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 can determine surgical strategy for total hip arthroplasty (THA), and perioperative fracture risk. The aims of this study were to use hip CT to measure femoral bone mineral density (BMD) using CT X-ray absorptiometry (CTXA), determine if systematic evaluation of preoperative femoral BMD with CTXA would improve identification of osteopenia and osteoporosis compared with available preoperative dual-energy X-ray absorptiometry (DXA) analysis, and determine if improved recognition of low BMD would affect the use of cemented stem fixation. Methods. Retrospective chart review of a single-surgeon database identified 78 patients with CTXA performed prior to robotic-assisted THA (raTHA) (Group 1). Group 1 was age- and sex-matched to 78 raTHAs that had a preoperative hip CT but did not have CTXA analysis (Group 2). Clinical demographics, femoral fixation method, CTXA, and DXA data were recorded. Demographic data were similar for both groups. Results. Preoperative femoral BMD was available for 100% of Group 1 patients (CTXA) and 43.6% of Group 2 patients (DXA). CTXA analysis for all Group 1 patients preoperatively identified 13 osteopenic and eight osteoporotic patients for whom there were no available preoperative DXA data. Cemented stem fixation was used with higher frequency in Group 1 versus Group 2 (28.2% vs 14.3%, respectively; p = 0.030), and in all cases where osteoporosis was diagnosed, irrespective of technique (DXA or CTXA). Conclusion. Preoperative hip CT scans which are routinely obtained prior to raTHA can determine bone health, and thus guide femoral fixation strategy. Systematic preoperative evaluation with CTXA resulted in increased recognition of osteopenia and osteoporosis, and contributed to increased use of cemented femoral fixation compared with routine clinical care; in this small study, however, it did not impact short-term periprosthetic fracture risk. Cite this article: Bone Joint J 2023;105-B(3):254–260

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

Introduction: Osteoporosis is a skeletal disorder characterised by decreased bone mineral density (BMD) and a subsequent increased risk of fragility fractures. This disease is commonly associated with postmenopausal females with an increasing incidence into later life, over 50% of females over 80 have osteoporosis. At the opposite spectrum of life, decreased BMD is traditionally associated with the female athletic triad, with hormonal imbalance leading to skeletal insufficiency. Considered a “silent disease” until a fracture occurs, as orthopaedic surgeons we must be able to identify those at risk of osteoporosis and refer promptly for dual energy x-ray absorptiometry (DEXA) scanning to prevent future fragility fractures in this specific patient cohort. Methods: We carried out an epidemiological analysis of all female patients under the age of 30 referred for DEXA scanning in a university teaching hospital over a 3 year period. We analysed mode of referral, risk factors, T-score and subsequent fractures with an aim to highlight an underestimated level of osteopenia/osteoporosis in the younger patient. Results: We identified 102 patients eligible for our study, with a mean age of 25.34 (Range- 17–29). As per the World Health Organisation (WHO) osteopenia was defined as osteopenia as a T-Score between −1 and −2.5, with osteoporosis below −2.5. The mean T score of these patients was −1.037 (range −3.2 to 2.4). Medical teams initiated the majority of referrals (77%), followed by General Practitioners (17%), Gynaecologists (4%), Paediatricians (1%) and Surgeons(1%). Risk factors included excess steroid use for medical conditions (41%), decreased body mass index (BMI) (27%), ceoliac disease (12%) and radiological evidence of osteopenia (7%). 34% of these patients had suffered a fall with 12% of patients suffering from a fragility fracture. Conclusion: We identified a definite cohort of young female patients who had a mean T-score within the levels for osteopenia. Over one third had suffered a fall and 12% had suffered a fragility fracture despite a young age. With ever increasing patient numbers in both fracture and orthopaedic clinics and increased pressure on resources, it is imperative that we still take thorough histories to identify those young female patients that are at risk of osteoporosis. With appropriate follow up and investigations, they can be started on necessary treatment and prevent subsequent fragility fractures, the incidence of which appears to be underestimated

1. Regional osteoporosis is a common finding in osteoid osteoma. It may in fact be a constant feature because it was present in all the patients reported in this paper and was suspected in others who have not been included in this report because of insufficient information. 2. Five of our six cases showed osteoporosis about the hip. Osteoporosis is more likely to be noticed in this region than in other parts of the extremities because both hips are usually radiographed on one film. We have seen several instances in which we suspected generalised osteoporosis of an extremity but Case 5 was the only one in which comparable radiographs had been taken of both feet. 3. When there is osteoporosis in the region of a joint with symptoms referred to that joint an osteoid osteoma may be the cause. The nidus may lie at some distance from the joint surfaces and may not be seen in standard radiographs of the joint (Case 4). Additional radiographs including a wider area than usual may be necessary to show the lesion, and tomography is sometimes required

Background & Objectives: Osteoporosis is one of the most prevalent bone diseases worldwide with fractures its major clinical consequence. Studies on the effect of osteoporosis on fracture repair are contradictory and although it might be expected for fracture repair to be delayed in osteoporotic individuals, a definitive answer still eludes us. Subsequently, the aim of this study was to attempt to clarify any such effect. Methods: Osteoporosis was induced in 53 female Sprague-Dawley rats by ovariectomy (OVX) at 3 months. A femoral fracture was produced in these animals 12 weeks later {OVX+Fracture group (OVX+F)}. A control group received the fracture only group (F) at 6 months. The fracture consisted of an open osteotomy held with a unilateral external fixator. Outcome measures include histology, motion detector analysis, pQCT, biomechanical strength testing (BST) and digital radiography. Digital radiographs were taken at time of OVX, fracture (confirming satisfactory reduction) and sacrifice from which relative bone density (BMD) measurements were calculated. Results: OVX+F animals were significantly heavier than F animals at fracture and sacrifice (p< 0.001 for both) and moved significantly less in days 1-4 (p=0.032) and 5-9 (p=0.020) post-fracture. Relative BMD measured in distal femur at fracture and sacrifice was significantly greater in F group (p< 0.001 for both). Furthermore, there was a significant decrease in relative BMD from fracture to sacrifice in OVX+F group (p< 0.001). pQCT showed a significantly greater total BMD {contralateral (p=0.021) and fractured femora (p< 0.001)} and trabecular BMD (p< 0.001 both limbs) in the distal femur of the F group. Histologically, no statistical differences were found, however, the F group generally displayed the most advanced repair. In the contralateral limb, the F group had significantly greater load to failure at 6 (p=0.026) and 8 (p=0.042) weeks and was significantly stiffer at 8 weeks (p=0.050). In the fractured leg, stiffness was significantly greater in the F group at 8 weeks (p=0.001). Conclusion: OVX was linked to increased body weight, decreased motion, decreased BMD (with particular loss in trabecular BMD), and reduced mechanical properties. OVX did not have a significant effect on fracture healing and although there was no reduction in BMD at the fracture site, histology and reduced stiffness suggest it was delayed

Osteoporosis is a disease when bone mass and tissue is lost, with a consequent increase in bone fragility and increase susceptibility to develop fracture. The osteoporosis prevalence increases markedly with age, from 2% at 50 years to more than 25% at 80 years. 1. in women. The vast majority of distal radius fractures (DRFs) can be considered fragility fractures. The DRF is usually the first medical presentation of these fractures. With an aging population, all fracture clinics should have embedded screening for bone health and falls risk. DRF is the commonest type of fracture in perimenopausal women and is associated with an increased risk of later non-wrist fracture of up to one in five in the subsequent decade. 2. . According to the national guidelines in managing the fragility fractures of distal radius with regards the bone health review, we, as orthopedic surgeons, are responsible to detect the risky patients, refer them to the responsible team to perform the required investigations and offer the treatment. We reviewed our local database (E-trauma) all cases of fracture distal radius retrospectively during the period from 01/08/2019 to 29/09/2019. We included total of 45 patients who have been managed conservatively and followed up in fracture clinic. Our inclusion criteria was: women aged 65 years and over, men aged 75 years and over with risk factors, patients who are more than 50 years old and sustained low energy trauma whatever the sex is or any patient who has major risk factor (current or frequent recent use of oral or systemic glucocorticoids, untreated premature menopause or previous fragility fracture). We found that 96% of patients were 50 years old or more and 84% of the patients were females. 71% of patients were not referred to Osteoporosis clinic and 11% were already under the orthogeriatric care and 18% only were referred. Out of the 8 referred patients, 3 were referred on 1st appointment, 1 on the 3rd appointment, 1 on discharge from fracture clinic to GP again and 3 were without clear documentation of the time of referral. We concluded that we as trust are not compliant to the national guidelines with regards the osteoporosis review for the DRF as one of the first common presentations of fragility fractures. We also found that the reason for that is that there is no definitive clear pathway for the referral in our local guidelines. We recommended that the Osteoporosis clinic referral form needs to be available in the fracture clinic in an accessible place and needs to be filled by the doctor reviewing the patient in the fracture clinic in the 1st appointment. A liaison nurse also needs to ensure these forms have been filled and sent to the orthogeriatric team. Alternatively, we added a portal on our online database (e-trauma), therefore the patient who fulfils the criteria for bone health review should be referred to the orthogeriatric team to review

1. The syndrome of osteoporosis is reviewed and its various causes are mentioned. Osteoporosis in youngish patients without any demonstrable cause is referred to as "idiopathic." The scant literature on this condition is reviewed. Its clinical, radiological, biochemical and histological features are considered. 2. A series of thirty-eight cases is analysed, and illustrative case histories are described. The peculiarities of the disease as it is seen in women are discussed, particularly the relationship to pregnancy and lactation, which appear to act as precipitating factors, rather than being primarily causative. 3. The differential diagnosis is discussed. Osteogenesis imperfecta may not always be easy to distinguish; since it is really a "congenital osteoporosis" this is hardly surprising. 4. The following possible etiological factors are propounded (apart from pregnancy): nutritional, occupational, lack of sex hormone, liver dysfunction, loss of protein, diabetes, premature ageing, hypophosphatasia, "alarm reaction," and inheritance. None of them can be incriminated except in the odd case. The relationship between osteoporosis and idiopathic hypercalcuria is mentioned. The only conclusion regarding etiology is that some people are simply more prone to bone loss than are others, and in these a variety of accentuating factors may render the disorder clinically apparent. 5. The treatment of the condition is unsatisfactory, although occasionally a positive calcium balance may be obtained with sex hormones or intravenous infusion of plasma albumin or whole plasma. The general tendency seems to be towards clinical improvement (biologically "stabilisation" rather than improvement), but some patients become permanently crippled

Nuclear factor erythroid 2–related factor 2 (Nrf2) is a crucial transcription factor to maintain cellular redox homeostasis, but is also affecting bone metabolism. As the association between Nrf2 and osteoporosis in elderly females is not fully elucidated, our aim was to shed light on the potential contribution of Nrf2 to the development of age-dependent osteoporosis using a mouse model.

Female wild-type (WT, n=18) and Nrf2-knockout (KO, n=12) mice were sacrificed at different ages (12 weeks=young mature adult, and 90 weeks=old), morphological cortical and trabecular properties of femoral bone analyzed by micro-computed tomography (µCT), and compared to histochemistry. Mechanical properties were derived from quasi-static compression tests and digital image correlation (DIC) used to analyze full-field strain distribution. Bone resorbing cells and aromatase expression by osteocytes were evaluated immunohistochemically and empty osteocyte lacunae counted in cortical bone. Wilcoxon rank sum test was used for data comparison and differences considered statistically significant at p<0.05.

