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Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 59 - 59
1 Jul 2020
Chim Y Cheung W Chow SK
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 75 - 75
1 Sep 2012
Delisle J Fernandes JC Troyanov Y Perreault S
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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


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 47 - 47
1 Aug 2020
Niedermair T Straub R Grässel S
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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


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_2 | Pages 50 - 50
1 Jan 2016
Hsiao C Tsai Y Yang T Hsu C Tu Y
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_III | Pages 17 - 17
1 Feb 2012
Hanusch B Fordham J Gregg P
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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.

Methods

A retrospective review was carried out including 91 patients (48 females, 43 males) who were admitted with a fragility hip fracture between March 2003 and April 2004. Data about age, sex, investigations and medication were collected from the case notes, GP surgeries and the bone densitometry database. Investigations and treatment were compared with current guideline recommendations (SIGN 2003, NICE 2005). Data were analysed using SPSS Version 13.0.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 39 - 39
1 Aug 2020
Ma C Li C Jin Y Lu WW
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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


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 77 - 77
1 Jul 2020
Choy VMH Wong RMY Chow SK Cheung W Cheng J
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Age-related fragility fractures are highly correlated with the loss of bone integrity and deteriorated morphology of the osteocytes. Previous studies have reported low-magnitude high-frequency vibration(LMHFV) promotes osteoporotic diaphyseal fracture healing to a greater extent than in age-matched normal fracture healing, yet how osteoporotic fractured bone responds to the mechanical signal has not been explored. As osteocytes are prominent for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance fracture healing in ovariectomized metaphyseal fracture through morphological changes and mineralisation in the osteocyte Lacuno-canalicular Network(LCN). As most osteoporotic fractures occur primarily at the metaphysis, an osteoporotic metaphyseal fracture model was established. A total of 72 six-month old female Sprague-Dawley rats (n=72) were obtained(animal ethical approval ref: 16–037-MIS). Half of the rats underwent bilateral ovariectomy(OVX) and kept for 3 months for osteoporosis induction. Metaphyseal fracture on left distal femur was created by osteotomy and fixed by a plate. Rats were then randomized to (1) OVX+LMHFV(20 mins/day and 5 days/week, 35Hz, 0.3g), (2) OVX control, (3) SHAM+LMHFV, (4) SHAM control. Assessments of morphological structural changes, functional markers of the LCN(Scanning Electron Microscopy, FITC-Imaris, immunohistochemistry), mineralization status(EDX, dynamic histomorphometry) and healing outcomes(X-ray, microCT, mechanical testing) were performed at week 1, 2 and 6 post-fracture. One‐way ANOVA with post-hoc test was performed. Statistical significance was set at p < 0.05. Our results showed LMHFV could significantly enhance the morphology of the LCN. There was a 65.3% increase in dendritic branch points(p=0.03) and 93% increase in canalicular length(p=0.019) in the OVX-LMHFV group at week 2 post-fracture. Besides, a similar trend was also observed in the SHAM+LMHFV group, with a 43.4% increase in branch points and 53% increase in canaliculi length at week 2. A significant increase of E11 and DMP1 was observed in the LMHFV groups, indicating the reconstruction of the LCN. The decreasing sclerostin and increasing FGF23 at week 1 represented the active bone formation phase while the gradual increase at week 6 signified the remodelling phase. Furthermore, Ca/P ratio, mineral apposition rate and bone formation rate were all significantly enhanced in the OVX+LMHFV group. The overall bone mineral density in BV was significantly raised in the OVX+LMHFV group at week 2(p=0.043) and SHAM+LMHFV at week 6(p=0.04). Quantitative analysis of microCT showed BV/TV was significantly increased at week 2 in OVX+LMHFV group(p=0.008) and week 6(p=0.001) in both vibration groups. In addition, biomechanical testing revealed that the OVX+LMHFV group had a significantly higher ultimate load(p=0.03) and stiffness(p=0.02) at week 2. To our best knowledge, this is the first report to illustrate LMHFV could enhance osteocytes' morphology, mineralisation status and healing outcome in a new osteoporotic metaphyseal fracture animal model. Our cumulative data supports that the mechanosensitivity of bone would not impair due to osteoporosis. The revitalized osteocyte LCN and upregulated osteocytic protein markers implied a better connectivity and transduction of signals between osteocytes, which may foster the osteoporotic fracture healing process through an enhanced mineralisation process. This could stimulate further mechanistic investigations with potential translation of LMHFV to our fragility fracture patients


