Basic and patient-oriented research
Histomorphometric Evaluation of the Effects of Zoledronic Acid on Mandibular Distraction Osteogenesis in Rabbits

https://doi.org/10.1016/j.joms.2007.12.004Get rights and content

Purpose

To assess the effect of systemic administration of zoledronic acid (ZA) on mineralization of newly formed bone and to determine strain-related osteoporosis on surrounding bone during lengthening of immature rabbit mandible.

Materials and Methods

Eighteen New Zealand white rabbits were divided randomly into 2 groups, and bone lengthening was carried out in the left portion of the mandible through distraction osteogenesis with a rate of 0.5 mm every 12 hours for 5 days. The experimental group was administered 0.1 mg/kg ZA intravenously. The control group was given saline infusion only during operation. All animals were sacrificed at the end of the 28-day consolidation period. The mandibles of all animals were removed and regenerate was evaluated. Osteoblasts, osteoclasts, collagen fibers, and fibroblasts were marked within 0.1-mm2 area and newly formed bone area was measured within 0.5-mm2 area. All data were analyzed using Mann-Whitney U test.

Results

Although irregular bone destruction spots were seen in the control group, the experimental group showed regular ossification areas and significant difference between osteoblast and osteoclast numbers (P < .05). In the regenerate zone, there was considerable difference between the 2 groups in terms of osteoblast, osteoclast, and collagen amounts (P < .05). Additionally, newly formed bone areas and fibroblast count were higher in experimental group.

Conclusions

The results of this study showed that ZA had positive effects on the new bone formation, which may potentially shorten the consolidation period.

Section snippets

Materials and Methods

Ethical approval was obtained from Selcuk University Faculty of Medicine Department of Experimental Medicine Research and Application Center Ethical Committee.

This experimental study was carried out with 18 5-month-old male New Zealand rabbits weighing 2.2 to 2.8 kg (mean weight, 2.4 ± 0.17 kg). All animals were divided into 2 groups (experimental group and control group).

General anesthesia was achieved via intramuscular injection of 50 mg/kg ketamine and 8 mg/kg xylazine hycloride (Rompun;

Results

One animal was excluded from study because of infection surrounding the pin. No other complications or problems were encountered with the animals during the procedures.

Discussion

Craniofacial bones are different from long bones with regard to their membranous structure and biomechanical condition. For example, long bones bear forces along their anatomical axis whereas the mandible faces strengths perpendicular to its anatomical axis. Additionally, mandible and long bones express different growth and development.10

Bisphosphonates affect bone resorption strongly and have been applied in management of several osteoclast originated bone diseases. Bisphosphonates are

References (34)

  • L.A. Assael

    New foundations in understanding osteonecrosis of the jaws

    J Oral Maxillofac Surg

    (2004)
  • R.E. Marx et al.

    Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: Risk factors, recognition, prevention, and treatment

    J Oral Maxillofac Surg

    (2005)
  • D. Paley

    Problems, obstacles, and complications of limb lengthening by the Ilizarov technique

    Clin Orthop Relat Res

    (1990)
  • S. Tsubota et al.

    Transplantation of osteoblast-like cells to the distracted callus in rabbits

    J Bone Joint Surg Br

    (1999)
  • H. Okazaki et al.

    Stimulation of bone formation by recombinant fibroblast growth factor-2 in callotasis bone lengthening of rabbits

    Calcif Tissue Int

    (1999)
  • H. El-Mowafi et al.

    The effect of low-intensity pulsed ultrasound on callus maturation in tibial distraction osteogenesis

    Int Orthop

    (2005)
  • D.G. Little et al.

    Intravenous pamidronate reduces osteoporosis and improves formation of the regenerate during distraction osteogenesisA study in immature rabbits

    J Bone Joint Surg Br

    (2001)
  • Cited by (30)

    • Investigation of effects of low level laser therapy in distraction osteogenesis

      2018, Journal of Stomatology, Oral and Maxillofacial Surgery
      Citation Excerpt :

      To shorten this period, several techniques and biologic materials have been investigated. Calcium sulfate, electrical stimulation, osteoblast like cell transplantation, growth hormone, bone morphogenetic proteins, insulin like growth factor-1 (IGF-1), trombosit-rich-plasma, ultrasound, calcitonine, simvastatine, zoledronic acid, calcium hydroxide, hyperbaric oxygen therapy have been used to stimulate bone callus and to achieve a good quality of bone in a shorter consolidation period [17–30]. The positive effects on low energy level laser bone healing suggests that it may also have biostimulatory role in distraction otoogenesis.

    • Enhancement of bone consolidation in mandibular distraction osteogenesis: A contemporary review of experimental studies involving adjuvant therapies

      2013, Journal of Plastic, Reconstructive and Aesthetic Surgery
      Citation Excerpt :

      Bone density was also noted to be improved with this adjuvant therapy. Zoledronic acid is another bisphosphonate that has been studied in MDO experimental models.26,27 Similar to alendronate, both of these studies showed significantly greater BMD and BMC in the treatment groups, suggesting a favorable bone healing effect of this medication.

    • Effects of alendronate on human osteoblast-like MG63 cells and matrix metalloproteinases

      2012, Archives of Oral Biology
      Citation Excerpt :

      The premise of this hypothesis is that the jaw has greater blood supply and higher remodelling rate than other skeleton tissues. In vivo animal experiments have shown that bisphosphonates can suppress normal bone turnover and remodelling, and inhibit bone reparative ability.22,29,30 Osteoblasts and osteoclasts are the two major players in the bone remodelling process and are both affected by bisphosphonates.

    View all citing articles on Scopus

    This study was supported by Scientific Research Project, Selçuk University, Konya, Turkey.

    View full text