The study of our team was driven by a clinical problem of age-dependent chronic degenerative disease of skeleton that includes osteoporosis (OP) and osteoarthritis (OA)-related phenotypes. The major aims of the study included evaluation of the putative genetic factors determining the rate and pattern of the bone and cartilage loss and identification of the specific genes involved in this process. In addition, we examined genetic effects on circulating molecular factors involved in bone and cartilage metabolism. The skeletal phenotypes were assessed from hand radiographs, in total on about 1200 individuals belonging to ethnically homogeneous nuclear and complex three-generational pedigrees of European origin. The results obtained until now can be divided into three sections: (1) genetic analysis of bone mass/size/geometry characteristics (OP) and traits related to hand OA; (2) pedigree-based investigation of circulating levels of calciotropic hormones, growth factors, cytokines, and biochemical indices of bone and cartilage remodelling; (3) linkage and linkage disequilibrium study of several candidate genes, such as estrogen receptor alpha, collagen type I alpha 1, genes related to extracellular inorganic pyrophosphate transport and OP/OA phenotypes, including biochemical variables. The study provides compelling evidence to suggest strong involvement of the genetic factors in determination of variation of the majority of the examined OP- and OA-related phenotypes.