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The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 11 | Pages 1539 - 1544
1 Nov 2007
Hibino N Hamada Y Sairyo K Yukata K Sano T Yasui N

This study was undertaken to elucidate the mechanism of biological repair at the tendon-bone junction in a rat model. The stump of the toe flexor tendon was sutured to a drilled hole in the tibia (tendon suture group, n = 23) to investigate healing of the tendon-bone junction both radiologically and histologically. Radiological and histological findings were compared with those observed in a sham control group where the bone alone was drilled (n = 19). The biomechanical strength of the repaired junction was confirmed by pull-out testing six weeks after surgery in four rats in the tendon suture group. Callus formation was observed at the site of repair in the tendon suture group, whereas in the sham group callus formation was minimal. During the pull-out test, the repaired tendon-bone junction did not fail because the musculotendinous junction always disrupted first. In order to understand the factors that influenced callus formation at the site of repair, four further groups were evaluated. The nature of the sutured tendon itself was investigated by analysing healing of a tendon stump after necrosis had been induced with liquid nitrogen in 16 cases. A proximal suture group (n = 16) and a partial tenotomy group (n = 16) were prepared to investigate the effects of biomechanical loading on the site of repair. Finally, a group where the periosteum had been excised at the site of repair (n = 16) was examined to study the role of the periosteum. These four groups showed less callus formation radiologically and histologically than did the tendon suture group. In conclusion, the sutured tendon-bone junction healed and achieved mechanical strength at six weeks after suturing, showing good local callus formation. The viability of the tendon stump, mechanical loading and intact periosteum were all found to be important factors for better callus formation at a repaired tendon-bone junction


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 2 | Pages 227 - 230
1 Feb 2012
Yang T Wang T Tsai Y Huang K

In patients with traumatic brain injury and fractures of long bones, it is often clinically observed that the rate of bone healing and extent of callus formation are increased. However, the evidence has been unconvincing and an association between such an injury and enhanced fracture healing remains unclear. We performed a retrospective cohort study of 74 young adult patients with a mean age of 24.2 years (16 to 40) who sustained a femoral shaft fracture (AO/OTA type 32A or 32B) with or without a brain injury. All the fractures were treated with closed intramedullary nailing. The main outcome measures included the time required for bridging callus formation (BCF) and the mean callus thickness (MCT) at the final follow-up. Comparative analyses were made between the 20 patients with a brain injury and the 54 without brain injury. Subgroup comparisons were performed among the patients with a brain injury in terms of the severity of head injury, the types of intracranial haemorrhage and gender. Patients with a brain injury had an earlier appearance of BCF (p < 0.001) and a greater final MCT value (p < 0.001) than those without. There were no significant differences with respect to the time required for BCF and final MCT values in terms of the severity of head injury (p = 0.521 and p = 0.153, respectively), the types of intracranial haemorrhage (p = 0.308 and p = 0.189, respectively) and gender (p = 0.383 and p = 0.662, respectively). These results confirm that an injury to the brain may be associated with accelerated fracture healing and enhanced callus formation. However, the severity of the injury to the brain, the type of intracranial haemorrhage and gender were not statistically significant factors in predicting the rate of bone healing and extent of final callus formation


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 81 - 81
1 Feb 2012
Mushtaq S Harwood P Ghoz A Branfoot T Roa A Giannoudis P
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The effect of head injury on systemic physiology, including bone healing is still a topic of vivid discussion. We aimed to investigate whether in patients with long bone fractures the presence of head injury is associated with excessive callus formation. Data on patients with head injury and femoral diaphyseal fracture admitted to our trauma unit between 1997- 2002 were collected and analysed. Patients with factors that could influence bone healing such as smoking, NSAIDs and hormonal disorders were excluded. The severity of head injury was quantified using GCS, AIS and CT scan reports. Patients matched for age, sex and ISS with femoral shaft fractures and no head injury formed the control group of the study. All the fractures were stabilised with reamed femoral nail. The quantification of fracture healing response was estimated by taking the radiological ratio of the largest diameter of callus formed into two planes and the adjacent normal diameter of femoral canal. The minimum follow-up of the patients was 12 months. In total 42 patients were studied, 17 with head injury and femoral fracture and 25 with an isolated femoral fracture, (control group). Both groups were comparable in terms of age, sex, ISS. The difference between the mean callus to diaphyseal ratio was statistically significant for both the AP and Lateral projections (AP – mean difference 0.462, 95% CI 0.312 to 0.602, p<0.0001, LAT – mean difference 0.289, 95% CI 0.142 to 0.436, p<0.001) with the head injured patients having more florid callus compared to the control group. This study supports the view that head injury leads to exuberant callus formation in patients with long bone fractures. The mechanisms of this response could be both central and local. Research is ongoing to elucidate the pathways involved in this biological phenomenon


