Background Patients with systemic sclerosis (SSc) are at an increased risk for osteoporosis (OP) and associated fragility fractures [1]. The prevalence of osteodensitometric OP has been estimated to range from 16% to 60% [2]. However, the risks factors and the mechanisms driving bone loss in patients with SSc remain elusive. The role of “general” determinants such as higher age and low body mass index (BMI) is well established (3) but their interaction with disease-specific factors is unclear. An association between OP and the cutaneous subset (diffuse or limited skin extent) (3, 4) or disease-specific antibodies (anti-centromere or anti-topoisomerase I antibodies) (5, 6) is controversial.

Objectives Our objectives in the present study were.

1. (i)to evaluate the prevalence of clinical OP and fragility fractures in a large population of SSc patients;

2. (ii)and to identify potential disease-specific factors for OP in this population.

Methods This cross-sectional study was based on two large European prospective cohorts of SSc patients with retrospective collection of bone health data. OP was defined as the presence of a T-score below -2.5 at femoral neck or lumbar spine and/or a previous major osteoporotic fracture and/or the prescription of anti-osteoporotic therapy. Long-term therapy with glucocorticoids (GCs) was defined by a daily prednisone equivalent dose above 2.5 mg for more than 3 months. Age, female sex, BMI and treatment with proton pump inhibitors (PPIs) as predefined risk factors according to published evidence, as well as clinically relevant factors associated with a p-value <0.05 in univariable analyses, after correction for multiple comparison, were implemented into a multivariable logistic regression model.

Results A total of 932 patients fulfilling the ACR/EULAR 2013 classification criteria were included in the study, followed prospectively in two university hospitals: Lille (n=485) and Berlin (n=447; of which 72 were patients of the Rh-GIOP prospective cohort). The two cohorts were studied separately. The prevalence of OP was 32% in Berlin and 23% in Lille (p=0.003), fragility fractures occurred in 22% and 18% respectively.

Multivariable analysis in the Berlin cohort (Figure 1A) indicated that higher age (OR 1.05 [95%CI 1.03 to 1.07], p<0.001), female sex (OR 2.70 [95%CI 1.29 to 5.65], p=0.009), diffuse skin extent (OR 5.03 [95%CI 2.50 to 10.10], p<0.001), low BMI (OR 0.94 [95%CI 0.88 to 0.99], p=0.009), WHO-FC III-IV dyspnea (OR 2.06 [95%CI 1.16-3.67], p=0.014), receiving GCs (OR 1.78 [95%CI 1.10 to 3.17], p=0.026) or PPIs (OR 1.87 [95%CI 1.10 to 3.17], p=0.020) were associated with OP.

In the Lille cohort, multivariable analysis (Figure 1B) confirmed the association of OP with higher age (OR 1.06 [95%CI 1.04 to 1.08], p<0.001), GCs use (OR 4.48 [95%CI 2.42 to 8.26], p<0.001), and with anti-topoisomerase I antibody positivity (OR 2.22 [95%CI 1.18 to 4.16], p=0.013).

Conclusion Our data support a multifactorial etiopathogenesis of OP in SSc: besides common risk-factors for OP such as higher age, female sex, and BMI, several disease specific characteristics were associated with OP, such as SSc severity as reflected by diffuse skin extent and presence of antitopoisomerase I antibodies as well as severe dyspnea and SSc treatment (PPIs and GCs). These findings help to identify patients with SSc at particular risk for OP in clinical practice.

References

1. J. Chen et al., Clin Rheumatol 39, 1181-1189 (2020).
2. Y.N. Wan et al., Int J Rheum Dis 17, 845-855 (2014).
3. C. Caimmi et al., Calcif Tissue Int 99, 23-29 (2016).
4. G. Kilic et al., Int J Rheum Dis 19, 405-411 (2016).
5. M. Marot et al., Oncotarget 6, 14865-14873 (2015).
6. Y. Ibn Yacoub et al., Rheumatol Int 32, 3143-3148 (2012).

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Acknowledgements The Rh-GIOP (Glucocorticoid-induced Osteoporosis in Patients With Chronic Inflammatory Rheumatic Diseases or Psoriasis) cohort study was supported by a joint funding of Amgen, Biogen, BMS, Chugai, Generic Assays, GSK, Hexal, Horizon Therapeutics, Lilly, Medac, Mundipharma, Novartis, Pfizer, Roche and Sanofi-Genzyme. The companies were given the opportunity to provide a courtesy review of the manuscript but the authors are solely responsible for final content and interpretation.

Disclosure of Interests Charles MIDOL: None declared, Edgar Wiebe Consultant of: Consultancy fees, honoraria and travel expenses from Medac and Novartis, Elise Siegert: None declared, Dörte Huscher Grant/research support from: Travel expenses from Shire, Hélène Béhal: None declared, David Launay Grant/research support from: Grants from GSK, Actelion, Boehringer Ingelheim, Takeda, CSL Behring, Biocryst, Eric Hachulla Speakers bureau: Consulting and speaking fees from Johnson&Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme, Consultant of: Consulting and speaking fees from Johnson&Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme, Grant/research support from: Research grants from CSL Behring, Johnson&Johnson, GSK, Roche-Chugai, Vincent Sobanski Speakers bureau: Consultancies and speaking fees from Boehringer Ingelheim, Grifols, Consultant of: Consultancies and speaking fees from Boehringer Ingelheim, Grifols, Grant/research support from: Research support from Actelion, Grifols, GSK, Octapharma, Pfizer, Shire, Frank Buttgereit Speakers bureau: Consultancy fees, honoraria, travel expenses and grant support from Abbvie, Horizon Therapeutics, Pfizer, and Roche, Consultant of: Consultancy fees, honoraria, travel expenses and grant support from Abbvie, Horizon Therapeutics, Pfizer, and Roche, Grant/research support from: Consultancy fees, honoraria, travel expenses and grant support from Abbvie, Horizon Therapeutics, Pfizer, and Roche.

Keywords: Bone diseases, Osteoporosis, Systemic sclerosis

DOI: 10.1136/annrheumdis-2023-eular.902