A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing. Cite this article: Bone Joint Res 2020;9(7):368–385

Osteoporotic fracture has become a major problem in ageing population and often requires prolonged healing time. Low Intensity Pulsed Ultrasound (LIPUS) can significantly enhance fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). DMP1 in osteocytes is responsible for maintaining LCN and mineralisation. This study aims to investigate osteocyte-specific DMP1's role in enhanced osteoporotic fracture healing in response to mechanical stimulation. Bilateral ovariectomy was performed in 6-month-old female SD rats to induce osteoporosis. Metaphyseal fracture was created at left distal femur using oscillating micro-saw. Rats were randomised to groups: (1) DMP1 KD, (2) DMP1 KD + LIPUS, (3) Control, or (4) Control + LIPUS, where KD stands for knockdown by injection of shRNA into marrow cavity 2 weeks before surgery. Assessments included weekly radiography, microCT and immunohistochemistry on DMP1, E11, FGF23 and sclerostin. DMP1 KD significantly impaired LIPUS-accelerated fracture healing when comparing KD + LIPUS group to Control + LIPUS group. The X-ray relative opacity showed less tissue growth at all timepoints (Week 1, 3 & 6; p=0.000, 0.001 and 0.003 respectively) and the bone volume fraction was decreased after DMP1 KD at Week 3 (p=0.006). DMP1 KD also significantly altered the expression levels of osteocyte-specific DMP1, E11, FGF23 and sclerostin during healing process. The lower relative opacity and bone volume fraction in DMP1 KD groups indicated that knockdown of DMP1 was associated with poorer fracture healing process compared to non-knockdown groups. The similar results between knockdown group with and without LIPUS showed that blockage of DMP1 would negate LIPUS-induced enhancement on fracture healing. Acknowledgment: General Research Fund (Ref: 14113018)

Aims. Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing. Methods. A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture. Results. All rats achieved healing, and x-ray relative radiopacity for OVX-VT was significantly higher compared to OVX at week 2. Martius Scarlet Blue (MSB) staining revealed a significant decrease of fibrin content in the callus in OVX-VT compared with OVX on day 3 (p = 0.020). Mean tPA from muscle was significantly higher for OVX-VT compared to OVX (p = 0.020) on day 3. Mechanical testing revealed the mean energy to failure was significantly higher for OVX-VT at 37.6 N mm (SD 8.4) and 71.9 N mm (SD 30.7) compared with OVX at 5.76 N mm (SD 7.1) (p = 0.010) and 17.7 N mm (SD 11.5) (p = 0.030) at week 2 and week 6, respectively. Conclusion. Metaphyseal fracture healing is enhanced by LMHFV, and one of the important molecular pathways it acts on is fibrinolysis. LMHFV is a promising intervention for osteoporotic metaphyseal fracture healing. The improved mechanical properties, acceleration of fracture healing, and safety justify its role into translation to future clinical studies. Cite this article: Bone Joint Res 2021;10(1):41–50

