Osteoporosis is a major public health problem producing disability through the development of fractures, particularly those of the hip, spine, and distal radius. It has been estimated that over a million new fractures occur each year related to this disorder. The number of hip fractures occurring in the United States is currently approaching 250,000 a year and is increasing. The major cause of the increased frequency of fractures is low bone mass at the site where fracture occurs. Other factors such as architectural abnormalities within the bone and increased frequency of falling are also important, but low bone mass is a necessary, if not, sufficient cause. Low bone mass among the elderly is related to either low peak bone mass or accelerated loss of bone. This Program Project is directed at studying both of these determinants- peak bone mass and subsequent loss. It consists of five projects, supported by three cores. Project 1 is a continuing study of the relationship between sex steroids an bone loss. Previous studies have focused on changes around the menopause. The current proposal focuses on studies of bone loss prior to menopause and in later life when androgen concentrations may be important. In addition, a population of elderly men will be studied. A study is proposed to determine whether there is a genetic contribution to androgen and estrogen concentrations which could partially explain the genetic effect previously found for bone mass. Project 2 will continue studies of genetic determinants of bone mass with studies of the genetic contribution to bone gain and bone loss and studies to determine whether there is evidence for a single gene effect on bone mass. Project 3 is a continuation of a clinical trial on the effects of calcium supplementation in growing children using the co-twin control model. Project 4 is a new proposal for a clinical tria to test the hypothesis that calcium will slow bone loss while vitamin D supplementation will increase bone mass in a population of individuals over age 63. Project 5 is a study of the effects of muscle strength on subsequent rehabilitation from hip fracture. These 5 projects are supporte by 3 cores. Core A is a biostatistic, epidemiology and administrative core which supports all of the projects. Core B is a steroid core which makes measurements of the sex steroids for Project 1, Project 3, and Project 4. Core C is a biochemical and calcium absorption core, making measurements fo Project 1, Project 3, and Project 4, as well as testing the hypothesis that calcium malabsorption contributes to the determination of bone mass.
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