Delay in weight bearing in surgically treated tibial shaft fractures is associated with impaired healing: a cohort analysis of 166 tibial fractures.

BACKGROUND: The relation between timing of weight bearing after a fracture and the healing outcome is yet to be established, thereby limiting the implementation of a possibly beneficial effect for our patients. The current study was undertaken to determine the effect of timing of weight bearing after a surgically treated tibial shaft fracture. MATERIALS AND METHODS: Surgically treated diaphyseal tibial fractures were retrospectively studied between 2007 and 2015. The timing of initial weight bearing (IWB) was analysed as a predictor for impaired healing in a multivariate regression. RESULTS: Totally, 166 diaphyseal tibial fractures were included, 86 cases with impaired healing and 80 with normal healing. The mean age was 38.7 years (range 16-89). The mean time until IWB was significantly shorter in the normal fracture healing group (2.6 vs 7.4 weeks, p < 0.001). Correlation analysis yielded four possible confounders: infection requiring surgical intervention, fracture type, fasciotomy and open fractures. Logistic regression identified IWB as an independent predictor for impaired healing with an odds ratio of 1.13 per week delay (95% CI 1.03-1.25). CONCLUSIONS: Delay in initial weight bearing is independently associated with impaired fracture healing in surgically treated tibial shaft fractures. Unlike other factors such as fracture type or soft tissue condition, early resumption of weight bearing can be influenced by the treating physician and this factor therefore has a direct clinical relevance. This study indicates that early resumption of weight bearing should be the treatment goal in fracture fixation. LEVEL OF EVIDENCE: 3b.

The effect of post-traumatic long bone non-unions on health-related quality of life.

BACKGROUND: Fracture non-unions have a detrimental effect on patients due to reduced mobility and severe pain. Current literature on the quality of life in non-unions is limited, hence the purpose of this study, to quantify the health-related quality of life (HRQoL) among patients with post-traumatic long bone non-unions. It was hypothesized that the HRQoL of these patients is lower than the Dutch population standard as well as for multiple chronic diseases and musculoskeletal disorders. PATIENTS AND METHODS: From January 2020 to December 2021, this study included consecutive patients who were referred to a multidisciplinary (trauma, orthopedic and plastic surgery), non-union clinic at the Maastricht UMC+. All non-unions were evaluated using the Non-Union Scoring System (NUSS) questionnaire. Patient reported HRQoL outcomes were acquired using the EQ-5D-5L questionnaire and the Lower Extremity Functional Scale (LEFS). RESULTS: 50 patients were included, 18 females and 32 males, with a mean age of 55 years (± 15.5 SD). Eighteen patients presented with an open fracture, nine non-unions were infected and 39 patients had a lower extremity non-union. The mean NUSS score was 39.61 (± 14.6 SD). The mean EQ-5D-5L index score was 0.490 (± 0.261 SD), where patients experienced most problems with mobility. The mean EQ-5D-5L VAS was 61.4 (± 19.6 SD). The patients had a mean LEFS score of 28.7 (± 16.4 SD). The health-related quality of life was well below the age-corrected normative score of the Dutch population (EQ-5D-5L 0.857(p < 0.001); LEFS 77(p < 0.001)). This cohort's HRQoL was significantly lower than the HRQoL of multiple chronic and musculoskeletal disorders, including different forms of cancer and osteoarthritis. CONCLUSIONS: This study has quantified the detrimental effect of post-traumatic long bone non-unions on patient's health-related quality of life, being significantly lower than the HRQoL of the Dutch population as well as for multiple chronic and musculoskeletal medical conditions. This cohort demonstrates a patient population in need of more specialized care with a low health-related quality of life.

The Diagnostic Value of Ultrasound of the Rectus Femoris for the diagnosis of Sarcopenia in adults: A systematic review.

