A Unitary Model for Involutional Osteoporosis: Estrogen Deficiency Causes Both Type I and Type II Osteoporosis in Postmenopausal Women and Contributes to Bone Loss in Aging Men

Abstract

We propose here a new unitary model for the pathophysiology of involutional osteoporosis that identifies estrogen (E) deficiency as the cause of both the early, accelerated and the late, slow phases of bone loss in postmenopausal women and as a contributing cause of the continuous phase of bone loss in aging men. The accelerated phase in women is most apparent during the first decade after menopause, involves disproportionate loss of cancellous bone, and is mediated mainly by loss of the direct restraining effects of E on bone cell function. The ensuing slow phase continues throughout life in women, involves proportionate losses of cancellous and cortical bone, and is associated with progressive secondary hyperparathyroidism. This phase is mediated mainly by loss of E action on extraskeletal calcium homeostasis which results in net calcium wasting and increases in the level of dietary calcium intake required to maintain bone balance. Because elderly men have low circulating levels of both bioavailable E and bioavailable testosterone (T) and because recent data suggest that E is at least as important as T in determining bone mass in aging men, E deficiency may also contribute substantially to the continuous bone loss of aging men. In both genders, E deficiency increases bone resorption and may also impair a compensatory increase in bone formation. For the most part, this unitary model is well supported by observational and experimental data and provides plausible explanations to traditional objections to a unitary hypothesis. (J Bone Miner Res 1998;13:763-773)

Icariin from Epimedium brevicornum Maxim promotes the biosynthesis of estrogen by aromatase (CYP19)

“…Although some herbicides, fungicides, and insecticides have been found to promote aromatase expression in a cAMP-dependent or -independent manner (Sanderson et al, 2000;You et al, 2001;Morinaga et al, 2004), further studies are required to identify potent aromatase agonists that produce less side-effects. Estrogen deficiency is the major cause of osteoporosis, a disease affecting over 200 million people worldwide (Riggs et al, 1998). Although estrogen supplementation is an established regimen for the prevention of these diseases, the side effects associated with its long-term use, such as increased risks of breast, ovarian, and endometrial cancers, limit its clinical use (Davison and Davis, 2003).…”

Helicobacter Pylori Seropositivity in Patients with Postmenopausal Osteoporosis

“…In postmenopausal females, one of the factors that determines the development of osteoporosis is estrogen deficiency 1) . Estrogen loss in the postmenopausal period is associated with differentiation of cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha).…”

Design, Synthesis, and Osteogenic Activity of Daidzein Analogs on Human Mesenchymal Stem Cells

“…5,6 Estrogen therapy has been shown to prevent the early phases of bone loss and decrease the incidence of subsequent osteoporosis-related fractures by about 50%. 5 However, the incidence of endometrial cancer is increased with estrogen therapy and outweighs the benefits of reducing osteoporosis. 6 As alternatives, calcium, vitamin D, calcitonin, and bisphosphates have been investigated.…”