When compared to old WT mice, old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness (Ct.Th), cortical area (Ct.Ar), and cortical bone fraction (Ct.Ar/Tt.Ar). Surprisingly, these parameters were not different in skeletally mature young adult mice. Metaphyseal trabeculae were thin but present in all old WT mice, while no trabecular bone was detectable in 60% of old KO mice. Occurrence of empty osteocyte lacunae did not differ between both groups, but a significantly higher number of osteoclast-like cells and fewer aromatase-positive osteocytes were found in old KO mice. Furthermore, female Nrf2-KO mice showed an age-dependently reduced fracture resilience when compared to age-matched WT mice.

Our results confirmed lower bone quantity and quality as well as an increased number of bone resorbing cells in old female Nrf2-KO mice. Additionally, aromatase expression in osteocytes of old Nrf2-KO mice was compromised, which may indicate a chronic lack of estrogen in bones of old Nrf2-deficient mice. Thus, chronic Nrf2 loss seems to contribute to age-dependent progression of female osteoporosis.

Subjects who have incurred an osteoporotic fracture are at high risk of further fracture. Recent publications by the Department of Health, the National Osteoporosis Society and the Royal College of Physicians have recommended that these patients should receive appropriate life-style advice and treatment for osteoporosis. The study aims to determine whether patients who had incurred a fracture of the hip or wrist were aware of the term osteoporosis and whether they had received advice or treatment for this condition following their fracture. All patients attending Stepping Hill hospital, Stock-port, with a fracture wrist or hip between 1 Jan and 31 May 2000 were identified. A postal questionnaire was sent to these patients in Jan 2001 (at least 6 months following their fracture). The questionnaire sought information on awareness, investigations, advice and treatment received for osteoporosis. After exclusion of patients who had died, 191 patients (102 wrist fractures, 89 fractured hip) were sent a questionnaire. Response rate was 87%. Although 79% of patients were aware of the term osteoporosis, only 22% had received any investigations, 21 % were given lifestyle advice and only 18% received treatment. Despite the strong evidence that early treatment decreases the incidence of subsequent fractures, the results from this study continue to confirm that most patients are neither investigated nor treated for osteoporosis. This illustrates the wide discrepancy between knowledge and action in this field. All the patients with minimal trauma fractures will pass through an orthopaedic department at some point in their ongoing management for the fracture – however little responsibility is taken for the management of osteoporosis within the orthopaedic departments – a missed opportunity

Introduction: Osteoporosis, a major public health burden, is associated with increased fracture risk. Fracture healing in osteoporosis is altered with reduced callus formation and impaired biomechanical properties of newly formed bone leading to high risk of fixation failure. Experimental data have shown decreased healing potential in aged animals and in animal models of post-menopausal bone loss. It is unclear whether fracture healing is similarly impaired in senile osteoporosis. The objective of this study is to investigate fracture healing in a small animal model of senile osteoporosis, senescence-accelerated mouse prone 6 (SAMP6). Materials & Methods: A mid-femur osteotomy was created in SAMP6-mice (n=24) and senescence-resistant inbred strains (SAMR1) (n=24) were used as controls. The osteotomy was rigidly fixed using a newly developed screw-plate-implant (MouseFix). Fracture healing was evaluated at 7, 14, 28 and 42 days after surgery using micro-CT and histomorphometry. Biochemical marker for bone formation (osteocalcin) and bone resorption (TRAP5b) were evaluated from serum samples. MSC were extracted from the femurs of mice and cultured in vitro and differentiated into either osteoblasts or adipocytes using standard induction media. Results: Studies carried out in vitro confirmed that MSC isolated from the bone marrow of SAMP6 mice had a reduced tendency to differentiate toward the osteoblast cell lineage as previously reported in human osteoporotic patients. Although osteoblastogenesis was clearly impaired, the formation of new bone in SAMP6 mice was comparable to that observed in SAMR1 mice. Similar results were found for histomorphometry data analyzing the degree of bone mineralisation. Interestingly, osteocalcin levels were significantly increased in serum samples from osteoporotic mice at day 7 and 14 following fracture. Discussion: The data presented here indicates that fracture healing proceeds normally in a mouse model for senile osteoporosis. This finding supports the clinical observation that although fracture fixation is difficult in osteoporosis, healing potential seems to be unchanged. MSC from osteoporotic patients as wells as from SAMP6-mice show reduced proliferation rate together with adipogenic rather than osteogenic differentiation pattern. However, decreased cell dynamics seems not to influence diaphyseal fracture healing. Other sources of MSC other than bone marrow-derived MSC may therefore be pivotal in determining the outcome of intramembranous bone repair in both normal and osteoporotic bone

1. Individuals who are normal and not osteoporotic seem to show retention of cortical bone at successive decades of life in proportion to the total lean body-mass. In patients with osteoporosis the weight of the skeleton decreases at a rate exceeding the physiological rate of atrophy of muscle, tendon and bone tissue that occurs with the time-dependent process of ageing. 2. Six patients representing the typical forms of osteoporosis commonly found in orthopaedic practice were investigated intensively over a period of three years and compared with individuals in whom there was no osteoporosis by studies of metabolic balance, Sr85 osteograms, and tetracycline deposition. 3. Studies of metabolic balance in patients with osteoporosis showed normal or negative calcium balances, but an equilibrium for the metabolism of nitrogen and phosphorus. Increased intake of calcium in the diet produced retention of calcium but not sufficient phosphorus, nitrogen or gain in weight to prove that the patient had made new bone and healed the osteoporosis. 4. Radio-isotope osteograms showed high, normal or low rates of change of uptake of Sr85 and the accretion rate was calculated to be normal or low in individuals with osteoporosis. High uptake of tetracycline by a small mass of bone tissue and by a relatively small percentage of the total number of osteons suggested that in an adult human being the calcium reserve in the skeleton is enormous. Thirty to 50 per cent of the total bone mass was sufficient to turn over 0·5 to 1·0 gramme, the amount of calcium utilised in twenty-four hours by the human adult. This was accomplished by structural or old bone throughout the entire skeleton, and by labile or newer bone located in approximately 10 per cent of the total number of Haversian cylinders or osteons. 5. Some of the unclosed or half-closed osteons were hyperactive in osteoporotic bones. In the process of remodelling of cortical bone a significant quantity of bone tissue was incompletely restored and there were, presumably as a result, intermittently large or small negative calcium balances. Osteoporosis may have been the cause, rather than the result, of the negative calcium balance. 6. The experimental and clinical literature of the past ten years, and studies on patients described in this critical review, were interpreted to indicate that prolonged calcium deficiency, castration, hyperadrenal corticoidism or a sedentary life may precipitate, accentuate and accelerate osteoporosis in individuals who are genetically predisposed to develop it. Sometimes high calcium intake or sex hormones, or both, may have slowed the rate of resorption but did not replace the deficit in cortical bone. 7. Further research is necessary to find the chief etiological factor and to produce the cure for this increasingly common disorder of the skeleton

Orthopedic surgeons treat numerous patients in whom osteoporosis (OP) is an important factor: inflammatory arthritides (rheumatoid arthritis); sports medicine (the anorexic, amenorrhoeic female athlete); in consultation to renal, transplant and cardiac units; patients on corticosteroids, as well as others. Orthopedic procedures in patients who have osteoporotic bone require special techniques and precautions. A common example is hip replacement, where, through endosteal resorption, the medullary canal is large, cortices are thin, and the risk of femoral fracture and a poor outcome is higher. The commonest interface of orthopedic surgery with OP is in the management of fractures. In North America, most orthopedic surgeons manage fractures in hospital and in the fracture clinic, where typically 3%–8% of patient visits are for classic fragility fractures. Traumatic fractures also commonly occur in osteoporotic bone. The yield of screening for OP in orthopedic wards and clinics, targeting fragility fracture patients, is much higher than screening in a general population. Published guidelines based on Level I evidence indicate that fragility fracture patients are at highest risk of future hip fractures, which often occur within one year of index fragility fracture, and that preventive treatment is economical and safe. Treatment prevents 30–50% of hip fractures in high risk groups. Unfortunately, less than 20% of fragility fracture patients generally receive appropriate OP care, in multiple studies in developed countries. There is a growing international focus on developing care delivery systems that will promote consistent OP investigation and treatment in the inpatient and outpatient orthopedic environment. In Ontario, Canada, an Osteoporosis Exemplary Care Program was initiated in 2003 to identify, educate, evaluate, refer, and treat female (> 40 years) and male (> 50 years) fragility fracture patients for OP. In the first year of the program, over 95% of inpatients and outpatients were appropriately diagnosed, treated, or referred for OP care. Success resulted from the presence of a dedicated coordinator and cooperation by orthopedic surgeons and residents, technologists, allied health professionals and administrative staff. Regional, national and international orthopedic associations have developed initiatives designed to improve processes of care for OP in the orthopedic environment

Osteoporosis can be caused by many miscellaneous factors. These factors include medical, lifestyle and socioeconomic variables, the latest being not well studied and defined in international bibliography. From these there are the factors regarding the working environment (house or office) and the living environment (urban or countryside). Our hypothesis is based on the fact that women living in an urban environment or working in an office environment should have lower Bone Mineral Density (BMD) and thus, greater fracture possibility because of their lower level of physical activity, greater alcohol/coffee consumption and increased smoking frequency compared to women living in the countryside or women housekeeping. In order to find whether this hypothesis is true, a population based observational retrospective study has been performed. The fracture rate of 4616 post-menopausal osteoporotic women (PMOW) (mean age=64,1±9,3 years) from 160 centers all over Greece has been compared with the two aforementioned possible risk factors. Descriptive statistics like the mean±SD and frequencies were used to present the data. In order to assess for relationships between categorical variables the chi-square (χ2) test was performed. Statistical analysis was conducted using the software SAS, version 9.1 and statistical significance was established as 5%. The results are as follow:. 16,2% of these PMOW had a history of fracture and for 80,3% of them was a hip fracture. 84,1% of PMOW lived in urban environment and had lower fracture rate than women living in the countryside (p< 0,05). 47,2% of the PMOW worked at home and had lower fracture rate than women working for more than 20 years in an office environment (p< 0,0001). It can be concluded that more fracture-susceptible PMOW are those working in an office environment and also living in the countryside. It can be assumed that the first is related with lower BMD and the second with the more ‘fall-prone’ nature of the country environment

