Identification and validation of miR-29b-3p and LIN7A as important diagnostic markers for bone non-union by WGCNA.

Bone non-union is a common fracture complication that can severely impact patient outcomes, yet its mechanism is not fully understood. This study used differential analysis and weighted co-expression network analysis (WGCNA) to identify susceptibility modules and hub genes associated with fracture healing. Two datasets, GSE125289 and GSE213891, were downloaded from the GEO website, and differentially expressed miRNAs and genes were analysed and used to construct the WGCNA network. Gene ontology (GO) analysis of the differentially expressed genes showed enrichment in cytokine and inflammatory factor secretion, phagocytosis, and trans-Golgi network regulation pathways. Using bioinformatic site prediction and crossover gene search, miR-29b-3p was identified as a regulator of LIN7A expression that may negatively affect fracture healing. Potential miRNA-mRNA interactions in the bone non-union mechanism were explored, and miRNA-29-3p and LIN7A were identified as biomarkers of skeletal non-union. The expression of miRNA-29b-3p and LIN7A was verified in blood samples from patients with fracture non-union using qRT-PCR and ELISA. Overall, this study identified characteristic modules and key genes associated with fracture non-union and provided insight into its molecular mechanisms. Downregulated miRNA-29b-3p was found to downregulate LIN7A protein expression, which may affect the healing process after fracture in patients with bone non-union. These findings may serve as a prognostic biomarker and potential therapeutic target for bone non-union.

Clinical outcomes and complications of S53P4 bioactive glass in chronic osteomyelitis and septic non-unions: a retrospective single-center study.

INTRODUCTION: Dead space management following debridement surgery in chronic osteomyelitis or septic non-unions is one of the most crucial and discussed steps for the success of the surgical treatment of these conditions. In this retrospective clinical study, we described the efficacy and safety profile of surgical debridement and local application of S53P4 bioactive glass (S53P4 BAG) in the treatment of bone infections. METHODS: A consecutive single-center series of 38 patients with chronic osteomyelitis (24) and septic non-unions (14), treated with bioactive glass S53P4 as dead space management following surgical debridement between May 2015 and November 2020, were identified and evaluated retrospectively. RESULTS: Infection eradication was reached in 22 out of 24 patients (91.7%) with chronic osteomyelitis. Eleven out of 14 patients (78.6%) with septic non-union achieved both fracture healing and infection healing in 9.1 ± 4.9 months. Three patients (7.9%) developed prolonged serous discharge with wound dehiscence but healed within 2 months with no further surgical intervention. Average patient follow-up time was 19.8 months ± 7.6 months. CONCLUSION: S53P4 bioactive glass is an effective and safe therapeutic option in the treatment of chronic osteomyelitis and septic non-unions because of its unique antibacterial properties, but also for its ability to generate a growth response in the remaining healthy bone at the bone-glass interface.

Bioinformatics Analysis and Experimental Validation of Differential Genes and Pathways in Bone Nonunions.

Non-union fractures pose a significant clinical challenge, often leading to prolonged pain and disability. Understanding the molecular mechanisms underlying non-union fractures is crucial for developing effective therapeutic interventions. This study integrates bioinformatics analysis and experimental validation to unravel key genes and pathways associated with non-union fractures. We identified differentially expressed genes (DEGs) between non-union and fracture healing tissues using bioinformatics techniques. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to elucidate the biological processes and pathways involved. Common DEGs were identified, and a protein-protein interaction (PPI) network was constructed. Fibronectin-1 (FN1), Thrombospondin-1 (THBS1), and Biglycan (BGN) were pinpointed as critical target genes for non-union fracture treatment. Experimental validation involved alkaline phosphatase (ALP) and Alizarin Red staining to confirm osteogenic differentiation. Our analysis revealed significant alterations in pathways related to cell behavior, tissue regeneration, wound healing, infection, and immune responses in non-union fracture tissues. FN1, THBS1, and BGN were identified as key genes, with their upregulation indicating potential disruptions in the bone remodeling process. Experimental validation confirmed the induction of osteogenic differentiation. The study provides comprehensive insights into the molecular mechanisms of non-union fractures, emphasizing the pivotal roles of FN1, THBS1, and BGN in extracellular matrix dynamics and bone regeneration. The findings highlight potential therapeutic targets and pathways for further investigation. Future research should explore interactions between these genes, validate results using in vivo fracture models, and develop tailored treatment strategies for non-union fractures, promising significant advances in clinical management.

