HOMOCYSTEINE AND FRACTURE RISK

Susan Dwan, who is 48, is at risk for osteoporosis. She has osteopenia, the precursor to full blown bone loss. The condition of reduced bone mass, known as osteoporosis, is very common. About 10 million Americans have it, and another 18 million, like Susan, are at risk. The problem is responsible for more than 1.5 fractures in the US each year. Osteoporosis can be a deadly disease if someone falls, for example, suffers a fracture, and dies of blood clot complications. Thus it is crucial to tackle osteoporosis at an early stage.

Important factors that increase osteoporosis risk include low calcium and vitamin D intake, lack of exercise, smoking, or a history of smoking, being thin, and a family history of osteoporosis. The problem and its complicating fractures become a big issue after the menopause.
Now, two new studies in the latest New England Journal of Medicine identify another, and what appears to be, a major factor for osteoporosis risk: a high homocysteine level.
Homocysteine is a byproduct of amino acid metabolism. Amino acids are the building blocks for normal proteins. A high homocysteine level has already been identified as a major risk for heart attacks, stroke, and even Alzheimer’s disease. Researchers believe that when body cells dump too much homocysteine into the blood, artery linings become irritated, encouraging the formation of plaque—fatty deposits that cling to artery walls.
Because of the identified association between osteoporosis, and severe, inherited forms of high homocysteine levels, researchers in the Netherlands and in the US looked at the effect of moderately elevated homocysteine levels, present in about five to seven percent of the population. Both studies, looking at more than 2000 patients each, showed essentially the same thing: in people 55 and older, those with the highest levels of homocysteine had twice the risk of non-spinal fractures i.e. fractures of the hip and wrist.

The risk of hip fracture was increased by nearly a factor of four in men and a factor of two in women for those with the highest blood homocysteine levels. These osteoporosis risk factors were found to be independent of all the other factors that can cause osteoporosis. The risk of fracture because of an elevated homocysteine level is on par with that caused by low bone density itself.
The mechanism underlying the association between the homocysteine level and the risk of fracture may involve interference by homocysteine in cross-linking in the bone of the connective tissue called collagen. This then presumably results in fragile bone.
Experts believe if the homocysteine concentration truly is a reason for the risk of fracture, the public health implications could be substantial. The 1996 mandate of the Food and Drug Administration to fortify enriched grain products with folic acid has helped to markedly reduce the prevalence of low folate concentrations (<7 nmol per liter) in persons who are not taking vitamin supplements. It also cut in half the prevalence of homocysteine concentrations higher than 13 ¼mol per liter. It remains to be seen whether this intervention will affect future rates of hip fracture in the United States.
Authors in the New England Journal say, “Whereas randomized, controlled trials have shown that folic acid–based vitamin supplements can effectively reduce homocysteine levels and reduce the rate of coronary artery blockage after being opened, additional studies are needed to assess whether the use of such therapy will reduce the risk of fracture.” Until then people need to take some precautions to guard against osteoporosis risk.