Bones, genes and fractures

Osteoporosis is a complex disease characterized by a reduction in bone mass with associated bone microarchitectural deterioration and a high risk of fractures. Although environmental factors like nutrition and mechanical load, as well as lifestyle, may influence the development of the disease, family and twin pair studies have suggested that there is also a strong genetic component in a predisposition to osteoporosis. Two separate approaches have guided the research of scientists interested in understanding the genetics of osteoporosis. On one side, basic molecular biologists are unravelling the regulatory cascades that control osteoblast and osteoclast differentiation and thereby bone mass. On the other, geneticists, epidemiologists and clinical researchers are looking for genetic mutations and factors that can predispose individuals to the development of the disease. The objective of this EMBO workshop on the genetics of osteoporosis (http:// ermes.cba.unige.it/genospora/EMBO.htm) was to bring together clinicians and basic scientists and to stimulate mutual discussion and the transfer of ideas. The regulation of bone mass depends on the balance between the amount of bone formed by osteoblasts and the amount of bone resorbed by osteoclasts. Insight into the genetic factors predisposing to the disease depends on understanding the mechanisms that control the differentiation and the function of these cells. This knowledge is emerging from three major areas. First, many functional data on the transcriptional regulatory cascades that control differentiation of bone cells are accumulating. Some of the major highlights and new discoveries presented at this meeting were indeed reports of new bonespecific trans and cis regulatory elements. Secondly, the signalling pathways involved in osteoclast and osteoblast differentiation, including those that mediate estrogen receptor (ER) functions are gradually being elucidated, opening new therapeutic perspectives. Finally, the interface between the clinic and basic biology could come in the area of bone growth. It was shown that bone size is a major determinant of bone strength, and therefore genes involved in the control of bone growth and apposition could have a role in the development of osteoporosis and their study could ultimately lead to the development of new therapies.