Abstract
This study aimed to evaluate the effect of two methods of local application of alendronate and parathyroid hormone (PTH) on bone repair and the systemic implications. A critically sized defect (5 mm) was created in the cranial region of twenty-five male Wistar rats, and the bone removed was particulated, and grafted back to the defect with different treatments. The animals were randomly divided into five groups: A1- bone graft immersion in alendronate solution (3 mg/kg) for 5 minutes; P1- bone graft immersion in PTH solution (20 µg); A2- weekly local applications of alendronate 1 mg/kg; P2- weekly local applications of PTH (20 µg); C- no drugs were used. The animals were euthanized 60 days after surgery. Cranial bone blocks were removed for histological, histomorphometric, and immunohistochemical analyses. MMP-2 and MMP-9 were used for immunolabeling. The kidneys, liver, and brain were also removed from all the rats for histological analysis. The data were submitted for statistical analysis with a level of significance of 0.05 (One-way ANOVA). The group C and group P2 presented a higher quantity of viable bone particles than the remaining groups. Groups A1, A2, and P1 presented with fewer viable bone particles than the control group, with a predominance of non-mineralized connective tissue. The histomorphometric analysis revealed no differences in relative bone area or MMP-2 or MMP-9 immunolabeling between the groups (p>0.05). Group A2 showed presence of fat in the liver consistent with hepatic steatosis. Changes in brain tissue were observed in groups A1 and P1.
Highlights
IntroductionBisphosphonates (BFs) are a class of drugs that are used to fight the effects of diseases affecting bone remodeling [1]
Bisphosphonates (BFs) are a class of drugs that are used to fight the effects of diseases affecting bone remodeling [1]. They are the first-line drugs for treatment of osteoporosis [2] and are used for treatment of other skeletal pathologies, such as multiple myeloma, bone pathologies associated with malignant neoplasia, and Paget’s disease [3]
In 2008, Ichinose et al [8] found that, in presence of physiological concentrations of plasmin, bisphosphonates reduced the amount of MMP2 in osteoblast-conditioned media, suggesting that BFs inhibit bone resorption by abrogating matrix metalloproteinases (MMPs)-2 protection induced by plasmin-mediated degradation
Summary
Bisphosphonates (BFs) are a class of drugs that are used to fight the effects of diseases affecting bone remodeling [1]. They are the first-line drugs for treatment of osteoporosis [2] and are used for treatment of other skeletal pathologies, such as multiple myeloma, bone pathologies associated with malignant neoplasia, and Paget’s disease [3]. Alendronate is a part of the second generation of the BFs class, and is the most widely used anti-resorptive drug [4]. It has been proven that BFs exert effects on the matrix metalloproteinases (MMPs), and the production of these proteins influences bone resorption. Another study [9] examining the effects of alendronate on growth of the condylar cartilage verified that the number of chondroclasts engaged in hypertrophied cartilage resorption was reduced significantly by alendronate treatment, at the same time reducing the expression of the level of MMP-9 at both the transcription and translation levels
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
