Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis. In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment

In an interdisciplinary project involving electronic engineers and clinicians, a telemetric system was developed to measure the bending load in a titanium internal femoral fixator. As this was a new device, the main question posed was: what clinically relevant information could be drawn from its application? As a first clinical investigation, 27 patients (24 men, three women) with a mean age of 38.4 years (19 to 66) with femoral nonunions were treated using the system. The mean duration of the nonunion was 15.4 months (5 to 69). The elasticity of the plate-callus system was measured telemetrically until union. Conventional radiographs and a CT scan at 12 weeks were performed routinely, and healing was staged according to the CT scans. All nonunions healed at a mean of 21.5 weeks (13 to 37). Well before any radiological signs of healing could be detected, a substantial decrease in elasticity was recorded. The relative elasticity decreased to 50% at a mean of 7.8 weeks (3.5 to 13) and to 10% at a mean of 19.3 weeks (4.5 to 37). At 12 weeks the mean relative elasticity was 28.1% (0% to 56%). The relative elasticity was significantly different between the different healing stages as determined by the CT scans. Incorporating load measuring electronics into implants is a promising option for the assessment of bone healing. Future application might lead to a reduction in the need for exposure to ionising radiation to monitor fracture healing

This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This ‘bone-healing unit’ produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff’s law, Perren’s strain theory and Frost’s concept of the “mechanostat”. In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture – healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. Cite this article: Bone Joint J 2016;98-B:884–91

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

Aims. Tobacco, in addition to being one of the greatest public health threats facing our world, is believed to have deleterious effects on bone metabolism and especially on bone healing. It has been described in the literature that patients who smoke are approximately twice as likely to develop a nonunion following a non-specific bone fracture. For clavicle fractures, this risk is unclear, as is the impact that such a complication might have on the initial management of these fractures. Methods. A systematic review and meta-analysis were performed for conservatively treated displaced midshaft clavicle fractures. Embase, PubMed, and Cochrane Central Register of Controlled Trials (via Cochrane Library) were searched from inception to 12 May 2022, with supplementary searches in Open Grey, ClinicalTrials.gov, ProQuest Dissertations & Theses, and Google Scholar. The searches were performed without limits for publication date or languages. Results. The meta-analysis included eight studies, 2,285 observations, and 304 events (nonunion). The random effects model predicted a pooled risk ratio (RR) of 3.68 (95% confidence interval 1.87 to 7.23), which can be considered significant (p = 0.003). It indicates that smoking more than triples the risk of nonunion when a fracture is treated conservatively. Conclusion. Smoking confers a RR of 3.68 for developing a nonunion in patients with a displaced middle third clavicle fracture treated conservatively. We know that most patients with pseudarthrosis will have pain and a poor functional outcome. Therefore, patients should be informed of the significantly higher risks of nonunion and offered smoking cessation efforts and counselling. Moreover, surgery should be considered for any patient who smokes with this type of fracture. Cite this article: Bone Joint J 2023;105-B(7):801–807

We examined the effect of periosteal devascularisation upon the early healing of osteotomies of sheep tibiae held in an instrumented external fixation system with an axial stiffness of 240 N/mm. At 14 days, cortical blood flow measured by the microsphere technique was 19.3 ml/min/100g in the well-vascularised osteotomies, but only 1.7 ml/min/100g in the devascularised osteotomies, despite an increase in medullary flow (p less than 0.0005). Delay in healing of the devascularised osteotomies was suggested by an in vivo monitoring system and confirmed by post-mortem mechanical testing. We suggest that the osteogenic stimulus of dynamic external fixation is dependent on the early restoration of cortical blood flow in devascularised fractures.

The re-establishment of vascularity is an early event in fracture healing; upregulation of angiogenesis may therefore promote the formation of bone. We have investigated the capacity of vascular endothelial growth factor (VEGF) to stimulate the formation of bone in an experimental atrophic nonunion model.

Three groups of eight rabbits underwent a standard nonunion operation. This was followed by interfragmentary deposition of 100 μg VEGF, carrier alone or autograft.

After seven weeks, torsional failure tests and callus size confirmed that VEGF-treated osteotomies had united whereas the carrier-treated osteotomies failed to unite. The biomechanical properties of the groups treated with VEGF and autograft were identical. There was no difference in bone blood flow.

