Pre-menopausal changes in bone structure may contribute to fracture risk

It is well established that post-menopausal women are at increased risk for developing osteoporosis, but could that be related to subtle pre-menopausal changes in bone structure?

That may very well be, according to two new sets of data presented at the IOF World Congress on Osteoporosis.

The findings were made possible by the use of a new sophisticated X-ray scanner that can measure tiny, three-dimensional changes in bone architecture.

In two additional presentations, researchers from Ireland and the U.S.A. reported a direct relationship between body weight and bone mineral density. Their studies emphasize the importance of maintaining adequate nutrition and suggest that simple weight cut-offs for men and women could be used to predict osteoporosis.

Bone Geometry and Architecture Change with Age

In any complex structure, geometry and architecture are important determinants of strength. Bone is no exception. That is why studies from IOF President Pierre Delmas and colleagues at the INSERM, Claude Bernard University of Lyon, France, may lead to better understanding of bone fragility. In separate presentations, lead authors Stephanie Boutroy and Elizabeth Sornay-Rendu report that gradual remodelling may change the overall architecture of bones as pre-menopausal women age, while in post-menopausal women similar architectural changes correlate with fragility fractures.

Changes in bone geometry and micro-architecture in young women have not been well studied to date, but the new findings indicate that there may be two distinct types of bone remodelling related to aging. Studying the tibia, the larger of the two calf bones, Boutroy and colleagues found that though older pre-menopausal women have an increase in bone size, there is no change in the thickness of the cortical layer, or tough envelope, that makes up the bone circumference. They also found that spongy tissue that makes up the bone core is less dense in older pre-menopausal women compared to their younger peers. Their findings suggest that minerals are slowly lost from the inside of the bone, while at the same time there is increased deposition of mineral in the cortical or outer envelope of the bone that increases the circumference but not the thickness.

To arrive at their conclusions, the researchers tested 251 pre-menopausal women aged between 19 and 50 years old. Each were scanned with a sophisticated quantitative computerized tomography (QCT) scanner (CAT scan) to develop a three-dimensional picture of the bone. They found that in older women, the sponge-like tissue, or trabecular bone, that makes up the bone core, is less dense and individual trabeculae are sparser and more widely separated. The researchers are now planning to follow individual volunteers to determine if age-related changes in bone mineral density are indeed due to this type of bone remodelling. Because bone mineral density is generally used as a surrogate for bone strength the research could have important implications for our understanding of bone fragility and osteoporosis.

In fact, in the second presentation, Sornay-Rendu reported that micro-architectural changes can be detected in post-menopausal women who have sustained a fragility fracture.

In this study the researchers compared post-menopausal women, average age 72 years, who had a fracture over the past 13 years with women who did not have a fracture over that period of time. The researchers found that there were significant differences in terms of bone architecture measured with this new high-resolution peripheral QCT scanner.

The scanner allows researchers to get a much more detailed picture of bone density than is allowed by traditionally dual X-ray absorption (DXA) scanners, which are routinely used worldwide to diagnose osteoporosis. "One interesting finding is that when you look at the differences between the fracture cases and the controls, if you adjust by their level of bone mineral density measured by DXA, the difference between the two groups is still significant. That means that, clearly, by this new technique we are measuring something that is different to what we measure using DXA. That difference is basically the architecture of the trabecular bone," said Delmas.

Sornay-Rendu and colleagues found that in the women who suffered a fragility fracture, the number of trabeculae and the thickness of the trabecular layer was reduced, as was the thickness of the cortical bone. These changes cannot be picked up by traditional DXA scanning.

Weight Loss may Put Bones at Risk

Bone remodelling is well known to be heavily influenced by the load placed upon it. Heavier people, for example, are more likely to have heavier bones. But how does weight loss impact bone density?

Laurie Milliken and colleagues at the University of Massachusetts, Boston, reported that changes in body weight account for a substantial change in bone density recorded in post-menopausal women.

"These findings demonstrate that in this population of postmenopausal women, changes in body composition are more important than the current public health messages regarding preserving bone may reflect," said Milliken.

For four years the researchers followed 167 post-menopausal women taking part in the Bone Estrogen Strength Training study. Correcting for other factors such as level of exercise, use of hormone replacement therapy and taking supplemental calcium, Milliken and colleagues found that 6%-32% of the change in bone mineral density (BMD) could be accounted for by change in body mass, with weight loss leading to lower BMD.

"These findings confirm the 'bone loading' role of body weight. However, it may add confusion for those who are trying to reduce the likelihood of developing osteoporosis, especially those who are also trying to prevent heart disease and Type II diabetes. The public health messages for heart disease and diabetes are to lose weight but that advice may be counterproductive for bone," said Milliken.

That sentiment was echoed by Dr. Bryan Whelan and colleagues at Cork University Hospital, Ireland. In a study of over 22,000 subjects, they found that there was a direct correlation between weight and bone mineral density at the hip, spine, and thigh bone.

"Our main finding was that setting a weight cut-off in postmenopausal women and men over 50 is a simple way of determining if they are likely to have osteoporosis or not," said Whelan.

Those cut-offs are 72kg for women 81 kg for men. The research suggests that people should be mindful of not dieting to a level where their weight falls below these limits. "In this age, when there is such an emphasis on being thin and losing weight, it must be said that a good balance--not too thin, not too heavy--is still best because there are drawbacks to being too light, said Whelan.

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