Chondrocyte-to-osteoblast transformation in mandibular fracture repair.

The majority of fracture research has been conducted using long bone fracture models, with significantly less research into the mechanisms driving craniofacial repair. However, craniofacial bones differ from long bones in both their developmental mechanism and embryonic origin. Thus, it is possible that their healing mechanisms could differ. In this study we utilize stabilized and unstabilized mandible fracture models to investigate the pathways regulating repair. Whereas fully stable trephine defects in the ramus form bone directly, mechanical motion within a transverse fracture across the same anatomical location promoted robust cartilage formation before boney remodeling. Literature investigating long bone fractures show chondrocytes are a direct precursor of osteoblasts during endochondral repair. Lineage tracing with Aggrecan-CreERT2 ::Ai9 tdTomato mice demonstrated that mandibular callus chondrocytes also directly contribute to the formation of new bone. Furthermore, immunohistochemistry revealed that chondrocytes located at the chondro-osseous junction expressed Sox2, suggesting that plasticity of these chondrocytes may facilitate this chondrocyte-to-osteoblast transformation. Based on the direct role chondrocytes play in bone repair, we tested the efficacy of cartilage grafts in healing critical-sized mandibular defects. Whereas empty defects remained unbridged and filled with fibrous tissue, cartilage engraftment produced bony-bridging and robust marrow cavity formation, indicating healthy vascularization of the newly formed bone. Engrafted cartilage directly contributed to new bone formation since a significant portion of the newly formed bone was graft/donor-derived. Taken together these data demonstrate the important role of chondrocyte-to-osteoblast transformation during mandibular endochondral repair and the therapeutic promise of using cartilage as a tissue graft to heal craniofacial defects.

Insulin impedes osteogenesis of BMSCs by inhibiting autophagy and promoting premature senescence via the TGF-ß1 pathway.

The dysfunction of bone marrow stromal cells (BMSCs) may be a core factor in Type 2 diabetes mellitus (T2DM) associated osteoporosis. However, the underlying mechanism is not well understood. Here, we delineated the critical role of insulin impeding osteogenesis of BMSCs in T2DM. Compared with BMSCs from healthy people (H-BMSCs), BMSCs from T2DM patient (DM-BMSCs) showed decreased osteogenic differentiation and autophagy level, and increased senescent phenotype. H-BMSCs incubated in hyperglycemic and hyperinsulinemic conditions similarly showed these phenotypes of DM-BMSCs. Notably, enhanced TGF-ß1 expression was detected not only in DM-BMSCs and high-glucose and insulin-treated H-BMSCs, but also in bone callus of streptozocin-induced diabetic rats. Moreover, inhibiting TGF-ß1 signaling not only enhanced osteogenic differentiation and autophagy level of DM-BMSCs, but also delayed senescence of DM-BMSCs, as well as promoted mandible defect healing of diabetic rats. Finally, we further verified that it was TGF-ß receptor II (TßRII), not TßRI, markedly increased in both DM-BMSCs and insulin-treated H-BMSCs. Our data revealed that insulin impeded osteogenesis of BMSCs by inhibiting autophagy and promoting premature senescence, which it should be responsible for T2DM-induced bone loss, at least in part. These findings suggest that inhibiting TGF-ß1 pathway may be a potential therapeutic target for T2DM associated bone disorders.

Relationship between arthroscopic findings of synovitis and levels of tumour necrosis factor-alpha and matrix metalloproteinases in synovial lavage fluid from patients with unilateral high mandibular condyle fractures.