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 116 - 116
11 Apr 2023
Buettmann E DeNapoli R Abraham L Denisco J Lorenz M Friedman M Donahue H
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Patients with bone and muscle weakness from disuse have higher risk of fracture and worse post-injury mortality rates. The goal of this current study was to better inform post-fracture rehabilitation strategies by investigating if physical remobilization following disuse by hindlimb unloading improves osteochondral callus formation compared to continued disuse by hindlimb suspension (HLS). We hypothesized that continued HLS would impair callus bone and cartilage formation and that physical rehabilitation after HLS would increase callus properties. All animal procedures were approved by the VCU IACUC. Skeletally mature, male and female C57BL/6J mice (18 weeks) underwent HLS for 3 weeks. Mice then had their right femur fractured by open surgical dissection (stabilized with 24-gauge pin). Mice were then either randomly assigned to continued HLS or allow normal physical weight-bearing remobilization (HLS + R). Mice allowed normal cage activity throughout the experiment served as controls (GC). All mice were sacrificed 14-days following fracture with 4-8 mice (male and female) per treatment. Data analyzed by respective ANOVA with Tukey post-hoc (*p< 0.05; # p < 0.10). Male and female mice showed conserved and significant decreases in hindlimb callus bone formation from continued HLS versus HLS + R. Combining treatment groups regardless of mouse sex, histological analyses using staining on these same calluses demonstrated that HLS resulted in trends toward decreased cartilage cross-sectional area and increased osteoclast density in woven bone versus physically rehabilitated mice. In support of our hypothesis, physical remobilization increases callus bone formation following fracture compared to continued disuse potentially due to increased endochondral ossification and decreased bone resorption. In all, partial weight-bearing exercise immediately following fracture may improve callus healing compared to delayed rehabilitation regimens that are frequently used


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 364 - 364
1 Oct 2006
Murnaghan J Li G Marsh D
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Introduction: Angiogenesis is essential during bone formation. Many studies have looked at the developing vascular network during normal and abnormal bone growth, using histological, immunohistological and contrast-radiological techniques; however all require sacrifice of animals to obtain tissue samples for examination and consequently chronological investigation of angiogenesis is not possible. We have endeavoured to produce an animal model, whereby quantitative assessment of blood flow, and callus formation across a fracture gap, can be repeatedly assessed. Methods: The model is an adaptation of a 4-pin externally fixated murine femoral fracture previously developed in this department. Three extra conduits have been drilled onto the fixator cross-bar, such that it now links with an x-ray jig and implantable optical cable. The x-ray jig permits repeated lateral x-rays whereas the optical cable which is implanted adjacent to the fracture gap and connected to a laser, measures blood flow using the principle of the Doppler shift of light. Ten mice underwent surgery. Doppler readings and x-rays were taken on the day of surgery and subsequently at days 1, 2, 4, 8, 12, 16, 24 and 32. Results: Fracture gap pixel density was seen to rise steadily and plateau at day 24, with significant statistical differences between the day of surgery and early time points, and then again between these early time-points (days 2, 4 and 8) and the late time-point day 24. Blood flow was noted to fall following the day of surgery and then slowly increase, with a rapid rise in flow at day 8 until day 16, when levels began to fall again to resting levels. Conclusion: The data correlates with previous histo-morphological work performed in this department and also with early results from immunohistochemical studies. The above graph for blood flow conforms to that expected in a murine model of fracture healing, with a short initial drop in flow followed by a large rise as angiogenesis follows chondrocyte hypertrophy at the end of the first week, leading to callus formation. This in vivo model may be used to assess the effects on angiogenesis and callus formation of osteogenic compounds and investigate possible antiangiogenic mechanisms of action of medications such as NSAIDs that are known to be detrimental to fracture repair


