Aims. Little is known about the effect of haemorrhagic shock and resuscitation on fracture healing. This study used a rabbit model with a femoral osteotomy and fixation to examine this relationship. Materials and Methods. A total of 18 male New Zealand white rabbits underwent femoral osteotomy with intramedullary fixation with ‘shock’ (n = 9) and control (n = 9) groups. Shock was induced in the study group by removal of 35% of the total blood volume 45 minutes before resuscitation with blood and crystalloid. Fracture healing was monitored for eight weeks using serum markers of healing and radiographs. Results. Four animals were excluded due to postoperative complications. The serum concentration of osteocalcin was significantly elevated in the shock group postoperatively (p < 0.0001). There were otherwise no differences with regard to serum markers of bone healing. The callus index was consistently increased in the shock group on anteroposterior (p = 0.0069) and lateral (p = 0.0165) radiographs from three weeks postoperatively. The control group showed an earlier decrease of callus index. Radiographic scores were significantly greater in the control group (p = 0.0025). Conclusion. In a rabbit femoral osteotomy model with intramedullary fixation, haemorrhagic shock and resuscitation produced larger callus but with evidence of delayed remodelling. Cite this article: Bone Joint J 2018;100-B:1234–40

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing. The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone. Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue

This prospective multicentre study was undertaken to determine whether the timing of the post-operative administration of bisphosphonate affects fracture healing and the rate of complication following an intertrochanteric fracture. Between August 2008 and December 2009, 90 patients with an intertrochanteric fracture who underwent internal fixation were randomised to three groups according to the timing of the commencement of risedronate treatment after surgery: Group A (from one week after surgery), Group B (from one month after surgery), and Group C (from three months after surgery). The radiological time to fracture healing was assessed as the primary endpoint, and the incidence of complications, including excessive displacement or any complication requiring revision surgery, as the secondary endpoint. The mean time to fracture healing post-operatively in groups A, B and C was 10.7 weeks (. sd. 4.4), 12.9 weeks (. sd. 6.2) and 12.3 weeks (. sd. 7.1), respectively (p = 0.420). At 24 weeks after surgery, all fractures had united, except six that had a loss of fixation. Functional outcomes at one year after surgery according to the Koval classification (p = 0.948) and the incidence of complications (p = 0.386) were similar in the three groups. This study demonstrates that the timing of the post-operative administration of bisphosphonates does not appear to affect the rate of healing of an intertrochanteric fracture or the incidence of complications

Biochemical markers of bone-turnover have long been used to complement the radiological assessment of patients with metabolic bone disease. Their implementation in daily clinical practice has been helpful in the understanding of the pathogenesis of osteoporosis, the selection of the optimal dose and the understanding of the progression of the onset and resolution of treatment. Since they are derived from both cortical and trabecular bone, they reflect the metabolic activity of the entire skeleton rather than that of individual cells or the process of mineralisation. Quantitative changes in skeletal-turnover can be assessed easily and non-invasively by the measurement of bone-turnover markers. They are commonly subdivided into three categories; 1) bone-resorption markers, 2) osteoclast regulatory proteins and 3) bone-formation markers. Because of the rapidly accumulating new knowledge of bone matrix biochemistry, attempts have been made to use them in the interpretation and characterisation of various stages of the healing of fractures. Early knowledge of the individual progress of a fracture could help to avoid delayed or nonunion by enabling modification of the host’s biological response. The levels of bone-turnover markers vary throughout the course of fracture repair with their rates of change being dependent on the size of the fracture and the time that it will take to heal. However, their short-term biological variability, the relatively low bone specificity exerted, given that the production and destruction of collagen is not limited to bone, as well as the influence of the host’s metabolism on their concentration, produce considerable intra- and inter-individual variability in their interpretation. Despite this, the possible role of bone-turnover markers in the assessment of progression to union, the risks of delayed or nonunion and the impact of innovations to accelerate fracture healing must not be ignored

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague–Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm. -2. (. sd. 7.63) vs 24.65 Nmm. -2. (. sd. 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (. sd. 0.75) vs 4.6 mmAl (. sd. 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007). . Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing. Cite this article: Bone Joint J 2013;95-B:1263–8

We studied the effect of vitamin C on fracture healing in the elderly. A total of 80 elderly Osteogenic Disorder Shionogi rats were divided into four groups with different rates of vitamin C intake. A closed bilateral fracture was made in the middle third of the femur of each rat. Five weeks after fracture the femora were analysed by mechanical and histological testing. The groups with the lower vitamin C intake demonstrated a lower mechanical resistance of the healing callus and a lower histological grade. The vitamin C levels in blood during healing correlated with the torque resistance of the callus formed (r = 0.525). Therefore, the supplementary vitamin C improved the mechanical resistance of the fracture callus in elderly rats. If these results are similar in humans, vitamin C supplementation should be recommended during fracture healing in the elderly

