The influence of locally applied granulocyte-colony stimulating factor on osteoporotic bone.

OBJECTIVES: The compromised capacity of bone healing in osteoporotic population renders a serious concern of patients and clinicians. This study aimed to investigate the influence of G-CSF on bone reconstruction using an osteoporotic animal model. MATERIALS AND METHODS: Sixty skeletal mature female Spraque-Dawley rats underwent bilateral ovariectomy (OVX) and were assigned into three groups (n = 20). Three months after OVX, defects of 5 mm in cranial and 2 mm in femur were surgically created on all the animals. The defects were left unfilled, filled with gelatin sponge (GS), or filled with granulocyte-colony stimulating factor (G-CSF) infused GS. Specimens were retrieved for histomorphometric and micro-CT analyses at weeks 1, 4, 8, and 12 after surgery. RESULTS: At early stage of week 1 to week 8, the histomorphometric and micro-CT analysis demonstrated more advanced bone formation in femur in the control group; by week 12, all groups achieved cortical closure. In cranial bone, more advanced bone formation was exhibited in G-CSF-treated group at both early and late stages, although this observation was not statistically significant. CONCLUSIONS: The results indicated that in osteoporotic bone, G-CSF may advance bone healing in cranial bone where spontaneous bone formation was insufficient.

Skeletal site-specific response to ovariectomy in a rat model: change in bone density and microarchitecture.

OBJECTIVES: Ovariectomized (OVX) rat model has been widely used in osteoporosis-related studies. However, the discrepancies in age and skeletal sites being investigated make it difficult to compare the results from different studies. The purpose of this study was to provide information of systemic skeletal site-specific changes in a stable OVX rat model. MATERIAL AND METHODS: Thirty-three 6-month Spraque-Dawley female rats were used. Fifteen rats underwent ovariectomy, and fifteen received sham surgery. Three animals without any surgery were sacrificed at week 0 to serve as baseline. Three animals in the OVX and sham group, respectively, were euthanized at week 2, 4, 12, 24 and 36 post-surgery. Ten bone sites, including parietal bone, interparietal bone, maxilla, mandible, humerus, ulna, femur, tibia, lumber vertebra, and ilium, were subjected to micro-CT. RESULTS: Overall, long bones, lumber vertebra, and ilium showed similar trend of bone loss post-OVX, with tibia and femur suffered the most bone loss and spine the least (decreased by 75.0%, 70.4% and 36.6% in bone mineral density BMD at week 36 from base line, respectively). Upon OVX, jaw bones and cranial bones only showed a minor reduction in BMD (decreased by 1~3% from baseline) at week 36. Significant deterioration of trabecular structure was detected in long bones, lumber vertebra, and ilium post-OVX, while jaw bones remained relatively stable. CONCLUSIONS: This study for the first time assessed the systemic site-specific bone loss and microarchitecture changes in OVX rat model. It provided valuable information for selecting bone site and observation time in osteoporosis-related study.

Wound healing of osteotomy defects prepared with piezo or conventional surgical instruments: a pilot study in rabbits.

AIM: The aim of the present study was to evaluate and compare the wound-healing process following osteotomies performed with either conventional rotary burs or piezoelectric surgery in a rabbit model. METHODS: Two types of osteotomy window defects of the nasal cavities were prepared on the nasal bone of 16 adult New Zealand white rabbits with either a conventional rotary bur or piezo surgery. The defects were covered with a resorbable membrane. Four animals were killed at 1, 2, 3, and 5 weeks after the surgical procedure, respectively. Histological and morphometric evaluations were performed to assess the volumetric density of various tissue components: the blood clot, vascularized structures, provisional matrix, osteoid, mineralized bone, bone debris, residual tissue, and old bone. RESULTS: Significantly more bone debris was found at 1 week in the conventionally-prepared defects compared to the piezo surgically-prepared defects. At 2 and 3 weeks, a newly-formed hard tissue bridge, mainly composed of woven bone, was seen; however, no statistically-significant differences were observed. At 5 weeks, the defects were completely filled with newly-formed bone. CONCLUSION: The defects prepared by piezo surgery showed a significantly decreased proportion of bone debris at 1 week, compared to conventional rotary bur defect.

