Moderate static magnetic field promotes fracture healing and regulates iron metabolism in mice.

BACKGROUND: Fractures are the most common orthopedic diseases. It is known that static magnetic fields (SMFs) can contribute to the maintenance of bone health. However, the effect and mechanism of SMFs on fracture is still unclear. This study is aim to investigate the effect of moderate static magnetic fields (MMFs) on bone structure and metabolism during fracture healing. METHODS: Eight-week-old male C57BL/6J mice were subjected to a unilateral open transverse tibial fracture, and following treatment under geomagnetic field (GMF) or MMF. The micro-computed tomography (Micro-CT) and three-point bending were employed to evaluate the microarchitecture and mechanical properties. Endochondral ossification and bone remodeling were evaluated by bone histomorphometric and serum biochemical assay. In addition, the atomic absorption spectroscopy and ELISA were utilized to examine the influence of MMF exposure on iron metabolism in mice. RESULTS: MMF exposure increased bone mineral density (BMD), bone volume per tissue volume (BV/TV), mechanical properties, and proportion of mineralized bone matrix of the callus during fracture healing. MMF exposure reduced the proportion of cartilage in the callus area during fracture healing. Meanwhile, MMF exposure increased the number of osteoblasts in callus on the 14th day, and reduced the number of osteoclasts on the 28th day of fracture healing. Furthermore, MMF exposure increased PINP and OCN levels, and reduced the TRAP-5b and ß-CTX levels in serum. It was also observed that MMF exposure reduced the iron content in the liver and callus, as well as serum ferritin levels while elevating the serum hepcidin concentration. CONCLUSIONS: MMF exposure could accelerate fracture healing via promote the endochondral ossification and bone formation while regulating systemic iron metabolism during fracture healing. This study suggests that MMF may have the potential to become a form of physical therapy for fractures.

Expression of Musashi-1 Increases in Bone Healing.

Musashi-1 (MSI1) is an RNA-binding protein that regulates progenitor cells in adult and developing organisms to maintain self-renewal capacities. The role of musashi-1 in the bone healing environment and its relation with other osteogenic factors is unknown. In the current study, we analyze the expression of MSI1 in an experimental model of rat femoral bone fractures. We also analyze the relation between MSI1 expression and the expression of two osteogenic markers: periostin (POSTN) and runt-related transcription factor 2 (RUNX2). We use histological, immunohistochemical, and qPCR techniques to evaluate bone healing and the expression of MSI1, POSTN, and RUNX2 over time (4, 7, and 14 days). We compare our findings with non-fractured controls. We find that in bone calluses, the number of cells expressing MSI1 and RUNX2 increase over time and the intensity of POSTN expression decreases over time. Within bone calluses, we find the presence of MSI1 expression in mesenchymal stromal cells, osteoblasts, and osteocytes but not in hypertrophic chondrocytes. After 14 days, the expression of MSI1, POSTN, and RUNX2 was significantly correlated. Thus, we conclude that musashi-1 potentially serves in the osteogenic differentiation of mesenchymal stromal cells and bone healing. Therefore, further studies are needed to determine the possibility of musashi-1's role as a clinical biomarker of bone healing and therapeutic agent for bone regeneration.

Carbon/PEEK nails: a case-control study of 22 cases.

