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Commentary and Perspective   |    
Important Preliminary Findings on the Potential Role for Nandrolone Decanoate in the Treatment of Chronic Rotator Cuff Tears.Commentary on an article by C. Gerber, MD, FRCS, et al.: “Anabolic Steroids Reduce Muscle Damage Caused by Rotator Cuff Tendon Release in an Experimental Study in Rabbits”
Vincent M. Wang, PhD
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The author received no payments or services, either directly or indirectly (i.e., via his institution), from a third party in support of any aspect of this work. Neither the author nor his institution has had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, the author has not had any other relationships, or engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 Dec 07;93(23):e144 1-2. doi: 10.2106/JBJS.K.01213
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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.
Barton  ER;  Gimbel  JA;  Williams  GR;  Soslowsky  LJ. Rat supraspinatus muscle atrophy after tendon detachment. J Orthop Res.  2005;23:259-65.[CrossRef][PubMed]
 
Coleman  SH;  Fealy  S;  Ehteshami  JR;  MacGillivray  JD;  Altchek  DW;  Warren  RF;  Turner  AS. Chronic rotator cuff injury and repair model in sheep. J Bone Joint Surg Am.  2003;85:2391-402.[PubMed]
 
Fuchs  B;  Weishaupt  D;  Zanetti  M;  Hodler  J;  Gerber  C. Fatty degeneration of the muscles of the rotator cuff: assessment by computed tomography versus magnetic resonance imaging. J Shoulder Elbow Surg.  1999;8:599-605.[CrossRef][PubMed]
 
Gladstone  JN;  Bishop  JY;  Lo  IK;  Flatow  EL. Fatty infiltration and atrophy of the rotator cuff do not improve after rotator cuff repair and correlate with poor functional outcome. Am J Sports Med.  2007;35:719-28.  Epub 2007 Mar 2.[CrossRef][PubMed]
 
Goutallier  D;  Postel  JM;  Bernageau  J;  Lavau  L;  Voisin  MC. Fatty muscle degeneration in cuff ruptures. Pre- and postoperative evaluation by CT scan. Clin Orthop Relat Res.  1994;304:78-83.[PubMed]
 
Rowshan  K;  Hadley  S;  Pham  K;  Caiozzo  V;  Lee  TQ;  Gupta  R. Development of fatty atrophy after neurologic and rotator cuff injuries in an animal model of rotator cuff pathology. J Bone Joint Surg Am.  2010;92:2270-8.[CrossRef][PubMed]
 
Gerber  C;  Meyer  DC;  Frey  E;  von Rechenberg  B;  Hoppeler  H;  Frigg  R;  Jost  B;  Zumstein  MA. Neer Award 2007: Reversion of structural muscle changes caused by chronic rotator cuff tears using continuous musculotendinous traction. An experimental study in sheep. J Shoulder Elbow Surg.  2009;18:163-71.  Epub 2008 Dec 18.[CrossRef][PubMed]
 
Björkenheim  JM. Structure and function of the rabbit's supraspinatus muscle after resection of its tendon. Acta Orthop Scand.  1989;60:461-3.[CrossRef][PubMed]
 
Fabiś  J;  Kordek  P;  Bogucki  A;  Mazanowska-Gajdowicz  J. Function of the rabbit supraspinatus muscle after large detachment of its tendon: 6-week, 3-month, and 6-month observation. J Shoulder Elbow Surg.  2000;9:211-6.[CrossRef][PubMed]
 
Rubino  LJ;  Stills  HF  Jr;  Sprott  DC;  Crosby  LA. Fatty infiltration of the torn rotator cuff worsens over time in a rabbit model. Arthroscopy.  2007;23:717-22.[CrossRef][PubMed]
 
Papaspiliopoulos  A;  Papaparaskeva  K;  Papadopoulou  E;  Feroussis  J;  Papalois  A;  Zoubos  A. The effect of local use of nandrolone decanoate on rotator cuff repair in rabbits. J Invest Surg.  2010;23:204-7.[CrossRef][PubMed]
 
Kim  HM;  Galatz  LM;  Lim  C;  Havlioglu  N;  Thomopoulos  S. The effect of tear size and nerve injury on rotator cuff muscle fatty degeneration in a rodent animal model. J Shoulder Elbow Surg.   2011 Aug 9. [Epub ahead of print]
 
