Repurposing denosumab for recalcitrant bone healing.

Fracture healing has four phases: haematoma formation, soft callus, hard callus and remodelling. Often, non-healing fractures have an arrest of one of these phases, which need resurgery. We have repurposed denosumab for impaired fracture healing cases to avoid surgical intervention. Here, we report a series of three cases of impaired fracture healing where denosumab was given 120 mg subcutaneous dosages for 3 months to enhance healing. All the three cases have shown complete bone union at a mean follow-up of 6.7 months (5-9 months) as assessed clinically and radiologically, and have observed no adverse effect of the therapy. Denosumab given in this dose aids fracture healing by increasing callus volume, density and bridges the fracture gap in recalcitrant fracture healing cases where the callus fails to consolidate.

Treatment of Isolated Posterolateral Tibial Plateau Fracture with a Horizontal Belt Plate through the Anterolateral Supra-Fibular-Head Approach.

The posterolateral tibial plateau fracture was not easy to be exposed and fixed with usual techniques. The aim of this study was to investigate the biomechanical stability and clinical outcome of the isolated posterolateral tibial plateau fracture fixed with a single horizontal belt plate through the anterolateral supra-fibular-head approach. Fracture models were created by 18 synthetic tibias and fixed with three different fixation modes. Each group was fixed and tested on the loading machine, and final vertical displacement of the fragment was detected and calculated. Clinically, a retrospective analysis of 12 cases of posterolateral tibial plateau fracture from January 2013 to December 2017 was performed. There were 8 males and 4 females, aged 33-72 years, with an average age of 49.6 years. Isolated posterolateral tibial plateau fractures were identified according to preoperative X-ray and computed tomography scan. Through the modified anterolateral supra-fibular-head approach, the fracture was reduced and fixed by a prebending T-shaped distal radius plate and rafting screws, with bone substitute grafting or autogenous iliac bone implantation. Patients were followed up to a minimum one year of time period, and the outcome was evaluated clinically and radiologically. The biomechanical study shows that horizontal belt plate fixation for the isolated PL tibial plateau fracture can provide sufficient stability, allowing early knee functional exercise and partial weight bearing. For clinical case series, the average operation time in this group was 73.3 ± 10.2 mins (range: 55-90), and the average duration of hospitalization was 9.1 ± 3.3 days (range: 5-16). Patients were followed up for 12-24 months with an average of 16.5 months, and all patients achieved radiological fracture union after an average of 13.7 weeks. At one year after operation, the average knee score of the Hospital for Special Surgery (HSS) scale was 93.2 ± 4.2 points(range: 90-98), the average score of SMFA was 21.1 ± 5.6 points (range: 14-31), and the average knee range of motion (ROM) was 121.48° ± 8.88° (range: 105°-135°). There were 8 cases that were very satisfied and 3 cases that were satisfied with the operation. For an isolated posterolateral tibial plateau fracture, the supra-fibular-head approach can fully expose the fracture site; the horizontal belt plate fixation of the fracture is stable and reliable to allow for early-stage knee rehabilitation, and the outcome of medium-term clinical follow-up was satisfactory.

Medial malleolus: Operative Or Non-operative (MOON) trial protocol - a prospective randomised controlled trial of operative versus non-operative management of associated medial malleolus fractures in unstable fractures of the ankle.

