Current Modalities for Fracture Healing Enhancement

Previously, most fractures have been treated through bone reduction and immobilization. With an increase in the patients’ need for an early return to their normal function, development in surgical techniques and materials have accelerated. However, delayed union or non-union of the fracture site sometimes inhibits immediate return to normal life. To enhance fracture healing, diverse materials and methods have been developed. This is a review on the current modalities of fracture healing enhancement, which aims to provide a comprehensive knowledge regarding fracture healing for researchers and health practitioners.

Refracture after locking compression plate removal in displaced midshaft clavicle fractures after bony union: a retrospective study

Background@#A midshaft clavicle fracture is a common fracture that typically responds well to open reduction and internal fixation (ORIF). However, refracture can occur after implant removal (IR). This study aimed to analyze the rate of refracture and related factors after removal of the locking compression plate (LCP) for displaced midshaft clavicle fractures. @*Methods@#We retrospectively reviewed the medical records of 201 patients who had undergone ORIF with LCP for midshaft clavicle fractures after IR after bony union from January 2011 to May 2018 at our institute. We evaluated basic demographic characteristics and radiographic parameters. All patients were treated with an LCP for primary fracture. The patients were divided into two groups: a refracture group that experienced a second fracture within 1 year after IR and a no-fracture group. @*Results@#There were four cases (1.99%) of refracture; three were treated conservatively, while one was treated surgically. All patients achieved bony union. The average interval between refracture and IR was 64 days (range, 6–210 days). There was a significant difference in classification of fractures (AO Foundation/Orthopaedic Trauma Association [AO/OTA] classification) between the two groups. However, other patient demographics and radiographic measurements between refracture and IR, such as bone diameter, showed no significant difference between the two groups. @*Conclusions@#This study showed that one in 50 patients suffered from refracture after removal of the LCP. Thus, if patients desire IR, the surgeon should explain that there is a relatively higher possibility of refracture for cases with simple or segmental fractures than for other types of fracture.

Refracture after locking compression plate removal in displaced midshaft clavicle fractures after bony union: a retrospective study

Background@#A midshaft clavicle fracture is a common fracture that typically responds well to open reduction and internal fixation (ORIF). However, refracture can occur after implant removal (IR). This study aimed to analyze the rate of refracture and related factors after removal of the locking compression plate (LCP) for displaced midshaft clavicle fractures. @*Methods@#We retrospectively reviewed the medical records of 201 patients who had undergone ORIF with LCP for midshaft clavicle fractures after IR after bony union from January 2011 to May 2018 at our institute. We evaluated basic demographic characteristics and radiographic parameters. All patients were treated with an LCP for primary fracture. The patients were divided into two groups: a refracture group that experienced a second fracture within 1 year after IR and a no-fracture group. @*Results@#There were four cases (1.99%) of refracture; three were treated conservatively, while one was treated surgically. All patients achieved bony union. The average interval between refracture and IR was 64 days (range, 6–210 days). There was a significant difference in classification of fractures (AO Foundation/Orthopaedic Trauma Association [AO/OTA] classification) between the two groups. However, other patient demographics and radiographic measurements between refracture and IR, such as bone diameter, showed no significant difference between the two groups. @*Conclusions@#This study showed that one in 50 patients suffered from refracture after removal of the LCP. Thus, if patients desire IR, the surgeon should explain that there is a relatively higher possibility of refracture for cases with simple or segmental fractures than for other types of fracture.

