homocysteine tied to Alzheimer’s).