Atrophic Nonunion Research Articles

What is the Optimal Treatment of Atrophic Scaphoid Non-Union?

What is the Optimal Treatment of Atrophic Scaphoid Non-Union?

上腕骨骨幹部骨折後の偽関節手術に対し術後合併症を回避し得た1例

We report a case of a patient with a history of surgery for insufficient pseudoarthrosis after a humeral diaphyseal fracture. Although most humeral nonunions are successfully treated with a single procedure, some humeral nonunions are more difficult to heal and require multiple procedures. A-61-year-old man presented at our hospital with pain and deformity in his left upper arm. The humeral diaphyseal fracture had been previously treated elsewhere with open reduction and internal fixation. Some days prior to his visit at our hospital, he had had pain in his left upper arm, without a particular cause, and was admitted to our hospital for initial evaluation. After a complete physical examination, symptoms of infection and any neurovascular deficit were ruled out. Radiographic examination revealed atrophic nonunion of the middle third of the humeral shaft associated with disuse osteopenia. Anterograde intramedullary nailing and bone grafting were performed for the resistant atrophic nonunion of the humeral diaphysis. In addition to the intramedullary nailing, additional fixation was performed for residual rotational instability. A postoperative evaluation revealed a periprosthetic fracture in the distal part of the humerus. Poor bone quality or a deficient plate technique might have lead to the facture. We performed open reduction and internal fixation (ORIF): he underwent fixation with a 2-plate construct for the nonunion of the humeral diaphyseal fracture, together with decortication, debridement, and bone grafting. Eight months after surgery, the patient's bone had healed and he had recovered flexion (110°) and extension (-30°) without complications. An orthopedic surgeon should be aware of these complications when choosing open reduction and internal fixation for the treatment of a history of insufficient pseudoarthrosis. Patients should be closely followed up for evidence of any complications such as infections and malunions. Fracture fixation in patients with pseudoarthrosis requires strategies to overcome the technical difficulties faced during the procedure.

Long Bone Nonunion

The percentage of delayed or non-unions after fractures of long bones depends on the individual risk profile at approximately 10 %. The current definition states that a non-union is a fracture that will not consolidate without any further intervention - independent from the treatment time. At the early stage of a non-union a conservative treatment is possible in case of an adequately stable situation. The operative treatment depends on the type of the non-union. There are one-step or two-step procedures, all according to the principles of the "diamond concept". This means improvement of the mechanical situation - in most cases by means of a reosteosynthesis - and vascularization, local application of osteoconductive carriers e.g. tricalciumphosphate, vital cells from autologous bone and osteoinductive substances like bone morphogenetic proteins (BMP-2 or BMP-7). Hypertrophic and atrophic non-unions without large defect gaps or signs of infection can be treated with a one-step procedure. For treating infected non-unions or non-unions with large defect gaps the Masquelet technique is recommended.

Are atrophic long-bone nonunions associated with low-grade infections?

Impaired fracture healing, especially when associated with bacterial infection, is a severe complication following long-bone fractures and requires special treatment. Because standard diagnostic techniques might provide falsely negative results, we evaluated the sonication method for detection of bacteria on implants of patients with fracture nonunions. A total of 49 patients with a nonunion (group NU) and, for comparison, 45 patients who had undergone routine removal of osteosynthetic material (group OM), were included in the study. Five different diagnostic methods (culture of tissue samples, culture of intraoperative swabs, histopathology of tissue samples, culture of sonication fluid, and 16S ribosomal DNA polymerase chain reaction of sonication fluid) were compared and related to clinical data. Among the diagnostic tests, culture of sonication fluid demonstrated by far the highest detection rate of bacteria (57%) in group NU, and rather unexpectedly 40% in group OM. Culture of sonication samples also revealed a broad spectrum of bacteria, in particular Propionibacterium spp. In conclusion, our results indicate that more bacteria can be detected on implants of patients with atrophic nonunions of long-bone fractures by means of the sonication procedure, which provides a valuable additional diagnostic tool to decide on a surgical procedure (eg, two-step procedure) and to further specify antimicrobial therapy.

Augmentation of bone healing in delayed and atrophic nonunion of fractures of long bones by partially decalcified bone allograft (decal bone).

