Aims. Osteoporosis and abnormal bone metabolism may prove to be significant factors influencing the outcome of arthroplasty surgery, predisposing to complications of aseptic loosening and peri-prosthetic fracture. We aimed to investigate baseline bone mineral density (BMD) and bone turnover in patients about to undergo arthroplasty of the hip and knee. Methods. We prospectively measured bone mineral density of the hip and lumbar spine using dual-energy X-ray absorptiometry (DEXA) scans in a cohort of 194 patients awaiting hip or knee arthroplasty. We also assessed bone turnover using urinary deoxypyridinoline (DPD), a type I collagen crosslink, normalised to creatinine. Results. The prevalence of DEXA proven hip osteoporosis (T-score ≤ -2.5) among hip and knee arthroplasty patients was found to be low at 2.8% (4 of 143). Spinal osteoporosis prevalence was higher at 6.9% (12 of 175). Sixty patients (42% (60 of 143)) had osteopenia or osteoporosis of either the hip or spine. The mean T-score for the hip was -0.34 (. sd. 1.23), which is within normal limits, and the mean hip Z-score was positive at 0.87 (. sd. 1.17), signifying higher-than-average BMD for age. The median urinary DPD/creatinine was raised in both female patients at 8.1 (interquartile range (IQR) 6.6 to 9.9) and male patients at 6.2 (IQR 4.8 to 7.5). Conclusions. Our results indicate hip and knee arthroplasty patients have higher BMD of the hip and spine compared with an age-matched general population, and a lower prevalence of osteoporosis. However, untreated osteoporotic patients are undergoing arthroplasty, which may negatively impact their outcome. Raised DPD levels suggest abnormal bone turnover, requiring further investigation. Cite this article: Bone Joint Res 2014;3:14–19

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.

Femoroacetabular impingement (FAI) results from a morphological deformity of the hip and is associated with osteoarthritis (OA). Increased bone mineral density (BMD) is observed in the antero-superior acetabulum rim where impingement occurs. It is hypothesized that the repeated abnormal contact leads to damage of the cartilage layer, but could also cause a bone remodelling response according to Wolff's Law. Thus the goal of this study was to assess the relationship between bone metabolic activity measured by PET and BMD measured in CT scans. Five participants with asymptomatic cam deformity, three patients with uni-lateral symptomatic cam FAI and three healthy controls were scanned in a 3T PET-MRI scanner following injection with [18F]NaF. Bone remodelling activity was quantified with Standard Uptake Values (SUVs). SUVmax was analyzed in the antero-superior acetabular rim, femoral head and head-neck junction. In these same regions, BMD was calculated from CT scans using the calibration phantom included in the scan. The relationship between SUVmax and BMD from corresponding regions was assessed using the coefficient of determination (R. 2. ) from linear regression. High bone activity was seen in the cam deformity and acetabular rim. SUVmax was negatively correlated with BMD in the antero-superior region of the acetabulum (R. 2. =0.30, p=0.08). SUVmax was positively correlated with BMD in the antero-superior head-neck junction of the femur (R. 2. =0.359, p=0.067). Correlations were weak in other regions. Elevated bone turnover was seen in patients with a cam deformity but the relationship to BMD was moderate. This study demonstrates a pathomechanism of hip degeneration associated with FAI deformities, consistent with Wolff's law and the proposed mechanical cause of hip degeneration in FAI. [18F]-NaF PET SUV may be a biomarker of degeneration, especially in early stages of degeneration, when joint preservation surgery is likely to be the most successful