Arthrocentesis has an effect of washing out inflammatory products that accumulate in the joint compartment of a dysfunctional temporomandibular joint (TMJ). The procedure removes inflammatory cytokines, which are pain-causing substances, for early reduction of TMJ pain and quick recovery of jaw function, thus increasing the possibility of a successful rehabilitation. The aim of this study was to investigate the relationship between arthroscopy synovitis grade in patients with unilateral high condylar fractures and concentrations of the pro-inflammatory cytokines tumour necrosis factor (TNF)-alpha as well as of matrix metalloproteinases (MMPs) in washed-out synovial fluid (SF) samples obtained from those patients. A total of 26 patients with unilateral high condylar fractures who underwent arthrocentesis for a therapeutic purpose were examined. SF samples were collected before performing arthroscopy to determine synovitis grade. The detection rates and concentrations of TNF-alpha and MMPs were determined, and their association with synovitis grade was analysed. TNF-alpha was detected in 23 and MMP-3 in 22 of the TMJs. There was a correlation between synovitis grade and concentration of TNF-alpha in the fracture group. Furthermore, the concentrations of TNF-alpha and MMP-3 were significantly higher as compared to the control group, comprised of TMJs on the non-fracture side of the same patients, while a correlation was also noted between TNF-alpha concentration and synovitis grade in the fracture group. The present findings may provide a biological/biochemical rationale for arthrocentesis as a reasonable treatment modality for high condylar fractures.

Platelet-rich plasma and its effect in bone regeneration in mandibular fractures. Controlled clinical trial / Plasma rico en plaquetas y su efecto en la regeneración ósea en fracturas mandibulares. Ensayo clínico controlado

Background: Currently there is great interest in developing clinical applications of platelet-rich plasma to enhance bone repair. Aim: To assess bone regeneration in mandibular fractures, with the application of this adjuvant. Methods: Twenty patients with mandibular fractures were included in a randomized clinical trial. Patients of the experimental group (n = 10) were submitted to internal fracture reduction and administration of platelet-rich plasma, and patients of the control group (n = 10) were submitted to the same surgical procedure without plasma application. Radiologic assessment was made before and at 1 and 3 months after surgery. X-rays were digitalized for analyze intensity and density as reflection of bone regeneration. Results: The average age was 32 ± 11.3 years and 31.2 ± 8.48 years respectively (p = 0.76). The radiographic intensity and density in the experimental group at the 1st and 3rd month were higher in contrast to the control group (p < 0.005). Bone regeneration time was 3.7 ± 0.48 and 4.5 ± 0.52 weeks respectively (p = 0.002). There was no morbidity related to the application of the platelet-rich plasma. Conclusion: The platelet-rich plasma increased the bone intensity and density in the fracture trace allowing bone regeneration and recovery in shorter time than patients in which it was not used.

Antecedentes: Actualmente existe interés en el desarrollo de aplicaciones clínicas del plasma rico en plaquetas (PRP) para mejorar la regeneración ósea (RO). Objetivo: Evaluar la RO en fracturas mandibulares con la aplicación de PRP. Métodos: Ensayo clínico controlado. Se incluyeron 20 pacientes con fractura de ángulo mandibular. El grupo de estudio (n = 10) se sometió a reducción de la fractura, fijación interna y aplicación de PRP, y el grupo control (n = 10) al mismo procedimiento sin administración de plasma. Se evaluaron en el preoperatorio y al primer y tercer mes posterior a la reducción mediante digitalización radiográfica para evaluar la regeneración ósea. Resultados: El promedio de edad fue de 32 ± 11.3 y 31.2 ± 8.48 años, respectivamente (p = 0.76). La intensidad y la densidad radiográfica al mes y a los 3 meses fueron superiores en el grupo de estudio que en el grupo control (p< 0.005). El tiempo de regeneración fue de 3.7 ± 0.48 y 4.5 ± 0.52 semanas, respectivamente (p = 0.002). Conclusiones: El PRP aumentó la intensidad y la densidad ósea en el trazo de las fracturas, sugestivas de RO, y recuperación en menor tiempo, en contraste con el grupo control.

Facilitation of bone resorption activities in synovial lavage fluid patients with mandibular condyle fractures.