It has been previously shown that Low-Magnitude High-Frequency Vibration (LMHFV) is able to enhance ovariectomy-induced osteoporotic fracture healing in rats. Fracture healing begins with the inflammatory stage, and all subsequent stages are regulated by the infiltration of immune cells such as macrophages and the release of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). Therefore, the aim of this study was to investigate the effect of LMFHV treatment on the inflammatory response in osteoporotic fracture healing. In this study, ovariectomy-induced osteoporotic and sham-operated closed-femoral fracture SD-rats were randomized into three groups: sham control (SHAM), ovariectomized control (OVX-C) or ovariectomized vibration (OVX-V) (n=36, n=6 per group per time point). LMHFV (35Hz, 0.3g) was given 20 min/day and 5 days/week to OVX-V group. SHAM operation and ovariectomy were performed at 6-month and closed femoral fracture was performed at 9-month. Callus morphometry was determined by callus width from weekly radiography. Local expressions of inducible nitric oxide synthase (iNOS) (macrophage M1 marker), CD206 (macrophage M2 marker), TNF-α, IL-6 and IL-10 were detected by immunohistochemistry and quantified by colour threshold in ImageJ, assessed at weeks 1 and 2 post-fracture. Significant difference between groups was considered at p≤0.05 by one-way ANOVA. Callus formation was higher in OVX-V than that of OVX-C as shown by callus width at weeks 1 and 2 (p=0.054 and 0.028, respectively). Immunohistochemistry results showed that CD206 positive signal and the M2/M1 ratio which indicates the progression of macrophage polarization were significantly higher in OVX-V rats (p=0.053 and 0.049, respectively) when compared to OVX-C at week 1. Area fraction of TNF-α positive signal was significantly higher in SHAM and OVX-V rats at week 1 (p=0.01 and 0.033, respectively). IL-6 signal was also significantly higher in SHAM and OVX-V groups at week 1 (p=0.004 and 0.029, respectively). IL-10 expression was significantly lower in SHAM and OVX-V groups at week 1 (p=0.013 and 0.05, respectively). Here we have shown that LMHFV treatment promoted the shift from pro-inflammatory stage towards anti-inflammatory stage earlier. It has been reported that the polarization of pro-inflammatory macrophages M1 to anti-inflammatory macrophages M2 was indicative of the endochondral ossification process in the long bone fracture model. Besides, we found that LMHFV treatment enhanced pro-inflammatory markers of TNF-α and IL-6 and suppressed anti-inflammatory marker of IL-10 at week 1, showing that inflammatory response was enhanced at week 1 post-fracture. These inflammatory cytokines involved in fracture healing were shown to coordinate different fracture healing processes such as mesenchymal stem cell recruitment and angiogenesis. Our previous study has demonstrated that ovariectomized rats exhibit lower levels of inflammatory response after fracture creation. Therefore, we report that LMHFV treatment can modulate macrophage polarization from M1 to M2 at an earlier time-point and partly restore the impaired inflammatory response in OVX bones at the early stage of fracture healing that may lead to accelerated healing of osteoporotic fracture as shown by promoted callus formation

Purpose. In 2010, the new clinical guideline of Osteoporosis Canada for the diagnosis of osteoporosis, clearly indicates that patients with high-risk of fracture are those that have already sustained a fracture (osteoporotic fracture). Until now, only 12% of the 3,400 fractures that we treat each year receive a treatment for osteoporosis. We are validating an evaluation protocol and a multidisciplinary systematic follow-up approach for osteoporosis. Patients are managed by a clinical nurse specialist. We are recruiting 543 patients with an osteoporotic fracture at Hal du Sacré-Coeur de Montréal. We aim to evaluate: 1) the incidence of a second osteoporotic fracture, 2) the initiation of a treatment and determine the compliance and adherence to treatment and 3) the evaluation of CTX-1 and Osteocalcin at Baseline, 6, 12,18 et 24 months (treatment efficacy) and 4) the functional outcome and quality of life post-fracture. Method. We've enrolled 153 subjects (men and women) over 40 years of age who were treated for an osteoporotic fracture at the orthopaedic clinic of Hal du Sacré-Coeur de Montréal. After starting a treatment protocol for osteoporosis, the subjects will be followed for a 24 months period at different time intervals. During these visits, they fill up functional outcome questionnaires, undergo physical exam, blood test, x rays and their compliance to treatment is evaluated. Results. Mean patients age was 65 y.o (+ 13). Two hundred seventeen patients were approached and 153 patients were enrolled (23 men and 130 women). Eleven patients refused to be part of the systematic follow up because they were satisfied with their family doctors osteoporosis management. Fifty-three were explained treatment and follow up and refused to participate. Thirteen patients (9%) dropped out after six months. One patient died. Twenty-one patients (13.7%) were already on bisphosphonates and 53 pts (34.6 %) had already sustained a fragility fracture. All patients were prescribed risedronate except three that were prescribed zoledronic acid or pamidronate for intolerance or contraindication to oral bisphosphonates. Up to now, we obtained 71% adherence and 91% persistence. After validation, 10% of the patients needed to be referred to a rheumatologist and 90% of the patients were managed by the clinical nurse specialist. Conclusion. Our multidisciplinary systematic follow up of osteoporotic fracture improved the osteoporosis treatment rate from 12 to 71 % in our orthopaedic surgery department. Clinical Nurse Specialists could represent the best approach to manage the underlying osteoporosis that leads to fragility fractures

