Osteoporosis is a classical age-related disease that affects women more often than men. The hypothesis that osteoporosis is a consequence of estrogen deficiency, has been proposed as early as 1941 by Albright and colleagues. The exact mechanisms of this steroid hormone deficiency in postmenopausal women as well as in the elderly men are continuously being unraveled. Collectively, estrogen deficiency has direct as well as indirect impacts on bone metabolism all of which promote osteoclastogenesis. This review aims at shedding light on the endocrine and osteoimmunological mechanisms that lead to involutional osteoporosis.