Real-world effectiveness of denosumab compared to teriparatide in patients with severe osteoporosis

Context The potent inhibitory action on bone resorption and concomitant stimulatory effect on bone modeling make denosumab (DEN) as a possible alternative to anabolic drugs for treatment of severe osteoporosis. Objective To compare the real-world effectiveness of DEN and teriparatide (TPTD) in patients with severe osteoporosis. Methods This retrospective study included 357 patients (300 females, 57 males; mean age 70.2 ± 10.7 years) attending a referral center for osteoporosis in the period between July 2021 and June 2025. All the patients had indications for treatment with TPTD according to the national drug reimbursement criteria. However, 198 patients were treated with TPTD for 24 months, whereas 159 patients received DEN for contraindications to TPTD (110 cases), patient preference (39 cases) or side effects after few doses of the drug (10 cases). Patients were evaluated for clinical/morphometric VFs and non-vertebral fractures (NVFs) at baseline and after 24 months of treatment. Results During the study period, 34 patients (9.5%) developed new VFs (clinical in 13 cases) and 7 patients (2.0%) experienced NVFs. The risk of new VFs was significantly associated with vertebroplasty procedure (odds ratio 2.409; p=0.037). Moreover, new VFs occurred less frequently in patients treated with TPTD as compared to DEN (12/198 vs. 22/159; p=0.013). In the multivariable analysis, the favorable effect of TPTD on risk of VFs was still significant after correction for vertebroplasty (odds ratio 0.39; confidence interval 95% 0.19-0.83; p=0.014). No significant difference in NVFs was found between DEN and TPTD (2/159 vs. 5/198; p=0.468). Conclusions This real-world study shows that DEN might be less effective than TPTD in preventing VFs in patients with severe osteoporosis.