The aim of this study was to investigate the bone resorption effect of the mediators delivered in joint cavity of patients with mandibular condyle fractures by detecting osteoclast markers using cellular biochemistry methods, and by analysing bone resorption activities via inducing osteoclast differentiation of the infiltrated cells from arthrocentesis. Sixteen joints in 10 patients with mandibular condyle fractures were evaluated. The control group consisted of synovial fluid (SF) samples from seven joints of four volunteers who had no clinical signs or symptoms involving the temporomandibular joint (TMJ) or disc displacement. We collected SF cells from all patients during therapeutic arthrocentesis. The infiltrating cells from TMJ SF were cultured, differentiated into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and examined bone resorption activities. We also investigated factors related to osteoclast induction of SF, using ELISA procedures. Osteoclast-like cells were induced from the SF cells obtained from all patients with condylar fractures. These multinucleated giant cells were positive for TRAP and actin, and had the ability to absorb dentin slices. The levels of macrophage colony-stimulating factor (M-CSF), prostaglandin E2 (PGE2), soluble form of receptor activator of nuclear factor kappa-B ligand (sRANKL) and osteoprotegerin (OPG), in SF samples from the patients, were significantly higher than in the controls. These findings indicate that bone resorption activities in SF from patients with mandibular condyle fractures were upregulated and may participate in the pathogenesis and wound healing.

[The effect of nerve growth factor on the expression of BMP-2 in the healing of rabbits' mandibular fracture with partial nerve injury].

Objective:To observe the effect of NGF on the expression of BMP-2 in rabbit model and explore the molecular mechanism of NGF which might promote the healing of mandibular fracture with nerve injury. Method:The 48 New-Zealand white rabbits were randomly divided into the experimental group (mandibular fracture+to cut off the nerve bundle+NGF by GS), the control group (mandibular fracture+to cut off the nerve bundle+NS by GS), the blank group (mandibular fracture+to cut off the nerve bundle) and the full-set group (mandibular fracture+retains the nerve bundle). After 2 weeks, 4 weeks, 6 weeks and 8 weeks, 3 rabbits were sacrificed in each group for HE staining and RT-PCR, respectively. Result:HE staining showed the osteogenesis phenomenon: the experimental group was clearer than control group, the full-set group was clearer than the blank group and the control group is similarly to the blank group. RT-PCR results revealed that there was a statistically significance in the early stage. The expression of BMP-2 peaked in 2 weeks and decreased later with time. Conclusion:The local application of NGF can prompt BMP-2 expression in the early stages of the mandibular fracture with partial nerve injury healing and this may be one of the molecular mechanisms.

Low-intensity pulsed ultrasound enhances bone morphogenetic protein expression of human mandibular fracture haematoma-derived cells.

We previously demonstrated that human mandibular fracture haematoma-derived cells (MHCs) play an important role in mandibular fracture healing and that low-intensity pulsed ultrasound (LIPUS) accelerates this effect by stimulating various osteogenic cytokines. In the present study, we investigated how LIPUS affects the expression of bone morphogenetic proteins (BMPs), which are also known to have the ability to induce bone formation. MHCs were isolated from human mandibular fracture haematomas and the cells were divided into two groups: a LIPUS (+) group and a LIPUS (-) group, both of which were cultured in osteogenic medium. LIPUS was applied to the LIPUS (+) group 20 min a day for 4, 8, 14, and 20 days (1.5 MHz, 30 mW/cm(2)). Real-time PCR and immunofluorescence studies were carried out to determine the expression of BMP-2, 4, and 7. Compared to the LIPUS (-) group, gene expression levels were significantly increased in the LIPUS (+) group for BMP-2 on day 20 (67.38 ± 26.59 vs. 11.52 ± 3.42, P < 0.001), for BMP-4 on days 14 (45.12 ± 11.06 vs. 9.20 ± 2.88, P = 0.045) and 20 (40.96 ± 24.81 vs. 3.22 ± 1.53, P = 0.035), and for BMP-7 on day 8 (48.11 ± 35.36 vs. 7.03 ± 3.96, P = 0.034). These findings suggest that BMP-2, 4, and 7 may be mediated by LIPUS therapy during the bone repair process.

