Glycation and Rotator Cuff Degeneration
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.
Advanced glycation end products (AGEs) form through a nonenzymatic process by which reducing sugars undergo Maillard rearrangement with amino acids. During rearrangement, the carbonyl group of the sugar reacts with the amino group of the amino acid, producing N-substituted glycosylamine and water.
During cooking, glycation occurs at 140° to 165° C (280° to 330° F), resulting in the browning of foods such as bread and French fries. This nonenzymatic reaction also occurs at human body temperature over decades. AGE formation can decrease the viscoelasticity and tensile strength of human tissue, resulting in increased mechanical stiffness that affects bone, ligaments, cartilage, and menisci. In cartilage, the excessive accumulation of AGEs leads to a more brittle matrix that is susceptible to fatigue and failure. AGEs also contribute to the etiology of several diabetic complications, including adhesive capsulitis of the shoulder.
Rotator cuff degeneration and tears become more common with age. Accumulated mechanical loads and anatomic variation play a large role. The role of AGEs in rotator cuff degeneration and tears has been suspected, but the exact mechanisms remain in question. Investigators recently showed that AGEs have detrimental effects on human rotator cuff-derived cells in vitro and on intact rat infraspinatus tendons ex vivo.1
In Vitro Findings
Rotator cuff-derived cells were obtained from 12 torn cuff edges during supraspinatus tendon repairs in patients with an average age 64.8 years. The cells were cultured in (1) regular medium with 500 μg/mL AGEs (high-AGE group), (2) regular medium with 100 μg/mL AGEs (low-AGE group), and (3) regular medium alone (control group). Cell viability was significantly suppressed in the high-AGE group relative to the control group. Vascular endothelial growth factor secretion was significantly greater in the high- and low-AGE groups than in the control group. Immunofluorescence stain demonstrated enhancement of hypoxia-inducible factor-1α, reactive oxygen species expressions, and cell apoptosis in the high- and low-AGE groups compared with the control group.
Ex Vivo Findings
Four upper limbs with intact rotator cuff tendons were harvested from 10-week old rats and cultured in regular medium or regular medium with 500 μg/mL AGEs. Mechanical testing showed significantly higher tensile strength in the control group than in the AGE group.
These results beg the question as to whether reduction of AGEs might delay or prevent rotator cuff senescence-related degeneration.
Reference
- Mifune Y, Inui A, Muto T, Nishimoto H, Kataoka T, Kurosawa T, Yamaura K, Mukohara S, Niikura T, Kokubu T, Kuroda R. Influence of advanced glycation end products on rotator cuff. J Shoulder Elbow Surg. 2019 Aug;28(8):1490-1496. doi: 10.1016/j.jse.2019.01.022. Epub 2019 Apr 10. PMID: 30981546
JBJS 100: Arthroscopic Supraspinatus Repair and OCD of the Talus
Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.
Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.
Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.
We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more:
Arthroscopic Repair of Full-Thickness Tears of the Supraspinatus
P Boileau, N Brassart, D J Watkinson, M. Carles, A M Hatzidakis, S G Krishnan: JBJS, 2005 June; 87 (6): 1229
This evaluation of the arthroscopic tension-band suture technique demonstrated that arthroscopic repair of an isolated supraspinatus detachment delivers good to excellent functional and tendon-healing results—and that the absence of tendon healing does not necessarily compromise pain relief and patient satisfaction.
Transchondral Fractures (Osteochondritis Dissecans) of the Talus
A L Berndt and M Harty: JBJS, 1959 Sept; 41 (6): 988
Berndt and Harty’s elegant clinical and anatomic study included a four-stage radiological classification scheme for traumatic talar lesions that still provides a valid foundation for decision-making with regard to operative or nonoperative treatment.
Rotator Cuff Repair Integrity is Important
Among the estimated 250,000 surgical rotator cuff repairs performed annually in the US, a growing percentage are being done on younger patients to prevent tear propagation and tissue degeneration. But how durable are the outcomes of those procedures?
In the August 16, 2017 issue of The Journal, Collin et al. report the 10-plus-year results of surgical repair of isolated supraspinatus tears. In this rather large cohort (288 patients with an average age of 57 years evaluated clinically, with 210 of those also evaluated with MRI), complications were not uncommon at 10.4%. On a more positive note, the average Constant score improved from about 52 before surgery to 78 at 10 years after surgery. The 10-year Constant scores correlated with MRI-determined repair integrity but were inversely associated with preoperative fatty infiltration of the supraspinatus.
These findings imply that careful patient selection based on both clinical factors and imaging studies is critically important in identifying patients with the best chance for good, long-term functional results. The presence of a cuff tear, particularly a large chronic one, is not always a surgical indication for repair. For example, Collin et al. found that the rate of retears was significantly higher in patients >65 years old than in those who were younger.
As is frequently the case in orthopaedics, we need additional prospective research with long-term functional and anatomic repair outcomes to better understand which patients are most likely to benefit from early repair of an isolated supraspinatus tear.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
JBJS Editor’s Choice—Better Prognoses for Aging Shoulders
We have long been taught that among people fortunate enough to survive into their 80s, 70% to 80% will have a torn rotator cuff— that it’s part of life just like degenerating lumbar discs. These figures were based on cadaveric studies, a study design that comes with a whole spectrum of issues around detection and selection bias.
However, in the January 21, 2015 issue of The Journal, Keener et al. provide us with much more reliable data regarding the progression of asymptomatic rotator cuff tears in a population of 224 subjects. The cohort included people with an asymptomatic rotator cuff tear in one shoulder and pain due to rotator cuff disease in the contralateral shoulder. As determined by ultrasound, 118 had full thickness tears, and 56 had partial thickness tears. Importantly, the study also included 50 controls with no ultrasound evidence of rotator cuff tear in one shoulder and painful cuff disease in the contralateral shoulder. Researchers followed the cohort for a mean of more than 5 years.
The good news is that neither age nor gender was found to be related to the risk of tear enlargement. Tear enlargement occurred in 49% of all the shoulders at a median of 2.8 years, and the risk of enlargement was 4.2 times and 1.5 times higher in subjects with full thickness tears, relative to controls and those with partial thickness tears, respectively. Both tear type and tear enlargement were associated with the onset of “new pain,” further assuring us that following our rotator cuff patients clinically is a sound and cost-efficient strategy.
What I found most interesting is that progressive muscular degeneration in the supraspinatus muscle belly, as detected by ultrasound, was associated with tear enlargement. This strengthens our recommendations—to our patients and ourselves—to engage in rotator cuff strengthening as a part of overall resistance training for lifelong maintenance of function and preservation of muscle mass.
So…. to protect our cuff integrity and for innumerable other reasons, back to the gym we go.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
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