Objectives. Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. Methods. MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts. Results. MSCs from OVX rats migrate significantly (p < 0.05) less towards SDF-1 (9%, . sd. 5%) compared with MSCs from adult (15%, . sd. 3%) and young rats (25%, . sd. 4%). Cells transfected with CXCR4 migrated significantly more towards SDF-1 compared with non-transfected cells, irrespective of whether these cells were from OVX (26.5%, . sd. 4%), young (47%, . sd. 17%) or adult (21%, . sd. 4%) rats. Transfected MSCs differentiated to osteoblasts express CXCR4 but do not migrate towards SDF-1. Conclusions. MSC migration is impaired by age and osteoporosis in rats, and this may be associated with a significant reduction in bone formation in osteoporotic patients. The migration of stem cells can be ameliorated by upregulating CXCR4 levels which could possibly enhance fracture healing in osteoporotic patients. Cite this article: A. Sanghani-Kerai, M. Coathup, S. Samazideh, P. Kalia, L. Di Silvio, B. Idowu, G. Blunn. Osteoporosis and ageing affects the migration of stem cells and this is ameliorated by transfection with CXCR4. Bone Joint Res 2017;6:–365. DOI: 10.1302/2046-3758.66.BJR-2016-0259.R1

Objectives

To assess the sensitivity and specificity of self-reported osteoporosis compared with dual energy X-ray absorptiometry (DXA) defined osteoporosis, and to describe medication use among participants with the condition.

Purpose: To evaluate the impact of the Osteoporosis Exemplary Care Program (OECP) on orthopaedic surgeons’ practice patterns at St. Michael’s Hospital. Methods: A chart audit was performed to collect data on two groups of 54 patients identified with fragility fractures. The intervention group consisted of patients treated during the first four months of the OECP, while the control (pre-intervention) group consisted of age, sex, and fracture-type matched patients treated prior to implementation of the OECP. Characteristics of the intervention and control groups were compared using chi-square tests. Multivariable logistic regression analysis was then performed to identify significant correlates of OP care. Results: Preliminary results from 54 matched pairs (108 patients in total) indicate that the OECP group was more likely to have OP risk or OP diagnosis documented (unadjusted OR 2.49; 95% CI 1.05–5.87), as well as to be referred for further investigation of OP (unadjusted OR 3.08; 95% CI 1.37–6.91) or to receive treatment or follow-up related to OP (unadjusted OR 9.01; 95% CI 3.77–21.54). As one surgeon was known to have been providing a high level of OP care prior to implementation of the OECP, the analysis was repeated after removing his patients. In addition, the analysis was repeated after removing patients who were already being treated for OP at the time of their fragility fracture. In both cases, larger increases in the likelihood of OP documentation and care were observed. Through multivariable analysis, age and fracture type (i.e. wrist vs. hip) were found to be significant correlates of having received OP care for patients with fragility fractures treated prior to implementation of the OECP. Following implementation of the OECP, there were no significant correlates of receiving OP care. Conclusions: Preliminary results indicate that the OECP had a significant impact on orthopedic surgeons’ practice patterns. Following implementation of the OECP all patients were equally likely to receive appropriate referral, treatment, and follow-up whereas, prior to implementation of the program, age and fracture type affected the likelihood that a patient would receive such care. Funding: Commerical funding. Funding Parties: The Osteoporosis Exemplary Care Program is funded by an unrestricted program grant provided by Merck Frosst Canada and Co. Dr. Beaton is supported by a New Investigators Award, from the Canadian Institute of Health Research