BACKGROUND: There are limited data reporting the outcome of patients with non-operatively managed medial malleolus fractures compared to those treated surgically in the presence of fibular stabilisation for unstable fractures of the ankle. Conservative management could result in fewer complications, reduced surgical time and lower cost. The purpose of this study is to determine if any difference exists in patient reported and surgical outcomes 1 year after surgery between operative and non-operative treatment of medial malleolar fractures in combination with stabilisation of the lateral malleolus. METHODS/DESIGN: This is a single-centre, prospective, randomised controlled trial that aims to randomise 154 participants with an unstable ankle fracture to 'non-fixation' (n = 77) or 'fixation' (n = 77) of an associated well-reduced medial malleolus fracture following fibular stabilisation. The study will include patients ≥ 16 years of age with a closed bimalleolar or trimalleolar ankle fracture who are able to consent, complete questionnaires in the English language, and complete follow-up over a 1-year period. Randomisation will occur intra-operatively when the medial malleolus fracture is deemed 'well-reduced', with 2 mm or less of fluoroscopic displacement. The technique for fixation of both the medial and lateral malleoli is at the discretion of the operating surgeon. Patient-reported, observer-rated, and radiographic assessments will be collected at baseline and then at the following post-operative assessment points: 2 weeks, 6 weeks and 1 year. Postal questionnaire outcome data will be collected at 3 and 6 months. The primary outcome measure will be the Olerud Molander Ankle Score (OMAS) at 1 year following surgery. Secondary outcome measures will include the Manchester-Oxford Foot Questionnaire (MOXFQ), EuroQol-5D (EQ-5D), pain, treatment satisfaction, time to return to activity, operative tourniquet time, and complications. DISCUSSION: There is only one previous randomised trial comparing non-fixation with fixation of associated medial malleolus fractures but that was limited by the lack of baseline patient-reported outcome data and an inferior sample size. This current prospective trial aims to provide high-quality evidence regarding the requirement for medial malleolar fixation in unstable ankle fractures. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03362229 . Registered retrospectively on 5 December 2017.

Bone callus formation is highly disrupted by dietary restriction in growing rats sustaining a femoral fracture

Abstract Purpose: To evaluate the effects of food restriction on fracture healing in growing rats. Methods: Sixty-eight male Wistar rats were assigned to two groups: (1) Control and (2) Dietary restriction. After weaning the dietary restricted animals were fed ad libitum for 42 days with 50% of the standard chow ingested by the control group. Subsequently, the animals underwent bone fracture at the diaphysis of the right femur, followed by surgical stabilization of bone fragments. On days 14 and 28 post-fracture, the rats were euthanized, and the fractured femurs were dissected, the callus was analyzed by dual-energy X-ray absorptiometry, micro-computed tomography, histomorphometry, mechanical tests, and gene expression. Results: Dietary restriction decreased body mass gain and resulted in several phenotypic changes at the bone callus (a delay in cell proliferation and differentiation, lower rate of newly formed bone and collagen deposition, reductions in bone callus density and size, decrease in tridimensional callus volume, deterioration in microstructure, and reduction in bone callus strength), together with the downregulated expression of osteoblast-related genes. Conclusion: Dietary restriction had detrimental effects on osseous healing, with a healing delay and a lower quality of bone callus formation.

Clinical characteristics and short to mid term functional outcomes of surgically treated occult hip fractures in the elderly.

BACKGROUND: Occult hip fractures in the elderly are challenging to diagnose and often result in surgical delays which may worsen outcomes. However, the minimally displaced nature of these fractures may conversely lead to better outcomes. The aim of this study was to determine if surgically treated occult hip fractures have better short to mid term functional outcomes when compared to non-occult fractures. The secondary aim was to determine if there are any differences in clinical characteristics of patients who present with occult hip fractures. METHODS: This was a retrospective cohort study of all elderly patients aged 65 years and above who presented with hip fractures in a single institution from January 2012 to December 2013. Elderly patients who presented with hip fractures were enrolled into an Ortho-geriatric carepath and were eligible for recruitment. The exclusion criteria included patients with pathological fractures and multiple injuries. Demographic and pre-injury variables were collected. The functional outcome measurement was the Modified Barthel's Index (MBI). Patients were divided into non-occult hip fractures (Group 1) and occult hip fractures (Group 2). RESULTS: A total of 1017 patients were admitted during this period into the hip fracture carepath, of which 49 (4.8%) were diagnosed to have occult hip fractures. There was no significant difference between the demographics, Charlson co-morbidity index, abbreviated mental test scores or pre-morbid patient dependence between the groups. There was a significant delay to surgery for occult hip fractures when compared to non-occult fractures. (p = 0.03) Subgroup analysis showed that pre-morbidly, patients with occult inter-trochanteric fractures were significantly more independent than patients with non-occult inter-trochanteric fractures. (p = 0.03) There was no significant difference between the length of stay, surgical complications and 1-year mortality between the 2 groups. Occult inter-trochanteric fractures had better MBI scores at all time points when compared to non-occult inter-trochanteric fractures. CONCLUSIONS: Despite the significant delay to surgical intervention for patients with occult hip fractures, the short to mid term functional outcomes for this group of patients are comparable to surgically treated non-occult hip fractures. There are no distinctive clinical characteristics of elderly patients who are more likely to suffer occult hip fractures.