BACKGROUND: Interest around carbon/PEEK plates and nails has been raising. The elastic modulus close to the bone, the high load-carrying capacity and radiolucency make CFR/PEEK materials a potential breakthrough. In the literature, there are abundant data about CFR/PEEK plates in the treatment of proximal humerus, distal radius and distal fibula fractures. In patients affected by bone metastasis, CFR/PEEK nails were proved effective and safe with 12 months of follow-up. Very little is known about performances of CFR/PEEK nails in patients affected by other pathologies. PURPOSES: The aim of the study was to evaluate safety and efficacy of CFR/PEEK nails in the treatment of various pathological conditions. It was also investigated whatever radiolucency of this nails could lead to a more objective evaluation of bone callus or disease site. PATIENTS AND METHODS: In the study group were included 20 patients (22 bone segments) who underwent CFR/PEEK nail implantation (eight humerus, one tibia, nine femur and four knee arthrodesis). They were affected by pathological fractures, and in four cases, they required an arthrodesis of the knee. They were retrospectively evaluated considering nail failures and bone callus or disease progression (RUSH scores). Mean follow-up time was 11 months (min 6.8-max 20.3). In the control group were included patients treated with titanium nails in the same institution for the same pathologies. An interclass correlation coefficient (ICC) analysis was performed in both groups considering RUSH scores by two expert surgeon from two institution to assess whether radiolucency could lead to a more objective evaluation of disease or bone callus site. RESULTS: The ICC of mean values between RUSH scores was 0.882 (IC 95%: 0.702-0.953) in the CFR/PEEK group, while it was 0.778 (IC 95%: 0.41-0.91) in the titanium group. Observers' evaluation showed a significantly higher obscuration by titanium nails than by CFR/PEEK nails. No osteosynthesis failures were reported in both groups. CONCLUSIONS: Our results confirm the safety of CFR/PEEK nails in the short-medium term. The radiolucency of these materials led our observers to perform more objective evaluations of bone callus formation or disease progression compared to the titanium group given the higher ICC. LEVEL OF EVIDENCE: III Case-control therapeutic study.

Role of muscle stem cells during skeletal regeneration.

Although the importance of muscle in skeletal regeneration is well recognized clinically, the mechanisms by which muscle supports bone repair have remained elusive. Muscle flaps are often used to cover the damaged bone after traumatic injury yet their contribution to bone healing is not known. Here, we show that direct bone-muscle interactions are required for periosteum activation and callus formation, and that muscle grafts provide a source of stem cells for skeletal regeneration. We investigated the role of satellite cells, the muscle stem cells. Satellite cells loss in Pax7(-/-) mice and satellite cell ablation in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice impaired bone regeneration. Although satellite cells did not contribute as a large source of cells endogenously, they exhibited a potential to contribute to bone repair after transplantation. The fracture healing phenotype in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice was associated with decreased bone morphogenetic proteins (BMPs), insulin-like growth factor 1, and fibroblast growth factor 2 expression that are normally upregulated in response to fracture in satellite cells. Exogenous rhBMP2 improved bone healing in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice further supporting the role of satellite cells as a source of growth factors. These results provide the first functional evidence for a direct contribution of muscle to bone regeneration with important clinical implications as it may impact the use of muscle flaps, muscle stem cells, and growth factors in orthopedic applications.

Inter-trabecular bone formation: a specific mechanism for healing of cancellous bone.

Background and purpose - Studies of fracture healing have mainly dealt with shaft fractures, both experimentally and clinically. In contrast, most patients have metaphyseal fractures. There is an increasing awareness that metaphyseal fractures heal partly through mechanisms specific to cancellous bone. Several new models for the study of cancellous bone healing have recently been presented. This review summarizes our current knowledge of cancellous fracture healing. Methods - We performed a review of the literature after doing a systematic literature search. Results - Cancellous bone appears to heal mainly via direct, membranous bone formation that occurs freely in the marrow, probably mostly arising from local stem cells. This mechanism appears to be specific for cancellous bone, and could be named inter-trabecular bone formation. This kind of bone formation is spatially restricted and does not extend more than a few mm outside the injured region. Usually no cartilage is seen, although external callus and cartilage formation can be induced in meta-physeal fractures by mechanical instability. Inter-trabecular bone formation seems to be less sensitive to anti-inflammatory treatment than shaft fractures. Interpretation - The unique characteristics of inter-trabecular bone formation in metaphyseal fractures can lead to differences from shaft healing regarding the effects of age, loading, or drug treatment. This casts doubt on generalizations about fracture healing based solely on shaft fracture models.

In-vivo imaging of the fracture healing in medaka revealed two types of osteoclasts before and after the callus formation by osteoblasts.