Relating the results of our investigations to the knowledge hitherto acquired about the etiology of osteoporosis (which I have already referred to), I am inclined to interpret the pathogenesis of osteoporosis in the following way: 1) Primary osteoblastic deficiency: congenital (Lobstein); involutive (senile osteoporosis?); 2) Reduced osteoblastic activity from absence of trophic stimuli: (inactivity, ovarian agenesia, eunuchoidism, menopause); 3) Reduced osteoblastic activity from inhibitory stimuli: (cortisone, adrenocorticotrophic hormone (A.C.T.H.), stress, Cushing's disease, thyrotoxicosis); 4) Normal osteoblastic activity but insufficiency of constructive material: (malnutrition, disturbances of the digestive system, insufficiency of vitamin C, diabetes, thyrotoxicosis, cortisone, A.C.T.H., stress, Cushing's disease). Osteoporosis may therefore be the consequence either of a congenital osteoblastic deficiency, such as that found in cases of osteogenesis imperfecta, or of reduced osteoblastic activity due to absence of trophic stimuli such as mechanical stress and the sex hormones, or of reduced activity of the bone cells due to anti-anabolic substances which inhibit them, such as cortisone and its derivatives and the thyroid hormone in strong doses, or lastly of reduced availability of construction material due to its introduction in reduced quantities (starvation, dysfunction of the digestive system) or due to hindering of synthesis (deficiency of vitamin C, diabetes, cortisone and its derivatives) or due to an excessive degree of destruction (thyrotoxicosis). In the case of anti-anabolic hormones from the adrenal cortex, the mechanism may thus be twofold: inhibition of the osteoblasts and deprivation of the osteoblasts of glucoprotein material due to a general anomaly of metabolism. This may perhaps explain the most serious forms of bone atrophy which are usually observable in cases of hyperfunction of the adrenal cortex. Senile osteoporosis should, in my opinion, be included in the first of our groups because it cannot be said to be brought about by any of the causes usually cited for osteoporosis– such as deficiency of sex hormones, excess of hormones from the adrenal cortex, deficiency of calcium, etc.–and in all probability it will depend on a progressive involution of the osteoblasts brought about by old age. Senile involution is an expression of the descending phase of life's parabola and it involves all the organs and all the parenchymatous tissues in the human body, but it does not cause a parallel reduction of functions and activities on all of them equally. The skeletal system is one of the first to feel these reductions, because in old age life necessarily becomes less intense. Consequently in the economy of the ageing subject the generally reduced level of metabolism brings about a sort of selection in the nourishment of the different organs and systems, and sometimes almost a dismantling of some of these in an attempt to fall in with the new and reduced level of activities of some of the parenchymatous tissues, activities which may be incomplete or even transferred elsewhere. We believe that the moment which originally determines the beginning of senile osteoporosis coincides with the involutional process of cellular metabolism that strikes at all parenchymatous tissue during old age–striking, in the case of osteoporosis, hardest of all at the bony tissues. There is, indeed, no doubt that certain essential processes of cellular metabolism do alter with age, and that the reduction in the activity of the gonads does have considerable importance. In any case, just as adolescence and old age cannot be explained only in terms of gonadal activity, so the involution of the skeleton cannot be due merely to the involution of the gonads. How should one then interpret the well known benefit afforded by administration of sex hormones in cases of osteoporosis? Probably the action of oestrogens and androgens is, in this case, of a pharmacological nature, and comparable, for instance, to the action of digitalis on the cardiac muscle. It will be remembered how digitalis acts almost exclusively on myofibrils which have become inadequate, and has little or no effect on a normal myocardium. Similarly, the sex hormones would seem to exert a stimulating action on osteoblasts that are on the way to involution, while they exert little or no action on normal osteoblasts. In support of this we have the findings of Urist and other workers, who demonstrated that the administration of sex hormones produces calcium and nitrogen retention only in osteoporotics, while in non-osteoporotic subjects of the same age it produces no effect. On the other hand, the action of the sex hormones might act in cases of senile osteoporosis by returning the changed level of protein metabolism to normal. From the data in the literature and from the results of our own investigations, I conclude that osteoporosis in general, and senile osteoporosis in particular, are first and foremost the result of a disturbance in the metabolism of bone, and that the metabolic disturbance is closely and exclusively related to the degree of activity and the state of activity of the cells in the bone. Lastly, I believe that senile osteoporosis should not be considered an actual disease but rather as one limited aspect of the normal descending parabola which affects to a greater or less degree all the tissues of the body

Osteoporosis is an increasing problem due to increasing age and inactivity. Distal radial fractures are often the first symptom of this disease. Medical treatment can reduce the risk of further fractures (including hip fractures with the associated mortality and morbidity). To develop a method for accurate assessment of bone density from routine wrist radiographs:. Various bone substitutes were tested until one was found that gave reasonable density matches with fresh bone over a limited X-ray kV range;. Twenty patients with distal radius fractures had the bone substitute placed beside the wrist being X-rayed. Wrist and radius thickness were measured from the radiograph. This was combined with the optical density of the distal radius (relative to the bone substitute) to calculate a value for the bone density. The patients subsequently underwent a DEXA scan of the contralateral (uninjured) wrist. [The X-ray calculated bone density and the DEXA density compare well. (R> 0.5]. Conclusion: This technique gives reasonably accurate results. It is not yet ready for clinical practice. A larger study is required to improve the accuracy of this technique, perhaps comparing results with lumbar spine DEXA

Current evidence suggests that in Australia more than 80% of individuals are not receiving treatment for osteoporosis following an initial osteoporotic fracture. The earliest opportunity to identify many individuals with osteoporosis is following their first osteoporotic fracture, which is usually less severe than subsequent fractures. As these fractures are usually treated by orthopaedic surgeons it was decided to survey Australian orthopaedic surgeons to determine their understanding, attitudes and involvement in the management of osteoporosis. Methods: The AOA in conjunction with the BJD distributed a questionnaire to 945 members. The results of 449 (48%) returned questionnaires were collated and sent to the Swedish National Competence Centre for Musculo-skeletal Disorders for analysis. Results: Responding surgeons claimed to treat at least 24,000 osteoporotic fractures per year. Sixty per cent felt they had ‘none’ or ‘insufficient’ training in osteoporosis and considered they had ‘no’ or only ‘slight knowledge’ in managing the condition. Approximately 65% of surgeons either ‘never’ or only ‘sometimes’ initiated investigation or treatment of patients with osteoporotic fractures; only 11% ‘always’ or ‘very often’ initiated investigation or treatment. If an osteoporotic fracture is suspected most (70%) refer to a GP or osteoporosis specialist, with only 22% evaluating the condition themselves. Although 46% claimed that they referred patients for a BMD study always or most of the time, only 14% did so routinely. Fifty percent felt it was the GP’s responsibility to identify and initiate the evaluation of the underlying osteoporosis of patients with fragility fractures, compared with 29% who considered that this was the orthopaedic surgeon’s responsibility. Eighty five per cent of the respondents do not prescribe any pharmacological treatment for osteoporosis management. Most commonly (36%) there was a preference for surgery rather than drug prescription. Twenty four percent had access to a specific osteoporosis team for treating osteoporosis. No experience with treating osteoporosis (23%) and no formal education in osteoporosis (16%) were other common reasons. Very few orthopaedic surgeons felt it was their responsibility to treat osteoporosis, however 52% were interested in attending a course on osteoporosis. The findings are contrasted with those of an international study conducted by the Bone and Joint Decade and the International Osteoporosis Foundation, using the same questionnaire. Conclusions: The evidence of under- treatment of osteoporosis after first fragility fractures, suggests that it may be necessary for orthopaedic surgeons to re-evaluate their approach to the management of osteoporosis, either by themselves or others. Further educational opportunities in this area should be considered

Osteoporosis is common in elderly patients and is commonly associated with fractures of the neck of the femur. It is known that this condition is not treated optimally by orthopaedic services around the world. We aim to examine the level of osteoporosis treatment in this fracture and how effective we were in improving treatment for osteoporosis. We retrospectively examined hospital documents from patients admitted between 1 January and 31 December 2004 with femoral neck fracture. All notes were retrieved and were complete. We examined the medications on admission, the place of residence, place of discharge, frequency of DEXA scanning and medications. One hundred and twenty patients were admitted with fracture of the neck of the femur. This group consisted of 23 males with an average age of 76.7, 97 females with an average age of 83.7. Seventy five of these patients were admitted from home, 45 from a rest home. Four patients died prior to treatment, one refused treatment and subsequently died in a hospice. Osteoporotic medications on admission showed that 13 patients were on Bisphosphonate, 6 on Vitamin D and twelve on calcium supplements. Only 14 patients had had DEXA scans prior to admission. On admission eight patients were on no medications of any sort, 53 were on 1–4 medications, 53 were on 5–9 medications and 6 were on greater than 10 medications. On discharge from orthopaedic of the 120 patients 13 were on Bisphosphonate, six on Vitamin D, 13 on calcium supplements. Six patients were on no medications, 47 on 1–4 medications, 55 on 5–9 medications, nine on greater than 10 medications. On discharge from geriatric service, to which 69 patients had been referred 25 were on Bisphosphonate, 13 on Vitamin D, 18 on calcium supplements. One patient was on no medication. 20 were on 1–4 medications, 41 on 5–9 medications and seven on greater than 10 medications. Fifty four had had DEXA scans. We found that the rate of treatment of osteoporosis in the community remains poor with no improvement while in the orthopaedic service. On discharge from the geriatric service significant improvement in osteoporotic medication occurred but there was also an increased in polypharmacy. Further work on the investigation and treatment of osteoporosis in this country is required

The primary purpose of this study was to evaluate the appropriate use of Dual Energy X-ray absorptiometry (DEXA) scanning in the follow-up of osteoporosis. The secondary aim was to ascertain the correlation between body mass index (BMI) and osteoporosis in the study population. Six hundred and sixty six patients were sent for DEXA scanning from the Osteoporosis clinic at 1-Military Hospital from June 1998 to February 2004. A descriptive expost facto study of primary data was undertaken, consisting of patient records, test results and post treatment test results. Patients were classified according to their World Health Organization (WHO) classification of bone density. Each of the categories was then followed-up to determine an improvement or deterioration in a specific category. A total number of 307 (46.1%) follow-up DEXA scans were done over a period of five years. The majority of patients’ bone mineral density (BMD) remained in the same WHO category while a significant number improved to a higher category. The biggest improvement was in elevating patients from an osteoporosis category to an osteopenic category. Only a small number of patients’ BMD deteriorated. A significant positive correlation between BMI and T-scores for all the patients who received DEXA scans was found. It is therefore apparent that it is safe to follow-up patients with osteoporosis by means of DEXA scanning only once every four to five years. The correlation between BMI and bone mineral density, might serve as a useful guide to identify patients qualifying for more frequent follow up scans

Introduction: Osteoporosis is a common skeletal disease characterized by a combination of low bone mass and altered bone microarchitecture with a consequent increase of fragility. The human CER1 is a novel candidate gene for osteoporosis that can bind directly to bone morphogenetic proteins and inhibit their activity. In this study we evaluated the contribution of five novel gene single-nucleotide polymorphisms (SNPs) of CER1 in blood samples from osteoporotic and control groups. Materials and Methods: Peripheral blood samples from 100 postmenopausal women with osteoporosis and 50 healthy Greek women, between 45 and 85 years of age, were collected and DNA was extracted. CER1 polymorphisms genotyping was carried out by PCR and sequencing of the whole gene. Bone mineral density (BMD) was examined by DXA. Statistical analysis was performed using Pearson χ2 or Fisher’s exact test in order to compare allelic frequency distribution. Results: Genetic analysis of the CER1 gene revealed five SNPs at the positions 239C> G (rs3747532), 1058G> T (rs1494360), 2160A> G, 2355A> G (rs17289263), and 2749T> C of the CER1 gene. The above genotypes were distributed differently among osteoporotic and controls. In osteoporotic patients, the SNPs frequencies were: 78.6% heterozygotes and 3.6% homozygotes for 239C> G SNP, 66.7% and 4.3% heterozygotes and homozygotes, respectively, with T allele at the position 1058, 52.4% heterozygotes and 9.5% homozygotes for the polymorphic site A> G nt.2160, 51.2% heterozygotes and 2.4% homozygotes for the G allele at 2355 position of the CER1 gene, whereas only heterozygotes (38.9%) for the 2749T> C polymorphic site were determined (P< 0.001). However, in the control group the polymorphisms were detected only in heterozygosity and the overall distributions of the polymorphisms 239C> G, 1058G> T, 2160A> G, 2355A-> G, and 2749T> C, were 38.9%, 31.3%, 15.6%, 9.4%, 6.9% (P< 0.001), respectively. Discussion: All the above polymorphisms, except the SNP rs3747532, are correlated with osteoporotic patients for the first time. Allele frequencies of the control group are significantly lower than those of osteoporotic for any of the five polymorphisms. These data provide the first evidence of an association (and most possible significant cumulative contribution) between the aforementioned genotypes in CER1 gene and the risk for osteoporosis in postmenopausal women

Low-energy fractures complications are a major public health issue that make osteoporosis even worse. In sub-Saharan Africa, the prevalence of osteoporosis varies from 18.2% to 65.8%. There was no change in bone mineral density between HIV-infected and non-HIV-infected women in Sub-Saharan Africa, where HIV is widespread. Other investigations that demonstrated that HIV-infected people had poor BMD both before and after starting anti-retroviral treatment did not consistently show a low BMD finding. Inflammation-mediated bone remodelling has been associated with low BMD in HIV-infected patients. Antiretroviral Therapy has been demonstrated to exacerbate bone loss in addition to the pre-existing intrinsic risk of developing osteoporosis.

