Background: Idiopathic osteoporosis in men represents one of the most common causes of osteoporosis in young individuals and is frequently associated with a family history of osteoporosis, suggesting a relevant genetic contribution. In addition, certain genetic variants may influence therapeutic decision-making in selected patients.

Objectives: The aim of this study was to evaluate the prevalence of genetic variants and their associated clinical characteristics in men with idiopathic osteoporosis.

Methods: We conducted a retrospective study including 52 men with idiopathic osteoporosis after exclusion of secondary causes. Clinical characteristics, anthropometric data, personal and family history of fractures, bone mineral density (BMD) and trabecular bone score (TBS), parameters of bone metabolism (including bone turnover markers [BTMs]), and genetic data were analyzed. Genetic testing was performed using next-generation sequencing of a 39-gene panel related to bone homeostasis, followed by bioinformatic analysis to assess the potential clinical relevance of identified variants.

Results: The mean age (±SE) was 44.8 ± 1.8 years. A history of fractures was present in 90% of patients, with a mean of 3.7 ± 0.4 fractures per patient. A family history of osteoporosis was reported in 40.4% of cases, and 30.8% presented with associated hypercalciuria. Overall, 22 of 52 patients (42%) harbored genetic variants potentially associated with increased bone fragility. The most frequently involved genes were LRP5 (5 patients), COL1A1 or COL1A2 (5 patients), WNT1 (4 patients), and ALPL (3 patients). No significant differences were observed between patients with and without genetic variants regarding age, anthropometric parameters, clinical phenotype, BMD, bone metabolism parameters, or BTMs (BALP, PINP, NTX, and CTX). Likewise, no differences were found between patients with and without associated hypercalciuria.

Conclusions: Nearly 40% of men with idiopathic osteoporosis carry genetic variants potentially contributing to their bone disease. As some variants, particularly those involving WNT1 or ALPL, may have therapeutic implications, these findings support the consideration of genetic screening in men with idiopathic osteoporosis.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.