Outcomes in children with delayed surgical treatment of medial humeral condyle fractures.

PURPOSE: Medial humeral condyle (MHC) fractures are easily overlooked in young patients. This can lead to delayed or incorrect diagnosis, resulting in delayed treatment, which is often associated with complications such as nonunion, osteonecrosis, fishtail deformity, and cubitus varus. The purpose of this study is to evaluate the clinical and radiographic outcomes in a cohort of paediatric patients who underwent delayed surgery for an untreated MHC fracture. METHODS: From January 2017 to December 2022, we conducted a retrospective study of paediatric patients who underwent delayed treatment for a MHC fracture. In all cases, the initial diagnosis was incorrect and surgery was performed at least one week after injury. Patients were divided into two groups based on the time between trauma and surgery: Group 1 consisted of individuals who underwent early delayed treatment within seven to 30 days of injury, while Group 2 consisted of those who underwent late delayed treatment more than one month after injury. Elbow function was assessed using the Mayo Elbow Performance Score (MEPS) and range of motion (ROM). The related literature was also reviewed (1970-2023). RESULTS: We enrolled 12 patients (7 boys, 5 girls); the average age at the time of surgery was 7.7 years (range, 2-14 years). Six patients underwent early delayed treatment (Group 1) while another six underwent late delayed treatment (Group 2). The mean time from injury to surgery was 17.7 days (range, 7-30 days) and 33.3 months (range, 70 days-9 years) in Groups 1 and 2, respectively. Open reduction and internal fixation were performed via a medial approach in 11 patients, while one patient underwent closing wedge osteotomy and internal fixation to correct cubitus varus deformity. The mean duration of follow-up was 39.4 months (range, 8-60 months). The average MEPS score was 98.3 in Group 1 (range, 95-100) and 94.2 in Group 2 (range, 85-100; P = 0.21). The following postoperative complications were recorded: heterotopic ossification (n = 2), fishtail deformity (n = 1), MHC necrosis (n = 1), and reduction of elbow ROM (n = 1); one complication occurred in Group 1 and five occurred in Group 2 (P = 0.18). We reviewed nine related studies (n = 14 patients). CONCLUSIONS: Diagnosis of MHC fractures can be challenging in paediatric patients, especially in younger individuals with incompletely ossified trochlea. Patients requiring surgery for delayed MHC fractures with an unossified trochlea should undergo ORIF to prevent progressive varus deformity. On the other hand, in patients with cubitus varus and an already ossified trochlea, distal humeral osteotomy should be considered instead of ORIF. This will minimize the potential negative impact on joint mobility.

The effect of valgus reduction on resistant subtrochanteric femoral non-unions: a single-centre report of twenty six cases.

PURPOSE: Re-revision of subtrochanteric non-unions is technically challenging and lacks robust evidence. The results of managing subtrochanteric fractures after multiple failed procedures have rarely been reported in the literature. This study aims to evaluate the effect of valgus reduction on non-united subtrochanteric fractures with single or multiple failed revision surgeries. METHODS: Twenty-six patients with aseptic subtrochanteric fracture non-union underwent failed single or multiple revision procedures after index fracture fixation surgery between 2011 and 2019. The exclusion criteria were as follows: septic non-union, peri-prosthetic, and pathological fractures. Lateral-based wedge valgus reduction and compression at the non-union site using a valgus-contoured DCS together with decortication, debridement, and bone grafting were used. The main outcome measurement was radiological union, pain, LLD, HHS, and restoration of pre-fracture activities. RESULTS: The mean follow-up was 4.5 years (range 3 to 7); prior revision surgeries range from two to five and union at 6.5 months (range 3 to 10) and the delayed union in one case and an infected non-union in one case. The mean LLD was 4 cm (range 3 to 5), which improved to 1.5 cm (range 1 to 4) (P-value < 0.001). The mean VAS was 7 (range 6 to 8), and 24 patients achieved painless ambulation without a walking aid after the union. The mean HHS was 40 (range 25 to 65), which improved to 85 (range 55 to 95) (P-value < 001), achieving 15 excellent, ten good, and one poor results. CONCLUSION: Mechanical optimisation by lateral closing wedge and stable fixation with pre-contoured DCS with biological enhancement resulted in a successful outcome in recalcitrant subtrochanteric non-unions.