Question: Is there loss of bone in HIV-infected patients before initiating ART?

The patients who were HIV-positive and enrolled in the ADVANCE research were retrospectively reviewed on a desk. All of the 1053 individuals in the ADVANCE research had a DXA scan performed to evaluate BMD as part of the initial screening and recruitment approach. The ADVANCE research enrolled HIV-positive people and randomly assigned them to three ART arms.

A total of 400 patients were reviewed. Of these 400 records reviewed, 62.3% were female. 80% of the participants were younger than 40 years old, and 3% were older than 50 years. 82% were virally suppressed with less than 50 viral copies. The prevalence of osteopenia was 25.5% and osteoporosis was 2.8%, observed in predominantly African female participants aged between 30 and 39 years.

The findings of this study confirm that there is pre-existing bone loss among HIV-infected ART naïve individuals. Approximately 28.3% in our study had clinically confirmed evidence of bone loss and of these, 2.8% of the entire cohort had osteoporosis. Bone loss was most prevalent in black females who are virologically suppressed.

Introduction: Osteoporosis is an increasing problem due to increasing age and inactivity. Distal radial fractures are often the first symptom of this disease. Medical treatment can reduce the risk of further fractures (including hip fractures with the associated mortality and morbidity). Aims: To develop a method for accurate assessment of bone density from routine wrist radiographs. Material and Methods: 1. Various bone substitutes were tested until one was found that gave reasonable density matches with fresh bone over a limited X-ray kV range. 2. Patients with distal radius fractures had the bone substitute placed beside the wrist being X-rayed. Wrist and radius thickness were measured from the radiograph. This was combined with the optical density of the distal radius (relative to the bone substitute) to calculate a value for the bone density. The patients subsequently underwent a DEXA scan of the contralateral (uninjured) wrist. Results: 20 patients. The X-ray calculated bone density and the DEXA density compare well. (R> 0.5)Discussion and Conclusion: This technique gives reasonably accurate results. It is not yet ready for clinical practice. A larger study is required to improve the accuracy of this technique, perhaps comparing results with lumbar spine DEXA

Patients most at risk of osteoporosis are post-menopausal women. However, for many such women, presentation of osteoporosis is only made following their first fragility fracture. Often in the UK, osteoporosis investigation occurs following discharge, and any subsequent secondary prevention starts in the community. This may result in patients with osteoporosis not being investigated or not receiving correct prophylactic treatment. 143 post-menopausal women (av. age 77.7 years) starting secondary osteoporosis prophylaxis following fragility fractures requiring operative intervention were included in this retrospective study. Osteoporosis was defined by DEXA scan using the WHO criteria (122 hip fractures and 21 wrist fractures), following the UK's national guidelines for osteoporosis prophylaxis. Treatment was started following discussion and explanation of treatment with each patient, and either commenced by the surgical team during the acute hospital admission with the fracture, or in an out-patient setting within 6 weeks of the fracture by an orthopaedic specialist nurse. To check compliance, either the patient themselves or the patients' family physician was contacted. Results showed that 120 of the women (83.9%, 102 hip fractures, and 18 wrist fractures) were still compliant with secondary osteoporosis prophylaxis at an average follow-up of 200 days (5 hip fractures lost to follow-up, 0 wrist fractures). 12 women with hip fractures died (0 wrist fractures), and 6 women stopped taking their prophylaxis (3 hip fractures, 3 wrist fractures): 4 for medical reasons, and 2 for unknown reasons. No women sustained further fractures. Few studies have previously investigated compliance of osteoporosis secondary prevention, and our results compare favorably. We therefore recommend the prompt commencement of secondary prevention treatment by the orthopaedic surgical team following osteoporotic fractures

Summary Statement. The structure of bone inside a porous bone graft substitute can be quantified and compared by using a combination of novel measurements of surface area and connectivity. This allows for a numerical representation of the bone structure to be calculated. Introduction. Variation in absolute bone volume as a function of bone graft porosity has been well documented. However quantification of the 3D shape of bone and it's connectivity has always been difficult to assess let alone quantify. By use of novel computational methods the shape and connectivity of the bone can be characterised giving more insight to the relative quality of the bone ingrowth within the different porous grafts. Materials & Methods. Cylindrical monoliths of hydroxyapatite (HA) of varying total porosities (60, 70 and 80% total) were implanted into a lapin model (subchondral distal femur) and the implants removed and XMT (resolution ∼30μm) scans taken at 3, 6, 12 and 24 weeks. The regions of bone and HA were defined using a modified tri-axial histogram with multiple boundaries. The volume and surface area was then collected for the bone in each of the samples, a controlled virtual multi centre degradation was also carried out to calculate the connectivity of the bone. A non-dimensional linear measurement of the surface to volume ratio Kcube value was calculated, which is the number of thousand equal cubes which have the same volume to surface area ratio as the bone. A bone connectivity index is also calculated where a low value indicates the presence of an open interconnected bone structure within the graft. While a high value indicates the presence of bone within the graft as distinct islands distributed throughout the porosity. Results. The change in volume, surface area, Kcube value and bone connectivity index against time for the samples. The volume and surface area values are of limited use when quantifying the shape of the bone, as the surface area generally increases with the volume regardless of surface area to volume ratio. The Kcube values shows that the largest change in shape for the bone occurs between 3 and 6 weeks which fits with the change between woven and lamella structure of the bone. Both the 80 and 60% drop in relative surface area at 6 weeks while the 70% increases. The 70 and 80% show a general increase in surface area while the 60% decreases. The bone connectivity index shows that the 80% has a more open structure than the 60% and they both open up with time. The 70% is close to the structure of the 80% with the exception of 6 weeks which as with the Kcube value is the exception, showing a closing of the bone structure. Discussion/Conclusion. The using the Kcube and bone connectivity index values the structure of the bone in the differing bone graft substitutes can be meaningfully compared and quantified. In the case of the HA samples the significant different between the more closed, lower surface area bone produced by the 60% implant can be easily compared to the much higher surface area, open structures of the bone growing in the 70 and 80% HA

Summary Statement. A population based finite element study that accounts for subject-specific morphology, density and load variations, suggests that osteoporosis does not markedly lower the mechanical compliance of the proximal femur to routine loads. Introduction. Osteoporosis (OP) is a bone disease defined by low bone density and micro-architectural deterioration. This deterioration is neither uniform nor symmetric at the proximal femur. Evidence from analyses performed at the tissue level suggests that the cortical shell at the femoral neck is thinner in OP patients, especially in the superior regions, but not in the infero-anterior ones [Poole, Rubinacci]. Analogously, OP femurs show a higher anisotropy of the trabecular bone than controls [Ciarelli], suggesting a preservation of load bearing capacity in the principal loading direction vs. the transverse one. There is general consensus that the regions subjected to higher loads during walking, which is the predominant motor activity in the elderly, are mostly preserved. All these findings suggest that the OP femur should exhibit an almost normal mechanical competence during daily activities. This would be in accordance with the very low incidence of spontaneous fractures [Parker] and with the moderate fracture predictivity of BMD. Although reasonable, this hypothesis has never been tested at the organ level. Aim of the present study was to verify it with a population-based finite element (FE) study. Patients & Methods. Whole femur Computed Tomography (CT) scans of 200 patients (115 women) with normal femoral anatomy were retrieved from a repository of the Istituto Ortopedico Rizzoli. The database is representative of an adult Italian population (mean 57yrs, range 23–84), and spans a wide range of morphological and densitometric characteristics (CT-simulated T-score of femoral neck BMD ranging from 1 to −4.6). Personalised FE models of all femurs were built from CT data using a validated procedure [Schileo]. A personalised estimate of the variability of loads acting on the proximal femur during normal walking (NW) and stair climbing (SC) was obtained by querying an indexed and searchable database of joint and muscle loads obtained from musculoskeletal models of 90 subjects. 78 possible loading combinations for NW and 50 for SC were defined for each subject, taking into account individual characteristics (height, weight, femoral antetorsion, CCD angle and neck length). Risk of fracture (RF) was defined for each subject as the maximum principal strain / limit strain (1.04% compressive, 0.73% tensile) ratio over the whole loading spectrum. Results and Discussion. No fracture was predicted by the FE models throughout the entire population, yielding an average safety coefficient of between 4 and 5, which is consistent with experimentally determined failure loads in the single leg stance configuration (around 11 BW [Cristofolini]). While a general inverse association was observed with R2∼0.2, no clear correlation was present between the fracture risk and the T-score. The hypothesis that OP does not macroscopically influence the mechanical competence of the femur for daily activities was therefore corroborated, suggesting that the highest risk of fracture in OP patients might be related to a lower OP induced compliance to accidental loads

Osteoporosis is a very common disease in the elderly, generally undertreated. Hip fracture is often the first clinical painful symptom of osteoporosis. It would seem that hip fracture should be a good opportunity to convince the patient of the importance of osteoporosis treatment. We conducted this study to check whether a simple intervention improved the compliance of osteoporosis treatment. 100 consecutive elderly patients with osteoporotic hip fracture received, during postoperative hospital stay, a 5–10 minutes long explanation about osteoporosis, its sequelae, treatment options and their effectiveness in further fracture prevention. Patients received an explanatory brochure and a letter to family physician that included a recent article on fracture rate reduction with osteoporosis treatment. Compliance was examined by telephone survey 3 and 6 months postoperatively. 100 consecutive patients with similar demographic characteristics who were treated for hip fracture prior to intervention served as a historical control. All patients received a recommendation for osteoporosis treatment in the discharge letter. At follow up, 40% of patients in the study group were receiving biphosphonates, as opposed to 20% in the control group (p< 0.01). 77% of control patients received no treatment for osteoporosis compared to 37% of patients after intervention (p< 0.01). Giving the patient a short explanation about osteoporosis combined with a letter to family physician, resulted in a significant improvement in their compliance The orthopaedic surgeon, who treats the patient at the first painful symptom of osteoporosis, has an excellent opportunity to improve patient’s understanding of the disease and her or his compliance to treatment

Osteoporosis has been implicated as one of the causative factors for Colles’ fracture. The current study was designed to establish whether the degree of osteoporosis has any influence on the radiological severity of Colles’ fracture in active elderly peri-menopausal female patients. Female peri-menopausal patients who sustained a Colles’ fracture were studied. The ultra distal Bone Mineral Density (uBMD) was determined using DXA in the contralateral non-fractured wrists, which were also x-rayed. Anthropometric measurements were recorded, the radiological severity of the fracture was assessed using a computerised image analysis system, which measured the radial angle, height and width on AP view and the dorsal tilt on lateral view. Measurements were carried out on the fractured and the normal wrist. Pearson’s correlations between age, height, weight, BMI, uBMD and fracture measurements were carried out. The Bone Deformity Index (BDI) was defined as the summation of all the differences of the previous parameters between the normal and fractured wrists on the AP view. ANOVA, with bonferroni correction, was used to compare the parameters and the radiological measurements between normal, osteopenic and osteoporotic patients. Sixty-seven patients were recruited. Those with Barton fractures, previous fractures of the wrist or a previous history of chronic treatment with bone modifying drugs were excluded. Forty eight patients were analysed. The parameters measured had a tendency to be worse with increasing degree of osteoporosis, although the only significance was in the measurement of dorsal tilt on the lateral view (p = 0.05). The normal patients were significantly heavier (89.3 kg) than the other two groups (p =0.03). In the osteoporotic group the correlation between uBMD and the BDI was −0.6, between uBMD and radial height difference was –0.5 and between uBMD and the angle difference in AP was also –0.5. Similar correlations in normal patients were not statistically significant. Power estimates were performed. Because of the relatively large variability within the samples, a sample size of 550 cases will be necessary to reach a power of 80% to detect a pre-defined clinically significant difference of 3 units in the BDI between groups. The evidence from this study suggests that the initial radiological deformity in osteoporotic patients was greater in those patients with severe degree of osteoporosis. The deformity in normal patients did not have a correlation with the uBMD but these patients were significantly heavier, indicating a different combination of causative factors in these two groups. The precision of the current method of x-ray measurements has enabled a precise definition of the variability within the different groups, resulting in the production of information that was not previously available

