Inferential statistics comparing the baseline age, sex, regional, and comorbidity distributions of the two 25D-stratified cohorts was performed using chi-square analysis. A two-sided Student t-test was used to assess CCI between the two cohorts. Statistical significance was defined as P < 0.05. PearlDiver's statistics package was used to fit a multivariate logistic regression using age, sex, and CCI as covariates, and to calculate the adjusted odds ratios (ORs), 95% confidence intervals (CIs), and associated P-values for each surgical complication with 25D-deficient patients defined as the exposed group. All additional analysis was performed using SPSS version 21 software (IBM Corp).
Between 2007 and 2016, 1,881 patients undergoing arthroscopic RCR had measured preoperative 25D levels in the Humana database (Table 2). Of these, 229 (229/1,881 = 12.2%) were found to be 25D deficient (<20 mg/dL). Both 25D-deficient and -sufficient groups were similar in distribution and had a median and mode age in the 65 to 69 years group (P = 0.237) (Table 2). In addition, sex distribution was equivalent between the two groups, as females comprised 66.8% and 63.8% of the 25D-deficient and -sufficient cohorts, respectively (P = 0.373). Most cases were reported in the South geographic region (25D-deficient 80.3%; 25D-sufficient 81.4%). The 25D-deficient cohort had a higher comorbid rates of diabetes mellitus (P = 0.002), hypertension (P = 0.022), obesity (P = 0.006), and cerebrovascular disease (P = 0.036) (Table 3).
The most common complication after arthroscopic RCR was arthroscopic débridement (25D-deficient 24.0%; 25D-sufficient 28.7%), followed by revision RCR (25D-deficient 8.3%; 25D-sufficient 6.6%) and stiffness, requiring MUA (25D-deficient 4.8%; 25D-sufficient 3.8%) (Table 4). After adjusting for age, sex, and comorbidities using multivariate logistic regression, 25D-deficient patients undergoing arthroscopic RCR were more likely to undergo future revision RCR (OR 1.54, 95% CI 1.21 to 1.97, P < 0.001) and MUA for postoperative stiffness (OR 1.16, 95% CI 1.03 to 2.03, P = 0.035). Risks of postoperative SSI, arthroscopic débridement, and conversion to arthroplasty were not statistically significantly different between the two cohorts (Table 4).
As shown, vitamin D deficiency is associated with increased postoperative complications in arthroscopic RCR. This finding comes in light of other studies highlighting the significance of 25D as a potential modifiable risk factor to limit muscle strains, improve fracture outcomes, promote articular cartilage health, and decrease postoperative complications in arthroplasty.10,13-16 Although mechanistically it is unclear how normalizing 25D can lead to improved outcomes in arthroscopy, addressing deficiency preoperatively is, in principle, a simple task and has the potential to improve clinical results at a relatively low cost. Further study is warranted to investigate what role preoperative normalization of 25D may have on decreasing rates of revision RCR and stiffness requiring MUA.
The role of 25D in human biology is constantly evolving, though with ample evidence to support bone, muscle, and calcium and phosphoregulatory mechanisms. Conversely, 25D's role in tendon-to-bone healing is poorly understood. Rotator cuff surgery heavily relies on this healing mechanism, and failure is often attributed to ineffective tendon-to-bone repair. Some studies report as high as a 22% to 36% rate of recurrent tears after arthroscopic RCR.6,17,18 In turn, this has stimulated the need for augmentation of the procedure, with recent developments including dermal allografts and scaffolding to create more stable biomechanical constructs.19,20 Similarly, the role of supplementing 25D in these repairs is under consideration because it has been shown to mitigate the inflammatory milieu, with reports of improved healing in animal models.21 Theoretically, this implies that a lack of 25D could promote an environment hostile to adequate repair and predispose the patient to increased postoperative complications. Irrespective, a deeper understanding of the biochemical role of 25D in facilitation of tendon-to-bone healing is required to validate these conclusions and should be a target of future study.
As predicted, vitamin D deficiency was associated with a greater average CCI and associated medical comorbidities. Within the 25D-deficient cohort, there were higher rates of obesity (P = 0.006), diabetes mellitus (P = 0.002), hypertension (P = 0.022), and cerebrovascular disease (P = 0.036) than in the 25D-sufficient group. In the current literature, 25D deficiency has been associated with each of these conditions, although its role in pathogenesis is still an active topic of debate. In the obese, 25D deficiency is thought to be diluted by body mass because some data have shown obese individuals have identical serum concentrations to nonobese after controlling for body size.22 This deficiency, whether dilutional or not, is thought to allow inflammatory processes in the metabolic syndrome, leading to damage of β-cells in the pancreas and cardiovascular dysfunction. This subsequently leads to an increase in insulin resistance and coronary, cerebral, and peripheral vascular diseases.23 Notably, these comorbidities suggest that the 25D-deficient cohort inherently comprises a sicker population, and may confound why this group had more complications overall.