Docking site interventions following bone transport using external fixation: a systematic review of the literature.

PURPOSE: Although bone transport is a well-recognised technique to address segmental bone defects, optimal management of docking sites is not absolutely determined. Some surgeons routinely intervene in all cases, and others prefer to observe and intervene only if spontaneous union does not occur. Primary aim of the study was to compare rates of docking site union between patients who underwent routine docking site intervention and those who did not. METHODS: A systematic literature review using the keywords "bone transport", "docking", "tibia", and "femur" was performed in PubMed using PRISMA guidelines. Studies published in English from January 2000 to August 2022 were included and assessed independently by two reviewers. Pooled analysis was undertaken dividing patients into two groups: those managed by routine intervention and those initially observed. RESULTS: Twenty-three clinical studies met the eligibility criteria for pooled analysis, including 1153 patients, 407 in the routine intervention and 746 in the observed group. The rate of union after initial treatment was 90% in the routine intervention group and 66% in the observed group (p < 0.0001). Overall union rates at the end of treatment were similar at 99% in both groups. Patients in the observed group required an average of 2.2 procedures to achieve union overall compared with 3.8 in the routine intervention group. Time in frame was similar between groups. CONCLUSION: Based on the current literature, routine docking site interventions cannot be recommended, since this may lead to unnecessary interventions in two thirds of patients. Timely selective intervention in those at high risk or after a defined period of observation would appear to be a logical approach.

Do multiple fractures affect risk of fixation failure after surgical treatment of midshaft clavicle fracture? A retrospective cohort study.

BACKGROUND: Surgical treatment of midshaft clavicle fractures is associated with quick recovery and low risk of non-union. However, fixation failure may occur in case of severe comminution fractures. Moreover, clinical outcomes may be affected when clavicle fractures occur in combination with other injuries, particularly those involving the lower extremities, as the use of crutches or walkers may hinder the process of rehabilitation by adding strain on the acromioclavicular (AC) joint, resulting in possible fixation failure. This study aims to identify risk factors for fixation failure of midshaft clavicle fractures and elucidate the role of combined fractures in treatment outcomes. METHODS: This study included patients diagnosed with midshaft clavicle fractures who underwent initial surgery between January 2012 and November 2021 at a designated regional trauma center hospital. Retrospective evaluation of fixation failure was carried out in 352 patients with midshaft clavicle fractures using standard clinical evaluation protocols and conventional radiographs. The prevalence of fixation failure and the effects of several demographic variables on the risk of fixation failure and non-union were examined. Multivariate logistic regression analysis was carried out to identify independent risk factors for fixation failure. RESULTS: Fixation failure occurred in 40 patients (11.4%). Multivariate analysis identified comminution [odds ratio (OR) 3.532, p value = 0.003, 95% confidence interval (CI) 1.55-8.05)] and fewer number of screws (OR 0.223, p value = 0.022, 95% CI 0.06-0.80) as risk factors for fixation failure. Surgical techniques using wire cerclage reduced the chances of fixation failure in comminuted fractures (OR 0.63, p value = 0.033, 95% CI 0.05-0.80). Combined fractures that required rehabilitation using walkers or crutches increased the risk of non-union (OR 19.043, p value = 0.032, 95% CI 1.28-282.46). CONCLUSIONS: Additional fixation of comminuted fractures using cerclage can reduce the risk of treatment failure, while multiple fractures or rehabilitation for ambulation increases the risk of the same. LEVEL OF EVIDENCE: III.

Versatility of the medial corticoperiosteal flap: from recalcitrant non-unions up to large bony defects.