The Journal of Bone & Joint Surgery British Volume
Vol. 35-B, Issue 3 | Pages 417 - 422
1 Aug 1953
Strach EH

A case of hyperplastic callus formation is reported in a girl of eleven; several bones were affected. There were no associated fractures. She is believed to be suffering from a mild non-familial type of osteogenesis imperfecta without blue sclerotics and presents multiple bony excrescences unassociated with injury. The relevant literature is reviewed. The effect of a trial of treatment with A.C.T.H. and with deep x-ray is reported


The Journal of Bone & Joint Surgery British Volume
Vol. 35-B, Issue 3 | Pages 411 - 416
1 Aug 1953
Hilton G

In osteogenesis imperfecta the formation of callus is usually plentiful and sometimes rather excessive but the excess is absorbed in the normal way as consolidation occurs. In hyperplastic callus formation the amount of callus formed is large, or even enormous; and, once its limits are defined and ossification has occurred, some part of the original swelling remains as a thickening of the bone. "Callus" may form with or without injury and with or without fracture. The interest of the present case lies partly in the fact that there is no history of multiple fractures to indicate classical osteogenesis imperfecta, and partly in the familial incidence which has also been noted in other records. It is important to recognise the true nature of the condition in order to avoid the tragedy of unnecessary amputation. In one of Brailsford's cases the lesion is said to have become malignant but there is no other evidence in the literature that the condition has any relationship to malignancy. The clinical appearance can easily give rise to the suspicion of malignancy, and on histological examination the highly cellular and rapidly growing callus can be confused with a malignant condition. In fact, for the short time in which the bone formation runs riot the behaviour of a malignant neoplasm is closely simulated. It is thought that the present account may be of interest because of the invariable relief of pain after x-ray treatment of each new lesion, the length of time over which the case has been followed and the resemblance between the radiographic appearances in the patient now and those of her aunt taken twenty years ago


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 28 - 28
1 Jan 2003
Yamaji T Ando K Washimi O Terada N Yamada H Seki T
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Our purpose is to use radiographs to compare callus formation with two types of intramedullary nailing for femoral shaft fractures: reamed interlocking (IL) and Ender nails. Femoral shaft type A fractures according to AO classification were studied. From 1991 to 1995, 27 patients with 27 fractures were treated with reamed IL nailing and 79 patients with 81 fractures were treated with Ender nailing. IL group included with an average of 22 (range, 16–28) years, and the Ender group included with an average of 28 (range, 15–72) years. Patients had been followed for an average of 1.8 (range, 1–2.8) years after surgery. In all cases of IL group, the femoral canal was reamed. For type A3 fractures, an interlocking screw was inserted only at the distal site. For type A1 and A2 fractures, both proximal and distal locking screws were placed. In the Ender nailing cases, 3 to 5 Ender nails were inserted from medial or lateral side of the supracondylar or intertrochanteric regions of the femur as was dictated by the fracture site. All of these fractures were reduced by a closed technique. The measurement of postoperative callus area was calculated from the maximum cross-sectional area on the anteroposterior and lateral radiographs. Fracture healing was successful in all patients. On the radiograph, the callus for the IL group appeared at a mean of 3.9 weeks after surgery, and at a mean of 2.8 weeks for the Ender group. In the IL and Ender groups, fracture healing was noted at a mean of 3.4 and 2.0 months, respectively. The mean area of callus formation in the IL and Ender nailing was 439.5mm2 and 699.4 mm2, respectively. To compare the two groups by using a Mann-Whitney U test, the significant differences were seen in the callus appearance period (p< 0.05) and in the callus area (p< 0.01). Dynamization at the fracture site is reported to increase external callus formation. Our results indicate that the elasticity of the fixation obtained with Ender nailing promotes callus formation


The Journal of Bone & Joint Surgery British Volume
Vol. 69-B, Issue 4 | Pages 521 - 524
1 Aug 1987
Perkins R Skirving A

