The Effect of Recombinant Human Parathyroid Hormone (rhPTH) on Tendon-to-Bone Healing in a Rat Rotator Cuff Model

Abstract

Objectives:Successful rotator cuff tendon repair is predicated upon secure tendon-to-bone healing. A recent study has shown that recombinant human parathyroid hormone (rhPTH) treatment results in improved tendon-to-bone healing at the latter stages of healing, but not at early time points. We hypothesized that delaying administration of rhPTH until after the acute inflammatory phase would improve tendon-to-bone healing at all time points in a rat rotator cuff repair model.Methods:One hundred and eight male Sprague Dawley rats underwent detachment and subsequent repair of the supraspinatus tendon based on an a priori power analysis. Fifty four rats underwent repair alone and 54 rats received repair plus daily subcutaneous injections of 10 µg/kg of rhPTH beginning on postoperative day 7 and continuing for 12 weeks. Rats were sacrificed at 2 and 16 weeks postoperatively for biomechanical testing or histologic and immunohistochemical analysis. Histologic slides were digitized, and the enthesis was evaluated quantitatively using NIH Image J and VisioMorph software.Results:At 2 weeks postoperatively, the rhPTH group had significantly higher load to failure than the control group (10.85 versus 5.16 N; p = 0.003). At 16 weeks, there was no significant difference in load to failure between the two groups (Figure 1). With respect to stiffness of the repair, there was no significant difference between the two groups at either time point, but there was a trend toward increased stiffness in the rhPTH group at 2 weeks postoperatively compared to the control group (5.09 vs. 3.77 N/mm; p = 0.12). Histologically, the rhPTH specimens had more fibrocartilage and osteoblasts at all time points, with significantly better collagen fiber orientation at 2 weeks.Conclusion:Administration of rhPTH significantly increased load to failure at 2 weeks postoperatively in a rat rotator cuff repair model, with improved collagen fiber organization and increased fibrocartilage formation. Delaying administration of rhPTH until postoperative day number 7, after the resolution of the acute inflammation from surgery had subsided, improved rotator cuff healing in the early postoperative period while maintaining later-stage mechanical strength.