Does temporary external fixation and staged protocol for closed fractures lead to bacterial contamination of the surgical site and associated complications? - A prospective trial.

INTRODUCTION: Temporary external fixation is a viable option for numerous conditions and fixations in orthopaedic and trauma surgery. If the external fixator is left in place it is necessary to disinfect it prior to surgery, yet the subsequent risk for bacterial contamination of the surgical site originating from the external fixator remains unknown. MATERIAL AND METHODS: In a prospective study, samples were taken at the time of definitive osteosynthesis to assess bacterial contamination of the surgical site and the external fixator in twenty consecutive patients treated with temporary external fixation for closed fractures from October 2016 until March 2017. RESULTS: Twenty external fixators of twenty patients with complete sampling and a mean follow-up of seven months (range: 3-14) were available for analysis. Ten out of 120 cultures of the surgical site (8.3%) were positive for bacterial growth in a total of seven patients (35%). Pathogen's detected were Propionibacterium acnes (60%) and Staphylococcus epidermidis (30%). No contamination of the external fixator was detected. CONCLUSION: We conclude that the presented perioperative management to decontaminate external fixators allows for a safe definitive osteosynthesis in a staged protocol without increasing bacterial contamination of the surgical site. It is safe to leave the external fixator in place for definitive osteosynthesis.

How can MRI change the treatment strategy in apparently isolated greater trochanteric fracture?

INTRODUCTION: The purpose of this study was to evaluate the proportion of greater trochanter (GT) fractures with occult extension to the intertrochanteric region on magnetic resonance imaging (MRI) among apparently isolated GT fractures and to investigate the use of MRI for formulating a treatment strategy in patients with isolated GT fractures. PATIENTS AND METHODS: This retrospective cohort study reviewed 37 patients with isolated GT fractures on plain radiography. Surgical or conservative treatment was decided according to MRI findings. We divided patients into 3 groups according to the extension of the fracture line. In group 1, the fracture line was within the lateral one-third in the coronal plane. In group 2, the fracture line extended from the lateral one-third to the medial one-third. In group 3, the fracture line extended over the medial one-third and/or to the medial cortex of the femur. Conservative treatment was performed in groups 1 and 2, and surgical treatment was performed in group 3. The clinical results, radiography findings, and MRI findings were investigated. RESULTS: MRI revealed hidden intertrochanteric fractures (groups 2 [n = 10] and 3 [n = 4]) in 38% of apparently isolated GT fractures on radiography. No displacement was found in groups 1 (n = 23) and 2. Of the 4 patients in group 3, 3 were treated surgically and achieved good functional results and 1 refused to undergo surgery and finally developed complete intertrochanteric fracture. This patient presented 5 days later with increased hip pain, and radiography demonstrated displacement of the fracture, prompting surgical intervention. CONCLUSIONS: The evaluation of apparently isolated GT fractures using MRI can be useful to diagnose the extent of the occult fracture and determine the treatment strategy.

Fifth Metatarsal Jones Fractures in the Athlete.

Fifth metatarsal fractures, otherwise known as "Jones" fractures, occur commonly in athletes and nonathletes alike. While recent occurrence in the popular elite athlete has increased public knowledge and interest in the fracture, this injury is common at all levels of sport. This review will focus on all three types of Jones fractures. The current standard for treatment is operative intervention with intramedullary screw fixation. Athletes typically report an acute episode of lateral foot pain, described as an ache. Radiographic imaging with multiple views of the weightbearing injured foot are needed to confirm diagnosis. If these images are inconclusive, further magnetic resonance imaging (MRI) or computed tomography (CT) is used. Nonoperative treatment is not commonly used as the sole treatment, except when following reinjury of a stable screw fixation. While screw selection is still controversial, operative treatment with intramedullary screw fixation is the standard approach. Technical tips on screw displacement are provided for Torg (types I, II, III) fractures, cavovarus foot fractures, recurrent fractures, revision surgery, occult fractures/high-grade stress reactions, and Jones' variants. Excellent clinical outcomes can be expected in 80% to 100% of patients when using the intramedullary screw fixation to "fit and fill" the medullary canal with threads across the fracture site. Most studies show the timing for return to sports with optimal healing to be seven to twelve weeks after fixation. LEVEL OF EVIDENCE: Level V, expert opinion.