Osteoporosis is a progressive, chronic disease of bone metabolism, characterized by decreased bone mass and mineral density, predisposing individuals to an increased risk of fractures. The use of animal models, which is the gold standard for the screening of anti-osteoporosis drugs, raises numerous ethical concerns and is highly debated because the composition and structure of animal bones is very different from human bones. In addition, there is currently a poor translation of pre-clinical efficacy in animal models to human trials, meaning that there is a need for an alternative method of screening and evaluating new therapeutics for metabolic bone disorders, in vitro. The aim of this project is to develop a 3D Bone-On-A-Chip that summarizes the spatial orientation and mutual influences of the key cellular components of bone tissue, in a citrate and hydroxyapatite-enriched 3D matrix, acting as a 3D model of osteoporosis. To this purpose, a polydimethylsiloxane microfluidic device was developed by CAD modelling, stereolithography and replica molding. The device is composed by two layers: (i) a bottom layer for a 3D culture of osteocytes embedded in an osteomimetic collagen-enriched matrigel matrix with citrate-doped hydroxyapatite nanocrystals, and (ii) a upper layer for a 2D perfused co-culture of osteoblasts and osteoclasts seeded on a microporous PET membrane. Cell vitality was evaluated via live/dead assay. Bone deposition and bone resorption was analysed respectively with ALP, Alizarin RED and TRACP staining. Osteocytes dendrite expression was evaluated via immunofluorescence. Subsequently, the model was validated as drug screening platform inducing osteocytes apoptosis and administrating standard anti-osteoporotic drugs. This device has the potential to substitute or minimize animal models in pre-clinical studies of osteoporosis, contributing to pave the way for a more precise and punctual personalized treatment

Abstract. Objectives. Osteoporotic fractures tend to be more challenging than fractures in healthy bone and the efficacy of metal screw fixation decreases with decreasing bone mineral density making it more difficult for such screws to gain purchase. This leads to increased complication rates such as malunion, non-union and implant failure (1). Bioresorbable polymer devices have seen clinical success in fracture fixation and are a promising alternative for metallic devices but are rarely used in the osteoporotic population. To address this, we are developing a system that may allow osteoporotic patients to avail of bioresorbable devices (2) but it is important to establish if patients have any reservations about having a plastic resorbable device instead of a metal one. Therefore the aim of this study was to explore the acceptability of bioresorbable fracture fixation devices to people with osteoporosis. Methods. A cross sectional descriptive study was conducted in a UK wide population using convenience sampling. An online survey comprising nine survey questions and nine demographic questions was developed in Microsoft Teams and tested for face validity in a small pilot study (n=6). Following amendments and ethical approval, the survey was distributed by the Royal Osteoporosis Society on their website and social media platforms. People were invited to take part if they lived in the UK, were over 18 years old and had been diagnosed with osteoporosis. The survey was open for three weeks in May 2023. Responses were analysed using descriptive statistics. Results. There were 112 responses. Eight participants had not been diagnosed with osteoporosis and therefore did not meet the study criteria. Of the remaining 104, 102 were female and 2 were male and 102 were white (2 chose not to disclose their ethnicity). The majority of participants were aged 55–64 (34.6%) or 65–74 (37.5%), were college/university educated (38.5%) and had previously sustained a fragility fracture (52.9%). Only 3.9% of participants had heard of bioresorbable fracture fixation devices compared to 62.5% for metal devices. Most people were unsure if they would trust one type of device over the other (58.7%) and would ask for more information if their surgeon were to suggest using a bioresorbable device to fix their fracture (61.5%). The most commonly reported concerns were about device safety and efficacy: toxicity of the degradation products and the device breaking down too early before the fracture had healed. Two participants cited environmental concerns about increased use of plastics as a reason they would decline such a device. Conclusions. As expected, participants had little to no knowledge of bioresorbable polymer fixation devices. In general, they were willing to be guided by their surgeon but would require supporting information on the safety and efficacy of their long-term use. The results of this study show that it will be important to have relevant and understandable information to give patients when recommending these devices as treatments to ensure and support a shared-decision approach to patient care. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age. Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts. Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency. Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers. These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis

