Baumgarten KM, Oliver HA, Foley J, et al. Human growth hormone may be detrimental when used to accelerate recovery from acute tendon-bone interface injuries. J Bone Joint Surg Am 2013;95(9):783-9. http://jbjs.org/article.aspx?articleid=1679100
BACKGROUND: There have been few scientific studies that have examined usage of human growth hormone to accelerate recovery from injury. The hypothesis of this study was that human growth hormone would accelerate tendon-to-bone healing compared with control animals treated with placebo in a rat model of acute rotator cuff injury repair.
METHODS: Seventy-two rats underwent repair of acute rotator cuff injuries and were randomized into the following postoperative dosing regimens: placebo, and human growth hormone at 0.1, 1, 2, 5, and 10 mg/kg/day, administered subcutaneously once per day for fourteen days (Protocol 1). An additional twenty-four rats were randomized to receive either (1) placebo or (2) human growth hormone at 5 mg/kg, administered subcutaneously twice per day for seven days preoperatively and twenty-eight days postoperatively (Protocol 2). All rats were killed twenty-eight days postoperatively. Mechanical testing was performed. Ultimate stress, ultimate force, stiffness, energy to failure, and ultimate distension were determined.
RESULTS: For Protocol 1, analysis of variance testing showed no significant difference between the groups with regard to ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension. In Protocol 2, ultimate force to failure was significantly worse in the human growth hormone group compared with the placebo group (21.1 +/- 5.85 versus 26.3 +/- 5.47 N; p = 0.035). Failure was more likely to occur through the bone than the tendon-bone interface in the human growth hormone group compared with the placebo group (p = 0.001). No significant difference was found for ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension between the groups in Protocol 2.
CONCLUSIONS: In this rat model of acute tendon-bone injury repair, daily subcutaneous postoperative human growth hormone treatment for fourteen days failed to demonstrate a significant difference in any biomechanical parameter compared with placebo. Furthermore, subcutaneous administration of 5 mg/kg of human growth hormone twice daily from seven days preoperatively until twenty-eight days postoperatively demonstrated lower loads to ultimate failure and a higher risk of bone fracture failure compared with placebo.
CLINICAL RELEVANCE: This study suggests that human growth hormone treatment does not identifiably accelerate the strength of tendon-to-bone healing from acute injury and may have negative biomechanical consequences.
Chutkan NB, Kelly JDt. Human growth hormone may be detrimental when used to accelerate recovery from acute tendon-bone interface injuries. Orthopedics 2013;36(7):539-40. Human growth hormone may be detrimental when use... [Orthopedics. 2013] - PubMed - NCBI
The authors of this elegant article investigate the use of growth hormone as a mean to enhance rotator cuff repair in Rats. Seventy-two rats underwent repair of surgically created rotator cuff tears and were randomized into the following postoperative doses of subcutaneously administered human growth hormone (HGH): 0.1, 1, 2, 5, and 10 mg/kg/day, administered for fourteen days in addition to a placebo group (Protocol 1).
An additional cohort of twenty-four rats were randomized to receive either placebo or HGH at 5 mg/kg, twice daily for seven days preoperatively and twenty-eight days postoperatively (Protocol 2) All rats were sacrificed at 28 days and underwent mechanical testing to determine ultimate stress, ultimate force, stiffness, energy to failure, and ultimate distension.
Results, as determined by analysis of variance testing, showed no significant difference between any of the groups administered HGH postoperatively and placebo. (Protocol1) For the subjects receiving the pre op dose and prolonged post operative regime, (Protocol2) ultimate force to failure was significantly less than the placebo group (21.1 ± 5.85 versus 26.3 ± 5.47 N; p = 0.035).
While no significant difference was found for ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension between was found, mechanical failure was more likely to occur through the bone than the tendon-bone interface in the treatment group when compared to placebo (p = 0.001).
Perspective
Human growth hormone has been used by athletes and clinicians alike as a means of accelerating recovery after injury. Firm scientific evidence for its efficacy in enhancing soft tissue repair is lacking.
Growth hormone does indeed have an anabolic effect on muscle growth by increasing sarcomere amino acid and glucose uptake while it potentiates lipolysis . Indeed, many aging athletes regard it as the ‘fountain of youth’. HGH does in fact accelerate collagen synthesis; thus the authors ask a pertinent question about its effects on bone-tendon healing.
This fairly well designed prospective study indicates that systemically administered HGH confers no anabolic effect on rotator cuff repair and may prove deleterious to healing in higher dosing schedules. The rat model for rotator cuff disorders is well established and appears to correlate well to the human condition.
While slightly underpowered, this investigation is another testament of failure in search of the ‘Holy Grail’ of cuff healing enhancement. The inconsistent results of platelet rich plasma, with noted potential negative effects, mirror those of this study.
Of note, the prolonged dosage group gained appreciable weight, raising the specter of adverse metabolic consequences with HGH administration–i.e hyperglycemia. Weight gain and its accompanying metabolic syndrome is ‘pro inflammatory’ and is associated with increased cytokine production.
Perhaps modulation of inflammation, as Rodeo et al have shown with matrix metalloproteinase inhibitors, will prove to be the most effective means of enhancing soft tissue repair.
Before I give my patients HGH, which promotes hypertension, hyperglycemia and acromegaly, I would much rather choose tight glucose control, smoking cessation, and both Vit. D and Omega 3 fatty acid supplementation in order to mitigate inflammation and enhance healing.