Associations of timing of surgery with postoperative length of stay, complications, and functional outcomes 3-6 years after operative fixation of closed ankle fractures.

AIMS: To evaluate the associations of timing of surgery with postoperative length of stay (LOS), complications, and functional outcomes 3-6 years after open reduction and internal fixation (ORIF) in closed ankle fractures. PATIENTS AND METHODS: Historical cohort study by chart review of 1011 patients for postoperative LOS and complications; 959 individuals were invited to participate in a postal survey with functional outcomes questionnaires. Complications were classified as perioperative, early, or late. The associations with time from trauma to surgery (<8h, 8h to 6days, >6days) were assessed with (1) postoperative LOS using multivariable random-effects negative binomial regression, (2) complications using multivariable binary and multinomial logistic regression, and (3) three different functional outcomes using multivariable linear regression. RESULTS: The mean patient age was 51.4 (range 18-94) years, 556 (55%) were female, and 567 individuals (59%) responded to the questionnaire. There were no statistically significant associations between time to surgery and either postoperative LOS or complications after adjusting for several patient and fracture characteristics. Patients operated on >6days after the trauma had significantly worse scores on the Olerud and Molander Ankle Score (OMAS) (p=0.039) and somewhat worse, but non-significant, scores on the Lower Extremity Functional Scale (LEFS; p=0.573) and the Self-Reported Foot and Ankle Score (SEFAS) scale (p=0.161) than those operated on <8h after trauma. CONCLUSION: In ankle-fracture surgery, there was no apparent association between timing of surgery and postoperative LOS or complications. A delay of surgery for 8h to 6days resulted in similar functional outcomes after 3-6 years suggesting there may be a safe window of time for surgery of up to 6days after trauma that can be used to plan and perform the final ORIF.

A prospective multi-center study of intramedullary nailing vs casting of stable tibial shaft fractures.

BACKGROUND: The purpose of this study was to determine optimal treatment of stable tibial shaft fractures using intramedullary nailing (IMN) or casting. MATERIALS AND METHODS: We performed a multi-center prospective study cohort. Patients with stable tibia shaft fractures meeting Sarmiento's criteria (isolated closed fractures with less than 12 mm of shortening and 10° of angulation) were enrolled prospectively and treated with either a reamed IMN with static interlocking screws or closed reduction followed by long-leg casting. Both groups were weight bearing following surgery. Radiographs were taken until union, and range of motion of knee and ankle joints was assessed. Malalignment (>5°) and malunion (>10°) were determined. Functional outcome measures using short musculoskeletal assessment scores (SMFA) and a knee pain score were scheduled at 6 weeks, 3 months and 6 months. RESULTS: At 3 months, differences between the casting and IMN groups were noted in return to work (6/15 vs 3/17, P < 0.05); ankle dorsiflexion (7° vs 12°, P < 0.05); plantar flexion (28° vs 39°, P < 0.05); and SMFA domains of Dysfunction Index, Bother Index, daily activities, emotional status, and arm/hand function (P < 0.05). The SMFA mobility function demonstrated a significant trend (P = 0.065). At 6 months, malalignment was present in 3/15 in the casting group and in 1/17 in the IMN group (P = 0.02). Malunion was present in 1/15 in the cast group. One fracture in the casting group went on to nonunion and required late IMN placement at 7 months and eventually healed. There were no differences in ankle motion, SMFA scores, or return to work. There was no difference in knee pain between the groups as measured by VAS and Court-Brown pain scale at 6 months. CONCLUSIONS: Patients with stable tibia fractures treated with intramedullary nailing have improved clinical and functional outcomes at 3 months compared with those treated with casting, but there are no differences in any other outcome measure. Patients treated in a cast may have a higher incidence of malalignment or malunion. LEVEL OF EVIDENCE: Level-II prognostic.

