Jakob E Schanda1,2,3, Claudia Keibl2,3, Patrick Heimel2,3,4, Xavier Monforte2,3,5, Stefan Tangl2,3,4, Xaver Feichtinger1,2,3, Andreas H Teuschl2,3,5, Andreas Baierl6, Christian Muschitz7, Heinz Redl2,3, Christian Fialka1,8, Rainer Mittermayr1,2,3. 1. AUVA Trauma Center Vienna-Meidling, Department for Trauma Surgery, Vienna, Austria. 2. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria. 3. Austrian Cluster for Tissue Regeneration, Vienna, Austria. 4. Medical University of Vienna, Department of Oral Surgery, Karl Donath Laboratory for Hard Tissue and Biomaterial Research, Vienna, Austria. 5. University of Applied Sciences Technikum Wien, Department of Life Science Engineering, Vienna, Austria. 6. University of Vienna, Department of Statistics and Operations Research, Vienna, Austria. 7. St Vincent Hospital Vienna, II. Medical Department, Metabolic Bone Disease Unit, Vienna, Austria. 8. Sigmund Freud University, Medical Faculty, Center for the Musculoskeletal System, Vienna, Austria.
Abstract
BACKGROUND: Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density. HYPOTHESIS: Zoledronic acid improves bone mineral density of the humeral head and biomechanical properties of the enthesis after reconstruction of chronic rotator cuff tears in rats. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 32 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy with delayed transosseous rotator cuff reconstruction after 3 weeks. All rats were sacrificed 8 weeks after rotator cuff repair. Animals were randomly assigned to 1 of 2 groups. At 1 day after rotator cuff reconstruction, the intervention group was treated with a single subcutaneous dose of zoledronic acid at 100 µg/kg bodyweight, and the control group received 1 mL of subcutaneous saline solution. In 12 animals of each group, micro-computed tomography scans of both shoulders were performed as well as biomechanical testing of the supraspinatus enthesis of both sides. In 4 animals of each group, histological analyses were conducted. RESULTS: In the intervention group, bone volume fraction (bone volume/total volume [BV/TV]) of the operated side was higher at the lateral humeral head (P = .005) and the medial humeral head (P = .010) compared with the control group. Trabecular number on the operated side was higher at the lateral humeral head (P = .004) and the medial humeral head (P = .001) in the intervention group. Maximum load to failure rates on the operated side were higher in the intervention group (P < .001). Cortical thickness positively correlated with higher maximum load to failure rates in the intervention group (r = 0.69; P = .026). Histological assessment revealed increased bone formation in the intervention group. CONCLUSION: Single-dose therapy of zoledronic acid provided an improvement of bone microarchitecture at the humeral head as well as an increase of maximum load to failure rates after transosseous reconstruction of chronic rotator cuff lesions in rats. CLINICAL RELEVANCE: Zoledronic acid improves bone microarchitecture as well as biomechanical properties after reconstruction of chronic rotator cuff tears in rodents. These results need to be verified in clinical investigations.
BACKGROUND: Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density. HYPOTHESIS: Zoledronic acid improves bone mineral density of the humeral head and biomechanical properties of the enthesis after reconstruction of chronic rotator cuff tears in rats. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 32 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy with delayed transosseous rotator cuff reconstruction after 3 weeks. All rats were sacrificed 8 weeks after rotator cuff repair. Animals were randomly assigned to 1 of 2 groups. At 1 day after rotator cuff reconstruction, the intervention group was treated with a single subcutaneous dose of zoledronic acid at 100 µg/kg bodyweight, and the control group received 1 mL of subcutaneous saline solution. In 12 animals of each group, micro-computed tomography scans of both shoulders were performed as well as biomechanical testing of the supraspinatus enthesis of both sides. In 4 animals of each group, histological analyses were conducted. RESULTS: In the intervention group, bone volume fraction (bone volume/total volume [BV/TV]) of the operated side was higher at the lateral humeral head (P = .005) and the medial humeral head (P = .010) compared with the control group. Trabecular number on the operated side was higher at the lateral humeral head (P = .004) and the medial humeral head (P = .001) in the intervention group. Maximum load to failure rates on the operated side were higher in the intervention group (P < .001). Cortical thickness positively correlated with higher maximum load to failure rates in the intervention group (r = 0.69; P = .026). Histological assessment revealed increased bone formation in the intervention group. CONCLUSION: Single-dose therapy of zoledronic acid provided an improvement of bone microarchitecture at the humeral head as well as an increase of maximum load to failure rates after transosseous reconstruction of chronic rotator cuff lesions in rats. CLINICAL RELEVANCE: Zoledronic acid improves bone microarchitecture as well as biomechanical properties after reconstruction of chronic rotator cuff tears in rodents. These results need to be verified in clinical investigations.
Authors: Jakob E Schanda; Barbara Obermayer-Pietsch; Gerhard Sommer; Philipp R Heuberer; Brenda Laky; Christian Muschitz; Klaus Pastl; Eva Pastl; Christian Fialka; Rainer Mittermayr; Johannes Grillari; Ines Foessl Journal: BMC Musculoskelet Disord Date: 2022-05-05 Impact factor: 2.562