BACKGROUND: Reconstructive microsurgery techniques using vascularized bone grafts have revolutionized the treatment of complex cases associated with recalcitrant non-unions or osteomyelitis. The medial femoral corticoperiosteal flap (MFCP flap) has emerged as a valuable option in bone reconstruction. Its clinical applications have been extended over the years considering this flap from non-unions with minimal bone lost, up to large intercalary defects of the upper and lower extremities. This article aims to present the clinical applications and outcomes of the MFCP flap in various reconstructive scenarios. METHODS: Seventy-nine patients with persistent non-union and bone defects of the upper and lower limb were evaluated from June 2008 to October 2020. All of them were reconstructed with a corticoperiosteal flap from the medial femoral condyle in our hospital. Previous procedures, bone gap and type of flap used were recorded. Postoperative functional status was assessed with time of bone healing, complications and clinical final outcome. RESULTS: Radiological evidence of bone union was observed at 4.09 months (range 2-9). Healing rate was 97% with periosteal corticocancellous flaps (PCC flaps) and 93% with corticoperiosteal flaps (CP flaps). Average follow-up was 14.5 months (range 5-28). There were no significant donor site complications. CONCLUSIONS: The MFCP flap offers a versatile and reliable option for bone reconstruction. Its ability to provide vascularized bone tissue with low morbidity enhances the healing process and improves outcomes. The MFCP flap has been increasing its applications and it serves as a valuable option in the treatment of recalcitrant non-unions or bony defects irrespective of site and size up to 5 cm in the upper and lower extremities.

A morphological review of medial malleolar fractures - A large single centre series.

BACKGROUND: Many approaches to management of medial malleolar fractures are described in the literature however, their morphology is under investigated. The aim of this study was to analyse the morphology of medial malleolar fractures to identify any association with medial malleolar fracture non-union or malunion. METHODS: Patients who had undergone surgical fixation of their MMF were identified from 2012 to 2022, using electronic patient records. Retrospective analysis of their preoperative, intraoperative, and postoperative radiographs was performed to determine their morphology and prevalence of non-union and malunion. Lauge-Hansen classification was used to characterise ankle fracture morphology and Herscovici classification to characterise MMF morphology. RESULTS: A total of 650 patients were identified across a 10-year period which could be included in the study. The overall non-union rate for our cohort was 18.77% (122/650). The overall malunion rate was 6.92% (45/650). Herscovici type A fractures were significantly more frequently mal-reduced at time of surgery as compared to other fracture types (p = .003). Medial wall blowout combined with Hercovici type B fractures showed a significant increase in malunion rate. There is a higher rate of bone union in patients who had been anatomically reduced. CONCLUSION: The morphology of medial malleolar fractures does have an impact of the radiological outcome following surgical management. Medial wall blowout fractures were most prevalent in adduction-type injuries; however, it should not be ruled out in rotational injuries with medial wall blowouts combined with and Herscovici type B fractures showing a significant increase in malunions. Herscovici type A fractures had significantly higher malreductions. LEVEL OF EVIDENCE: Level 3 - Retrospective Cohort Study.

Scaphoid nonunion: a novel modification of Matti-Russe technique with enhanced recovery and full clinical and radiographic union.

BACKGROUND: A scaphoid fracture is a common injury affecting the wrist joint. A fracture of the carpus scaphoid can heal uneventfully or be complicated by non-union. Scaphoid non-union can result in persistent wrist pain, and with functional difficulties affecting all activities of daily living of the patients, this disability is expected to be significant since most of these patients are young active adults. HYPOTHESIS: Extensive removal of the bone from the scaphoid, with the application of a large amount of cancellous bone graft and fixation with two to three wires, could lead to a high union rate and a good functional outcome. METHODS: Eighteen patients with scaphoid fracture non-union were recruited during their visit to the upper limb clinic at our institute. Demographic data were collected, and data regarding comorbidities, smoking, manual work, and others were recorded. Data regarding the interval between injury and surgery, time to radiographic union, and functional wrist scores were reported as well. RESULTS: A cohort of 18 patients was included. The mean age of patients was 30 years; most of our patients were healthy (83.3%), and more than two-thirds were smokers (72.2%). The mean follow-up time was 18 months (1.5 years), 15 patients (83.3%) achieved radiographic unions by 2-3 months, and the remaining 3 patients (16.7%) achieved radiographic unions by (4-5) months, i.e., all patients achieved successful radiographic unions by 5 months at maximum. The mean Mayo score for our series was 83.6 (± 12.4), with 5 patients (27%) achieved ≥ 95% which indicates a significantly high functioning wrist in our cohort. CONCLUSION: Our modified technique with enhanced stability from using three k-wires can achieve full clinical and radiographic unions and result in enhanced recovery postoperatively with cast immobilization limited to 6 weeks total. LEVEL OF EVIDENCE: IV Case series study.