Osteoporosis is a common problem in postmenopausal women and the elderly. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates glucocorticoids (GCs) in vivo, which is a considerable potential target as treatment for osteoporosis. Previous studies have demonstrated its effect on osteogenesis, and our study aimed to demonstrate its effect on osteoclast activation. In vivo, we used 11β-HSD1 knock-off (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, In vivo, We used 11β-HSD1 knockoff (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, bone marrow-derived macrophages (BMM) and bone marrow mesenchymal stem cell (BMSC) of KO and C57BL6/J mice were extracted to test their osteogenic and osteoclastic abilities. We then created osteoclastic 11β-HSD1 elimination mice (Ctsk::11β-HSD1fl/fl) and treated them with OVX. Micro-CT analysis, H&E, immunofluorescence staining, and qPCR were performed. Finally, we conducted the high-throughput sequencing to find out 11β-HSD1 and osteoclast activation related genes. We collected 6w samples after modeling. We found that KO mice were resistant to loss of bone trabeculae. The same effect was observed in osteoclastic 11β-HSD1 elimination mice. Meanwhile, BVT-2733, a classic inhibitor of 11β-HSD1, inhibited the osteoclast effect of cells without affecting osteogenic effect in vitro. High-throughput sequencing suggested that glucocorticoid receptor (GR) may play a key role in the activation of osteoclasts, which was verified by immunofluorescence staining and WB in vivo and in vitro. In the process of osteoporosis, 11β-HSD1 expression of osteoclasts is abnormally increased, which may be a new target for inhibiting osteoclast activation and treating osteoporosis

Osteoporosis is a worldwide disease with a high prevalence in elderly population; it results in bone loss and decreased bone strength that lead to low-energy fractures. Since antiresorptive treatments could lead to long-term adverse effects, the ERC BOOST project aims to propose a biomimetic 3D-printed scaffold reproducing the architecture and chemistry of healthy bone. In this study, the structural parameters of healthy bone were studied in order to reproduce them through 3D printing; furthermore, structural and mechanical differences between healthy and osteoporotic (OP) bones were assessed. Healthy and OP humeral heads discarded during surgical interventions (following ethical approval by Istituto Ortopedico Rizzoli-Italy) were tomographically analysed to obtain bone structural parameters. Successively, 8 mm diameter biopsies were harvested from the heads and underwent compression and nanoindentation tests to investigate macroscopic and microscopic mechanical properties, respectively. XRD measurements were performed on bone fragments. OP bone samples exhibited inferior mechanical properties to their less interconnected and more anisotropic structure, with thinner trabeculae and larger pores. On the other hand, nanoindentations performed on OP trabeculae showed increased Young Modulus compared to healthy samples probably due to their increased hydroxyapatite crystal size, as revealed by XRD. Osteoporosis causes the weakening of the trabecular structure that leads to a decrease of bone mechanical properties. However, OP trabeculae are stiffer due to increased dimensions of hydroxyapatite crystals

Aims. Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis. Methods. This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine. Results. The prevalence of DXA-proven hip osteoporosis (T-score ≤ -2.5) among THA patients was 8.8% (35 of 398). The spinal osteoporosis prevalence rate was 4.5% (18 of 398), and 244 patients (61.3%; 244 of 398) had osteopenia (-2.5 < T-score ≤ -1) or osteoporosis of either the hip or spine. The rate of pharmacological osteoporosis treatment was 22.1% (88 of 398). TRACP-5b was significantly lower in the osteoporosis-treated group than in the untreated group (p < 0.001). Conclusion. Osteoporosis is common in patients undergoing THA, but the diagnosis and treatment for osteoporosis were insufficient. The lower TRACP-5b levels in the osteoporosis-treated group — that is, osteoclast suppression — may contribute to the reduction of the postoperative revision rate after THA. Cite this article: Bone Joint Res 2022;11(12):873–880

A postal questionnaire was sent to 225 GPs and 225 Orthopaedic Surgeons (Consultant and Specialist Registrars) in 20 hospitals in North West England. They were asked to give their routine clinical practice with regard to investigation of underlying osteoporosis in 3 clinical scenarios :. 55 year old lady with a low trauma Colles fracture. 60 year old lady with a vertebral wedge fracture. 70 year old lady with a low trauma femoral neck fracture. The participants were asked whether patients over 50 years old with low trauma fractures required investigation for osteoporosis, and whether an osteoporosis Nurse Specialist would provide a beneficial service. The response rate was 52% (n=l17) from Orthopaedic Surgeons and 49% (n=l11) from GPs. Both groups agreed that patients over 50 years old with low trauma fractures required investigation for osteoporosis (81 % surgeons and 96% GPs), and that Osteoporosis Nurse Specialists may provide a beneficial Service (81% Surgeons and 94% of GPs). A majority of surgeons (56%) replied that they would routinely discharge the Colles fracture patient without requesting or initiating investigation for underlying osteoporosis. However, a majority of GPs (67%) would not investigate a similar patient for osteoporosis, unless prompted by the surgeon or patient. A greater proportion of both surgeons (71%) and GPs (64%) would routinely initiate investigations or treatment for osteoporosis in the Vertebral Wedge fracture patient. 65% of surgeons would simply discharge a patient with a femoral neck fracture after orthopaedic treatment and 40% of GPs will simply file the hospital discharge letter. Most Orthopaedic Surgeons and GPs are aware that low trauma fractures in patients over 50 years old require investigation for Osteoporosis, however, a large population of patients with Colles and Femoral Neck fractures are not being given the advantages of secondary prevention of Osteoporosis. This may lead to greater workload for Orthopaedic Surgeons in the future