Introduction. Osteoporosis is a metabolic disease of the bone responsible for a loss of bone resistance and an increase in fracture risk. World Health Organization (WHO) estimations are about 6.3 millions of femoral neck fractures in the world by 2050. These estimations make osteoporosis a real problem in term of public health. Knowledge in biological tissues mechanical behaviour and its evolution with age are important for the design of diagnosis and therapeutic tools. From the mechanical aspect, bone resistance is dependent on bone density, bone architecture and bone tissue quality. If the importance of bone density and bone architecture has been well explored, the bone tissue quality still remains unstudied because of the lack of biomechanical tools suitable for testing bone at this microscopic dimension. Therefore the goal of this study is to estimate the osteoporotic cancellous bone tissue mechanical behaviour at its microscopic scale, using an approach coupling mechanical assays and digital reconstruction. Materials and methods. The experimental study is based on cancellous bone tissue extracted from human femoral head. Forty 8mm diameters bone cylinders have been removed from femoral head explanted after a femoral neck fracture treated by arthroplasty. These cylinders have been submitted to a digitally controlled compressive trial. Before and after the trials, microscanner analyses with an 8 μm spatial resolution have been realized in order to determine the micro structural parameters. The cylinders have been rebuilt with the digital model-building in order to estimate the mechanical behaviour and the bone quality. Results. The results will be presented from a macroscopic and microscopic point of view and will show the relationship between gender and age of the patients. At the macroscopic scale, we will look at that apparent young modulus heterogeneity and the cracking strength. At the microscopic scale, we will confirm that the cancellous bone tissue mechanical behaviour is close to the Haversian bone tissue mechanical behaviour. Finally, the parametric study will permit us to point out the main microstructural components influencing cancellous bone tissue quality. Conclusion. This study allows a precise estimation of the osteoporotic cancellous bone tissue mechanical behaviour. It seems to be a great step in the understanding of this disease and it could probably lead to great improvements in the diagnosis, prognostic, medical and surgical approaches of osteoporosis

To assess the percentage of patients with an osteoporotic distal radial fracture who had any subsequent investigation or treatment for osteoporosis, and to compare this to the gold standard, all patients seen in a hospital fracture clinic with an osteoporotic fracture should be advised of the possibility of osteoporosis and their primary care team informed of the need for follow-up (Royal College of Physicians, National Osteoporosis Society and The Advisory Group on Osteoporosis). All patients over 50 years old who sustained a distal radial fracture and a subsequent fractured neck of femur after simple falls, over a 7-year period, were included. Evidence of any treatment for, or investigation of, osteoporosis between the initial radial fracture and subsequent neck of femur fracture was recorded. 74 patients met the above criteria. 7 male and 67 female, median age 83 (54 to 99). Eight percent of cases were on treatment for osteoporosis at time of first fracture. A further 8% had evidence of treatment for, or investigation of, osteoporosis commenced by time of their 2nd fracture. 84% of patients received no advice, investigation or treatment. As orthopaedic surgeons we have a duty to inform the primary care team of the need to follow-up patients with osteoporotic fractures. There is a significant cost benefit both to the patient and the health service. We aim to introduce a system whereby a letter is automatically sent to the GP informing them that their patient has been seen in fracture clinic with an osteoporotic distal radial fracture. The letter will also advise them of the current Royal College and Government guidelines on investigation and treatment of osteoporosis. We aim to repeat the audit cycle after a 5-year period with the new system in place

Aims. The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone. Methods. Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted. Results. A total of 30 studies were included, of which six studies used rats and 24 studies used mice. Osteoporosis or bone loss was induced in 14 studies. Interventions included ten with probiotics, three with prebiotics, nine with antibiotics, two with short-chain fatty acid (SCFA), six with vitamins and proteins, two with traditional Chinese medicine (TCM), and one with neuropeptide Y1R antagonist. In general, probiotics, prebiotics, nutritional interventions, and TCM were found to reverse the GM dysbiosis and rescue bone loss. Conclusion. Despite the positive therapeutic effect of probiotics, prebiotics, and nutritional or pharmaceutical interventions on osteoporosis, there is still a critical knowledge gap regarding the role of GM in rescuing bone loss and its related pathways. Cite this article: Bone Joint Res 2021;10(1):51–59

Obesity is correlated with the development of osteoporotic diseases. Gut microbiota-derived metabolite trimethylamine-n-oxide (TMAO) accelerates obesity-mediated tissue deterioration. This study was aimed to investigate what role TMAO may play in osteoporosis development during obesity.

Mice were fed with high-fat diet (HFD; 60 kcal% fat) or chow diet (CD; 10 kcal% fat) or 0.2% TMAO in drinking water for 6 months. Body adiposis and bone microstructure were investigated using μCT imaging. Gut microbiome and serum metabolome were characterized using 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry. Osteogenic differentiation of bone-marrow mesenchymal cells was quantified using RT-PCR and von Kossa staining. Cellular senescence was evaluated by key senescence markers p16, p21, p53, and senescence association β-galactosidase staining.

HFD-fed mice developed hyperglycemia, body adiposis and osteoporosis signs, including low bone mineral density, sparse trabecular microarchitecture, and decreased biomechanical strength. HFD consumption induced gut microbiota dysbiosis, which revealed a high Firmicutes/Bacteroidetes ratio and decreased α-diversity and abundances of beneficial microorganisms Akkermansiaceae, Lactobacillaceae, and Bifidobacteriaceae. Serum metabolome uncovered increased serum L-carnitine and TMAO levels in HFD-fed mice. Of note, transplantation of fecal microbiota from CD-fed mice compromised HFD consumption-induced TMAO overproduction and attenuated loss in bone mass, trabecular microstructure, and bone formation rate. TMAO treatment inhibited trabecular and cortical bone mass and biomechanical characteristics; and repressed osteogenic differentiation capacity of bone-marrow mesenchymal cells. Mechanistically, TMAO accelerated mitochondrial dysfunction and senescence program, interrupted mineralized matrix production in osteoblasts.

Gut microbial metabolite TMAO induced osteoblast dysfunction, accelerating the development of obesity-induced skeletal deterioration. This study, for the first time, conveys a productive insight into the catabolic role of gut microflora metabolite TMAO in regulating osteoblast activity and bone tissue integrity during obesity.

Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated. Cite this article: Bone Joint Res 2020;9(8):524–530

Osteoporosis investigation following a low-trauma fracture is often missed. The aim of this study was to (i) measure the current rate of osteoporosis investigation and (ii) to test a simple intervention that seeks to increase patient awareness and physician alerting following these sentinel events. Our study showed that 92% of the intervention group was investigated compared to 18% of the control group. This study suggests that a simple inexpensive intervention can increase the rate of osteoporosis investigation in an at risk population. National guidelines (1–3) emphasize that low-trauma fractures should prompt to investigate for osteoporosis but more than 80% of “at risk” people are not investigated. To measure the rate of diagnosis of osteoporosis when patients with low-trauma wrist fractures obtain usual care compared to a patient education and physician alerting intervention. This is a prospective, controlled trial of patient education and physician alert following a distal radius fracture. Participants in the intervention group received four-parts: (i) an information sheet, (ii) a letter from the treating orthopedic surgeon to the patient’s family physician signaling the recent low-trauma fracture (iii) a follow-up reminder call to return to the family doctor for assessment and (iv) a fax to the family physician suggesting assessment and management of osteoporosis. The control group received usual care of the fracture and no specific information about osteoporosis. All participants were telephoned at 6 months to assess investigation status. Fifty-one participants > 50 yrs. with a fragility wrist fracture were enrolled: 92% of the Intervention participants were investigated for osteoporosis by the family physician compared to 18% of the Control group. This is a significant difference (p ≤ 0.01). This study suggests that a simple inexpensive intervention by the surgeon can increase the rate of osteoporosis investigation in an at risk population. Orthopedic surgeons can contribute to the care of osteoporosis by readily adopting simple clinical actions which will make patients more likely to be investigated for osteoporosis

Purpose: Recognizing Osteoporosis and Its Consequences in Québec revealed that 73% of women 50y and over are not provided anti-fracture therapy following fragility fracture. This study’s objectives were to determine predictors of osteoporosis (OP) diagnosis (DX) and treatment (TX) 6 to 8 months after fragility fracture. Method: At phase 1, women were recruited at cast or out-patient clinics within 16 weeks post-fracture. Consenting patients answered a short questionnaire classifying them as experiencing a fragility or traumatic fracture; no reference to the association between fracture and OP was made and no investigation or intervention was proposed. At phase 2, 6–8 months post-fracture, the women completed a questionnaire on demographic features, clinical characteristics and risk factors for OP. The DX (informed of OP and/or BMD measurement with diagnosis of OP) and TX (bisphosphonates, raloxifene, nasal calcitonin or teriparatide) rates of OP were determined via this questionnaire. This analysis included only women with a fragility fracture who were not receiving OP TX at phase 1. Results: Of the 1273 women completing phase 1, 1001 (79%) sustained a fragility fracture; 818 were untreated at phase 1 and completed the phase 2 questionnaire. Overall, 79% of these participants had not received a DX of osteoporosis or were without OP TX at phase 2. The highest rate of DX and TX of OP occurred 0–5 months post-fracture and decreased considerably thereafter. In multivariate analyses, the results of BMD tests before or after the fracture event (p< 0.0001) and mobility problems (p=0.03) were the only variables that influenced the DX of OP. BMD test results were the strongest predictor (p< 0.0001) of TX followed by the fracture site (hip, femur and pelvis; p=0.015) and administration of vitamin D supplements at the time of fracture (p=0.035). No other risk factors for OP significantly influenced the DX or TX rate. No demographic or clinical features or OP risk factors were significantly associated with the decision to refer women for BMD testing post-fracture. Conclusion: Although fragility fracture represents a greater risk of future fragility fracture than low BMD, physicians based their decision to treat on BMD and not the clinical event (fragility fracture)

Purpose: Only 20% of women presenting with fragility fracture are subsequently investigated for Osteoporosis (OP). Blurred lines of responsibility between the orthopedic surgeons (OS) and the general practitioners may partly explain this situation. OPTIMUS is a 3 year health management program, lead by an OS and a rheumatologist, whose objective is to improve the rate of initiation of and persistence on treatment of OP in patients sustaining a fragility fracture visiting an OS at the Centre hospitalier universitaire de Sherbrooke. Method: All outpatients aged 50 years and older in which a fragility fracture is suspected by the OS are informed by a nurse practitioner about the OPTIMUS program. The first 200 patients seen at the Hôtel-Dieu site of the CHUS represent the control group. Inpatients with hip fragility fracture are evaluated by a rheumatologist. After signed consent, outpatient participants are randomized to one out of two intervention groups: The Minimal Intervention group includes nurse counseling and written general information transmitted to both patient and treating physician. Same information is given in the Intensive Intervention group. Blood tests and osteodensitometry are also performed and results transmitted to the treating physician along with personalized guidelines for treatment of the patient’s OP. In both interventions, patients are reached by phone at fixed intervals. Additional rounds of intervention are repeated as needed to increase the rates and persistence of appropriate treatment. Results: Over the first 6 months, the OS team identified 300 patients, 30% of which suffered from hip fracture. Acceptance rates to OPTIMUS management program were close to 95% with direct contact as compared to 50% with delayed phone contact. 5% of outpatients could not name a treating physician and thus had to be seen in rheumatology. The results during the first 18 months of the project will assess the feasibility of OPTIMUS’ interventions. Conclusion: There is a substantial care gap in the management of OP, despite the availability of diagnostic modalities and effective treatment. Involving orthopedic surgeons as key leaders of a multidisciplinary team implementing a systematic approach to identify patient with OP should help to close this care gap

To evaluate the effects of 6 and 18 months of abaloparatide (ABL) compared with placebo (PBO) on bone mineral density (BMD) in the acetabular regions of postmenopausal women with osteoporosis (OP).