The fracture healing research, which has been performed in mammalian models not only for clinical application but also for bone metabolism, revealed that generally osteoblasts are induced to enter the fracture site before the induction of osteoclasts for bone remodeling. However, it remains unknown how and where osteoclasts and osteoblasts are induced, because it is difficult to observe osteoclasts and osteoblasts in a living animal. To answer these questions, we developed a new fracture healing model by using medaka. We fractured one side of lepidotrichia in a caudal fin ray without injuring the other soft tissues including blood vessels. Using the transgenic medaka in which osteoclasts and osteoblasts were visualized by GFP and DsRed, respectively, we found that two different types of functional osteoclasts were induced before and after osteoblast callus formation. The early-induced osteoclasts resorbed the bone fragments and the late-induced osteoclasts remodeled the callus. Both types of osteoclasts were induced near the surface on the blood vessels, while osteoblasts migrated from adjacent fin ray. Transmission electron microscopy revealed that no significant ruffled border and clear zone were observed in early-induced osteoclasts, whereas the late-induced osteoclasts had clear zones but did not have the typical ruffled border. In the remodeling of the callus, the expression of cox2 mRNA was up-regulated at the fracture site around vessels, and the inhibition of Cox2 impaired the induction of the late-induced osteoclasts, resulting in abnormal fracture healing. Finally, our developed medaka fracture healing model brings a new insight into the molecular mechanism for controlling cellular behaviors during the fracture healing.

Fractures in geriatric mice show decreased callus expansion and bone volume.

BACKGROUND: Poor fracture healing in geriatric populations is a significant source of morbidity, mortality, and cost to individuals and society; however, a fundamental biologic understanding of age-dependent healing remains elusive. The development of an aged-based fracture model system would allow for a mechanistic understanding that could guide future biologic treatments. QUESTIONS/PURPOSES: Using a small animal model of long-bone fracture healing based on chronologic age, we asked how aging affected (1) the amount, density, and proportion of bone formed during healing; (2) the amount of cartilage produced and the progression to bone during healing; (3) the callus structure and timing of the fracture healing; and (4) the behavior of progenitor cells relative to the observed deficiencies of geriatric fracture healing. METHODS: Transverse, traumatic tibial diaphyseal fractures were created in 5-month-old (n=104; young adult) and 25-month-old (n=107; which we defined as geriatric, and are approximately equivalent to 70-85 year-old humans) C57BL/6 mice. Fracture calluses were harvested at seven times from 0 to 40 days postfracture for micro-CT analysis (total volume, bone volume, bone volume fraction, connectivity density, structure model index, trabecular number, trabecular thickness, trabecular spacing, total mineral content, bone mineral content, tissue mineral density, bone mineral density, degree of anisotropy, and polar moment of inertia), histomorphometry (total callus area, cartilage area, percent of cartilage, hypertrophic cartilage area, percent of hypertrophic cartilage area, bone and osteoid area, percent of bone and osteoid area), and gene expression quantification (fold change). RESULTS: The geriatric mice produced a less robust healing response characterized by a pronounced decrease in callus amount (mean total volume at 20 days postfracture, 30.08±11.53 mm3 versus 43.19±18.39 mm3; p=0.009), density (mean bone mineral density at 20 days postfracture, 171.14±64.20 mg hydroxyapatite [HA]/cm3 versus 210.79±37.60 mg HA/cm3; p=0.016), and less total cartilage (mean cartilage area at 10 days postfracture, 101,279±46,755 square pixels versus 302,167±137,806 square pixels; p=0.013) and bone content (mean bone volume at 20 days postfracture, 11.68±3.18 mm3 versus 22.34±10.59 mm3; p<0.001) compared with the young adult mice. However, the amount of cartilage and bone relative to the total callus size was similar between the adult and geriatric mice (mean bone volume fraction at 25 days postfracture, 0.48±0.10 versus 0.50±0.13; p=0.793), and the relative expression of chondrogenic (mean fold change in SOX9 at 10 days postfracture, 135+25 versus 90±52; p=0.221) and osteogenic genes (mean fold change in osterix at 20 days postfracture, 22.2±5.3 versus 18.7±5.2; p=0.324) was similar. Analysis of mesenchymal cell proliferation in the geriatric mice relative to adult mice showed a decrease in proliferation (mean percent of undifferentiated mesenchymal cells staining proliferating cell nuclear antigen [PCNA] positive at 10 days postfracture, 25%±6.8% versus 42%±14.5%; p=0.047). CONCLUSIONS: Our findings suggest that the molecular program of fracture healing is intact in geriatric mice, as it is in geriatric humans, but callus expansion is reduced in magnitude. CLINICAL RELEVANCE: Our study showed altered healing capacity in a relevant animal model of geriatric fracture healing. The understanding that callus expansion and bone volume are decreased with aging can help guide the development of targeted therapeutics for these difficult to heal fractures.