Rapid Cartilage Regeneration of Spheroids Composed of Human Nasal Septum-Derived Chondrocyte in Rat Osteochondral Defect Model

Background@#Cell-based therapies have been studied for articular cartilage regeneration. Articular cartilage defects have little treatments because articular cartilage was limited regenerative capacity. Damaged articular cartilage is difficult to obtain a successful therapeutic effect. In additionally these articular cartilage defects often cause osteoarthritis. Chondrocyte implantation is a widely available therapy used for regeneration of articular cartilage because this tissue has poor repair capacity after injury. Human nasal septum-drived chondrocytes (hNCs) from the septum show greater proliferation ability and chondrogenic capacity than human articular chondrocytes (hACs), even across different donors with different ages. Moreover, the chondrogenic properties of hNCs can be maintained after extensive culture expansion. @*Methods@#In this study, 2 dimensional (2D) monolayer cultured hNCs (hNCs-2D) and 3 dimensional (3D) spheroids cultured hNCs (hNCs-3D) were examined for chondrogenic capacity in vitro by PCR and immunofluorescence staining for chondrogenic marker, cell survival during cultured and for cartilage regeneration ability in vivo in a rat osteochondral defect model. @*Results@#hNCs-3D showed higher viability and more uniform morphology than 3D spheroids cultured hACs (hACs-3D) in culture. hNCs-3D also showed greater expression levels of the chondrocyte-specific marker Type II collagen (COL2A1) and sex-determining region Y (SRY)-box 9 (SOX9) than hNCs-2D. hNCs-3D also expressed chondrogenic markers in collagen. Specially, in the osteochondral defect model, implantation of hNCs-3D led to greater chondrogenic repair of focal cartilage defects in rats than implantation of hNCs-2D. @*Conclusion@#These data suggest that hNCs-3D are valuable therapeutic agents for repair and regeneration of cartilage defects.

Treatment of unusual locked posterior fracture–dislocation of the shoulder: a case series

Background@#Locked posterior fracture-dislocation of the shoulder (LPFDS) is a very rare injury that occurs predominantly in young patients following high-energy trauma. The long-term outcome of the treatment of this injury is often poor. This study sought to present the characteristics of injury, discuss the pathological anatomy, and to report the treatment outcomes of our case series. @*Methods@#Between January 2012 and May 2018, a total of 234 patients who underwent surgical treatment for proximal humerus fractures were reviewed. Among them, six patients (mean age, 54.7 years; range, 35–76 years) with LPFDS were included in this study. Four patients were treated with open reduction and internal fixation (ORIF) with locking plates, one with hemiarthroplasty, and one with reverse total shoulder arthroplasty. Clinical results were evaluated by Constant, American Shoulder and Elbow Surgeons (ASES), and visual analog scale (VAS) scores and radiologic evaluation was conducted using follow-up radiographs. @*Results@#The mean length of follow-up was 26.2 months (range, 12–54). The mean Constant, ASES, and VAS scores were 66.7, 65.5, and 2.2, respectively. Four patients who underwent ORIF achieved bony union, but avascular necrosis (AVN) of the humeral head was observed in two patients. No complications were observed in the patients who underwent arthroplasty surgery until final follow-up. @*Conclusions@#In the treatment of LPFDS, replacement arthroplasty can produce predictable results. The approach of ORIF may be considered as a first choice of treatment in young patients but is sometimes correlated with postoperative complications such as AVN and the functional outcomes may be unpredictable. Therefore, patients should undergo careful diagnosis and treatment of this type of injury.

Treatment of unusual locked posterior fracture–dislocation of the shoulder: a case series

Background@#Locked posterior fracture-dislocation of the shoulder (LPFDS) is a very rare injury that occurs predominantly in young patients following high-energy trauma. The long-term outcome of the treatment of this injury is often poor. This study sought to present the characteristics of injury, discuss the pathological anatomy, and to report the treatment outcomes of our case series. @*Methods@#Between January 2012 and May 2018, a total of 234 patients who underwent surgical treatment for proximal humerus fractures were reviewed. Among them, six patients (mean age, 54.7 years; range, 35–76 years) with LPFDS were included in this study. Four patients were treated with open reduction and internal fixation (ORIF) with locking plates, one with hemiarthroplasty, and one with reverse total shoulder arthroplasty. Clinical results were evaluated by Constant, American Shoulder and Elbow Surgeons (ASES), and visual analog scale (VAS) scores and radiologic evaluation was conducted using follow-up radiographs. @*Results@#The mean length of follow-up was 26.2 months (range, 12–54). The mean Constant, ASES, and VAS scores were 66.7, 65.5, and 2.2, respectively. Four patients who underwent ORIF achieved bony union, but avascular necrosis (AVN) of the humeral head was observed in two patients. No complications were observed in the patients who underwent arthroplasty surgery until final follow-up. @*Conclusions@#In the treatment of LPFDS, replacement arthroplasty can produce predictable results. The approach of ORIF may be considered as a first choice of treatment in young patients but is sometimes correlated with postoperative complications such as AVN and the functional outcomes may be unpredictable. Therefore, patients should undergo careful diagnosis and treatment of this type of injury.