Acetabular bone loss, as may occur in OP, increases risk of acetabular fragility fractures^a. In total hip arthroplasty (THA), low acetabular BMD adversely affects primary stability, osseointegration, and migration of acetabular cups.^c ABL is an osteoanabolic agent for the treatment of men and postmenopausal women with OP at high risk for fracture. Effects of ABL on acetabular BMD are unknown.

Hip DXA scans were obtained at baseline, 6, and 18 months from a random subgroup of postmenopausal women (aged 49–86 y) from the phase 3 ACTIVE trial randomized to either ABL 80 µg/d or PBO (n=250/group). Anatomical landmarks were identified in each DXA scan to virtually place a hemispherical shell model of an acetabular cup and define regions of interest corresponding to DeLee & Charnley zones 1 (R1), 2 (R2), and 3 (R3). BMD changes compared to baseline were calculated for each zone. Statistical P values were based on a repeated mixed measures model.

BMD in all zones were similar at baseline in the ABL and PBO groups. BMD significantly increased in the ABL group at 6 and 18 months compared with PBO (all P<0.0001 vs PBO). BMD in the PBO group was relatively stable over time.

ABL treatment resulted in rapid and progressive increases in BMD of all 3 acetabular zones. Increasing acetabular BMD has the potential to improve acetabular strength, which may reduce risk of acetabular fragility fractures. In bone health optimization prior to THA, increased acetabular BMD via ABL may provide better primary stability and longevity of acetabular cups in postmenopausal women with OP.

Abstract

Bioabsorbable metals hold a lot of potential as orthopaedic implant materials. Three metal families are currently being investigated: iron (Fe), magnesium (Mg) and zinc (Zn). Currently, however, biodegradation of such implants is poorly predictable. We thus used Direct Metal Printing to additively manufacture porous implants of a standardized bone-mimetic design and evaluated their mechanical properties and degradation behaviour, respectively, under in vivo-like conditions.

Atomized powder was manufactured to porous implants of repetitive diamond unit cells, using a ProX DMP 320 (Layerwise, Belgium) or a custom-modified ReaLizer SLM50 metal printer. Degradation behaviour was characterized under static and dynamic conditions in a custom-built bioreactor system (37ºC, 5% CO₂ and 20% O₂) for up of 28 days. Implants were characterized by micro-CT before and after in vivo-like degradation. Mechanical characterization (according to ISO 13314: 2011) was performed on an Instron machine (10kN load cell) at different immersion times in simulated body fluid (r-SBF). Morphology and composition of degradation products were analysed (SEM, JSM-IT100, JEOL). Topographically identical titanium (Ti-6Al-4V, Ti64) specimen served as reference.

Micro-CT analyses confirmed average strut sizes (420 ± 4 μm), and porosity (64%), to be close to design values. After 28 days of in vivo-like degradation, scaffolds were macroscopically covered by degradation products in an alloy-specific manner. Weight loss after cleaning also varied alloy-specifically, as did the change in pH value of the r-SBF. Corrosion time-dependent changes in Young's moduli from 1200 to 800 MPa for Mg, 1000 to 700 MPa for Zn and 48-8 MPa for iron were statistically significant.

In summary, DMP allows to accurately control interconnectivity and topology of implants from all three families and micro-structured design holds potential to optimize their degradation speed. This first systematic report sheds light into how design influences degradation behaviour under in vivo-like conditions to help developing new standards for future medical device evaluation.

Chronic glucocorticoid use causes osteogenesis loss, accelerating the progression of osteoporosis. Histone methylation is shown to epigenetically increase repressive transcription, altering lineage programming of mesenchymal stem cells (MSC). This study is undertaken to characterize the action of histone demethylase UTX to osteogenic lineage specification of bone-marrow MSC and bone integrity upon glucocorticoid treatment.

Bone-marrow MSC were incubated in osteogenic medium containing supraphysiological dexamethasone. Osteogenic gene expression and mineralized nodule formation were probed using RT-PCR and von Kossa staining. The enrichment of trimethylated lysine 27 at histone 3 (H3K27me3) in Dkk1 promoter was quantified using chromatin immunoprecipitation-PCR. Bone mass and trabecular morphometry in methylprednisolone-treated skeletons were quantified using microCT analysis.

Supraphysiological dexamethasone decreased osteogenic genes Runx2 and osteocalcin expression and mineralized matrix production along with reduced UTX expression in MSC. Forced UTX expression attenuated the glucocorticoid-mediated loss of osteogenic differentiation, whereas UTX knockdown provoked osteogenesis loss and cytoplasmic oil overproduction. UTX demethylated H3K27 and reduced the glucocorticoid-mediated the H3K27 enrichment in Dkk1 promoter, reversing beta-catenin signal, but downregulating Dkk1 production by MSC. In vivo, treatment with UTX inhibitor GSK-J4 significantly suppressed bone mineral density, trabecular volume, and thickness along with porous trabecular, fatty marrow and disturbed beta-catenin/Dkk1 histopathology comparable with glucocorticoid-induced osteoporosis condition.

This study offers a productive insight into how UTX protects MSC from methylated histone-mediated osteogenesis repression in the development of glucocorticoid-induced osteoporosis.

Introduction and Objective

Senescent bone cell overburden accelerates osteoporosis. Epigenetic alteration, including microRNA signalling and DND methylation, is one of prominent features of cellular senescence. This study aimed to investigate what role microRNA-29a signalling may play in the development of senile osteoporosis.

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment. Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1

Osteoporosis is a mineral bone disease arising from the predominance of osteoclastic bone resorption. Bisphosphonates which inhibit osteoclasts are commonly used in osteoporosis treatment, but are not without severe adverse effects like osteonecrosis of the jaw. The mechanisms behind the development of such phenomena is not well understood. Bone homeostasis is achieved through an intimate cross-talk between osteoclasts and osteoblasts. Thus, it is important to visualise activities of these cells simultaneously in situ. Currently, there are means to visualise osteoclast shape and numbers with tartrate-resistant alkaline phosphatase (TRAP) staining but no practical and accurate methods to quantify osteoclast activity in situ. This investigation aims to establish the use of ELF97, a substrate of TRAP, to visualise and quantify osteoclast activity. This provides vital clues to mechanisms of various bone disorders. TRAP dephosphorylation of ELF97 results in a detectable fluorescent product at areas of osteoclast activity. Osteoclastic activity was initiated in zebrafish by inducing crush injuries in tail fin rays. Colocalisation of ELF97 fluorescence with osteoclast-specific DsRed in transgenic zebrafish, visualised under confocal microscopy, is used to further establish the specificity of ELF97 to sites of osteoclastic activity. Quantification is established by comparing fluorescence between wild type, osteoclast-deficient mutants and bisphosphonate-treated zebrafish. The utility of ELF97 will also be investigated in terms of the stability of the florescent product. The investigation revealed that ELF97 and DsRed fluorescence were found commonly at crush sites with osteoclastic activity. Wild type zebrafish had greater fluorescence compared to osteoclast-deficient (p<0.0001) and bisphosphonate-treated zebrafish (p<0.0001) after 7 and 14 days post-crush, revealing that fluorescence from ELF97 corresponds to expected osteoclastic activity. Fluorescence of tail fins treated with ELF97 did not diminish over a period of 21 days of storage, demonstrating its stability. ELF97 is thus a useful means to visualise osteoclast activity, potentially crucial in more advanced investigations to understand bone disorders. It could be used in combination with other cellular markers in whole biological samples to study and experimentally manipulate bone remodelling

Osteoporosis is an underdiagnosed and often neglected disease, with a huge impact on social costs arising from fracture management that could be avoided with an appropriate prevention programme. The approach to diagnosis is not always efficacious and cost-optimised, often suggesting instrumental densitometry in a somehow irrational way. The objective of this study is to evaluate the introduction and use of a simple score system, in order to optimise the access to instrumental diagnosis with quantitative ultrasound (QUS) densitometric technique for those patients at risk. We used the OSIRIS score system questionnaire in order to have a simple tool to manage the osteoporosis screening of patients in our centre from January to December 2003 (more than 2000 patients in total). The score risk derived for each patient was used to recommend the instrumental densitometric measurement (heel QUS) and the need for vertebral X-ray scan and morphometric evaluation. In a further analysis on a more limited number of patients, we searched for correlations between densitometry with other score systems (O.R.A.I.,N.O.F.,S.C.O.R.E.,A.B.O.N.E.) and with pre-existing fragility fractures (vertebral and non-vertebral). Our data suggest that a correlation exists between OSIRIS score risk and heel QUS densitometric T-score, suggesting the usefulness and validity of such a score system in order to optimise the access to instrumental diagnosis of osteoporosis

Objectives. Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation. Methods. MSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, in vivo experimentation explored bone mineral density, bone mineral content, and the ash weight and dry weight of femoral bone. Results. The results revealed that AP significantly promoted cell viability, upregulated cyclin D1 and increased RUNX2, OCN, ALP, and BMP-2 protein levels in MSCs. Moreover, we found that AP notably activated PI3K/AKT and Wnt/β-catenin signalling pathways in MSCs. Additionally, the relative expression level of H19 was upregulated by AP in a dose-dependent manner. The promoting effects of AP on cell proliferation and osteoblast differentiation were reversed by H19 knockdown. Moreover, in vivo experimentation further confirmed the promoting effect of AP on bone formation. Conclusion. These data indicate that AP could promote MSC proliferation and osteoblast differentiation by regulating H19. Cite this article: X. Xie, M. Liu, Q. Meng. Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone Joint Res 2019;8:323–332. DOI: 10.1302/2046-3758.87.BJR-2018-0223.R2

Objectives. Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis. Methods. Microarray data sets GSE56815 and GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta-MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify biological functions. Furthermore, the transcriptional regulatory network was established between the top 20 DEGs and transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating characteristic (ROC) analysis was applied to investigate the diagnostic value of several DEGs. Results. A total of 1320 DEGs were obtained, of which 855 were up-regulated and 465 were down-regulated. These differentially expressed genes were enriched in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways, mainly associated with gene expression and osteoclast differentiation. In the transcriptional regulatory network, there were 6038 interactions pairs involving 88 transcriptional factors. In addition, the quantitative reverse transcriptase-polymerase chain reaction result validated the expression of several genes (VPS35, FCGR2A, TBCA, HIRA, TYROBP, and JUND). Finally, ROC analyses showed that VPS35, HIRA, PHF20 and NFKB2 had a significant diagnostic value for osteoporosis. Conclusion. Genes such as VPS35, FCGR2A, TBCA, HIRA, TYROBP, JUND, PHF20, NFKB2, RPL35A and BICD2 may be considered to be potential pathogenic genes of osteoporosis and may be useful for further study of the mechanisms underlying osteoporosis. Cite this article: B. Xia, Y. Li, J. Zhou, B. Tian, L. Feng. Identification of potential pathogenic genes associated with osteoporosis. Bone Joint Res 2017;6:640–648. DOI: 10.1302/2046-3758.612.BJR-2017-0102.R1

