This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
Adhesive capsulitis (AC), colloquially known as frozen shoulder, is associated with conditions such as diabetes, cardiopulmonary disorders, stroke, Parkinsonism, and injury. However, many cases are idiopathic. Given the inflammatory nature of the condition, clinicians often administer intra-articular steroid injections in recalcitrant cases where physical therapy alone is too painful or nonproductive. Some cases, particularly in patients with diabetes, may require manipulation, brisement, or arthroscopic release.
To better understand the genetic basis of AC, investigators obtained punch tissue samples from the middle glenohumeral ligament and rotator cuff interval from AC patients undergoing arthroscopic release surgery (mean age of 53 years) and from a comparative group of patients undergoing arthroscopic surgery for shoulder instability (mean age of 24 years).1 The researchers performed RNA sequencing-based transcriptomics on the samples and, after identifying differentially expressed genes, they applied real-time reverse transcription polymerase chain reaction (RT-PCR) to obtain more detailed genetic data.
A total of 545 genes were differentially expressed. The top 50 were associated with extracellular matrix remodeling. Patient age and sex did not have a major influence on gene expression. The genes marked by overexpression (not necessarily protein expression) were genes for matrix metallopeptidase 13 and platelet-derived growth factor subunit B. Other suspects included the gene for metalloprotease 9 and COL18A1.
In the discussion, the authors comment on the association between AC and protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK). FAK activation is particularly sensitive to fibronectin and other integrins. Activated FAK also controls cell migration and focal adhesion assembly. These interesting associations may also shine light onto the etiology of other musculoskeletal diseases.
- Kamal N, McGee SL, Eng K, Brown G, Beattie S, Collier F, Gill S, Page RS.
Transcriptomic analysis of adhesive capsulitis of the shoulder. J Orthop Res. 2020 Oct;38(10):2280-2289. doi: 10.1002/jor.24686. Epub 2020 Apr 17. PMID: 32270543
You don’t need a PhD in molecular pathophysiology to appreciate the fact that inflammation is a complex biological process. And you don’t need to be a shoulder subspecialist in orthopaedics to realize that symptoms of frozen shoulder (aka idiopathic adhesive capsulitis, or IAC) are common presenting complaints among middle-aged patients, especially women. In the May 6, 2020 issue of The Journal of Bone& Joint Surgery, a retrospective case-control study by Park et al. reveals some new insights about the association between adhesive capsulitis and inflammation, with a specific focus on the inflammatory marker high-sensitivity C-reactive protein (hsCRP).
The authors analyzed blood-sample results from 202 patients diagnosed with IAC and 606 age- and sex-matched controls. In addition to hsCRP, Park et al. investigated HbA1c, cholesterol, triglycerides, inflammatory lipoproteins, thyroid-stimulating hormone, the ratio of triglycerides to HDL (TG/HDL), BMI, and diabetes.
Park et al. determine that a blood level of hsCRP >1.0 mg/L is an independent marker for IAC. They also conclude that the relationship between hsCRP and other findings in this study confirms the associations between IAC and previously cited risk factors of diabetes and dyslipidemia. Based on the fasting-glucose and HbA1c findings in this study, the authors additionally conclude that hyperglycemia and insulin resistance—frequent precursors to type-2 diabetes—are also strong risk factors for IAC.
Taken together, the results suggest the presence of an additive inflammatory effect among medical comorbidities in patients with IAC. But in his Commentary on this study, Michael Khazzam, MD says that these results alone cannot be used in clinical practice to counsel patients being treated for IAC. Ideally, he says, these findings could help inform future work that might provide a reliable method to predict, early in the disease process, the severity of IAC and the expected timetable for complete resolution of symptoms.
As new advances in medical technology lead to treatments for injuries and diseases, one concept that has emerged is the importance of genetic predisposition to health, sickness, and functional recovery after trauma. Indeed, as the future of medicine will most likely concentrate on health as opposed to health care, understanding the genetic predisposition to medical conditions will become paramount. In the February 2016 issue of JBJS Reviews, Prodromidis and Charalambous focus on the role of genetics in the development and treatment of frozen shoulder. This article represents a careful analysis of the relationship between genetics and disease.
Frozen shoulder, or adhesive capsulitis, is a common condition that leads to functional loss and impairment of activities of daily living. However, despite the prevalence of this condition, its pathogenesis is not fully understood. Prodromidis and Charalambous performed a systematic review and meta-analysis in order to assess the evidence that suggests a genetic link to frozen shoulder.
