A mix of bad genes and poor conditions in the womb and early life may be responsible for some cases of brittle bone disease, research suggests.
Osteoporosis is a growing problem
A team from Southampton University has pinpointed a genetic mutation that increases the risk of osteoporosis.
However, the gene is more likely to result in disease if the carrier also lacks nutrients before birth, and in their early years.
Details appear in the Journal of Clinical Endocrinology and Metabolism.
The Southampton team say their work provides a graphic illustration of the fact that disease is often the result of an interaction between genes and environmental factors, rather than each acting in isolation.
They identified a gene which regulates the amount of growth hormone produced by the body, and therefore plays a key role in how well bones develop and grow.
However, they also found that the function of the gene appears to be modulated in part by environmental factors in early life.
Carrying the wrong mutation only seemed significantly to increase the risk of osteoporosis if the carrier also had to endure harsh environmental conditions - such as poor nutrition - in the womb, and during the early years of life.
The researchers analysed data on a group of 300 Hertfordshire men and women who were born during the 1920s and 30s.
Many are still living locally, giving researchers a unique insight into the health of a group of people who are also representative of the population as a whole.
Researcher Professor Cyrus Cooper said: "This has altered our understanding of the complex relationship between genes and the early environment.
"We have known for a long time that genetic and environmental influences contribute to who we are and our health prospects.
"This is the first time research has shown the extent to which these early environmental factors (such as maternal nutrition, smoking and exercise) impact on the function of genes which have a key role to play in the development of a healthy skeleton.
"Although there is a strong genetic contribution to skeletal growth, our work also suggests that the impact of an adverse genetic make-up might be minimised by improving the environment in the womb."
Prof Cooper said the next challenge was to try to pinpoint the best diet and lifestyle that mothers could follow in order to reduce the risk of their children developing brittle bones.
Julia Thomson, of the National Osteoporosis Society, said the research was "an important step forward" in understanding why so many people suffered from osteoporosis.
"This new research adds even greater weight to the argument that we all need to take a cradle to grave attitude to better bone health if we are to keep our skeletons strong into our later years," she said.
Osteoporosis affects one in three women over the age of 50.