Secondary Causes of Bone Fragility

Bone fragility is most often linked to primary osteoporosis, of which postmenopausal and senile represent the two subtypes; however a wide range of secondary causes also contribute to weakened skeletal health. Endocrine disorders, chronic systemic diseases, medications, and lifestyle-related factors can all compromise bone health, often remaining underrecognized and undertreated. Unlike primary osteoporosis, secondary causes involve distinct mechanisms such as altered mineral metabolism, hormonal imbalance, impaired bone remodeling, or chronic low-grade inflammation. The suspicion of secondary osteoporosis may arise when there is a clinical manifestation of a specific disease, a Z-score more than -2 SD, a very low T-score value compared to patient’s fracture risk factors, a fragility fracture in the presence of normal/osteopenic BMD, osteoporosis or a fracture in eugonadal subjects or patients non-responders to osteoactive therapies with adequate adherence. Despite their impact, these contributors are still poorly understood and insufficiently addressed in standard clinical practice. Bridging this gap is crucial avoid inappropriate treatments for osteoporosis and at the same time to treat the underlying disease, finally preventing other serious comorbidities of the underlying disease.

This Research Topic aims to advance understanding of the secondary causes of bone fragility by clarifying the mechanisms through which systemic diseases and therapies impair bone health, promoting the development of diagnostic tools that distinguish secondary from primary fragility osteoporosis, and highlighting therapeutic approaches tailored to specific conditions. By integrating basic science, translational research, and clinical perspectives, the collection will provide a comprehensive view of how diverse factors contribute to bone fragility and identify opportunities for innovation in prevention and management.

Topics of interest include, but are not limited to:

• Endocrine disorders leading to bone fragility, including hyperparathyroidism, thyroid disease, adrenal disorders, hypogonadism and diabetes

• Chronic conditions associated with bone fragility, such as kidney, liver, haematological and autoimmune diseases, neuromuscular syndromes.

• Pharmacological causes of bone fragility, including glucocorticoids, cancer therapies, and antiepileptic medications

• Nutritional and lifestyle factors contributing to bone fragility, including malabsorption, vitamin D deficiency, smoking, and inactivity

• Advances in the assessment and treatment of secondary bone fragility, from imaging and biomarkers to personalized prevention strategies

By uniting clinicians, basic scientists, and translational researchers, this Research Topic seeks to improve patient-centred strategies that reduce fracture risk, enhance quality of life, and lessen the global burden of bone fragility.