Background:Autograft from iliac crest is considered as gold standard for augmentation of bone healing in delayed and nonunion of fractures. Bone demineralized with 0.6N hydrochloric acid has shown to retain its osteoinductive capacity. We report the outcome of partially decalcified bone allograft (decal bone) in the treatment of delayed union and atrophic nonunions of bones.Materials and Methods:Twenty patients with clinicoradiological diagnosis of delayed union or atrophic nonunion of long bone fractures were included in this retrospective study. Patients at extreme of ages (<18 years and >60 years), pathological fractures, metabolic bone diseases, infected nonunion, hypertrophic nonunion and those having systemic illness like diabetes mellitus and on drugs that impair fracture healing were excluded from the study. Decal bone was prepared in the bone bank and maintained in department of orthopedics. Allografting was done in 20 patients of delayed union (9/20) and atrophic nonunion (11/20) of long bone fractures with mean age of 34 years (range 18–55 years). The bones involved were humerus (8/20), tibia (7/20) and femur (5/20). Fourteen patients underwent treatment in the form of internal fixation and allografting and six patients were operated with osteoperiosteal allografting.Results:Nineteen patients achieved union in mean time of 14.9 weeks range (range 8–20 weeks). Eight patients had serous discharge from the operative site that subsided in 11 days (range 4–21 days). One patient had pus discharge that required repeat debridement and antibiotics for 6 weeks. The fracture healed in 16 weeks.Conclusion:The partially decalcified bone allograft is an effective modality for augmentation of bone healing without complication associated with autograft like donor site morbidity, increased blood loss and increase in the surgical time.

The treatment of atrophic, recalcitrant long-bone nonunion in the upper extremity with human recombinant bone morphogenetic protein-7 (rhBMP-7) and plate fixation: A retrospective review

IntroductionRecombinant Human Bone Morphogenetic Protein-7 (rhBMP-7) has been shown to promote fracture healing in both clinical studies and basic science models, however, there is little information from large-scale studies of its use for human nonunion. The purpose of this study was to determine the safety and efficacy of rhBMP-7 in the treatment of atrophic human long-bone nonunions in the upper extremity. Patients and methodsThis was a single center, retrospective, longitudinal cohort study of patients treated with compression plating and the application of rhBMP-7 in isolation to a long-bone nonunion. Patients over sixteen years of age with an atrophic, aseptic nonunion of a humerus, radius, ulna or clavicle were eligible for inclusion. ResultsWe identified seventy eligible patients who were treated with rhBMP-7 for a long-bone nonunion between July 1997 and April 2012. The mean age of the patients at the time of treatment with rhBMP-7 was 50.7 years (range, 20-92 years). Five patients were lost to follow-up prior to definitive clinical or radiographic union. During the one-year post-operative period fifty-six patients had achieved union and two patients developed a stable fibrous union after the index procedure. Two patients had early implant failure and five patients had persistent nonunion. Thus, the union rate following initial surgery was 89% (58/65) and four of the five nonunion patients went on to heal following revision open reduction and internal fixation. ConclusionWe found that the application of rhBMP-7 for upper extremity nonunion was an effective method (89% union rate) of treating this challenging pathology. Additionally, if not initially successful, further reconstruction was not compromised by rhBMP-7 use.

Treatment of atrophic bone nonunion of the elderly humerus shaft fracture with excision of the atrophic segment and locking plate fixation in 8 cases

Treatment of atrophic bone nonunion of the elderly humerus shaft fracture with excision of the atrophic segment and locking plate fixation in 8 cases

Mechanobiology in the management of mobile atrophic and oligotrophic tibial nonunions

BackgroundRecent research indicates that atrophic nonunions are biologically active and may heal in the optimal biomechanical environment. MethodsThirty-three patients with mobile atrophic and oligotrophic tibial nonunions were treated with circular external fixation and functional rehabilitation. Seven patients required autogenous bone graft procedures. ResultsBony union was achieved after the initial surgery in 31/33 (93.9%) tibias. Two persistent nonunions were successfully treated with repeat circular external fixation without bone graft. This resulted in final bony union in 33/33 (100%) patients. ConclusionMechanobiological stimulation of tibial nonunions can produce union even if the biological activity appears to be low.

Treatment of atrophic tibia non-unions according to ‘diamond concept’: Results of one- and two-step treatment

