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The bony callus.

The bony callus was investigated by staining with the PAS and von Gieson techniques. The callus appeared to be composed of two adjoining but distinct types of bone. The birefringence observed in the periosteum and callus cartilage revealed different sized collagen fibres, each oriented perpendicularly to the long axis of the diaphysis.

Animals↗

[Correlation between ultrasound and radiographic data for assessment of symphyseal bony callus maturation after distraction].

OBJECTIVE: To search for means of reducing ionizing radiation during treatment planning for transmandibular osteodistraction. MATERIAL AND METHODS: Eleven patients (6 female, 5 male) underwent combined bimaxillary osteodistraction at a mean age of 18 Years. The following investigations were performed to determine symphyseal callus maturation: occlusal radiographs (O-RX) preoperatively, after the active phase of distraction (mean 27 days); ultrasound investigations (US) after the active and consolidation phase. RESULTS: US showed calcification foci at the end of the active phase, when O-RX failed to do so. Both US and O-RX detected callus immaturity after 2 Months of consolidation in 1 patient. Both detected bridging ossification one Month later. DISCUSSION: US can replace radiography in the diagnosis of callus maturation related to distractor removal.

Adolescent↗

[The dynamic characteristics of regional muscle blood flow and the activity of mineralization processes in the bony callus with various methods of treating mandibular fractures].

RMBF was comparatively assessed in patients with lower jaw fractures under orthopedic therapy of the osteal suture. To this end, the 99m pertechnetate was injected bilaterally in masseter muscles. The data suggest that double jaw fixation had an adverse effect on RMBF, especially ipsilateral to the fracture. Nevertheless, the mineral metabolism intensity in the callus is higher under fixation as related to the cases surgically sutured.

Adult↗

Osteogenic growth peptide modulates fracture callus structural and mechanical properties.

The osteogenic growth peptide (OGP) is a key factor in the mechanism of the systemic osteogenic response to local bone marrow injury. Recent histologic studies have shown that OGP enhances fracture healing in experimental animals. To assess the effect of systemically administered OGP on the biomechanical and quantitative structural properties of the fracture callus, the present study used an integrated approach to evaluate the early stages (up to 4 weeks) of healing of unstable mid-femoral fractures in rats, which included biomechanical, micro-computed tomographic (microCT) and histomorphometric measurements. During the first 3 weeks after fracture, all the quantitative microCT parameters increased in the OGP- and vehicle-treated animals alike. After 4 weeks, the volume of total callus, bony callus, and newly formed bone was approximately 20% higher in animals administered with OGP, consequent to a decrease in the controls. The 4-week total connectivity was 46% higher in the OGP-treated animals. At this time, bridging between the fracture ends by newly formed bone was observed predominantly in the OGP-treated fractures. After 3 and 4 weeks, the OGP-treated animals showed higher biomechanical toughness of the fracture callus as compared to the PBS controls. Significant correlations between structural and biomechanical parameters were restricted to the OGP-treated rats. These data imply that the osteogenic effect of OGP results in enhanced bridging across the fracture gap and consequently improved function of the fracture callus. Therefore, OGP and/or its derivatives are suggested as a potential therapy for the acceleration of bone regeneration in instances of fracture repair and perhaps other bone injuries.

Animals↗

Heparanase mRNA expression during fracture repair in mice.

Bone fracture healing takes place through endochondral ossification where cartilaginous callus is replaced by bony callus. Vascular endothelial growth factor (VEGF) is a requisite for endochondral ossification, where blood vessel invasion of cartilaginous callus is crucial. Heparanase is an endoglucuronidase that degrades heparan sulfate proteoglycans (HSPG) and releases heparin-binding growth factors including VEGF as an active form. To investigate the role of heparanase in VEGF recruitment during fracture healing, the expression of heparanase mRNA and VEGF, and vessel formation were examined in mouse fractured bone. On days 5 and 7 after the fracture, when mesenchymal cells proliferated and differentiated into chondrocytes, heparanase mRNA was detected in osteo(chondro)clasts and their precursors, but not in the inflammatory phase (day 3). On day 10, both VEGF and HSPG were produced by hypertrophic chondrocytes of the cartilaginous callus and by osteoblasts of the bony callus; numerous osteo(chondro)clasts resorbing the cartilage expressed strong heparanase signals. Adjacent to the cartilage resorption sites, angiogenesis with CD31-positive endothelial cells and osteogenesis with osteonectin-positive osteoblasts were observed. On days 14 and 21, osteoclasts in the woven bone tissue expressed heparanase mRNA. These data suggest that by producing heparanase osteo(chondro)clasts contribute to the recruitment of the active form of VEGF. Thus osteo(chondro)clasts may promote local angiogenesis as well as callus resorption in endochondral ossification during fracture healing.