A comparison of stromal cell-derived factor-1 expression during distraction osteogenesis and bone fracture in the mandible.

Distraction osteogenesis (DO) has been a widely applied technique in orthopedics and craniofacial surgery. However, the exact molecular mechanism by which the mechanical stimulus is translated into biological signals is still poorly understood. In this study, we examined and compared the expression of stromal cell-derived factor-1 (SDF-1) during mandibular distraction osteogenesis and fracture in rats, respectively. Forty-eight male Sprague-Dawley rats were divided into 2 groups and received unilateral distraction osteogenesis and rigid internal fixation, respectively, after the osteotomy on the right mandible. The harvested mandibles were examined radiographically, histologically, and immunohistochemically. We found that the expression of SDF-1 was mainly detected in the osteoblasts and blood vessels, and there were more intensive expression of SDF-1 in DO zones than in bone fracture zones. The quantitative analysis by enzyme-linked immunosorbent assay showed that SDF-1 reached a greater peak and maintained a longer period of up-regulation in DO than in fracture healing (P < 0.05). These results suggest that the distraction procedure markedly promotes the high expression of SDF-1 which facilitates the induction of bone formation during DO.

[Expression and significance of TGF-beta1 and BMP-2 in mandibular callus].

OBJECTIVE: To investigate the expressions of transforming growth factor beta1 (TGF-beta1) and bone morphogenetic protein-2 (BMP-2) in human mandible fracture callus and their quantity changes in the process of healing. METHOD: Thirty callus samples from the fractured mandible bone stumps were collected during operation, and two callus samples were collected from the angle-square jaw patients as controls. The expressions of TGF-beta1 and BMP-2 were test by the immunohistochemistry technic-SABC-staining in different periods of human fractured mandibular callus and in osseous tissue of normal angle of mandible. RESULT: The TGF-beta1 and BMP-2 were expressed in callus of different periods but not in normal bone tissue. The expression of TGF-beta1 increased slowly during the first three weeks after fracture and reached its maximum in the third week, and then weakened gradually. The expression of BMP-2 increased gradually during the first two weeks after fracture and reached its maximum in the second week, then the expression weakened gradually. CONCLUSION: (1) BMP-2 may be one of the factors promoting the repair of fracture. (2) TGF-beta1 could be another signal pathway in repairment of fracture. (3) There could exist some synergistic effects between TGF-beta1 and BMP-2 in the process of fracture healing.

[Time effect of dentin matrix protein 1 and osteoclast expression during mandibular fracture healing in rats].

OBJECTIVE: To study the expression of dentin matrix protein 1 (DMP1) and osteoclast in callus at different healing period of mandibular fracture in a adult Wistar rat model. METHODS: The mandibular fracture model of Wistar rats at the left mandibular ramus was established. The callus in the fractured site and the normal mandible were amputated at the 5th, 7th, 14th and 21st day after the fracture. HE staining was used to observe the condition of fracture healing and TRAP staining used to observe the activation of osteoclast. The expression of DMP1 was detected in the callus by using immunohistochemical method. RESULTS: The number of osteoclasts reached a peak from the 14th to 21st day. The expression of DMP1 became very active from the 7th to 14th day. CONCLUSIONS: The expression of DMP1 and osteoclast during fracture healing exhibited time effect.

[Influence of mandibular fracture upon intensity and prevailing direction of carbonate and citrate transport between blood and bones].