Long-term clinical and radiological results after scaphoid non-union treatment: a retrospective study about 60 cases.

PURPOSE: Scaphoid non-union treatment remains nonconsensual and is based on vascularized or non-vascularized bone grafting. This study aimed to evaluate with a long follow-up the functional, clinical, and radiological outcomes, reported complications and reoperations and studied non-union treatment prognostic factors. METHODS: Patients who had undergone bone graft surgery for scaphoid non-union were retrospectively reviewed. The evaluated outcomes were pain, qDASH, PRWE and MWS scores, active range of motion, grip strength, union rate, scapholunate angle, carpal height, and presence of arthrosis. Complications and reinterventions were also reported. RESULTS: This study included 60 scaphoid non-union treatments with a mean follow-up of 7.7 (1.5-20.3) years. Twenty (33.3%) non-unions were located at the proximal pole, including 6 (10%) with preoperative avascular necrosis (AVN). Union occurred in 51 patients (85%). The functional, clinical, and radiological results were good. The complication rate was 21.3% and the reintervention rate was 16.7%. Subgroup union rate analysis found no difference if the non-union is localized in the proximal pole or if there is AVN. CONCLUSION: With a representative sample of the population and a long follow-up, we have found a good union rate, clinical and functional results regardless of the treatment method chosen. Scaphoid non-union treatment is still controversial and more studies are needed to accurate indications of each graft according to the patient and non-union characteristics. LEVEL OF EVIDENCE IV: Retrospective cohort study.

Antibiotic impregnated cement coated intramedullary nail (ACCIN) using bronchoscopy tubing: technical tips, case series and a review of the literature.

Antibiotic impregnated cement coated intramedullary nails (ACCINs) have been used in clinical practice for many years and have been shown to help eradicate infection in tibial osteomyelitis while providing stability. We present a novel technique for preparation using bronchoscopy tubing, as well as technical tips and a review of the literature, for ease of preparation and potential subsequent retrieval.

Functional outcome and risk of non-union for 5th metatarsal base fractures.

OBJECTIVES: Treatment of 5th metatarsal fractures via direct discharge from virtual fracture clinic (VFC) has become common practice in the NHS. We aim to assess the functional outcome and incidence of non-union in a series of 5th metatarsal base fractures, exposed to 1-year of follow-up. METHODS: 194 patients who sustained a fracture between the period February 2019 to April 2020 were included, referred via the VFC pathway. Radiographs were reviewed to classify in which zone, the fracture occurred along with union on subsequent follow-up. Telephone follow-up was used to measure patient functional outcomes (EQ-5D & FAAM survey) and satisfaction with the VFC service. RESULTS: Off 194 patients, 53 (27.3%) had zone 1, 99 (51%) had zone 2, and 42 (21.6%) had zone 3 fractures. 80 were discharged directly from VFC, with 114 patients being offered at least one face to face clinic follow-up. Six (3.1%) patients had clinical and radiological evidence of non-union; 4 in zone 2, and 2 in zone 3. No zone 1 injuries were identified as a non-union. Only 2 patients had surgery, 1 of which was for symptomatic non-union. Of the 6 non-union patients, 1 had surgery, 4 did not wish to have surgery and the final non-union patient was deemed unsuitable for surgery. CONCLUSION: The VFC is an effective way of managing 5th metatarsal fractures, with high patient satisfaction. Conservative management has excellent outcomes, with a low percentage of zone 2 and 3 injuries developing a symptomatic non-union. Functional outcome surveys provide further reassurance.