However, after controlling for these comorbidities, low levels of 25D were markedly associated with an increased need for RCR revisions. Re-tear or incomplete healing of the rotator cuff is common after RCR, although it may be of questionable clinical significance. Some studies note that the structural integrity of a RCR does not correlate with clinically notable differences in strength or pain, and patients will often report functional improvement despite failure to heal.24-28 As such, revision is often reserved for patients with persistent functional deficits or intolerable levels of residual pain.4,26,29 These outcomes, although likely multifactorial, could theoretically be affected by 25D deficiency. However, further investigation is required to determine how 25D is associated with the development of postoperative complications.
This study also found postoperative stiffness requiring MUA to be associated with 25D deficiency after controlling for age, sex, and comorbidities. Stiffness in the shoulder can be a direct result of postoperative inflammation because the upregulation of cytokines in an inflammatory response is thought to lead to myofibroblast-induced capsular hyperplasia and fibrosis. This subsequently decreases capsular volume and limits shoulder range of motion.30 Although speculative, 25D may have a role in this pathogenesis secondary to its role in inflammatory regulation. Some studies have highlighted 25D's ability to inhibit myofibroblast activity, and it is thought that supplementation of this nutrient may have a role in preventing fibrosis and scarring.31,32 As such, the increased incidence of stiffness in the 25D-deficient cohort may be explained by uninhibited myofibroblast proliferation, leading to increased scarring and decreased mobility at the glenohumeral joint. Of note, previous studies estimate the prevalence of comorbid adhesive capsulitis in the diabetic population to be around 10% to 30%.33 Given the large incidence of diabetes in the study population, it is possible that this condition explains part of the increased incidence of postoperative shoulder stiffness as well. Although no clear etiology exists regarding the development of shoulder stiffness in diabetics, it is believed to also be related to chronic inflammation and increased fibroblast activity.34 Theoretically, by acting through similar mechanisms, this implies that diabetes and 25D deficiency might synergistically increase the risk of developing postoperative shoulder stiffness. Future study should aim to identify the role of 25D in this pathogenesis and determine whether supplementation can decrease the risk of this outcome.
First, the PearlDiver database is less amenable to the study of patients on an individual level, and instead allows efficient analysis of larger groups. As such, ability to interpret and analyze patient-specific outcomes is likely inferior to that of chart review. Furthermore, data within PearlDiver is entirely driven by billing codes. As a result, entries may be subject to clerical error, miscategorization, or inconsistencies due to subjective interpretation of respective CPT or ICD codes. Similarly, given that the queried CPT and ICD codes were limited in detailing the specifics of a particular diagnosis or procedure, comparisons between severity of rotator cuff tear and different techniques for repair could not be accounted for in analysis. Next, some degree of selection bias was likely also present because not all patients had preoperative 25D levels drawn. This likely means providers ordered this laboratory test in a cohort at greater risk for 25D deficiency, which may have skewed the observed results. This could imply that a large portion of the 25D-sufficient cohort may represent a population receiving adequate repletion, thus strengthening the argument that supplementation may mitigate the outcomes observed in the deficient group. Last, although beyond the scope of this study, these results do not comment on postoperative function or other subjective, patient-reported outcomes.
Among the patients scheduled for an arthroscopic RCR between 2007 and 2016, 12.2% were found to be deficient in 25D in the 90 days preceding surgery. This was associated with a greater risk of postoperative stiffness requiring MUA and need for future RCR revision. Although the role of 25D in the development of postoperative complications is unclear at this time, this study suggests the possibility that preoperative repletion could have a role in mitigating adverse outcomes. Further study should aim to investigate what role 25D supplementation may have on markedly reducing postoperative complications after arthroscopic RCR.
Levels of evidence are described in the table of contents. In this article, references 3, 7, 12, 13, 14, and 27 are level II studies. References 1, 6, 10, 22, 23, and 29 are level III studies. References 4, 5, 11, 15, 17, 18, 20, 24, 25, 26, 28, 30, and 33 are level IV studies. References 2, 8, 9, 16, 19, 21, 31, 32, and 34 are level V studies.
1. Yamamoto A, Takagishi K, Osawa T: Prevalence and risk factors of a rotator cuff tear in the general population. J Shoulder Elb Surg 2010;19:116–120.
2. Sambandam SN, Khanna V, Gul A, Mounasamy V: Rotator cuff tears: An evidence based approach. World J Orthop 2015;6:902–918.
3. Milgrom C, Schaffler M, Gilbert S, Holsbeeck M: Rotator-cuff changes in asymptomatic adults. J Bone Joint Surg 1995;77:296–298.
4. Oh LS, Wolf BR, Hall MP, Levy BA, Marx RG: Indications for rotator cuff repair: A systematic review. Clin Orthop Relat Res 2007;455:52–63.
5. Sher J, Uribe J, Posada A, Murphy B, Zlatkin M: Abnormal findings on magnetic resonance images of asymptomatic shoulders. J Bone Joint Surg 1995;77:10–15.
6. Chung SW, Oh JH, Gong HS: Factors affecting rotator cuff healing after arthroscopic repair osteoporosis as one of the independent risk factors. Am J Sports Med 2008;39:2099–2107.
