Bone union formation in the rat mandibular symphysis using hydroxyapatite with or without simvastatin: effects on healthy, diabetic, and osteoporotic rats

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The objective is to compare new bone formation in critical defects in healthy, diabetic, and osteoporotic rats filled with hydroxyapatite (HA) alone and HA combined with simvastatin (SV).

Materials and methods

A total of 48 adult female Sprague-Dawley rats were randomized into three groups (n = 16 per group): Group, 1 healthy; Group 2, diabetics; and Group 3, osteoporotics. Streptozotocin was used to induce type 1 diabetes in Group 2, while bilateral ovariectomy was used to induce osteoporosis in Group 3. The central portion of the rat mandibular symphysis was used as a physiological critical bone defect. In each group, eight defects were filled with HA alone and eight with HA combined with SV. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2).


In all groups (healthy, diabetics, and osteoporotics), the defects filled with HA + SV presented greater radiological bone union, BMD, histological bone union, and more VEGF and BMP-2 positivity, in comparison with bone defects treated with HA alone.


Combined application of HA and SV improves bone regeneration in mandibular critical bone defects compared with application of HA alone in healthy, diabetic, and osteoporotic rats.

Clinical relevance

This study might help to patients with osteoporosis or uncontrolled diabetes type 1, but future studies should be done.

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Correspondence to F. Camacho-Alonso.

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The procedures and study protocol described here were approved by the University of Murcia Bioethics Committee (Spain) and the competent authority (A13160607).

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Camacho-Alonso, F., Martínez-Ortiz, C., Plazas-Buendía, L. et al. Bone union formation in the rat mandibular symphysis using hydroxyapatite with or without simvastatin: effects on healthy, diabetic, and osteoporotic rats. Clin Oral Invest (2020).

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  • Hydroxyapatite
  • Simvastatin
  • Critical bone defect
  • Mandibular symphysis
  • Bone regeneration
  • Rats
  • Diabetes
  • Osteoporosis