Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
European Journal of Medical Research
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Osteoarthrosis | Research

Causal relationship between sarcopenia and osteoarthritis: a bi-directional two-sample mendelian randomized study

Authors: Jiyong Yang, Peng Liu, Shuai Wang, Tao Jiang, Yilong Zhang, Wengang Liu

Published in: European Journal of Medical Research | Issue 1/2023

Login to get access

Abstract

Background

Previous studies have shown that osteoarthritis (OA) and sarcopenia (SP) are closely related to each other, but the causal relationships between them have not been established. The aim of this study was to investigate the causal associations between OA and SP via a bi-directional Mendelian randomization (MR) approach.

Methods

A bi-directional two-sample MR was adopted to research the causal relationship between SP and OA. The instrumental variables for SP and four types of OA: KOA, HOA, total knee replacement (TKR) and total hip replacement (THR) were derived from published large genome-wide association studies (GWAS). The inverse variance weighted (IVW), MR-Egger and weighted median estimator (WME) methods were used to estimate bi-directional causal effects.

Results

Low grip strength (GS) did not have a causal effect on four types of OA (KOA: OR = 1.205, 95% CI 0.837–1.734, p = 0.316; HOA: OR = 1.090, 95% CI 0.924–1.609, p = 0.307; TKR: OR = 1.190, 95% CI 1.084–1.307, p = 0.058; THR: OR = 1.035, 95% CI 0.792–1.353, p = 0.798), while appendicular lean mass (ALM) had a causal effect on four types of OA (KOA: OR = 1.104, 95% CI 1.041–1.171, p = 0.001; HOA: OR = 1.151, 95% CI 1.071–1.237, p < 0.001; TKR: OR = 1.114, 95% CI 1.007–1.232, p < 0.001; THR: OR = 1.203, 95% CI 1.099–1.316, p < 0.001). In the reverse direction, KOA or HOA did not have a significant causal effect on both GS and ALM (KOA-GS: OR = 1.077, 95% CI 0.886–1.309, p = 0.458; KOA-ALM: Beta = 0.004, p = 0.892; HOA-GS: OR = 1.038, 95% CI 0.981–1.099, p = 0.209; HOA-ALM: Beta = − 0.017, p = 0.196; TKR-GS: OR = 0.999, 95% CI 0.739–1.351, p = 0.997; TKR-ALM: Beta = 0.018, p = 0.501; THR-GS: OR = 1.037, 95% CI 0.978–1.101, p = 0.222; THR-ALM: Beta = − 0.023, p = 0.081).