Outcomes after plating of olecranon fractures: A multicenter evaluation.

INTRODUCTION: The aim of this study was to report the physical and functional outcomes after open reduction internal fixation of the olecranon in a large series of patients with region specific plating across multiple centres. PATIENTS/METHODS: Between January 2007 and January 2014, 182 consecutive patients with a displaced olecranon fracture treated with open reduction internal fixation were included in this study. Retrospective review across four trauma centres collected elbow range of motion, DASH scores, hardware complications, and hardware removal. Postoperative visits in the outpatient clinic were at two, six, and twenty-four weeks. After 24 weeks, patients were eligible for hardware removal if symptomatic. All patients were contacted, at least 1 year following surgery, to determine if hardware was removed. RESULTS: 182 patients (75 women, 105 men) average age 50 (16-89) with 162 closed and 19 open displaced olecranon fractures were treated with one region specific plate. Nineteen were lost to followup leaving 163 for analysis with all patients united. The most common deficiency was a lack of full extension with 39% lacking at least 10° of extension. Hardware was asymptomatic in 67%, painful upon leaning in 20%, and restricted activities in 11% resulting in a 15% rate of hardware removal. Hardware complaints were more common if a screw was placed in the corner of the plate (P=0.004). When symptomatic, the area of the plate that was bothersome encompassed the whole plate in 39%, was at the edge of the plate in 33%, and was a screw head in 28%. The DASH scores, collected at final follow-up of 24 weeks, was 10.1±16, indicating moderate disability was still present. Patients who lacked 10° of extension had a DASH of 12.3 as compared with 10.5 for those with near full extension, but this was not significant (P=0.5). CONCLUSION: Plating of the olecranon leads to predictable union. The most common complication was lack of full extension with 39% lacking more than 10°, although this did not have any effect on DASH scores. Overall results indicate that disability still exists after 6 months with an average DASH score of 10. LEVEL OF EVIDENCE: Therapeutic level III.

[Internal fixation with lag screws plus an anti-sliding plate for the treatment of Hoffa fracture of the lateral femoral condyle].

OBJECTIVE: To explore the clinical effects of internal fixation with lag screws plus an anti-sliding plate for the treatment of Hoffa fractures of the lateral femoral condyle. METHODS: From May 2006 to May 2014, 17 patients with Hoffa fractures of the lateral femoral condyle were treated with lag screws plus an anti-sliding plate. There were 13 males and 4 females, ranging in age from 27 to 59 years, with a mean of 32.5 years. All the fractures were fresh and closed fractures. According to the Letenneur's classification, 8 cases were type I, 4 cases were type II, 5 cases were type III. All the patients had no injuries of the cruciate ligament and the another part of the knee. Operative incision and fracture healing time were observed, knee joint function was evaluated by Letenneur system and HSS standard. RESULTS: The patients were followed up from 10 to 24 months with a mean of 14.6 months. All incisions achieved primary healing, and no internal fixation breakage, malunion, femoral candyle necrosis, deep vein thrombosis of lower extremity were found. Fracture healing time was from 4 to 9 months with an average of 4.7 months. According to Letenneur's functional assessment, 10 patients got an excellent results, 4 good, 3 fair. Total HSS score was 91.1 +/- 4.7 on average,15 cases obtained excellent results, 2 good. CONCLUSION: Internal fixation with lag screws and an anti-sliding plate can result in excellent effects for Hoffa fractures of the lateral femoral condyle. The key to a successful surgery is an anatomic reduction and rigid fixation of the fracture.

The effect of teicoplanin on fracture healing: an experimental study.

