Tissue Remodeling and Anterior Cruciate Ligament Injury in Female Athletes
Abstract & Commentary
Synopsis: Normal tissue remodeling may be related to susceptibility of ACL injury in female athletes.
Source: Slauterbeck JR, Hardy DM. Sex hormones and knee ligament injuries in female athletes. Am J Med Sci. 2001; 322(4):196-199.
Slauterbeck and Hardy discuss their research agenda and review the literature related to the potential involvement of normal tissue remodeling and susceptibility to anterior cruciate ligament (ACL) injury in females. In particular, they review the biochemistry of tissue remodeling, and the clinical, biomechanical, and molecular research findings related to the ACL. Finally, they review the clinical and basic scientific significance of this work, and discuss current and future studies to determine if tissue remodeling genes vary by gender.
Slauterbeck and Hardy explain that tissue remodeling occurs simultaneously in normal and injured tissue, and the balance between this degradative and biosynthetic process is controlled by activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The female sex hormones—estrogen and progesterone—regulate the transcription of several MMP and TIMP genes, and receptors for these hormones are found in the human ACL.
Slauterbeck and Hardy further cite their work and the work of others that support frequency of ACL injury as a function of day of the menstrual cycle. In general, the cited research points to increased rates of injury around menses, and that injury more likely occurs in the late luteal and early follicular phases of the cycle. Slauterbeck and Hardy had previously reported a decrease in load at failure for the ACL in ovariectomized rabbits supplemented with estrogen. In their work to identify tissue remodeling genes that might be targets regulated by sex hormones, the authors site research that suggests the MMPs are absent from the ACL.
Comment by David H. Perrin, PhD, ATC
The fact that female athletes have a higher susceptibility of injury to the ACL is well established,1 particularly in basketball and soccer. A host of potential predisposing factors for the higher incidence of injury in females has been proposed. These factors include anatomical, biomechanical, neuromuscular, social, and more recently hormonal differences between males and females. Slauterbeck and Hardy are pursuing an intriguing line of research that potentially implicates the interplay between tissue remodeling, estrogen and progesterone receptors in the ACL, and the regulation of several MMP and TIMP genes by these hormones. This research has potential implications on frequency of ACL injury and clinical outcome following ACL reconstruction. The research that points to frequency of ACL injury as a function of the day of the menstrual cycle is inconclusive. Nevertheless, Slauterbeck and Hardy present a compelling case that the remodeling response in females differs from that in males, and as such deserves further research as related to susceptibility of ACL injury.
An intriguing question for sports medicine practitioners is what can be done to prevent ACL injury if indeed a link exists between sex hormones and frequency of injury to the ACL in females? Certainly, the most dramatic strategy would be restriction of physical activity at the times identified as high risk during the menstrual cycle. This is obviously an unacceptable prevention strategy, yet there are others that might have a potential role in reducing injury to the ACL. For example, the role of muscular fatigue on incidence of ACL injury deserves further elucidation, as does the relationship between fatigue, sex hormones, and neuromuscular response to lower extremity perturbation. Prescriptive strength and conditioning strategies and targeted modifications in training schedule might be appropriate. Slauterbeck and Hardy also identify the potential role of prophylactic bracing and birth control pills formulated to modify the remodeling process in favor of ACL repair.
The exact reason for the discrepancy in frequency of ACL injury between female and male athletes remains unclear. In all probability, multiple risk factors are involved, and the solution will involve a multifaceted program of preventive strategies. It is clear that further research needs to explore the potential risk factors, with the ultimate goal being to reduce the disparate rate between physically active males and females.
Dr. Perrin, Dean, School of Health and Human Performance, University of North Carolina—Greensboro, is Associate Editor of Sports Medicine Reports.
Reference
1. Arendt EA, et al. Anterior cruciate ligament injury patterns among collegiate men and women. J Athletic Training. 1999;34:86-92.
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