Previously, we reported impaired biomechanical bone properties and inferior bone matrix quality in tachykinin1 (Tac1)-deficient mice lacking the sensory neuropeptide substance P (SP). Additionally, fracture callus development is affected by the absence of SP indicating a critical effect of sensory nerve fibers on bone health and regeneration. For α-calcitonin gene-related peptide (α-CGRP)-deficient mice, a profound distortion of bone microarchitecture has also been described. We hypothesize that SP and α-CGRP modulate inflammatory as well as pain-related processes and positively affect bone regeneration during impaired fracture healing under osteoporotic conditions. Therefore, this study investigates the effects of SP and α-CGRP on fracture healing and fracture-related pain processes under conditions of experimental osteoporosis using SP- and α-CGRP-deficient mice and WT controls. We ovariectomized female WT, Tac1−/− and α-CGRP−/− mice (age 10 weeks, all strains on C57Bl/6J background) and set intramedullary fixed femoral fractures in the left femora 28 days later. We analyzed pain threshold (Dynamic Plantar Aesthesiometer Test) and locomotion (recorded at day and night, each for 1 hour, EthoVision®XT, Noldus) at 5, 9, 13, 16 and 21 days after fracture. At each time point, fractured femora were prepared for histochemical analysis of callus tissue composition (alcian blue/sirius red staining). Pain threshold is significantly higher in Tac1−/− mice 13 days after fracture and tends to be higher after 21 days compared to WT controls. In contrast, touch sensibility was similar in α-CGRP−/− mice and WT controls but compared to Tac1−/− mice pain threshold was significantly lower in α-CGRP−/− mice 13 and 16 days and tends to be lower 21 days after fracture. Locomotion of Tac1−/− mice during daylight was by trend higher 9 days after fracture and significantly higher 16 days after fracture whereas nightly locomotion is reduced compared to WT mice. Analysis of locomotion during daylight or night revealed no differences between α-CGRP−/− and WT mice. During early fracture healing phase, 5 and 9 days after fracture, transition of mesenchymal to cartilaginous callus tissue tends to be faster in Tac1−/− mice compared to WT controls whereas no difference was observed during late stage of fracture healing, 13, 16 and 21 days after fracture. In contrast, callus tissue maturation seems to be similar in α-CGRP−/− and WT mice. Our data indicate different effects of SP and α-CGRP on fracture healing under conditions of experimental osteoporosis as a model for impaired bone tissue. Lack of α-CGRP seems to have no effects, but loss of SP affects locomotion throughout osteoporotic fracture healing and fracture-related pain processes during late phases of osteoporotic fracture healing. This indicates a modified role of SP during fracture healing under impaired versus healthy conditions, where SP changed early fracture-related pain processes and had no influence on callus tissue composition

Introduction. The proximal femur fracture in children is rare. Furthermore osteoporotic fracture associated with bone tumor make it difficult to decide the proper management method. The treatment plan should include both the treatment of the fracture and management of the condition responsible for the fracture. However, the reported literatures are rare and vary. Hypothesis. We identified the results of treatment associated with pathologic fracture of proximal femur in children. Material and Method. We retrospectively reviewed 56 patients who had fracture associated with benign bone femur between May 25th, 1995 and Jan. 14th, 2012. The patients’ mean age was 11.7(2–20) years old and follow-up duration was 55.3(5–132) months. Results. Fifty-six children with pathologic proximal femur fracture due to benign tumor were treated by various methods. Surgery consisted with combination of curettage, graft and internal fixation. We had 13(23%) complication. 6(11%) of them was related with fracture and 7(12%) of them was related with tumor. In six, malunion and shortening due to varus deformity developed after follow-up. In seven, recurrence was treated by curettage and internal fixation. There is no case of nonunion. Discussion and Conclusion. To manage the osteoporotic fracture of proximal femur in children, a thorough understanding of the risks associated with it is essential for decision making of increasing successful results