Rapid Cartilage Regeneration of Spheroids Composed of Human Nasal Septum-Derived Chondrocyte in Rat Osteochondral Defect Model

Background@#Cell-based therapies have been studied for articular cartilage regeneration. Articular cartilage defects have little treatments because articular cartilage was limited regenerative capacity. Damaged articular cartilage is difficult to obtain a successful therapeutic effect. In additionally these articular cartilage defects often cause osteoarthritis. Chondrocyte implantation is a widely available therapy used for regeneration of articular cartilage because this tissue has poor repair capacity after injury. Human nasal septum-drived chondrocytes (hNCs) from the septum show greater proliferation ability and chondrogenic capacity than human articular chondrocytes (hACs), even across different donors with different ages. Moreover, the chondrogenic properties of hNCs can be maintained after extensive culture expansion. @*Methods@#In this study, 2 dimensional (2D) monolayer cultured hNCs (hNCs-2D) and 3 dimensional (3D) spheroids cultured hNCs (hNCs-3D) were examined for chondrogenic capacity in vitro by PCR and immunofluorescence staining for chondrogenic marker, cell survival during cultured and for cartilage regeneration ability in vivo in a rat osteochondral defect model. @*Results@#hNCs-3D showed higher viability and more uniform morphology than 3D spheroids cultured hACs (hACs-3D) in culture. hNCs-3D also showed greater expression levels of the chondrocyte-specific marker Type II collagen (COL2A1) and sex-determining region Y (SRY)-box 9 (SOX9) than hNCs-2D. hNCs-3D also expressed chondrogenic markers in collagen. Specially, in the osteochondral defect model, implantation of hNCs-3D led to greater chondrogenic repair of focal cartilage defects in rats than implantation of hNCs-2D. @*Conclusion@#These data suggest that hNCs-3D are valuable therapeutic agents for repair and regeneration of cartilage defects.

Erratum to: Autologous Bone-marrow Mesenchymal Cell induced Chondrogenesis: Single-stage Arthroscopic Cartilage Repair

There was an error in Fig. 3 caption of the originally published article. Please find the correct figure and caption in this erratum

Autologous Bone Marrow Mesenchymal Cell Induced Chondrogenesis for the Treatment of Osteoarthritis of Knee

Healthy and high quality of life has become the main issue with increasing human life span. Many biological treatments for osteoarthritis of the knee have been tried with limited success. We compared data from 7 patients who underwent total knee arthroplasty and 46 patients who underwent autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) for osteoarthritis of grade IV of the Kellgren-Lawrence classification and grade IV of modified Outerbridge classification from 50 to 65 years of age. Clinical evaluation of the 2 groups showed significant improvement in the mean telephone Knee Society Scoring system (tKSS)-A (pain) and tKSS-B (function) scores throughout the postoperative follow-up period. There was no difference in the patients' satisfaction between the 2 groups. MCIC is a treatment option at least for delaying disease progression of osteoarthritis of the knee.