Conclusions

The present study suggests that SP may have a causal effect on OA through changes in muscle composition rather than muscle strength, while little evidence was provided for the causal effect of OA on SP.
Appendix
Available only for authorised users
Literature
1.
Liu S, Wang B, Fan S, Wang Y, Zhan Y, Ye D. Global burden of musculoskeletal disorders and attributable factors in 204 countries and territories: a secondary analysis of the global burden of disease 2019 study. BMJ Open. 2022;12:e062183.PubMedPubMedCentral
2.
Motta F, Barone E, Sica A, Selmi C. Inflammaging and osteoarthritis. Clin Rev Allerg Immu. 2022;64:1–17.
3.
Coaccioli S, Sarzi-Puttini P, Zis P, Rinonapoli G, Varrassi G. Osteoarthritis: new insight on its pathophysiology. J Clin Med. 2022;11:6013.PubMedPubMedCentral
4.
Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127:990S-991S.PubMed
5.
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:601–601.PubMedPubMedCentral
6.
Keevil VL, Romero-Ortuno R. Ageing well: a review of sarcopenia and frailty. P Nutr Soc. 2015;74:337–47.
7.
Prieto-Alhambra D, Judge A, Javaid MK, Cooper C, Diez-Perez A, Arden NK. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints. Ann Rheum Dis. 2014;73:1659.PubMed
8.
Feike Y, Zhijie L, Wei C. Advances in research on pharmacotherapy of sarcopenia. Aging Med. 2021;4:221–33.
9.
Abramoff B, Caldera FE. Osteoarthritis pathology, diagnosis, and treatment options. Med Clin N Am. 2019;104:293–311.PubMed
10.
Chung SM, Hyun MH, Lee E, Seo HS. Novel effects of sarcopenic osteoarthritis on metabolic syndrome, insulin resistance, osteoporosis, and bone fracture: the national survey. Osteoporosis Int. 2016;27:2447–57.
11.
Iijima H, Aoyama T. Increased recurrent falls experience in older adults with coexisting of sarcopenia and knee osteoarthritis: a cross-sectional study. BMC Geriatr. 2021;21:698.PubMedPubMedCentral
12.
Kim H-J, Hong Y-H. Age-related low skeletal muscle mass correlates with joint space narrowing in knee osteoarthritis in a South Korean population: a cross-sectional, case-control study. Yeungnam Univ J Med. 2022;39:285–93.
13.
Gao Q, Hu K, Yan C, Zhao B, Mei F, Chen F, et al. associated factors of sarcopenia in community-dwelling older adults: a systematic review and meta-analysis. Nutrients. 2021;13:4291.PubMedPubMedCentral
14.
Jeanmaire C, Mazières B, Verrouil E, Bernard L, Guillemin F, Rat A-C. Body composition and clinical symptoms in patients with hip or knee osteoarthritis: results from the KHOALA cohort. Semin Arthritis Rheu. 2018;47:797–804.
15.
Ruhdorfer A, Wirth W, Eckstein F. Association of knee pain with a reduction in thigh muscle strength—a cross-sectional analysis including 4553 osteoarthritis initiative participants. Osteoarthr Cartil. 2017;25:658–66.
16.
Yamauchi K, Suzuki S, Kato C, Kato T. Atrophy of individual thigh muscles measured by MRI in older adults with knee osteoarthritis: a cross-sectional study. Ann Phys Rehabilit Med. 2020;63:38–45.
17.
Suh DH, Han KD, Hong JY, Park JH, Bae JH, Moon YW, et al. Body composition is more closely related to the development of knee osteoarthritis in women than men: a cross-sectional study using the fifth Korea national health and nutrition examination survey (KNHANES V-1, 2). Osteoarthr Cartil. 2016;24:605–11.
18.
He C, He W, Hou J, Chen K, Huang M, Yang M, et al. Bone and muscle crosstalk in aging. Front Cell Dev Biol. 2020;8:585644.PubMedPubMedCentral
19.
Li G, Zhang L, Wang D, AIQudsy L, Jiang JX, Xu H, et al. Muscle-bone crosstalk and potential therapies for sarco-osteoporosis. J Cell Biochem. 2019;120:14262–73.PubMedPubMedCentral
20.
Scimeca M, Piccirilli E, Mastrangeli F, Rao C, Feola M, Orlandi A, et al. Bone morphogenetic proteins and myostatin pathways: key mediator of human sarcopenia. J Transl Med. 2017;15:34.PubMedPubMedCentral
21.
Florin A, Lambert C, Sanchez C, Zappia J, Durieux N, Tieppo AM, et al. The secretome of skeletal muscle cells: a systematic review. Osteoarthr Cartil Open. 2020;2:100019.PubMedPubMedCentral
22.
Biolo G, Cederholm T, Muscaritoli M. Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic diseases: From sarcopenic obesity to cachexia. Clin Nutr. 2014;33:737–48.PubMed
23.
24.
Bren-Mattison Y, Hausburg M, Olwin BB. Growth of limb muscle is dependent on skeletal-derived Indian hedgehog. Dev Biol. 2011;356:486–95.PubMedPubMedCentral
25.
Shen H, Grimston S, Civitelli R, Thomopoulos S. Deletion of connexin43 in osteoblasts/osteocytes leads to impaired muscle formation in mice. J Bone Miner Res. 2015;30:596–605.PubMed
26.
Qu Z, Yang F, Yan Y, Huang J, Zhao J, Hong J, et al. A Mendelian randomization study on the role of serum parathyroid hormone and 25-hydroxyvitamin D in osteoarthritis. Osteoarthr Cartil. 2021;29:1282–90.
27.
Funck-Brentano T, Nethander M, Movérare-Skrtic S, Richette P, Ohlsson C. Causal factors for knee, hip, and hand osteoarthritis: a mendelian randomization study in the UK biobank. Arthritis Rheumatol. 2019;71:1634–41.PubMedPubMedCentral
28.
Lyu L, Cai Y, Xiao M, Liang J, Zhang G, Jing Z, et al. Causal relationships of general and abdominal adiposity on osteoarthritis: a two-sample mendelian randomization study. J Clin Med. 2022;12:320.PubMedPubMedCentral
