Sclerostin Antibody Treatment Enhances Rotator Cuff Tendon-to-Bone Healing in an Animal Model (original) (raw)

2017, Journal of Bone and Joint Surgery

Background: Rotator cuff tears are a common source of pain and disability, and poor healing after repair leads to high retear rates. Bone loss in the humeral head before and after repair has been associated with poor healing. The purpose of the current study was to mitigate bone loss near the repaired cuff and improve healing outcomes. Methods: Sclerostin antibody (Scl-Ab) treatment, previously shown to increase bone formation and strength in the setting of osteoporosis, was used in the current study to address bone loss and enhance rotator cuff healing in an animal model. Scl-Ab was administered subcutaneously at the time of rotator cuff repair and every 2 weeks until the animals were sacrificed. The effect of Scl-Ab treatment was evaluated after 2, 4, and 8 weeks of healing, using bone morphometric analysis, biomechanical evaluation, histological analysis, and gene expression outcomes. Results: Injury and repair led to a reduction in bone mineral density after 2 and 4 weeks of healing in the control and Scl-Ab treatment groups. After 8 weeks of healing, animals receiving Scl-Ab treatment had 30% greater bone mineral density than the controls. A decrease in biomechanical properties was observed in both groups after 4 weeks of healing compared with healthy tendon-to-bone attachments. After 8 weeks of healing, Scl-Ab-treated animals had improved strength (38%) and stiffness (43%) compared with control animals. Histological assessment showed that Scl-Ab promoted better integration of tendon and bone by 8 weeks of healing. Scl-Ab had significant effects on gene expression in bone, indicative of enhanced bone formation, and no effect on the expression of genes in tendon. Conclusions: This study provides evidence that Scl-Ab treatment improves tendon-to-bone healing at the rotator cuff by increasing attachment-site bone mineral density, leading to improved biomechanical properties. Clinical Relevance: Scl-Ab treatment may improve outcomes after rotator cuff repair. R otator cuff tears do not heal spontaneously, can progress in size over time, and motivate >250,000 surgical repairs in the United States annually 1. Poor tendon-tobone healing after repair results in an alarmingly high rate of retears at the site of attachment, ranging from 20% in young healthy patients with small tears to 94% in older patients with massive tears 2,3. Rotator cuff tears are associated with loss of bone at the healing interface and a lack of regeneration of the functionally graded, mineralized fibrocartilage found in the healthy attachment 4. Bone loss has been observed at healing tendon-to-bone interfaces at multiple anatomic sites 5-11. The loss of mineralized tissue is likely caused by mechanical unloading during the period from tearing through surgical repair and by high osteoclast activity during the healing period after Disclosure: The study was supported by National Institutes of Health (NIH) grants F31-AR066452 and NIH R01-AR057836. Sclerostin antibody was provided by Amgen, Inc. One of the authors was an employee of Amgen, Inc. at the time of the study. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked "yes" to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work and "yes" to indicate that the author had a patent planned for the treatment that is the subject of this article (http://links.lww.com/JBJS/D272).