Osteoporosis can cause significant disability and cost to health services globally. We aim to compare risk fractures for both osteoporosis and fractures at the L1-L4 vertebrae (LV) and the neck of femurs (NOFs) in patients referred for DEXA scan in the North-West of England. Data was obtained from 31546 patients referred for DEXA scan in the North-West of England between 2004 and 2011. Demographic data was retrospectively analysed using STATA, utilising chi-squared and t-tests. Logistical models were used to report odds ratios for risk factors included in the FRAX tool looking for differences between osteoporosis and fracture risk at the LV and NOFs. In a study involving 2530 cases of LV fractures and 1363 of NOF fractures, age was significantly linked to fractures and osteoporosis at both sites, with a higher risk of osteoporosis at NOFs compared to LV. Height provided protection against fractures and osteoporosis at both sites, with a more pronounced protective effect against osteoporosis at NOFs. Weight was more protective for NOF fractures, while smoking increased osteoporosis risk with no site-specific difference. Steroids were unexpectedly protective for fractures at both sites, with no significant difference, while alcohol consumption was protective against osteoporosis at both sites and associated with increased LV fracture risk. Rheumatoid arthritis increased osteoporosis risk in NOFs and implied a higher fracture risk, though not statistically significant compared to LV. Results summarised in Table 1. Our study reveals that established osteoporosis and fracture risk factors impact distinct bony sites differently. Age and rheumatoid arthritis increase osteoporosis risk more at NOFs than LV, while height and steroids provide greater protection at NOFs. Height significantly protects LV fractures, with alcohol predicting them. Further research is needed to explore risk factors’ impact on additional bony sites and understand the observed differences’ pathophysiology. For any figures or tables, please contact the authors directly

Summary. Osteoporosis reduces particle-induced osteolysis in rat model. Introduction. Wear particle induced osteolysis is considered to be a vital factor that reduces the life span of joint prosthesis. Osteoporosis is not rare in patients with indication for arthroplasty. However, the influence of osteoporosis on wear particles induced osteolysis is not clear. This study is aimed to explore on this issue by using animal model. Methods. 42 female Sprague-Dawley (SD) rats aged 6 months were randomly divided into 3 groups: A, B and C group. Group A and B contained 18 rats each, and group C contained 6 rats. The rats in group A underwent bilateral ovariectomy. Group B was normal control, and group C was sham control. After 3 months, 6 rats in group A, 6 rats in group B and all the rats of group C were sacrificed. Bone mineral density (BMD), μCT and bone histomorphometry were conducted. The rest of rats in group A were randomly divided into 2 groups: group A1 and group A2, and so were the rats in group B. 5mg titanium particles were implanted onto the calvaria of groups A1 and B1, and isometric PBS solution were injected to group A2 and B2. Calvaria were harvested after 14 days. Calvaria were analyzed by μCT and histomorphometry to measure the osteolysis area of calvarial sagittal suture. Results. Compared with B and C group, BMD and bone histomorphometry index of group A was significantly reduced (P<0.05), and tibial trabeculae of group A was slimmer. Area of calvarial sagittal suture osteolysis were 0.262±0.009mm. 2. , 0.130±0.013mm. 2. , 0.307±0.013mm. 2. and 0.178±0.011mm. 2. in A1, A2, B1and B2 groups, respectively. There was significant difference among the groups. Conclusions. Osteoporosis may reduce particle-induced osteolysis in rat model

