Background: To date, no studies document the effect of anabolic steroids on rotator cuff tendons.
Study Design: Controlled laboratory study.
Hypothesis: Anabolic steroids enhance remodeling and improve the biomechanical properties of bioartificially engineered human supraspinatus tendons.
Methods: Bioartificial tendons were treated with either nandrolone decanoate (nonload, steroid, n = 18), loading (load, nonsteroid, n = 18), or both (load, steroid, n = 18). A control group received no treatment (nonload, nonsteroid [NLNS], n = 18). Bioartificial tendons’ remodeling was assessed by daily scanning, cytoskeletal organization by staining, matrix metalloproteinase-3 levels by ELISA assay, and biomechanical properties by load-to-failure testing.
Results: The load, steroid group showed the greatest remodeling and the best organized actin cytoskeleton. Matrix metallo-proteinase-3 levels in the load, steroid group were greater than those of the nonload, nonsteroid group (P < .05). Ultimate stress and ultimate strain in the load, steroid group were greater than those of the nonload, nonsteroid and nonload, steroid groups (P < .05). The strain energy density in the load, steroid group was greater when compared to other groups (P < .05).
Conclusions: Nandrolone decanoate and load acted synergistically to increase matrix remodeling and biomechanical properties of bioartificial tendons.
Clinical Relevance: Data suggest anabolic steroids may enhance production of bioartificial tendons and rotator cuff tendon healing in vitro. More research is necessary before such clinical use is recommended.
1. Alway SE, Starkweather LA. Effect of anabolic steroids on new fiber formation and fiber area during stretch-overload. J Appl Physiol. 1993;74:832-837.
2.
2. Banes AJ, Donlon K, Link GW, et al.Cell populations of tendon: a simplified method for isolation of synovial and internal fibroblasts: confirmation of origin and biologic properties. J Orthop Res. 1988;6:83-94.
3.
3. Banes AJ, Weinhold P, Yank X, et al.Gap junctions regulate responses of tendon cells ex vivo to mechanical loading. Clin Orthop. 1999;367(suppl):S356-S370.
4.
4. Bartsch W.Anabolic steroids: action on cellular level. Wien Med Wochenschr. 1993;143:363-366.
5.
5. Benjamin M, Ralphs JR. The cell and developmental biology of tendons and ligaments. Int Rev Cytol. 2000;196:85-130.
6.
6. Bigliani LU, McIlveen SJ, Cordasco F, et al.Operative repair of massive rotator cuff tears: long term results. J Shoulder Elbow Surg. 1992;1:120-130.
7.
7. Burkhart SS, Danacau SM, Pearce CE Jr.Arthroscopic rotator cuff repair: analysis of results by tear size and by repair technique—margin convergence versus direct tendon-to-bone repair. Arthroscopy. 2001;17:905-912.
8.
8. Celotti F, Negri Cesi P.Anabolic steroids: a review of their effects on the muscles, of their possible mechanisms of action and of their use in athletics. J Steroid Biochem. 1992;43:469-477.
9.
9. Chard MD, Cawston TE, Riley GP, et al.Rotator cuff degeneration and lateral epicondylitis: a comparative histological study. Ann Rheum Dis. 1994;53:30-34.
10.
10. Cofield RH. Current concepts review: rotator cuff disease of the shoulder. J Bone Joint Surg Am. 1985;67:974-979.
11.
11. David HG, Green JT, Grant AJ, et al.Simultaneous bilateral quadriceps rupture: a complication of anabolic steroid abuse. J Bone Joint Surg. 1995;77:159-160.
12.
12. Dejardin LN, Arnoczky SP, Cloud GL. Use of small intestinal submucosal implants for regeneration of large fascial defects: an experimental study in dogs. J Biomed Mater Res. 1999;46:203-211.
13.
13. Demling RH, Orgill DP. The anticatabolic and wound healing effects of the testosterone analog oxandrolone after severe burn injury. J Crit Care. 2000;15:12-17.
14.
14. DeOrio JK, Cofield RH. Results of a second attempt at surgical repair of a failed initial rotator-cuff repair. J Bone Joint Surg. 1984;66:563-567.
15.
15. Frankle MA, Leffers D.Anabolic androgenic steroids; a guide for the orthopaedic surgeon. Scientific exhibit at: Annual Meeting of the AAOS; 1989; Las Vegas, Nev.
16.
