Aging of muscle-tendon units influences common orthopaedic injuries and tendon-to-bone healing

Introduction: The underlying pathophysiology of many orthopaedic conditions including Achilles-tendon (AT) tears and rotator cuff (RC) tears that are thought to be age-related remains poorly understood. The overall aim of this study is to assess how age-related changes in muscle structure and function influence the occurrence of common orthopaedic injuries in older patients and how healing following the repair of these injuries may be impaired. Novel animal models such as non-human primates may allow the assessment of the natural aging process in an animal similar to human anatomy and extremity function.;Methods: Age-related changes in passive biomechanical properties of the gastrocnemius Achilles-tendon (GC-AT) muscle tendon unit were assessed in young and middle aged F344xBN rats from the National Institute on Aging (NIA) using Fung's quasilinear viscoelastic model. The influence of aging on active muscle-function and structure of the supraspinatus muscle was assessed by placing young and old F344xBN rats on a linear translating scale attached to a force transducer followed by stimulating of the suprascapular nerve. The effect of aging on tendon-to-bone healing was assessed in an established rat model following surgical transection of the supraspinatus tendon and acute by analyzing the biomechanical load-to-failure, load-relaxation, and histologic collagen organization. Naturally occurring bony and muscular degeneration in non-human primates was assessed using functionality testing, CT-scan, and histologic analysis to determine if age-related degeneration in non-human primates is consistent with aging human patients.;Results: The GC-AT stiffness increased 28% at peak tensions in middle-aged rats (2.7 +/- 0.2 N/mm) compared to young rats (1.9 +/- 0.2 N/mm; p=0.036) and the product of elastic parameters (A*B), was significantly increased by 50% in middle-aged rats (p=0.014). The supraspinatus muscle of old animals revealed significantly decreased peak tetanic muscle force at 0.5N and 0.7N pre-load tension (p<0.05). The age of the animal accounted for 20.9% of variance and significantly influenced muscle force (p=0.026). There was decreased MyoD and Myf5 old animals (p<0.05). Peak failure load of the supraspinatus tendon repair was significantly higher in young animals (86% of age-matched uninjured controls) compared to old animals (65% of age-matched uninjured controls, p<0.01) and old animals had decreased collagen fiber organization and altered structure compared to age-matched controls (49.8 +/- 3.1 gray scales, p<0.05) 8 weeks after repair. Elderly non-human primates had glenoid retroversion, decreased joint space, walked slower and spent less time climbing and hanging than middle-aged vervets (p<0.05). Supraspinatus muscles of elderly animals were less dense (p=0.001), had decreased fiber cross-sectional area (p<0.001), but similar amounts of nuclear material (p=0.085).;Discussion and Conclusion: The findings of this work suggest that normal aging influences passive biomechanical properties, muscle histologic structure, and decreases muscle functionality. Normal aging significantly influenced contractile strength of the supraspinatus muscle and led to decreased expression of muscle regulatory factors. High pre-load tensions led to a significant decrease in force production in both, middle-aged and old animals. Increased age was associated with diminished tendon-to-bone healing after rotator cuff injury and repair with significantly decreased failure strength and collagen fiber organization at the tendon-to-bone junction in old animals. This study implicates that animal age may need to be considered in future studies of rotator cuff repair in animal models. Non-human primates were found to undergo age-related functional, radiographic and histological changes of the shoulder and may qualify as an animal model for selected translational research of shoulder osteoarthritis.