Animals↗

[Effect of radix Salviae miltiorrhizae on calcium, zinc, copper content in serum, callus and bony tissue in early stage of healing process in rat closed tibial fracture].

Changes of calcium, zinc, copper contents in serum, callus and bony tissue in the early stage of the healing process of rat closed tibial fracture, also the changes of them with radix Salviae miltiorrhizae (RSM) treatment were studied. It was found that calcium, zinc contents and Zn/Cu ratio increased significantly and the rise of serum copper content was inhibited by the administration of RSM after fracture. Zn/Cu ratio in fracture callus was correlated to the calcium content in fracture callus. These findings suggested that the effect of the promotion of RSM on fracture healing was related to the increased zinc content in serum, also related to the acceleration of mobilization of zinc in fractured bone, and to the acceleration of fracture callus formation and mineralization process by the increased zinc and Zn/Cu ratio in the callus of the fracture.

Animals↗

[Experimental studies of the effect of direct electric micro-current on the healing processes of bone defects].

As a procedure to accelerate healing of the bone defect, the electric micro-current has attracted much attention in the field of clinical application and experimental research. However, investigation of the calcifying process and comparison of the elements of the newly formed bony callus have not yet been carried out. In order to get deeper understanding of the callus formation and calcifying process in bone defects, this experiment aimed at comparing the healing processes of bone defects in the rabbit humerus between stimulated and non-stimulated control group. The bone specimens were surgically removed, on the 4th postoperative day and 1st, 2nd, 3rd, and 4th postoperative weeks. The specimens were examined by the use of the computer aided microanalyser, the energy dispersive spectrometer, and the scanning electron-microscope (JCMA-733). Histological examination was also made. In the stimulated group, on the 4th day, Ca and P of low concentration were observed around the inner periosteum indicating initiation of the calcification with callus formation. On the 1st week Ca and P were distributed diffusely in the bone defect. On the 2nd and 3rd weeks, the bone defect was almost filled with new bony callus and the calcification became more intense. After the 4th week, the distribution and concentration of Ca and P in the bony callus were similar to those of the surrounding cortical bone. Furthermore, the molar ratio of Ca/P of the new bony callus was much greater in the stimulated group than in the control group, and was rather similar to the molar ratio of Ca/P in the surrounding cortical bone. The results showed that the electric micro-current facilitated not only callus formation but also calcification, thus shortening the healing period of the bone defect.

Animals↗

Osteopenia and impaired fracture healing in aged EP4 receptor knockout mice.

The EP4 receptor, one of the subtypes of the prostaglandin E2 (PGE2) receptor, plays a critical role in the anabolic effects of PGE2 on bone. However, its role in the maintenance of bone mass in aged animals and its role in fracture healing is not well known. Our studies addressed these issues by characterizing the skeletal phenotype of aged, EP4 receptor knockout (KO) mice, and by comparing fracture healing in aged KO mice versus wild type (WT) mice. There was no significant difference in body weight and femoral length between KO and WT mice at 15 to 16 months of age. Lower bone mass was seen radiographically in both axial and long bones of KO mice relative to WT mice. Micro-CT images of the distal femurs showed thinner cortices, fewer trabeculae, and a deteriorated trabecular network in KO mice. Total bone content, trabecular content, and cortical content, as assessed by pQCT in the distal femur, were lower in KO mice than WT controls. Histomorphometric measurements showed that trabecular bone volume and bone formation rate were significantly decreased whereas osteoclast number on trabecular surface and eroded surface on endocortical surface were significantly increased in KO mice. These data indicated that deleting the EP4 receptor resulted in an imbalance in bone resorption over formation, leading to a negative bone balance. The lower bone formation rate in EP4 KO mice was primarily due to decreased mineralizing surface, suggesting that the defect in overall bone formation was mainly due to the defect in osteoblastogenesis. Fracture healing was examined in KO and WT mice subjected to a transverse femoral fracture. Callus formation was significantly delayed as evidenced both radiographically and histologically in the fractured femurs of KO mice compared with those of WT mice. KO mice had significant decreases in total callus area, cartilaginous callus area, and bony callus area 2 weeks after fracture. By 4 weeks, complete bony bridging was seen in WT mice but not in KO mice. These data demonstrate that the absence of the EP4 receptor decreases bone mass and impairs fracture healing in aged male mice. Our findings indicate that the EP4 receptor is a positive regulator in the maintenance of bone mass and fracture healing.

Aging↗

[Clinical observation on effects of qianggu capsules in treating radius distal osteoporotic fractures].