Introduction: With a worldwide aging population, and an expected doubling in numbers of people older than 65 between 1990 and 2020, we are in the midst of a predicted increase in osteoporosis and resultant fractures. The International Osteoporosis Foundation recently surveyed consultant orthopaedic surgeons in mainland Europe and New Zealand to determine how patients with osteoporotic fractures were managed. Their conclusion was that treatment patterns were varied, and the findings supported the need to improve fragility fracture services to reduce the risk of recurrent fractures. Aim: The aim of our study was to see how Irish practices and opinions related to the IOF survey, in anticipation of a formal protocol being established in our unit. Methods: A modification of the International Osteoporosis Foundation survey used in 2002 was sent to 85 Consultant Orthopaedic Surgeons listed in the Irish Medical Directory. The questionnaire evaluated the surgeon’s education and knowledge of osteoporosis management, as well as estimated numbers of patients being treated with osteoporosis and the investigations available to their service. Treatment and referral patterns were also established. All responses were anonymous. Results: The Irish response rate to the survey of nearly 50% was higher than that of our European colleagues, and showed that only 25% of surgeons felt they received sufficient training in the area of osteoporosis, but only a minority were not confident managing the disease. One-quarter of those surveyed would treat a patient with a fragility fracture for osteoporosis themselves, while over half would refer the patient on to a General Practitioner for further management. 50% of Irish Consultants would first order bone mineral densitometry, and nearly three-quarters believe the General Practitioner is the most appropriate professional to follow up these patients. Significantly, 15% of Orthopaedic surgeons did not have any access to densitometry. The most popular treatment modality is a combination of calcium and vitamin D supplementation in conjunction with Alendronate. Conclusion: There is currently a lack of standarisation in the management and follow up of patients with osteoporosis. While the disease and its treatment is an internationally important topical issue, our study showed that at a national level there is a lack of consistency between the need for specialised services and implementation of treatment algorithms, due in part to lack of investigative facilities and organised management teams

Osteoporosis is common in elderly patients admitted to orthopaedic units with fractures. Fragility fractures place a large burden on health expenditure. Orthopaedic units are in a position to identify patients who require bone density assessment and possible treatment of osteoporosis. Previous surveys of orthopaedic surgeons have shown a wide variance in their perceived role in this. This study was a retrospective note review of 305 patients aged over 55 years with a fragility fracture, who were admitted under the orthopaedic service of eight New Zealand hospitals. Notes from any subsequent rehabilitation unit admission were also reviewed, if available. The mean age was 80.6 years (range 55–104). Seventy seven percent were female. The most common fracture was of the hip (61.6%). Two hundred and thirty-six patients (77.4%) were not taking osteoporosis medication at time of admission, 2.5% of these had a bone mineral density assessment ordered and 11.9% had osteoporosis treatment started, giving a combined intervention rate (investigation or treatment) of 14.4%. A visiting orthogeriatric service initiated treatment in 82.1% of cases. Osteoporosis was listed on the discharge summary in 31.8% of patients who were taking osteoporosis treatment on admission and in 10.7% of patients who had treatment started. Management of osteoporosis is mostly neglected by New Zealand orthopaedic units. This is similar to published data from other countries. Hospitals with the highest rates of osteoporosis intervention had an orthogeriatric service initiating the majority of treatment. Treatment started by the orthopaedic staff was not optimal. Osteoporosis is not identified in most documentation generated by the orthopaedic units

As a part of the European Union BIOMED I study “Assessment of Bone Quality in Osteoporosis,” Sixty-nine second lumbar vertebral body specimens (L2) were obtained post mortem from 32 women and 37 men (age 24–92 years). Our initial remit was to study variations in density of the calcified tissues by quantitative backscattered electron imaging (BSE-SEM). To this end, the para-sagittal bone slices were embedded in PMMA and block surfaces micro-milled and carbon coated. Many samples were re-polished to remove the carbon coat and stained with iodine vapour to permit simultaneous BSE imaging of non-mineralised tissues - especially disc, annulus, cartilage and ligament - uncoated, at 50Pa chamber pressure. We have now studied most of these samples by 30-μm resolution high contrast resolution X-ray microtomography (XMT), typically 72 hours scanning time, thus giving exact correlation between high resolution BSE-SEM and XMT. The 3D XMT data sets were rendered using Drishti software to produce static and movie images for visualisation and edification. We have now selected a set of the female samples for reconstruction by 3D printing - taking as examples the youngest, post-menopausal, oldest, best, worst, and anterior and central compression fractures and anterior collapse with fusion to L3 - which will be attached to the poster display. The most porotic cases were also the most difficult to reconstruct. A surprising proportion of elderly samples showed excellent bone architecture, though with retention of fewer, but more massive, load-bearing trabeculae

