Dipendra_for_pdf.docx https://doi.org/10.22502/jlmc.v10i2.482 Original Research Article Risk Factors Associated with Frozen Shoulder among Nepalese Population: A Hospital-based Comparative Study Dipendra Singh Chhetria,d, Ruban Raj Joshib,d, Sagar Tiwaric,e ABSTRACT: Introduction: Frozen shoulder is one of the common musculoskeletal disorders characterized by pain and restriction of motion of the shoulder joint. It is also considered a common self-limiting regional skeletal problem. This study aimed to evaluate related risk factors for frozen shoulder. Methods: This was a hospital-based comparative study involving 60 patients with a diagnosed frozen shoulder in the out-patient department as cases and 60 patients hospitalized during the same period with non-shoulder-related complaints as controls. A face-to-face interview was taken. Univariate and multivariate logistic regression analyses were performed. Results: A total of 120 consecutive subjects (60 patients with frozen shoulders and 60 controls) were taken. The mean age of cases was 54.7±3.21 years and that of controls was 42.08±2.74 years. Among the frozen shoulder patients, 33.3% had diabetes and 15% had a history of thyroid disorder. Multivariate logistic regression analysis showed age, diabetes mellitus, and thyroid dysfunction as independent risk factors for frozen shoulder (p<0.05). The frozen shoulder patients also had a higher prevalence of cardiac diseases and cervical spondylosis than the controls. No significant difference was found in body mass index, cholecystitis, history of surgical intervention, and uric acid level between the frozen shoulder group and the control group. Conclusion: The study findings indicated that diabetes, thyroid disease, and advanced age have been significantly associated with increased frozen shoulders. Keywords: Frozen shoulder; Musculoskeletal; Risk factors. Submitted: March 19, 2022. Accepted: January 16, 2023. Published: January 26, 2023. a- Lecturer, Department of Orthopedics b- Associate Professor, Department of Orthopedics c- Medical Epidemiologist d- Lumbini Medical College and Teaching Hospital, Palpa, Nepal e- Bharatpur Central Hospital Corresponding author: Dipendra Singh Chhetri Lecturer, Department of Orthopedics, Lumbini Medical College and Teaching Hospital. ORCID:https://orcid.org/0000-0001-9367-9566 Email: idipendrachhetri@gmail.com INTRODUCTION: Frozen shoulder is one of the common musculoskeletal disorders characterized by pain and restriction of motion of the shoulder joint. It is also considered the common self-limiting regional skeletal problem of unclear pathogenesis and is usually divided into primary and secondary causes. It usually How to cite this article: Chhetri DS, Joshi RR, Tiwari S. Risk Factors Associated with Frozen Shoulder among Nepalese Population: A Hospital-based Comparative Study. J Lumbini Med Coll. 2022;10(2):7 pages. DOI: https://doi.org/10.22502/jlmc.v10i2.482 Epub: January 26, 2023 J. Lumbini Med. Coll. Vol 10, No 2, Jul-Dec 2022 https://doi.org/10.22502/jlmc.v10i1 https://orcid.org/0000-0001-9367-9566 mailto:idipendrachhetri@gmail.com https://doi.org/10.22502/jlmc.v10i2.482 Chhetri DS, et al. Risk Factors Associated with Frozen Shoulder among Nepalese Population has an insidious onset and follows a protracted course, especially primary causes than secondary causes.[1] In a systematic review the point prevalence of shoulder pain among adults younger than 70 years was 7 to 27% and for adults older than 70 years was 13.2 to 26%.[2] The incidence of frozen shoulder in the general population is approximately 2 to 5% [3], but several conditions are associated with an increased incidence, including female gender, older age, diabetes mellitus (DM), cervical disc disease, prolonged immobilization, hyperthyroidism, stroke, or myocardial infarction, the presence of autoimmune diseases, and trauma. Individuals between the ages of 40 and 70 years are more commonly affected.[4,5] Frozen shoulder can be categorized into three stages: the first stage is a stage of pain, the second, the stage of stiffness, and the third, the stage of thawing which is usually self-limiting and resolves in 12 to18 months. [6] Identifying the risk factors of a disease is important to gain an understanding of its etiology. The best treatment of frozen shoulder is prevention.