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.
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. Data were obtained from a population-based longitudinal study
and assessed for the prevalence of osteoporosis, falls, fractures
and medication use. DXA scans were also undertaken.Objectives
Methods
Purpose: To evaluate the impact of the
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
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.
Aims.
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
Summary.
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
As a part of the European Union BIOMED I study “Assessment of Bone Quality in
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
Background.
Aims.
Aims.
Background:
Introduction:
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.
Background &
Objectives:
1. The syndrome of osteoporosis is reviewed and its various causes are mentioned.
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
Introduction:
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.
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
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).
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
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
Introduction:
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:
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.
Summary Statement. The structure of bone inside a
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.
Introduction.
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
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.
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.