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.
Purpose: Recognizing
Purpose: Only 20% of women presenting with fragility fracture are subsequently investigated for
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 fracturesa. 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 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 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.
Current therapies for osteoporosis are limited to generalised antiresorptive or anabolic interventions, which do not target specific regions to improve skeletal health. Moreover, the adaptive changes of separate and combined pharmacological and biomechanical treatments in the ovariectomised (OVX) mouse tibia has not been studied yet. Therefore, this study combines micro- computed tomography (micro-CT) imaging and computational modelling to evaluate the efficacies of treatments in reducing bone loss. In vivo micro-CT (10.4µm/voxel) images of the right tibiae of N=18 female OVX C57BL/6 mice were acquired at weeks 14, 16, 18, 20 and 22 of age for 3 groups: mechanical loading (ML), parathyroid hormone (PTH) or combined therapies (PTHML). All mice received either injection of PTH (100μg/kg/day, 5days/week) or vehicle from week 18. The right tibiae were mechanically loaded in vivo at week 19 and 21 with a 12N peak load, 40 cycles/day and 3 days/week. Bone adaptation was quantified through spatial changes in bone mineral density (BMD) and strain distribution was obtained from micro-CT-based finite element models.Abstract
Objectives
Methodology
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 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 Micro-CT analyses confirmed average strut sizes (420 ± 4 μm), and porosity (64%), to be close to design values. After 28 days of 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
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.
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. Bone biopsy and serum were harvested from 13 young patients and 15 senior patients who required spine surgery. Bone mass, microstructure, and biomechanics of miR-29a knockout mice (miR-29aKO) and miR-29a transgenic mice (miR-29aTg) were probed using mCT imaging and three-point bending material test. Senescent cells were probed using senescence-associated b-galactosidase (SA-b-gal) staining. Transcriptomic landscapes of osteoblasts were characterized using whole genome microarray and KEGG bioinformatics. miR-29a and senescence markers p16INK4a, p21Waf/cipl and inflammatory cytokines were quantified using RT-PCR. DNA methylome was probed using methylation-specific PCR and 5-methylcytosine immunoblotting.Introduction and Objective
Materials and Methods
Objectives.
Objectives.
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.
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.
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). PubMed, Embase, and Cochrane Library were systematically searched to retrieve relevant articles published before 15 November 2022. Studies focusing on the correlation between selenium and BMD, OP, or fracture were included. Effect sizes included regression coefficient (β), weighted mean difference (WMD), and odds ratio (OR). According to heterogeneity, the fixed-effect or random-effect model was used to assess the association between selenium and bone health.Aims
Methods
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. Osteoblast-specific transgenic mice overexpressing miR-29a driven by osteocalcin promoter (C57BL/6JNarl-TgOCN-mir29a) or wild-type mice were subjected to bilateral ovariectomy. Bone mineral density, trabecular microarchitecture and osteoclast distribution was quantified by μCT and histomorphometry. Primary CD11b+CSF-1R+ preosteoclasts were isolated for detecting ex vivo osteoclast differentiation. Gene expression and transcription factor-promoter interaction were quantified by RT-PCR and chromatin immunoprecipitation.Background
Methods
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. ASD patients with two-year data were included. Complications were categorized as follows: any complication, major, medical, surgical, major mechanical, major radiological, and reoperation. Modifiable risk factors included smoking, obesity, osteoporosis, alcohol use, depression, psychiatric diagnosis, and hypertension. Patients were stratified by the degree of baseline deformity (low degree of deformity (LowDef)/high degree of deformity (HighDef): below or above 20°) and age (Older/Younger: above or below 65 years). Complication rates were compared for modifiable risk factors in each age/deformity group, using multivariable logistic regression analysis to adjust for confounders.Aims
Methods
Arginine supplementation is helpful in treatment of osteoporosis. Nitric oxide (NO) is a short-lived free radical involved in several biological processes as a bioregulator and as a second messenger. It inhibits osteoclastic bone resorption in vitro and regulates bone remodeling. Zolendronic acid has been established as a treatment for post menopausal osteoporosis. Study was done to compare the efficacy of Nitic oxide donor (L-arginine) with that of Zolendronic acid for the treatment of osteoporosis.Summary
Introduction
This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images. The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm3). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis.Aims
Methods
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. In this study, a titanium rod was implanted in the medullary cavity of one femoral metaphysis in OVX rats, and then the rats were randomly divided into four groups: Sham group (Sham, n = 10), OVX rat group (OVX, n = 10), melatonin day treatment group (OVX + MD, n = 10), and melatonin night treatment group (OVX + MN, n = 10). The OVX + MD and OVX + MN rats were treated with 30 mg/kg/day melatonin at 9 am and 9 pm, respectively, for 12 weeks. At the end of the research, the rats were killed to obtain bilateral femora and blood samples for evaluation.Aims
Methods
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.
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 network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed.Aims
Methods
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 process4–6. 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
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.
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. Using quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined. Western blotting was used to examine the expression of PAK2 protein. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. To examine the osteogenic differentiation, Alizarin red along with ALP staining was used. RNA immunoprecipitation assay and bioinformatics analysis, as well as a dual-luciferase reporter, were used to study the association between PCBP1-AS1, PAK2, and miR-126-5p.Aims
Methods
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. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the expression of microRNA (miR)-760 and ankyrin repeat and FYVE domain containing 1 (ANKFY1) in OP tissues and hBMSCs. Cell viability was measured using the Cell Counting Kit-8 assay. The expression of cyclin D1 and osteogenic marker genes (osteocalcin (OCN), alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2)) was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mineral deposits were detected through Alizarin Red S staining. In addition, Western blotting was performed to detect the ANKFY1 protein levels following the regulation of miR-760. The relationship between miR-760 and ANKFY1 was determined using a luciferase reporter assay.Aims
Methods
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.
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. The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Aims
Methods
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.
Assessment of effectiveness of spinal fixation in conditions of general osteoporosis. 112 patients with multiple osteoporotic pathological vertebral body fractures were surgically treated. Multilevel laminar or transpedicular instrumentation with or without ventral stabilization (group A) was used on 64 of them. The cemented polyaxial screws were used in 48 cases (group B). The patients treated with multilevel transpedicular fixation with cemented screws were included in B-I subgroup. The patients treated with monosegmental fixation (around fractures) with same screws were included in B-II subgroup. The parameters of stability (bone resorption around screws and cement, dislocation of implants, clinical symptoms) were studied in both groups. Outcome results and discussion: In group “A” the parameters of stability were the purest. The displacement of instrumentation with lost of correction has been revealed in 21% of cases. The reoperations were done in 17% of them. In groups B-I and B-II the parameters of stability were the same. There were no clinical signs of instability up to2 years of supervision. In 75% of cases the bone resorption around bone cement has been revealed after 3–6 months. But there were no cases of instrumental displacement. Spinal fixation in treatment of multiple pathological vertebral body fractures in conditions of general osteoporosis using the vertebroplasty with cemented screws provide good stability of the spine for long outcome. This method allows to achieve the clinical result with less invasive approach by shortening of extent of fixation.Purpose
Material and methods of studies
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.
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.