BACKGROUND & AIM: Sarcopenia is defined as a loss of muscle mass and function, which can be caused by normal ageing or factors such as physical inactivity. Severe health consequences caused by sarcopenia highlight the need for early identification. Computed Tomography (CT) imaging, often mentioned as the gold standard due to its accuracy, is costly and not routinely performed in daily clinical care. Ultrasound of the rectus femoris, however, is low in costs and easily accessible. The aim is to present the current and most recent literature regarding the diagnostic value of ultrasound measurements of the rectus femoris for the diagnosis of sarcopenia in adults. METHODS: The databases PubMed and Web of Science were used to search for studies comparing ultrasound of the rectus femoris with a reference test to diagnose sarcopenia in adults. The quality of the final eligible studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies, version 2, tool (QUADAS-2). RESULTS: Six studies were included in this systematic review. The muscle thickness and cross-sectional area of the rectus femoris were assessed and compared with the reference tests CT, Dual-Energy X-ray Absorptiometry (DXA), and Bioelectrical Impedance Analysis (BIA). Half of the studies had a low risk of bias on all QUADAS-2 domains. Three studies reported statistical significant outcomes and diagnostic values ranging from 60 to 81% sensitivity and 51 to 94% specificity. CONCLUSIONS: Ultrasound of the rectus femoris muscle to diagnose sarcopenia has been shown to be a promising method in multiple clinical populations. However, there were some limitations such as a high methodological heterogeneity. Future research should develop standardized protocols and determine clear cut-off values to allow for a better implementation of ultrasound in clinical practice.

Treatment of infected tibial non-unions using a BMAC and S53P4 BAG combination for reconstruction of segmental bone defects: A clinical case series.

INTRODUCTION: Treatment of infected non-unions of the tibia is a challenging problem. The cornerstones of optimal infected non-union treatment consist of extensive debridement, fracture fixation, antimicrobial therapy and creation of an optimal local biological bone healing environment. The combination of S53P4 bioactive glass (BAG), as osteostimulative antibacterial bone graft substitute, and bone marrow aspirate concentrate (BMAC) for the implantation of mesenchymal stem cells and growth factors might be a promising combination. In this paper, preliminary results of a new treatment algorithm for infected non-unions of the tibia is presented. METHODS: In this retrospective case series patients with infected non-unions of the tibia are treated according to a new treatment algorithm. Patients are treated with extensive debridement surgery, replacement of the osteosynthesis and implantation of S53P4 BAG and BMAC in a one-stage or two-stage procedure based on non-union severity. Subsequently patients are treated with culture based antibiotic therapy and followed until union and infection eradication. RESULTS: Five patients with an infected non-union were treated, mean age was 55, average NUSS-score was 44 and the average segmental bone defect was 4.6cm. One patient was treated in a one-stage procedure and four patients in a two-stage induced membrane-, or "Masquelet"-procedure. On average, 23 ml S53P4 BAG and 6.2 ml BMAC was implanted. The mean follow-up period was 13.6 months and at the end of follow-up all patients had clinical consolidation with an average RUST-score of 7.8 and complete eradication of infection. DISCUSSION: These early data on the combined implantation of S53P4 BAG and BMAC in treatment of infected non-unions shows promising results. These fracture healing results and eradication rates resulted in promising functional recovery of the patients. To substantiate these results, larger and higher quality studies should be performed.

The Non-Union Scoring System: an interobserver reliability study.

PURPOSE: The Non-Union Scoring System (NUSS) aims to classify non-unions according to their severity and relate them to four treatment categories. The main purpose of this study was to evaluate the reliability of the NUSS. In addition we assessed its clinical validity. METHODS: Forty-four Patients with a tibia non-union between 2005 and 2015 were included in this study. Data from all included patients were scored independently by three observers according to the NUSS criteria. The interobserver agreement was evaluated using the intraclass correlation coefficient (ICC). The interobserver agreement of the Weber-Cech system was assessed using Fleiss' kappa. Finally, the clinical validity of the NUSS was analysed by comparing outcomes of the actual treatment groups to the proposed treatment groups following from the NUSS scores. RESULTS: Forty-four patients were included. The comparison of NUSS scores between observers showed substantial agreement [ICC; 0.78 (0.67-0.86)]. The comparison of the Weber-Cech classification between observers showed only fair agreement [Fleiss κ; 0.30 (0.17-0.42)]. The χ2 test for the treatment groups according to the NUSS and the treatments at index procedure showed an independent relation (χ2 = 5.794, 6 degrees of freedom, p: 0.447). In contrast, the proposed treatment strategy corresponds well to the definitive treatment (χ2 = 29.963, 9 degrees of freedom, p < 0.001). CONCLUSION: We conclude that the NUSS is both a reliable and valid system to classify non-unions.