Summary Statement. The present study demonstrates the beneficial effects of strontium (Sr) modified calcium phosphate cement to improve new bone formation in a metaphyseal osteoporotic fracture defects in rats compared to calcium phosphate cement and empty defects. Keywords: strontium, fracture, calcium phosphate, bone formation. Introduction. Impaired fracture healing with subsequent implant failure is a dramatic problem in osteoporotic fractures. Biomaterials are of interest to stimulate fracture healing in osteoporotic defects and the objective of the current study is to investigate the effects of Strontium modified calcium phosphate cement (SrCPC) in a critical-size metaphyseal fracture defect of osteoporotic rats compared to calcium phosphate (CPC) and empty defect control group. Methods. 45 female Sprague-Dawley rats were randomized into 3 groups: SrCPC, CPC and empty defect (n=15 for each). A combinatorial approach of multi-deficiency diet for 3 months after bilateral ovariectomy was used for induction of osteoporosis. Left femur of all animals underwent a 4mm wedge-shaped metaphyseal osteotomy that was internally fixed with a T-shaped plate. The defect was then either filled with CPC or SrCPC and internally stabilised with a T shaped mini-plate. Empty defect served as a control. After 6 weeks femora were harvested followed by histological, histomorphometrical, immunohistochemical (bone-morphogenic protein 2, osteocalcin and osteoprotegerin), and molecular biology analysis (alkaline phosphatase, collagen10a1 and osteocalcin) to demonstrate the effects of the biomaterials on new bone formation. Time of flight secondary ion mass spectrometry (TOF-SIMS) technology was used to assess the distribution of released strontium ions and calcium appearance of newly formed bone. Results. Histomorphometric analysis showed a statistically significant increase in the bone formation at the tissue-implant interface in the SrCPC group (p<0.001). A statistically significantly more cartilage and unmineralised bone formation was also seen in the SrCPC group in comparision to the CPC group alone (p<0.05) and also to the empty defect (p<0.05) in the former fracture defect zone. These data were confirmed by the immunohistochemistry results which revealed an increase in bone-morphogenic protein 2, osteocalcin and osteoprotegerin and an increase in expression of genes responsible for bone formation viz. alkaline phosphatase, collagen10a1 and osteocalcin. TOF-SIMs analysis showed a higher release of Sr from the SrCPC into the interface region and related to a higher calcium content in this area compared to CPC. Discussion/Conclusion. SrCPC treatment showed enhanced new bone formation in a metaphyseal osteoporotic fracture defect of rats after 6 weeks compared to CPC-filled and empty defects in histomorphometry, immunochemistry and gene expression analysis. Strontium ranelate is a well-known anti-osteoporotic drug increasing bone formation and reducing bone resorption. As revealed by TOF-SIMS release of Sr out of the the SrCPC cement is most likely attributable for new bone formation. Therefore, Sr seems to be a good candidate not only for systemic treatment in osteoporosis but also in Sr-modification of biomaterials for local stimulation of new bone formation in osteoporotic fracture defects

Introduction. Distal femur fracture is a critical issue in orthopedic trauma, because it is difficult to manage especially in cases with intra-articular fracture. Osteoporosis may cause instability of implant and increase complications. Few studies investigate on the stability of distal femur osteoporotic fracture and the behaviors under cycling. Our hypothesis was that the stiffness of construct would decrease as cycling in osteoporotic bone. Materials and Methods. Seven cadaver specimens were used in this study. Relative bone density for each specimen was evaluated using CT scanning by three known calibration phantoms scanned simultaneously with the specimen. All cadaver specimens were divided normal (group 1) and osteoporosis (group 2) in accordance with the bone density. The titanium distal femur locking plates with 6 screws placed in distal femur condyle and 4 in shaft. A 10 mm gap with 65 mm proximal to the center of articular surface and a vertical fractural line between intra-articular were created to simulate AO C2 type fracture. Each specimen was cyclically loaded in two-phase at a frequency of 2 Hz. Phase 1 was set at 1000 N for 10000 cycles. In phase 2, the load was set at 2000 N for 10000 cycles. Then, the specimen was loaded up to failure at a rate of 5 mm/min. Stiffness was evaluated from the linear portion of load-displacement curve at 2000 cycle interval. Results and Discussion. Figure 1 showed the stiffness deterioration during cycling. Group 1 expresses the cadaveric specimen with normal bone density, and group 2 expresses osteoporosis. The stiffness of group 1 (with normal bone density) decreased for 26.2 % after 20000 cycles, however, group 2 (osteoporotic bone) revealed 90.3 % decay in stiffness. The stiffness decay observably when the load increased from 0 to 1000 N and from 1000 to 2000 N. The maximum load for group1 and group 2 were 4883±134 N and 2538 N, respectively. It can be found the normal bone density group showed intact circular hole, however, the osteoporotic bone revealed an oval contour. The subsidence of screws increased the risk of screw loosening and instability. It can be concluded that the bone quality and cyclic loading could be the important factors that affect the stability and failure strength of the construct

