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Osteoporosis is a frequent skeletal disorder, particularly among postmenopausal women. It affects approximately 30% of women and 12% of men above 50 years of age. It is characterized by reduced bone mass and alterations in bone microarchitecture that result in impaired bone strength and a propensity to fracture. Decreased bone mass is the consequence of an imbalance in the bone remodeling process, resulting from complex interactions between acquired and genetic factors. The former include physical activity, nutrition and other lifestyle habits, as well as the skeletal effects of some diseases and drug therapies. Genetic factors have been extensively studied during the past 15 years. We will review some important studies that exemplify the advances and the difficulties in this research field.