In vivo biomechanical evaluation of a novel angle-stable interlocking nail design in a canine tibial fracture model.

OBJECTIVE: To compare clinical outcome and callus biomechanical properties of a novel angle stable interlocking nail (AS-ILN) and a 6 mm bolted standard ILN (ILN6b) in a canine tibial fracture model. STUDY DESIGN: Experimental in vivo study. ANIMALS: Purpose-bred hounds (n = 11). METHODS: A 5 mm mid-diaphyseal tibial ostectomy was stabilized with an AS-ILN (n = 6) or an ILN6b (n = 5). Orthopedic examinations and radiographs were performed every other week until clinical union (18 weeks). Paired tibiae were tested in torsion until failure. Callus torsional strength and toughness were statistically compared and failure mode described. Total and cortical callus volumes were computed and statistically compared from CT slices of the original ostectomy gap. Statistical significance was set at P < .05 RESULTS: From 4 to 8 weeks, lameness was less pronounced in AS-ILN than ILN6b dogs (P < .05). Clinical union was reached in all AS-ILN dogs by 10 weeks and in 3/5 ILN6b dogs at 18 weeks. Callus mechanical properties were significantly greater in AS-ILN than ILN6b specimens by 77% (failure torque) and 166% (toughness). Failure occurred by acute spiral (control and AS-ILN) or progressive transverse fractures (ILN6b). Cortical callus volume was 111% greater in AS-ILN than ILN6b specimens (P < .05). CONCLUSIONS: Earlier functional recovery, callus strength and remodeling suggest that the AS-ILN provides a postoperative biomechanical environment more conducive to bone healing than a comparable standard ILN.

Stress distribution on the mandibular condyle and the distraction area in distraction osteogenesis by finite element analysis.

PURPOSE: Many 3-dimensional (3-D) finite element analysis (FEA) models based on the virtual simulation have been constructed to explore the stress distribution during distraction osteogenesis (DO). The aim of this study is to achieve a better understanding of the biomechanical feature of mandible during DO procedure. MATERIALS AND METHODS: Using CT image data of a goat mandible that already has been elongated for 10 mm, an anatomical 3D model was reconstructed. This model was imported into MSC.Patran for monitoring mechanical parameters, including Von-Mises stress, max-principal stress, and mix-principal stress, on the distraction area and the mandibular condyle. RESULTS: The computed result showed special stress distribution on 9 slopes of the condyle and 3 cross-sections of the distraction area. From 0.8 MP to 17.2 MP, a dramatic increase in Von-Mises stress was discovered on the right side of the condyle compared with the left side. From 22.6 MP to 0.9 MP on the distraction area, Von-Mises stress decreased from the central zone to the peripheral zone gradually. CONCLUSIONS: During the process of mandibular DO, the special stress distribution may be an important factor on the physiopathological change of the mandibular condyle and the generation of new bone in the distraction area. The correlations between the value of the stress and physiopathological changes during DO process should be clarified in future research.

Distal radial fractures heal by direct woven bone formation.

BACKGROUND: Descriptions of fracture healing almost exclusively deal with shaft fractures and they often emphasize endochondral bone formation. In reality, most fractures occur in metaphyseal cancellous bone. Apart from a study of vertebral fractures, we have not found any histological description of cancellous bone healing in humans. PATIENTS AND METHODS: We studied histological biopsies from the central part of 12 distal radial fractures obtained during surgery 6-28 days after the injury, using routine hematoxylin and eosin staining. RESULTS: New bone formation was seen in 6 cases. It was always in the form of fetal-like, disorganized woven bone. It seldom had contact with old trabeculae and appeared to have formed directly in the marrow. Cartilage was scarce or absent. The samples without bone formation showed only necrosis, scar, or old cancellous bone. INTERPRETATION: The histology suggests that cells in the midst of the marrow respond to the trauma by direct formation of bone, independently of trabecular surfaces.

Deletion of estrogen receptor beta accelerates early stage of bone healing in a mouse osteotomy model.