Using new coefficient of the difference relative radioactivity (CD(RRA)) bone/blood there was studied [(14)C]-carbonate and [3-(14)C]-citrate in 1-month and 6-months rats after right-side fracture of the mandible in prevailing direction between blood and bone. Animals were taken out from the experiment 20 min after intraperitoneal injection of [(14)C]-carbonate and [3-(14)C]-citrate on 7th day after (stage of cell-fibrous callosity), on 14th day after (stage of chondroid callosity) and on 28th day after (stage of the primary bone callosity) the experiment start. Changes after injections of marked citrate and carbonate were similar. Input % (ratio pulse/min in bone and blood serum) and RRA in 1 week increased sharply, decreased in 2 weeks and less changing in 4 weeks. After fracture CD(RRA) in traumatized mandible and non traumatized femur in rats were changing in the opposite directions that testifies to the different prevailing directions of marked substances transport between blood and bones.

Bone morphogenetic protein 3 expression pattern in rat condylar cartilage, femoral cartilage and mandibular fracture callus.

Mandibular condylar cartilage differs from primary cartilage in morphological organization of the chondrocytes and in responses to biomechanical stress and humoral factors. For the first time, we describe the expression of Bmp3 mRNA in relation to types I, II and X collagen mRNA (as determined by in situ hybridization) in chondrocytes of the rat mandibular condylar cartilage, femoral articular cartilage, femoral growth plate cartilage, and temporal cartilage, which transiently appeared in the reparative response stage of mandibular ramus fracture healing. In all cartilages evaluated, Bmp3 was expressed in proliferating chondrocytes that expressed type I collagen in condylar cartilage, articular cartilage, and temporal cartilage appearing during fracture healing. Bmp3 was also found in hypertrophic chondrocytes that expressed type X collagen mRNA in all cartilages evaluated. Furthermore, in remodeling bone, Bmp3 mRNA was strongly expressed in active osteoblast cells in periosteal reaction layers formed after fracture. These findings suggest that Bmp3 expression in a special layer of typical articular cartilage may be regulated by mechanical stress stimulation. We also found that Bmp3 was expressed in the periosteal layers of the bone segments near the fracture site during fracture healing.

Healing of fractures in osteoporotic rat mandible shown by the expression of bone morphogenetic protein-2 and tumour necrosis factor-alpha.

We studied the healing process of mandibular closed fractures in osteoporotic rats using specific antibodies to bone morphogenetic protein-2 (BMP-2) and tumour necrosis factor-alpha (TNF-alpha). We confirmed the osteoporosis in rats after oophorectomy by micro-CT, and then caused unilateral closed fractures in the mandible and monitored the healing process after 7, 14, 21, and 28 days. Data were compared simultaneously with those from a group of rats that had a sham operation. During healing of the fracture in the osteoporotic group there was a prolonged phase of endochondral ossification, with an increased number of osteoclasts (p<0.01). Expressions of BMP-2 and TNFalpha were more pronounced in the osteoporotic group and there was an increase in the number of osteoblasts and TNFalpha(+) cells compared with the normal control (p<0.01). BMP-2 was related to the differentiation of osteoblasts and the higher values of TNFalpha were correlated with the up-regulation of osteoclasts during the prolonged phase of bone turnover. We conclude that the healing of fractures in osteoporotic bone is delayed about a week compared with controls. In the healing of fractures in osteoporotic bone, there were more osteoblasts and osteoclasts but there was a predominance of osteoclasts probably induced by TNFalpha. The prolonged phase of bone turnover with osteoclast predominance in the osteoporotic group is suggestive of the cause of delay in the healing of the fracture.

Effects of selenium-containing compounds and their metabolism in intact rats and in animals with bone fractures.

