Background: Patients with systemic sclerosis (SSc) are at risk for osteoporosis and often show decreased bone mineral density (BMD) [1]. Moreover, gastrointestinal involvement is a frequent feature of SSc and most patients report dysphagia and/or heart burn based on different degrees of gastric emptying disorder as well as malabsorption [2]. The efficacy of orally administered bisphosphonates is negated by calcium and is associated with risks such as esophageal ulceration.

Objectives: This retrospective study (DRKS00033393) aimed to evaluate the effectiveness and safety of oral vs. parenteral antiresorptive drugs in patients with SSc and osteoporosis.

Methods: SSc patients treated for osteoporosis at our rheumatology department between 2004 and 2024 were included if they had at least two dual-energy X-ray absorptiometry (DXA) measurements two years apart (before and during antiresorptive therapy). The primary endpoint was the change in BMD across the entire cohort. Secondary endpoints assessed changes in BMD for individual drugs, with a specific focus on oral versus parenteral administration. Adverse events were documented descriptively.

Results: Out of 194 screened SSc patients, 129 (66%) had reduced BMD, including 64 (33%) with osteopenia and 65 (34%) with osteoporosis. Thirty-eight patients met the inclusion criteria (baseline characteristics in Table 1). Esophageal atony was comparably distributed between groups (oral: n=11/17; parenteral: n=14/18). Antiresorptive therapies included alendronate (n=17), zoledronate (n=7), denosumab (n=11), risedronate (n=2), and ibandronate (n=1). Overall, antiresorptive treatment significantly improved axial BMD and corresponding T-score (p=0.046 and p=0.049), while changes in peripheral BMD were not statistically significant (Table 2). In subgroup analysis, axial BMD and T-scores showed statistically significant improvements with parenteral antiresorptive therapy (p=0.044 and p=0.045), whereas no significant improvements were observed with oral therapy. However, no significant differences were found when comparing parenteral to orally administered bisphosphonates (p=0.154 and p=0.193). Among individual treatments, only denosumab demonstrated a significant increase in axial BMD during therapy (p=0.049). No adverse events were reported.

Conclusion: Antiresorptive therapy appears effective and safe in patients with SSc. Subgroup analysis suggests that parenteral therapies may be more effective, with denosumab showing the most consistent improvements in axial BMD. Notably, both oral and parenteral antiresorptive drugs were well-tolerated, as no adverse events were observed.

REFERENCES: [1] Volkmann ER, Andréasson K, Smith V. Systemic sclerosis. Lancet. 2023 Jan 28;401(10373):304-318. doi: 10.1016/S0140-6736(22)01692-0. Epub 2022 Nov 25. PMID: 36442487; PMCID: PMC9892343.

[2] Volkmann ER, McMahan Z. Gastrointestinal involvement in systemic sclerosis: pathogenesis, assessment and treatment. Curr Opin Rheumatol. 2022 Nov 1;34(6):328-336. doi: 10.1097/BOR.0000000000000899. Epub 2022 Aug 19. PMID: 35993874; PMCID: PMC9547962.

Acknowledgements: NIL.

Disclosure of Interests: Nils Schulz: None declared , Jonas Neumann: None declared , Pascal van Wijnen: None declared , Ulf Müller-Ladner Has been paid as a speaker for the following companies: Boering Ingelheim, Lilly, Novartis, Philipp Klemm Has been paid as a speaker for the following companies: Abbvie, Lilly, Novartis.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.