Clinical and animal studies have shown that following chronic rotator cuff tendon tears, the muscle undergoes degeneration and profound architectural changes, including fatty infiltration and shortened muscle fibers, with an accompanying loss of contractility and elasticity1-6. These changes have been assumed to be irreversible and can lead to persistent disability despite technically successful tendon repair. Hence, there is an urgent need for reliable interventions to impede, and potentially reverse, these pathological changes after rotator cuff tears.
In the current rabbit study, Gerber et al. investigated the capacity of anabolic steroid treatment to diminish muscle atrophy and fatty infiltration following supraspinatus tendon release from its osseous insertion. To prevent spontaneous healing, the tendon-bone chip complex was wrapped in a Penrose drain. The authors examined three experimental groups: (I) untreated muscle, (II) weekly systemic and local injections of nandrolone decanoate (into the quadriceps femoris and supraspinatus muscles, respectively), and (III) weekly systemic administration of nandrolone decanoate during six weeks of muscle retraction.
Encouraging six-week results, suggestive of an apparent protective effect of nandrolone decanoate administration, are presented. Significantly decreased retraction of the musculotendinous unit in the steroid-treated groups was observed in comparison with the untreated controls. Work by the muscle (measured intraoperatively during one standardized contraction with supramaximal stimulation) was similar prior to and following tendon release for all groups. Muscle atrophy (reduction in nominal cross-sectional area measured by computed tomography) was greater for untreated rabbits in comparison with those that received systemic steroid treatment. Fatty infiltration, measured via histological analysis, was apparent only in the untreated rabbits. Finally, a strong statistical trend toward decreased muscle fiber diameter was reported for the untreated group, while similar fiber diameters were found prior to and following tendon release for both treatment groups.
This investigation is noteworthy as it is among the first reports (along with a prior study utilizing continuous elongation of the retracted myotendinous unit, performed by the same research group7) of inhibition of fatty infiltration following myotendinous retraction. The authors’ stated rationale for selecting nandrolone decanoate derives from literature demonstrating the efficacy of this androgen for the treatment of muscle wasting and osteoporosis. The present study is also intriguing, given the reliability of the rabbit rotator cuff model to produce rotator cuff muscle degeneration (following tendon release), which is similar to that seen in humans8-10.
The authors addressed well the numerous study limitations such as the reduced extent of fatty infiltration in rabbits compared with that in humans. Neither animal activity levels nor the potential side effects of the steroid administration were studied; a concern is that the investigators reported that two animals from the systemic treatment group developed a postoperative infection at the site of surgery and were excluded from the study.
An additional concern is that of potential detrimental effects of the steroid administration on tendon biology and function. Clearly, while healthy muscle is beneficial to the restoration of a functional muscle-tendon-bone unit, there is a possibility that the perceived benefits conferred to the retracted muscle by steroid treatment may, to some extent, be offset by compromised tendon healing. In particular, a recent rabbit study11 has noted impairment of rotator cuff tendon healing due to nandrolone decanoate administration following acute tendon injury and repair (which, one should note, likely does not mimic the chronicity of the tendon tear of the present study).
The data presented by Gerber et al. constitute novel, important findings that indicate a potential therapeutic role for nandrolone decanoate in the treatment of muscle pathology following chronic rotator cuff tears. However, further study of dose-response characteristics and drug delivery approaches are warranted in order to enhance the potential of this approach for clinical translation. In future studies, it may also be of interest to determine whether the currently reported findings are species-specific, particularly given the recent development of rat models of rotator cuff muscle degeneration and fatty infiltration following tendon tears12,13.