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18-12-2024 | Musculoskeletal Pain | ORIGINAL ARTICLE

Exploring the association of metabolic factors and chronic musculoskeletal pain over a period of 10 years – the Doetinchem Cohort Study

Authors: Lotte Meert, H. Susan J. Picavet, Sophie Vervullens, Mira Meeus, Sander M. J. Van Kuijk, W. M. Monique Verschuren, Rob J. E. M. Smeets

Published in: Clinical Rheumatology | Issue 2/2025

Abstract

Objective

To examine (a) the association between metabolic factors and chronic musculoskeletal pain (CMP), (b) metabolic predictors of CMP 10 years later, and (c) the association and evolution of metabolic factors across different CMP trajectory groups.

Design

Data from the longitudinal Doetinchem Cohort Study were used. We used round 4 (2003–2007), with 4519 participants aged 36–75 years, as the baseline for the present study, with follow-up measurements in round 5 (2008–2012), and 6 (2013–2017), including self-reported pain and metabolic factors, which were measured either via self-report or physical assessment. For the three research aims, (a) generalized linear mixed-effects models, (b) binary logistic regression analyses and (c) linear mixed-effects models were used.

Results

(a) Female sex, higher age, presence of diabetes, higher BMI, lower diastolic blood pressure (BP), and elevated cystatin C were significantly associated with CMP in multivariable logistic analyses. (b) Female sex and elevated BMI were predictors of CMP 10 years later. (c) Those pain-free for 10 years had the lowest BMI levels compared to other CMP groups (development, recovery, persistent, and recurrent CMP). BMI was higher in the persistent CMP group than in the development and recovery groups. The pain-free group had higher diastolic BP compared to those in the persistent CMP group. Participants in the persistent CMP group had higher Cystatin C levels than the free, development and recovery CMP groups. Regarding the evolution of metabolic factors over time, BMI, glucose and diastolic BP evolved differently across the CMP trajectory groups.

Conclusion

Our findings indicate the importance of metabolic factors, especially BMI, in the onset and progression of CMP. These findings underscore the need to consider metabolic health in the prevention and treatment of CMP.

Key Points

• Metabolic factors are associated with the presence of chronic musculoskeletal pain.

• Female sex and elevated BMI are predictive of musculoskeletal pain (MP) 10 years later.

• Metabolic factors evolve differently over time across different pain trajectory groups, with variations in BMI, glucose, and diastolic blood pressure.

Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R et al (2019) Chronic pain as a symptom or a disease: the IASP classification of chronic pain for the International Classification of Diseases (ICD-11). Pain 160(1):19–27. https://doi.org/10.1097/j.pain.0000000000001384CrossRefPubMed

Disease GBD, Injury I, Prevalence C (2017) Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (London, England) 390(10100):1211–1259. https://doi.org/10.1016/S0140-6736(17)32154-2CrossRef

Rikard SM, Strahan AE, Schmit KM, Guy GP, Jr (2023) Chronic pain among adults - United States, 2019–2021. MMWR Morb Mortal Wkly Rep 72(15):379–85. https://doi.org/10.15585/mmwr.mm7215a1

Heikkala E, Oura P, Paananen M, Ho E, Ferreira P, Tanguay-Sabourin C, Karppinen J (2023) Chronic disease clusters are associated with prolonged, bothersome, and multisite musculoskeletal pain: a population-based study on Northern Finns. Ann Med 55(1):592–602. https://doi.org/10.1080/07853890.2023.2177723CrossRefPubMedPubMedCentral

Narouze S, Souzdalnitski D (2015) Obesity and chronic pain: systematic review of prevalence and implications for pain practice. Reg Anesth Pain Med 40(2):91–111. https://doi.org/10.1097/aap.0000000000000218CrossRefPubMed

Walsh TP, Arnold JB, Evans AM, Yaxley A, Damarell RA, Shanahan EM (2018) The association between body fat and musculoskeletal pain: a systematic review and meta-analysis. BMC Musculoskelet Disord 19(1):233. https://doi.org/10.1186/s12891-018-2137-0CrossRefPubMedPubMedCentral

Ydberg M, Dahlin LB, Gottsäter A, Nilsson PM, Melander O, Zimmerman M (2020) High body mass index is associated with increased risk for osteoarthritis of the first carpometacarpal joint during more than 30 years of follow-up. RMD Open 6(3):e001368. https://doi.org/10.1136/rmdopen-2020-001368

Pozzobon D, Ferreira PH, Dario AB, Almeida L, Vesentini G, Harmer AR, Ferreira ML (2019) Is there an association between diabetes and neck and back pain? A systematic review with meta-analyses. PLoS ONE 14(2):e0212030CrossRefPubMedPubMedCentral

Alenazi AM, Alkhathami KM (2023) Hypertension is associated with joint pain severity among individuals with osteoarthritis. Pain Manag Nurs 24(5):e97–e101. https://doi.org/10.1016/j.pmn.2023.07.005CrossRefPubMed

10.

