Osteoporotic hip and wrist fractures--a common feature on the landscape of older Americans--may be partially rooted in a gene on chromosome 19, according to a study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Scientists led by Jane A. Cauley, Dr.P.H., at the University of Pittsburgh have found that older women with the gene for apolipoprotein E (APOE*4) are at increased risk for hip and wrist fractures. Previous studies of this gene have also shown its association with common, late-onset forms of Alzheimer's disease and with osteoporosis in patients on dialysis.

The study (J Bone Min Res. 1999;14(7):1175-1181), co-funded by the National Institute on Aging and the National Heart, Lung and Blood Institute, showed that the risk of hip and wrist fracture for women age 65 and over with the APOE*4 gene was nearly twice that of those without the gene, even after making adjustments for bone density, cognitive level, or tendency to fall. Women with at least one APOE*4 gene were more likely to have a maternal history of fracture after age 50.

"We have long suspected that these types of fractures are due to more than a single factor," says NIAMS Director Stephen I. Katz, M.D., Ph.D. "Here we have evidence of a specific genetic influence at work even when weak bones and balance problems are not at issue."

Osteoporosis, a major disease that weakens bones and causes fractures, is known to have a genetic component, but genes associated with fractures themselves had not been found before. The APOE*4 gene, say the scientists, might involve the following factors in increasing risk for hip and wrist fractures:

• Vitamin K. People with the gene may have reduced levels of this substance, which stimulates bone formation and reduces bone-cell loss.
• Alzheimer's disease. People with this disease have a higher risk of hip fracture, and the APOE*4 gene has now been found to have connections to both.
• Weight loss. Women with the gene experience greater weight loss than those who don't have it. Weight loss contributes to bone loss, which could affect fracture risk.

Osteoporosis, a major threat for 28 million Americans, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures--especially of the hip, spine, and wrist. It is the most prevalent of the bone diseases that affect Americans.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases.

Cauley JA, Zmuda JM, Yaffe K, Kuller LH, Ferrell RE,Wisniewski SR, Cummings SR. Apolipoprotein E polymorphism: a new genetic marker of hip fracture risk--the study of osteoporotic fractures. Journal of Bone and Mineral Research 1999;14(7):1175-1181.