OBJECTIVES: This study aims to investigate the effect of teicoplanin on fracture healing stereologically and histopatologically. MATERIALS AND METHODS: Twenty male Wistar albino rats were separated into two as the study (teicoplanin) and control groups. After intramedullary fixation of the right tibia of all the rats with 0.5 mm Kirschner wire under general anesthesia, standard closed shaft fractures were created using fracture formation apparatus. Teicoplanin (10 mg/kg) and saline were administered intraperitoneally to the study and control groups, respectively. Control radiographs were taken at the end of the procedure and the rats were sacrificed after 28 days. New bone and connective tissue volumes were calculated on obtained tissue samples using unbiased stereological and histopathological techniques. RESULTS: It was observed that teicoplanin increased the formation of bone, vascularization, and connective tissue. There was a statistically significant difference between the two groups in respect of bone and vascular total volume (p<0.05). Although an increase was observed in connective tissue total volume, no statistically significant difference was detected between the two groups (p>0.05). CONCLUSION: In addition to its antibacterial effect, teicoplanin may increase new bone formation; thus, it may be used safely in the treatment of bone defects accompanied with infection.

Augmentation of Fracture Healing Using Soft Callus.

OBJECTIVES: This study sought to investigate the effect of soft callus removal and reapplication in a rat closed femur fracture model. We hypothesized that removing soft callus will impair fracture healing, whereas reapplication will facilitate healing. METHODS: A closed midshaft femur fracture was created in 78 rats and stabilized with an intramedullary wire. Seven days later, rats were equally divided and fractures surgically exposed. In the control group, no callus was removed, whereas in the callus removal group CR(-) group, the callus was removed and in the callus replaced group CR(+), callus was removed and replaced. Half of the rats were killed at 4 and 7 weeks. Fracture healing was graded with radiographs and callus volume measured with micro-CT. Mechanical torsion properties were measured, and histologic analysis was conducted. RESULTS: At both end points, evidence of delayed healing was found on radiographs and micro-CT in CR(-) rats (P = 0.0001), whereas CR(+) rats showed normal fracture healing compared with controls. The normalized callus volume was similar in all groups at both end points. At 7 weeks, the maximum stiffness in CR(-) rats was 68% less than control (P = 0.0001). Stiffness increased 55% in CR(+) rats from CR(-) rats (P = 0.0017). Histology supported our findings with complete endochondral ossification in CR(+) rats but wide areas of hyaline cartilage in CR(-) rats at 7 weeks. CONCLUSIONS: Removal of soft callus in a rat model delays fracture healing at early and late time points, whereas replacement mitigates these negative consequences. Replacing the soft callus should be considered in all osteosynthesis procedures.

mir-21 overexpressing mesenchymal stem cells accelerate fracture healing in a rat closed femur fracture model.

MicroRNAs are small noncoding RNAs involved in numerous biological processes. Emerging pieces of evidence suggest that microRNAs play important roles in osteogenesis and skeletal homeostasis. Recent studies indicated the significant regulation function of mir-21 in osteogenesis in vitro, but little information is known about its veritable functions in vivo. In the present study, we aimed to investigate the effect of mir-21 intervention on osteogenic differentiation of rats bone marrow derived mesenchymal stem cells (rBMSCs) and repair capacity in rats closed femur fracture model with internal fixation. The results showed that the upregulation of mir-21 not only increased the expression of osteopontin and alkaline phosphatase in rBMSCs but also promoted mineralization in the condition of osteogenic induction. Furthermore, the bone healing properties were also improved in fracture healing model according to the results of micro-CT, mechanical test, and histological analysis. The current study confirms that the overexpression of mir-21 could promote osteogenesis and accelerate bone fracture healing, which may contribute to a new therapeutic way for fracture repair.

Parameters for lithium treatment are critical in its enhancement of fracture-healing in rodents.