Incisional negative pressure wound therapy may not protect against post-operative surgical site complications in bicondylar tibial plateau fractures.

PURPOSE: To determine if incisional negative pressure wound therapy is protective against post-operative surgical site complications following definitive fixation of bicondylar tibial plateau fractures. METHODS: A retrospective analysis of patients diagnosed with an acute bicondylar tibial plateau fracture (AO/OTA 41-C) undergoing ORIF from 2010 to 2020 was performed. Patients received either a standard sterile dressing (SD) or incisional negative pressure wound therapy (iNPWT). Primary outcomes included surgical site infection, osteomyelitis, and wound dehiscence. Secondary outcomes included non-union and return to the operating room. Multivariate logistic regression analyses were performed. RESULTS: 180 patients were included and 22% received iNPWT (n = 40) and 78% received standard dressings (n = 140). iNPWT was more common in active smokers (24.7% vs. 19.3%, p = 0.002) and the SD group was more likely to be lost to follow up (3.6% vs. 0%, p = 0.025). iNPWT was not protective against infection or surgical site complications, and in fact, was associated with higher odds of post-operative infection (OR: 8.96, p = 0.005) and surgical site complications (OR:4.874, p = 0.009) overall. Alcohol abuse (OR: 19, p = 0.005), tobacco use (OR: 4.67, p = 0.009), and time to definitive surgery (OR = 1.21, p = 0.033) were all independent risk factors for post-operative infection. CONCLUSION: In this series of operatively treated bicondylar tibial plateau fractures, iNPWT did not protect against post-operative surgical site complications compared to conventional dressings. Tobacco use, alcohol abuse, and time to definitive surgery, were independent risk factors for post-operative infection. Further studies are needed to determine if iNPWT offers a protective benefit in exclusively high-risk patients with relevant medical and social history.

Polytherapy versus monotherapy in the treatment of tibial non-unions: a retrospective study.

BACKGROUND: Treating tibial non-unions efficiently presents a challenge for orthopaedic trauma surgeons. The established gold standard involves implanting autologous bone graft with adequate fixation, but the addition of biologicals according to the so-called diamond concept has become increasingly popular in the treatment of non-unions. Previous studies have indicated that polytherapy, which involves implanting mesenchymal stem cells, bioactive factors and osteoconductive scaffolds, can improve bone healing. This study aims to evaluate the efficacy of polytherapy compared with monotherapy in treating tibial non-unions of varying severity. MATERIALS AND METHODS: Data from consecutive tibial non-unions treated between November 2014 and July 2023 were retrospectively analysed. The Non Union Scoring System (NUSS) score before non-union surgery, and the Radiographic Union Score for Tibial fractures (RUST), scored at 1, 3, 6, 9, 12 and 18 months post-surgery, were recorded. Initially, a comparison was made between the polytherapy and monotherapy groups. Subsequently, patients receiving additional surgical non-union treatment were documented, and the frequency of these treatments was tallied for a subsequent per-treatment analysis. RESULTS: A total of 34 patients were included and divided into a polytherapy group (n = 15) and a monotherapy group (n = 19). The polytherapy group demonstrated a higher NUSS score (44 (39, 52) versus 32 (29, 43), P = 0.019, z = -2.347) and a tendency towards a higher success rate (93% versus 68%, P = 0.104) compared with the monotherapy group. For the per-treatment analysis, 44 treatments were divided into the polytherapy per-treatment group (n = 20) and the monotherapy per-treatment group (n = 24). The polytherapy per-treatment group exhibited a higher NUSS score (48 (43, 60) versus 38 (30, 50), P = 0.030, z = -2.173) and a higher success rate (95% versus 58%, P = 0.006) than the monotherapy per-treatment group. Within the monotherapy per-treatment group, the NUSS score displayed excellent predictive performance (AUC = 0.9143). Setting the threshold value at 48, the sensitivity and specificity were 100.0% and 70.0%, respectively. CONCLUSIONS: Polytherapy is more effective than monotherapy for severe tibial non-unions, offering a higher success ratio. The NUSS score supports decision-making in treating tibial non-unions. LEVEL OF EVIDENCE: Level III.

