Research Article: The effect of graft application and allopurinol treatment on calvarial bone defect in rats1

Date Published: March 18, 2019

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em

Author(s): Nihat Laçin, Bozan Serhat İzol, Ebru Gökalp Özkorkmaz, Buşra Deveci, Mehmet Cudi Tuncer.


To investigate the effects of allopurinol administration on osteoinductive
reaction and bone development with graft material.

Thirty-six Wistar albino rats were divided into 3 groups. In the control
group, calvarial bone defect was only created without any treatment. In the
Defect + Graft group, allograft treatment was performed by forming 8 mm
calvarial bone defect. In the Defect + Graft + Allopurinol group,
alloplastic bone graft was placed in the calvarial bone defect and then,
allopurinol (50 mg/kg/day) treatment was intraperitoneally applied for 28

Histopathological examination revealed inflammation, congestion in the
vessels, and an increase in osteoclast cells in the defect area. We also
observed that new osteocyte cells, increase in connective tissue fibers, and
new bone trabeculae. Osteopontin expression was positive in osteoblast cells
and lacunated osteocyte cells were located in the periphery of the new bone
trabeculae. Osteopontin expression was also positive in osteoblasts and
osteocytes cells of new bone trabeculae in the graft site.

It has been shown that allopurinol treatment in rat calvaria defects may
induce osteoblastic activity, matrix development, mature bone cell formation
and new bone formation when used with autogenous grafts.

Partial Text

Bone defects in the maxillofacial region can appear after trauma, infection, bone
tumours or cysts and orthognathic surgical procedures. While small defects in the
bone can be repaired by natural bone healing processes, large defects require grafts
and implants, using various materials1. Calvarial critical dimension defects have been widely used to evaluate bone
regenerative materials. In these defects, it is important to maintain a suitable
area due to the competition between the surrounding soft tissues and bone formation
into the defect by using barrier membranes2. For the rat calvarial defect, 8 mm is generally accepted to be of critical

Every single surgical methodology and the consequent care and healing of the animals
utilized as a part of this investigation were in strict understanding with the
National Institutes of Health (NIH Publications No. 85-23, revised 1985) rules for
animal care. This study was approved by the Ethics Committee for Animal
Experimentation of the Faculty of Medicine at Dicle University,Turkey.

The histopathological results of the present study were evaluated under light
microscope. We compared histopathological findings in the control and other
experimental groups (Table 1, Fig. 1).

The calvarial bone defect model is appropriate for the examination of maxillary bone
regeneration because it has several similarities to the maxillofacial area38,39. The critical-size rat calvarial defect, compared with other experimental
bone defects, is a convenient model for evaluating bone regenerative effects of
biomaterials. Research mainly including experimental calvarial defect models are
also currently conducted to find out materials with potential, if any,
osteopromotive effect in bone repair or regeneration40. Healing occurs after regeneration of bone, infiltration of granulation
tissue, remodelization of osteogenic cells with proliferation. The following case
continues with a cellular activity that begins with an acute inflammatory response.
Bone formation depends on the cooperation of various factors such as specific cell
types like mesenchymal stem cells and soluble molecules such as osteoclasts,
hydroxyapatite, extracellular matrix molecules, cytokines, and bone morphogenetic
proteins, hormones, vitamins and various factors such as growth factors have been

It has been shown that that allopurinol treatment in rat calvaria defects can induce
osteoblastic activity, matrix development, mature bone cell formation and new bone
formation by using autogenous grafts.




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