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Updated: Jan 31, 2026

An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Effects of Estrogen-Deficient State on Rotator Cuff Healing
Koji Tanaka1, Tomonoshin Kanazawa1, Masafumi Gotoh2
1Department of Orthopaedic Surgery, Kurume University School of Medicine, Kurume, Japan.
Background:
Rotator cuff retears after surgical repair are a concern, despite advances in operative techniques, but few studies have investigated the effects of the estrogen-deficient state on tendon-to-bone healing at the repair site.
Purpose:
We evaluated the effect of the estrogen-deficient state on tendon-to-bone healing after rotator cuff repair in an ovariectomized rat model.
Study Design:
Controlled laboratory study.
Methods:
Female Sprague Dawley rats underwent detachment and immediate repair of the supraspinatus tendon. Surgery was performed in 24 rats at 4.5 weeks of age 17 weeks after ovariectomy (OVX group) and in 24 age-matched control rats without ovariectomy (control group). Animals were sacrificed at 2, 4, 8, and 12 weeks after surgery for biomechanical and histological evaluations of reattachment. Bone mineral density (BMD) at the insertion site and cancellous bone in the humeral head was assessed by micro-computed tomography.
Results:
BMD was significantly lower both at the insertion site and in cancellous area in the OVX group than in the control group at weeks 2 to 12. Ultimate load to failure, ultimate stress, linear stiffness, and the Young modulus were significantly lower in the OVX group than in the control group at 2 and 4 weeks, but the difference was no longer significant at 8 and 12 weeks. At 2 and 4 weeks, relatively immature granulation tissue was observed in the OVX group compared with the control group. At 8 and 12 weeks after surgery, there were differences in the tendon-bone interface in the 2 groups: Direct insertion with well-established chondroid tissue was seen in the control group, and indirect insertion without chondroid tissue was seen in the OVX group. Consistently, the amount of chondroid tissue was greater and collagen organization was better in the control group than in the OVX group. Cells expressing cathepsin K were significantly more numerous both at the insertion site and in cancellous bone in the OVX group than in the control group.
Conclusion:
The estrogen-deficient state by ovariectomy, compared with control rats, led to decreased biomechanical properties and poor development of chondroid tissue that influenced the repair of the tendon insertion after surgery.
Clinical Relevance:
Agents that modulate bone metabolism might improve tendon-to-bone healing in patients with an estrogen-deficient state, such as postmenopausal women who undergo rotator cuff surgery.
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