Introduction: Osteoporotic fractures affect certain bones more than others, suggesting that systemic bone loss is not the only underlying cause. We have shown that age-related intervertebral disc degeneration causes the anterior vertebral body (VB) to be stress-shielded in erect postures, and yet severely loaded when the spine is flexed (1). We hypothesise that this unequal loading causes exaggerated bone loss from the anterior vertebral body, making it vulnerable to fracture when the spine is heavily loaded in a forward stooping (flexed) posture. Materials and Methods: Regional volumetric bone mineral density (BMD) was measured in 35 thoracolumbar motion segments (aged 64–92 yrs) using dual-energy x-ray absorptiometry. The distribution of compressive stress was measured along the mid-sagittal diameter of each intervertebral disc using a miniature pressure transducer. Stresses were integrated over area to give the compressive force acting on the anterior and posterior halves of the VB (1). Motion segment compressive strength was measured in moderate flexion. Results: BMD of the anterior half of the VB was 26% (STD 13%) lower than that of the posterior half (p< 0.0001), was correlated with % load on the anterior VB in erect posture (r. 2. =0.48, p< 0.0001), and was a better predictor of motion segment compressive strength (in flexion) than was BMD of the whole vertebral body (r. 2. = 0.79 compared to r. 2. = 0.59). Conclusion: These results clearly support our hypothesis. It appears that intervertebral disc degeneration leads to exaggerated bone loss from the anterior VB, leaving it more vulnerable to fracture when the spine is flexed. Future work aims to confirm this important result on a larger number of specimens, and to compare the relative importance of disc degeneration and overall bone loss on vertebral compressive strength. Pollintine P et al (2001). SBPR Annual Meeting, Bristol. Backcare Research Award 2002

Aims

Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

The burden of non vertebral fractures on the National Health Service is enormous. Osteoporotic fractures have an associated morbidity and mortality and as a consequent incur heavy financial burden with a current cost to the National Health Service of some £1.7 billion per year, hip fractures accounting for the greater part. We know from our own local experience in the North of Ireland that this previous service had failed to target these fracture patients for secondary prevention of osteoporosis (Northern Ireland Colles Fracture Study). Although hip fractures account for only 7% of all fractures they result in the utilisation of 25% of acute orthopaedic beds. The silent nature of osteoporosis makes a diagnosis prior to fracture difficult and attendance at a fracture clinic may be the first opportunity to diagnose this condition and to intervene with anti-resportive treatment. An osteoporosis service commenced in Greenpark Health Care Trust in 1996. In 2001, guidelines (Crest guidelines) for the prevention and treatment of osteoporosis were established and in April 2003 a pilot study for the fracture liaison service commenced with the appointment of a Fracture Liaison Nursing Sister. The responsibility of this Nurse included:. Liaison and attendance at Out-Patient Fracture Clinic to ensure that all patients presenting with a low trauma fragility fracture were assessed and referred appropriately for bone densitometry. An education and awareness role for patients regarding osteoporosis and fall prevention. To conduct additional nurse led osteoporosis clinic at Green Park Healthcare Trust for patients referred from the Out-Patient Fracture Service at the Royal Victoria Hospital. Current activity levels include 18 fracture clinics per week at the Royal Victoria Hospital site with approximately 35 patients per clinic. To date, the Fracture Liaison Nurse has been able to attend 54% of these clinics. The patients were identified by Fracture Clinic chart reviews to identify those greater than fifty years of age with a low trauma fracture and approximately 115 charts were reviewed weekly. At risk patients were interviewed with approximately 35 interviews carried out weekly. Patients were then recruited first for assessment and dexa scanning, measurements were made at both lumbar spine L1-L4 and at the femoral neck with approximately 22 patients weekly recruited. An assessment of osteoporosis risk was made, a plain bed dexa scanner (lunar prodigy scanner) and treatment options were decided depending on the patients T score and according to the CREST Guidelines. The patients were given bone health advice at their scanning visit. Clinic activity was recorded on a database (Gismo) and a computer generated letter to the GP was produced. Provisional outcomes included arrangements to rescan after 24 months, referral to falls assessment and referral to a Consultant Specialist Osteoporosis Clinic. Results: To date, 198 patients have been scanned. 28 were male and 170 were female. BMD results were as follows (T score at hip or spine):. - Normal (0 to −1 SD) 16.6%. - Osteopenic (−1 to −2.5 SD) 46.7%. - Osteoporotic (> −2.5 SD) 36.7%. The mean age for those scanned was 66 years and 3 months. Osteoporotic risk factors identified include a previous fracture (18%). Early menopause (19%), fall history (12%), Back pain and height loss (18%), smokers (11%), family history of osteoporosis (13%), alcohol excess (5%). Outcome – no treatment recommended 26%, 13% were already on treatment, 17% were prescribed treatment, 43% were prescribed Calcium and Vitamin D, 27% a Bisphosphonate, 20% a Bisphosphonate and Calcium and Vitamin D and 12% Evista (serm). Patient follow-up outcome included a follow-up of dexa scan at 24 months 20%, no hospital review planned 74%, 7% referred to a Specialist Osteoporosis Clinic and 6% were referred for a FALLS assessment. Conclusion: This service has highlighted the high prevalence of osteoporosis in patients attending a Fracture Clinic. An osteoporosis fracture increases significantly the risk of future fracture. Our current programme for evaluation and managing a patient with osteoporosis fractures is currently being audited to measure quality of service, treatment outcome and trends