[7] So the purpose of the present study was to examine the presumed risk factors and to warn about the disease progression and its early management. Frozen shoulder presents with pain and stiffness in the shoulder which may lead to an inability to work and or to carry out household and leisure-time activities, Therefore, this study precisely assesses the potential influence of several factors on frozen shoulder development and evaluate the possible relationship between these factors in elevating the risk for frozen shoulder in individuals. METHODS: This was a hospital-based comparative study in which cases and controls were taken from 2021 Jan to 2022 Jan. Informed consent was obtained from each study participant. The sample size was calculated using the power and sample size program[8].We planned a study of independent cases and controls with one control per case. Prior data indicate that the probability of exposure among controls is 0.07.[2,3] If the true probability of exposure among cases is 0.27 [2,3], we needed to study 54 cases and 54 controls to be able to reject the null hypothesis that the exposure rates for cases and controls were equal with a probability (power) of 0.8. The Type I error probability associated with this test of the null hypothesis is 0.05. A total of 120 consecutive subjects (60 cases with frozen shoulder and 60 controls) were included. Ethical approval was obtained from the institutional review committee of the institute (IRC-LMC13-J/020). Participants were taken from those with newly diagnosed frozen shoulders who presented to the outpatient department of orthopedics in Lumbini medical college and Teaching Hospital (LMC-TH). The inclusion criteria were: age more than 18 years; the presence of pain associated with active and passive restriction of glenohumeral motion with external rotation less than 50% of the normal side; normal radiograph and the shoulder ultrasound demonstrating no significant rotator cuff tear. The patients were excluded in case there was the presence of shoulder diseases like shoulder fracture, dislocations, impingement syndrome, supraspinatus calcific tendinitis, and rotator cuff injuries. For control, we included hospitalized patients without shoulder disease, frozen shoulder, and trauma history. J. Lumbini Med. Coll. Vol 10, No 2, Jul-Dec 2022 jlmc.edu.np http://jlmc.edu.np Chhetri DS, et al. Risk Factors Associated with Frozen Shoulder among Nepalese Population All the subjects were randomly interviewed using a common questionnaire set in proforma by two practicing doctors. They were trained to conduct the survey, with the written protocol. An in-person interview was conducted for all the participants and information on potential risk factors were collected. For Body Mass Index (BMI), we used the WHO category for obesity (< 25, 25 to 29.9, 30 to 39.9, and ≥ 40).[9] and age range were categories (≤ 40 and > 40) years as median age group. Statistical analysis: We used STATA version 16.1 for statistical analysis. The quantitative results were expressed as frequency, percentage, and mean±standard deviation. We used the Chi-Square or Fisher’s exact test where applicable to evaluate categorical variables. Univariate logistic regression analysis was performed to assess the effect of each risk factor for frozen shoulder. Furthermore, we performed a multivariate logistic regression analysis using those variables that were significant in the single-factor analysis. We used the forward direction to calculate the logistic model. Possible interactions between risk factors were calculated using multivariate logistic regression models. A p-value of ≤0.005 was considered statistically significant. RESULTS: There were a total of 120 patients, 60 each in cases and controls. For those presented with frozen shoulder, the durations of symptoms were one, two, three, and four months among 38.33%, 30%, 23.33%, and 8.33% respectively. The mean age of the cases was 54.7±2.37 years and that of the controls was 42.08±2.49 years. The distribution of demographic variables and the risk factors of frozen shoulder namely: age, gender, diabetes