A practical clinical framework is proposed that integrates endocrine phenotype, vertebral imaging, trabecular bone score, and biochemical assessment into fracture-risk stratification and therapeutic decision-making, enabling improved identification of high- and very-high-risk patients and facilitating the appropriate use of anabolic and antiresorptive therapies.
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.
Effective care in cases of male osteoporosis requires an integrated risk-based approach that extends beyond BMD to include clinical risk factors, secondary causes, and functional status, and improved recognition and sex-specific management strategies are essential to reduce the fracture burden and improve long-term outcomes in men.
Selin Tekin, Alper Gürlek· Turkish Journal of Medical S...· 0 citations
Results indicate that radiofrequency echographic multispectrometry provides BMD and fracture risk assessment comparable to DXA in patients on peritoneal dialysis, while also highlighting the impact of vascular calcifications on the diagnostic accuracy of lumbar spine DXA measurements.
O. Nishkumay, O. Iaremenko, V.E. Kondratiuk et al.· International Journal of End...· 0 citations
Postmenopausal osteoporosis (PMO) is a systemic skeletal disorder characterized by reduced bone mass and microarchitectural deterioration of bone tissue, leading to increased fragility and fracture risk. The decline in estrogen levels after menopause accelerates bone remodelin, favoring osteoclastic bone resorption over osteoblastic bone formation. Osteoporotic fractures remain a major cause of morbidity, mortality, and healthcare expenditure worldwide. While dual- energy X- ray absor Ptiometry (DXA) remains the gold standard for diagnosis and monitoring, growing evidence suggests that molecular laboratory techniques can provide earlier and more sensitive insights into bone metabolism, treatment response, and fracture risk. Recent advances in molecular diagnostics, including bone turnover biomarkers, genomics, epigenomics, transcriptomics, proteomics, metabolomics, and liquid biopsy approaches, are transforming the laboratory follow-up of postmenopausal osteoporosis.
Dr. Erhan Oktay· Jana Nexus: Journal of Healt...· 0 citations
Postmenopausal osteoporosis (PMO) is a systemic skeletal disorder caused primarily by estrogen deficiency, leading to impaired bone remodeling, progressive loss of trabecular bone, disruption of bone microarchitecture, increased bone marrow adiposity, and a substantially elevated risk of fragility fractures. As population aging accelerates worldwide, optimizing therapeutic strategies that effectively improve bone strength while ensuring long-term safety and cost-effectiveness has become an important clinical priority. This review summarizes recent advances in combination and sequential therapies for PMO, with a particular focus on their mechanisms of action, clinical efficacy, safety profiles, and practical applications. Current treatment strategies aim to restore the balance between bone formation and bone resorption through the complementary use of anabolic and antiresorptive agents. Emerging evidence indicates that combination therapies, such as receptor activator of nuclear factor-κB ligand inhibitors with platelet-derived growth factor-BB activators, and sequential regimens, including teriparatide followed by denosumab, can improve bone mineral density, reduce fracture risk, and modulate the osteogenic–adipogenic differentiation balance of mesenchymal stem cells. This review also compares the clinical outcomes, economic considerations, and safety concerns associated with different therapeutic approaches, including medication-related osteonecrosis of the jaw and vascular calcification. In addition, the potential roles of genomics, bone metabolism biomarkers, and artificial intelligence in supporting personalized treatment strategies are discussed. Overall, combination and sequential therapies represent promising approaches for improving the management of PMO by maximizing therapeutic efficacy while minimizing adverse effects. Continued clinical research and the integration of precision medicine are expected to further refine individualized treatment strategies and improve long-term patient outcomes.
Jiazhen Liu, Yuqing Hu, Zhen Yao et al.· Beni-Suef University Journal...· 0 citations
Osteoporosis is a systemic skeletal disorder characterized by low bone density and microarchitectural deterioration, both of which lead to increased risk of fracture, disability, institutionalization, and mortality. Dual-energy X-ray absorptiometry (DEXA) remains the gold standard for evaluating bone mineral density and establishing diagnostic thresholds. However, accurate interpretation requires more than the application of numerical cut-offs. Interpretation requires careful evaluation of graphical bands, artifact recognition, awareness of site discordance, and application of least significant change for precise longitudinal assessment. With a structured approach that distinguishes between universal screening from targeted testing, laboratory evaluation further complements imaging by identifying secondary causes. Although bone turnover markers offer additional value in monitoring therapeutic response, their use is limited by assay variability. From an orthopedic perspective, fragility fractures are sentinel events that highlight underlying skeletal fragility. Often the first to encounter these patients, orthopedic surgeons are uniquely positioned to initiate comprehensive evaluation and secondary prevention. This review synthesizes international guidelines and recent literature to provide a practical framework for DEXA interpretation, laboratory integration, and holistic management aimed at reducing refracture risk, improving functional outcomes, and lowering healthcare costs.
J. Lee, Se Lim Kim, G. Kong· Hip & Pelvis· 0 citations
Osteoporosis is a systemic skeletal disease characterized by progressive bone loss and an increased risk of fracture, and it represents a major public health challenge worldwide. Osteoporosis has multiple pathogenic determinants, including age, endocrine disorders and medication. Current therapeutic approaches primarily aim to promote osteogenesis directly or inhibit osteoclast activity; however, these strategies may limit therapeutic efficacy and increase the risk of adverse effects. The present review provided an integrated perspective on the pathogenesis of osteoporosis from the standpoint of glucose metabolism. Glucose oxidation generates ATP and metabolic intermediates that are key to bone homeostasis. During early differentiation, mesenchymal stem cells rely predominantly on glycolysis during commitment toward pre-osteoblasts, whereas maturation into functional osteoblasts depends more notably on oxidative phosphorylation. The fusion and differentiation of osteoclasts require robust mitochondrial oxidation. Lactate derived from anaerobic metabolism has a dual role in bone metabolism. High-risk populations for osteoporosis include postmenopausal women, patients with type 2 diabetes mellitus and individuals with obesity. Estrogen exerts anti-inflammatory and antioxidant effects through receptor activation. Excessive production of advanced glycation end-products disrupts the bone matrix, whereas hyperlipidemia promotes inflammatory factor-induced bone resorption. These pathological changes disrupt the insulin receptor substrate/PI3K/AKT signaling pathway, compromise glucose transporter-mediated cellular glucose uptake and thus, contribute to relative insulin resistance and insufficiency compared with physiological states. In conclusion, the present review demonstrated that abnormal glucose metabolism is a key pathogenic mechanism in osteoporosis and that targeting insulin signaling may represent a fundamental strategy for correcting glucose metabolic abnormalities across diverse etiologies.
Sheng-Yao Peng, Z. Yao, Junzhe Guo et al.· International Journal of Mol...· 0 citations