Histological Evidence of Muscle Degeneration in Advanced Human Rotator Cuff Disease

Abstract

Background: Cellular remodeling in rotator cuff muscles following a massive rotator cuff tear is poorly understood. The aim of the current study was to provide histological evidence to elucidate the mode of muscle loss in advanced human rotator cuff disease and to assess tissue-level changes in relation to findings on noninvasive imaging. Methods: Rotator cuff muscle biopsy samples were taken from the scapular fossae from 23 consecutive patients undergoing reverse total shoulder arthroplasty in order to evaluate muscle composition in severe rotator cuff disease. Markers of vascularity; inflammation; fat distribution; and muscle atrophy, degeneration, and regeneration were quantified. Results: The samples primarily consisted of dense, organized connective tissue (48.2% ± 19.1%) and disorganized, loose connective tissue (36.9% ± 15.9%), with substantially smaller fractions of muscle (10.4% ± 22.0%) and fat (6.5% ± 11.6%). Only 25.8% of the biopsy pool contained any muscle fibers at all. Increased inflammatory cell counts (111.3 ± 81.5 macrophages/mm2) and increased vascularization (66.6 ± 38.0 vessels/mm2) were observed across biopsies. Muscle fiber degeneration was observed in 90.0% ± 15.6% of observable muscle fascicles, and the percentage of centrally nucleated muscle fibers was pathologically elevated (11.3% ± 6.3%). Fat accumulation was noted in both perifascicular (60.7% ± 41.4%) and intrafascicular (42.2% ± 33.6%) spaces, with evidence that lipid may replace contractile elements without altering muscle organization. Conclusions: Dramatic degeneration and inflammation of the rotator cuff muscles are characteristics of the most chronic and severe rotator cuff disease states, suggesting that muscle loss is more complicated than, and distinct from, the simple atrophy found in less severe cases. Clinical Relevance: In order to address degenerative muscle loss, alternative therapeutic approaches directed at muscle regeneration must be considered if muscle function is to be restored in late-stage rotator cuff disease.

The role of mechanobiology in progression of rotator cuff muscle atrophy and degeneration

“…Increased calcium may then increase calcium‐sensitive calpain activity, which along with their role in contractile protein turnover in atrophy are also implicated in cellular apoptosis and necrosis . Together with the direct overload/shear injury, these indirect mediators of protein turnover and cell death (as well as the hypothesized increase in oxidative stress and a protease‐rich inflammatory environment discussed below) likely explain the recently described muscle damage and degeneration of muscle fibers found in advanced rotator cuff disease (Fig. , Damage and Degeneration ).…”

“…Notably, while SCs are required for muscle regeneration, they are dispensable in the context of fiber hypertrophy . Given the muscle degeneration present in advanced RC disease, understanding the fate of SCs in RC disease is paramount to understanding why muscle loss is generally irreversible after RC tear.…”

“…, ECM Stiffening ). In advanced RC disease, muscle degeneration and reduced muscle fiber numbers driven by these mechanobiological changes appear to be the prominent mode of muscle loss (Fig. , Degenerative Stage ).…”

Lumbar multifidus muscle degenerates in individuals with chronic degenerative lumbar spine pathology

“…ImageJ (http://imagej.nih.gov/ij) was used to automatically quantify the relative fractions of muscle, adipose, loose collagen, and dense collagen in Trichrome‐stained biopsy . Briefly, tissue type was determined by manual intensity thresholding of the red (muscle), green (loose collagen), and blue (dense collage) channels of whole‐section RGB images, while adipose tissue was identified morphologically and traced . Inflammatory cells were quantified by calculating the number of CD68+ macrophages (Novocastra, CD68‐L‐CE) per square millimeter of tissue in the whole biopsy cross section .…”

The MRL/MpJ Mouse Strain Is Not Protected From Muscle Atrophy and Weakness After Rotator Cuff Tear

“…Although patients generally experience pain relief after rotator cuff repair, many remain unsatisfied with persistent muscle weakness . The strength deficits that patients experience are due to the pathological changes that occur in torn rotator cuff muscles, including fibrosis, muscle fiber atrophy, and fat accumulation in and around muscle fibers . These combined pathological changes, often referred to as fatty degeneration or myosteatosis, limit successful surgical repair and prevent the restoration of strength through postoperative rehabilitation .…”