BACKGROUND: Lithium, a treatment for bipolar disorder, is not clinically indicated for use in fracture management but has been reported to positively influence bone biology. It is hypothesized that lithium dosing for beneficial effects on bone health may be much lower than the dosing required for psychotropic benefits in patients with bipolar disorder. A preclinical study with a rodent fracture model was utilized to best define the lowest effective dose, best timing of treatment onset, and optimal treatment duration for the use of lithium as a new treatment in fracture care. METHODS: A design-of-experiments approach was used to assess the parameters of dose, timing of treatment onset, and treatment duration. Closed femoral shaft fractures were generated and analyzed with use of destructive torsional mechanical testing and microcomputed tomography-based image analysis. Eleven different outcome measures were quantified, with maximum yield torque as the primary study outcome, to assess the quality of long-bone fracture-healing. RESULTS: Fracture-healing was maximized with a lithium treatment combination of a low dose (twenty milligrams per kilogram of body weight per day), later onset of lithium treatment (seven days after fracture), and longer treatment duration (two weeks), with maximum yield torque displaying a 46% increase compared with nontreated and sham-treated controls (481.1 ± 104.0 N-mm compared with 329.9 ± 135.8 N-mm; p = 0.04). Design-of-experiments analysis determined the timing of treatment onset to be the most influential parameter for improving fracture-healing, with femora treated at a later onset (seven days after fracture) showing a significant (21%) increase in maximum yield torque compared with those treated at an earlier onset (three days after fracture) (p = 0.01). CONCLUSIONS: A later onset of lithium administration significantly improved femoral fracture-healing. Trends indicated that a lower dose and longer treatment duration also had a positive effect on fracture repair. CLINICAL RELEVANCE: Orally administered low-dose lithium therapy with a large postfracture administration window has the potential to yield a safe, reliable, and cost-effective treatment to enhance bone-healing and restore earlier function and mobility pending appropriate large-animal proof-of-concept models, safety data, and U.S. Food and Drug Administration clinical trials approval.

Operative versus non-operative treatment for closed, displaced, intra-articular fractures of the calcaneus: randomised controlled trial.

OBJECTIVE: To investigate whether surgery by open reduction and internal fixation provides benefit compared with non-operative treatment for displaced, intra-articular calcaneal fractures. DESIGN: Pragmatic, multicentre, two arm, parallel group, assessor blinded randomised controlled trial (UK Heel Fracture Trial). SETTING: 22 tertiary referral hospitals, United Kingdom. PARTICIPANTS: 151 patients with acute displaced intra-articular calcaneal fractures randomly allocated to operative (n=73) or non-operative (n=78) treatment. MAIN OUTCOME MEASURES: The primary outcome measure was patient reported Kerr-Atkins score for pain and function (scale 0-100, 100 being the best possible score) at two years after injury. Secondary outcomes were complications; hindfoot pain and function (American Orthopaedic Foot and Ankle Society score); general health (SF-36); quality of life (EQ-5D); clinical examination; walking speed; and gait symmetry. Analysis was by intention to treat. RESULTS: 95% follow-up was achieved for the primary outcome (69 in operative group and 74 in non-operative group), and a complete set of secondary outcomes were available for 75% of participants. There was no significant difference in the primary outcome (mean Kerr-Atkins score 69.8 in operative group v 65.7 in non-operative group; adjusted 95% confidence interval of difference -7.1 to 7.0) or in any of the secondary outcomes between treatment groups. Complications and reoperations were more common in those who received operative care (estimated odds ratio 7.5, 95% confidence interval 2.0 to 41.8). CONCLUSIONS: Operative treatment compared with non-operative care showed no symptomatic or functional advantage after two years in patients with typical displaced intra-articular fractures of the calcaneus, and the risk of complications was higher after surgery. Based on these findings, operative treatment by open reduction and internal fixation is not recommended for these fractures.Trial registration Current Controlled Trials ISRCTN37188541.

A novel low-molecular-weight compound enhances ectopic bone formation and fracture repair.

