Osteoporosis Due to Hormone Imbalance: An Overview of the Effects of Estrogen Deficiency and Glucocorticoid Overuse on Bone Turnover

Abstract

Osteoporosis is a serious health issue among aging postmenopausal women. The majority of postmenopausal women with osteoporosis have bone loss related to estrogen deficiency. The rapid bone loss results from an increase in bone turnover with an imbalance between bone resorption and bone formation. Osteoporosis can also result from excessive glucocorticoid usage, which induces bone demineralization with significant changes of spatial heterogeneities of bone at microscale, indicating potential risk of fracture. This review is a summary of current literature about the molecular mechanisms of actions, the risk factors, and treatment of estrogen deficiency related osteoporosis (EDOP) and glucocorticoid induced osteoporosis (GIOP). Estrogen binds with estrogen receptor to promote the expression of osteoprotegerin (OPG), and to suppress the action of nuclear factor-κβ ligand (RANKL), thus inhibiting osteoclast formation and bone resorptive activity. It can also activate Wnt/β-catenin signaling to increase osteogenesis, and upregulate BMP signaling to promote mesenchymal stem cell differentiation from pre-osteoblasts to osteoblasts, rather than adipocytes. The lack of estrogen will alter the expression of estrogen target genes, increasing the secretion of IL-1, IL-6, and tumor necrosis factor (TNF). On the other hand, excessive glucocorticoids interfere the canonical BMP pathway and inhibit Wnt protein production, causing mesenchymal progenitor cells to differentiate toward adipocytes rather than osteoblasts. It can also increase RANKL/OPG ratio to promote bone resorption by enhancing the maturation and activation of osteoclast. Moreover, excess glucocorticoids are associated with osteoblast and osteocyte apoptosis, resulting in declined bone formation. The main focuses of treatment for EDOP and GIOP are somewhat different. Avoiding excessive glucocorticoid use is mandatory in patients with GIOP. In contrast, appropriate estrogen supplement is deemed the primary treatment for females with EDOP of various causes. Other pharmacological treatments include bisphosphonate, teriparatide, and RANKL inhibitors. Nevertheless, more detailed actions of EDOP and GIOP along with the safety and effectiveness of medications for treating osteoporosis warrant further investigation.

Osteosarcopenic obesity and its components—osteoporosis, sarcopenia, and obesity—are associated with blood cell count-derived inflammation indices in older Chinese people

“…Osteoporosis, obesity, and sarcopenia have been studied extensively as individual conditions, and strong evidence has been uncovered for the roles of inflammatory cytokines, such as IL-6, IL-1, and TNF-α, in their pathogenesis [39][40][41]. Osteoporosis represents an imbalance in bone metabolism wherein bone absorption exceeds bone formation [42]. Its development requires the participation of inflammatory cytokines, which promote the formation of osteoclasts from its precursors through a series of signal transduction pathways [43][44][45][46].…”

Critical illness and bone metabolism: where are we now and what is next?

“…Estrogen binds to the estrogen receptor, which regulates the expression of proteins encoded by estrogen target genes, such as insulin-like growth factor 1 (IGF1) and transforming growth factor-β (TGFβ) [ 41 ]. Studies have shown that estrogen can directly affects cell differentiation and apoptosis [ 42 ].…”

Patient-specific risk factors for adverse outcomes following geriatric proximal femur fractures

“…New approaches include bone turnover markers to evaluate the therapeutic response [ 43 ] or genetic analysis [ 44 ]. Among elderly individuals, osteoporosis is particularly prevalent in postmenopausal women, mainly due to estrogen deficiency [ 45 ]. However, long-term corticoid treatment and systemic diseases affecting bone formation and turnover (such as diabetes, chronic kidney diseases, multiple myeloma, primary hyperparathyroidism or immobilization) are also relevant factors leading to osteoporosis [ 46 ].…”