ASSESSMENT OF TRABECULAR BONE SCORE AS AN INDEX OF SKELETAL FRAGILITY ACROSS DIFFERENT SETTINGS OF SECONDARY OSTEOPOROSIS

Background: Osteoporosis is a chronic skeletal disorder characterized by reduced bone strength and an increased susceptibility to fragility fractures. While bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) is the standard diagnostic tool, its limitations are evident in secondary osteoporosis, where many fractures occur in individuals with normal or osteopenic BMD. In these settings, skeletal fragility often depends on bone quality and microarchitecture, which are not captured by BMD. The trabecular bone score (TBS) is a non-invasive texture parameter derived from lumbar spine DXA images that serves as an indirect index of trabecular microarchitectural health. Aim: This thesis evaluated the clinical utility of TBS as an index of skeletal fragility across five distinct conditions associated with secondary osteoporosis: acromegaly, chronic kidney disease (CKD), hyponatremia, chronic proton pump inhibitor (PPI) use, and arterial hypertension. Methods: The research combined two systematic reviews with meta-analyses (on acromegaly and CKD) and three population-based studies (on hyponatremia, chronic PPI use, and arterial hypertension). Results: 1. Acromegaly: In a meta-analysis of 8 studies, TBS was found to be consistently impaired in acromegalic patients, despite comparable BMD at all skeletal sites. TBS was also significantly lower in patients with prevalent vertebral fractures compared to those without. These findings remained consistent regardless of gonadal status or disease activity. 2. CKD: In a meta-analysis of 17 studies, TBS was found to be consistently impaired across the spectrum of CKD, including non-dialysis patients, dialysis patients, and kidney transplant recipients. With respect to fracture risk, TBS was able to predict incident fractures in non-dialysis patients; moreover, dialysis patients with prevalent fractures had lower TBS values compared to unfractured ones. 3. Hyponatremia: In a cohort of 4204 subjects, mild hyponatremia was associated with reduced BMD, particularly at the total hip. BMD reduction was directly proportional to the severity of sodium reduction below the normal range. Conversely, hyponatremia was not associated with a significant degradation of TBS. 4. Chronic PPI Use: In a cohort of 7478 subjects, chronic PPI use was associated with a worse bone health profile in men, with lower TBS and lower BMD at all skeletal sites. Notably, the association between chronic PPI use and degraded TBS remained statistically significant even after adjustment for BMD. In contrast, no significant association was observed between chronic PPI use and either TBS or BMD in women. 5. Hypertension: In a cohort of 7503 subjects, hypertension was independently associated with lower TBS values. On the contrary, no association was observed between hypertension and BMD at any skeletal site. No class of anti-hypertensive medications was significantly associated with TBS. Thiazide diuretics and angiotensin receptor blockers were associated with higher BMD values, whereas loop diuretics and non-dihydropyridine calcium channel blockers with lower BMD values. Conclusions: These findings reinforce the concept that secondary osteoporosis comprises heterogeneous conditions with distinct skeletal phenotypes. TBS is emerging as a potential adjunctive tool for evaluating bone microarchitectural quality and refining fracture risk assessment. However, its added value in patients with secondary osteoporosis may be context-dependent and may vary according to the specific underlying condition. Future prospective studies are needed to better evaluate the longitudinal prognostic value of TBS for predicting incident fractures in these settings