We considered that VEGF stimulated the formation of competent bone in an environment deprived of its normal vascularisation and osteoprogenitor cell supply. It could be used to enhance the healing of fractures predisposed to nonunion.

Aims. To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (β-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes. Methods. A review of the medical records was conducted of consecutive 35 lower limbs (30 males and five females; median age 46 years (interquartile range (IQR) 40 to 61)) treated with IMT using β-TCP between 2014 and 2018. Lower Extremity Functional Score (LEFS) was examined preoperatively and at final follow-up to clarify patient-centered outcomes. Bone healing was assessed radiologically, and time from the second stage to bone healing was also evaluated. Patients were divided into ≥ 50 mm and < 50 mm defect groups and into femoral reconstruction, tibial reconstruction, and ankle arthrodesis groups. Results. There were ten and 25 defects in the femur and tibia, respectively. Median LEFS improved significantly from 8 (IQR 1.5 to 19.3) preoperatively to 63.5 (IQR 57 to 73.3) at final follow-up (p < 0.001). Bone healing was achieved in all limbs, and median time from the second stage to bone healing was six months (IQR 5 to 10). Median time to bone healing, preoperative LEFS, or postoperative LEFS did not differ significantly between the defect size groups or among the treatment groups. Conclusion. IMT using β-TCP provided satisfactory clinical and radiological outcomes for segmental bone defects in the lower limbs; surgical outcomes were not influenced by bone defect size or operated part. Cite this article: Bone Joint J 2021;103-B(3):456–461

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529

Aims. As an alternative to external fixators, intramedullary lengthening nails (ILNs) can be employed for distraction osteogenesis. While previous studies have demonstrated that typical complications of external devices, such as soft-tissue tethering, and pin site infection can be avoided with ILNs, there is a lack of studies that exclusively investigated tibial distraction osteogenesis with motorized ILNs inserted via an antegrade approach. Methods. A total of 58 patients (median age 17 years (interquartile range (IQR) 15 to 21)) treated by unilateral tibial distraction osteogenesis for a median leg length discrepancy of 41 mm (IQR 34 to 53), and nine patients with disproportionate short stature treated by bilateral simultaneous tibial distraction osteogenesis, with magnetically controlled motorized ILNs inserted via an antegrade approach, were retrospectively analyzed. The median follow-up was 37 months (IQR 30 to 51). Outcome measurements were accuracy, precision, reliability, bone healing, complications, and patient-reported outcome assessed by the Limb Deformity-Scoliosis Research Society Score (LD-SRS-30). Results. A median tibial distraction of 44 mm (IQR 31 to 49) was achieved with a mean distraction index of 0.5 mm/day (standard deviation 0.13) and median consolidation index of 41.2 days/cm (IQR 34 to 51). Accuracy, precision, and reliability were 91%, 92%, and 97%, respectively. New temporary range of motion limitations occurred in 51% of segments (34/67). Distraction-related equinus deformity treated by Achilles tendon lengthening was the most common major complication recorded in 16% of segments (11/67). In 95% of patients (55/58) the distraction goal was achieved with 42% unplanned additional interventions per segment (28/67). The median postoperative LD-SRS-30 score was 4.0 (IQR 3.6 to 4.3). Conclusion. Tibial distraction osteogenesis using motorized ILNs inserted via an antegrade approach appears to be a reliable and precise procedure. Temporary joint stiffness of the knee or ankle should be expected in up to every second patient. A high rate and wide range of complications of variable severity should be anticipated. Cite this article: Bone Joint J 2024;106-B(3):293–302

Aims. Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue. Methods. Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Pad4-/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure. Results. NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition (Pad4-/-) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice. Conclusion. This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury bone remodelling caused by implant loosening. By inhibiting or resolving NETs in an osseointegration failure murine model, fibrotic tissue encapsulation around an implant is reduced and osseointegration is enhanced, despite loose implant conditions. Cite this article: Bone Joint J 2021;103-B(7 Supple B):135–144

Aims. Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. Materials and Methods. Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. Results. We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. Conclusion. This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126–31

