Insights and implications of sexual dimorphism in osteoporosis

Abstract

Osteoporosis, a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture, has led to a high risk of fatal osteoporotic fractures worldwide. Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis, with sex-specific differences in epidemiology and pathogenesis. Specifically, females are more susceptible than males to osteoporosis, while males are more prone to disability or death from the disease. To date, sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells. Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men. This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis, mainly in a population of aging patients, chronic glucocorticoid administration, and diabetes. Moreover, we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men. Additionally, the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.

Investigating and Practicing Orthopedics at the Intersection of Sex and Gender: Understanding the Physiological Basis, Pathology, and Treatment Response of Orthopedic Conditions by Adopting a Gender Lens: A Narrative Overview

“…On the other hand, secondary osteoporosis, which is associated with pharmacological agents, including glucocorticoids (cortisone, prednisone, dexamethasone, and hydrocortisone), or underlying comorbidities like diabetes type 1 (lower bone strength), types 2 (increased bone cortical porosity), and other dysmetabolic conditions (the so-called "diabetic osteoporosis"), is more prevalent in men. Also, men have a higher risk of mortality following (either primary or secondary) osteoporotic fractures than women [42], as shown in the following section.…”

Proteomic Insights into Osteoporosis: Unraveling Diagnostic Markers of and Therapeutic Targets for the Metabolic Bone Disease

“…Among these, CDH-13 was found to inhibit osteoclast differentiation and delay age-related bone loss in aged mice, suggesting its potential therapeutic role in preventing osteopenia [120]. Another study illustrated, through proteomic analysis, that estrogen promotes autophagy in human osteoblasts during differentiation to promote survival and mineralization by upregulating RAB3 GTPase-activating protein [135,136]. Furthermore, through proteomic techniques and functional validation, ubiquitin C-terminal hydrolase 1 (UCHL1) was shown to stabilize the transcriptional coactivator with PDZbinding motif (TAZ) by deubiquitination, inhibiting osteoclast formation.…”

Author Correction: Insights and implications of sexual dimorphism in osteoporosis

“…Following publication of the original article, 1 the authors reported an error in figure 1. During re-reading our previously published article entitled “Insights and implications of sexual dimorphism in osteoporosis” 1 in Bone Research, we regrettably found that the terms of “hematopoietic precursors” and “mesenchymal precursors” in Figure 1b were wrongly reversed, which have been corrected below.…”

“…Following publication of the original article, 1 the authors reported an error in figure 1. During re-reading our previously published article entitled “Insights and implications of sexual dimorphism in osteoporosis” 1 in Bone Research, we regrettably found that the terms of “hematopoietic precursors” and “mesenchymal precursors” in Figure 1b were wrongly reversed, which have been corrected below. Although those modifications do not affect the results and conclusion in the article, all the authors agree to correct this negligence by providing corrected Figure 1, to guarantee the accuracy of the article.…”