Callus formation and the rate of union of nailed fractures of the femur has been determined in 22 patients with associated head injuries and compared with that in a group of patients with similarly treated fractures but without head injuries. The comparison confirms the widely held view that, in patients with head injuries, fractures frequently heal with excessive callus and at a faster rate than normal


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 11 | Pages 1534 - 1538
1 Nov 2007
Hammer TO Wieling R Green JM Südkamp NP Schneider E Müller CA

This study investigated the quality and quantity of healing of a bone defect following intramedullary reaming undertaken by two fundamentally different systems; conventional, using non-irrigated, multiple passes; or suction/irrigation, using one pass. The result of a measured re-implantation of the product of reaming was examined in one additional group. We used 24 Swiss mountain sheep with a mean tibial medullary canal diameter between 8 mm and 9 mm. An 8 mm ‘napkin ring’ defect was created at the mid-diaphysis. The wound was either surgically closed or occluded. The medullary cavity was then reamed to 11 mm. The Reamer/Irrigator/Aspirator (RIA) System was used for the reaming procedure in groups A (RIA and autofilling) and B (RIA, collected reamings filled up), whereas reaming in group C (Synream and autofilling) was performed with the Synream System. The defect was allowed to auto-fill with reamings in groups A and C, but in group B, the defect was surgically filled with collected reamings. The tibia was then stabilised with a solid locking Unreamed Humerus Nail (UHN), 9.5 mm in diameter. The animals were killed after six weeks. After the implants were removed, measurements were taken to assess the stiffness, strength and callus formation at the site of the defect. There was no significant difference between healing after conventional reaming or suction/irrigation reaming. A significant improvement in the quality of the callus was demonstrated by surgically placing captured reamings into the defect using a graft harvesting system attached to the aspirator device. This was confirmed by biomechanical testing of stiffness and strength. This study suggests it could be beneficial to fill cortical defects with reaming particles in clinical practice, if feasible


The Journal of Bone & Joint Surgery British Volume
Vol. 34-B, Issue 3 | Pages 472 - 476
1 Aug 1952
Labdoff GA

The experiments showed that the administration of sodium citrate retards fracture healing. This is probably due to a change in the solubility of the calcium or to a relative calcium deficiency on account of the excretion in the urine, or to a combination of both factors. Other reasons cannot, however, be excluded, such as a biochemical effect on the ground substance or an enzyme deficiency.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 618 - 618
1 Oct 2010
Muljacic A Guberina M Poljak-Guberina R Turcic J Zivkovic O
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The aim of this study was to examine whether the assessment BsALP as a biochemical parameter in the early posttraumatic phase may indicate the course of fracture healing. The methods used for monitoring the bone healing process have been based on the patient’s subjective evaluation and radiographic findings. The activity of bone-specific alkaline phosphatase was measured in the sera of 41 patients who had sustained fractures of long bones. All the patients had been treated surgically. The activity of BsALP was assessed every seven days over a four-week period. The same patients were subject to radiology follow-ups for several months. Our research showed that the increase of alkaline phosphatase correlated with an increase of BsALP levels. The volume of callus correlated with a decrease, no change or an increase in the level of ALP and BsALP in the same way. It can be concluded that the monitoring of changes in the biochemical parameters of alkaline phosphatase and bone-specific alkaline phosphatase allows the early detection of the fracture healing dynamics.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 279 - 279
1 May 2010
Olender G Augat P Habermann B Kurth A
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Introduction: Patients who are prescribed bisphosphonates are still at risk to endure a fracture from weak and brittle bones. The question is what pharmacologic strategy should be taken to accelerate fracture healing when the patient is currently taking a bisphosphonate. Ibandronate, was tested in an osteoporotic rat model to determine how it modified the callus healing and resistance to torsion after a transverse fracture was produced in a femur.

Materials and Methods: 36 female rats were divided into 3 groups; ovariectomized (OVX) placebo control, non-OVX control and Ibandronate. Prior to the osteotomy, the Ibandronate treatment group was injected with the drug over 21 days healing. Each sample was scanned by the SCANCO uCT 80 to measure volume of the callus and quality of the trabeculae in the proximal femur. Instron testing recorded the modulus of rigidity and torque until failure. Yield point and toughness were also calculated.