mellitus (DM), BMI, thyroid dysfunction, history of cardiac disease, cervical spondylosis, cholecystitis, past surgery, uric acid are outlined in Table 1. Further, we divided the age range into two categories (≤ 40 and > 40) years. We performed a single-factor logistic regression analysis including all the mentioned risk factors of which the result is shown in Table 2. No significant difference in gender (p=0.58), BMI (0.05), cervical spondylosis (p=0.69), cholecystitis (p=0.20), uric acid (hyperuricemia) (p=0.69), cardiac diseases like hypertension (p=0.08) among those with and without frozen shoulder. Whereas age, DM, thyroid dysfunction showed a statistical significance (p values<0.009, <0.002, 0.04 respectively). These were further analyzed using multivariate logistic regression analysis, which showed that age, DM, and thyroid dysfunction were independent risk factors for frozen shoulder (Table 3). DISCUSSION: This comparative study found that age, DM, and thyroid dysfunction were the risk factors associated with frozen shoulder significantly. In addition, we found several other predictive factors for the risk of frozen shoulder, namely gender, BMI, cardiac disease, cervical spondylosis, and hyperuricemia. The result of this study can help for a better understanding of the underlying risk factor of frozen shoulder. We found out that DM was an independent risk factor for the frozen shoulder with the risk nearly 12 times more than in the control group, which was consistent with the previous studies done by Dias R et al.[10], Miligrom C et al.[11],Cho c-h et al.[12] and Wei Li et al.[4] Above result and studies indicated that diabetes is by far the most common association with frozen shoulder. This may be due to high glucose causing collagen to be sticky resulting in movement restriction and stiffness which is also known as glycosylation[13].The study by Moren et al. reported that painful stiff shoulders among diabetics had 90% of painful shoulders with restricted mobility and difficulty in daily J. Lumbini Med. Coll. Vol 10, No 2, Jul-Dec 2022 jlmc.edu.np http://jlmc.edu.np Chhetri DS, et al. Risk Factors Associated with Frozen Shoulder among Nepalese Population Table 1: Distribution of selected demographic variables and risk factors in frozen shoulder cases and controls. Factors Cases (n=60) Controls (n=60) p value Frequency (%) Frequency (%) Age <40 years 2 (3.33) 31 (51.66) <0.001 ≥40 years 58 (96.67) 29 (48.33) Gender Male 33 (55) 36 (60) 0.58 Female 27 (45) 24 (40) BMI <25 16 (26.67) 22 (36.67) 0.09 25-29.9 34 (56.67) 35 (58.33) >30 10 (16.67) 3 (5) Diabetes mellitus Yes 20 (33.33) 2 (9.33) <0.001No 40 (66.67) 58 (96.67) Thyroid dysfunction Yes 8 (13.33) 2 (3.33) 0.048 No 52 (86.67) 58 (96.67) Cardiac disease Yes 5 (8.33) 1 (1.67) 0.094 No 55 (91.62) 59 (98.33) Cervical Spondylosis Yes 4 (6.67) 3 (5) 0.69 No 56 (93.33) 57 (95) Past Surgery (other than shoulder surgery) Yes 0 (0) 14 (23.33) No 60 (100) 46 (76.67) Cholecystitis Yes 4 (6.67) 8 (13.33) 0.22 No 56 (93.33) 52 (86.67) Uric acid High 4 (6.67) 3 (5) NA Normal 56 (93.33) 57 (95) J. Lumbini Med. Coll. Vol 10, No 2, Jul-Dec 2022 jlmc.edu.np http://jlmc.edu.np Chhetri DS, et al. Risk Factors Associated with Frozen Shoulder among Nepalese Population Table 2: Univariate logistic regression analysis of the potential risk factors associated with a frozen shoulder between case and control groups. Factor OR 95% CI p value Gender 1.22 0.59 to 2.53 0.58 Age 30.99 6.93 to 138.62 <0.001 BMI 1.70 0.98 to 3.27 0.053 Thyroid dysfunction 4.46 0.90 to 21.97 0.041 Cardiac disease 5.36 0.61 to 47.3 0.08 Cervical spondylosis 1.36 0.29 to 6.34 0.69 Cholecystitis 2.15 0.61 to 7.57 0.20 hyperuricemia 1.36 0.29 to 6.34 0.69 DM 14.5 3.2 to 65.5 <0.001 OR: Odds Ratio; CI: Confidence Interval; DM: Diabetes Mellitus Table 3: Multivariate logistic regression analysis Factors OR 95% CI p value Age 1.03 1.01 to 1.07 0.009 Diabetes mellitus 12.07 2.43 to 59.83 0.002 Thyroid dysfunction 5.45 1.03 to 28.67 0.045 activity in the acute phase[14]. This signifies the need for early detection and prevention of frozen shoulder among patients with DM. Considering those with thyroid dysfunction, the result of our study indicated that the individuals with thyroid dysfunction have around five times more risk of developing frozen shoulder than the control group which was to the previous studies done by Miligron C et al.