STX0119 Ameliorates Arthritis in SKG Mice via Inhibiting T Helper 17

Rheumatoid arthritis (RA) is an autoimmune disease with chronic and excessive inflammation. Upregulation of interleukin (IL)-17 is involved in the pathogenesis of RA. STX0119 is a specific inhibitor of signal transducer and activator of transcription 3 (STAT3) as a potential target for the treatment of RA. STAT3 is a member of DNA-binding molecules that regulates the expression of proinflammatory cytokines involved in the pathogenesis of RA. The objective of this study was to determine whether STX0119 could inhibit STAT3 and IL-17. We demonstrated that STX0119 decreased T helper (Th) 17 differentiation and IL-17 expression in vitro. STX0119 also improved the severity of zymosan induced arthritis and reduced joint inflammation. STX0119 reduced the proliferation of Th17 and phosphorylated STAT3 expression while increasing Treg differentiation and phosphorylated STAT5 expression. Moreover, STX0119 decreased the expression of IL-6 and -17 but not IL-10. These findings suggest that STX0119 can be used to treat autoimmune RA through inhibiting the activation of STAT3.

Treatment of Articular Cartilage Injury Using Mesenchymal Stem Cells / 대한정형외과연구학회지

Articular cartilage lesions can be a debilitating disease resulting in the development of osteoarthritis (OA). In recent years, mesenchymal stem cell (MSC) strategies combined with the microfracture technique are emerging as a powerful tool for cartilage repair. Even though there are some successful reports of MSCs treatments, many aspects have to be optimized such as best cell source and application method. The interest in this field is growing and randomized controlled trials are needed to show the potential of MSC treatment.

Stem Cell Therapy in Articular Cartilage Injury

The natural history after articular cartilage injury is unclear. However, it is generally accepted that once articular cartilage is injured, its ability to regenerate is limited and that injury progresses to arthritis with time. Over the years various treatments have been developed and are used, such as arthroscopic debridement, microfracture, multiple drilling, osteochondral transfer, and Autologous Chondrocyte Implantation (ACI). These can be divided into treatment methods which apply cells and those which apply tissue. The former include abrasion chondroplasty, microfracture, multiple drilling, and ACI. The latter include osteochondral transfer and allograft. Combination treatments using both cells and tissues are new-generation ACI and microfracture with biomaterials. The clinical applications of stem cell therapy is still at an early stage, but shows much promise, particularly in the management of cartilage defects.

Intertrochanteric Varus Open Wedge Osteotomyin Legg-Calve-Perthes Disease Patients Older than 9 Years Old / 대한정형외과학회잡지

PURPOSE: To evaluate the outcome of intertrochanteric varus open wedge osteotomy in LCP in patients over 9 years old. MATERIALS AND METHODS: Thirty-three patients over 9 years old, who were diagnosed with LCP were treated by intertrochanteric varus open wedge osteotomies, from August 1989 to August 2002. The mean age of the patients was 10.2 years old (range, 9 to 14 years old), with a mean duration of follow-up of 7.7 years (range, 3.2 to 14.1 years). According to the Harring classification system, there were 3 group A, 21 group B, and 11 group C patients. There were thirty male and three female patient. There were 2 cases of female patients with bilateral extremity involvement of LCP. Radiographic outcome was assessed utilizing Stulberg's classification to grade residual deformities. RESULTS: 10 cases were Stulberg classes I and II (spherically congruent), 15 were classes III and IV (aspherically congruent), and 10 were class V (aspherically incongruent). Less involvement of the disease and treatment in the early stages produced better outcomes. CONCLUSION: Intertrochanteric varus open wedge osteotomy is a reliable treatment for LCP after the age of 9 years old, if the disease is evaluated individually according to the extent and stage of its involvement.