BackgroundThe successful treatment of atrophic tibia non-unions and tibia non-unions with large bone defects or infections is a major challenge in orthopedic and trauma surgery. This article evaluates the use of the ‘diamond concept’ using a one-step or two-step procedure according to ‘Masquelet technique’ in the treatment of atrophic tibia non-unions. MethodsBetween February 2010 and March 2014, 102 patients with atrophic non-unions were treated according to the ‘diamond concept’ in our center. Ninety-nine were available for follow-up. Forty-nine received a one-step treatment (Group 1, G1) and 50 patients received a two-step treatment according to the ‘Masquelet technique’ (Group 2, G2). Clinical and radiological parameters were measured preoperatively as well as 4, 6, and 12 weeks and 6 and 12 months postoperatively. In order to evaluate the subjective health of patients, we used the SF-12 questionnaire. Data analysis was performed one year after treatment. ResultsThe rate of consolidation in G1 was 84% and 80% in G2. The time to heal in G2 was 8.6 ± 2.9 months, which is significantly longer than in G1 being 6.9 ± 3.1 months. In comparison patients in G1/G2 had an average of 3.2/6.7 previous major surgeries. In G1, 4 of 8 patients who did not heal successfully showed positive intraoperative cultures. In G2, 26 patients (52%) initially presented with positive cultures. The results of the SF-12 questionnaire improved in both groups during the postoperative follow-up, but showed no significant differences between groups. In 29 patients a gentamycin-coated nail was used for reosteosynthesis. These patients showed by trend a lower rate of complications at a higher rate of consolidation. ConclusionsOur study showed that the ‘diamond concept’ is a suitable method for safely and effectively treating non-unions with large defects or infections. The use of an antibiotic-coated nail provides a therapeutic benefit. For large bone defects of infected non-unions the two-step procedure after Masquelet is an efficient way to eradicate the infection and treat the bone defect successfully.

Profiling microRNA expression in fracture nonunions: Potential role of microRNAs in nonunion formation studied in a rat model.

MicroRNAs (miRNAs ) are small non-coding RNAs that regulate gene expression. We hypothesised that the functions of certain miRNAs and changes to their patterns of expression may be crucial in the pathogenesis of nonunion. Healing fractures and atrophic nonunions produced by periosteal cauterisation were created in the femora of 94 rats, with 1:1 group allocation. At post-fracture days three, seven, ten, 14, 21 and 28, miRNAs were extracted from the newly generated tissue at the fracture site. Microarray and real-time polymerase chain reaction (PCR) analyses of day 14 samples revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p, were highly upregulated in nonunion. Real-time PCR analysis further revealed that, in nonunion, the expression levels of all five of these miRNAs peaked on day 14 and declined thereafter. Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p may play an important role in the development of nonunion. These findings add to the understanding of the molecular mechanism for nonunion formation and may lead to the development of novel therapeutic strategies for its treatment.

Complication management for failed bone fracture healing: pseudarthrosis

Delayed fracture healing for more than 6-8 months is defined as non-union (pseudarthrosis). Non-unions are classifiable as septic, aseptic, hypertrophic and atrophic non-unions. In case of septic non-unions the infection is treated primarily followed by treatment of the delayed fracture healing. Aseptic non-unions may be treated non-operatively (e.g. shock wave therapy and/or ultrasound) or by various surgical strategies to stimulate bone regeneration and healing.

Extracorporeal shockwave therapy (ESWT) in the treatment of atrophic non-unions of femoral shaft fractures

IntroductionAs of now, the role of extracorporeal shockwave therapy (ESWT) in the treatment of atrophic non-unions is inconclusive. The purpose of the study was to investigate the effectiveness of ESWT and the role of this technology in the treatment of atrophic non-union of femurs. MethodsWe retrospectively analyzed 22 patients treated between July 1999 and September 2007 in our hospital with ESWT for atrophic non-unions of isthmic femoral shaft fractures that were initially treated surgically using closed reamed nailing procedure. Patients with open fractures, skeletal immaturity, on anti-osteoporotic medications, with infections, pathological fractures, smokers, with systemic disease compromising bone healing, and excessive deformity were excluded from this study. Due to incomplete follow-up one (1) patient who moved abroad after ESTW treatment was not included in this study and as part of the 22-patients cohort. Radiographs were obtained before treatment and once a month after treatment for 12 months. ResultsUsing ESWT we showed that 14 fractures out of 22 (63.6%) achieved bony union with an average union time of 9.2 months (range 6–13 months). The union rate was 100% (8 of 8 cases) when ESWT was performed within 12 months from closed reamed nailing surgery versus 42.9% (6 of 14 cases) when ESWT was performed after 12 months from initial surgery. The eight (8) patients out of the total 22 patients cohort, who did not achieve bony union after ESWT, received subsequent treatment with bone grafting with augmentative plating surgery and all achieved bony union within 5 months after intervention. ConclusionFor patients with atrophic non-unions of femoral shaft fractures, ESWT can be used as an alternative and effective non-invasive method of treatment. ESWT treatment does not negatively influence/compromise previous surgeries and if needed it can be followed by additional surgeries without any complications.

