SUN-791 - Comparative Real-World Outcomes of Bisphosphonate Monotherapy Versus Combined Testosterone and Bisphosphonate Therapy in Hypogonadal Men with Osteoporosis

Background:
Hypogonadism adversely affects bone health in men and is a well-recognized cause of secondary osteoporosis associated with increased fracture risk. Bisphosphonates are standard first-line therapy for fracture prevention. Although the TRAVERSE trial reported that testosterone replacement therapy (TRT) increases bone mineral density, it was also associated with a higher incidence of clinical fractures. Whether the addition of TRT to bisphosphonate therapy provides any incremental fracture risk reduction beyond antiresorptive therapy remains uncertain.

Methods:
Using the TriNetX Research Network, we conducted a retrospective propensity score–matched cohort study of men aged ≥40 years with hypogonadism due to testicular hypofunction or hypopituitarism and radiologic or clinical evidence of osteoporosis. Patients initiated either bisphosphonate monotherapy (BIS) or combined TRT plus bisphosphonate therapy (BTRT). Patients with chronic kidney disease stage 4–5, prostate cancer, Paget’s disease, or cross-therapy contamination were excluded. The index event was the first qualifying osteoporosis diagnosis, followed by treatment exposure. After a 1:1 propensity-score match, 769 patients per cohort were well balanced across demographics, comorbidities, medication exposures, laboratory values, and DXA utilization. Major osteoporotic fractures (hip, vertebral, humeral, distal radius/ulna) were assessed from 1 to 1,825 days following treatment initiation, excluding patients with prior fractures. Outcomes were evaluated using comparative risk estimates and Kaplan–Meier survival analysis.

Results:
After exclusion of pre-index fractures, 627 BIS-treated and 620 BTRT-treated men remained at risk. Major osteoporotic fractures occurred in 57/627 BIS patients (9.1%) and 55/620 BTRT patients (8.9%). The absolute risk difference was 0.2% (95% CI −3.0% to 3.4%; p=0.892). There was no significant difference in fracture risk between groups (risk ratio 1.03, 95% CI 0.72–1.46; odds ratio 1.03, 95% CI 0.70–1.52). Fracture-free survival was similar (log-rank p=0.720; hazard ratio 1.07, 95% CI 0.74–1.55), and median survival was not reached in either cohort.

Conclusion:
In this real-world cohort of hypogonadal men with osteoporosis, concomitant TRT and bisphosphonate therapy was not associated with reduced fracture risk compared with bisphosphonate monotherapy. These findings suggest that improvements in bone density reported with TRT do not necessarily translate into incremental fracture protection when combined with standard antiresorptive therapy. This distinction has significant implications for treatment expectations and clinical decision-making in men with osteoporosis. Interpretation is limited by the retrospective design and lack of fracture adjudication.

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