madman
Super Moderator
ABSTRACT
Despite the well-documented effects of testosterone and its synthetic derivatives—collectively termed anabolic-androgenic steroids (AASs)— on the musculoskeletal system, the therapeutic use of these agents has received limited investigation within the field of orthopaedic surgery. In the last 2 decades, preclinical and clinical research has started to identify promising applications of the short-term use of AASs in the perioperative period. There is evidence to suggest that AASs may improve postoperative recovery after anterior cruciate ligament reconstruction and total joint arthroplasty. In addition, AASs may augment the biological healing environment in specific clinical scenarios including muscle injury, fracture repair, and rotator cuff repair. Current literature fails to present strong evidence for or against the use of AASs in orthopaedics, but there is continuous research on this topic. The purpose of this study was to provide a comprehensive overview of the current status of AAS applications in orthopaedic surgery, with an emphasis on preclinical data, clinical studies, and future directions.
Anabolic-androgenic steroids (AASs) are synthetic testosterone derivatives designed to maximize anabolic activity and minimize androgenic effects.1 AASs has gained considerable notoriety in the last half-century, which is attributable to their illegal use in athletic competition.2,3 Despite their reputation, AASs have a number of therapeutic applications. The anabolic effects of AASs may play a significant role in the treatment of muscle wasting associated with severe burns and a wide spectrum of chronic diseases such as human immunodeficiency virus, cancer, renal failure, hepatic cirrhosis, pulmonary disease, and muscular dystrophy.4-10 AASs have also been studied in the context of prolonged immobilization after spinal cord injury, which is characterized by volumetric bone and muscle loss; preclinical studies have shown beneficial effects, and a clinical trial is underway to validate these promising findings.11-13 The use of AASs to counteract muscle and bone loss is supported by a growing body of evidence showing a positive effect of AASs on muscle mass, strength, and bone metabolism.14-17 The applications of AASs related to the field of orthopaedic surgery have been historically limited. A notable exception is the use of AASs in the treatment of osteoporosis, which has been studied more extensively.18-22 Although testosterone may be indicated for men with osteoporosis, other AASs have been studied as a possible alternative, particularly in women, due to the lower risk of virilizing side effects.23,24 The clinical results with the use of AAS as an adjunct therapy in osteoporosis remains a subject of inquiry in both the male and female population.24-27 AASs have mostly been evaluated at a relatively low dose and with long-term administration in studies on osteoporosis.4,24-28 Only in the last two decades has short-term administration of AAS received investigation in orthopaedics.
Orthopaedic injury and accompanying surgery are almost always associated with the development of disuse muscle atrophy, which lengthens recovery and delays return to full strength.29 Disuse atrophy has been linked to negative outcomes in common orthopaedic procedures including but not limited to anterior cruciate ligament (ACL) reconstruction, total knee arthroplasty (TKA), and lower extremity fracture repair.30-34 Recent evidence suggests that the anabolic effects of AASs in muscle may be an effective method to improve postoperative recovery after such procedures.35-37 For example, the anabolic environment induced by AAS may also improve biological healing in specific clinical scenarios including muscle injury, fracture repair, and rotator cuff repair.21,38-40 Although the degree of direct muscle and bone healing from AAS administration remains inconclusive, a recent series of preclinical experiments demonstrated that AASs may halt fatty infiltration and improve healing of a repaired rotator cuff.39-41 This application highlights the potential of AASs to address the underlying pathophysiology in one of the most common causes of musculoskeletal pain and disability.42,43
To our knowledge, the last review to focus on the therapeutic applications of AAS in orthopaedic surgery was published in 2004, which was before many recent studies on the short-term use of AAS.28 The purpose of this present review is to provide a summary of the current status of AAS applications in orthopaedic surgery, with an emphasis on preclinical data, clinical studies, and future directions.
*Mechanism of Action and Effects of Anabolic-Androgenic Steroids on Musculoskeletal Tissues
*Effect of Anabolic-Androgenic Steroids on Skeletal Muscles
*Effect of Anabolic-Androgenic Steroids on Bone
*Effect of Anabolic-Androgenic Steroids on Tendons
*Effect of Anabolic-Androgenic Steroids on Ligaments
*Side Effects of Anabolic-Androgenic Steroids
*Orthopaedic Applications of Anabolic-Androgenic Steroids
A. Augmented Biological Healing Environment
A1. Muscle Regeneration After Injury
A2. Fracture Repair
A3. Rotator Cuff Repair
B. Improved Postoperative Recovery
B1. Hip Fracture Repair
B2. Anterior Cruciate Ligament Reconstruction
*Total Joint Arthroplasty
Summary
AASs have shown great promise as potential therapeutic tools in a variety of clinical scenarios relevant to orthopaedic surgeons. Based on current evidence, AASs can augment biological healing after muscle injury, fracture repair, or rotator cuff repair and have the potential to improve postoperative recovery after ACL reconstruction or total joint arthroplasty. To realize the clinical potential of AASs in orthopaedic surgery, substantial efforts are needed in the preclinical and clinical arenas to better characterize their effects on tissues and establish optimized regimens.