Sildenafil, a phosphodiesterase-5 inhibitor, stimulates angiogenesis and bone regeneration in an atrophic non-union model in mice.

Non-union formation represents a major complication in trauma and orthopedic surgery. The phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been shown to exert pro-angiogenic and pro-osteogenic effects in vitro and in vivo. Therefore, the aim of the present study was to analyze the impact of sildenafil in an atrophic non-union model in mice. After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. Bone regeneration was analyzed by means of X-ray, biomechanics, photoacoustic and micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses at 2, 5 and 10 weeks after surgery. The animals were treated daily with either 5 mg/kg body weight sildenafil (n = 35) or saline (control; n = 35) per os. Bone formation was markedly improved in defects of sildenafil-treated mice when compared to controls. This was associated with a higher bending stiffness as well as an increased number of CD31-positive microvessels and a higher oxygen saturation within the callus tissue. Moreover, the bone defects of sildenafil-treated animals contained more tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68-positive macrophages and exhibited a higher expression of the pro-angiogenic and pro-osteogenic markers cysteine rich protein (CYR)61 and vascular endothelial growth factor (VEGF) when compared to controls. These findings demonstrate that sildenafil acts as a potent stimulator of angiogenesis and bone regeneration in atrophic non-unions.

Parathyroid hormone stimulates bone regeneration in an atrophic non-union model in aged mice.

BACKGROUND: Non-union formation still represents a major burden in trauma and orthopedic surgery. Moreover, aged patients are at an increased risk for bone healing failure. Parathyroid hormone (PTH) has been shown to accelerate fracture healing in young adult animals. However, there is no information whether PTH also stimulates bone regeneration in atrophic non-unions in the aged. Therefore, the aim of the present study was to analyze the effect of PTH on bone regeneration in an atrophic non-union model in aged CD-1 mice. METHODS: After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. The animals were treated daily with either 200 mg/kg body weight PTH 1-34 (n = 17) or saline (control; n = 17) subcutaneously. Bone regeneration was analyzed by means of X-ray, biomechanics, micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses. RESULTS: In PTH-treated animals bone formation was markedly improved when compared to controls. This was associated with an increased bending stiffness as well as a higher number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD31-positive microvessels within the callus tissue. Furthermore, PTH-treated aged animals showed a decreased inflammatory response, characterized by a lower number of MPO-positive granulocytes and CD68-positive macrophages within the bone defects when compared to controls. Additional Western blot analyses demonstrated a significantly higher expression of cyclooxygenase (COX)-2 and phosphoinositide 3-kinase (PI3K) in PTH-treated mice. CONCLUSION: Taken together, these findings indicate that PTH is an effective pharmacological compound for the treatment of non-union formation in aged animals.

The value of bone SPECT/CT in evaluation of foot and ankle arthrodesis and adjacent joint secondary osteoarthritis.