Results: uCT images taken over the fracture gap showed that the Ibandronate rats had greater bone volume fraction of woven callus by ANOVA compared to control groups (p< 0.05). Significant in total callus volume for Ibandronate, were shown to be 32% larger than the non-OVX control group and 45% larger than the placebo group. Ibandronate also increased BMD of woven bone in the callus by 14%. Ibandronate showed the highest polar moment of inertia as well.

The torsion testing in Ibandronate had 51% greater toughness than placebo and 69% greater than the non-OVX group. Ibandronate increased trabecular number significantly over the placebo and was not significantly different from the non-OVX group. Trabecular separation was less in Ibandronate compared to the placebo group. Volume in the trabecular neck increased by 35% for the Ibandronate over the placebo.

Discussion: Ibandronate had an anabolic effect to produce more callus tissue at the fracture site, most likely by suppressing osteoclast remodelling activity. A large callus with more bone would increase fracture stability and reduce risk of non union. This is supported by a larger polar moment of inertia. Ibandronate had greater resistance to torsion, which could indicate better healing. However increased rigidity would not entirely benefit the healing unless the bone could handle load plastically. The toughness results showed that Ibandronate can absorb more energy than the control groups before refracturing. Continued treatment with this drug after a fracture could form a larger callus with greater mechanical toughness while also treating the disease of osteoporosis in other fracture risk sites of the body.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 1 | Pages 128 - 133
1 Jan 2012
Kim S Agashe MV Song S Choi H Lee H Song H

Lengthening of the humerus is now an established technique. We compared the complications of humeral lengthening with those of femoral lengthening and investigated whether or not the callus formation in the humerus proceeds at a higher rate than that in the femur. A total of 24 humeral and 24 femoral lengthenings were performed on 12 patients with achondroplasia. We measured the pixel value ratio (PVR) of the lengthened area on radiographs and each radiograph was analysed for the shape, type and density of the callus. The quality of life (QOL) of the patients after humeral lengthening was compared with that prior to surgery. The complication rate per segment of humerus and femur was 0.87% and 1.37%, respectively. In the humerus the PVR was significantly higher than that of the femur. Lower limbs were associated with an increased incidence of concave, lateral and central callus shapes. Humeral lengthening had a lower complication rate than lower-limb lengthening, and QOL increased significantly after humeral lengthening. Callus formation in the humerus during the distraction period proceeded at a significantly higher rate than that in the femur. . These findings indicate that humeral lengthening has an important role in the management of patients with achondroplasia


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 751 - 758
1 Jul 2024
Yaxier N Zhang Y Song J Ning B

Aims. Given the possible radiation damage and inaccuracy of radiological investigations, particularly in children, ultrasound and superb microvascular imaging (SMI) may offer alternative methods of evaluating new bone formation when limb lengthening is undertaken in paediatric patients. The aim of this study was to assess the use of ultrasound combined with SMI in monitoring new bone formation during limb lengthening in children. Methods. In this retrospective cohort study, ultrasound and radiograph examinations were performed every two weeks in 30 paediatric patients undergoing limb lengthening. Ultrasound was used to monitor new bone formation. The number of vertical vessels and the blood flow resistance index were compared with those from plain radiographs. Results. We categorized the new bone formation into three stages: stage I (early lengthening), in which there was no obvious callus formation on radiographs and ultrasound; stage II (lengthening), in which radiographs showed low-density callus formation with uneven distribution and three sub-stages could be identified on ultrasound: in Ia punctate callus was visible; in IIb there was linear callus formation which was not yet connected and in IIc there was continuous linear callus. In stage III (healing), the bone ends had united, the periosteum was intact, and the callus had disappeared, as confirmed on radiographs, indicating healed bone. A progressive increase in the number of vertical vessels was noted in the early stages, peaking during stages IIb and IIc, followed by a gradual decline (p < 0.001). Delayed healing involved patients with a prolonged stage IIa or those who regressed to stage IIa from stages IIb or IIc during lengthening. Conclusion. We found that the formation of new bone in paediatric patients undergoing limb lengthening could be reliably evaluated using ultrasound when combined with the radiological findings. This combination enabled an improved assessment of the prognosis, and adjustments to the lengthening protocol. While SMI offered additional insights into angiogenesis within the new bone, its role primarily contributed to the understanding of the microvascular environment rather than directly informing adjustments of treatment. Cite this article: Bone Joint J 2024;106-B(7):751–758


