• Users Online: 89
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2020  |  Volume : 12  |  Issue : 1  |  Page : 58-61

Assessment of musculoskeletal pain in rheumatoid arthritis patients and its relation to vitamin D levels

Department of Orthopaedics, AIIMS, Raipur, Chhattisgarh, India

Date of Submission17-Apr-2020
Date of Acceptance20-Apr-2020
Date of Web Publication26-Jun-2020

Correspondence Address:
Dr. J Rakshit
Department of Orthopaedics, AIIMS, Raipur, Chhattisgarh
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jotr.jotr_23_20

Rights and Permissions

Vitamin D is associated with musculoskeletal function in our body, and its deficiency is a common health problem all over the world. The role of Vitamin D in rheumatoid arthritis (RA) is well established due to its immunomodulatory effect. The aim of this study was to assess the musculoskeletal pain in patients with RA in relation to Vitamin D levels. We found a negative correlation and found an increase in the pain intensity among RA patients with low levels of Vitamin D.

Keywords: Rheumatoid arthritis, visual analog scale, Vitamin D

How to cite this article:
Agrawal AC, Rakshit J, Sakale H, Kar BK. Assessment of musculoskeletal pain in rheumatoid arthritis patients and its relation to vitamin D levels. J Orthop Traumatol Rehabil 2020;12:58-61

How to cite this URL:
Agrawal AC, Rakshit J, Sakale H, Kar BK. Assessment of musculoskeletal pain in rheumatoid arthritis patients and its relation to vitamin D levels. J Orthop Traumatol Rehabil [serial online] 2020 [cited 2020 Oct 30];12:58-61. Available from: https://www.jotr.in/text.asp?2020/12/1/58/287713

  Introduction Top

Vitamin D, a secosteroid hormone, is involved in the metabolism of calcium and bone. It is involved in the regulation of calcium homeostasis since it regulates the absorption of calcium from the gastrointestinal tract. The major source of Vitamin D for most of the vertebrates including Homo sapiens is exposure of the skin to sunlight.[1]

Vitamin D deficiency and insufficiency is the most common nutritional deficiency in the world. Vitamin D deficiency has been defined as a 25(OH) D as <20 ng/ml and Vitamin D insufficiency as 21–29 ng/ml. These definitions are based in part on provocative testing in healthy adults.[2]

Rheumatoid arthritis (RA) is an inflammatory rheumatic disease with a progressive course affecting articular and extra-articular structures. This results in pain, disability, and mortality. Persistent inflammation leads to erosive joint damage and functional impairment in the vast majority of patients. The course of the disease may be different according to the absence or presence of several parameters including genetics, frequency of swollen joints, autoantibody in the serum, and the severity of inflammatory process.[3],[4]

With a prevalence ranging from 0.4% to 1.3% of the population depending on both sex (women two to three times more often than men), age (frequency of new RA diagnoses peaks in the sixth decade of life), and studied patient collective (RA frequency increases from south to north and is higher in urban than rural areas),[5],[6],[7],[8],[9] RA is one of the most prevalent chronic inflammatory diseases.

The cause of RA is unknown, both genetic and environmental factors are shown to contribute to RA development.[10] As it is hypothesized for other autoimmune diseases, it is likely that the triggering event of RA requires two separate events: (1) genetic predisposition of the respective patient resulting in the generation of autoreactive T- and B-cells and (2) a triggering event, such as viral and bacterial infections or tissue injury, providing the activated antigen-presenting cells to activate the previously generated autoreactive lymphocytes, resulting in disrupted tolerance and subsequent tissue/organ destruction. Therefore, RA develops likely in a genetically predisposed individual due to a combination of genetic variation, epigenetic modification, and environmental factors initiated by a stochastic event (e.g., injury or infection).[5] Risk factors for the development of RA include smoking, obesity, exposure to ultraviolet light, sex hormones, drugs, and infections.[9],[11],[12],[13],[14]

There is a raising interest in the role of Vitamin D in the field of rheumatology as a potential treatment for a number of inflammatory diseases.[15] Vitamin D has a broad range of roles from its biological effects ranging from the classic role as a mediator of calcium and phosphorous metabolism promoting the healthy mineralization and growth and remodeling of the bone to antimicrobial activity and modulation of cellular differentiation.[16] In addition, Vitamin D exerts suppressive functions on cells of the adaptive immune response, i.e., those which are directly involved in the RA development.[17],[18]

With this in mind, this study is conducted to assess the musculoskeletal pain in RA patients and its relation with Vitamin D levels.