Introduction and Aims: There is good preliminary evidence that Bone Morphogenic Protein 7 (BMP-7) plays an integral role in fracture healing and metabolism of bone. It is not known, however, whether the implantation of an OP-1 device will enhance the rate of fracture healing in the presence of osteoporosis. The object of this study was to determine the effects of OP-1 on osteoporotic fracture healing in rats. Method: An open fracture of the mid-shaft of the femur was created in 60, three months post-surgical ovarectomised female Sprague Dawley rats. Thirty rats had OP-1 device with CMC putty implanted into the fracture site and 30 rats had CMC putty implanted without OP-1. The fracture was stabilised with a 1.4mm K-wire. Muscle and skin closed. Ten rats from each group were sacrificed at three time points – 12, 20 and 31 days post-surgery, and bilateral femurs harvested. The fractured femurs were analysed by DEXA scanning, high-resolution radiography, cross-sectional area, biomechanical assessment and histology. Results: There was a statistically significant acceleration of fracture healing with the use of OP-1 in DEXA, radiological, cross-sectional area and biomechanical analysis and a qualitative enhancement by histological analysis. Conclusion: The results show that an OP-1 device can enhance fracture healing in the presence of osteoporosis in a rat

Introduction

The purpose of this study was to establish whether men and women with a fragility hip fracture were equally investigated and treated for osteoporosis.

Aims. There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. Methods. A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining. Results. Healing capacities in DMP1 KD groups were impaired. Results showed that DMP1 KD significantly abolished vibration-enhanced fracture healing at week 6. DMP1 KD significantly altered the expression of osteocyte-specific markers. The lower mineralization rate in DMP1 KD groups indicated that DMP1 knockdown was associated with poor fracture healing process. Conclusion. The blockage of DMP1 would impair healing outcomes and negate LMHFV-induced enhancement on fracture healing. These findings reveal the importance of DMP1 in response to the mechanical signal during osteoporotic fracture healing. Cite this article: Bone Joint Res 2022;11(7):465–476

Objectives. The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. Materials and Methods. A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted. Results. Fracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures. Conclusion. For a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation. Cite this article: R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6–11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2

Aims. The optimal choice of management for proximal humerus fractures (PHFs) has been increasingly discussed in the literature, and this work aimed to answer the following questions: 1) what are the incidence rates of PHF in the geriatric population in the USA; 2) what is the mortality rate after PHF in the elderly population, specifically for distinct treatment procedures; and 3) what factors influence the mortality rate?. Methods. PHFs occurring between 1 January 2009 and 31 December 2019 were identified from the Medicare physician service records. Incidence rates were determined, mortality rates were calculated, and semiparametric Cox regression was applied, incorporating 23 demographic, clinical, and socioeconomic covariates, to compare the mortality risk between treatments. Results. From 2009 to 2019, the incidence decreased by 11.85% from 300.4 cases/100,000 enrollees to 266.3 cases/100,000 enrollees, although this was not statistically significant (z = -1.47, p = 0.142). In comparison to matched Medicare patients without a PHF, but of the same five-year age group and sex, a mean survival difference of -17.3% was observed. The one-year mortality rate was higher after nonoperative treatment with 16.4% compared to surgical treatment with 9.3% (hazard ratio (HR) = 1.29, 95% confidence interval (CI) 1.23 to 1.36; p < 0.001) and to shoulder arthroplasty with 7.4% (HR = 1.45, 95% CI 1.33 to 1.58; p < 0.001). Statistically significant mortality risk factors after operative treatment included age older than 75 years, male sex, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, chronic kidney disease, a concomitant fracture, congestive heart failure, and osteoporotic fracture. Conclusion. Mortality risk factors for distinct treatment modes after PHF in elderly patients could be identified, which may guide clinical decision-making. Cite this article: Bone Joint Res 2023;12(2):103–112