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_11 | Pages 56 - 56
1 Nov 2022
Thimmegowda A Gajula P Phadnis J Guryel E
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Abstract. Aim. To identify the difference in infection rates in ankle fracture surgery in Laminar and Non Laminar flow theatres. Background. The infection rates in ankle fracture surgery range between 1–8%. The risk factors include diabetes, alcoholism, smoking, open fractures, osteoporotic fractures in the elderly, and high BMI. Laminar flow has been shown to reduce infections in Arthroplasty surgeries. Therefore, it has become mandatory to use in those procedures. However, it's not the same with ankle fracture surgery. Materials and Methods. It was a retrospective study. The data was collected over a 5 year period between 2015 and 2020. It was collected from Blue spier, Panda, and theatre register. There were 536 cases in each group i.e. Laminar flow (LF) and Non-Laminar flow (NLF). The variables looked at were: 1. Superficial and deep infection rates in LF and NLF theatres, 2. The number of open fractures, 3. Type of ankle fractures (Bimalleolar, Trimalleolar), 4. The number of infected cases who had external fixation prior to ORIF, 5. The number of cases that had Plastics reconstructive procedures, and 6. The grade of the operating surgeon. Conclusions. Superficial infection rate between NLF and LF was not significantly different 11.5% vs 10.3%. The deep infection rate was statistically significant against NLF theatres at 6.34% vs 4.29%. The open fracture was a major contributing factor for deep SSI (14.7% vs 26%). The application of an external fixator in LF and NLF theatres did not alter the infection. rates. Bimalleolar fractures were associated with a higher infection rate


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 78 - 78
1 Dec 2022
Willms S Matovinovic K Kennedy L Yee S Billington E Schneider P
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The widely used Fracture Risk Assessment Tool (FRAX) estimates a 10-year probability of major osteoporotic fracture (MOF) using age, sex, body mass index, and seven clinical risk factors, including prior history of fracture. Prior fracture is a binary variable in FRAX, although it is now clear that prior fractures affect future MOF risk differently depending on their recency and site. Risk of MOF is highest in the first two years following a fracture and then progressively decreases with time – this is defined as imminent risk. Therefore, the FRAX tool may underestimate true fracture risk and result in missed opportunities for earlier osteoporosis management in individuals with recent MOF. To address this, multipliers based on age, sex, and fracture type may be applied to baseline FRAX scores for patients with recent fractures, producing a more accurate prediction of both short- and long-term fracture risk. Adjusted FRAX estimates may enable earlier pharmacologic treatment and other risk reduction strategies. This study aimed to report the effect of multipliers on conventional FRAX scores in a clinical cohort of patients with recent non-hip fragility fractures. After obtaining Research Ethics Board approval, FRAX scores were calculated both before and after multiplier adjustment, for patients included in our outpatient Fracture Liaison Service who had experienced a non-hip fragility fracture between June 2020 and November 2021. Patients age 50 years or older, with recent (within 3 months) forearm (radius and/or ulna) or humerus fractures were included. Exclusion criteria consisted of patients under the age of 50 years or those with a hip fracture. Age- and sex-based FRAX multipliers for recent forearm and humerus fractures described by McCloskey et al. (2021) were used to adjust the conventional FRAX score. Low, intermediate and high-risk of MOF was defined as less than 10%, 10-20%, and greater than 20%, respectively. Data are reported as mean and standard deviation of the mean for continuous variables and as proportions for categorical variables. A total of 91 patients with an average age of 64 years (range = 50-97) were included. The majority of patients were female (91.0%), with 73.6% sustaining forearm fractures and 26.4% sustaining humerus fractures. In the forearm group, the average MOF risk pre- and post-multiplier was 16.0 and 18.8, respectively. Sixteen percent of patients (n = 11) in the forearm group moved from intermediate to high 10-year fracture risk after multiplier adjustment. Average FRAX scores before and after adjustment in the humerus group were 15.7 and 22.7, respectively, with 25% (n = 6) of patients moving from an intermediate risk to a high-risk score. This study demonstrates the clinically significant impact of multipliers on conventional FRAX scores in patients with recent non-hip fractures. Twenty-five percent of patients with humerus fractures and 16% of patients with forearm fractures moved from intermediate to high-risk of MOF after application of the multiplier. Consequently, patients who were previously ineligible for pharmacologic management, now met criteria. Multiplier-adjusted FRAX scores after a recent fracture may more accurately identify patients with imminent fracture risk, facilitating earlier risk reduction interventions