[Earlier weight-bearing mobilisation after fracture fixation]. / Eerder belast mobiliseren na fractuurfixatie.

Almost all the literature dictates a period of non-weight-bearing after surgical treatment of articular and peri-articular fractures of the pelvis and lower extremities. This is followed by partial weight-bearing which is based on the number of weeks after surgery. However, none of these recommendations are based on evidence. When taking muscle force and gravity into account, non-weight-bearing is actually impossible. In addition, lack of patient compliance, lack of muscle force in the elderly and four-fold energy expenditure make it almost impossible to ensure that patients will adhere to their surgeon's restrictions. Based on our experiences in a large cohort of patients with fractures of the pelvis and lower extremities, we see no drawbacks in permissive weight-bearing and early recovery in most cases. We strongly believe that most patients are able to listen to their body and understand body awareness, while the creation of a safe environment makes more personalised follow-up treatment possible.

Effect of recombinant human osteogenic protein-1 on the healing of a freshly closed diaphyseal fracture.

Osteogenic protein-1 (OP-1), or bone morphogenetic protein-7, is an osteoinductive morphogen that is involved in embryonic skeletogenesis and in bone repair. In bone defect models without spontaneous healing, local administration of recombinant human OP-1 (rhOP-1) induces complete healing. To investigate the ability of rhOP-1 to accelerate normal physiologic fracture healing, an experimental study was performed. In 40 adult female goats a closed tibial fracture was made, stabilized with an external fixator, and treated as follows: (1) no injection; (2) injection of 1 mg rhOP-1 dissolved in aqueous buffer; (3) injection of collagen matrix; and (4) injection of 1 mg rhOP-1 bound to collagen matrix. The test substances were injected in the fracture gap under fluoroscopic control. At 2 and 4 weeks, fracture healing was evaluated with radiographs, three-dimensional computed tomography (CT), dual-energy X-ray absorptiometry, biomechanical tests, and histology. At 2 weeks, callus diameter, callus volume, and bone mineral content at the fracture site were significantly increased in both rhOP-1 groups compared with the no-injection group. As signs of accelerated callus maturation, bending and torsional stiffness were higher and bony bridging of the fracture gap was observed more often in the group with rhOP-1 dissolved in aqueous buffer than in uninjected fractures. Treatment with rhOP-1 plus collagen matrix did not result in improved biomechanical properties or bony bridging of the fracture gap at 2 weeks. At 4 weeks there were no differences between groups, except for a larger callus volume in the rhOP-1 plus collagen matrix group compared with the control groups. All fractures showed an advanced stage of healing at 4 weeks. In conclusion, the healing of a closed fracture in a goat model can be accelerated by a single local administration of rhOP-1. The use of a carrier material does not seem to be crucial in this application of rhOP-1.

Biomechanical and histological aspects of fracture healing, stimulated with osteogenic protein-1.

Fracture healing could be stimulated with osteoinductive bone morphogenetic proteins (bmp's), such as osteogenic protein-1 (OP-1), but little is known about its effectiveness in stimulation of fracture healing. In this study, biomechanical and histological aspects of fracture healing after an injection of OP-1 in the fracture gap were investigated. In 40 goats, a closed fracture was created in the left tibia. The fractures were stabilized with an external fixator and the animals were assigned to four different groups: no injection, injection of 1 mg OP-1, injection of 1 mg OP-1 with collagenous carrier material, and injection of carrier material alone. Twenty-one animals were sacrificed after 2 weeks and 19 after 4 weeks. Biomechanical testing was perfomed on both explanted tibiae. Four longitudinal samples of the fracture were sawn, processed for histology, and examined by two observers. Biomechanical evaluation showed a higher stiffness and strength at 2 weeks after injection of OP-1. Histological evaluation showed normal fracture healing patterns in all animals without adverse effects of the given injections. These data show that fracture healing can be accelerated with a single injection of OP-1, eventually resulting in normally healed bone.

Long-term evaluation of Bennett's fracture. A comparison between open and closed reduction.