Picavet HSJ, Monique Verschuren WM, Groot L, Schaap L, van Oostrom SH (2019) Pain over the adult life course: 15-year pain trajectories-the doetinchem cohort study. Eur J Pain (London, England) 23(9):1723–1732. https://doi.org/10.1002/ejp.1450CrossRef

11.

Picavet HSJ, Blokstra A, Spijkerman AMW, Verschuren WMM (2017) Cohort Profile Update: The Doetinchem Cohort Study 1987–2017: lifestyle, health and chronic diseases in a life course and ageing perspective. Int J Epidemiol 46(6):1751-g. https://doi.org/10.1093/ije/dyx103

12.

Verschuren WM, Blokstra A, Picavet HS, Smit HA (2008) Cohort profile: the Doetinchem Cohort Study. Int J Epidemiol 37(6):1236–1241. https://doi.org/10.1093/ije/dym292CrossRefPubMed

13.

Loef B, Herber G-CM, Wong A, Janssen NAH, Hoekstra J, Picavet HSJ, Verschuren WMM (2023) Predictors of healthy physiological aging across generations in a 30-year population-based cohort study: the Doetinchem Cohort Study. BMC Geriatrics 23(1):107. https://doi.org/10.1186/s12877-023-03789-2

14.

Rijksinstituut voor Volksgezondheid en Milieu (2021) Doetinchem Cohort Studie Bilthoven: Rijksinstituut voor Volksgezondheid en Milieu; [Available from: https://www.rivm.nl/doetinchem-cohort-studie.

15.

Bokshan SL, DePasse JM, Eltorai AE, Paxton ES, Green A, Daniels AH (2016) An evidence-based approach to differentiating the cause of shoulder and cervical spine pain. Am J Med 129(9):913–918. https://doi.org/10.1016/j.amjmed.2016.04.023CrossRefPubMed

16.

Lesher JM, Dreyfuss P, Hager N, Kaplan M, Furman M (2008) Hip joint pain referral patterns: a descriptive study. Pain Med 9(1):22–25. https://doi.org/10.1111/j.1526-4637.2006.00153.xCrossRefPubMed

17.

Prather H, Cheng A, Steger-May K, Maheshwari V, Van Dillen L (2017) Hip and lumbar spine physical examination findings in people presenting with low back pain, with or without lower extremity pain. J Orthop Sports Phys Ther 47(3):163–172. https://doi.org/10.2519/jospt.2017.6567CrossRefPubMedPubMedCentral

18.

Kongsted A, Kent P, Hestbaek L, Vach W (2015) Patients with low back pain had distinct clinical course patterns that were typically neither complete recovery nor constant pain. A latent class analysis of longitudinal data. Spine J:Off J North Am Spine Soc 15(5):885–94. https://doi.org/10.1016/j.spinee.2015.02.012

19.

De Rop L, De Burghgraeve T, De Sutter A, Buntinx F, Verbakel JY (2022) Point-of-care C-reactive protein test results in acute infections in children in primary care: an observational study. BMC Pediatr 22(1):633. https://doi.org/10.1186/s12887-022-03677-5CrossRefPubMedPubMedCentral

20.

Mickey RM, Greenland S (1989) The impact of confounder selection criteria on effect estimation. Am J Epidemiol 129(1):125–137. https://doi.org/10.1093/oxfordjournals.aje.a115101CrossRefPubMed

21.

Hair JF, Babin BJ, Black WC, Anderson RE (2019) Multivariate data analysis. 8 ed. Andover, Hampshire: Cengage

22.

Hosmer DW Jr, Lemeshow S, Sturdivant RX (2013) Applied logistic regression, 3rd edn. Wiley, Hoboken, NJ

23.

Overstreet DS, Strath LJ, Jordan M, Jordan IA, Hobson JM, Owens MA, Williams AC, Edwards RR, Meints SM (2023) A brief overview: sex differences in prevalent chronic musculoskeletal conditions. Int J Environ Res Public Health 20(5):4521. https://doi.org/10.3390/ijerph20054521

24.

Keogh E, Boerner KE (2024) Challenges with embedding an integrated sex and gender perspective into pain research: recommendations and opportunities. Brain Behav Immun 117:112–121. https://doi.org/10.1016/j.bbi.2023.12.027CrossRefPubMed

25.

Olsen RB, Bruehl S, Nielsen CS, Rosseland LA, Eggen AE, Stubhaug A (2013) Hypertension prevalence and diminished blood pressure-related hypoalgesia in individuals reporting chronic pain in a general population: the Tromsø study. Pain 154(2):257–262. https://doi.org/10.1016/j.pain.2012.10.020CrossRefPubMed

26.

Bruehl S, Olsen RB, Tronstad C, Sevre K, Burns JW, Schirmer H et al (2018) Chronic pain-related changes in cardiovascular regulation and impact on comorbid hypertension in a general population: the Tromsø study. Pain 159(1):119–127. https://doi.org/10.1097/j.pain.0000000000001070CrossRefPubMed

27.