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 86 - 86
1 Jul 2020
Ashjaee N Johnston G Johnston J
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Distal radius fractures are the most common osteoporotic fractures among women. The treatment of these fractures has been shifting from a traditional non-operative approach to surgery, using volar locking plate (VLP) technology. Surgery, however, is not without risk, complications including failure to restore an anatomic reduction, fracture re-displacement, and tendon rupture. The VLP implant is also marked by bone loss due to stress-shielding related to its high stiffness relative to adjacent bone. Recently, a novel internal, composite-based implant, with a stiffness less than the VLP, was designed to eradicate the shortcomings associated with the VLP implant. It is unclear, however, what effect this less-stiff implant will have upon adjacent bone density distributions long-term. The objective of this study was to evaluate the long-term effects of the two implants (the novel surgical implant and the gold-standard VLP) by using subject-specific finite element (FE) models integrated with an adaptive bone formation/resorption algorithm. Specimen: One fresh-frozen human forearm specimen (female, age = 84 years old) was imaged using CT and was used to create a subject-specific FE model of the radius. Finite element modeling: In order to simulate a clinically relevant (unstable) fracture of the distal radius, a wedge of bone was removed from the model, which was approximately 10 mm wide and centered 20 mm proximal to the tip of the radial styloid. Bone remodeling algorithm: A strain-energy density (SED) based bone remodeling theory was used to account for bone remodeling. With this approach, bone density decreased linearly when SED per bone density was less than 67.5 µJ/g and increased when it was more than 232.5 µJ/g. When it was in the lazy zone (67.5 to 232.5 µJ/g), no changes in density occurred. Boundary conditions: A 180 N quasi-static force representing the scaphoid, and a 120 N quasi-static force representing the lunate was applied to the radius. The midshaft of the radius was constrained. FE outcomes: To examine the effects of stress shielding associated with each implant, the long-term changes of bone density within proximal transverse cross-sections of radius were inspected. The regional density analysis focused on three transverse cross-sections. The transverse cross-sections were positioned proximal to the subchondral plate, and were distanced 50 (cross-section A), 57 (cross-section B), and 64 mm (cross-section C) from the subchondral endplate. For both implants in all three cross-sections, cortical bone was reserved completely at the volar side. On the dorsal side, the cortical bone was completely resorbed in the VLP model. In all cross-sections, the averaged resultant density was higher for the “novel implant”. The difference ranged from 33% (cross-section A) to 36% (cross-section C) in favor of the “novel implant”. On average, the density values of the novel implant were 34% higher in transverse cross-sections (A, B, and C). This study showed that the novel implant offered higher density distributions compared to the VLP, which suggests that the novel implant may be superior to the VLP in terms of avoiding stress shielding


Bone & Joint Research
Vol. 13, Issue 8 | Pages 411 - 426
28 Aug 2024
Liu D Wang K Wang J Cao F Tao L