18 patients with Bennett's fracture were evaluated after a mean follow-up period of 10.7 years. Treatment consisted of closed reduction and K-wire fixation in seven cases and open reduction with osteosynthesis in 11 cases. Overall, symptoms were few and restricted mobility of the thumb could not be demonstrated. The strength of the affected hand was decreased in all patients regardless of the type of treatment. Osteoarthritis was found to correlate with the quality of reduction of the fracture, but had developed in almost all cases even after exact reduction. Exact reduction, either by the open or closed method, should be the aim of treatment of Bennett's fracture.

Results of radio frequency ablation of primary and secondary liver tumors: long-term follow-up with computed tomography and positron emission tomography-18F-deoxyfluoroglucose scanning.

BACKGROUND: In the literature, promising results have been obtained with radiofrequency ablation (RFA) of primary liver malignancies (e.g. hepatocellular carcinoma, HCC) and secondary liver malignancies (e.g. metastases of colorectal tumors). In our center, positron emission tomography with FDG (FDG-PET) and computed tomography (CT) were used for follow-up. Patient outcome was compared with that in the literature, and PET and CT were analyzed regarding positive and negative predictive values for early detection of tumor recurrence. METHODS: The data were analyzed of patients who were treated with RFA for primary or secondary liver tumors between January 1999 and December 2002. Indications for treatment with RFA were liver tumors that could not be resected owing to size, number, or tumor location. In all patients, a CT scan was performed before RFA, and follow-up was performed with a CT scan in all patients and with an additional PET scan at various intervals in 11 patients. At evaluation with PET, tumor recurrence was defined as positive uptake of tracer either at the previous RFA lesion or at a new site in the liver. RESULTS: In total, 15 patients (8 M, 7 F) were treated in 21 sessions with RFA. The mean follow-up period was 16.8 months (range: 7-42). Average age of the patients was 63 years (range: 40-74). One patient had a primary liver tumor; all other patients had metastases of the breast (1), ovary (1), renal cells (1), and colorectal carcinoma (11 patients). The mean number of tumors per patient was 2.7 (range: 1-5). No treatment-related morbidity or mortality occurred. In 4 of 11 patients evaluated with PET at a mean period of 6.8 months, positive uptake of tracer was noted. At CT evaluation, tumor recurrence was observed in 4 of these patients, at a mean time of 9.8 months. Two patients (13.3%) died of cancer recurrence during follow-up. CONCLUSIONS: Tumor recurrence is comparable with that in other studies. Centrally located tumors showed more recurrence than peripheral tumors. The use of PET in combination with CT scan at follow-up may lead to earlier detection of tumor recurrence than contrast-enhanced CT alone.

BMP-7 stimulates early diaphyseal fracture healing in estrogen deficient rats.

Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti-resorptive agents or with anabolic agents such as bone morphogenetic proteins (BMPs). To investigate the influence of estrogen deficiency as well as the effect of early intervention, forty female wistar rats underwent ovarectomy (OVX) followed by low calcium diet. Ten rats underwent sham operations, followed by normal diet. After 6 weeks, a closed midshaft femoral fracture was induced. Ten animals received a systemic bisphosphonate injection, 10 injection of BMP-7 in the fracture, and 10 a combination. All then received a normal diet. After 2 weeks healing was evaluated using radiographs, CT, biomechanical testing, and histology. Radiography showed significant increase of bridging in groups treated with BMP-7. Callus volume was higher in these groups. Bending stiffness and strength were similar between OVX and sham, and not influenced by bisphosphonates. Significant increase was seen in groups treated with BMP-7. Histology was in accordance with other endpoints. Early fracture healing was not affected by estrogen deficiency. While no beneficiary effect of bisphosphonate treatment was found, injection of BMP-7 stimulated healing in ovarectomized rats.

Bioactive and osteoinductive bone graft substitutes: definitions, facts and myths.

The use of artificial bone grafts has been developed over recent years and is expected to increase further, for some indications even replacing the gold standard, autograft, in trauma and reconstructive surgery. However, the effectiveness of these materials is still a subject of debate, mostly because of unclear definitions or limited market surveillance. In this overview several facts and myths regarding bone-graft substitutes are summarized.

The value of clinical examination in diagnosing pelvic fractures in blunt trauma patients: a brief review.

