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Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis.

ABSTRACT: Arthrofibrosis is a prevalent condition affecting greater than 5% of the general population and leads to a painful decrease in joint range of motion (ROM) and loss of independence due to pathologic accumulation of periarticular scar tissue. Current treatment options are limited in effectiveness and do not address the underlying cause of the condition: accumulation of fibrotic collagenous tissue. Herein, the naturally occurring peptide hormone relaxin-2 is administered for the treatment of adhesive capsulitis (frozen shoulder) and to restore glenohumeral ROM in shoulder arthrofibrosis. Recombinant human relaxin-2 down-regulates type I collagen and ? smooth muscle actin production and increases intracellular cAMP concentration in human fibroblast-like synoviocytes, consistent with a mechanism of extracellular matrix degradation and remodeling. Pharmacokinetic profiling of a bolus administration into the glenohumeral joint space reveals the brief systemic and intraarticular (IA) half-lives of relaxin-2: 0.96 h and 0.62 h, respectively. Furthermore, using an established, immobilization murine model of shoulder arthrofibrosis, multiple IA injections of human relaxin-2 significantly improve ROM, returning it to baseline measurements collected before limb immobilization. This is in contrast to single IA (sIA) or multiple i.v. (mIV) injections of relaxin-2 with which the ROM remains constrained. The histological hallmarks of contracture (e.g., fibrotic adhesions and reduced joint space) are absent in the animals treated with multiple IA injections of relaxin-2 compared with the untreated control and the sIA- and mIV-treated animals. As these findings show, local delivery of relaxin-2 is an innovative treatment of shoulder arthrofibrosis.

SUBMITTER: Blessing WA

PROVIDER: S-EPMC6589647 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis.

Blessing William A WA Okajima Stephen M SM Cubria M Belen MB Villa-Camacho Juan C JC Perez-Viloria Miguel M Williamson Patrick M PM Sabogal Angie N AN Suarez Sebastian S Ang Lay-Hong LH White Suzanne S Flynn Evelyn E Rodriguez Edward K EK Grinstaff Mark W MW Nazarian Ara A

Proceedings of the National Academy of Sciences of the United States of America 20190603 25

Arthrofibrosis is a prevalent condition affecting greater than 5% of the general population and leads to a painful decrease in joint range of motion (ROM) and loss of independence due to pathologic accumulation of periarticular scar tissue. Current treatment options are limited in effectiveness and do not address the underlying cause of the condition: accumulation of fibrotic collagenous tissue. Herein, the naturally occurring peptide hormone relaxin-2 is administered for the treatment of adhesi ...[more]

PMID: 31160441

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Project description:Purpose To determine the effect of perioperative angiotensin II receptor blocker (ARB) or angiotensin-converting enzyme inhibitors (ACEi) on postoperative arthrofibrosis, as defined by requiring manipulation under anesthesia (MUA) or new diagnosis of adhesive capsulitis (AC) following arthroscopic shoulder procedures. Methods Patients were retrospectively identified using Current Procedural Terminology surgical billing codes to identify patients who underwent any shoulder arthroscopic procedure at a single urban academic institution from 2012 to 2020 with a minimum 2-year follow-up. Patients were excluded if <30 years old at time of surgery, as these patients rarely use ARB and ACEi medications, or if they had pre-existing AC. Demographics, active medication prescriptions at the time of surgery, and medical comorbidities were recorded. Multivariable logistic regression was performed to determine the effect of ARB/ACEi on subsequent MUA or AC by 90 days, 1 year, and 2 years. Results In total, 5,559 patients were included in the final analysis. A majority of the cohort (53.4%) underwent arthroscopic surgery between the ages of 50 to 69 years. Most patients were male (61.8%) and without obesity (67.3%). In total, 18.9% and 15.0% were taking an ARB or ACEi medication perioperatively, respectively. Within 2 years’ postoperatively, 51 patients (0.9%) underwent subsequent ipsilateral MUA, and 174 patients (3.1%) developed AC. Patients taking ARBs had a 17.5% rate of postoperative arthrofibrosis within 2-years compared with 19.1% in those not on ARBs, although this difference was not significant (P = .58). Likewise, no significant difference was found between those taking ACEi versus not (15.0% vs 15.0%, P = .99). Individual generic ARB/ACEi subgroup analysis did not demonstrate any significant associations with rate of postoperative arthrofibrosis (P > .05). Conclusions ARBs or ACEi did not significantly affect the rate of postoperative arthrofibrosis following shoulder arthroscopy, however female sex, diabetes mellitus, and Black/African American race were associated with an increased rate of necessitating MUA or developing AC within 2 years postoperatively. Level of Evidence Level III, retrospective cohort study.

Dataset Information

Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis.

Publications

Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis.

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