Longitudinal analysis of osteogenic and angiogenic signaling factors in healing models mimicking atrophic and hypertrophic non-unions in rats.

Impaired bone healing can have devastating consequences for the patient. Clinically relevant animal models are necessary to understand the pathology of impaired bone healing. In this study, two impaired healing models, a hypertrophic and an atrophic non-union, were compared to physiological bone healing in rats. The aim was to provide detailed information about differences in gene expression, vascularization and histology during the healing process. The change from a closed fracture (healing control group) to an open osteotomy (hypertrophy group) led to prolonged healing with reduced mineralized bridging after 42 days. RT-PCR data revealed higher gene expression of most tested osteogenic and angiogenic factors in the hypertrophy group at day 14. After 42 days a significant reduction of gene expression was seen for Bmp4 and Bambi in this group. The inhibition of angiogenesis by Fumagillin (atrophy group) decreased the formation of new blood vessels and led to a non-healing situation with diminished chondrogenesis. RT-PCR results showed an attempt towards overcoming the early perturbance by significant up regulation of the angiogenic regulators Vegfa, Angiopoietin 2 and Fgf1 at day 7 and a further continuous increase of Fgf1, -2 and Angiopoietin 2 over time. However µCT angiograms showed incomplete recovery after 42 days. Furthermore, lower expression values were detected for the Bmps at day 14 and 21. The Bmp antagonists Dan and Twsg1 tended to be higher expressed in the atrophy group at day 42. In conclusion, the investigated animal models are suitable models to mimic human fracture healing complications and can be used for longitudinal studies. Analyzing osteogenic and angiogenic signaling patterns, clear changes in expression were identified between these three healing models, revealing the importance of a coordinated interplay of different factors to allow successful bone healing.

Präfabrikation von Knochentransplantaten

Prefabrication of bone transplants is a promising option for large defects of the long bones, especially if there is compromised vascularization of the defect. This is especially true for postinfection bone defects and other types of atrophic nonunion. The generation of a foreign body membrane (Masquelet's technique) has been investigated in order to ameliorate the response of the host tissue surrounding the defect. In an experimental animal study, a blood vessel within a bone construct could be used to generate customized, vascularized osteogenic constructs that can be used to treat large bone defects in the future.

Nonunion in a distal radius metaphyseal fracture in a child: Role of intact periosteal sleeve in management.

We present an adolescent with distal radius nonunion following an open fracture and failed surgery which eventually united when the length and stability was restored for eight weeks duration. The intact periosteal sleeve at the nonunion site formed new bone when its tension was restored by gradual differential distraction. This case report highlights the possibility of stimulating bony union in an established atrophic nonunion by distracting the minimally disturbed soft tissue and thick osteogenic periosteal envelope in the paediatric age group.

Novel rat model of nonunion fracture with vascular deficit

Nonunion fractures occur frequently in humans, with profound implications (medical and non-medical). Although there are numerous animal models to study pathogenesis and treatment of nonunion fractures, there is apparently the lack of a definitive model for atrophic nonunion fracture. Therefore, the objective was to develop a low-cost rat model of nonunion fracture with a vascular deficit that enabled standardized quantitative analysis of bone growth and regeneration. The model was developed with two surgeries, performed apart. The first involved osteotomy of the femur diaphysis, removal of periosteum and endosteum, isolation of the fracture site using a latex artefact (Penrose drain tube), and reduction of the fracture using an intramedullary pin, whereas the second surgery was to remove the latex artefact. Based on radiographic imaging, micro-CT and histological analyses done 125 days after the fracture was induced, there was clear evidence of atrophic nonunion fracture, without pin migration or specimen loss. Perceived advantages of this model included low cost, ease of reproducibility, lack of specimen loss, and, finally, the potential to assess bone growth and regeneration under poor vascular conditions.

Ilizarov fixator in management of nonunited and infected tibial shaft fractures

Background: Management of nonunion with bony defect and infection in long bones is a challenging problem for orthopedic surgeons. Objectives: Evaluation of Ilizarov circular fixation method of treatment for the management of nonunited and infected fractures of tibia. Materials and Methods: This prospective study was conducted in a tertiary care hospital of eastern region of India on 30 subjects in a time span of 3 years after taking clearance of the Institutional Ethical Committee and informed consent of the patients. Results: All the patients had infected nonunion before undergoing Ilizarov procedure. Following initial injury, 22 patients were treated with external fixation and 8 cases were treated with internal fixation. At the time of presentation, 18 patients had infected gap nonunion, 5 patients had infected hypertrophic and 2 patients had atrophic nonunion. The Ilizarov fixator was kept for an average period of 303.7 days. Based on Association for the Study and Application of Methods of Ilizarov scoring system, bony and functional results were assessed. The bony result was excellent in 16 patients, good in eight, fair in four and poor in two. The functional result was excellent in 10 patients, good in 16, fair in two, poor in two. Conclusion: Ilizarov ring fixator still remains an excellent treatment modality for tibial nonunion with a defect, regarding bone union, deformity correction, infection eradication, limb-length achievement, and limb function.