The investigators performed a literature search of MEDLINE, EMBASE, and CINAHL using relevant keywords and found an initial 5506 studies. After further screening, seven studies were analyzed. The results were fascinating. One study, involving 1828 twin pairs, showed an 11.6% prevalence and demonstrated a heritability of 42% for frozen shoulder after adjusting for age. In a second study, involving 273 patients, 20% of patients with frozen shoulder had a positive family history involving a first-degree relative. A third study, involving 87 patients, showed that 29% of patients with frozen shoulder had a first-degree relative with this condition.
Two further studies evaluated racial predilection. One of these studies (50 patients) showed a substantially higher number of white patients with frozen shoulder than black patients with the condition. The other study (87 patients) showed that being born or having parents or grandparents who were born in the British Isles were risk factors for this condition.
Finally, four immunological studies investigated HLA-B27 as a risk factor for frozen shoulder. A meta-analysis of two of these studies with clearly defined controls showed higher rates of HLA-B27 positivity in patients with this condition as compared with controls (p < 0.001).
Thomas Einhorn, Editor
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from Level I and II studies cited in the October 21, 2015 Specialty Update on shoulder and elbow surgery:
–A prospective evaluation of 224 subjects with asymptomatic rotator cuff tears followed annually for an average of five years found that the risk of tear enlargement and muscle degeneration was greater in full-thickness tears, and that pain and supraspinatus muscle degeneration were associated with tear enlargement.
–The authors of a randomized trial comparing physical therapy and primary surgical repair for initial management of degenerative rotator cuff tears concluded that the effects of surgery were not profound enough to justify surgical management for patients who present initially with painful degenerative cuff tears.
–A randomized trial comparing clinical outcomes in 58 patients with a rotator cuff tear and symptomatic acromioclavicular joint arthritis found no differences in function or pain scores between those who underwent cuff repair + distal clavicle resection and those who underwent cuff repair alone.1
–After two years of follow-up, no differences in functional outcomes or rate or quality of postoperative tendon healing were found in a randomized trial comparing patients who received platelet-rich plasma following surgical cuff repair and those who did not.2
–In a three-way randomized trial comparing physical therapy, acromioplasty + physical therapy, and cuff repair + acromioplasty + physical therapy for treating symptomatic, nontraumatic supraspinatus tendon tears in patients older than 55, there were no between-group differences in the mean Constant score one year after treatment.3
–A randomized trial comparing treatments for calcific tendinitis found that ultrasound-guided needling plus a subacromial corticosteroid injection resulted in better functional scores and larger decreases in calcium-deposit size than extracorporeal shock wave therapy.4
–A randomized trial of 196 patients with recurrent traumatic anterior shoulder instability found no significant differences in WOSI and ASES scores or range of motion between groups that underwent open or arthroscopic stabilization procedures.
–A randomized study comparing the effectiveness of immobilization in abduction (15°) and external rotation (10°) versus adduction and internal rotation after primary anterior shoulder dislocation found that after two years, only 3.9% of patients in the abduction/external-rotation group had repeat instability, compared to 33.3% in the adduction/internal-rotation group.5 A separate randomized trial found no significant difference in instability recurrence after one year between a group immobilized in internal rotation (sling) and a group immobilized in adduction and external rotation (brace).6
–A randomized trial of 250 patients (mean age of 65 years) with displaced surgical neck fractures of the proximal humerus compared surgical treatment (internal fixation or hemiarthroplasty) with conservative treatment. Finding no statistically or clinically significant difference in outcomes, the authors concluded that these results do not support the recent trend toward surgical management for proximal humeral fractures.7
–A randomized trial comparing reverse shoulder arthroplasty with hemiarthroplasty for acute proximal humeral fractures found that after two years of follow-up, reverse arthroplasty yielded better functional scores, better active elevation, and fewer complications than hemiarthroplasty.8
–A randomized trial comparing the use of concentric and eccentric glenospheres in reverse shoulder arthroplasty revealed no differences in scapular notching rates or clinical outcomes at a minimum follow-up of two years.
–A systematic review comparing radiographic and clinical survivorship of all-polyethylene versus metal-backed glenoid components used in total shoulder arthroplasty found that all-poly glenoids had a higher rate of radiolucencies and radiographic loosening but a much lower rate of revision after a mean follow-up of 5.8 years.
–A retrospective review found that arthroscopic biopsy was much more accurate than fluoroscopically guided fluid aspiration in diagnosing periprosthetic shoulder infections caused by Propionibacterium acnes.