Introduction: The incidence of osteoporosis is increasing as the population ages. Amongst the recommended treatment modalities for osteoporosis is the use of bisphosphonates. The National Osteoporosis Foundation (U.S.A.) recommends DEXA scanning prior to commencing treatment with bisphosphonate therapy. However, in the Irish setting the availability of DEXA scanning is often limited. We hypothesised that a high percentage of elderly women presenting with fragility fractures of the distal radius (following a simple fall from standing height) had underlying osteoporosis. As such, the initiation of treatment with bisphosphonates prior to obtaining a DEXA scan may be warranted in this patient cohort. Aim: To assess the incidence of osteoporosis in a continuous cohort of women over 60 years of age presenting with fractures of the distal radius. Patients and Methods: All female patients aged > 60 years old presenting to the fracture service over a five month period with distal radial fragility fractures were evaluated. Exclusion criteria included:. non-English speakers. non-resident in Ireland. previous diagnosis of osteoporosis or commenced on treatment for osteoporosis. not fit to attend for DEXA scan. not willing to participate in the study. 100 consecutive patients presenting to the fracture service with distal radial fragility fractures were prospectively identified. Data was collected, including body mass index (BMI), risk factors for osteoporosis, and the OST risk index calculated. A DEXA scan was then performed on the patient’s hips and lumbar spine. Results: The mean patient age was 74.3 (95%CI + 10.6) years. Mean BMI was 17.3 kg/m2. The mean Osteoporosis Self-assessment Tool (OST) index score was 0.65 correlating with a moderate risk for osteoporosis. The mean T score for the patients’ hips was −2.0 while that for the lumbar spine was −1.7. 64% of patients were osteoporotic with a T score of less than −2.5. Conclusions A significant incidence of osteoporosis was noted in the study cohort. It is imperative that orthopaedic surgeons recognise the high incidence of osteoporosis in the elderly female population presenting with fragility fractures. The high morbidity and mortality associated with hip and vertebral fractures in this population may be prevented by early treatment of underlying osteoporosis

Background. Osteoporosis and bone fractures lead to immobility, chronic pain and high patient care costs. Mesenchymal stem cells (MSCs) from postmenopausal women have a slower growth rate and osteogenic differentiation ability causing lower bone density and reduced fracture healing capacity compared to MSCs from premenopausal women. Cellular movement and relocalisation are necessary for many physiologic properties. Local MSCs from injured tissues and circulating MSCs are involved in fracture healing. Cytokines and chemokines such as SDF-1 and its receptor CXCR4 play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. This study investigated the effect of CXCR4 over-expression on the migration of MSCs from ovariectomised, normal and young rats. Methods. MSCs were harvested from femora of young, normal and OVX rats, genetically modified to over-express CXCR4and put in a Boyden chamber to establish their migration towards SDF-1. This was compared to the non-transfected stem cells. Results. MSCs from OVX rats migrate less towards SDF1 compared to MSCs from normal and juvenile rats. When the MSCs were differentiated to osteoblasts their migration towards SDF1 reduced as well and this was not enhanced by over-expression of CXCR4. Cell transfected with CXCR4 migrated more towards SDF-1 compared to non-transfected cells irrespective of whether these cells were from OVX, young or normal rats. Conclusions. MSCs migration is impaired by age and osteoporosis explaining the significant reduction in bone formation in osteoporotic patients. The migration of stem cells can be ameliorated by up regulating the CXCR4 levels which could possibly enhance fracture healing in osteoporotic patients. Level of Evidence. IIb