Benefits for the patients and for the Health Care System could rise from the adoption of a global clinical approach (“disease management approach”) for osteoporosis and its fracture complications vs the current “component-based approach”. Disease management is a kind of method aimed to manage (from a clinical and managerial perspective) highly prevalent and expensive diseases from the prevention to treatment and rehabilitation in order to improve patient outcome and to lower costs in general. Osteoporosis and its fracture complications in the Italian population meet the criteria of being highly prevalent and expensive. Four million women and 800,000 men in Italy suffer from osteoporosis. Furthermore, incidence and costs of hip fractures in the elderly Italian population (> 65 years old) are comparable to those of acute myocardial infarction in people aged > 45. Accordingly, we built a simulation model to evaluate potential benefits of a disease management approach. Incidence and costs (including drug-related costs) of hip fractures registered in Italy in 2001 were compared to those predictable in the hypothesis of treating all individuals who have at least one vertebral fracture with bisphosphonates. Almost 1.5 million people in Italy are supposed to have a vertebral fracture and consequently an increased risk of hip fracture. We considered a NTT value of 40 (“Number To Treat”: number of patients to treat in order to prevent one hip fracture), according to the FIT study (Fracture Intervention Trial, involving 6,500 patients). Only 6.4% of subjects with a vertebral fracture is currently receiving treatment with bisphosphonates. In this simulation, the extension of this anti-resorptive therapy to all individuals with vertebral fractures would produce a 48% reduction in the incidence of hip fractures (NTT=40) among people aged > 65 and increase global costs to an acceptable 21% rate. The number of hospitalisations for hip fractures in the elderly would be reduced from 78,350 (2001) to 40,850 (simulation); direct costs for hospitalisation and surgery would pass from 438 million (2001) to 236 million Euros (simulation); general costs for rehabilitation from 416 million (2001) to 224 million Euros (simulation); indirect costs from 171 to 93 million Euros; drug-related costs would rise from 46 million (0.29% of the national pharmaceutical expenses) to 750 million Euros (4.4% of the national expenses). This study seems to confirm the benefits (with regards to health and cost of illness) of a disease management approach for osteoporosis and its fracture complications

Sclerostin (SOST) is an endogenous inhibitor of Wnt/β-catenin signalling pathway to impair osteogenic differentiation and bone anabolism. SOST immunotherapy like monoclonal antibody has been observed to control bone remodeling and regeneration. This study is aimed to develop a SOST vaccine and test its protective effects on estrogen deficiency-induced bone loss in mice. Gene sequences coded SOST peptide putative targeting Wnt co-receptor LRP5 were cloned and constructed into vectors expressing Fc fragment to produced SOST-Fc fusion protein. Mice were subcutaneously injected SOST-Fc to boost anti-SOST antibody. Bone mineral density, microstructure, and mechanical property were quantified using μCT scanning and material testing system. Serum bone formation and resorption markers and anti-SOST levels were measured using ELISA. SOST-Fc injections significantly increased serum anti-SOST antibody levels but reduced serum SOST concentrations. SOST-Fc vaccination significantly reduced estrogen deficiency-induced serum bone resorption markers CTX-1 increased serum bone formation marker osteocalcin. Of note, it significantly alleviated the severity of estrogen-induced loss of bone mineral density, trabecular morphometric properties, and biomechanical forces of bone tissue. Mechanistically, SOSF-Fc vaccination attenuated trabecular loss histopathology and restored immunostaining of Wnt pathway like Wnt3a, β-catenin, and TCF4 in bone tissue along with increased serum osteoclast inhibitor OPG levels but decreased serum osteoclast enhancer RANKL concentrations. Taken together, SOST-Fc vaccination boosts anti-SOST antibody to neutralize SOST and mitigates the estrogen deficiency-induced bone mass and microstructure deterioration through preserving Wnt signalling. This study highlights an innovative remedial potential of SOST vaccine for preventing osteoporosis.

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

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).

Background

MicroRNAs are non-coding small RNAs that reportedly regulate mRNA targets or protein translation of various tissues in physiological and pathological contexts. This study was undertaken to characterise the contributions of microRNA-29a (miR-29a) to the progression of estrogen deficiency-mediated excessive osteoclast resorption and bone loss.

Aims

Postoperative complication rates remain relatively high after adult spinal deformity (ASD) surgery. The extent to which modifiable patient-related factors influence complication rates in patients with ASD has not been effectively evaluated. The aim of this retrospective cohort study was to evaluate the association between modifiable patient-related factors and complications after corrective surgery for ASD.

Summary

Arginine supplementation is helpful in treatment of osteoporosis.

Aims

This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images.

Aims

This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

The current treatment for osteoporosis such as bisphosphonates inhibits the catabolic activity of osteoclasts and subsequent bone resorption, but does not increase bone formation. There is therefore interest in using anabolic factors such as stem cells to augment fracture repair. The poor bone formation in postmenopausal women could be due to poor retention and function of Mesenchymal stem cells (MSCs) resulting into delayed unions. Another factor associated with fracture healing is the retention and migration of stem cells to the site of injury (1–3). The aim of this study was to isolate stem cells from osteopenic rats and investigate and compare the CD marker expression, proliferation, migration, osteogenic and adipogenic differentiation. The hypothesis of this study is that the migration of MSCs from young, adult and ovariectomised (OVX) rats will have different proliferation, differentiation and migratory abilities.

Ovariectomy was performed in 6–9 month old Wistar rats and osteopenia developed over a 4 month post-op period. MSCs were harvested from the femora of young, adult and osteopenic Wistar rats. Proliferation of the these MSCs from the three group of rats was measured using Alamar blue, osteogenic differentiation was measured using ALP expression at day 0, 7, 14 and 21 and alizarin red at day 21. Adipogenic differentiation was measured at day 7, 14 and 21 using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF1. For analysis, the number of cells migrating across the membrane was expressed as a percentage of the cells remaining on the upper membrane surface. Data was analysed using a Student t-test where p values < 0.05 were considered significant.

The stem cells from all 3 groups of rats expressed on average the same amount of CD29 (>90%), CD90 (>96%), CD34 (<5%) and CD45 (approx 10%). The proliferation rate measured by Alamar blue normalised against DNA was also similar at day 3, 7, 10 and 14. However, interestingly the migration and differentiation ability was significantly different between the MSCs from the 3 groups of rats. The young MSCs were not only better at differentiating into bone and fat as well, but they also migrated significantly more towards SDF1. The migration of SDF-1 doubled with young rats compared to the adult rats (p = 0.023) and it was four times higher when compared to cells isolated from OVX rats (p = 0.013).

MSCs from OVX rats are similar to MSCs from young rats. However when induced to turn into bone, fat and migrate towards SDF1, young MSCs are significantly more responsive than MSCs from OVX and adult control rats. The poor homing ability and differentiation of the stem cells and their retention may result in a reduction in bone formation leading to delayed union in fractures of osteoporotic patients(4).

We invited 1604 randomly selected women, all 75 years of age, to participate in a study on the risk factors for fracture. The women were divided into three groups consisting of 1044 (65%) who attended the complete study, 308 (19%) respondents to the study questionnaire only and 252 (16%) who did not respond. The occurrence of the life-time fracture was ascertained from radiological records in all groups and by questionnaires from the attendees and respondents.

According to the radiological records, fewer of the questionnaire respondents (88 of 308, 28.6%) and non-respondents (68 of 252, 27%) had sustained at least one fracture when compared with the attendees (435 of 1044, 41.7%; chi-squared test, p < 0.001). According to the questionnaire, fewer of the respondents (96 of 308, 31.1%) had sustained at least one previous fracture when compared with the attendees (457 of 1044, 43.7%; chi-squared test, p < 0.001).

Any study concerning the risk of fracture may attract those with experience of a fracture which explains the higher previous life-time incidence among the attendees. This factor may cause bias in epidemiological studies.

Aims

The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice.

The pathogenesis of falling bone mineral density (BMD) as a universal feature of advancing age is poorly understood¹. Frequently culminating in the development of osteoporosis, the process is attributable to more than 500,000 fragility fractures occurring every year in the UK Such injuries are associated with great levels of morbidity, mortality and a £3.5 billion cost to the healthcare economy².

With age, humans are known to accumulate somatic mitochondrial DNA (mtDNA) mutations in mitotic and post mitotic tissue, and stem cell precursors³. Compelling evidence in recent years, particularly that provided by animal models suggests that these mutations are intrinsic to the ageing process^4–6. We provide evidence for the first time that mitochondrial dysfunction contributes significantly to the failure of bone homeostasis and falling BMD.

We have utilised a mouse model that accumulates mtDNA mutations at 3–5 times the rate of normal mice, consequently ageing and developing osteoporosis prematurely⁷, to clearly demonstrate that osteoblasts are vulnerable to mtDNA mutations. We have developed a new quadruple immunofluorescent assay to show that mitochondrial respiratory chain dysfunction occurs in osteoblasts as a consequence (p < 0.0001). We show that this mitochondrial dysfunction is associated with reduced BMD in female and male mice by 7 (p = 0.003) and 11 (p = 0.0003) months of age respectively. Using osteoblasts derived from mesenchymal stem cells extracted from male and female mice with mitochondrial dysfunction aged 4, 7 and 11 months, we demonstrate a vastly reduced capacity to produce new mineralised bone in vitro when compared to wild type cell lines (p < 0.0001). Exercise was found to have no beneficial effect on osteoblast and whole bone phenotype in this mouse model. It is likely that mtDNA mutations accumulating over a longer time period in human ageing have significantly detrimental effects on bone biology and diminishing BMD.

There is increasing interest in using anabolic factors such as stem cells to augment fragility fracture repair. One of the factors associated with fracture healing is the retention and migration of stem cells to the site of injury (1–3). The aim of this study was to isolate stem cells from osteopenic rats and investigate and compare the CD marker expression, proliferation, migration, osteogenic and adipogenic differentiation. The hypothesis of this study is that the migration of MSCs from young, adult and ovariectomised (OVX) rats will have different proliferation, differentiation and migratory abilities.

CD marker expression of MSCs from young, adult and osteopenic rats was measured using flow cytometry. Proliferation, osteogenic differentiation and adipogenic differentiation was measured using Alamar Blue, ALP expression and Alizari n Red and quantitative Oil red O respectively. Cells were incubated in Boyden chambers to quantify their migration towards SDF1. Data was analysed using a Student t-test where p values < 0.05 were considered significant.

MSCs from all 3 groups of rats had similar proliferation and expression of CD29(>90%), CD90(>96%), CD34(<5%) and CD45(approx 10%). The proliferation rate was also similar. However, interestingly the migration and differentiation ability was significantly different between the MSCs from the 3 groups of rats. The young MSCs were not only better at differentiating into bone and fat, but they also migrated significantly more towards SDF1. MSCs from OVX rats are similar to MSCs from young rats. However when induced to turn into bone, fat and migrate towards SDF1, young MSCs are significantly more responsive than MSCs from OVX and adult control rats. The poor homing ability and differentiation of the stem cells and their retention may result in a reduction in bone formation leading to delayed union in fractures of osteoporotic patients(4).