7. Sprague S, Petrisor B, Scott T, et al: What is the role of vitamin D supplementation in acute fracture patients? A systematic review and meta-analysis of the prevalence of hypovitaminosis D and supplementation efficacy. J Orthop Trauma 2015;30:1.
8. Watkins RR, Lemonovich TL, Salata RA: An update on the association of vitamin D deficiency with common infectious diseases. Can J Physiol Pharmacol 2015;93:363–368.
9. Oda Y, Tu C, Menendez A, Nguyen T, Bikle DD: Vitamin D and calcium regulation of epidermal wound healing. J Steroid Biochem Mol Biol 2017;1:379–385.
10. Hegde V, Arshi A, Wang C, et al: Associated with higher postoperative complication rates in total knee arthroplasty. Orthopedics 2018;201:1–7.
11. Hatfield DP, Sweeney KP, Lau J, Lichtenstein AH: Critical assessment of high-circulation print newspaper coverage of the Institute of Medicine report dietary reference intakes for calcium and vitamin D. Public Health Nutr 2014;17:1868–1876.
12. Charlson ME, Pompei P, Ales KL, Mackenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373–383.
13. Nurmi-Luthje I, Luthje P, Kataja M: Positive effects of a sufficient pre-fracture serum vitamin D level on the long-term survival of hip fracture patients in Finland: A minimum 11-year follow-up. Drugs Aging 2015;32:477–486.
14. Maier GS, Horas K, Seeger JB, Roth KE: Is there an association between periprosthetic joint infection and low vitamin D levels? Int Orthop 2014;38:1499–504.
15. Rebolledo B, Bernard J, Rodeo S: Extremity muscle strains and core muscle injuries at the national football league combine. J Arthrosc Relat Surg 2018;34:1280–1285.
16. Pascual-garrido C, Angeline ME, Ma R, et al: Low levels of vitamin D have a deleterious effect on the articular cartilage in a rat model. HSS J 2016;12:150–157.
17. Diebold G, Lam P, Walton J, Murrell GAC: Relationship between age and rotator cuff retear. J Bone Joint Surg 2017;99-A:1198–1205.
18. Galatz LM, Ball CM, Yamaguchi K: The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears. J Bone Joint Surg 2004;86-A:219–224.
19. Lipner J, Shen H, Cavinatto L, et al: In vivo evaluation of adipose-derived stromal cells delivered with a nanofiber scaffold for tendon-to-bone repair. Tissue Eng 2015;21:2766–2774.
20. Gupta AK, Hug K, Berkoff DJ, et al: Dermal tissue allograft for the repair of massive irreparable rotator cuff tears. Am J Sports Med 2012;40:141–147.
21. Angeline ME, Ma R, Pascual-Garrido C, et al: Effect of diet-induced vitamin D deficiency on rotator cuff healing in a rat model. Am J Sports Med 2014;42:27–34.
22. Drincic AT, Armas LAG, Van Diest EE, Heaney RP: Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity 2012;20:1444–1448.
23. Anderson JL, May HT, Horne BD, et al: Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 2010;106:963–968.
24. Jost BYB, Pfirrmann CWA, Gerber C: Clinical outcome after structural failure of rotator cuff repairs. J Bone Joint Surg 2000;82-A:304–314.
25. Jost B, Zumstein M, Pfirrmann CWA, Gerber C: Long-term outcome after structural failure of rotator cuff repairs. J Bone Joint Surg 2006;88-A:472–479.
26. Lädermann A, Denard PJ, Burkhart SS: Management of failed rotator cuff repair: A systematic review. Br J Sports Med 2016;16:1–6.
27. Russell RD, Knight JR, Mulligan E, Khazzam MS: Not correlate with patient function and pain. J Bone Joint Surg 2014;96:265–271.
28. Lafosse BL, Jost B, Reiland Y: Structural integrity and clinical outcomes after arthroscopic repair of isolated subscapularis tears. J Bone Joint Surg 2007;89:1184–1193.
29. Namdari S, Donegan RP, Chamberlain AM, Galatz LM, Yamaguchi K, Keener JD: Factors affecting outcome after structural failure of repaired rotator cuff tears. J Bone Joint Surg 2014;96:99–105.
30. Uppal HS: Frozen shoulder: A systematic review of therapeutic options. World J Orthop 2015;6:263.
31. Zerr P, Vollath S, Palumbo-Zerr K, et al: Vitamin D receptor regulates TGF-β signalling in systemic sclerosis. Ann Rheum Dis 2015;74:1–8.
32. Lee SA, Yang HW, Um JY, Shin JM, Park IH, Lee HM: Vitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway. Sci Rep 2017;7:1–12.
33. Zreik NH, Malik RA, Charalambous CP: Adhesive capsulitis of the shoulder and diabetes: A meta-analysis of prevalence. Muscles Ligaments Tendons J 2016;6:26–34.
Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons
34. Pons-Villanueva J, Escalada San Martín J: The stiff shoulder in diabetic patients. Int J Rheum Dis 2016;19:1226–1236.