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 49 - 49
1 Nov 2021
Barcik J Ernst M Buchholz T Constant C Zeiter S Gueorguiev B Windolf M
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Introduction and Objective. It is widely accepted that interfragmentary strain stimulus promotes callus formation during secondary bone healing. However, the impact of the temporal variation of mechanical stimulation on fracture healing is still not well understood. Moreover, the minimum strain value that initiates callus formation is unknown. The goal of this study was to develop an active fixation system that allows for in vivo testing of varying temporal distribution of mechanical stimulation and that enables detection of the strain limit that initiates callus formation. Materials and Methods. We employed a previously established wedge defect model at the sheep tibia. The model incorporates two partial osteotomies directed perpendicularly to each other, thus creating a bone fragment in the shape of a wedge. The defect was instrumented with an active fixator that tilts the wedge around its apex to create a gradient of interfragmentary strain along the cutting line. The active fixator was equipped with a force and displacement sensors to measure the stiffness of the repair tissue during the course of healing. We developed a controller that enabled programming of different stimulation protocols and their autonomous execution during the in vivo experiment. The system was implanted in two sheep for a period of five weeks. The device was configured to execute immediate stimulation for one animal (stimulation from Day 1), and delayed stimulation for the other (stimulation from Day 22). The daily stimulation protocol consisted of 1’000 loading events evenly distributed over 12 hours from 9:00 am to 9:00 pm. The healing progression was monitored by the in vivo stiffness measurements provided by the fixator and by weekly radiographs. The impact of the local strain magnitude on bone formation was qualitatively evaluated on a post-mortem high-resolution CT scan of the animal with immediate stimulation. Results. The animals tolerated the fixator system well. Both devices operated seamlessly throughout the entire experiment. Callus formation was initiated earlier for the immediately stimulated animal which was also confirmed by a faster stiffness increase. In this pilot feasibility experiment, the initiation of callus formation was observed between 0% and 4% local interfragmentary strain. Conclusions. We developed an autonomous stimulation system for large animal research that enables systematic investigation of fracture healing processes. The in vivo pilot study demonstrated the feasibility of the system and delivered first interesting insides on temporal stimulation impact and callus induction strain limit. These observations, however, require further validation


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 112 - 112
11 Apr 2023
Oliver W Nicholson J Bell K Carter T White T Clement N Duckworth A Simpson H
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The primary aim was to assess the reliability of ultrasound in the assessment of humeral shaft fracture healing. The secondary aim was to estimate the accuracy of ultrasound assessment in predicting humeral shaft nonunion. Twelve patients (mean age 54yrs [20–81], 58% [n=7/12] female) with a non-operatively managed humeral diaphyseal fracture were prospectively recruited and underwent ultrasound scanning at six and 12wks post-injury. Scans were reviewed by seven blinded observers to evaluate the presence of sonographic callus. Intra- and inter-observer reliability were determined using the weighted kappa and intraclass correlation coefficient (ICC). Accuracy of ultrasound assessment in nonunion prediction was estimated by comparing scans for patients that united (n=10/12) with those that developed a nonunion (n=2/12). At both six and 12wks, sonographic callus was present in 11 patients (10 united, one developed a nonunion) and sonographic bridging callus (SBC) was present in seven patients (all united). Ultrasound assessment demonstrated substantial intra- (6wk kappa 0.75, 95% CI 0.47-1.03; 12wk kappa 0.75, 95% CI 0.46-1.04) and inter-observer reliability (6wk ICC 0.60, 95% CI 0.38-0.83; 12wk ICC 0.76, 95% CI 0.58-0.91). Absence of sonographic callus demonstrated a sensitivity of 50%, specificity 100%, positive predictive value (PPV) 100% and negative predictive value (NPV) 91% in nonunion prediction (accuracy 92%). Absence of SBC demonstrated a sensitivity of 100%, specificity 70%, PPV 40% and NPV 100% (accuracy 75%). Of three patients at risk of nonunion based on reduced radiographic callus formation (Radiographic Union Score for HUmeral fractures <8), one had SBC on 6wk ultrasound (and united) and the other two had non-bridging or absent sonographic callus (both developed a nonunion). Ultrasound assessment of humeral shaft fracture healing was reliable and predictive of nonunion, and may be a useful tool in defining the risk of nonunion among patients with reduced radiographic callus formation