–In a randomized trial of 76 workers’-comp patients with a displaced midshaft clavicular fracture, those receiving surgical management had faster time to union and return to work and better Constant scores than those managed conservatively.9
–Two studies compared plate fixation with intramedullary fixation for stabilizing clavicular fractures. One that randomized 59 patients found no differences in functional outcomes or time to healing. The other, which randomized 120 patients, found no between-group differences in DASH or Constant-Murley scores, but shoulder function improved more quickly in the plate-fixation group.
–A study that compared standard arthroscopic capsular release with capsular release extending to the posterior capsule for treating frozen shoulder found no difference in postoperative clinical or range-of-motion outcomes between the two groups.10
–A randomized trial comparing regional analgesia to local anesthetic injections in patients undergoing elbow arthroscopy found no differences in pain, oral analgesic use, or patient satisfaction within 48 hours after surgery.11
–A randomized trial comparing eccentric and concentric resistance exercises for the treatment of chronic lateral epicondylitis found that the eccentric-exercise group had faster pain regression, lower pain scores at 12 months, and greater strength increases.12
- Park YB, Koh KH, Shon MS, Park YE, Yoo JC. Arthroscopic distal clavicle resection in symptomatic acromioclavicular joint arthritis combined with rotator cuff tear: a prospective randomized trial. Am J Sports Med. 2015 Apr;43(4):985-90.Epub 2015 Jan 12.
- Malavolta EA, Gracitelli ME, Ferreira Neto AA, Assunção JH, Bordalo-RodriguesM, de Camargo OP. Platelet-rich plasma in rotator cuff repair: a prospective randomized study. Am J Sports Med. 2014 Oct;42(10):2446-54. Epub 2014 Aug 1.
- Kukkonen J, Joukainen A, Lehtinen J, Mattila KT, Tuominen EK, Kauko T, Aärimaa V.Treatment of non-traumatic rotator cuff tears: a randomised controlled trial with one-year clinical results. Bone Joint J. 2014 Jan;96-B(1):75-81.
- Kim YS, Lee HJ, Kim YV, Kong CG. Which method is more effective in treatment of calcific tendinitis in the shoulder? Prospective randomized comparison between ultrasound-guided needling and extracorporeal shock wave therapy. J Shoulder Elbow Surg. 2014 Nov;23(11):1640-6. Epub 2014 Sep 12.
- Heidari K, Asadollahi S, Vafaee R, Barfehei A, Kamalifar H, Chaboksavar ZA,Sabbaghi M. Immobilization in external rotation combined with abduction reduces the risk of recurrence after primary anterior shoulder dislocation. J Shoulder Elbow Surg. 2014 Jun;23(6):759-66. Epub 2014 Apr 13.
- Whelan DB, Litchfield R, Wambolt E, Dainty KN; Joint Orthopaedic Initiative for National Trials of the Shoulder (JOINTS).External rotation immobilization for primary shoulder dislocation: a randomized controlled trial. Clin Orthop Relat Res. 2014 Aug;472(8):2380-6.
- Rangan A, Handoll H, Brealey S, Jefferson L, Keding A, Martin BC, Goodchild L,Chuang LH, Hewitt C, Torgerson D; PROFHER Trial Collaborators. Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial. JAMA. 2015 Mar 10;313(10):1037-47.
- Sebastiá-Forcada E, Cebrián-Gómez R, Lizaur-Utrilla A, Gil-Guillén V. Reverse shoulder arthroplasty versus hemiarthroplasty for acute proximal humeral fractures. A blinded, randomized, controlled, prospective study. J Shoulder Elbow Surg. 2014Oct;23(10):1419-26. Epub 2014 Jul 30
- Melean PA, Zuniga A, Marsalli M, Fritis NA, Cook ER, Zilleruelo M, Alvarez C.Surgical treatment of displaced middle-third clavicular fractures: a prospective, randomized trial in a working compensation population. J Shoulder Elbow Surg.2015 Apr;24(4):587-92. Epub 2015 Jan 22.
- Kim YS, Lee HJ, Park IJ. Clinical outcomes do not support arthroscopic posterior capsular release in addition to anterior release for shoulder stiffness: a randomized controlled study. Am J Sports Med. 2014 May;42(5):1143-9. Epub 2014 Feb 28.
- Wada T, Yamauchi M, Oki G, Sonoda T, Yamakage M, Yamashita T. Efficacy of axillary nerve block in elbow arthroscopic surgery: a randomized trial. J Shoulder Elbow Surg. 2014 Mar;23(3):291-6. Epub 2014 Jan 15.
- Peterson M, Butler S, Eriksson M, Svärdsudd K.A randomized controlled trial of eccentric vs. concentric graded exercise in chronic tennis elbow (lateral elbow tendinopathy). Clin Rehabil. 2014 Sep;28(9):862-72. Epub 2014 Mar 14.