Platelet-derived growth factor (PDGF) is known to stimulate osteoblast or osteoprogenitor cell activity. We investigated the effect of locally applied PDGF from poly-. d. ,l-lactide (PDLLA)-coated implants on fracture healing in a rat model. A closed fracture of the right tibia of four-month-old Sprague-Dawley rats (n = 40) was stabilised with implants coated with a biodegradable PDLLA versus implants coated with PDLLA and PDGF. Radiographs were taken throughout the study, and a marker of DNA activity, bromodeoxyuridine (BrdU), was injected before the rats were killed at three, seven and ten days. The radiographs showed consolidation of the callus in the PDGF-treated group compared with the control group at all three time points. In the PDGF-treated group, immunohistochemical staining of BrdU showed that the distribution of proliferating cells in all cellular events was higher after ten days compared with that at three and seven days. These results indicate that local application of PDGF from biodegradable PDLLA-coated implants significantly accelerates fracture healing in experimental animals. Further development may help fracture healing in the clinical situation.

We studied 56 patients with fractures of the tibial shaft in a multicentre prospective randomised trial of three methods of external fixation. Group I was treated with a fixator which was unlocked at 4 to 6 weeks to allow free axial compression (axial dynamisation) with weight-bearing. Group II was treated with a fixator that was similarly unlocked at 4 to 6 weeks but included a small silicone spring which on weight-bearing could be compressed by up to 2 mm. this spring returns to its original length on cessation of weight-bearing thus allowing cycles of motion of up to 2 mm. Group III had a spring fixator like group II, but it was unlocked from the start to allow cyclical micromovement as soon as weight-bearing began. Fracture healing was monitored by the measurement of fracture stiffness. We defined healing as achieving a stiffness of 15 Nm per degree. The mean time was 14.1 weeks in group I, 15.9 weeks in group II, and 19.3 weeks in group III. The difference between groups was statistically significant (p = 0.004). The 95% confidence intervals for the average delay in healing with early cyclical micromovement (group III) as compared with later axial dynamisation (group I) was 1.8 to 8.7 weeks. The healing time in patients whose cyclical micromovement was delayed for 4 to 6 weeks (group II) was between these two extremes, but the differences from either of the other groups could have been due to patient selection. In the patients who completed the full trial, there were pin-track infections in over 60% of those in the cyclical micromovement groups compared with 20% in the axial dynamisation group (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

We measured the adenosine triphosphate (ATP) content of callus at various intervals during healing in 78 fractured tibiae in 10- to 12-week-old rabbits. The results, compared with the level in normal tissues, showed a high rate of energy metabolism in the early phase of fracture healing, which persisted until the callus was corticalised and remodelling had started. The ATP content could provide a more sensitive index to monitor fracture healing in animal studies. Our findings lend support to the need for nutritional supplements for patients with multiple fractures

Using a simple method of quantifying fracture healing, 53 patients who had limb fractures and also severe head injuries were studied; they were compared with 30 patients who had limb fractures but no head injury. Those with head injuries had a greater healing response and united more rapidly. Radiological and histological analysis revealed that the terms "myositis ossificans" and "heterotopic bone" may be more appropriate than "fracture callus" to describe the healing response in these patients

This paper reviews the current literature concerning the main clinical factors which can impair the healing of fractures and makes recommendations on avoiding or minimising these in order to optimise the outcome for patients. The clinical implications are described.

We have investigated whether assessment of blood flow to the proximal scaphoid can be used to predict nonunion in acute fractures of the scaphoid. We studied 32 fractures of the scaphoid one to two weeks after injury, by dynamic fat-suppressed T1-weighted gradient-echo MRI after the intravenous administration of gadopentetate dimeglumine (0.1 mmol/kg body-weight). Steepest slope values (SSV) and percentage enhancement values (%E) were calculated for the distal and proximal fragments and poles. All the fractures were treated by immobilisation in a cast, and union was assessed by CT at 12 weeks.

Nonunion occurred in four fractures (12%), and there was no statistically significant difference between the proximal fragment SSV and %E values for the fractures which united and those with nonunion. The difference between the proximal pole SSV and %E values for the union and nonunion groups reached statistical significance (p < 0.05), but with higher enhancement parameters for the nonunion group. Our results suggest that poor proximal vascularity is not an important determinant of union in fractures of the scaphoid.

The uptake of 99mTc-MDP was studied in 73 patients after a tibial fracture. The image obtained five minutes after injection during a period between one and four weeks after fracture was found to be related to the incidence of non-union after six months. A ratio of 1.3 between the uptake at the fracture site and at normal bone adjacent to it predicted non-union in an individual patient with a sensitivity of about 70% and a specificity of 90%.

In 65 mature Wistar rats a Kirschner wire was introduced into the medullary cavity of each femur. A closed transverse mid-shaft fracture of one femur was produced by a three-point bending technique. Subsequently the mechanical characteristics of the healing fracture, including the torque and angle of twist required to take the callus to its yield point and to ultimate failure, were compared with those for the opposite femur of each rat. Controls were killed in groups at two, three, four, five and seven weeks. Test animals were given bovine growth hormone in a daily dose of five milligrams before being killed in groups at two, three and four weeks. A significant increase in torque index was found in the two-week group of test animals but not in subsequent groups. No evidence was found that growth hormone given alone could produce an overall shortening of the healing time in fresh fractures.

