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Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study
  1. Jiangwei Xia1,2,
  2. Shu-Yang Xie3,
  3. Ke-Qi Liu4,
  4. Lin Xu3,
  5. Pian-Pian Zhao1,2,
  6. Si-Rui Gai1,2,
  7. Peng-Lin Guan1,2,
  8. Jin-Qiu Zhao5,
  9. Yan-Ping Zhu3,
  10. Lam C Tsoi6,7,
  11. Philip E Stuart6,7,
  12. Rajan P Nair6,7,
  13. Han-Qi Yang8,
  14. Yu-Ting Liao9,
  15. Kaijing Mao10,
  16. Mo-Chang Qiu4,
  17. Zhi-Min Ying11,
  18. Bin Hu11,
  19. Zhi-Hua Yang11,12,
  20. Wei-Yang Bai1,2,
  21. Xiao-Wei Zhu1,2,
  22. Pei-Kuan Cong1,2,
  23. James T Elder6,13,
  24. Zhao-Ming Ye11,
  25. Bin Wang3,
  26. Hou-Feng Zheng1,2
  1. 1 Diseases & Population (DaP) Geninfo Lab, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
  2. 2 Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
  3. 3 Binzhou Medical University, Yantai, Shandong, China
  4. 4 Jiangxi Medical College, Shangrao, Jiangxi, China
  5. 5 The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  6. 6 Department of Dermatology, University of Michigan, Ann Arbor, Michigan, United States
  7. 7 Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, United States
  8. 8 School of Public Health, Boston University, Boston, Massachusetts, United States
  9. 9 School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
  10. 10 School of Cellular and Molecular Medicine, University of Bristol, Bristol, Bristol, United Kingdom
  11. 11 Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
  12. 12 Department of Orthopedic Surgery, Zhejiang Xiaoshan hospital, Hangzhou, Zhejiang, China
  13. 13 Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, United States
  1. Correspondence to Dr Hou-Feng Zheng, Diseases & Population Geninfo Lab, School of Life Sciences, Westlake University, Hangzhou, China; zhenghoufeng{at}westlake.edu.cn

Abstract

Objectives and methods With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them.

Results Lower eBMD were observed in patients with PsA than in controls in both model0 (β-coefficient=−0.014, p=0.0006) and model1 (β-coefficient=−0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (β-coefficient=−0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture.

Conclusions The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

  • arthritis, psoriatic
  • bone density
  • osteoporosis
  • epidemiology
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Footnotes

  • Handling editor Josef S Smolen

  • Contributors H-FZ conceived and designed the experiments. JX conducted the experiments and analysed the data. JTE, PES, LCT and RPN provided the summary data and critically reviewed the manuscript. BW, S-YX, Y-PZ, K-QL, M-CQ, W-YB, X-WZ, P-KC, P-PZ, S-RG, P-LG, H-QY, KM and Y-TL assisted in the data preparation, cleaning and analysis. Z-MYe, Z-MYing, BH, J-QZ, LX, Z-HY provided comprehensive advices on the clinical explanation of the results and critically reviewed the manuscript. H-FZ supervised the study. JX wrote the manuscript. All authors have read and approved the final manuscript.

  • Funding This work was supported by the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars of China (LR17H070001) and by the National Natural Science Foundation of China (81871831).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval All individuals provided written informed consent. North West Multi-centre Research Ethics Committee approved the UK Biobank ethical application.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. Data URLs: https://www.ukbiobank.ac.uk; http://www.gefos.org/.

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