  Materials and Methodology Top

Subjects and methods

This is a cross-sectional study.

Source of data

The study was conducted in accordance with the Declaration of Helsinki. We included 77 patients who had appealed to our polyclinic and a known case of RA whose level of Vitamin D had been measured.

Sampling procedure

The data of patients between 18 and 70 years of age with a diagnosis of RA were included in the study. Patients were divided into three groups as Vitamin D deficient (Group 1) with a Vitamin D level <20 ng/mL, Vitamin D insufficient (Group 2) with levels <30, and normal (Group 3) with a value >30 ng/mL. The relationship between severity of pain and Vitamin D levels was evaluated.

Method of collection of data

Inclusion criteria

Patients whose

  • Pain has been defined
  • Pain level has been determined by the visual analog scale (VAS)
  • Vitamin D levels have been determined in ng/mL.

Exclusion criteria

  • Patients who have missing demographic or study data
  • Trauma, infection, and endocrinologic, neurological, and rheumatologic patients diagnosed with diseases, tumors, and depression
  • Patients who are followed up with osteomalacia diagnosis
  • Patients with advanced osteoporosis and compression fracture in X-ray were excluded from the screening.

As a result of the screening, 77 patients were eligible to be included and participated in the present study. Patients' demographic data including age, gender, and occupation were recorded.

Pain level was evaluated as nominal data determined by 10-cm VAS. VAS is resulted from marking on a horizontal line where patients have no pain shown as “0” and where the pain is the most severe shown as “10.”

Statistical analysis

All the analyses were carried out by means of Windows SPSS software (IBM Corp., Released 2013. IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, NY, USA). The appropriateness of variables was investigated with visual and analytical methods. Descriptive statistical data were presented as mean, standard deviation (SD), numbers, and percentage. There was no difference between the normally distributed group and the nonnormally distributed group in terms of Vitamin D levels.

  Results Top

The study included 77 patients who were diagnosed with RA according to the 2010 American College of Rheumatology and European League against Rheumatism criteria. Patients were mostly female (56 of 77), with a mean (SD) age of 45 ± 12 years and median disease duration (SD) of 24 ± 13 weeks.

Sociodemographic data of the groups are as follows. The mean age of the groups (44 vs. 45 ± 12.3 years vs. 46.78 ± 17.6 years), sex, and occupation were compared, but there was no statistically significant difference between the results (P > 0.05).

The mean Vitamin D levels calculated were lower in men (12.8 ± 7 ng/ml) than in women (17.88 ± 6.2 ng/ml). The mean of various parameters recorded is depicted in [Table 1].
Table 1: Depicts the mean values of various parameters studied

Click here to view

Visual analog score calculated in Group 1 was 5 in 16.21% of the patients and was not elicitable in 45% of the patients; in Group 2, it was 7 in 25% of the patients and was not elicitable in 50% of the patients; and it was 5 in 66% patients of Group 3, which is depicted in the charts [Chart 1], [Chart 2], [Chart 3], [Chart 4], [Chart 5], [Chart 6], [Chart 7].

While a negative correlation was found between Vitamin D level and VAS score, no correlation was found between body mass index (BMI), age, education level, marital status, and working status (P > 0.05).

  Discussion Top

In our study, we investigated the relationship between the severity of pain and the level of Vitamin D in patients with RA. Data we obtained showed that patients with RA had a deficiency of Vitamin D and there was a negative correlation between the level of Vitamin D and pain severity.