Blood content of MDA in rats increased 1 and 2 weeks after mandibular bone fracture at stages of cellular fibrous and chondroid callus and decreased 4 weeks after fracture at the stage of primary bone callus. Treatment with Se (intragastrically and electrophoretically) reduced this increase by activating selenium-containing glutathione peroxidase. In order to clear out the relationship between Se and carbohydrate metabolism in different ages, the distribution of Se between the blood and mandibular bone, diaphysis and metaepiphyseal zone of the femoral bone was studied using the bone/blood relative radioactivity coefficient after intraperitoneal injection of [(75)Se]selenate. In control 1-month-old rats the radioactivity had 2 peaks corresponding to 6 and 48 h. The first peak was presumably caused by Se adsorption on hydroxyapatite, the second by chemosorption on hydroxyapatite and protein binding. Only one peak of relative radioactivity (after 12-48 h) was observed in 3-month-old control rats, and it could be increased by sucrose diet. The relative radioactivity was higher in rats receiving sucrose ration for 2 months starting from the age of 1 month in comparison with the control.

Collagen type I and III metabolism in assessment of mandible fractures healing.

PURPOSE: The aim of this work was estimation of the PIIINP, PICP and ICTP concentrations in blood serum during non-complicated mandible fracture healing; settlement of dependences between kinetics of changes of examined markers with reference to particular bone fracture phases and applied treatment methods; the determination of usefulness of collagen metabolism markers type III and I for the monitoring of mandibular fracture healing. MATERIAL AND METHODS: The material was blood serum of men aged 20-30 years, who were treated for mandible fractures in Maxillofacial Clinic Medical University of Bialystok. Depending on the treating method, examined patients were divided into two groups. Patients treated with non-operative method were I group (n = 31), II group was made of patients treated with surgery (n = 33). The concentrations of markers measured on the 2nd, 14th, 42nd, 90th day after trauma and in II group these substances were measured additionally on the 2nd and 14th day after surgery. Control group consisted of 20 healthy men the same age. Concentrations of markers were measured with the radioimmunological method (RIA). RESULTS: Regular process of mandible fracture healing in men in various periods occurs with PICP, PIIINP and ICTP concentration changes in blood serum. CONCLUSIONS: Changes of maker concentration show that, mandible fracture healing treated non-operatively is a more dynamic process than stable osteosynthesis method applied. Lack of positive correlation of the PIIINP and PICP concentration in blood serum of patients in two examined groups can indicate on the different mechanisms of mandible fracture healing connected with different methods of the treatment.

[Immunohistochemical research of integrin alpha 5 expression during mandibular fracture healing].

OBJECTIVE: To investigate the expression change of integrin alpha 5 during mandibular fracture healing. METHODS: Using rabbit mandibular fracture model, the fractured bone tissues were obtained and paraffin slices were made on the days of 1, 3, 5, 7, 14, 30, 60 and 90 after surgery, respectively. Non-fractured mandibles were used as normal control. LsAB immunohistochemical method was used to detect the expression of integrin alpha 5 in bone tissue, especially on osteoblasts and osteoclasts. RESULTS: Integrin alpha 5 was widely expressed in fractured bone and surrounding soft tissues. The expression of integrin alpha 5 increased 7 days after fracture, peaked in 14 to 30 days and returned to nearly normal in 60-90 days. CONCLUSION: During mandibular fracture healing, the expression of integrin alpha 5 in bone tissue increased clearly. It is estimated that integrin alpha 5 players an important role in fracture healing.

Inducible nitric oxide synthase and apoptosis-related factors in the synovial tissues of temporomandibular joints with internal derangement and osteoarthritis.

PURPOSE: In this study, we investigated the relationship between oxidative stress and apoptosis in synovial tissues in temporomandibular joint diseases (TMDs), including internal derangement (ID) and osteoarthritis (OA), comparing immunohistochemical, arthroscopic, and histologic findings. MATERIALS AND METHODS: Synovial specimens obtained from patients with ID (31 patients), osteoarthritis (11 patients), and condylar fractures of the mandible (5 patients) during arthroscopy were examined immunohistochemically using antibodies against CD68, inducible nitric oxide synthase (iNOS), Fas, and single-stranded DNA (ssDNA). RESULTS: CD68 and iNOS immunoreactivity were detected mainly in synovial lining cells and subintimal macrophages, and tended to increase with synovial hyperplasia. Fas and ssDNA immunoreactivity was detected mainly in synovial lining cells, and Fas-positive regions exhibited a number of ssDNA-positive cells. Fas expression was significantly greater in fractures than in OA, and ssDNA expression was significantly greater in OA than in ID. Fas expression was significantly greater in iNOS-positive versus iNOS-negative TMJs, and ssDNA expression tended to increase with iNOS expression. CONCLUSION: These immunohistochemical findings suggest that oxidative stress and apoptosis in synovial tissues are involved in the onset and progression of TMDs.