UNLABELLED: This study examined the role of estrogen receptor (ER) beta during mouse femoral fracture healing by employing ER knockout (KO) mice. The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification. INTRODUCTION: This study was conducted to examine the role of ER beta during fracture healing. METHODS: Female ERbeta knockout (KO) mice (18 weeks old) and age-matched female wild-type (WT) mice underwent open osteotomy on the right femur. They were sacrificed at 1, 2, 4 and 6 weeks post-fracture. The sera and callus samples were subjected to the following analyses: micro-computed tomography (CT)-based angiography, micro-CT evaluation, histological examination, histomorphometry examination, real-time polymerase chain reaction (PCR) analysis, biochemical marker, and mechanical testing. RESULTS: Micro-CT-based angiography showed that the total vessel volume at the fracture site was larger in the KO group than the WT group at 1 and 2 weeks post-fracture. Micro-CT analysis revealed that the callus volume was significantly higher in the KO group from week 2 to week 4 post-fracture when compared with the WT group consistent with the histological data. Analysis of biochemical markers indicated that circulating P1NP levels in the KO mice were significantly higher than in the WT mice from week 2 to week 4 and that temporal expression of circulating C-terminal telopeptide of type I collagen (CTX) levels was also higher in the KO mice than in the WT mice. These results were consistent with quantitative real-time PCR analysis. The ultimate load, stiffness, and energy to failure were significantly higher in the KO mice than in the WT mice at week 4. CONCLUSIONS: The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification, but not by the end of healing. Blockade of ERbeta can be considered as another therapeutic strategy for osteoporotic fracture and non-union fracture.

In vivo tracking of segmental bone defect healing reveals that callus patterning is related to early mechanical stimuli.

This study addresses the hypothesis that callus formation, patterning, and mineralisation are impaired during the early phase of critical sized bone defect healing, and may relate to inter-fragmentary tissue strains within the bone defect area. Twenty four 12 week old Sprague Dawley rats were used for this study. They were divided into two groups defined by the femur bone defect size: (i) 1 mm resulting in normal healing (NH), and (ii) a large sized 5 mm defect resulting in critical healing (CH). Callus formation, patterning, and mineralisation kinetics in both groups were examined in the periosteal and osteotomy gap regions using a novel longitudinal study setup. Finite element analyses on µCT generated tomograms were used to determine inter-fragmentary tissue strain patterns and compared to callus formation and patterning over the course of time. Using a novel longitudinal study technique with µCT, in vivo tracking and computer simulation approaches, this study demonstrates that: (i) periosteal bone formation and patterning are significantly influenced by bone defect size as early as 2 weeks; (ii) osteotomy gap callus formation and patterning are influenced by bone defect size, and adapt towards a non-union in critical cases by deviating into a medullary formation route as early as 2 weeks after osteotomy; (iii) the new bone formation in the osteotomy gap enclosing the medullary cavity in the CH group is highly mineralised; (iv) inter-fragmentary strain patterns predicted during the very early soft callus tissue phase (less than 2 weeks) are concurrent with callus formation and patterning at later stages. In conclusion, bone defect size influences early onset of critical healing patterns.

Cysteine-rich matricellular protein improves callus regenerate in a rabbit trauma model.

PURPOSE: Open fractures with severe soft-tissue trauma are predisposed to poor bone healing. The vital coupling between osteo- and angiogenesis is disturbed. Cysteine-rich protein 61 (CYR61) is an angiogenic inducer promoting vascularisation. However, little is known about the effect of CYR61 on the callus regenerate after acute musculoskeletal trauma. Therefore, our aim was to determine whether local administration of CYR61: (1) has an influence on callus formation and remodelling, (2) increases bone volume and (3) partially restores callus stability. METHODS: A musculoskeletal trauma was created in 20 rabbits. To simulate fracture-site debridement, the limb was shortened. In the test group, a CYR61-coated collagen matrix was locally applied around the osteotomy. After ten days, gradual distraction was commenced (0.5 mm/12 h) to restore the original length. New bone formation was evaluated histomorphometrically, radiographically and biomechanically. RESULTS: Osseus consolidation occured in all animals. Average maximum callus diameter was higher in the test group [1.39 mm; standard deviation (SD) = 0.078 vs 1.26 mm (SD = 0.14); p = 0.096]. In addition, bone volume was higher (p = 0.11) in the test group, with a mean value of 49.73 % (SD = 13.68) compared with 37.6 % (SD = 5.91). Torsional strength was significantly higher (p = 0.005) in the test group [105.43 % (SD = 31.68 %) vs. 52.57 % (SD = 24.39)]. Instead, stiffness of the newly reconstructed callus decreased (64.21 % (SD = 11.52) vs. 71.30 % (SD = 32.25) (p = 0.81)). CONCLUSIONS: CYR61 positively influences callus regenerate after acute trauma, not only histologically and radiographically but also biomechanically, most probably by a CYR61-associated pathway.