We also found that Vitamin D levels in male patients were lower than female patients but were statistically insignificant. This could be because in this particular region, females are more exposed to sunlight which is the main source of Vitamin D.

In a review study that supports our study partially, the relationship between Vitamin D and RA has been investigated, and it has been found that patients with RA have lower serum 25(OH)D levels and more common in younger women. The mean age of the groups (44 ± 12.3 years vs. 45 ± 17.6 years), sex, and working conditions were compared, and any statistically significant differences were not found.[19]

On the literature review, there were few studies investigating the relationship between D Vitamin and pain severity. In those studies, there was a significant correlation between serum 25(OH)D and pain severity. However, in some studies, serum 25(OH)D and pain severity were not significantly correlated. Considering these conflicting findings, careful evaluation of Vitamin D supplementation is required.

Gheita et al. found that decreased 25(OH) Vitamin D levels in RA patients compared with controls, and, among RA patients, Vitamin D was considerably lower in patients with fibromyalgia syndrome in addition to RA.[20]

The synthesis of > 90% of Vitamin D in the body occurs under the influence of sunlight. Vitamin D, taken parenterally, does not have a significant contribution, especially after a supplement is not taken.[21],[22],[23] The average prevalence in Vitamin D deficiency prevalence studies in the USA is reported as 41.6%, which is 82.1% in dark people and 69.2% in Hispanics.[24] Gokcek et al.[25] reported a 50.8% prevalence of Vitamin D deficiency in the young adult population.

Patients with RA are prone to osteoporosis[26] and suffer from pain when the disease is in a flare. Vitamin D supplementation has been proposed for patients with RA for the prevention and treatment of osteoporosis as well as for its possible effects on disease activity.[27]

Vitamin D has also an effect on the recurrence rate of RA. A study by Yang et al. stated that the recurrence rate was less in patients supplemented with Vitamin D.