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Methods

We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_14 | Pages 13 - 13
1 Jul 2016
Sha S Holt G
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Although there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that they may be associated with rare atypical femoral fractures. 1480 patients of proximal femur and shaft fractures over a period of 2 years from Jan 2014 to Jan 2016 were retrospectively reviewed in Gloucestershire Hospitals NHS trust. Hospital trauma database was used.195 patients had fractures in subtrochancteric and femoral shaft area. 11 patients had atypical femur fractures as defined by American society for bone and mineral research (ASBMR) task force 2013, revised criteria. Ten were female, one was male. Patients were aged from 68 to 97. In 6 patients, fractures were in the shaft, 5 in subtrochancteric area and 4 patients out of these had bilateral fractures. 10 out of 11 patients were on bisphosphonates. 4 patients had delayed diagnosis. 5 out of 11 patients did not have contralateral femoral x-rays. Treatment, 9 patients had intramedullary nail, one blade plate, and one treated conservatively. One patient in the IM group, had bilateral nailing. Average follow up was 7.6 months (range 1 to 16 months). At the end of the study, only 4 had united, 6 had not united and one not followed up. 4 out of 7 had low Vitamin D levels, 3 out of 7 had their bisphosphonate treatment stopped and 2 had histology which showed necrotic bone with trabeculae surrounded by fibrosis. Increasing number of patients are on bisphosphonates for osteoporosis. Atypical femur fractures from bisphosphonates are often occult, often bilateral, with delayed healing. Patients on bisphosphonatetreatment should be advised to report any thigh or groin pain. Painful incomplete fractures need treatment with cephalomedullary nailing. Bone biology needs correcting by stopping bisphosphonatesand administering calcium & vitamin D supplements. Implications: We need to raise awareness amongst treating clinicians and have national guidelines


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_6 | Pages 4 - 4
1 May 2015
Shah S Divekar M
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There is strong evidence to support the use of bisphosphonates in the prevention of osteoporotic fractures. There has, however, been growing concern that prolonged use of bisphosphonates can lead to the development of atypical femoral fractures and can protract healing time. We conducted a retrospective study looking at all femoral fractures between 2011–2013. Of 109 patients, 12 were diagnosed with atypical femoral fractures. The mean age of presentation was 69 (52–92). Five patients held no history of falls and presented with hip pain. The remaining seven sustained minor falls. Seven patients were on bisphosphonates on presentation. Bisphosphonates were discontinued in five cases and continued in two. Bisphosphonates commenced in one patient who subsequently developed second fracture. All fractures were managed with intramedullary nailing. Healing time was prolonged in all cases (mean healing time 7.3 months). Three patients needed further surgeries to achieve union. Overall, we observed that patients with prolonged bisphosphonate intake were more susceptible to atypical fractures with a delayed recovery time. Increasing awareness amongst medical professionals may aid timely diagnoses and subsequent referrals to orthopaedics. Recognition of these fractures may also permit early discontinuation of bisphosphonates, which may prevent future fractures and reduced healing times


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 11 - 11
1 Nov 2016
Vachhani K Wang Y Nam D Whyne C
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Predictable fracture healing fails to occur in 5–10% of cases. This is particularly concerning among individuals with osteoporosis. With an increasing aging population, one in three women and one in five men above the age of 50 experience fragility fractures. As such, there is a critical need for an effective treatment option that could enhance fracture healing in osteoporotic bone. Lithium, the standard treatment for bipolar disorder, has been previously shown to improve fracture healing through modulation of the Wnt/beta-catenin pathway. We optimised the precise oral lithium administration parameters to improve mechanical strength and enhance healing of femoral fractures in healthy rats. A low dose of Lithium (20 mg/kg) administered seven days post fracture for a two week duration improved torsional strength by 46% at four weeks post fracture compared to non-treated animals. Application of lithium to enhance fracture healing in osteoporotic bone would have a significant healthcare impact and requires further study. Aim: To evaluate the efficacy of optimal lithium administration post fracture on quality of fracture healing in a rat osteoporotic model. Hypothesis: Lithium treatment in osteoporotic rats will improve the structural and mechanical properties of the healing bone despite the impaired nature of bone tissue. Sprague Dawley female rats (∼350 g, age ∼3 months) were bilaterally ovariectomised and maintained for 3 months to establish the osteoporotic phenotype. A unilateral, closed mid-shaft femoral fracture was created using a weight-drop apparatus. At seven days post fracture, the treatment group received 20 mg/kg-wt lithium chloride via oral gavage daily for 14 days. The control group received an equivalent dose of saline. All animals were sacrificed at day 28 and the femurs harvested bilaterally. Treatment efficacy was evaluated based on torsional loading and stereologic analysis. Lithium treatment positively impacted the healing femurs, with an average yield torque ∼1.25-fold higher than in the saline group (200±36 vs. 163±31 N-mm, p=0.15). Radiographically, the lithium-treated rats had a high level of restored periosteal continuity, larger bridging and intercortical callus at the fracture site. These hallmarks of healing were generally absent in the saline group. The Lithium group had significantly higher total volume (624±32 vs. 568±95 mm3), lower bone volume fraction (41±4 vs. 50±5%) and higher theoretical torsional rigidity (477±50 vs. 357±93 kN-mm2) compared to the saline group. Torsional strength and stereology values were similar for the contralateral femurs of the two groups. Lithium was found to enhance fracture healing in osteoporotic bone under the dosing regimen optimised in healthy femora. This is promising data as treatment represents an easily translatable pharmacological intervention for fracture healing that may ultimately reduce the healthcare burden of osteoporotic fractures


