Endocrine-related osteoporosis: bone quality, clinical phenotype, and targeted management

Abstract

Secondary osteoporosis is a major but frequently under-recognized contributor to skeletal fragility, particularly in men, premenopausal women, patients with fragility fractures at unexpectedly preserved bone mineral density, and individuals with rapid bone loss or inadequate response to standard therapy. Endocrine disorders are among the leading causes because they affect bone remodeling, mineral metabolism, sex steroid signaling, glucocorticoid pathways, insulin-like growth factor activity, and parathyroid hormone regulation. Management requires both correction of the underlying endocrine disorder and pharmacological treatment of skeletal fragility according to fracture risk. This review provides a clinically oriented and guideline-informed synthesis of endocrine-related secondary osteoporosis, with a focus on disease-specific skeletal phenotypes, diagnostic red flags, and targeted management strategies. Particular emphasis is placed on the concept of bone quality as a major determinant of fracture risk and on the limitations of conventional tools such as BMD and FRAX in this setting. We propose a practical clinical framework that integrates endocrine phenotype, vertebral imaging, trabecular bone score, and biochemical assessment into fracture-risk stratification and therapeutic decision-making. This approach supports a shift from a purely densitometric model toward a mechanism-based strategy, enabling improved identification of high- and very-high-risk patients and facilitating the appropriate use of anabolic and antiresorptive therapies.