  Conclusion Top

In conclusion, it appears that Vitamin D deficiency is highly prevalent in patients with RA, and Vitamin D deficiency may be linked to disease severity in RA. Vitamin D-deficient patients are more prone to musculoskeletal pain. Vitamin D supplementation may be needed for the prevention of osteoporosis and for pain relief in patients with RA.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Holick M. Vitamin D: Evolutionary, physiological and health perspectives. Curr Drug Targets 2011;12:4-18.  Back to cited text no. 1
Malabanan A, Veronikis IE, Holick MF. Redefining Vitamin D insufficiency. Lancet 1998;351:805-6.  Back to cited text no. 2
Gossec L, Combescure C, Rincheval N, Saraux A, Combe B, Dougados M,et al. Relative clinical influence of clinical, laboratory, and radiological investigations in early arthritis on the diagnosis of rheumatoid arthritis. Data from the French early arthritis cohort ESPOIR. J Rheumatol 2010;37:2486-92.  Back to cited text no. 3
Finckh A, Liang MH, van Herckenrode CM, de Pablo P. Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A meta-analysis. Arthritis Rheum 2006;55:864-72.  Back to cited text no. 4
Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet Lond Engl 2016;388:2023-38.  Back to cited text no. 5
Littlejohn EA, Monrad US. Early diagnosis and treatment of rheumatoid arthritis. Prim Care Clin Pract 2018;45:237-55.  Back to cited text no. 6
Sacks JJ, Luo YH, Helmick CG. Prevalence of specific types of arthritis and other rheumatic conditions in the ambulatory health care system in the United States, 2001-2005. Arthritis Care Res (Hoboken) 2010;62:460-4.  Back to cited text no. 7
Sangha O. Epidemiology of rheumatic diseases. Rheumatology 2000;39:3-12.  Back to cited text no. 8
Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence of rheumatoidarthritis rising? Results from Olmsted County, Minnesota, 1955–2007. Arthritis Rheum 2010;62:1576-82.  Back to cited text no. 9
Deane KD, Demoruelle MK, Kelmenson LB, Kuhn KA, Norris JM, Holers VM. Genetic and environmental risk factors for rheumatoid arthritis. Best Pract Res Clin Rheumatol 2017;31:3-18.  Back to cited text no. 10
Littlejohn EA, Monrad S. Early diagnosis and treatment of rheumatoid arthritis. Prim Care Clin Pract 2018;45:237-55.  Back to cited text no. 11
Aletaha D, Ramiro S. Diagnosis and management of rheumatoid arthritis. JAMA 2018;320:1360-72.  Back to cited text no. 12
McGraw WT, Potempa J, Farley D, Travis J. Purification, characterization, and sequence analysis of a potential virulence factor from porphyromonasgingivalis, peptidylargininedeiminase. Infect Immun 1999;67:3248-56.  Back to cited text no. 13
Tan EM, Smolen JS. Historical observations contributing insights on etiopathogenesis of rheumatoidarthritis and role of rheumatoid factor. J Exp Med 2016;213:1937-50.  Back to cited text no. 14
Jeffery LE, Razak K, Hewinson M. Vitamin D in rhheumatoid arthritis towards clinical application. Nat Rev Rheumatol 2016;12:201-10.  Back to cited text no. 15
Hall AC, Juckett MB. The role of Vitamin D in hematologic disease activity, pain and disability in RA. Clinexprheumatol 2013;28:745-7.  Back to cited text no. 16
Alluno A, Manetti M, Catelbi S, Manneschi LI, Bistoni O, Saroloni E, et al. Altered immunoregulation in RA; the role of regulatory T-cells and pro inflammatory Th 17 cells and therapeutic implications. Mediators Inflamm 2015;2015:751793.  Back to cited text no. 17
Chaudharit K, Rizvi S, Syed BA. RA, current and future trends. Nat Rev Drug Discov 2016;15;305-8.  Back to cited text no. 18
Nielen MM, van Schaardenburg D, Lems WF, van de Stadt RJ, de Koning MH, Reesink HW, et al. Vitamin D deficiency does not increase the risk of rheumatoid arthritis: Comment on the article by Merlino et al. Arthritis Rheum 2006;54:3719-20.  Back to cited text no. 19
Gheita TA, Sayed S, Gheita HA, Kenawy SA. Vitamin D status in rheumatoid arthritis patients: Relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome. Int J Rheum Dis 2016;19:294-9.  Back to cited text no. 20
Fidan F, Alkan BM, Tosun A. Pandemic of the Era: Vitamin D deficiency and insufficiency. Türk Osteoporoz Derg 2014;20:71-4.  Back to cited text no. 21
Yilmaz H, Bodur S, Karaca G. The association between Vitamin D level and chronic Pain and depression in premenopausal women. Turk J Phys Med Rehabil 2014;60:1215.  Back to cited text no. 22
Wacker M, Holick MF. Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol 2013;5:51-108.  Back to cited text no. 23
Forrest KY, Stuhldreher WL. Prevalence and correlates of Vitamin D deficiency in US adults. Nutr Res 2011;31:48-54.  Back to cited text no. 24
Gokcek E, Kaydu A. Assessment of relationship between Vitamin D deficiency and pain severity in patients with low back pain: A retrospective, observational study. Anesth Essays Res 2018;12:680-4.  Back to cited text no. 25
Deal C. Bone loss in rheumatoid arthritis: Systemic, periarticular, and focal. Curr Rheumatol Rep 2012;14:231-7.  Back to cited text no. 26
Varenna M, Manara M, Cantatore FP, Del Puente A, Di Munno O, Malavolta N, et al. Determinants and effects of Vitamin D supplementation on serum 25-hydroxy-Vitamin D levels in patients with rheumatoid arthritis. Clin Exp Rheumatol 2012;30:714-9.  Back to cited text no. 27


  [Table 1]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Materials and Me...
Article Tables

 Article Access Statistics
    PDF Downloaded23    
    Comments [Add]    

Recommend this journal