Mobility plays an important role, in particular for patients with osteoporosis and after trauma surgery, both as an outcome and as treatment. Mobility is closely linked to the patient”s quality of life and exercise is a powerful additional treatment option. In order to be able to generate an evidence base to evaluate various surgical and non-surgical treatment options, objective measurements of patient mobility and exercise over a certain time period are needed. Wearables are a promising candidate, with obvious advantages compared to questionnaires and/or PROs. However, when extracting parameters with wearables, one often faces the problem of algorithms not performing well enough for special cases like slow gait speeds or impaired gait, as they typically appear in this patient group. We plan to further extend the applicability of the actibelt system (3D accelerometer, 100Hz), in particular to improve the measurement precision of real-world walking speed in slow and impaired walking. We are using a special measurement wheel including a rotating 3D accelerometer that allows to capture high quality real-world walking speed and distance measurements, and a mobile high resolution camera system. In a first block 20 patients with osteoporosis were included in the study at the Ludwigs-Maximilians-University”s Department of General, Trauma and Reconstructive Surgery in Munich, Germany and equipped with an actibelt. Patients were asked to walk as “normal” as possible, while wearing their usual apparel, in the building and outside the building. They climbed stairs and had to deal with all unexpected “stop and go” events that appear in real-world walking. Various gait parameters will be extracted from the recorded data and compared to the gold standard. We will then tune the existing algorithms as well as new algorithms (e.g. step detection based on continuous wavelet transformation) to explore potential improvements of both step detection and speed estimation algorithms. Further refinement and validation using real world data is warranted.

Orthopaedic surgeons frequently assess fragility fractures (FF), however osteoporosis (OP) is often managed by primary care physicians (PCP). Up to 48% of FF patients have had a previous fracture (Kanis et al., 2004). Discontinuity between fracture care and OP management is a missed opportunity to reduce repeat fractures. This studied aimed to evaluate current OP management in FF patients presenting to cast clinic.

A single centre, prospective observational study where seven traumatologists screened for FF in cast clinic. FF was defined as a hip, distal radius (DR), proximal humerus (PH), or ankle fracture due to a ground level fall. Patients completed a self-administered questionnaire for demographics, fracture type and treatment, medical and fracture history, and previous OP care. The primary outcome was number of FF patients who received OP investigation and/or treatment. Secondary outcomes included Fracture Risk Assessment Tool (FRAX), repeat fracture rate, and anti-resorptive related fractures. Descriptive statistics were used for analysis.

Between November 17, 2014 and October 13, 2015, a total of 1,677 patients attended cast clinic for an initial assessment. FF were identified in 120 patients (7.2%). The FF cohort had a mean age of 65.3 (± 14.3) years, mean BMI of 26.1 (± 5.3), and was comprised of 83.3% females. Fracture distribution was 69 (57.5%) DR, 23 (19%) ankle, 20 (16.5%) PH, and seven (5.8%) hip fractures, with 24 of the FF (19.8%) treated operatively. Thirteen (10.8%) were current smokers and 40 (33.3%) formerly smoked. A history of steroid use was present in 13 patients (10.8%). Ninety (n = 117; 76.9%) of patients ambulated independently. Twenty-two patients (18.3%) reported prior diagnosis of OP, most often by a PCP (n = 19; 73.7%) over 5 years previously. Calcium (n = 59; 49.2%) and Vitamin D (n = 70; 58.3%) were common and 26 patients (21.5%) had a prior anti-resorptive therapy, with Alendronate (n = 9) being most common. One patient had an anti-resorptive-related fracture. Raloxifene was used in ten patients. Forty-seven patients (39.2%) had a prior fracture at a mean age of 61.3 (± 11.9) years, with DR and PH fractures being most common. Eleven patients had two or more prior fractures. A family history of OP was found in 34 patients (28.1%). Mean FRAX score was 20.8% (± 10.8%) 10-year major fracture risk and 5.9% (± 6.6%) 10-year hip fracture risk (n = 30 bone densiometry within one-year). Of the 26 patients with a Moderate (10–20%) or High (> 20%) 10-year major fracture risk, only eight (30.8%) reported a diagnosis of OP and only three (11.5%) had seen an OP specialist.

Cast clinics provide an opportunity for OP screening, initiation of treatment, and patient education. This cohort demonstrated a high rate of repeat fractures and poor patient reporting of prior OP diagnosis. This study likely underestimated FF and calls for resource allocation for quantifying true burden of disease and outpatient fracture liaison service.

Aims

Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP.

Aims

Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation.

Transient osteoporosis of the hip is a rare condition of unknown aetiology affecting middle aged men with no risk factors and women in their third trimester of pregnancy. The condition invariably resolves spontaneously, however, due to its rarity and initially normal plain radiographs, the syndrome is often not appreciated early in its development, and particularly represents a diagnostic problem of differentiation from osteonecrosis.

We present a case of unilateral transient osteoporosis of the hip in a 52 year old male and a case of bilateral hip involvement in a 32 year old female in her 35th week of pregnancy. Both cases include the initial and follow-up plain radiographs, MRI and DEXA scan findings, through to symptomatic resolution.

We present a literature review of the disease and analyse the current evidence on aetiology, the problems in diagnosis and the current treatment modalities.

Aims

Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.

Introduction and aims: Minimal trauma fractures may be the first indication of osteoporosis [OP]. Available data suggests that the continuum of care [EDorthopaedic service-GP] is breaking down with respect to identification and treatment of osteoporosis. Our aim was to determine the extent of this breakdown in the Australasian context.

Methods: Observational retrospective cohort study of patients aged 50 years or over who were treated and discharged with wrist fracture due to minimal trauma. Data collected included demographics, fracture details, cause of injury, bone density testing and osteoporosis-related medication change. Outcomes of interest were the proportion of patients who underwent bone density testing and treatment in the follow-up period.

Results: 131 patients were studied; 83% were female with median age of 71 years. No patient was referred by ED or fracture clinic for bone density testing [0%, 95% CI 0–3.5%]. Telephone follow-up was obtained from 91 patients, of whom 28 [31%] reported having bone density testing after their fracture. 50% [14, 95% CI 32–67%] of these were found to have osteoporosis. Seven patients [8%] commenced treatment with a bisphosphonate and one [1%] commenced a selective oestrogen receptor modulator.

Conclusion: Follow-up of ‘at risk’ patients suffering minimal trauma wrist fractures treated in the ED is poor. Systems to improve identification and treatment of osteoporosis in this group are needed if future osteoporotic fractures and their consequences are to be avoided. Possible models will be put forward.

While it is not denied that immobilisation of a diseased joint may be essential, there is a growing mass of evidence that immobilisation in recumbency of the whole patient has severe effects both in the neighbourhood of the actual lesion and upon the skeleton as a whole. Further search for measures to counteract the undesirable skeletal effects of recumbency is much needed.

Purpose

Assessment of effectiveness of spinal fixation in conditions of general osteoporosis.

An osteoporosis screening service for patients presenting to the fracture clinic in Derriford Hospital Plymouth was established in February 2009. We report on the findings of the first year of patients referred for dual energy X-ray absorptiometry (DEXA) screening.

Patients between 50 and 75 years of age, who sustained a fracture as a result of a fall from standing height or less, who had not previously had a DEXA scan within the last two years, were referred. Patients outside these age limits with other risk factors for osteoporosis were scanned at the discretion of the fracture clinic consultant. Of those patients who were referred, 96% subsequently attended for a scan timed to coincide with their scheduled fracture clinic follow-up appointment.

402 patients were scanned in total, of which 351 were female and 51 were male. The mean patient age was 65. The results for women were as follows: 21% normal, 45% osteopenic, 34% osteoporotic. The results for men were: 19% normal, 43% osteopenic, 38% osteoporotic. The scan results were forwarded to the patient's general practitioner for action as deemed necessary.

These findings support the establishment of this screening service for both men and women.

TOH was first described by Curtis and Kinkade in 1959, in women in the 3rd trimester of pregnancy. Later the disease was described in middle-aged males (4th-6th decade). Very rare occurrence was described in children and in females not connected to pregnancy.

Thirty-six patients with sudden hip pain with normal radiographs but increase uptake on bone scan and bone marrow edema in the head and neck on MRI were investigated by the senior author. Two patients (age 16 and 18) had Osteoid osteoma in the neck and two elderly patients (72 female and 75 male) had stress fracture in the neck were excluded from the study. The rest, 32 patients (28 males and 4 females – not connected to pregnancy) are the study group. Three male patients had bilateral involvement 1 to 3 years apart. The initial symptoms were pain, limping with minimal or no restriction in range of motion. All patients had plain radiographs, bone scan and MRI. Bone scan was positive in all and MRI showed bone edema in the neck and head in all. All patients were initially treated by non-weight bearing for six weeks followed by additional MRI every 6 weeks till the bone edema and symptoms subsided. In all patients the third MRI showed improvement in bone edema and were allowed to weight bear. None of the patients showed progression from TOH to AVN even in 7 patients with Crescent lines on T-1 images.

The mean F.U. was 51 months (4 to 131 months). Five patients still complained of mild pain in the affected hip, all with the exception of one had full range of motion. None of the patients had limping. All the plain radiographs were normal, with no signs of AVN or deformity of the head. In contrast the Dexa measurements of all patients showed decreased bone density in the affected hip compared to the other.

Conclusion: TOH is a benign disease. Even when Crescent lines are present all patients heal successfully without signs of AVN. Excellent correlation was found between subsidence of pain and improvement of bone edema on MRI. AVN and TOH are two distinct entities and therefore the treatment of TOH should always be conservative.

In order to assess the effect of osteoporosis on healing time we retrospectively reviewed the files of 165 patients with femoral shaft fractures that were treated in our service by locked, intramedullary nailing. Patients were divided in two age groups; Group A (study group) consisted of patients over 65 years old with radiological evidence of osteoporosis and group B (control group) of patients between 18 and 40 years old with no signs of osteoporosis.

Sixty-six out of 165 patients fulfilled the inclusion criteria for this study. Patients with open fractures, pathological fractures, revision surgery, severe brain injuries, prolonged ITU stay and severe co morbidities were excluded. Twenty-nine patients were classified in group A and 37 in group B. All patients had been assigned the Injury Severity Score (ISS) and had been followed-up clinically and radiographically until fracture union.

In all patients the Singh Index Score for osteoporosis was assigned. In all group A patients Singh score 4 or less was assigned, suggesting the presence of installed osteoporosis, whereas group B patients were assigned with Sighn score 5 or 6. Fracture healing was significantly different between the groups.

Fractures of Group A healed in 19.38±5.9 weeks (12–30) and in group B 16.19±5.07 weeks (10–28) (P=0.02) Fracture healing of nailed femoral diaphyseal fractures significantly delays in older osteoporotic patients. Further studies are mandatory to clarify the exact impact of osteoporosis in the whole healing process and the possible future therapeutic strategies.

Vertebral fracture (VF) is a common complication of osteoporosis. Patients with osteoporotic VFs are often without symptoms and many of these fractures are detected by chance. Only one third of VFs is clinically diagnosed. However, osteoporotic VFs may also be very painful and cause severe discomfort during several weeks. In both genders low bone mineral density (BMD), prevalent VF and increasing age are strong predictors of VF. About one fifth of the patients with a VF suffer a new VF during the following year.

Clinical consequences of VF include acute and chronic back pain, decreased quality of life and increased mortality. The care of patients with VF includes proper pain management and early rehabilitation. The use of elastic lumbosacral brace reduces pain when mobilising patient after VF. Calcitonin has been shown to have an analgetic effect. Sometimes the vertebral fracture causes a diagnostic problem and reasons other than osteoporosis should be ruled out (e.g. myeloma, lymphoma, metastases, other malign diseases). If feasible, the diagnosis of osteoporosis should be confirmed by BMD measurement. Osteoporotic VFs are seldom unstable requiring operative treatment. In case of neurological complications operative decompression and stabilisation should be considered. Impaired bone quality causes problems in pedicle screw fixation. Cement augmentation and special anchorage screws may provide increase in holding power in osteoporotic bone. Percutaneous vertebroplasty and balloon kyphoplasty are mini-invasive procedures that provide immediate and long lasting pain relief in VF patients. These techniques are technically demanding and require careful patient selection. Recent, prospective, randomized studies have shown that antiresorptive drugs can prevent new fractures in patients who had experienced previous fractures.