Bone & Joint Research
Vol. 12, Issue 10 | Pages 657 - 666
17 Oct 2023
Sung J Barratt KR Pederson SM Chenu C Reichert I Atkins GJ Anderson PH Smitham PJ

Aims. Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Methods. Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results. Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion. These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients. Cite this article: Bone Joint Res 2023;12(10):657–666


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 14 - 14
1 Mar 2021
Hofmann-Fliri L Epari D Schwyn R Zeiter S Windolf M
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Fracture fixation has advanced significantly with the introduction of locked plating and minimally invasive surgical techniques. However, healing complications occur in up to 10% of cases, of which a significant portion may be attributed to unfavorable mechanical conditions at the fracture. Moreover, state-of-the-art plates are prone to failure from excessive loading or fatigue. A novel biphasic plating concept has been developed to create reliable mechanical conditions for timely bone healing and simultaneously improve implant strength. The goal of this study was to test the feasibility and investigate the robustness of fracture healing with a biphasic plate in a large animal experiment. Twenty-four sheep underwent a 2mm mid-diaphyseal tibia osteotomy stabilized with either the novel biphasic plate or a control locking plate. Different fracture patterns in terms of defect location and orientation were investigated. Animals were free to fully bear weight during the post-operative period. After 12 weeks, the healing fractures were evaluated for callus formation using micro-computer tomography and strength and stiffness using biomechanical testing. No plate deformation or failures were observed under full weight bearing with the biphasic plate. Osteotomies stabilized with the biphasic plate demonstrated robust callus formation. Torsion tests after plate removal revealed no statistical difference in peak torsion to failure and stiffness for the different fracture patterns stabilized with the biphasic plate. However, the biphasic plate group specimens were 45% stronger (p=0.002) and 48% stiffer (p=0.007) than the controls. The results of this large animal study demonstrate the clinical potential of this novel stabilization concept


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 4 - 4
1 Dec 2020
Tashmetov E Tuleubaev B Saginova D Koshanova A Rustambek I
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Introduction. Cancellous and cortical bone used as a delivery vehicle for antibiotics. Recent studies with cancellous bone as an antibiotic carrier in vitro and in vivo showed high initial peak concentrations of antibiotics in the surrounding medium. However, high concentrations of antibiotics can substantially reduce osteoblast replication and even cause cell death. Objectives. To determine whether impregnation with gentamycine impair the incorporation of bone allografts, as compared to allografts without antibiotic. Materials and method. Seventy two healthy rabbits (24 rabbits in each group) were used for this study. Bone defects (3-mm diameter, 10-mm depth) were created in the femur. Human femoral head prepared according to the Marburg bone bank system was used as bone allograft. In the experimental groups, in 1 group - the defects were filled with bone allografts, in 2 group – Perforated Gentamycin-impregnated bone allografts. The control group did not receive any filling. The animals were killed after 14, 30 and 60 days. Evaluations consisted of X-ray plain radiography, histology at 14-, 30- and 60-days post-surgery. Results. Active osteoblast activity and active formation of new bones were detected around the defect area in all groups, but the amount of new bone formation was greater in the experimental groups than the control group. We found no statistically significant differences in the rate of bone formation between 1 and 2 groups at 14, 30 and 60 days in any of the parameters studied. X-ray results showed no significant difference in bony callus formation around allografts in 1 and 2 groups. In contrast, no significant callus formation was observed in the control group. Conclusion. The use of gentamycin-impregnated bone allografts may be of value in procedures performed at the site of osteomyelitis which require a second stage reconstruction with impacted bone grafting techniques