Leg Length Discrepancy Associated with Idiopathic Hemihypertrophy / 대한정형외과학회잡지

PURPOSE: To evaluate the changes in the leg length discrepancy in idiopathic hemihypertrophy as a function of time. MATERIALS AND METHODS: A lower extremity scannogram was performed on 33 patients (16 boys and 17 girls) who were clinically diagnosed with idiopathic hemihypertrophy from September, 1985 to December, 1996. The leg length discrepancy was compared every 6 months. The mean age of the patients on the first visit was 1.6 years (range, 1 to 5 years) and the average follow up period was 9.1 years (range, 8 to 15 years). RESULTS: Not all the discrepancies continued to increase at a constant rate with time. The developmental discrepancy patterns identified were classified as follows: type I, increasing pattern; type II, increasing-plateau pattern; type III, plateau pattern; type IV, increasing-decreasing pattern; type V, decreasing pattern. Twenty five patients (75%) had types I and II discrepancy patterns. CONCLUSION: A continual periodic follow up of the leg length is important in idiopathic hemihypertrophy patients because the developmental patterns of a discrepancy in the length of a lower extremity can vary.

Treatment of Long Tubular Bone Defect of Rabbit Using Autologous Cultured Osteoblasts Mixed with Fibrin / 대한정형외과연구학회지

PURPOSE: The osteogenic potential of autologous cultured osteoblasts mixed with fibrin when transplanted to bone defects was evaluated. MATERALS AND METHODS: Radial shaft defects over 15 mm were made in 30 New Zealand white rabbits. Fifteen rabbits in the control group underwent an iliac bone graft and 15 rabbits in the experimental group underwent an autologous cultured osteoblast injection mixed with fibrin. Both groups were compared radiologically and 5 rabbits in each group were sacrificed for histological evaluation using H-E and Masson's trichrome stains at 3, 6, and 9 weeks. RESULTS: Osteogenesis in the control group progressed more rapidly than in the experimental group. However, at 9 weeks, bone formation in both groups were similar and showed no significant difference in terms of the amount of bone formation and the quality of bone union. CONCLUSION: Autologous cultured osteoblast transplantation mixed with fibrin in bone defects was found to produce bone efficiently.

Bone Formation of Cultured Osteoblasts in Bone Defect of Radial Shaft of Rabbit / 대한정형외과학회잡지

PURPOSE: To evaluate the osteogenic potential of an autologous cultured osteoblast transplant to the bone defects. MATERIALS AND METHODS: Radial bone defects over 15 mm were made in 20 New Zealand white rabbits using the anterior approach. There were 10 rabbits in the control group, which underwent an iliac bone graft to the preformed bone defect 3 weeks from the initial operation. There were 10 rabbits in the experimental group that underwent an autologous cultured osteoblasts injection. After 9 weeks, both groups were compared radiologically and histologically. RESULTS: The osteogenesis in both groups were progressed similarly and there was no difference in terms of the amount of bone formation and the duration of the bone union. CONCLUSION: An autologous cultured osteoblast transplant to the bone defect produces bone efficiently.In addition, it can be applied to a wide field, which requires a bone grafting operation.

Lower Limb Position in Oxford Unicompartmental Knee Arthroplasty

PURPOSE: To compare the accuracy of tibial cutting between in dangling position and standing position of the lower limb for Oxford unicompartmental knee arthroplasty. MATERIALS AND METHODS: From September 2001 to September 2003, While performing Oxford unicompartmental knee arthroplasty, we cut tibial plateau with lower extremity in dangling position and standing position alternately. Group 1 consisted of 12 cases underwent tibial cutting in dangling position. Group 2 consisted of 12 cases underwent tibial cutting in standing position. Clinical assessments consisted of radiologic evaluation and HSS knee score. RESULTS: There were no significant differences in limb alignments and HSS knee scores between group 1 and group 2 at one year postoperatively. In anteroposterior radiographs, the mean alignment of tibial component of group 1 was measured 4.07+/-5.7 degrees varus to the tibial axis and that of group 2 was measured 2.34+/-2.4 degrees varus to the tibial axis(P=0.35). CONCLUSION: In Oxford unicompartmental knee arthroplasty, tibial cutting in standing position showed a tendency to cut tibia more perpendicular to the tibial axis. But it was statistically not significant.