Novel approach to estimate distraction forces in distraction osteogenesis and application in the human lower leg.

PURPOSE: In distraction osteogenesis (DO) of long bones, new bone tissue is distracted to lengthen limbs or reconstruct bone defects. However, mechanical boundary conditions in human application such as arising forces are mainly based on limited empirical data. Our aim was the numerical determination of the callus distraction force (CDF) and the total distraction force (TDF) during DO in the tibia of adults to advance the understanding of callus tissue behavior and optimize DO procedures. METHOD: We implemented a mathematical model based on an animal experiment to enable the calculation of forces arising while distracting callus tissue, excluding the influence of surrounding soft tissue (muscles, skin etc.). The CDF progression for the distraction period was calculated using the implemented model and varying distraction parameters (initial gap, area, step size, time interval, length). Further, we estimated the CDF based on reported forces in humans and compared the results to our model predictions. In addition, we calculated the TDF based on our CDF predictions in combination with reported resisting forces due to soft tissue presence in human cadavers. Finally, we compared the progressions to in vivo TDF measurements for validation. RESULTS: Due to relaxation, a peak and resting CDF is observable for each distraction step. Our biomechanical results show a non-linear degressive increase of the resting and peak CDF at the beginning and a steady non-linear increase thereafter. The calculated resting and peak CDF in the tibial metaphysis ranged from 0.00075 to 0.0089 N and 0.22-2.6 N at the beginning as well as 20-25 N and 70-75 N at the end of distraction. The comparison to in vivo data showed the plausibility of our predictions and resulted in a 10-33% and 10-23% share of resting CDF in the total resting force for bone transport and elongation, respectively. Further, the percentage of peak CDF in total peak force was found to be 29-58% and 27-55% for bone transport and elongation, respectively. Moreover, our TDF predictions were valid based on the comparison to in vivo forces and resulted in a degressive increase from 6 to 125 N for the peak TDF and from 5 to 76 N for the resting TDF. CONCLUSION: Our approach enables the estimation of forces arising due to the distraction of callus tissue in humans and results in plausible force progressions as well as absolute force values for the callus distraction force during DO. In combination with measurements of resisting forces due to the presence of soft tissue, the total distraction force in DO may also be evaluated. We thus propose the application of this method to approximate the behavior of mechanical callus properties during DO in humans as an alternative to in vivo measurements.

Macroscopic and microscopic process of long bone fracture healing.

The growth of each type of callus (cortical, medullary and periosteal) depends on the mechanical condition of fracture fixation (elastic fixation and instability or rigid immobilization), the type of treatment (non-operative, close or open surgical procedure, intra-medullary nailing, external fixation, plate...) and the high or poor quality of soft tissue and the specific characteristics of the local vascularisation.

Bone lengthening (distraction osteogenesis): a literature review.

Distraction osteogenesis (DO) is a surgical technique widely used in orthopedic surgery for the treatment of various pathological conditions such as leg length discrepancy, bone deformity or bone defects. The basic principle of the callotasis technique includes performing a transverse bone section before gradually distracting the two bone segments. New bone tissue is generated in the gap between the two segments. Bone regeneration during DO is believed to occur in response to the longitudinal mechanical strain applied to the callus during healing. One of the limitations of this technique is the long period of time required for the newly formed bone tissue to mineralize and consolidate. Various studies have reported that among growth factors, bone morphogenetic proteins (BMPs) may play a central role in the molecular signaling cascade leading to bone renegeration and remodeling in a DO procedure. Ongoing research is aimed at developing methods to accelerate bone consolidation in order to reduce the time required to obtain consolidation. One of these methods is to test the ability of exogenous BMPs to increase bone regeneration and accelerate bone consolidation.

Influence of gender and fixation stability on bone defect healing in middle-aged rats: a pilot study.