BACKGROUND: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is expensive and may cause local side effects. A small synthetic molecule, SVAK-12, has recently been shown in vitro to potentiate rhBMP-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype. The aims of this study were to test the ability of SVAK-12 to enhance bone formation in a rodent ectopic model and to test whether a single percutaneous injection of SVAK-12 can accelerate callus formation in a rodent femoral fracture model. METHODS: Collagen disks with rhBMP-2 alone or with rhBMP-2 and SVAK-12 were implanted in a standard athymic rat chest ectopic model, and radiographic analysis was performed at four weeks. In a second set of rats (Sprague-Dawley), SVAK-12 was percutaneously injected into the site of a closed femoral fracture. The fractures were analyzed radiographically and biomechanically (with torsional testing) five weeks after surgery. RESULTS: In the ectopic model, there was dose-dependent enhancement of rhBMP-2 activity with use of SVAK-12 at doses of 100 to 500 µg. In the fracture model, the SVAK-12-treated group had significantly higher radiographic healing scores than the untreated group (p = 0.028). Biomechanical testing revealed that the fractured femora in the 200 to 250-µg SVAK-12 group were 43% stronger (p = 0.008) and 93% stiffer (p = 0.014) than those in the control group. In summary, at five weeks the femoral fracture group injected with SVAK-12 showed significantly improved radiographic and biomechanical evidence of healing compared with the controls. CONCLUSIONS: A single local dose of a low-molecular-weight compound, SVAK-12, enhanced bone-healing in the presence of low-dose exogenous rhBMP-2 (in the ectopic model) and endogenous rhBMPs (in the femoral fracture model). CLINICAL RELEVANCE: This study demonstrates that rhBMP-2 responsiveness can be enhanced by a novel small molecule, SVAK-12. Local application of anabolic small molecules has the potential for potentiating and accelerating fracture-healing. Use of this small molecule to lower required doses of rhBMPs might both decrease their cost and improve their safety profile.

Delayed fracture healing in aged senescence-accelerated P6 mice.

BACKGROUND: Osteoporosis is characterized by poor bone quality. However, it is still controversially discussed whether osteoporosis compromises fracture healing. Herein, we studied whether the course of healing of a femur fracture is affected by osteoporosis or age. METHODS: Using the senescence-accelerated osteoporotic mouse, strain P6 (SAMP6), and a closed femur fracture model, we studied the process of fracture healing in 5- and 10-month-old animals, including biomechanical, histomorphometric, and protein biochemical analysis. RESULTS: In five-month-old osteoporotic SAMP6 mice, bending stiffness, callus size, and callus tissue distribution as well as the concentrations of the bone formation marker osteocalcin and the bone resorption markers tartrate-resistant acid phosphatase form 5b (TRAP) and deoxypyridinoline (DPD) did not differ from that of non-osteoporotic, senescence-resistant, strain 1 (SAMR1) controls. In contrast, femur fractures in 10-month-old SAMP6 mice showed a significantly reduced bending stiffness and an increased callus size compared to fractures in age-matched SAMR1 controls. This indicates a delayed fracture healing in advanced age SAMP6 mice. The delay of fracture healing was associated with higher concentrations of TRAP and DPD. Significant differences in osteocalcin concentrations were not found between SAMP6 animals and SAMR1 controls. CONCLUSION: In conclusion, the present study indicates that fracture healing in osteoporotic SAMP6 mice is not affected in five-month-old animals, but delayed in animals with an age of 10 months. This is most probably due to the increased osteoclast activity in advanced age SAMP6 animals.

[Distal radius fracture: clinico-radiographic correlation after fixation with volar plate]. / Fractura de radio distal, correlación clínica-radiográfica posterior a fijación con placa volar.

UNLABELLED: The purpose of the study was to assess and correlate the clinical and radiographic results of patients with distal radius fracture treated with a volar approach and plate osteosynthesis thus identifying the factors that determine or contribute to functional results in these patients. METHODS: All patients who underwent surgical treatment for distal radius fracture with a volar approach and plate osteosynthesis from May 2010 to May 2011 were identified. They were radiographically assessed with measurements of the volar and radial angle and clinically with the Mayo Wrist Score; the correlation coefficient was used to obtain the results. RESULTS: A total of 35 patients met the selection criteria; 23 females and 12 males; mean age was 40 years (18-62); the right extremity was predominant (25:10) and was the dominant limb in 57% of cases. The assessment using the MWS was done at postoperative year one; mean score was 81 (50-100): 37% were excellent, 31% good, 26% satisfactory, and 6% poor. The correlation showed that the MWS-radial angle and the MWS-volar angle had statistically significant values with p values of 0.0001 and 0.0008 respectively, both with a 95% confidence interval. CONCLUSION: The clinical and radiographic correlation showed that the radial and volar angles are determining factors for a satisfactory course. Age, sex, the dominant limb, the number of days elapsed and the AO classification did not show statistically significant values for patient course.