PURPOSE OF THE STUDY: To evaluate the value of a pelvic X-ray compared to clinical examination in diagnosing pelvic ring fractures, using computed tomography (CT) as the gold standard, in alert [Glasgow Coma Scale (GCS) ≥ 13] adult blunt trauma patients in the emergency room. METHODS: A systematic literature search was performed in PubMed and Embase. The results were screened on their titles and abstracts using in- and exclusion criteria. Subsequently, the selected articles were critically appraised for their relevance and validity. RESULTS: Two studies investigating the diagnostic value of clinical examination and pelvic X-ray compared to CT were identified. Both studies demonstrate higher negative predictive values for clinical examination [0.99 (95% confidence interval [CI] 0.98-1.0) and 1.0 (95% CI 0.99-1.0)] compared to the negative predictive values of pelvic X-ray [0.98 (95% CI 0.93-0.99) and 0.99 (95% CI 0.99-1.0)]. The positive predictive values for clinical examination were low [0.18 (95% CI 0.16-0.23) and 0.35 (95% CI 0.30-0.42)] compared to pelvic X-ray [0.97 (95% CI 0.96-0.98) and 0.97 (95% CI 0.90-0.99)]. CONCLUSIONS: In alert blunt trauma patients, pelvic X-ray only has additional diagnostic value for the detection of pelvic ring fractures if the clinical examination is positive. Pelvic X-ray should not be performed if the clinical examination is negative. In this manner, the expenditure of time, costs, and radiation are optimized.

Historic overview of treatment techniques for rib fractures and flail chest.

INTRODUCTION: From the beginning of the twentieth century till the current time, an overview is presented of the surgical treatment for rib fractures and flail chest. METHODS: Many techniques have been used to stabilize the thorax wall. There has been no follow-up for the most described techniques and the evidence provided is at its best at L3-4. This, together with the noninvasiveness of mechanical ventilation, has made the latter the golden standard. CONCLUSION: However, the recent introduction of better and fully dedicated materials provides the possibility of exploring the surgical treatment of chest injuries. The authors make a case for operative treatment of rib fractures and flail chest.

Application of bone morphogenetic proteins to femoral non-unions: a 4-year multicentre experience.

Fracture non-unions often complicate orthopaedic trauma. BMPs (bone morphogenetic proteins) are currently considered the most appealing osteoinductive agents. Applications of BMP-7 since January 2004 were prospectively recorded in a multicentre registry of aseptic femoral non-unions. The study included 30 patients who had undergone a median of 1 revision operation before BMP-7 application and who were followed up for a median 24 months. In 23/30 cases the application of BMP-7 was combined with revision of the fixation, and in 12 it was combined also with autograft. Non-union healing was verified in 26/30 cases in a median period of 6 months. No adverse events were associated with BMP-7 application. Our case series supports the safety and efficacy of BMP-7 in femoral non-unions. Multicentre networks and systematic, long-term follow-up of patients may improve understanding of this promising osteoinductive bone substitute.

Allograft and bone morphogenetic proteins: an overview.

SUMMARY: Allograft is frequently used in orthopaedic and trauma surgery. On top of safety issues its biological activity is limited also due to processing. Consequently, the combination of allograft with osteoinductive substances may increase its effectiveness and decrease failure rates. In particular Bone Morphogenetic Proteins (BMPs) seem to be a promising partner for clinical applications. This overview focuses on the combined application of allograft/BMPs. Current points of view from available literature are summarized.

The influence of hydroxyapatite granules on the healing of a segmental defect filled with autologous bone marrow.

