Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Postmenopausal osteoporosis is a major public health problem. Estrogen deficiency is a key factor in the pathogenesis of postmenopausal osteoporosis. Among the several types therapeutic intervention in osteoporosis, hormone replacement therapy (HRT) has traditionally been seen as the gold standard method of preventing osteoporotic fractures among postmenopausal women.The estrogenic effect on bone is dose-dependent. For oral therapy, studies have demonstrated that doses of 0.625 mg of conjugated equine estrogen and 2 mg of micronized estradiol prevent postmenopausal bone loss. Percutaneous 17 beta-estradiol prevents skeletal bone loss as effectively as oral HRT. Although the greatest benefits from HRT in terms of bone sparing effects can be obtained shortly after the menopause, the literature contains clear evidence that HRT prevents bone loss in all stages of postmenopausal life. However, estrogen therapy must be long-term, possibly lifelong, to have any lasting impact on bone health. One strategy to improve long term continuation of HRT is to reduce the dosage of estrogen and the consequent side-effects of the higher dose HRT. Various studies have assessed the efficacy of low-dose HRT (LD-HRT) as well as the standard dose HRT in the prevention of osteoporosis in postmenopausal women. LD-HRT may enhance patient acceptability and continuation, ensuring adequate bone protection and menopausal symptoms control, and given physicians the possibility to personalize the doses on the basis of each individual patient's needs.