PMID- 32452208 OWN - NLM STAT- MEDLINE DCOM- 20201110 LR - 20210702 IS - 1552-3365 (Electronic) IS - 0363-5465 (Print) IS - 0363-5465 (Linking) VI - 48 IP - 8 DP - 2020 Jul TI - The Use of Recombinant Human Growth Hormone to Protect Against Muscle Weakness in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Pilot, Randomized Placebo-Controlled Trial. PG - 1916-1928 LID - 10.1177/0363546520920591 [doi] AB - BACKGROUND: Anterior cruciate ligament (ACL) tears are common knee injuries. Despite undergoing extensive rehabilitation after ACL reconstruction (ACLR), many patients have persistent quadriceps muscle weakness that limits their successful return to play and are also at an increased risk of developing knee osteoarthritis (OA). Human growth hormone (HGH) has been shown to prevent muscle atrophy and weakness in various models of disuse and disease but has not been evaluated in patients undergoing ACLR. HYPOTHESIS: Compared with placebo treatment, a 6-week perioperative treatment course of HGH would protect against muscle atrophy and weakness in patients undergoing ACLR. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 19 male patients (aged 18-35 years) scheduled to undergo ACLR were randomly assigned to the placebo (n = 9) or HGH (n = 10) group. Patients began placebo or HGH treatment twice daily 1 week before surgery and continued through 5 weeks after surgery. Knee muscle strength and volume, patient-reported outcome scores, and circulating biomarkers were measured at several time points through 6 months after surgery. Mixed-effects models were used to evaluate differences between treatment groups and time points, and as this was a pilot study, significance was set at P < .10. The Cohen d was calculated to determine the effect size. RESULTS: HGH was well-tolerated, and no differences in adverse events between the groups were observed. The HGH group had a 2.1-fold increase in circulating insulin-like growth factor 1 over the course of the treatment period (P < .05; d = 2.93). The primary outcome measure was knee extension strength, and HGH treatment increased normalized peak isokinetic knee extension torque by 29% compared with the placebo group (P = .05; d = 0.80). Matrix metalloproteinase-3 (MMP3), which was used as an indirect biomarker of cartilage degradation, was 36% lower in the HGH group (P = .05; d = -1.34). HGH did not appear to be associated with changes in muscle volume or patient-reported outcome scores. CONCLUSION: HGH improved quadriceps strength and reduced MMP3 levels in patients undergoing ACLR. On the basis of this pilot study, further trials to more comprehensively evaluate the ability of HGH to improve muscle function and potentially protect against OA in patients undergoing ACLR are warranted. REGISTRATION: NCT02420353 ( ClinicalTrials.gov identifier). FAU - Mendias, Christopher L AU - Mendias CL AD - Hospital for Special Surgery, New York, New York, USA. AD - Department of Physiology & Biophysics, Weill Cornell Medical College, New York, New York, USA. AD - Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA. AD - Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Enselman, Elizabeth R Sibilsky AU - Enselman ERS AD - Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Olszewski, Adam M AU - Olszewski AM AD - Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Gumucio, Jonathan P AU - Gumucio JP AD - Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA. AD - Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Edon, Daniel L AU - Edon DL AD - Hospital for Special Surgery, New York, New York, USA. FAU - Konnaris, Maxwell A AU - Konnaris MA AD - Hospital for Special Surgery, New York, New York, USA. FAU - Carpenter, James E AU - Carpenter JE AD - Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Awan, Tariq M AU - Awan TM AD - Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Jacobson, Jon A AU - Jacobson JA AD - Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Gagnier, Joel J AU - Gagnier JJ AD - Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Barkan, Ariel L AU - Barkan AL AD - Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Bedi, Asheesh AU - Bedi A AD - Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA. LA - eng SI - ClinicalTrials.gov/NCT02420353 GR - F31 AR065931/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200526 PL - United States TA - Am J Sports Med JT - The American journal of sports medicine JID - 7609541 RN - 0 (Recombinant Proteins) RN - 12629-01-5 (Human Growth Hormone) SB - IM MH - Adolescent MH - Adult MH - *Anterior Cruciate Ligament Injuries/surgery MH - *Anterior Cruciate Ligament Reconstruction MH - Human Growth Hormone/*therapeutic use MH - Humans MH - Knee Joint MH - Male MH - Muscle Strength MH - Muscle Weakness/drug therapy/*prevention & control MH - Pilot Projects MH - Quadriceps Muscle/physiology MH - Recombinant Proteins/therapeutic use MH - Young Adult PMC - PMC7351248 MID - NIHMS1598109 OTO - NOTNLM OT - anterior cruciate ligament OT - human growth hormone OT - muscle atrophy OT - orthobiologics OT - somatropin EDAT- 2020/05/27 06:00 MHDA- 2020/11/11 06:00 PMCR- 2021/07/01 CRDT- 2020/05/27 06:00 PHST- 2020/05/27 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2020/05/27 06:00 [entrez] PHST- 2021/07/01 00:00 [pmc-release] AID - 10.1177/0363546520920591 [doi] PST - ppublish SO - Am J Sports Med. 2020 Jul;48(8):1916-1928. doi: 10.1177/0363546520920591. Epub 2020 May 26.