Open Reduction of Developmental Dislocation of the Hip in Patients Older than Eight Years / 대한정형외과학회잡지

PURPOSE: To evaluate the outcome and effectiveness of an open reduction in DDH for the patients 8 years and older. MATERIALS AND METHODS: Fourteen patients older than 8 years and diagnosed with DDH were treated by an open reduction, femoral shortening, and varus derotational osteotomy, combined with or without a Chiari osteotomy from August, 1981 to November, 2002 However, one patient was treated without femoral shortening. The mean age of the patients besides the 2 patients of failure at the time of surgery was 13.1 years (range 8-23), the mean follow up duration was 9.1 years (range 1-22 years). There were 6 cases of left side involvement of DDH, and 5 cases of right side involvement, while the remaining were both sides. One case was male and the others were female, and all hips were dislocated completely. RESULTS: One hip out of 14 patients was not unreduced intraoperatively. One hip showed a redislocation during the follow up period. Eleven patients gained almost the full range of motion of the affected hip except for one patient. Five out of the 12 patients showed a normal gait without limping and pain, and 3showed a slight limping gait but was much improved compared with the preoperative state. Four patients showed a limping gait due to a leg length discrepancy, and the limping gait of one patient was corrected by femoral lengthening. The average Harris hip score among the patients except for 2 cases of failure was 94.6. Nine patients were excellent and 3 patients were good. CONCLUSION: A neglected DDH should be treated positively Because a functionally good hip joint can be obtained after an open reduction of a developmentally dislocated hip, even after the age of 8.

CT Arthrography and Virtual Arthroscopy in the Diagnosis of the Anterior Cruciate Ligament and Meniscal Abnormalities of the Knee Joint

OBJECTIVE: To determine the diagnostic accuracy of CT arthrography and virtual arthroscopy in the diagnosis of anterior cruciate ligament and meniscus pathology. MATERIALS AND METHODS: Thirty-eight consecutive patients who underwent CT arthrography and arthroscopy of the knee were included in this study. The ages of the patients ranged from 19 to 52 years and all of the patients were male. Sagittal, coronal, transverse and oblique coronal multiplanar reconstruction images were reformatted from CT arthrography. Virtual arthroscopy was performed from 6 standard views using a volume rendering technique. Three radiologists analyzed the MPR images and two orthopedic surgeons analyzed the virtual arthroscopic images. RESULTS: The sensitivity and specificity of CT arthrography for the diagnosis of anterior cruciate ligament abnormalities were 87.5%-100% and 93.3-96.7%, respectively, and those for meniscus abnormalities were 91.7%-100% and 98.1%, respectively. The sensitivity and specificity of virtual arthroscopy for the diagnosis of anterior cruciate ligament abnormalities were 87.5% and 83.3-90%, respectively, and those for meniscus abnormalities were 83.3%-87.5% and 96.1-98.1%, respectively. CONCLUSION: CT arthrography and virtual arthroscopy showed good diagnostic accuracy for anterior cruciate ligament and meniscal abnormalities.

Clinical Applications of Autologous Cultured Osteoblasts: Case Report

We treated 3 cases of fracture and 1 case of avascular necrosis of femoral head using autologous cultured osteoblasts injection. The stromal cells from the bone marrow were cultured to differentiate to osteoblasts for 4 weeks. The fracture sites of each patients were right ulnar shaft, left radial shaft, and left 5th metatarsal base. All of the fractures showed callus formations after 1 week of osteoblasts injection to the fracture site. After 4 weeks, callus formations were progressed. Avascular necrosis of femoral head was bilateral and both were Ficat stage II. Core decompression and allograft impaction were performed to the left, and core decompression and autologous cultured osteoblasts injection percutaneously after 4 weeks of the decompression operation were done to the right femoral head. CT images of 1 year from the operations showed trabecular bone formation and well maintained femoral head contour of the right femur, but resorption of the grafted bone for the left.