To explore a novel machine learning model to evaluate the vertebral fracture risk using Decision Tree model and train the model by Bone Mineral Density (BMD) of different compartments of vertebral body. We collected a Computed Tomography image dataset, including 10 patients with osteoporotic fracture and 10 patients without osteoporotic fracture. 40 non-fracture Vertebral bodies from T11 to L5 were segmented from 10 patients with osteoporotic fracture in the CT database and 53 non-fracture Vertebral bodies from T11 to L5 were segmented from 10 patients without osteoporotic fracture in the CT database. Based on the biomechanical properties, 93 vertebral bodies were further segmented into 11 compartments: eight trabecular bone, cortical shell, top and bottom endplate. BMD of these 11 compartments was calculated based on the HU value in CT images. Decision tree model was used to build fracture prediction model, and Support Vector Machine was built as a compared model. All BMD data was shuffled to a random order. 70% of data was used as training data, and 30% left was used as test data. Then, training prediction accuracy and testing prediction accuracy were calculated separately in the two models. The training accuracy of Decision Tree model is 100% and testing accuracy is 92.14% after trained by BMD data of 11 compartments of the vertebral body. The type I error is 7.14% and type II error is 0%. The training accuracy of Support Vector Machine model is 100% and the testing accuracy is 78.57%. The type I error is 17.86% and type II error is 3.57%. The performance of vertebral body fracture prediction using Decision Tree is significantly higher than using Support Vector Machine. The Decision Tree model is a potential risk assessment method for clinical application. The pilot evidence showed that Decision Tree prediction model overcomes the overfitting drawback of Support Vector Machine Model. However, larger dataset and cohort study should be conducted for further evidence

Osteoporosis is a worldwide disease resulting in the increase of bone fragility and enhanced fracture risk in adults. In the context of osteoporotic fractures, bone tissue engineering (BTE), i.e., the use of bone substitutes combining biomaterials, cells, and bone inducers, is a potential alternative to conventional treatments. Pre-clinical testing of innovative scaffolds relies on in vitro systems where the simultaneous presence of osteoblasts (OBs) and osteoclasts (OCs) is required to mimic their crosstalk and molecular cooperation for bone remodelling. To this aim, two composite materials based on type I collagen were developed, containing either strontium-enriched mesoporous bioactive glasses or rod-like hydroxyapatite nanoparticles. Following chemical crosslinking with genipin, the nanostructured materials were tested for 2–3 weeks with an indirect co-culture of human trabecular bone-derived OBs and buffy coat-derived OC precursors. The favourable structural and biological properties of the materials proved to successfully support the viability, adhesion, and differentiation of bone cells, encouraging a further investigation of the two bioactive systems as biomaterial inks for the 3D printing of more complex scaffolds for BTE

Introduction. Most common osteoporotic fracture. 20-30% of patients with OVFs are presented to hospital while 2.2 million remain undiagnosed, as diagnosis is usually opportunistic. 66,000 OVFs occur annually in the UK with increase by 18,000 cases a year until 2025. 20% chance of another OVF in next 12 months and 3 times risk of hip fracture. Acute painful OVFs poorly tolerated by infirm elderly patients, leading to significant morbidity and 8 times increase in age-adjusted mortality. Materials and Methods. Classify fracture severity and patents with ovfs in 12-month period. To assess follow-up status and if kyphoplasty was offered within 6 weeks as per NICE guidelines. To introduce Royal Osteoporosis Society and GIRFT guidelines on management of symptomatic osteoporotic vertebral fractures. Results. Total no. of patients- 62. Initial pain assessment=40. Pain assessed at ≤6 weeks- 21. Duration from decision to operate to kyphoplasty 8.7 weeks. 11% had kyphoplasty of which 50% noted improvement in pain. 11 deaths. Nearly similar findings to NoSH study. Conclusion. To improve pain assessment on admission of patients with acute osteoporotic vertebral fractures. To follow GIRFT guidelines for early assessment and intervention in patients with acute osteoporotic vertebral fractures to improve pain, mobility and early discharge from hospital. Conflicts of interest. None. Sources of funding. None