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_13 | Pages 19 - 19
1 Jun 2016
Nataraj A Harikrishna M Puduval M Sridhar M
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Vitamin D is vital for bone health because it assists in the absorption and utilisation of calcium. Vitamin D deficiency may predispose individuals to developing osteoporosis and subsequent osteoporotic fracture. There are various studies in elderly females with hip fractures correlating the low bone mineral density (BMD) with vitamin D levels. But very few studies have evaluated the influence on elderly males. Therefore this study was conducted. All male patients aged more than 50 years presenting to orthopaedic department, in JIPMER, Puducherry, with either fracture neck of femur or intertrochanteric fracture were included. Serum vitamin D level was assessed in them and BMD of both the hips was evaluated by DEXA scan. The vitamin D levels, T-scores, Z-scores were then analysed and correlated. Of the total 41 patients evaluated 21 (51%) had fracture neck of the femur and 20 (49%) patients had intertrochanteric fractures. We found that 11 (26.8%) patients had osteoporosis, 17 (41.5%) had osteopenia, and 13 (31.7%) had normal values. The mean value of total T-scores on fracture side was −1.55 and on no fracture side was −1.88. Among them 9 (22%) patients had vitamin D level <20 ng /mL, 15 (36%) had levels between 20ng–30ng/mL and 17 (41%) had >30ng/mL. Total T-score and Z-score on fracture side and no fracture side showed no correlation with vitamin D (p value >0.05) in these patients. We found significant osteoporosis in both neck and trochanteric regions on both fracture and no fracture sides, yet we had some patients with trochanteric fracture and some with neck fracture on only one side. In view of this other factors like mode of injury, velocity of injury, muscle wasting might have contributed significantly to the type of fracture and side involved. The BMD was found to be lower in patients with neck of femur fracture compared to intertrochanteric fracture, but no correlation was found between vitamin D and BMD scores at neck and trochanteric region. From this study it appears that there is no direct relationship between the vitamin D level and BMD in elderly males with hip fractures. It may emphasise that in male patients with hip fractures vitamin D may not have critical role in development of osteoporosis. The treatment of such patients with vitamin D supplements to prevent hip fractures is still debatable. However further studies in very large groups and controls may bring more light on this subject


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 129 - 129
1 May 2012
Findlay D
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Osteocytes (OCY) are the end stage differentiation cells of the osteoblast lineage, and are incorporated in the bone matrix during bone formation. In doing so, OCY control the mineralisation of osteoid. OCY form a dense inter-connected network of cell bodies and cell processes throughout the mineralised matrix of bone. OCY viability depends on interstitial fluid flow along the OCY canaliculi, driven by pulsatile blood flow and loading of the skeleton. Maintenance of the density and viability of OCY are essential for bone health because OCY perform many important functions in bone. Firstly, OCY appear to initiate bone repair of bone microdamage. Secondly, OCY are almost certainly the cells, which initiate new bone formation in response to increased loading of bone. Thirdly, OCY are able to regulate the amount of new bone formation in bone remodelling cycles, at least in part by the production of a molecule called sclerostin (SCL). Mutations in the SCL gene, or deletion of the SCL gene in transgenic mice, are associated with particularly dense, fracture resistant bones. This information has led to development of anti-SCL antibodies as a potential anabolic therapy for bones. Bone loss in ovariectomised aged rats was shown recently to be reversed by treatment with neutralising SCL antibodies. There is also some data to suggest that these antibodies may promote fracture healing. Reduced OCY viability and/or density have been reported in association with osteoporotic fracture. OCY viability seems to be dependent on skeletal loading, adequate skeletal blood flow and estrogen in females. OCY viability is adversely affected by hypoxia, unloading of the skeleton and pharmacobiology, such as chronic exposure to glucocorticoids. Both micro and macro-fractures result in disruption of the OCY network, as do procedures such as drilling and cutting of bone. Because of the important roles of OCY in bone, new approaches to bone health may require the identification of agents to protect these cells from harmful influences in disease and ageing


