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(March 7, 2002, Gazette)

Breaking new ground in bone metabolism
Of mice and women

Dr. Christopher KovacsPhoto by HSIMSDr. Christopher Kovacs

Osteoporosis is a well-known bone disease that is usually associated with older women. As women age, the ability to gain bone mass through calcium absorption is totally lost, and after menopause, the skeleton actually starts to lose calcium and bone mass. This decrease in bone mass leaves women vulnerable to breaks and fractures. There is only limited effectiveness to current available treatments, and the skeleton can never be restored to normal levels of bone mass.

Dr. Christopher Kovacs, an endocrinologist in Memorial’s Faculty of Medicine, is conducting research that might one day affect how osteoporosis and other such conditions are treated. Endocrinology is the medical speciality that deals with diseases of the glands and hormones.

Recently Dr. Kovacs was awarded more than three-quarters of a million dollars from the Canadian Institute of Health Research for his research on the bone metabolism in genetically-altered mice during pregnancy, lactation and fetal development. Studying how bone mineralisation occurs in mice, Dr. Kovacs hopes to identify the factors that regulate the process and to ultimately determine what can be done to prevent or remedy the loss of bone mass that occurs in the common condition of osteoporosis in humans.

The current treatments are based on our understanding of how the adult skeleton is regulated. This is where Dr. Kovacs is breaking new ground.

“The treatments that we have are based largely on what we know about adult skeletons, and the hormones that regulate calcium metabolism in the adult,” he said.

His research is based on the fetal development of the skeleton. The fetal skeleton goes from zero to full mineralization in a very short time and it is clear that there are hormones and factors regulating the process that may not be active later in adult life. By studying what happens during development of the fetal skeleton, Dr. Kovacs hopes to identify the factors that affect the rate of calcium transfer and absorption, which may lead to changes in treatments of conditions such as osteoporosis.

Studying pregnant and lactating women could also provide some clues to the factors affecting calcium levels in the skeleton. The human skeleton’s ability to gain calcium is actually lost once the adult reaches mid-twenties, with one very interesting exception — pregnant and breastfeeding women. Evidence from animal studies suggests that pregnant animals actually absorb more calcium than usual during pregnancy in order to provide for the offspring. Women that are breastfeeding actually lose calcium from their skeleton as it is transferred to their babies through their breast milk, a fact that is not well-known and continues to surprise people, according to Dr. Kovacs.

“In six months of breastfeeding, the woman will temporarily lose five to 10 per cent of all the calcium in her skeleton, so her bone density will actually drop by five to 10 per cent.”

After a period of months, though, the woman’s skeleton naturally rebuilds the bone mass. The process by which this occurs is not yet understood, and learning more about this process will also help isolate the factors affecting the body’s ability to regain bone mass in the reproductive periods.

Similar processes in mice make them good subjects of inquiry. “In mice, mothers can lose a full one-third, 33-35 per cent, of their skeleton in three weeks of lactation,” Dr. Kovacs said.

His research employs mice that are genetically altered, so that normal and genetically-altered siblings serve as controls for each other. In isolating particular genes, he hopes to discover which genes are important to the process. If, for example, one set of mice lose bone mass but cannot regain, this will indicate that the gene that they are missing is an important piece of the puzzle. Studying what happens to the mice during pregnancy and lactation will give some clues as to what happens in humans. He hopes that by understanding how a fetus builds a skeleton and how lactating women regain skeletal calcium, there might be some application to treating osteoporosis in adults. Studying fetal mice is no easy task and some of the research money Dr. Kovacs has been awarded will be used to purchase a bone densitometer that will yield accurate measurements of bone density in small animals.

So, will Dr. Kovacs research unlock the door to curing osteoporosis? He is cautious about making such claims.

“My goals are more modest,” explained Dr. Kovacs. “In the history of science, advances are made by stepping on others’ shoulders. I’m hoping to lay the groundwork in the area and in the end, maybe I’ll show the things that are not important factors in the process. But the hope is that I will help identify what is important. It may be someone else who comes along and investigates it further that will have a breakthrough.”