As there is little information on the factors that influence fracture union following intramedullary nailing of the tibia we retrospectively investigated patient-, injury- and treatment-related factors in 161 patients with closed or grade I open fractures of the tibial diaphysis. The patients were reviewed until clinical and radiological evidence of union at a mean of 13.3 months (4 to 60). Multivariate statistical analysis using a Cox proportional hazards model showed that the risk of failure of union increased by 2.38 times for highly comminuted fractures, by 3.14 times when nail dynamisation was applied, and by 1.65 times when the locking screws failed. In fractures with no or only minimal comminution the risk of nonunion increased if the post-reduction gap was ≥ 3 mm.

Aims. Minimally invasive fixation of pelvic fragility fractures is recommended to reduce pain and allow early mobilization. The purpose of this study was to evaluate the outcome of two different stabilization techniques in bilateral fragility fractures of the sacrum (BFFS). Methods. A non-randomized, prospective study was carried out in a level 1 trauma centre. BFFS in 61 patients (mean age 80 years (SD 10); four male, 57 female) were treated surgically with bisegmental transsacral stablization (BTS; n = 41) versus spinopelvic fixation (SP; n = 20). Postoperative full weightbearing was allowed. The outcome was evaluated at two timepoints: discharge from inpatient treatment (TP1; Fitbit tracking, Zebris stance analysis), and ≥ six months (TP2; Fitbit tracking, Zebris analysis, based on modified Oswestry Disability Index (ODI), Majeed Score (MS), and the 12-Item Short Form Survey 12 (SF-12). Fracture healing was assessed by CT. The primary outcome parameter of functional recovery was the per-day step count; the secondary parameter was the subjective outcome assessed by questionnaires. Results. Overall, no baseline differences were observed between the BTS and SP cohorts. In total, 58 (BTS = 19; SP = 39) and 37 patients (BTS = 14; SP = 23) could be recruited at TP1 and TP2, respectively. Mean steps per day at TP1 were median 308 (248 to 434) in the BTS group and 254 (196 to 446) in the SP group. At TP2, median steps per day were 3,759 (2,551 to 3,926) in the BTS group and 3,191 (2,872 to 3,679) in the SP group, each with no significant difference. A significant improvement was observed in each group (p < 0.001) between timepoints. BTS patients obtained better results than SP patients in ODI (p < 0.030), MS (p = 0.007), and SF-12 physical status (p = 0.006). In all cases, CT showed sufficient fracture healing of the posterior ring. Conclusion. Both groups showed significant outcome improvement and sufficient fracture healing. Both techniques can be recommended for BFFS, although BTS was superior with respect to subjective outcome. Step-count tracking represents a reliable method to evaluate the mobility level. Cite this article: Bone Joint J 2021;103-B(3):462–468

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). Methods. The study involved a retrospective analysis of 23 patients. All had a previous, operatively managed, femoral shaft fracture with malunion due to hardware failure. They were treated with a clamshell osteotomy between May 2015 and March 2020. The mean age was 42.6 years (26 to 62) and 15 (65.2%) were male. The mean follow-up was 2.3 years (1 to 5). Details from their medical records were analyzed. Clinical outcomes were assessed using the quality of correction of the deformity, functional recovery, the healing time of the fracture, and complications. Results. The mean length of time between the initial injury and surgery was 4.5 years (3 to 10). The mean operating time was 2.8 hours (2.05 to 4.4)), and the mean blood loss was 850 ml (650 to 1,020). Complications occurred in five patients (21.7%): two with wound necrosis, and three with deep vein thrombosis. The mean coronal deformity was significantly corrected from 17.78° (SD 4.62°) preoperatively to 1.35° (SD 1.72°) postoperatively (p < 0.001), and the mean sagittal deformity was significantly corrected from 20.65° (SD 5.88°) preoperatively to 1.61° (SD 1.95°; p < 0.001) postoperatively. The mean leg length discrepancy was significantly corrected from 3.57 cm (SD 1.27) preoperatively to 1.13 cm (SD 0.76) postoperatively (p < 0.001). All fractures healed at a mean of seven months (4 to 12) postoperatively. The mean Lower Extremity Functional Scale score improved significantly from 45.4 (SD 9.1) preoperatively to 66.2 (SD 5.5) postoperatively (p < 0.001). Partial cortical nonunion in the deformed segment occurred in eight patients (34.8%) and healed at a mean of 2.4 years (2 to 3) postoperatively. Conclusion. A clamshell osteotomy combined with IMN fixation in the treatment of patients with a femoral shaft fracture and a previous post-traumatic femoral malunion achieved excellent outcomes. Partial cortical nonunions in the deformed segment also healed satisfactorily. Cite this article: Bone Joint J 2023;105-B(4):449–454