OBJECTIVE: To evaluate the value of SPECT/CT (single photon emission computed tomography/computed tomography) in foot and ankle arthrodesis and development of secondary osteoarthritis in the adjacent joints. MATERIALS AND METHODS: SPECT/CT of 140 joints in the foot and ankle (34 upper ankle (UA), 28 lower ankle (LA), 27 talonavicular (TN), 12 calcaneo-cuboidal (CC), and 39 other smaller joints after arthrodesis in 72 patients were evaluated retrospectively regarding fusion grade in CT (0 = no fusion, 1 = < 50% fusion, 2 = > 50% fusion, 3 = complete fusion) and radiotracer uptake (0 = no uptake, 1 = mild uptake, 2 = moderate uptake, 3 = high uptake) on SPECT/CT. Severity of osteoarthritis (1 = mild, 2 = moderate, 3 = severe) and radiotracer uptake grade in adjacent joints was also assessed. In 54 patients, clinical information about interventions in the follow-up was available. RESULTS: According to the SPECT/CT, arthrodesis was successful (grade 2 or 3 CT fusion and grade 0 or 1 uptake) in 73% (25/34) of UA joints, 71% (20/28) of LA joints, 67% (18/27) TN, 100% (12/12) CC joints, and 62% (24/39) of other smaller joints. In 12 joints, there were discrepant findings in SPECT/CT (fusion grade 2 and uptake grade 2 or 3 (n = 9); or, fusion grade 0 or 1 and uptake grade 1 (n = 3)). The fusion rate 6-12 months after arthrodesis was 42% (14/33), 59% (20/34) after 13-24 months, and 89% (65/73) after more than 24 months, respectively. Average radiotracer uptake in arthrodesis decreased with age: 6-12 months: 1.60, 12-24 months: 1.32, > 24 months: 0.38. There was a significant negative correlation between radiotracer uptake grade and CT fusion grade. Osteoarthritis was observed in 131 adjacent joints. During the post scan follow-up, additional arthrodeses were performed in 33 joints, of which 11 joints were re-arthrodesis and 22 were new arthrodeses in osteoarthritic adjacent joints. All these 11 joints with failed arthrodesis had grade 0 of CT fusion and grade 2 or 3 of radiotracer uptake. All 22 adjacent joints with osteoarthritis, which subsequently underwent arthrodesis, had grade 2 or 3 radiotracer uptake, and the primary arthrodesis joints were healed and fused in all these cases. CONCLUSION: Bone SPECT/CT is a valuable hybrid imaging tool in the evaluation of foot and ankle arthrodesis and gives additional useful information about the development of secondary osteoarthritis in the adjacent joints with higher value for the assessment of secondary osteoarthritis. A practical four-type classification ('Lucerne Criteria') combining metabolic and morphologic SPECT/CT information for evaluation of arthrodesis joints has been proposed.

Biomechanical evaluation of different sizes of 3D printed cage in lumbar interbody fusion-a finite element analysis.

OBJECTIVE: To study the biomechanical characteristics of various tissue structures of different sizes of 3D printed Cage in lumbar interbody fusion. METHODS: A finite element model of normal spine was reconstructed and verified. Pedicle screws and Cage of different sizes were implanted in the L4/5 segment to simulate lumbar interbody fusion. The range of motion of the fixed and cephalic adjacent segment, the stress of the screw-rod system, the stress at the interface between cage and L5 endplate, and intervertebral disc pressure of the adjacent segment were calculated and analyzed. RESULTS: The range of motion and intervertebral disc pressure of the adjacent segment of each postoperative model were larger than those of the intact model, but there was not much difference between them. The stress of cage-endplate interface was also larger than that of the intact model. However, the difference is that the stress of the endplate and the screw-rod system has a tendency to decrease with the increase of the axial area of cage. CONCLUSIONS: Cage with larger axial area in lumbar interbody fusion can reduce the stress of internal fixation system and endplate, but will not increase the range of motion and intervertebral disc pressure of adjacent segment. It has a certain effect in preventing the cage subsidence, internal fixation system failure and screw rod fracture.

Patient outcome scores between 1,2- and 2,3-intercompartmental supra-retinacular artery (ICSRA) pedicled vascularised bone grafts (PVBGs) in the treatment of proximal pole scaphoid fracture non-union - a questionnaire study.

BACKGROUND: Numerous studies have been published on the use of 1,2-intercompartmental supra-retinacular artery (ICSRA) as a pedicled vascularised bone graft (PVBG) in scaphoid fracture non-union, however, only very few studies have reported their results of 2,3-ICSRA. The aim of this study was to compare the patient-rated outcome scores between these two PVBGs in proximal pole scaphoid fracture non-union. METHODS: Nineteen patients who underwent surgery for scaphoid non-union between 2017 and 2021 at a single institution were recruited retrospectively in this study. All patients were operated by a one senior orthopaedic surgeon. A mailed questionnaire with the modified mayo wrist (MMW) and the patient rated wrist evaluation (PRWE) scores were sent to the patients. RESULTS: All patients were males with a mean age of 22.5 years. There was no statistically significant difference in the PRWE score between the two PVBGs. However, a statistically significant difference was found in the MMW score, with the 1,2-ICSRA PVBG having better scores. CONCLUSION: Despite the 2,3-ICSRA having a longer arc of rotation, longer nutrient arteries, and is technically easier to incorporate in a PVBG, when compared with the 1,2-ICSRA it did not result in better patient-rated outcome scores.