RANKL and its decoy receptor osteoprotegerin (OPG) is a mediator system involved in bone resorption and may be responsible for the homeostatic mechanism of normal bone remodeling. The serum levels of both OPG and soluble RANKL (sRANKL), the level of RANKL in primary cultures of osteoblasts, and the bone level of Zn(2+) were measured in six women with postmenopausal osteoporosis and three women without osteoporosis (control group). As compared to control cases, patients with less than 15 years of estrogenic deprivation (cohort 1, n=3) presented increased levels of OPG (109.82%, p<0.002), sRANKL (229.13%, p<0.001) and RANKL OBL (272.35%, p<0.001), and decreased levels of Zn(2+) (67.81%, p<0.001), whereas patients with more than 15 years of estrogenic deprivation (cohort 2, n=3) showed decreased levels of OPG (70.44%, p<0.003), and Zn(2+) (61.41%, p<0.001), and increased levels of sRANKL (181.69%, p<0.002) and RANKL OBL (201.1%, p<0.002). The significantly increased levels of sRANKL and RANKL OBL in postmenopausal osteoporosis demonstrate osteoclastogenesis activation. According to the length of the estrogenic deprivation period, postmenopausal women with osteoporosis presented either increased (cohort 1) or decreased (cohort 2) OPG levels demonstrating osteoblast activation and osteoblast apoptosis stimulation, respectively. The bone levels of Zn(2+) were significantly decreased showing limited proliferation and differentiation of the osteoblasts.