BACKGROUND: Gender and stability of fixation independently influence bone regeneration but their combined effects are unclear. QUESTIONS/PURPOSES: In a pilot study we determined the combined influence of gender and fixation stability on the callus of middle-aged rats regarding (1) biomechanical properties; (2) bridging over time; (3) callus formation; and (4) callus size, geometry, mineralization, and microstructure. METHODS: We osteotomized the left femur of 32 Sprague-Dawley rats (12 months old). Femurs were externally fixed with a gap of 1.5 mm in four groups of eight animals each: female semirigid, male semirigid, female rigid, and male rigid. Qualitative and quantitative in vivo radiographic analyses were performed twice weekly. Six weeks postoperatively, harvested femora were evaluated using micro-CT and biomechanical testing. RESULTS: Torsional stiffness and maximum torque at failure were higher in male and in semirigidly fixed fractures. Radiographic analysis revealed earlier bridging and callus formation in both male groups. Micro-CT analysis showed a larger callus size, altered geometry, and microstructure in males and semirigidly fixed animals, whereas mineralization was similar in all animals. CONCLUSION: Our data suggest female gender represents an independent risk factor for bone healing in middle-aged rats. Although healing in females was delayed compared with males, they exhibited a similar response (superior callus properties) to a more semirigid fixation. CLINICAL RELEVANCE: While female gender appears to reflect a risk for impaired bone healing in middle-aged female rats, clinical studies would be required to confirm the finding in humans.

Comparative study of callus progression in limb lengthening with or without intramedullary nail with reference to the pixel value ratio and the Ru Li's classification.

INTRODUCTION: Callus progression is a great concern during limb lengthening. In this study, we investigated the difference in callus progression between tibial lengthenings with and without intramedullary nail. METHOD: Seventy tibiae in 38 patients with an average age of 24 years were lengthened with Ilizarov external fixator and nail; 56 tibiae in 40 patients with an average age of 28.6 years were lengthened with the same Ilizarov external fixator but without nail. The callus progression was compared with reference to pixel value ratio (PVR) and Ru Li's classification. Statistical analysis was performed to compare the variation trend of PVR and incidence of various callus pathways (particular patterns of callus progression as outlined in Ru Li's classification) and shapes of each aspect of callus between the two groups. RESULTS: The trend of PVR was not statistically different in posterior, lateral and medial aspects of the callus between the two groups, but averagely lower in the anterior aspect in the group without nail than that with nail. The group without nail presented less incidence of homogeneous pathway, greater incidence of heterogeneous pathway; also greater incidence of fusiform callus, less incidence of cylindrical callus. CONCLUSION: It was concluded that with nail, the callus underwent a more favorable progression and even longer lengthening could be allowed.

Analysis of the performance of different orthodontic devices for mandibular symphyseal distraction osteogenesis.

The aim of this study was to investigate the performance of different orthodontic devices for mandibular symphyseal distraction osteogenesis (MSDO). Two performance parameters were analysed, the first of which concerned the stability guaranteed by a distractor in the fracture gap under mastication loads and the second the level of reliability with which a distractor transfers a given expansion to the mandibular bone, inasmuch as the more reliable the device the smaller the difference between the degree of expansion provided to the device and the displacement achieved on the mandibular arch. Hence, a non-linear finite element (FE) model of a human mandible with different devices (tooth-borne, bone-borne, and hybrid) was constructed and then utilized to assess the structural behaviour of the mandibular bone under distraction and mastication loads. An ad hoc algorithm was developed to simulate progressive expansion of the devices; a distraction protocol comprising a 10 day latency period and a 6 day distraction period was hypothesized. The first hypothetical expansion given to the device was 2 mm, and the five subsequent expansions were 1 mm. The results showed that the hybrid device was the most stable appliance under mastication loads, followed by the tooth- and bone-borne devices. However, parasitic rotations of the mandibular arms caused by mastication might counteract the benefits of distraction. The tooth-borne device was found to have the highest reliability in transferring expansion to the mandibular bone. For this device, mandibular expansion was less than the nominal aperture of the distractor by no more than 15 per cent. Lower values of reliability were achieved with the bone-borne device. As the values of the aperture of the appliances increased, the stability guaranteed in the fracture gap increased while the reliability in transferring expansion to the mandibular arch decreased.