Skip to main content

Advertisement

SpringerLink
Log in

Elevated serum leptin may be associated with disease activity and secondary osteoporosis in Chinese patients with rheumatoid arthritis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Introduction

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease in adults that is associated with significant joint issues and systemic inflammation. One of the signs of bone damage in RA is osteoporosis (OP). Leptin is an inflammatory protein that has been reported to be related to RA. The potential relationships among leptin, disease activity, and OP in Chinese patients with RA are not well known.

Methods

In total, 245 patients with RA and 120 healthy controls were included in this study. Detailed data on the clinical characteristics and laboratory features were collected. Information about physical activity and functional status was recorded using specific questionnaires. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). The MECALL castor-50-hf model X-ray scanner was used for the two-hand (including wrist) photographs.

Results

Serum leptin levels differed significantly between the RA group and healthy control subjects (1.27/3.29 vs. 0.17/0.24, Z=13.29, P<0.001). The positive rate of leptin protein in RA patients was 86.35%, which was higher than that in controls (19.55%) (χ2=28.51, P<0.001). Pearson’s correlation test showed that morning stiffness, disease duration, joint swelling, joint tenderness, swollen joint count (SJC), tender joint count (TJC), health assessment questionnaire (HAQ) score, and Sharp-van der Heijde method (Sharp) score were positively correlated with the level of serum leptin (r=0.212, r=0.312, r=0.322, r=0.501, r=0.291, r=0.334, P<0.05). There was a clear increasing trend in the level of serum leptin according to the different disease activity scores and in the 28 joint activity (DAS28) groups (F=13.936, P<0.001). Elevated leptin was a risk factor for increased disease activity and OP according to logistic regression analysis. The median leptin level differed significantly between the normal bone mass group, osteopenia group, and OP group (P<0.001). An increased serum leptin level was a risk factor for RA-induced osteoporosis according to logistic regression analysis (P<0.001).

Conclusion

These results suggest that the level of serum leptin is associated with disease activity and secondary OP among Chinese patients with RA.

Key Points

• Serum leptin levels in RA patients are higher than those in normal control group.

• Leptin was associated with disease activity.

• Leptin was associated with the occurrence of systemic osteoporosis and affects bone erosion in RA patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Goldring SR (2003) Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology 42:11–16

    Article  Google Scholar 

  2. Friedman M, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763–770

    Article  CAS  PubMed  Google Scholar 

  3. Toussirot E, Fabrice M, Delphine B, Dumoulin G (2015) The role of leptin in the pathophysiology of rheumatoid arthritis. Life Sci 140:29–36

    Article  CAS  Google Scholar 

  4. Bernotiene E, Palmer G, Talabot AD, Szalay QI, Gabay C (2004) Delayed resolution of acute inflammation during zymosan-induced arthritis in leptin-deficient mice. Arthritis Res Ther 12:256–263

    Article  Google Scholar 

  5. Otero M, Lago R, Gomez R, Dieguez C, Gualillo O (2006) Towards a pro-inflammatory and immunomodulatory emerging role of leptin. Rheumatology 45:944–950

    Article  CAS  PubMed  Google Scholar 

  6. Seven A, Guzel S, Aslan M, Hamuryudan V (2009) Serum and synovial fluid leptin levels and markers of inflammation in rheumatoid arthritis. Rheumatol Int 29:743–747

    Article  CAS  Google Scholar 

  7. Auwerx J, Staels B (1998) Leptin. Lancet 351:737–742

    Article  CAS  Google Scholar 

  8. Hill JW, Williams KW, Ye C, Luo J, Balthasar N et al (2008) Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice. J Clin Invest 118:1796–1805

    Article  CAS  PubMed Central  Google Scholar 

  9. Ptak A, Gregoraszczuk EL (2012) Bisphenol a induces leptin receptor expression, creating more binding sites for leptin, and activates the JAK/STAT, MAPK/ERK and PI3K/AKT signaling pathways in human ovarian cancer cell. Toxicol Lett 210:332–337

    Article  CAS  PubMed  Google Scholar 

  10. McKay M, Ruben R, Gonzalez P (2016) Leptin-induced JAK/STAT signaling and cancer growth. Vaccines 4:26–29

    Article  Google Scholar 

  11. Landry DA, Sormany F, Hache J, Roumaud P, Martin LJ (2017) Steroidogenic genes expressions are repressed by high levels of leptin and the JAK/STAT signaling pathway in MA-10 leydig cells. Mol Cell Biochem 433:79–95

    Article  CAS  PubMed  Google Scholar 

  12. Idelevich A, Sato K, Baron R (2013) What are the effects of leptin on bone and where are they exerted? J Bone Miner Res 28:18–21

