However, possible implications of the reduced stiffness and modulus at uninjured attachments should be further considered

However, possible implications of the reduced stiffness and modulus at uninjured attachments should be further considered. There were several limitations to the current study. 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. Rotator cuff tears do not heal spontaneously, can progress in size over time, and motivate >250,000 surgical repairs in the United States annually1. Poor tendon-to-bone 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 tears2,3. 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 attachment4. Bone loss has been observed at healing tendon-to-bone interfaces at multiple anatomic sites5-11. 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 repair10,12. Chronic rotator cuff tears lead to unloading-induced osseous changes to the humeral head13. Chronic degeneration of the muscle before repair is usually associated with greater bone loss in the humeral head and leads to low cellular remodeling and poor extracellular matrix formation14. However, Ditsios et al. showed that mechanical unloading is not the only factor Prohydrojasmon racemate accountable for the reduction in bone mineral density (BMD) at the healing tendon-to-bone attachment15. Injury to the flexor digitorum profundus tendon in an animal model without any alteration of limb loading resulted in a sevenfold increase in osteoclast surface after 7 days, leading to a 7% decrease in BMD after 21 days. To address the bone loss that occurs during tendon-to-bone Prohydrojasmon racemate healing, investigators in a previous study suppressed osteoclast activity using bisphosphonate treatment8,9,16. Treatment led to improved mechanical properties in the treatment group compared with the control group. However, therapy with bisphosphonates is not ideal, especially in the younger populace, because of its association with reduced bone turnover and increased risk for bone fracture17-19. Another approach to increase bone mass at the site of healing is to administer a bone-anabolic agent to stimulate new bone formation. Sclerostin antibodies that block sclerostin, a negative regulator of bone formation produced largely by osteocytes, systemically increase bone formation and bone mass in animal models and osteoporotic patients20-22. In the current study, a novel application of sclerostin antibody (Scl-Ab) treatment was tested for enhancing tendon-to-bone healing. Using a well-established animal model of the rotator cuff, we tested the hypothesis that Scl-Ab treatment would prevent bone loss during tendon-to-bone healing, leading to improved outcomes. == Materials and Methods == == Animal Model and Study Design == Eighty-seven adult male Sprague-Dawley rats Rabbit Polyclonal to MRPS18C (approximately 4 months aged and weighing approximately 350 g) were used in this study, as approved by the Institutional Animal Care and Use Committee. Fifty-three rats received surgical injury and repair, and 34 rats were used as uninjured controls (the normal group). Of the 53 injured-and-repaired rats, 10 (5 that received Scl-Ab [the Scl-Ab group] and 5 that had no treatment [the control (CTL) group]) were used to study 2 weeks of healing, 20 (10 in the Scl-Ab treatment group and 10 in the CTL group) were used to study 4 weeks of healing, and 23 Prohydrojasmon racemate (12 in the Scl-Ab treatment group and 11 in the CTL group) were used to study 8 weeks of healing. Of the 34 uninjured control animals, 17 were used to study the effect.