Healing of osteotomy sites applying either piezosurgery or two conventional saw blades: a pilot study in rabbits.

PURPOSE: The purpose of this study was to compare bone healing of experimental osteotomies applying either piezosurgery or two different oscillating saw blades in a rabbit model. METHODS: The 16 rabbits were randomly assigned into four groups to comply with observation periods of one, two, three and five weeks. In all animals, four osteotomy lines were performed on the left and right nasal bone using a conventional saw blade, a novel saw blade and piezosurgery. RESULTS: All three osteotomy techniques revealed an advanced gap healing starting after one week. The most pronounced new bone formation took place between two and three weeks, whereby piezoelectric surgery revealed a tendency to faster bone formation and remodelling. Yet, there were no significant differences between the three modalities. CONCLUSIONS: The use of a novel as well as the piezoelectric bone-cutting instrument revealed advanced bone healing with a favourable surgical performance compared to a traditional saw.

Responses of distraction regenerate to high-frequency traction at a rapid rate.

BACKGROUND: Continuous traction is capable of creating an optimal biological environment for bone healing which may finally compensate for the rapid distraction rate in distraction osteogenesis. This study was designed to investigate the response of distraction callus to continuous distraction at a rapid rate using a rabbit model of mandibular lengthening. METHODS: Thirty adult New Zealand white rabbits were randomly assigned to the intermittent (1 step/d) or continuous distraction (8 steps/s) group, with 15 in each. After osteotomy, manual-driven or autodriven distractor was adapted accordingly. The distraction was activated at a rate of 3.0 mm/d for 4 days. Five rabbits in each group were killed at week 2, week 4, and week 12 of consolidation, respectively. Plain radiography, microcomputed tomography, and histology examinations were used to evaluate the bone regeneration status. RESULTS: Plain radiographs and histologic studies demonstrated more advanced bone healing in continuous distraction group than that in intermittent distraction group at all the examined time points. Quantitative microcomputed tomography analysis showed significantly higher bone volume in continuous distraction group at week 2 (p < 0.01) and week 4 (p < 0.05) of consolidation. CONCLUSIONS: Continuous traction by autodriven distractor could be a promising clinical alternative to shorten the treatment course of distraction osteogenesis. Further studies to test its clinical potential using large animals that have similar metabolic rate and muscular resistance with human being are necessary.

Comparison of gene expression of tissue inhibitor of matrix metalloproteinase-1 between continuous and intermittent distraction osteogenesis: a quantitative study on rabbits.

BACKGROUND: Distraction osteogenesis is a controlled surgical procedure that initiates a regenerative process and uses mechanical strain to enhance the biological responses of the injured tissues to create new bone. To explore the effect of high-frequency mechanical traction on the expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), we compared the gene expression of TIMP-1 between continuous and intermittent distraction osteogenesis using a rabbit model of mandibular lengthening. MATERIALS AND METHODS: Forty adult New Zealand white rabbits were randomly assigned to the intermittent and continuous distraction groups. A unilateral mandibular osteotomy was performed and a custom-designed manual-driven or auto-driven distractor was bridged over the osteotomy segments. Animals were sacrificed at day-6, day-10, day-14 and day-21 after osteotomy. Samples were examined with real-time polymerase chain reaction (PCR). RESULTS: Real-time PCR examination showed significantly higher mRNA levels of TIMP-1 under continuous distraction than that under intermittent distraction at day-6 and day-10. No significant differences were found at day-14 and day-21. CONCLUSION: High-frequency traction provides a good mechanical environment for accelerating bone formation by up-regulating TIMP-1.