Bone tissue is metabolically active throughout life. The annual skeletal turnover as a result of the continuous cortical and trabecular bone remodeling is about 10% of skeletal mass. Osteoporosis is the most common disorder in bone resorption. One in three women and one in five men, over the age of 50, suffer from this disorder. Twin and family studies have shown that most of the risk of developing osteoporosis is genetically determined [1]. It is likely that the genetic risk consists of several common polymorphisms of genes that have weak effects individually, but severe effects when acting together [1].

The genetic predisposition, as a pathogenetic factor with the etiologic factors including changes in the systemic and local hormone levels and environment, create the morbidity risk [2]. The benefits of defining the genes involved in osteoporosis are: 1) the ability to identify those at risk, and 2) deeper understanding of the patho­physiology which should facilitate the identification of novel therapeutic and preventive strategies. The important role of genetic factors in regulating bone mineral density(BMD), and the need for more effective treatment and prevention, means that the potential of such research is great. Genes identified so far make a weak contribution individually to bone density and fracture risk and are not of clinical value. As osteoporosis is a polygenic disease, predictive tests must involve several genes. In this article we discuss the current state of gene mapping in osteoporosis.

      Resistance to bone fracture is determined by the amount of bone present and by its strength. Bone mass in later life is determined by the peak bone mass achieved during life, and the subsequent rate of bone loss. Males lose about 20-30% and females about 30-40% of their peak bone mass. This loss affects the cortical and trabe­cular components of bone at a different rate. Bone loss is linear throughout life, about 0.5-1.0% and increases in menopause to 3.0-5.0% due to decrease in estrogen production [1]. The age at which bone loss begins is not clear.

      Bone loss appears to be less genetically determined than the bone mass [2,3]. Some studies have analyzed bone loss by measuring markers of the turnover and synthesis of bone, but the clinical significance of these markers has not been established [4].

      Parent-child studies have shown that peak bone mass is an important predictor of the risk of developing osteoporosis in later life [2,5]. Bone mass in the children of parents with osteoporotic fractures is lower than in the general population. Peak bone mass is achieved in the second decade of life, is less in females than in males, is genetically determined, and depends on the hormonal status and individual way of life [5]. Bones of boys and girls have similar bone mass, but boys have a bigger skeleton with greater biomechanical capabilities. The peak bone mass, at different points of the skeleton, is at different ages; the femoral neck maturity in girls being achieved at 16-18 years of age. In boys, the total mineral bone composition is 90.0% at 16.9 ± 1.3 years and 99.0% at 26.2 ± 3.7 years. Finally, the peak bone mass is achieved at 25 years of age for both males and females. After that, males slowly lose bone mass, while females suffer quick loss in the period of menopause. After 60 years of age, the bone loss is again similar in both sexes, with a deficit in the mechanical bone properties. It is accepted that about 0.5% of young females have osteoporosis [6]. It is important to stress the fact that the achievement of peak bone mass during the first two decades of life is one of the greatest causes for osteoporosis, especially in young people without an increase in bone loss [7]. It may be the main cause for fractures in young people [8]. The higher peak bone mass is protective in the period of life when bone loss increases with age. The peak bone mass is determined by genetic factors, sex hormones, food intake and physical exercise. Once achieved, the peak bone mass is kept as a result of the fine processes of bone remodelling as a balance between bone formation and bone resorption. They are under the influence of sex hormones, food intake and physical activity. Testosterone and estrogen concentrations increase during puberty. During early puberty, low testosterone concentration stimulates skeleton growth, while in late puberty, the higher testosterone level stimulates the epiphysis maturity and inhibits bone growth. Estrogens take part in the calcium intake, bone formation, mineralization and epiphysis maturation. Many other growth hormones and factors regulate bone growth and turnover, such as IGF-1, IGF-binding protein 3, IGF-binding protein 5 [5].

      The patient selection in most genetic studies of osteoporosis is based on a single measurement of bone density using dual energy X-ray absorptiometry (DEXA). Bone density measurements are reported as absolute values: t-scores-relative to young, normal values, and Z-scores matched for age and sex of the patients. However, these measurements do not take into account differences in skeletal or endocrine maturity of individual subjects of the same age. A further problem is how to control the effect of skeletal size. A measurement technique that is both volumetric and non invasive, and reflects bone fragility, is required but not yet available. Thus, the interpretation of the results of genetic studies must take into account the individual strengths and weakness of the measurement techniques employed [1].

      There has been valuable progress in the identification of specific environmental factors, genetic factors regulating BMD, measurement of bone density and turnover. However, few cross-sectional studies, and association studies of candidate genes that may affect bone density, have been performed. The study of genes which regulate bone mass, bone turnover and other aspects of bone metabolism, and their interaction with each other, and environmental fators to cause osteoporosis in individual patients will provide the possibility for prevention and therapy. [7]. Genetic studies are believed to identify women with better response to hormone replacement therapy [9].