OBJECTIVE: To explore the effects of qianggu capsules (QGC) on the fracture healing and the bone mineral density (BMD) in radius distal osteoporosis fracture (RDOF) patients. METHODS: Bone mineral density (BMD) of femoral neck in 65 patients with RDOF was detected after the fracture was fixed manually. They were then randomly divided into two groups. Thirty-three patients in the treated group took QC, 1 capsule (180 mg) each time, three times a day, while 32 patients in the control group took D-Cal Biocal 2 tablets (1500 mg) each time, once daily. The therapeutic course for both groups was three months. X-ray examination on the broken end of the fractured bone was taken every month to observe the bony callus formation for comparing the curative effect, and BMD of femoral neck were detected again after patients were treated for 3 months. The bony callus appeared earlier, more in volume with thicker cortex in the treated group after 2 months of treatment versus that in the control group. The fracture healing time in the treated group was 9.4 +/- 2.5 weeks and that in the control group was 12.5 +/- 2.9 weeks, showing significant difference between them (P < 0.05). BMD in the treated group before treatment was 0.621 +/- 0.085 g/cm2, which was lower than that after treatment (0.646 +/- 0.090 g/cm2) with significant difference showing between them (P < 0.05), while no significant change of BMD was found in the control group between before and after treatment, and significant difference was found in BMD between the two groups after treatment (P < 0.05). CONCLUSION: QGC can promote the formation of bony callus ahead of time, increase the volume of bony callus and BMD, improve the bone structure, and thus the time of external fixation in treating RDOF could be reduced.

Aged↗

The course of the nerve root in the neural foramen and its relationship with foraminal entrapment or impingement in adult patients with lumbar isthmic spondylolisthesis and radicular pain.

The purpose of this study was to demonstrate the course of a nerve root in the neural foramen and its relationship with foraminal entrapment or impingement in 19 adult patients with isthmic spondylolisthesis and radicular pain. Myelo-computed tomography and magnetic resonance imaging showed that the course of the nerve root was normal (ie, medial and then inferior, along the pedicle) in 10 patients and was deviated posteriorly in 9 patients. The patients with a normal nerve root course (N-NRC) had either a bony callus projecting medially into the spinal canal (n = 6) or a low mean percentile of vertebral slip (n = 4; 13.9 +/- 1.3). Those nine patients with a posteriorly deviated nerve root course (PD-NRC) had no medially projecting bony callus in the spinal canal but had a higher mean percentile of vertebral slip (n = 9; 31.5 +/- 10.1; P = 0.005). In the neural foramen, nerve roots of the N-NRC patients were entrapped craniocaudally between the pedicle and superior part of the intervertebral disc. In contrast, nerve roots of the PD-NRC patients were impinged ventrodorsally between the posterosuperior part of the intervertebral disc and either bony callus projecting inferiorly toward the neural foramen or fibrocartilaginous mass arising around the isthmic defect. The foraminal craniocaudal entrapment and ventrodorsal impingement highly agreed with the side of radicular pain (kappa= 0.73, P < 0.001). Our results demonstrate that the medially projecting bony callus and the percentile of vertebral slip affect the course of the nerve root in the neural foramen, which in turn determines the foraminal craniocaudal entrapment or ventrodorsal impingement. These two mechanisms, based on the course of the nerve root, correlate well with the side of radicular pain.

Adult↗

Expression of dentin matrix protein 1 (DMP1) during fracture healing.

Dentin matrix protein 1 (DMP1) is one of the acidic phosphorylated extracellular matrix proteins called the SIBLING (small integrin-binding ligand, N-linked glycoproteins) family. Recent studies showed that DMP1 is expressed in the mineralized tissues and suggested that DMP1 is involved in the mineralization. We investigated the precise localization of DMP1 messenger RNA (mRNA) and protein during fracture healing. In situ hybridization demonstrated that DMP1 mRNA was strongly expressed in preosteocytes and osteocytes in the bony callus during intramembranous and endochondral ossification while DMP1 mRNA was not detected in osteoblasts and chondrocytes. During endochondral ossification, however, a low number of DMP1-expressing cells were identified in the cluster of hypertrophic chondrocytes. However, these DMP1-expressing cells were not hypertrophic and were likely to be osteoblast-lineage cells, which were embedded in the matrix of bone or cartilage, because type I collagen-expressing cells and invasion of capillary vessels were observed in the same area. Northern blot, in situ hybridization, and immunohistochemical analyses showed that DMP1 mRNA and protein expressions were increased until day 14 postfracture, when bony callus was formed, and then declined to a lower level during remodeling of the bony callus. Therefore, DMP1 is likely to play an important role in the mineralization of the bony callus.

Animals↗