[11] and Cakir M et al.[15]Milgrom et al. reported that among those with frozen shoulder, 13.5% were with thyroid dysfunction. While it was 10.9% in a study conducted in an endocrinology clinic among 137 patients by Cakir m et al.[15] Wohlgethan et al.[16] also found a possible link between frozen shoulder and altered thyroid function. J. Lumbini Med. Coll. Vol 10, No 2, Jul-Dec 2022 jlmc.edu.np http://jlmc.edu.np Chhetri DS, et al. Risk Factors Associated with Frozen Shoulder among Nepalese Population In this study, the patients with cervical spondylosis were 1.4 times high likely of having frozen shoulders than the control group although not statistically significant. This result is consistent with the result of the hospital-based case-control study conducted in China where the prevalence of frozen shoulder was 23.6 % and 15.3% among those with cervical spondylosis and the control group respectively.[4] In this study regarding age, about 96% participated patients were above 40 years with a p-value less than 0.005 which is similar to other studies.[17,18] We found a significant relationship between frozen shoulder with some comorbidities. We performed a hospital-based case-control study and analyzed the potential risk factors associated with a frozen shoulder in western Nepal. We found out overlapped as well as different patterns, comprising with other previous studies. This reflects the race-dependent effect on frozen shoulder. Yet, the result of the present study should be considered with certain limitations. We carried out this study in small groups of 60 participants in each case and control. We could not include some of the suspected risk factors as mentioned in various articles like Parkinson’s disease, stroke, hyperlipidemia, and Dupuytren’s contracture. CONCLUSION: This study showed that diabetes mellitus, thyroid disorder, and advanced age were associated with the frozen shoulder in Western, Nepal. However, more future prospective cohort studies will prove and simplify the association. Conflict of Interest: The authors declare that no competing interests exist. Source of Funds: None. REFERENCES: 1. Wang K, Ho V, Hunter-Smith DJ, Beh PS, Smith KM, Weber AB. Risk factors in idiopathic adhesive capsulitis: a case control study. J Shoulder Elbow Surg. 2013;22(7):e24-9. PMID: 23352186 DOI: https://doi.org/10.1016/j.jse.2012.10.049 2. Luime JJ, Koes BW, Hendriksen IJM, Burdorf A, Verhagen AP, Miedema HS, et al. Prevalence and incidence of shoulder pain in the general population; a systematic review. Scand J Rheumatol. 2004;33(2):73-81. PMID: 15163107 DOI: https://doi.org/10.1080/030097403100046 67 3. Buchbinder R, Hoving JL, Green S, Hall S, Forbes A, Nash P. Short course prednisolone for adhesive capsulitis (frozen shoulder or stiff painful shoulder): a randomised, double-blind, placebo controlled trial. Ann Rheum Dis. 2004;63(11):1460-9. PMID: 15479896 DOI: https://doi.org/10.1136/ard.2003.018218 4. Li W, Lu N, Xu H, Wang H, Huang J. Case control study of risk factors for frozen shoulder in China. Int J Rheum Dis. 2015;18(5):508-13. PMID: 24438046 DOI: https://doi.org/10.1111/1756-185x.12246 5. Schiefer M, Teixeira PFS, Fontenelle C, Carminatti T, Santos DA, Righi LD, et al. Prevalence of hypothyroidism in patients with frozen shoulder. J Shoulder Elbow Surg. 2017;26(1):49-55. PMID: 27424251 DOI: https://doi.org/10.1016/j.jse.2016.04.026 6. Chan HBY, Pua PY, How CH. Physical therapy in the management of frozen shoulder. Singapore Med J. 2017;58(12):685-9. PMID: 29242941 DOI: https://doi.org/10.11622/smedj.2017107 7. Le H V, Lee SJ, Nazarian A, Rodriguez EK. Adhesive capsulitis of the shoulder: review of pathophysiology and current J. Lumbini Med. Coll. Vol 10, No 2, Jul-Dec 2022 jlmc.edu.np https://pubmed.ncbi.nlm.nih.gov/23352186/ https://doi.org/10.1016/j.jse.2012.10.049 https://pubmed.ncbi.nlm.nih.gov/15163107/ https://doi.org/10.1080/03009740310004667 https://doi.org/10.1080/03009740310004667 https://pubmed.ncbi.nlm.nih.gov/15479896/ https://doi.org/10.1136/ard.2003.018218 https://pubmed.ncbi.nlm.nih.gov/24438046/ https://doi.org/10.1111/1756-185x.12246 https://pubmed.ncbi.nlm.nih.gov/27424251/ https://doi.org/10.1016/j.jse.2016.04.026 https://pubmed.ncbi.nlm.nih.gov/29242941/ https://doi.org/10.11622/smedj.2017107 http://jlmc.edu.np Chhetri DS, et al. Risk Factors Associated with Frozen Shoulder among Nepalese Population clinical treatments. Shoulder Elbow. 