The Effect of Antiosteoporosis Therapy With Risedronate on Rotator Cuff Healing in an Osteoporotic Rat Model

Abstract

Background: Osteoporosis increases the revision rate of rotator cuff repair (RCR). Weak fixation might not be the only cause of high RCR failure rates. The biological mechanism associated with tendon-to-bone healing after RCR in osteoporosis should be investigated. Hypothesis: (1) Osteoporosis would impair rotator cuff healing through the high osteoclastic activity at the repaired interface. (2) Risedronate would promote rotator cuff healing by reducing osteoclastic activity at the repaired interface. Study Design: Controlled laboratory study. Methods: A total of 84 female Sprague Dawley rats were randomly treated using ovariectomy or sham surgeries to establish osteoporotic and nonosteoporotic rat models. After confirming osteoporosis, a chronic rotator cuff tear model was created and RCR was performed. Postoperatively, osteoporotic rats were randomly divided into osteoporosis (OP) and osteoporosis with risedronate administration (OP+RIS) groups. Nonosteoporotic rats were used as the control (CON) group. Osteoclastic activity was measured at 1 and 3 weeks after RCR, and histologic analysis of the tendon-to-bone interface, bone morphometric evaluation, and biomechanical tests were performed at 4 and 8 weeks. Results: At the early healing stages of 1 and 3 weeks after RCR, the OP group showed the highest osteoclast density at the repaired interface. Compared with the OP group, risedronate administration significantly decreased osteoclast density in the OP+RIS group. At 8 weeks, histologic scores were greater in the OP+RIS group than in the OP group but still lower than in the CON group. Histologic scores at 8 weeks were negatively correlated with osteoclast density at the early healing stage. Additionally, the OP+RIS group showed better bone morphometric parameters and biomechanical properties than did the OP group. Conclusion: Osteoporosis impaired rotator cuff healing, which might be related to the high osteoclast density at the repaired interface at the early healing stage. Postoperative risedronate administration decreased osteoclast density and enhanced rotator cuff healing in osteoporotic rats, although the effect was inferior to that in nonosteoporotic rats. Clinical Relevance: Postoperative risedronate administration can be considered a potential therapy to enhance rotator cuff healing in patients with postmenopausal osteoporosis. However, this needs to be verified in a clinical setting.

Abaloparatide Improves Rotator Cuff Healing via Anabolic Effects on Bone Remodeling in a Chronic Rotator Cuff Tear Model of Rat With Osteoporosis: A Comparison With Denosumab

“…After 12 weeks, the osteoporotic rat model was confirmed using micro-CT, according to a previous report. 52…”

“…4-0 Prolene suture (Ethicon). 33,52 After the greater tuberosity was prepared by debriding all the fibrocartilage and soft tissue until bleeding was noted, 2 bone tunnels were created using a 22-gauge needle (Olympus) at the articular margin of the footprint in a crossed fashion. Then the tendon was reattached to its footprint using the free suture ends shuttled through the tunnels, followed by a routine closure in layers.…”

“…To analyze the bone anabolic or catabolic effects of Dmab and ABL on the supraspinatus tendon reattachment site, the samples at 2 weeks were used to detect osteoclast using tartrate-resistant acid phosphatase staining and osteocalcin-positive osteoblast using immunohistochemistry at the repaired site according to the protocols. 15,17,20,52 The osteoblast or osteoclast activity was quantified by counting the number of positive cells in the area of the bony portion of the tendon enthesis and the trabecular bone directly adjacent to the enthesis, which was recorded as cell density (cells/mm 2 ). 20,52 The balance between osteoblasts and osteoclasts at the repaired site was analyzed using the osteoblast-to-osteoclast ratio.…”

“…The general morphological characteristics of the maturation of the tendon-to-bone interface, including cellularity, vascularity, collagen fiber, and interface remodeling, were quantitatively determined using a histological scoring system that has been previously described (Table 1). 40,52 The scoring was checked by 2 experienced investigators (Z.Y and J.C.), who were blinded to the group allocation and time points. A perfect score in this system was 28 points, and a higher score indicated a better healing interface.…”

“…50 The sections stained with picrosirius red for the semiquantitative analysis of collagen deposition and maturity at the repair site were examined by quantifying the collagen birefringence under polarized light microscopy (Eclipse E800; Nikon). 1,26,52 The brightness (gray value) was measured according to previously reported procedures, 9,26 where a higher value suggested an increased amount of mature type I collagen. 26,52 All quantitative measurements were performed using the Image J software program (National Institutes of Health) by 2 independent observers (Z.Y.…”