Hydroxyapatite(HA) ceramics are frequently used as a bone graft substitutes for the filling of bony defects. The addition of autologous bone marrow to HA ceramics does improve defect healing. There is conflicting evidence in the literature whether autologous bone marrow transplantation alone is as effective as the combination of HA ceramics and bone marrow combined. It was the purpose of this study to identify the role of additional HA ceramic granules on the healing of a sheep tibia segmental defect filled with autologous bone marrow. After permission of the local animal rights committee was obtained, a 3 cm segmental defect in the midshaft of 31 adult sheep was stabilized with an unreamed tibia nail. The animals were divided into 4 groups according to the mode of defect filling: HA plus autologous bone marrow (HA + MAR) (n = 8), autologous bone marrow (MAR) (n = 9), empty defect (DEF) (n = 6), cancellous bone graft (CAN) (n = 8). After three months follow up animals were sacrificed and analysed for the key parameters of union and maximum torque at failure. One nonunion was present in each of the HA + MAR, MAR, and CAN groups. Four of the six animals in the DEF group developed a nonunion. Maximum torque at failure was reported as percentage of the intact contralateral tibia: HA + MAR 39% +/- 24%, MAR 26% +/- 17%, DEF 22% +/- 13%, CAN 41% +/- 20%. The difference between the groups was statistically significant, but appeared to be relevant. We conclude from our data, that HA ceramics do improve healing of a segmental defect in the sheep tibia filled with autologous bone marrow. The results of this combination are comparable to cancellous autograft.

Evaluation of strength of healing fractures with dual energy Xray absorptiometry.

Dual energy xray absorptiometry was investigated as a method for evaluation of the strength of closed tibial fractures. In 40 goats, a closed midshaft fracture was created in the left tibia. The fractures were stabilized with an external fixator. After 2 weeks (n = 21) and after 4 weeks (n = 19), both tibias were explanted and, using dual energy xray absorptiometry, bone mineral density and bone mineral content were measured in a 1 cm region. With nondestructive bending tests, area ratio and stiffness index were determined and torsional strength and torsional stiffness were determined with a torsional test to failure. Linear regression analysis was used to calculate the squared correlation coefficients for the relations between dual energy xray absorptiometry and the outcome of the mechanical tests. The squared correlation coefficients for the relation between bone mineral density and torsional strength, torsional stiffness, and area ratio and stiffness index were 0.72, 0.76, 0.64, and 0.72, respectively. The squared correlation coefficients for the relation between bone mineral content and these mechanical parameters were 0.72, 0.77, 0.63, and 0.77, respectively. The results using dual energy xray absorptiometry indicate the strength of healing closed fractures. Additional research is required to investigate specific aspects of this technique.

Resorbable calcium phosphate particles as a carrier material for bone marrow in an ovine segmental defect.

Resorbable calcium phosphate ceramics are only osteoconductive; therefore, their combination with osteogenic substances may lead to stimulation of bone healing. In the present study this combination, using autologous bone marrow, was investigated. In 31 sheep, a 3-cm tibial segmental defect was created and stabilized with an intramedullary nail. The animals were divided into four groups: empty defects (group 1, n = 7), and defects filled with 10-mL dense resorbable calcium phosphate particles (group 2, n = 8), with 10-mL particles soaked in bone marrow (group 3, n = 8), or with 10-mL autologous bone (group 4, n = 8). On evaluation after 12 weeks, significantly higher values were seen in group 3 than in group 2 for callus volume (p = .016), bone mineral density ratio (p = .03), bone mineral content ratio (p = .04), torsional strength (p = .005), and torsional stiffness (p = .01). For all end points, the outcome of group 3 was lower than that of group 4. In the histology, there was direct contact between newly formed bone and remnants of the particles. There were no signs of inflammatory reactions. Although a stimulatory effect of bone marrow was seen, the combination of resorbable calcium phosphate particles with bone marrow does not provide an alternative for autologous bone grafting.

The reliability of plain radiography in experimental fracture healing.

OBJECTIVE: To investigate the reliability of radiographs in the evaluation of healing of closed fractures. DESIGN: A closed midshaft tibial fracture was created in 40 goats and stabilized with an external fixator. The animals were assigned to four groups: no injection, injection of 1 mg osteogenic protein-1 (OP-1), 1 mg OP-1 with collagenous carrier, or carrier alone. Radiographs were performed weekly until the animals were killed after 2 and 4 weeks. Healing was evaluated using radiographs, biomechanical testing, and histological examination. All radiographs were examined by two independent observers. Interobserver agreement was calculated and radiographic scores were compared with mechanical and histological scores using regression analysis. RESULTS: Regression analysis showed poor correlation between radiographic scores and biomechanical and histological data. Correlation coefficients varied between 0.39 and 0.63. Good agreement between the observers was seen in only three parameters: visibility of the fracture line, weightbearing ability, and a combined healing parameter. CONCLUSION: Plain radiography provides poor parameters for monitoring the fracture healing process.