Insulin-like growth factor-I (IGF-I) in serum and bone tissue during rat mandible fracture healing.

Insulin-like growth factor-I (IGF-I) is potent stimulator of proliferation and differentiation of osteoblasts, the biosynthesis of collagen type-I and noncollagenous proteins and alkaline phosphatase activity. The role of IGF-I in bone repair has not as yet been clearly defined. The aim of the present study was the quantitative analysis of IGF-I in the serum and tissue in four phases of fractured jaws healing in rat models. IGF-I concentrations in the serum and bone extracts were determined by RIA. In respect to the control group (K) the significant increase of IGF-I occurred in the serum in phase I (211 +/- 68 ng/ml, K-153 +/- 50 ng/ml) (p < 0.05). At the tissue levels a statistically significant increase in IGF-I was confirmed in phase II (262 +/- 60 ng/g, K-182 +/- 56 ng/g) (p < 0.05). The present results demonstrate that in rat models with fractured jaws in the first two phases of healing elevated levels of IGF-I in the serum and bone tissue were observed which indicate the significant role of this polypeptide in the early healing stages.

[A study on mRNA expression levels of integrin beta 1 during the healing process of mandibular fractures].

OBJECTIVE: The aim of this study was to investigate the spatial and temporal mRNA expression changes of integrin beta 1 during the healing process of mandibular fractures. METHODS: The in situ hybridization was performed using digoxigenin-labeled integrin beta 1 mRNA oligonucleotide probe. During the healing process of mandibular fractures, the staining pattern of beta 1 mRNA was examined both spatially and time-dependently. RESULTS: Integrin beta 1 was widely present in the cells of the fractured bone, especially in osteoblasts. The positive staining was observed in the cytoplasm and nucleolus of osteoblasts. After 7 days of fracture, the expression level of integrin beta 1 increased. The peak appeared between the 14th and the 30th day, and almost recovered to normal between the 60th and 90th day. CONCLUSION: During the healing process of mandibular fracture, the expression level of integrin beta 1 in bone, especially in osteoblasts rose. It is suggested that integrin beta 1 may play an important role in the fracture healing process.

Nutritional status of substance abusers with mandible fractures.

PURPOSE: The purposes of this study were 1) to assess the validity of patient self-report in identifying illegal substance abuse and 2) to identify nutritional deficiencies in substance abusers presenting for treatment of mandible fractures. PATIENTS AND METHODS: To address the research purposes, a prospective cohort study was conducted of patients presenting for treatment of mandible fractures. A urine drug screen was used to determine the validity of patient self-report of substance abuse. For purposes of assessing nutritional status, 2 categories of substance abusers were identified: illegal and legal (alcohol). The nutritional status was measured using various laboratory markers. RESULTS: The sample was composed of 93 subjects. Urine drug studies were available for 32 patients. Of the 22 patients who denied illegal drug use, 12 (55%) had a positive drug screen. Of the 10 patients reporting a positive history of illicit drug use, 7 (70%) had a positive urine drug screen (P = .47). A positive correlation was found between alcohol exposure and serum aspartate aminotransferase, mean corpuscular volume, and lactate dehydrogenase. Positive drug screens also were associated with increased serum ferritin levels. CONCLUSIONS: The results of this study suggest that patient self-report of illicit drug use may be unreliable. The findings also suggest that legal and illegal substance abusers presenting for treatment of mandible fractures have minimal nutritional deficiencies.