16. Garvin J, Qi J, Maloney M, Banes A.A novel system for engineering bioartificial tendons and application of mechanical load. J Tissue Eng. 2003;9:967-979.
17.
17. Gerber C, Fuchs B, Hodler J.The results of repair of massive tears of the rotator cuff. J Bone Joint Surg. 2000;82:505-515.
18.
18. Gomez DE, Alonso DF, Yoshiji H, et al.Tissue inhibitors of metallo-proteinases: structure, regulation and biological functions. Eur J Cell Biol. 1997;74:111-122.
19.
19. Grisby JS, Bergen WG, Merkel RA. The effect of testosterone on skeletal muscle development and protein synthesis in rabbits. Growth. 1976;40:303-316.
20.
20. Hart DW, Wolf SE, Ramzy PI, et al.Anabolic effects of oxandrolone after severe burn. Ann Surg. 2001;233:556-564.
21.
21. Hausmann DF, Nutz V, Rommelsheim K, et al.Anabolic steroids in polytrauma patients. Influence on renal nitrogen and amino acid losses: a double-blind study. J Parenter Enteral Nutr. 1990;14:111-114.
22.
22. Hervey GR, Knibbs AV, Burkinshaw L, et al.Effects of methandienone on the performance and body composition of men undergoing athletic training. Clin Sci (Lond). 1981;60:457-461.
23.
23. Hill JA, Suker JR, Sachs K, et al.The athletic polydrug abuse phenomenon: a case report. Am J Sports Med. 1983;11:269-271.
24.
24. Iannotti JP, Bernot MP, Kuhlman JR, et al.Postoperative assessment of shoulder function: a prospective study of full-thickness rotator cuff tears. J Shoulder Elbow Surg. 1996;5:449-457.
25.
25. Ireland D, Harall R, Curry V, et al.Multiple changes in gene expression in chronic human Achilles tendinopathy. Matrix Biol. 2001;20:159-169.
26.
26. Karpaka JA, Pesola MK, Takala ES. The effects of anabolic steroids on collagen synthesis in rat skeletal muscle and tendon: a preliminary report. Am J Sports Med. 1992;20:262-266.
27.
27. Kennedy JM, Eisenberg BR, Reid SK, et al.Nascent muscle fibers appearance in overloaded chicken slow-tonic muscle. Am J Anat. 1988;181:203-215.
28.
28. Kirkland RT, Harrist RB, Clayton GW. Results of four years of inter-mittent human growth hormone (hGH) and fluoxymesterone therapy in hypopituitary dwarfism. Pediatrics. 1980;65:562-566.
29.
29. Kramhoft M, Solgaard S.Spontaneous rupture of the extensor pollicis longus tendon after anabolic steroids. J Hand Surg [Br]. 1986;11:87-88.
30.
30. Kubista M, Akareman B, Norden B.Characterization of interaction between DNA and 4’,6-diamidino-2-phenylindole by optical spectroscopy. Biochemistry. 1987;26:4545.
31.
31. Lambert MI, St Clair Gibson A, Noakes TD. Rupture of the triceps tendon associated with steroid injections. Am J Sports Med. 1995;23:778.
32.
32. Lewis L, Dahn M, Kirkpatrick JR. Anabolic steroid administration during nutritional support: a therapeutic controversy. J Parenter Enteral Nutr. 1981;5:64-66.
33.
33. Liow RY, Tavares S.Bilateral rupture of the quadriceps tendon associated with anabolic steroids. Br J Sports Med. 1995;29:77-79.
34.
34. MacGillivray MH, Kolotkin M, Munschauer RW. Enhanced linear growth responses in hypopituitary dwarfs treated with growth hormone plus androgen versus growth hormone alone. Pediatr Res. 1974;8:103-108.
35.
35. Manicourt DH, Fujimoto N, Obata K, et al.Serum levels of collagenase, stromelysins-1, and TIMP-1. Age-related and sex-related differences in normal subjects and relationship to the extend of joint involvement and serum levels of antigenic keratan sulfate in patients with osteoarthritis. Arthritis Rheum. 1994;37:1774-1783.
36.
36. McNeilly CM, Banes AJ, Benjamin M, et al.Tendon cells in vivo form a three dimensional network of cell processes linked by gap junctions. J Anat. 1996;189:593-600.
37.
37. Michelson CB, Askanazi J, Kinney JM, et al.Effect of an anabolic steroid on nitrogen balance and amino acid patterns after total hip replacement. J Trauma. 1982;22:410-413.