Rowe PC, Calkins H (1998) Neurally mediated hypotension and chronic fatigue syndrome. Am J Med 105(3a):15s–21s. https://doi.org/10.1016/s0002-9343(98)00167-3CrossRefPubMed

28.

Bou-Holaigah I, Rowe PC, Kan J, Calkins H (1995) The relationship between neurally mediated hypotension and the chronic fatigue syndrome. JAMA 274(12):961–967CrossRefPubMed

29.

Yeater TD, Clark DJ, Hoyos L, Valdes-Hernandez PA, Peraza JA, Allen KD, Cruz-Almeida Y (2021) Chronic pain is associated with reduced sympathetic nervous system reactivity during simple and complex walking tasks: potential cerebral mechanisms. Chronic Stress (Thousand Oaks) 5:24705470211030270. https://doi.org/10.1177/24705470211030273CrossRefPubMed

30.

Kornaat PR, Kloppenburg M, Sharma R, Botha-Scheepers SA, Le Graverand MP, Coene LN et al (2007) Bone marrow edema-like lesions change in volume in the majority of patients with osteoarthritis; associations with clinical features. Eur Radiol 17(12):3073–3078. https://doi.org/10.1007/s00330-007-0711-1CrossRefPubMedPubMedCentral

31.

Davies-Tuck ML, Hanna F, Davis SR, Bell RJ, Davison SL, Wluka AE et al (2009) Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women - a prospective cohort study. Arthritis Res Ther 11(6):R181CrossRefPubMedPubMedCentral

32.

Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N (2014) Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 105(2):141–150. https://doi.org/10.1016/j.diabres.2014.04.006CrossRefPubMed

33.

Wang T, He C (2018) Pro-inflammatory cytokines: the link between obesity and osteoarthritis. Cytokine Growth Factor Rev 44:38–50. https://doi.org/10.1016/j.cytogfr.2018.10.002CrossRefPubMed

34.

Totsch SK, Sorge RE (2017) Immune system involvement in specific pain conditions. Mol Pain 13:1744806917724559. https://doi.org/10.1177/1744806917724559CrossRefPubMedPubMedCentral

35.

Baral P, Udit S, Chiu IM (2019) Pain and immunity: implications for host defence. Nat Rev Immunol 19(7):433–447. https://doi.org/10.1038/s41577-019-0147-2CrossRefPubMedPubMedCentral

36.

Zhang JM, An J (2007) Cytokines, inflammation, and pain. Int Anesthesiol Clin 45(2):27–37. https://doi.org/10.1097/AIA.0b013e318034194eCrossRefPubMedPubMedCentral

37.

Peralta CA, Katz R, Sarnak MJ, Ix J, Fried LF, De Boer I et al (2011) Cystatin C identifies chronic kidney disease patients at higher risk for complications. J Am Soc Nephrol 22(1):147–155. https://doi.org/10.1681/asn.2010050483CrossRefPubMedPubMedCentral

38.

Pham PC, Dewar K, Hashmi S, Toscano E, Pham PM, Pham PA, Pham PT (2010) Pain prevalence in patients with chronic kidney disease. Clin Nephrol 73(4):294–299PubMed

39.

Lambourg E, Colvin L, Guthrie G, Murugan K, Lim M, Walker H et al (2021) The prevalence of pain among patients with chronic kidney disease using systematic review and meta-analysis. Kidney Int 100(3):636–649. https://doi.org/10.1016/j.kint.2021.03.041CrossRefPubMed

Title: Exploring the association of metabolic factors and chronic musculoskeletal pain over a period of 10 years – the Doetinchem Cohort Study
Authors: Lotte Meert
H. Susan J. Picavet
Sophie Vervullens
Mira Meeus
Sander M. J. Van Kuijk
W. M. Monique Verschuren
Rob J. E. M. Smeets
Publication date: 18-12-2024
Publisher: Springer International Publishing
Keyword: Musculoskeletal Pain
Published in: Clinical Rheumatology / Issue 2/2025
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-024-07251-5

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Exploring the association of metabolic factors and chronic musculoskeletal pain over a period of 10 years – the Doetinchem Cohort Study

Abstract

Objective

Design

Results

Conclusion

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A critical overview of systematic reviews and meta-analyses of intra-articular injection of platelet rich plasma versus hyaluronic acid for knee osteoarthritis

Dose effect of corticosteroids on peripheral lymphocyte profiles in patients with systemic lupus erythematosus

New insights into the interplay between MALAT1 and miRNA-155 to unravel potential diagnostic and prognostic biomarkers of Behçet’s disease

Clinical features and prognosis of anti-MDA5-positive dermatomyositis with coexistent anti-aminoacyl-tRNA synthetase antibodies

Analysis of expression and its clinical significance of the ADAMTS-2 in systemic lupus erythematosus

Establishment and validation of a nomogram for predicting intravenous immunoglobulin resistance and coronary artery lesion involvement in Kawasaki disease: a retrospective study

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