29.
McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JPA, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet. 2008;9:356–69.PubMed
30.
Ebrahim S, Smith GD. Mendelian randomization: can genetic epidemiology help redress the failures of observational epidemiology? Hum Genet. 2008;123:15–33.PubMed
31.
Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration. BMJ. 2021;375:n2233.PubMedPubMedCentral
32.
Boer CG, Hatzikotoulas K, Southam L, et al. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell. 2021;184(24):6003–5.PubMedPubMedCentral
33.
Pei Y-F, Liu Y-Z, Yang X-L, Zhang H, Feng G-J, Wei X-T, et al. The genetic architecture of appendicular lean mass characterized by association analysis in the UK biobank study. Commun Biol. 2020;3:608.PubMedPubMedCentral
34.
Jones G, Trajanoska K, Santanasto AJ, Stringa N, Kuo C-L, Atkins JL, et al. Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women. Nat Commun. 2021;12:654.PubMedPubMedCentral
35.
Holmes MV, Ala-Korpela M, Smith GD. Mendelian randomization in cardiometabolic disease: challenges in evaluating causality. Nat Rev Cardiol. 2017;14:577–90.PubMedPubMedCentral
36.
Bowden J, Smith GD, Haycock PC, Burgess S. Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40:304–14.PubMedPubMedCentral
37.
Verbanck M, Chen C-Y, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:693–8.PubMedPubMedCentral
38.
Judd DL, Thomas AC, Dayton MR, Stevens-Lapsley JE. Strength and functional deficits in individuals with hip osteoarthritis compared to healthy, older adults. Disabil Rehabil. 2014;36:307–12.PubMed
39.
Karlsson MK, Magnusson H, Cöster MC, vonSchewelov T, Karlsson C, Rosengren BE. Patients with hip osteoarthritis have a phenotype with high bone mass and low lean body mass. Clin Orthop Relat R. 2014;472:1224–9.
40.
Andrews JS, Gold LS, Nevitt M, Heagerty PJ, Cawthon PM. Appendicular lean mass, grip strength, and the development of knee osteoarthritis and knee pain among older adults. Acr Open Rheumatol. 2021;3:566–72.PubMedPubMedCentral
41.
Misra D, Fielding RA, Felson DT, Niu J, Brown C, Nevitt M, et al. Risk of knee osteoarthritis with obesity, sarcopenic obesity, and sarcopenia. Arthritis Rheumatol. 2019;71:232–7.PubMedPubMedCentral
42.
Lovett M, Negm A, Ioannidis G, Petrucelli D, Winemaker M, Adachi JD, et al. Identifying patients with osteoarthritis at risk of sarcopenia using the SARC-F. Can Geriatrics J. 2021;24:1–7.
43.
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2018;48:16–31.PubMedCentral
44.
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older People. Age Ageing. 2010;39:412–23.PubMedPubMedCentral
45.
Studenski SA, Peters KW, Alley DE, Cawthon PM, McLean RR, Harris TB, et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol Ser. 2014;69:547–58.
46.
Chaisson CE, Zhang Y, Sharma L, Kannel W, Felson DT. Grip strength and the risk of developing radiographic hand osteoarthritis: results from the framingham study. Arthritis Rheum. 1999;42:33–8.PubMed
47.
Sharma L, Dunlop DD, Cahue S, Song J, Hayes KW. Quadriceps strength and osteoarthritis progression in malaligned and lax knees. Ann Intern Med. 2003;138:613.PubMed
48.
49.
Society O behalf of the TFG on “Arthritis” of the EGM, Veronese N, Punzi L, Sieber C, Bauer J, Reginster J-Y, et al. Sarcopenic osteoarthritis: a new entity in geriatric medicine? Eur Geriatr Med. 2018;9:141–8.
50.
Pickering M-E, Chapurlat R. Where two common conditions of aging meet: osteoarthritis and sarcopenia. Calcif Tissue Int. 2020;107:203–11.PubMed
51.
Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB, Ferrucci L. Sarcopenic obesity: definition, cause and consequences. Curr Opin Clin Nutr. 2008;11:693–700.
52.
Berenbaum F, Eymard F, Houard X. Osteoarthritis, inflammation and obesity. Curr Opin Rheumatol. 2013;25:114–8.PubMed
53.
Liu C, Liu N, Xia Y, Zhao Z, Xiao T, Li H. Osteoporosis and sarcopenia-related traits: a bi-directional mendelian randomization study. Front Endocrinol. 2022;13:975647.
54.
Pegreffi F, Balestra A, Lucia OD, Smith L, Barbagallo M, Veronese N. Prevalence of sarcopenia in knee osteoarthritis: a systematic review and meta-analysis. J Clin Med. 2023;12:1532.PubMedPubMedCentral
Metadata
Title
Causal relationship between sarcopenia and osteoarthritis: a bi-directional two-sample mendelian randomized study
Authors
Jiyong Yang
Peng Liu
Shuai Wang
Tao Jiang
Yilong Zhang
Wengang Liu
Publication date
01-12-2023

Other articles of this Issue 1/2023

European Journal of Medical Research 1/2023 Go to the issue

Review

Repurposing approved non-oncology drugs for cancer therapy: a comprehensive review of mechanisms, efficacy, and clinical prospects

Research

Seroprevalence of hepatitis C virus in Jinan, China, 2008–2020

Research

TRMT6 promotes hepatocellular carcinoma progression through the PI3K/AKT signaling pathway

Review

Speech deficits in multiple sclerosis: a narrative review of the existing literature

Research

Coagulation parameters for the differential diagnosis of pancreatic cancer in the early stage: a retrospective study

Research

Visualization of breast cancer-related protein synthesis from the perspective of bibliometric analysis