38.
38. Michna H.Tendon injuries induced by exercise and anabolic steroid in experimental mice. Internat Orthop. 1987;11:157-162.
39.
39. Miles JW, Grana WA, Eagle D, et al.The effect of anabolic steroid on the biomechanical and histological properties of rat tendon. J Bone Joint Surg Am. 1992;74:411-422.
40.
40. Miniaci A, MacLeod M.Transfer of the latissimus dorsi muscle after failed repair of a massive tear of the rotator cuff: a two to five-year review. J Bone Joint Surg Am. 1999;81:1120-1127.
41.
41. Nemoto O, Yamagishi M, Yamada H, et al.Matrix metalloproteinase-3 production by human degenerated intervertebral disc. J Spinal Disord. 1997;10:493-498.
42.
42. Neviaser JS, Neviaser RJ, Neviaser TJ. The repair of chronic massive ruptures of the rotator cuff of the shoulder by use of a freeze-dried rotator cuff. J Bone Joint Surg Am. 1978;60:681-684.
43.
43. Okada Y, Shinmei M, Tanaka O, et al.Localization of matrix metallo-proteinase 3 (stromelysin) in osteoarthritic cartilage and synovium. Lab Invest. 1992;66:680-690.
44.
44. Post M.Rotator cuff repair with carbon filament: a preliminary report of five cases. Clin Orthop. 1985;196:154-158.
45.
45. Ralphs JR, Waggett AD, Benjamin M.Actin stress fibers and cell-cell adhesion molecules in tendons: organization in vivo and response to mechanical loading of tendon cells in vitro. Matrix Biol. 2002;21:67-74.
46.
46. Riley GP, Curry V, DeGroot J, et al.Matrix metalloproteinase activities and their relationship with collagen remodeling in tendon pathology. Matrix Biol. 2002;21:185-195.
47.
47. Riley GP, Harall RL, Constant CR, et al.Glycosaminoglycans of human rotator cuff tendons; changes with age and in chronic rotator cuff tendinitis. Ann Rheum Dis. 1994;53:367-376.
48.
48. Riley GP, Harall RL, Constant CR, et al.Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis. Ann Rheum Dis. 1994;53:359-366.
49.
49. Rodeo SA, Suzuki K, Deng X, et al.Use of recombinant human bone morphogenetic protein-2 to enhance tendon healing in a bone tunnel. Am J Sports Med. 1999;27:476-488.
50.
50. Rogozkin V.Metabolic effects of anabolic steroid on skeletal muscle. Med Sci Sports. 1979;11:160-163.
51.
51. Shahidi NT. A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids. Clin Ther. 2001;23:1355-1389.
52.
52. Sheffield-Moore M.Androgens and the control of skeletal muscle protein synthesis. Ann Med. 2000;32:181-186.
53.
53. Small J.Visualizing the actin cytoskeleton. Microsc Res Tech. 1999;47:3.
54.
54. Stannard JP, Bucknell AL. Rupture of the triceps tendon associated with steroid injections. Am J Sports Med. 1993;21:482-485.
55.
55. Tsuzaki M, Guyton G, Garrett W, et al.IL-1 beta induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells. J Orth Res. 2003;21:256-264.
56.
56. Uhthoff HK, Sano H, Trudel G, et al.Early reactions after reimplantation of the tendon of supraspinatus into bone: a study in rabbits. J Bone Joint Surg Br. 2000;82:1072-1076.
57.
57. Waggett AD, Benjamin M, Ralphs JR. Gap junction inhibitors abolish strain response in tendon cells in vitro. Trans Orthop Res Soc. 1999;24:630.
58.
58. Warner JJ, Parsons IM IV. Latissimus dorsi tendon transfer: a comparative analysis of primary and salvage reconstruction of massive, irreparable rotator cuff tears. J Shoulder Elbow Surg. 2001;10:514-521.
59.
59. Woo SL-Y, Ritter MA, Amiel D, et al.The biomechanical and biochemical properties of swine tendons: long-term effects of exercise on the digital extensors. Connect Tissue Res. 1980;7:177-183.
60.
60. Wood TO, Cooke PH, Goodship AE. The effect of exercise and anabolic steroids on the mechanical properties and crimp morphology of the rat tendon. Am J Sports Med. 1988;16:153-158.