    Article  CAS  PubMed  Google Scholar 

  13. Iacob D, Lighezan R, Bonte D, Camelia R, Anghel E (2013) The evaluation of the leptin implication in postmenopausal osteoporosis. J Food Agric Environ 11:244–245

    Google Scholar 

  14. Chen CY, Tsai CY, Lee PC, Pui C, Shou D (2013) Long-term etanercept therapy favors weight gain and ameliorates cachexia in rheumatoid arthritis patients: roles of gut hormones and leptin. Curr Phar Des 19:1956–1964

    Article  CAS  Google Scholar 

  15. Francisco V, Ruiz-Fernandez CPJ, Mera A, Gonzalez-Gay MA, Gomez R, Logo F et al (2019) Adipokines: linking metabolic syndrome, the immune system, and arthritic diseases. Biochem Pharmacol 165:196–206

    Article  CAS  PubMed  Google Scholar 

  16. Abella V, Scotece M, Conde J, Pino J, Gonzalez-Gay MA, Gomez-Reino JJ et al (2017) Leptin in the interplay of inflammation, metabolism and immune system disorders. Nat Rev Rheumatol 10:100–109

    Article  Google Scholar 

  17. Navarini L, Margiotta DPE, Vadacca M, Antonella A, Roma BCV, Med D et al (2018) Leptin in autoimmune mechanisms of systemic rheumatic diseases. Cancer Lett 423:139–146

    Article  CAS  PubMed  Google Scholar 

  18. Scott DL, Symmons DP, Coulton BL, Popert AJ (1987) Long-term outcome of treating rheumatoid arthritis: results after 20 years. Lancet 329:1108–1111

    Article  Google Scholar 

  19. Launay D, Sande MG, Hair JH, Aleksander MG, Sande GP et al (2012) Selective involvement of ERK and JNK mitogen-activated protein kinases in early rheumatoid arthritis (1987 ACR criteria compared to 2010 ACR/EULAR criteria): a prospective study aimed at identification of diagnostic and prognostic biomarkers as well as therapeutic targets. Ann Rheum Dis 71:415–423

    Article  PubMed  Google Scholar 

  20. Aletaha D, Neogi T, Silman AJ，Funovits J，Felson DF，et al. 2010 rheumatoid arthritis classification criteria. Arthritis Rheum 2010;69:1580-1588.

    Google Scholar 

  21. Terao C, Hashimoto M, Yamamoto K, Murakami K, Mimori T (2013) Three groups in the 28 joints for rheumatoid arthritis synovitis-analysis using more than 17000 assessments in the KURAMA database. PLoS One 8:341–349

    Article  Google Scholar 

  22. Aletaha D, Martinez-Avila J, Kvien TK, Smolen JS (2012) Definition of treatment response in rheumatoid arthritis based on the simplified and the clinical disease activity index. Ann Rheum Dis 71:1190–1196

    Article  PubMed  Google Scholar 

  23. Kirwan JR, Reeback JS (1986) Stanford health assessment questionnaire modified to assess disability in British patients with rheumatoid arthritis. Br J Rheumatol 25:206–209

    Article  CAS  PubMed  Google Scholar 

  24. Seymour RA, Simpson JM, Charlton JE, Phillips J, Michael E (1985) An evaluation of length and end-phrase of visual analogue scales in dental pain. Pain 21:177–185

    Article  Google Scholar 

  25. Gong X, Xu SQ, Tong H, Wang XR, Zong HX, Pan MJ et al (2019) Correlation between systemic osteoporosis and local bone erosion with rheumatoid arthritis patients in Chinese population. Rheumatol 9:1443–1452

    Google Scholar 

  26. Kosta PE, Voulgari PV, Zikou AK (2011) The usefulness of magnetic resonance imaging of the hand and wrist in very early rheumatoid arthritis. Arthritis Res Ther 13:R84

    Article  PubMed  PubMed Central  Google Scholar 

  27. Vander HD (1999) How to read radiographs according to the Sharp-vander Heijde method. J Rheumatol 26:743–745

    Google Scholar 

  28. van der Heijde D, Mease PJ, Landewé RBM, Rahman P, Tahir H, Singhal A, Boettcher E, Navarra S, Zhu X, Ligozio G, Readie A, Mpofu S, Pricop L (2020) Secukinumab provides sustained low rates of radiographic progression in psoriatic arthritis: 52-week results from a phase 3 study, future 5. Rheumatol 6:1325–1334

    Article  Google Scholar 

  29. Richards AM, Coleman NW, Knight TA, Belkoff SM, Mears SC (2010) Bone density and cortical thickness in normal, osteopenic, and osteoporotic sacra. J Osteoporos 4(7):123–125