Aims. The aim of this double-blind prospective randomised controlled trial was to assess whether low intensity pulsed ultrasound (LIPUS) accelerated or enhanced the rate of bone healing in adult patients undergoing distraction osteogenesis. Patients and Methods. A total of 62 adult patients undergoing limb lengthening or bone transport by distraction osteogenesis were randomised to treatment with either an active (n = 32) or a placebo (n = 30) ultrasound device. A standardised corticotomy was performed in the proximal tibial metaphysis and a circular Ilizarov frame was used in all patients. The rate of distraction was also standardised. The primary outcome measure was the time to removal of the frame after adjusting for the length of distraction in days/cm for both the per protocol (PP) and the intention-to-treat (ITT) groups. The assessor was blinded to the form of treatment. A secondary outcome was to identify covariates affecting the time to removal of the frame. Results. There was no difference in the time to removal of the frame between the PP (difference in favour of the control group was 10.1 days/cm, 95% confidence interval (CI) -3.2 to 23.4, p = 0.054) or ITT (difference 5.0 days/cm, 95% CI -8.2 to 18.21, p = 0.226) groups. The smoking status was the only covariate which increased the time to removal of the frame (hazard ratio 0.47, 95% CI 0.22 to 0.97, p = 0.042). Conclusion. LIPUS does not influence the rate of bone healing in patients who undergo distraction osteogenesis. Smoking may influence bone healing. . Cite this article: Bone Joint J 2017;99-B:494–502

Aims

The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes.

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

Aims

Tibial tubercle osteotomy (TTO) facilitates surgical exposure and protects the extensor mechanism during revision total knee arthroplasty (rTKA). The purpose of this study was to determine the rates of bony union, complications, and reoperations following TTO during rTKA, to assess the functional outcomes of rTKA with TTO at two years’ minimum follow-up, and to identify the risk factors of failure.

Aims. The aim of this study was to evaluate the efficacy of the surgical dislocation approach and modified trapdoor procedure for the treatment of chondroblastoma of the femoral head. Patients and Methods. A total of 17 patients (ten boys, seven girls; mean age 16.4 years (11 to 26)) diagnosed with chondroblastoma of the femoral head who underwent surgical dislocation of the hip joint, modified trapdoor procedure, curettage, and bone grafting were enrolled in this study and were followed-up for a mean of 35.9 months (12 to 76). Healing and any local recurrence were assessed via clinical and radiological tests. Functional outcome was evaluated using the Musculoskeletal Tumour Society scoring system (MSTS). Patterns of bone destruction were evaluated using the Lodwick classification. Secondary osteoarthritis was classified via radiological analysis following the Kellgren–Lawrence grading system. Steinberg classification was used to evaluate osteonecrosis of the femoral head. Results. The epiphyseal plate was open, closing, and closed in five, five, and seven patients, respectively. In total, eight, six, and three patients were classified as having Lodwick classification IA, IB, and IC, respectively. Allogeneic and autogenous bone grafting was used in 13 and four patients, respectively. All patients had good bone healing and no local recurrence was observed. One patient developed osteonecrosis of the femoral head (Steinberg IA) and one developed secondary osteoarthritis of the hip joint (Kellgren–Lawrence Grade II). The mean postoperative MSTS functional score was 27.7 (24 to 30). Conclusion. Surgical dislocation and modified trapdoor procedures are safe and effective techniques for treating chondroblastoma in the femoral head. Cite this article: Bone Joint J 2019;101-B:732–738

Aims

Distraction osteogenesis with intramedullary lengthening devices has undergone rapid development in the past decade with implant enhancement. In this first single-centre matched-pair analysis we focus on the comparison of treatment with the PRECICE and STRYDE intramedullary lengthening devices and aim to clarify any clinical and radiological differences.

Aims

The aim of this study was to assess the safety and clinical outcome of patients with a femoral shaft fracture and a previous complex post-traumatic femoral malunion who were treated with a clamshell osteotomy and fixation with an intramedullary nail (IMN).

Aims. It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. Materials and Methods. An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium. RNA sequencing analysis was performed using sorted CD31. hi. EMCN. hi. endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. Results. Flow cytometry revealed that anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. Conclusion. VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31. hi. EMCN. hi. endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108–114