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 24 - 24
1 Feb 2012
Prasad N Sunderamoorthy D Martin J Murray J
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To discover whether orthopaedic surgeons follow the BOA guidelines for secondary prevention of fragility fractures, a retrospective audit on neck of femur fractures treated in our hospital in October/November 2003 was carried out. There were 27 patients. Twenty-six patients (96%) had full blood count measured. LFT and bone-profile were measured in 18 patients (66%). Only nine patients (30%) had treatment for osteoporosis (calcium and vitamin D). Only one patient was referred for DEXA scan. Steps were taken to create better awareness of the BOA guidelines among junior doctors and nurse practitioners. In patients above 80 years of age it was decided to use abbreviated mental score above 7 as a clinical criterion for DEXA referral. A hospital protocol based on BOA guidelines was made. A re-audit was conducted during the period August-October 2004, with 37 patients. All of them had their full blood count and renal profile checked (100%). The bone-profile was measured in 28 (75.7%) and LFT in 34 (91.9%) patients. Twenty-four patients (65%) received treatment in the form of calcium + Vit D (20) and bisphosphonate (4). DEXA scan referral was not indicated in 14 patients as 4 of them were already on bisphosphonates and 10 patients had an abbreviated mental score of less than 7. Among the remaining 23 patients, nine (40%) were referred for DEXA scan. This improvement is statistically significant (p=0.03, chi square test). The re-audit shows that, although there is an improvement in the situation, we are still below the standards of secondary prevention of fragility fractures with 60% of femoral fragility fracture patients not being referred for DEXA scan. A pathway lead by a fracture liaison nurse dedicated to osteoporotic fracture patients should improve the situation


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 10 | Pages 1313 - 1320
1 Oct 2012
Middleton RG Shabani F Uzoigwe CE AS Moqsith M Venkatesan M

Osteoporosis is common and the health and financial cost of fragility fractures is considerable. The burden of cardiovascular disease has been reduced dramatically by identifying and targeting those most at risk. A similar approach is potentially possible in the context of fragility fractures. The World Health Organization created and endorsed the use of FRAX, a fracture risk assessment tool, which uses selected risk factors to calculate a quantitative, patient-specific, ten-year risk of sustaining a fragility fracture. Treatment can thus be based on this as well as on measured bone mineral density. It may also be used to determine at-risk individuals, who should undergo bone densitometry. FRAX has been incorporated into the national osteoporosis guidelines of countries in the Americas, Europe, the Far East and Australasia. The United Kingdom National Institute for Health and Clinical Excellence also advocates its use in their guidance on the assessment of the risk of fragility fracture, and it may become an important tool to combat the health challenges posed by fragility fractures.


Bone & Joint 360
Vol. 5, Issue 1 | Pages 26 - 28
1 Feb 2016


Bone & Joint Research
Vol. 4, Issue 6 | Pages 99 - 104
1 Jun 2015
Savaridas T Wallace RJ Dawson S Simpson AHRW

Objectives

There remains conflicting evidence regarding cortical bone strength following bisphosphonate therapy. As part of a study to assess the effects of bisphosphonate treatment on the healing of rat tibial fractures, the mechanical properties and radiological density of the uninjured contralateral tibia was assessed.

Methods

Skeletally mature aged rats were used. A total of 14 rats received 1µg/kg ibandronate (iban) daily and 17 rats received 1 ml 0.9% sodium chloride (control) daily. Stress at failure and toughness of the tibial diaphysis were calculated following four-point bending tests.