    Google Scholar 

  30. Wang M, Wei J, Li H, Ouyang X, Sun XT, Tang YW et al (2018) Leptin upregulates peripheral CD4+ CXCR5+ ICOS+ T cells via increased IL-6 in rheumatoid arthritis patients. J Interferon Cytokine Res 38:86–92

    Article  CAS  Google Scholar 

  31. Otero M, Lago R, Lago F, Reino JJG, Gualillo O (2005) Signaling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1. Arthritis Res Ther 7:581–591

    Article  Google Scholar 

  32. Bokarewa M, Bokarew D, Hultgren O, Tarkowski A (2003) Leptin consumption in the inflamed joints of patients with rheumatoid arthritis. Ann Rheum Dis 62:952–956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Popa C, Netea MG, Radstake TRDS, van Riel PL, Barrera P, vander Meer JWM. (2005) Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann Rheum Dis 64:1195–1199

    Article  CAS  PubMed Central  Google Scholar 

  34. Wisiowska M, Rok M, Jaszczyk B, Stdpiej K, Cicha M (2007) Serum leptin in rheumatoid arthritis. Rheumatol Int 27:947–954

    Article  Google Scholar 

  35. Hizmetli S, Kisa M, Gokalp N, Bakici MZ (2007) Are plasma and synovial fluid leptin levels correlated with disease activity in rheumatoid arthritis? Rheumatol Int 27:335–338

    Article  CAS  Google Scholar 

  36. Shereen MO, Mohammed KS, Mohammed E (2012) Synovial/serum leptin ratio in rheumatoid arthritis: the association with activity and erosion. Rheumatol Int 32:683–690

    Article  Google Scholar 

  37. Gunaydin R, Kaya T, Atay A, Olmez N, Hur A et al (2006) Serum leptin levels in rheumatoid arthritis and relationship with d activity. South Med J 99:1078–1083

    Article  PubMed  Google Scholar 

  38. Bernotiene E, Palmer G, Gabay C (2006) The role of leptin in innate and adaptive immune response. Arthritis Res Ther 8:217–226

    Article  PubMed  PubMed Central  Google Scholar 

  39. Wang H, Gary JL, Martina SE, Gareth IK, Tim EC et al (2012) Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases. Ann Rheum Dis 71:455–462

    Article  Google Scholar 

  40. Deng J, Liu Y, Yang M, Wang S, Zhang MJ, Wang XH, Ko KH, Hua ZC, Sun LY, Cao XT, Lu LW (2012) Leptin exacerbates collagen-induced arthritis via enhancement of Th17 cell response. Arthritis Rheum 64:3564–3573

    Article  CAS  Google Scholar 

  41. Argonska SB, Majdan M, Dryglewska M (2008) Leptin serum levels in rheumatoid arthritis patients: relation to disease duration and activity. Rheumatol Int 28:585–591

    Article  Google Scholar 

  42. Taylan A, Akinci B, Toprak B, Birlik M, Engin B (2021) Association of leptin levels and disease activity in patients with early rheumatoid arthritis. Association of leptin levels and disease activity in patients with early rheumatoid arthritis. Arch Med Res 2:17–26

    Google Scholar 

  43. Kim KS, Choi HM, Ji HI, Song R, Park YB (2014) Serum adipokine levels in rheumatoid arthritis patients and their contributions to the resistance to treatment. Mol Med Rep 9:255–260

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the individuals who have helped us in this study.

Funding

The study was supported by grants from Medical Education Collaborative Innovation Fund of Jiangsu University (No. JDYY2023009) and the National Natural Science Foundation of China (81571582).

Author information

Authors and Affiliations

  1. Department of Rheumatology & Immunology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

    Xun Gong, Yu Tang, Wei Shi, Yan-Run Wang, Jia-Liang Deng, Jin-Bin Rui & Ying-Ying Qiu

  2. Zhenjiang First People’s Hospital, Zhenjiang, China

    Shao-shuai Yu

Authors
  1. Xun Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shao-shuai Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan-Run Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jia-Liang Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jin-Bin Rui
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ying-Ying Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu Tang.

Ethics declarations

Disclosures

None.

Disclaimer

The work described has not been published before; it is not under consideration for publication anywhere else; its publication has been approved by all co-authors, if any, as well as by the responsible authorities—tacitly or explicitly—at the institute where the work has been carried out. The publisher will not be held legally responsible should there be any claims for compensation.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gong, X., Tang, Y., Yu, Ss. et al. Elevated serum leptin may be associated with disease activity and secondary osteoporosis in Chinese patients with rheumatoid arthritis. Clin Rheumatol 42, 3333–3340 (2023). https://doi.org/10.1007/s10067-023-06725-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-023-06725-2

Keywords

Search

Navigation