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Commentary and Perspective

Human Growth Hormone May Not Have Biomechanical Benefits, But Is It Detrimental?

Commentary on an article by Keith M. Baumgarten, MD, et al.: “Human Growth Hormone May Be Detrimental When Used to Accelerate Recovery from Acute Tendon-Bone Interface Injuries”

Brown, Thomas D. PhD*,1

Author Information
The Journal of Bone & Joint Surgery: May 1, 2013 - Volume 95 - Issue 9 - p e63
doi: 10.2106/JBJS.M.00049
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Commentary

Off-label usage of biopharmaceuticals has sometimes been the source of anecdotal clinical impressions that in turn have led to suboptimal patient care. In the case of human growth hormone, these issues are further confounded by controversies regarding inappropriate performance enhancements in athletics, which have been well publicized in the lay media. The laboratory research study by Baumgarten et al. is an important contribution in this area, in that it provides an objective assessment of the level of efficacy of human growth hormone for accelerating the healing of acute tendon-bone interface injuries. The model adopted, which involves acute rotator cuff repair in the rat, has become well established in the orthopaedic scientific literature for studying the pathophysiology and treatment of these common human injuries.

The authors chose to concentrate on biomechanical outcome measures with their rationale being that, unless human growth hormone could demonstrably accelerate the functional healing that would otherwise occur, there was little point in detailed histologic or molecular biological assessments. The rat model held substantial attraction logistically, in that it allowed usage of a relatively large number of study animals (ninety-six), thus providing reasonable statistical power to consider a clinically relevant range of plausible dosage regimens. While using the rat model required trading off for a number of simplifications relative to the human clinical setting, the authors insightfully reviewed those considerations in the Discussion section of the article, providing well-reasoned arguments with substantiation from precedent literature in order to justify their model.

The study’s findings were both definitive and convincing: No benefits whatsoever were statistically demonstrable biomechanically from human growth hormone usage for any of the dosage regimens considered. The biomechanical testing itself involved a single configuration of loading, applying tension across the originally failed tendon-bone interface. The raw load-versus-deformation data from that single testing configuration were processed to arrive at a number of repair performance metrics: ultimate stress (i.e., failure stress), ultimate force, ultimate displacement, energy to failure, and stiffness. Each of these biomechanical performance metrics has a different specific interpretation physically, although all of them are reflective of interfacial mechanical integrity. For example, the tensile force necessary to cause interface failure on the one hand, and the energy absorbed during the course of the event of interface failure on the other hand, are physically distinct quantities, although both are reflective of the degree of mechanical integrity of the interface repair.

Since these various biomechanical performance metrics involved different aspects of interface repair integrity, they did not all respond totally in lockstep for the respective dosage regimens. For the great majority of permutations of performance metric and dosage regimen, human growth hormone showed no significant effect. For some permutations, there was an upward trend, and for others there was a downward trend, with no apparent evidence of a dose-response effect. The single exception was that significance was reached (p = 0.035) for the case of ultimate force for a dosage regimen of 5 mg/kg/day given twice a day for twenty-eight days, for which human growth hormone caused a 19.8% decrement.

While there clearly was no evidence that human growth hormone was of any biomechanical benefit in this setting, opinions might legitimately differ as to whether or not human growth hormone might in fact be actively detrimental. The authors interpreted the 19.8% ultimate force reduction for the twenty-eight-day regimen as evidence of a plausibly detrimental effect, and they opted not to qualify such an effect as being “mild” or “moderate.” Readers are invited to review the actual data in Tables I and III to form their own impressions in that regard.

*The author did not receive payments or services, either directly or indirectly (i.e., via his institution), from a third party in support of any aspect of this work. He, or his institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. 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 © 2013 by The Journal of Bone and Joint Surgery, Incorporated