The biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in rats

Abstract Background Although, glucocorticoid (GC) and calcitonin-induced changes in bone repair have been studied previously, the exact effects of these on fracture healing remain controversial. Hence, the purpose of this experimental study is to determine biochemical and histological effects of loc...

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Main Authors: Salim Ersozlu, Bartu Sarisozen, Ozgur Ozer, Saduman Balaban Adim, Orcun Sahin
Format: Article
Language:English
Published: SpringerOpen 2017-07-01
Series:Journal of Experimental Orthopaedics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40634-017-0100-x
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author Salim Ersozlu
Bartu Sarisozen
Ozgur Ozer
Saduman Balaban Adim
Orcun Sahin
author_facet Salim Ersozlu
Bartu Sarisozen
Ozgur Ozer
Saduman Balaban Adim
Orcun Sahin
author_sort Salim Ersozlu
collection DOAJ
description Abstract Background Although, glucocorticoid (GC) and calcitonin-induced changes in bone repair have been studied previously, the exact effects of these on fracture healing remain controversial. Hence, the purpose of this experimental study is to determine biochemical and histological effects of locally administrated GC and systemically administrated calcitonin on the kinetics of healing response after bone marrow ablation in rats. Methods After having undergone marrow ablation, a steroid-treated group of rats (n = 24) received a single dose of intramedullary methylprednisolone (2 mg/kg), a calcitonin-treated group (n = 24) received intermittently administrated subcutaneous salmon calcitonin (16 IU/kg), and a control group (n = 24) received intramedullary saline (25 μl). Results Blood samples taken on days 1, 3, 7, 9, and 15 after ablation showed an increase in serum calcium, alkaline phosphatase (ALP), and phosphate levels in the Calcitonin and Control groups. Levels of calcium and ALP peaked on day 7 after ablation. However, an increase in phosphate levels indicated a biphasic reaction that peaked on the third and ninth day after ablation. Hypercalcemia was not observed in Steroid group because of the inhibition of osteoclastic bone resorption. In that group, the serum levels of ALP and phosphate were lower than baseline levels. The levels of urinary calcium excretion peaked 3 to 7 days after marrow ablation in the control group and 7 to 9 days after that procedure in the steroid group. Histologic evaluation showed that the rats in the control group demonstrated the expected healing period according to the histological grades and that a delay in healing occurred in the calcitonin group after day 9 because of the inhibition of osteoclastic bone resorption. All rats in the steroid group exhibited a decrease and delayed healing response. Conclusion Total serum calcium, phosphate, and ALP levels increased after bilateral tibial bone marrow ablation and urine calcium and hydroxyproline excretion also increased as a factor of bone resorption. Subcutaneously administrated salmon calcitonin did not affect biochemical changes after marrow ablation. Single-dose intramedullary methylprednisolone inhibited extra-tibial bone resorption induced by cytokines after bone marrow ablation.
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spelling doaj.art-7d0c7eea0b2443dab75d3a325c9008532024-02-02T18:16:36ZengSpringerOpenJournal of Experimental Orthopaedics2197-11532017-07-01411910.1186/s40634-017-0100-xThe biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in ratsSalim Ersozlu0Bartu Sarisozen1Ozgur Ozer2Saduman Balaban Adim3Orcun Sahin4Faculty of Medicine, Department of Orthopaedics and Traumatology, Istinye University, Liv HospitalFaculty of Medicine, Department of Orthopaedics and Traumatology, Uludag UniversityFaculty of Medicine, Department of Orthopaedics and Traumatology, Uludag UniversityFaculty of Medicine, Department of Pathology, Uludag UniversityFaculty of Medicine, Department of Orthopaedics and Traumatology, Baskent UniversityAbstract Background Although, glucocorticoid (GC) and calcitonin-induced changes in bone repair have been studied previously, the exact effects of these on fracture healing remain controversial. Hence, the purpose of this experimental study is to determine biochemical and histological effects of locally administrated GC and systemically administrated calcitonin on the kinetics of healing response after bone marrow ablation in rats. Methods After having undergone marrow ablation, a steroid-treated group of rats (n = 24) received a single dose of intramedullary methylprednisolone (2 mg/kg), a calcitonin-treated group (n = 24) received intermittently administrated subcutaneous salmon calcitonin (16 IU/kg), and a control group (n = 24) received intramedullary saline (25 μl). Results Blood samples taken on days 1, 3, 7, 9, and 15 after ablation showed an increase in serum calcium, alkaline phosphatase (ALP), and phosphate levels in the Calcitonin and Control groups. Levels of calcium and ALP peaked on day 7 after ablation. However, an increase in phosphate levels indicated a biphasic reaction that peaked on the third and ninth day after ablation. Hypercalcemia was not observed in Steroid group because of the inhibition of osteoclastic bone resorption. In that group, the serum levels of ALP and phosphate were lower than baseline levels. The levels of urinary calcium excretion peaked 3 to 7 days after marrow ablation in the control group and 7 to 9 days after that procedure in the steroid group. Histologic evaluation showed that the rats in the control group demonstrated the expected healing period according to the histological grades and that a delay in healing occurred in the calcitonin group after day 9 because of the inhibition of osteoclastic bone resorption. All rats in the steroid group exhibited a decrease and delayed healing response. Conclusion Total serum calcium, phosphate, and ALP levels increased after bilateral tibial bone marrow ablation and urine calcium and hydroxyproline excretion also increased as a factor of bone resorption. Subcutaneously administrated salmon calcitonin did not affect biochemical changes after marrow ablation. Single-dose intramedullary methylprednisolone inhibited extra-tibial bone resorption induced by cytokines after bone marrow ablation.http://link.springer.com/article/10.1186/s40634-017-0100-xFracture healingMarrow ablationCalcitoninMethylprednisoloneBone repair
spellingShingle Salim Ersozlu
Bartu Sarisozen
Ozgur Ozer
Saduman Balaban Adim
Orcun Sahin
The biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in rats
Journal of Experimental Orthopaedics
Fracture healing
Marrow ablation
Calcitonin
Methylprednisolone
Bone repair
title The biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in rats
title_full The biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in rats
title_fullStr The biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in rats
title_full_unstemmed The biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in rats
title_short The biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in rats
title_sort biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation an experimental comparative study in rats
topic Fracture healing
Marrow ablation
Calcitonin
Methylprednisolone
Bone repair
url http://link.springer.com/article/10.1186/s40634-017-0100-x
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