Sci. Aging Knowl. Environ., 3 December 2003
Vol. 2003, Issue 48, p. nw164
[DOI: 10.1126/sageke.2003.48.nw164]


Dense Matter

Compact bones can still break easily

Mary Beckman

Key Words: heterozygous • homozygous • COLIA1 • Sp1

SAN DIEGO, CALIFORNIA--Irregularly placed studs can weaken a house's frame. A small change in a bone protein similarly disrupts the skeleton and dramatically reduces its strength, according to new research presented here 23 November 2003 at the Gerontological Society of America annual meeting. The results reveal that a characteristic other than density enfeebles bone.

As people age, their hips, spine, and wrists are more likely to fracture and break. Diminished bone density, a condition that occurs in osteoporosis, frequently makes bones fragile (see "The Plot Thickens on Thin Bones"). To understand how bones become weak, researchers study genes that affect bone density. The gene that encodes {alpha}-collagen--the most common bone protein--comes in two varieties: The more common form carries a G at a particular DNA position, and the other sports a T. Seventy percent of people carry two copies of the common form (G/G), whereas 25% have one of each variant (G/T). Previously, geneticist Stuart Ralston of the University of Aberdeen, U.K., showed that elderly G/T people were 1.56 times more likely to fracture a bone than were G/G seniors. To determine how the T variant weakens bones, Ralston and colleagues examined hipbone from about 25 people with an average age of 75 who had received prosthetic hips.

The researchers tested the activity of bone-building cells called osteoblasts. In a petri dish, osteoblasts from G/G individuals crafted a greater number of bonelike structures than did cells from G/T subjects, suggesting that the T version of {alpha}-collagen impairs bone construction. Surprisingly, they found that bones from G/T people were only slightly less dense than bones from G/G volunteers. Among osteoporosis patients, that density difference translates to a modest 6% to 7% increased risk of fracture. But G/T elderly fracture their bones 10 times more often than normal, the researchers found. Together, these results suggest that G/T bones are unusually fragile despite having nearly normal density.

To find additional factors that might weaken bones, Ralston and colleagues extracted collagen from the hip samples. Usually, {alpha}-collagen teams up with another form of collagen--{beta}-collagen--in a ratio of 2-to-1 within bones. In G/T hips, however, an {alpha} surplus skewed the ratio to 2.4-to-1. Further analysis revealed that {alpha}-collagen molecules grouped themselves in threesomes, an unusual arrangement known to make bones brittle. To look more closely at the bone organization, the researchers applied an imaging technique that measured its mineral content; G/G bones contained about 25% calcium, but the frailer G/T bones contained only about 20%. This difference might compromise bone strength without drastically reducing its density.

The demonstration that dense bones can still be fragile is "really surprising," says molecular biologist Marian Young of the National Institute of Dental and Craniofacial Research in Bethesda, Maryland. The requirement for the right collagen ratio suggests that the architecture of bone is as important as the density, says cell biologist Arnold Kahn of the University of California, San Francisco: "If the struts are put in the wrong place, the structure won't be as solid." With more knowledge of bone structure, researchers might gain the skills necessary to launch a new renovation show, This Old Hip.

--Mary Beckman

December 3, 2003
  1. S. A. Ralston, Genetic control and gene-environment interaction affect susceptibility to osteoporosis. 56th Annual Scientific Meeting of the Gerontological Society of America, 21-25 November 2003, San Diego, California. [Meeting Web Site]
Citation: M. Beckman, Dense Matter. Sci. Aging Knowl. Environ. 2003 (48), nw164 (2003).

Science of Aging Knowledge Environment. ISSN 1539-6150