Liu  X;  Manzano  G;  Kim  HT;  Feeley  BT. A rat model of massive rotator cuff tears. J Orthop Res.  2011;29:588-95.  Epub 2010 Oct 14.[CrossRef][PubMed]
 

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References

Barton  ER;  Gimbel  JA;  Williams  GR;  Soslowsky  LJ. Rat supraspinatus muscle atrophy after tendon detachment. J Orthop Res.  2005;23:259-65.[CrossRef][PubMed]
 
Coleman  SH;  Fealy  S;  Ehteshami  JR;  MacGillivray  JD;  Altchek  DW;  Warren  RF;  Turner  AS. Chronic rotator cuff injury and repair model in sheep. J Bone Joint Surg Am.  2003;85:2391-402.[PubMed]
 
Fuchs  B;  Weishaupt  D;  Zanetti  M;  Hodler  J;  Gerber  C. Fatty degeneration of the muscles of the rotator cuff: assessment by computed tomography versus magnetic resonance imaging. J Shoulder Elbow Surg.  1999;8:599-605.[CrossRef][PubMed]
 
Gladstone  JN;  Bishop  JY;  Lo  IK;  Flatow  EL. Fatty infiltration and atrophy of the rotator cuff do not improve after rotator cuff repair and correlate with poor functional outcome. Am J Sports Med.  2007;35:719-28.  Epub 2007 Mar 2.[CrossRef][PubMed]
 
Goutallier  D;  Postel  JM;  Bernageau  J;  Lavau  L;  Voisin  MC. Fatty muscle degeneration in cuff ruptures. Pre- and postoperative evaluation by CT scan. Clin Orthop Relat Res.  1994;304:78-83.[PubMed]
 
Rowshan  K;  Hadley  S;  Pham  K;  Caiozzo  V;  Lee  TQ;  Gupta  R. Development of fatty atrophy after neurologic and rotator cuff injuries in an animal model of rotator cuff pathology. J Bone Joint Surg Am.  2010;92:2270-8.[CrossRef][PubMed]
 
Gerber  C;  Meyer  DC;  Frey  E;  von Rechenberg  B;  Hoppeler  H;  Frigg  R;  Jost  B;  Zumstein  MA. Neer Award 2007: Reversion of structural muscle changes caused by chronic rotator cuff tears using continuous musculotendinous traction. An experimental study in sheep. J Shoulder Elbow Surg.  2009;18:163-71.  Epub 2008 Dec 18.[CrossRef][PubMed]
 
Björkenheim  JM. Structure and function of the rabbit's supraspinatus muscle after resection of its tendon. Acta Orthop Scand.  1989;60:461-3.[CrossRef][PubMed]
 
Fabiś  J;  Kordek  P;  Bogucki  A;  Mazanowska-Gajdowicz  J. Function of the rabbit supraspinatus muscle after large detachment of its tendon: 6-week, 3-month, and 6-month observation. J Shoulder Elbow Surg.  2000;9:211-6.[CrossRef][PubMed]
 
Rubino  LJ;  Stills  HF  Jr;  Sprott  DC;  Crosby  LA. Fatty infiltration of the torn rotator cuff worsens over time in a rabbit model. Arthroscopy.  2007;23:717-22.[CrossRef][PubMed]
 
Papaspiliopoulos  A;  Papaparaskeva  K;  Papadopoulou  E;  Feroussis  J;  Papalois  A;  Zoubos  A. The effect of local use of nandrolone decanoate on rotator cuff repair in rabbits. J Invest Surg.  2010;23:204-7.[CrossRef][PubMed]
 
Kim  HM;  Galatz  LM;  Lim  C;  Havlioglu  N;  Thomopoulos  S. The effect of tear size and nerve injury on rotator cuff muscle fatty degeneration in a rodent animal model. J Shoulder Elbow Surg.   2011 Aug 9. [Epub ahead of print]
 
Liu  X;  Manzano  G;  Kim  HT;  Feeley  BT. A rat model of massive rotator cuff tears. J Orthop Res.  2011;29:588-95.  Epub 2010 Oct 14.[CrossRef][PubMed]
 
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