Despite the well-documented effects of testosterone and its synthetic derivatives—collectively termed anabolic-androgenic steroids (AASs)— on the musculoskeletal system, the therapeutic use of these agents has received limited investigation within the field of orthopaedic surgery. In the last 2 decades, preclinical and clinical research has started to identify promising applications of the short-term use of AASs in the perioperative period. There is evidence to suggest that AASs may improve postoperative recovery after anterior cruciate ligament reconstruction and total joint arthroplasty. In addition, AASs may augment the biological healing environment in specific clinical scenarios including muscle injury, fracture repair, and rotator cuff repair. Current literature fails to present strong evidence for or against the use of AASs in orthopaedics, but there is continuous research on this topic. The purpose of this study was to provide a comprehensive overview of the current status of AAS applications in orthopaedic surgery, with an emphasis on preclinical data, clinical studies, and future directions.
Anabolic-androgenic steroids (AASs) are synthetic testosterone derivatives designed to maximize anabolic activity and minimize androgenic effects.1 AASs has gained considerable notoriety in the last half-century, which is attributable to their illegal use in athletic competition.2,3 Despite their reputation, AASs have a number of therapeutic applications. The anabolic effects of AASs may play a significant role in the treatment of muscle wasting associated with severe burns and a wide spectrum of chronic diseases such as human immunodeficiency virus, cancer, renal failure, hepatic cirrhosis, pulmonary disease, and muscular dystrophy.4-10 AASs have also been studied in the context of prolonged immobilization after spinal cord injury, which is characterized by volumetric bone and muscle loss; preclinical studies have shown beneficial effects, and a clinical trial is underway to validate these promising findings.11-13 The use of AASs to counteract muscle and bone loss is supported by a growing body of evidence showing a positive effect of AASs on muscle mass, strength, and bone metabolism.14-17 The applications of AASs related to the field of orthopaedic surgery have been historically limited. A notable exception is the use of AASs in the treatment of osteoporosis, which has been studied more extensively.18-22 Although testosterone may be indicated for men with osteoporosis, other AASs have been studied as a possible alternative, particularly in women, due to the lower risk of virilizing side effects.23,24 The clinical results with the use of AAS as an adjunct therapy in osteoporosis remains a subject of inquiry in both the male and female population.24-27 AASs have mostly been evaluated at a relatively low dose and with long-term administration in studies on osteoporosis.4,24-28 Only in the last two decades has short-term administration of AAS received investigation in orthopaedics.
Orthopaedic injury and accompanying surgery are almost always associated with the development of disuse muscle atrophy, which lengthens recovery and delays return to full strength.29 Disuse atrophy has been linked to negative outcomes in common orthopaedic procedures including but not limited to anterior cruciate ligament (ACL) reconstruction, total knee arthroplasty (TKA), and lower extremity fracture repair.30-34 Recent evidence suggests that the anabolic effects of AASs in muscle may be an effective method to improve postoperative recovery after such procedures.35-37 For example, the anabolic environment induced by AAS may also improve biological healing in specific clinical scenarios including muscle injury, fracture repair, and rotator cuff repair.21,38-40 Although the degree of direct muscle and bone healing from AAS administration remains inconclusive, a recent series of preclinical experiments demonstrated that AASs may halt fatty infiltration and improve healing of a repaired rotator cuff.39-41 This application highlights the potential of AASs to address the underlying pathophysiology in one of the most common causes of musculoskeletal pain and disability.42,43
To our knowledge, the last review to focus on the therapeutic applications of AAS in orthopaedic surgery was published in 2004, which was before many recent studies on the short-term use of AAS.28 The purpose of this present review is to provide a summary of the current status of AAS applications in orthopaedic surgery, with an emphasis on preclinical data, clinical studies, and future directions.
*Mechanism of Action and Effects of Anabolic-Androgenic Steroids on Musculoskeletal Tissues
*Effect of Anabolic-Androgenic Steroids on Skeletal Muscles
*Effect of Anabolic-Androgenic Steroids on Bone
*Effect of Anabolic-Androgenic Steroids on Tendons
*Effect of Anabolic-Androgenic Steroids on Ligaments
*Side Effects of Anabolic-Androgenic Steroids
*Orthopaedic Applications of Anabolic-Androgenic Steroids
A. Augmented Biological Healing Environment
A1. Muscle Regeneration After Injury
A2. Fracture Repair
A3. Rotator Cuff Repair
B. Improved Postoperative Recovery
B1. Hip Fracture Repair
B2. Anterior Cruciate Ligament Reconstruction
*Total Joint Arthroplasty
Summary
AASs have shown great promise as potential therapeutic tools in a variety of clinical scenarios relevant to orthopaedic surgeons. Based on current evidence, AASs can augment biological healing after muscle injury, fracture repair, or rotator cuff repair and have the potential to improve postoperative recovery after ACL reconstruction or total joint arthroplasty. To realize the clinical potential of AASs in orthopaedic surgery, substantial efforts are needed in the preclinical and clinical arenas to better characterize their effects on tissues and establish optimized regimens.