2017;9(2):75-84. PMID: 28405218 DOI: https://doi.org/10.1177/175857321667678 6 8. Dupont WD, Plummer WD Jr. Power and sample size calculations. A review and computer program. Control Clin Trials. 1990;11(2):116-28. PMID: 2161310 DOI: https://doi.org/10.1016/0197-2456(90)900 05-m 9. Dwyer JT, Melanson KJ, Sriprachy-anunt U, Cross P, Wilson M. Dietary Treatment of Obesity. In: Feingold KR, Anawalt B, Boyce A, et al (eds). Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000 Available from: https://www.ncbi.nlm.nih.gov/books/NBK 278991/table/diet-treatment-obes.table4cl as/ 10. Dias R, Cutts S, Massoud S. Frozen shoulder. BMJ. 2005;331(7530):1453-6. DOI: https://doi.org/10.1136/bmj.331.7530.145 3 11. Milgrom C, Novack V, Weil Y, Jaber S, Radeva-Petrova DR, Finestone A. Risk factors for idiopathic frozen shoulder. Isr Med Assoc J. 2008;10(5):361-4. PMID: 18605360 12. Cho CH, Bae KC, Kim DH. Treatment Strategy for Frozen Shoulder. Clin Orthop Surg. 2019;11(3):249-57. PMID: 31475043 DOI: https://doi.org/10.4055/cios.2019.11.3.249 13. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114(6):597-605. PMID: 16894049 DOI: https://doi.org/10.1161/circulationaha.106. 621854 14. Morén-Hybbinette I, Moritz U, Scherstén B. The clinical picture of the painful diabetic shoulder--natural history, social consequences and analysis of concomitant hand syndrome. Acta Med Scand. 1987;221(1):73-82. PMID: 2436441 DOI: https://doi.org/10.1111/j.0954-6820.1987.t b01247.x 15. Cakir M, Samanci N, Balci N, Balci MK. Musculoskeletal manifestations in patients with thyroid disease. Clin Endocrinol (Oxf). 2003;59(2):162-7. PMID: 12864792 DOI: https://doi.org/10.1046/j.1365-2265. 2003.01786.x 16. Wohlgethan JR. Frozen shoulder in hyperthyroidism. Arthritis & Rheumatology. 1987;30(8):936-9. DOI: https://doi.org/10.1002/art.1780300815 17. Pietrzak M. Adhesive capsulitis: An age related symptom of metabolic syndrome and chronic low-grade inflammation? Med Hypotheses. 2016;88:12-7. PMID: 26880627 DOI: https://doi.org/10.1016/j.mehy.2016.01.00 2 18. Lewis J. Frozen shoulder contracture syndrome – Aetiology, diagnosis and management. Man Ther. 2015;20(1):2-9. PMID: 25107826 DOI: https://doi.org/10.1016/j.math.2014.07.00 6 J. Lumbini Med. Coll. Vol 10, No 2, Jul-Dec 2022 jlmc.edu.np https://pubmed.ncbi.nlm.nih.gov/28405218/ https://doi.org/10.1177/1758573216676786 https://doi.org/10.1177/1758573216676786 https://pubmed.ncbi.nlm.nih.gov/2161310/ https://doi.org/10.1016/0197-2456(90)90005-m https://doi.org/10.1016/0197-2456(90)90005-m https://www.ncbi.nlm.nih.gov/books/NBK278991/table/diet-treatment-obes.table4clas/ https://www.ncbi.nlm.nih.gov/books/NBK278991/table/diet-treatment-obes.table4clas/ https://www.ncbi.nlm.nih.gov/books/NBK278991/table/diet-treatment-obes.table4clas/ https://doi.org/10.1136/bmj.331.7530.1453 https://doi.org/10.1136/bmj.331.7530.1453 https://pubmed.ncbi.nlm.nih.gov/18605360/ https://pubmed.ncbi.nlm.nih.gov/31475043/ https://pubmed.ncbi.nlm.nih.gov/31475043/ https://doi.org/10.4055/cios.2019.11.3.249 https://pubmed.ncbi.nlm.nih.gov/16894049/ https://doi.org/10.1161/circulationaha.106.621854 https://doi.org/10.1161/circulationaha.106.621854 https://pubmed.ncbi.nlm.nih.gov/2436441/ https://doi.org/10.1111/j.0954-6820.1987.tb01247.x https://doi.org/10.1111/j.0954-6820.1987.tb01247.x https://pubmed.ncbi.nlm.nih.gov/12864792/ https://pubmed.ncbi.nlm.nih.gov/12864792/ https://doi.org/10.1046/j.1365-2265.2003.01786.x https://doi.org/10.1046/j.1365-2265.2003.01786.x https://doi.org/10.1002/art.1780300815 https://pubmed.ncbi.nlm.nih.gov/26880627/ https://pubmed.ncbi.nlm.nih.gov/26880627/ https://doi.org/10.1016/j.mehy.2016.01.002 https://doi.org/10.1016/j.mehy.2016.01.002 https://pubmed.ncbi.nlm.nih.gov/25107826/ https://doi.org/10.1016/j.math.2014.07.006 https://doi.org/10.1016/j.math.2014.07.006 http://jlmc.edu.np