Lentivirus-mediated Wnt10b overexpression enhances fracture healing in a rat atrophic non-union model.

Lentivirus vectors encoding Wnt10b gene (LV-Wnt10b) or luciferase gene (LV-luc) were constructed to determine whether Wnt10b overexpression improved fracture healing in a rat atrophic non-union model. After fracture, rats were injected with LV-Wnt10b or LV-luc. Luciferase signals were clearly detected. At 2 and 4 weeks, LV-Wnt10b group had 107 and 98% more proliferating cell nuclear antigen (PCNA) positive cells, respectively, and promoted expression of bone morphogenetic protein-2 (BMP-2) in the callus compared with controls. LV-Wnt10b injection significantly increased bone mass density and bone mineral content: 46-84 and 96-193%, respectively, at the site of fracturein the LV-Wnt10b group compared with controls. At 8 weeks, fractured femora were healed in the LV-Wnt10b group compared with atrophic non-unions formed in controls. Thus, Wnt10b overexpression associated with lentiviral gene therapy is effective in healing atrophic non-unions in rats.

Expression of bone morphogenetic protein 2 in human nonunion tissue and the clinical significance

To explore the difference of bone formation potential between hypertrophic nonunion tissue and atrophic nonunion tissue, which may be beneficial to nonunion therapy. From October 2010 to March 2014, 40 nonunion tissue samples were collected in Department of Orthopedics, Second Xiangya Hospital. The samples were divided into a hypertrophic nonunion group (n=20) and an atrophic nonunion group (n=20) according to nonunion character; or a 20 to 35 years old group (n=18), a 36 to 50 years old group (n=18), a more than 50 years old group (n=4) according to different ages; or a 9-12 months group (n=21), 13-24 months group (n=14) and a more than 24 months group (n=5) according to different nonunion time. Semi-quantification was performed by SP immunohistochemical method and IPP6.0 was used to analyze the expression of bone morphogenetic protein-2 (BMP-2) through measuring the mean optical density. The mean optical density of BMP-2 was 0.1540±0.0408 in hypertrophic nonunion tissue, 0.1372±0.0372 in atrophic nonunion tissue, there was no significant difference between the 2 groups (P>0.05). The mean optical density of BMP-2 was 0.1477±0.0379 in the 20 to 35 years old group, 0.1419±0.0399 in the 35 to 50 years old group, 0.1456±0.0595 in the more than 50 years old group, there was no significant difference among the three groups (P>0.05). The mean optical density of BMP-2 was 0.1449±0.0366 in the 9-12 months group, 0.1472±0.0400 in the 13-24 months group, 0.1445±0.0541 in the more than 24 months group, there was no significant difference among the 3 groups (P>0.05). The present results suggest that the hypertrophic nonunion tissue share similar osteogenic potential with the atrophic nonunion tissue.

A pilot study investigating the histology and growth factor content of human non-union tissue.

The reason for the formation of an atrophic non-union is not clear and an altered vascularization as well as a deregulation of endogenous growth factors is hypothesized. To obtain more information, we analysed human non-union tissue regarding the histology and quantity of several growth factors. Tissue from patients with an atrophic non-union (n = 44) or with a healed fracture (n = 13) was analysed. Using histological and immunohistochemical methods the tissue composition was investigated. On the protein level the amount of several growth factors important for bone healing was analysed. The tissue composition was very inhomogeneous containing fibrous, cartilaginous and bony tissue. Vessels were present in all investigated samples without a difference between the tissue from non-union and control patients. The growth factor BMP-2 was below the detection limit in all samples, whereas IL-6 and IGF-I were measured only in a few samples of both groups. TGF-ß1, VEGF-A and BMP-4 were detectable in the majority of the samples of both groups with a high variability in the amount but no difference between the groups. The quantity of both growth factors, BMP-7 and PDGF-AB, was significantly lower in the non-union tissue compared to the healed controls. The reduced quantity of BMP-7 and PDGF-AB might be responsible for the impaired healing. Further studies analysing material from more patients and investigating the early healing phases, however, are necessary to obtain further information and consequently improve healing strategies.