Aims. Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. Methods. We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects. Results. Through discovery and replication integrative analysis for BMD GWAS and rSNP annotation database, we identified 36 common BMD-associated genes for BMD irrespective of regulatory elements, such as FAM3C (p. discovery GWAS. = 1.21 × 10. -25. , p. replication GWAS. = 1.80 × 10. -12. ), CCDC170 (p. discovery GWAS. = 1.23 × 10. -11. , p. replication GWAS. = 3.22 × 10. -9. ), and SOX6 (p. discovery GWAS. = 4.41 × 10. -15. , p. replication GWAS. = 6.57 × 10. -14. ). Then, for the 36 common target genes, multiple gene ontology (GO) terms were detected for BMD such as positive regulation of cartilage development (p = 9.27 × 10. -3. ) and positive regulation of chondrocyte differentiation (p = 9.27 × 10. -3. ). Conclusion. We explored the potential roles of rSNP in the genetic mechanisms of BMD and identified multiple candidate genes. Our study results support the implication of regulatory genetic variants in the development of OP. Cite this article: Bone Joint Res 2023;12(2):147–154

Background: Osteoporosis is a significant cause of morbidity and disability through an increase in bone fragility and susceptibility to fracture. In March 2001 guidelines were produced by The Clinical Resource Efficiency Support Team (CREST) on the Prevention and Treatment of Osteoporosis, which were distributed throughout the primary and secondary care groups. Aim: The aim of this audit was to analyse the use of the CREST guidelines within the secondary care sector. Methods: The audit was conducted from January 2002 until March 2003. The sample group was identified retrospectively from September 2001 to February 2002 from patients over 45 years of age with diagnosis of osteoporosis / osteopenia and an osteoporotic fracture. All patients sampled were admitted to the secondary care sector, and data was collected using the CREST audit tool data collection form, utilising the information on the central fracture database located at the Royal Victoria Hospital Belfast. Results: 213 patients studied (165 female). Mean age 73 yrs (Range 41 to 100yrs). 5% had a risk factor for osteoporosis. 30 patients had previous fragility fracture, 9 male and 21 female, 21 of which were either wrist, hip or spine. Of these 30 patients, 4 (13%) had a diagnosis of osteoporosis considered. Regarding most recent fracture; in males (n=46); 24 (52% hip, 15 (33%) vertebra and 7 (15%) colles, in females (n=156); 66 (42%) hip, 62 (40%) colles, 18 (12%) and 10 (6%) hip and colles. 28 patients (13%) received lifestyle advice concerning osteoporosis. Pharmacological intervention; in males 1 (2%) calcium and vitamin D and 47 (98%) no treatment, in females 10 (6%) calcium, 18 (11%) calcium and vitamin D, 5 (3%) bisphosphonate, 4 (2%) SERM, 3 (2%) HRT and 125 (76%) no treatment. 91 patients underwent operation for hip fracture, 33% of operations were completed within 24 hour period, and 74% completed with 72 hour period. Grade of anaesthetist supervising operations: 80% Consultant, 12% Specialist Registrar, 7% Senior House Officer and 1% Staff Grade. 93% of patients received both prophylactic antibiotics and anti-coagulation prior to surgery. 83% of patients were identified at risk of falling, but only 17% had documented evidence that fall prevention advice had been given. Summary: Only 5% of patients were identified as having a risk factor for osteoporosis; 14% of patients had a previous low trauma fracture – a strong independent risk factor – however in only 13% of these 30 patients had osteoporosis been considered at time of fracture; only 13% of patients received any form of lifestyle advice; only 17% had advice given regarding fall prevention. These low figures could be due to improper recording, or simply that advice was not given. The vast majority of patients received no form of pharmacological intervention. In regards to surgery; time to operation, grade of anaesthetist and prophylactic treatments were appropriate in the vast majority of cases. Conclusion: The current cost of hip fractures in Northern Ireland is £21 million per year and with 90% of these fractures related to osteoporosis it is important that steps are taken to ensure early diagnosis, and that appropriate action is taken in the prevention and treatment. As can be seen, the CREST Guidelines are being adhered to in parts, however patients at risk are not being identified and appropriate pharmacological treatment and lifestyle advice is not being given