Stand-alone anterior lumbar interbody fusion (ALIF) provides the opportunity to avoid supplemental posterior fixation. This may reduce morbidity and complication rate, which is of special interest in patients with reduced bone mineral density (BMD). This study aims to assess immediate biomechanical stability and radiographic outcome of a stand-alone ALIF device with integrated screws in specimens of low BMD. Eight human cadaveric spines (L4-sacrum) were instrumented with SynFix-LR™ (DePuy Synthes) at L5/S1. Quantitative computed tomography was used to measure BMD of L5 in AMIRA. Threshold values proposed by the American Society of Radiology 80 and 120 mg CaHa/mL were used to differentiate between Osteoporosis, Osteopenia, and normal BMD. Segmental lordosis, anterior and posterior disc height were analysed on pre- and postoperative radiographs (Fig 1). Specimens were tested intact and following instrumentation using a flexibility protocol consisting of three loading cycles to ±7.5 Nm in flexion-extension, lateral bending, and axial rotation. The ranges of motion (ROM) of the index level were assessed using an optoelectronic system. BMD ranged 58–181mg CaHA/mL. Comparison of pre- and postoperative radiographs revealed significant increase of L5/S1 segmental lordosis (mean 14.6°, SD 5.1, p < 0.001) and anterior disc height (mean 5.8mm, SD 1.8, p < 0.001), but not posterior disc height. ROM of 6 specimens was reduced compared to the intact state. Two specimens showed destructive failure in extension. Mean decrease was most distinct in axial rotation up to 83% followed by flexion-extension. ALIF device with integrated screws at L5/S1 significantly increases segmental lordosis and anterior disc height without correlation to BMD. Primary stability in the immediate postoperative situation is mostly warranted in axial rotation. The risk of failure might be increased in extension for some patients with reduced lumbar BMD, therefore additional posterior stabilization could be considered. For any figures or tables, please contact the authors directly

Osteoporosis is a common disorder characterized by low bone mass and reduced bone quality that affects the bone strength negatively and leads to increased risk of fracture. Bone mineral density (BMD) has been the standard instrument for the diagnosis of osteoporosis and the determination of fracture risk. Despite the approximation of the bone mass, BMD does not provide information about the bone structure. Trabecular bone score (TBS), which provides an indirect evaluation of skeletal microarchitecture, is calculated from dual X-ray absorptiometry and a simple and noninvasive method that may contribute to the prediction of osteoporotic fractures in addition to the measure of bone density. The goal of this study was to determine the mean TBS values in healthy postmenopausal women and the overall association between TBS and demographic features, bone mineral density of the lumbar spine and femoral neck and bone mineral density to body mass index ratio (BMD/BMI) of the lumbar spine. Fifty-three postmenopausal healthy women participated. The bone mineral density of the lumbar spine and femoral neck were measured dual X-ray absorptiometry. Anteroposterior lumbar spine acquisitions were used to calculate TBS for L1-L4. Age, height, weight, BMI and the ratio of BMD to BMI, which was considered to be a simple tool for assessing fracture risk in especially obese individuals, were calculated. The relationship between TBS and other variables was examined using Spearman's rank correlation coefficients. Mean BMD of the lumbar spine and the femoral neck were 0.945 ± 0.133 and 0.785 ± 0.112 g/cm2, respectively (Table 1). Mean TBS was 1.354 ± 0.107. There was a significant positive moderate correlation between TBS and total lumbar BMD/BMI ratio (r=0.595, pTBS values of postmenopausal women were negatively correlated with age and BMI and positively with bone mineral density and BMD/BMI ratio. The ratio between lumbar BMD and BMI presented a stronger correlation with TBS than that of BMD with TBS. Because of the better correlation, the BMD/BMI ratio may be used as a simple tool for the assessment of the risk of fractures. Further investigation may be needed to evaluate the factors influencing exercise intervention on TBS on this population of patients

Objectives. Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data. Method. We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05. Results. We identified multiple gene sets associated with BMD in one or more regions, including relevant known biological gene sets such as the Reactome Circadian Clock (GSEA p-value = 1.0 × 10. -4. for LS and 2.7 × 10. -2. for femoral necks BMD in eQTLs-based GSEA) and insulin-like growth factor receptor binding (GSEA p-value = 5.0 × 10. -4. for femoral necks and 2.6 × 10. -2. for lumbar spines BMD in meQTLs-based GSEA). Conclusion. Our results provided novel clues for subsequent functional analysis of bone metabolism, and illustrated the benefit of integrating eQTLs and meQTLs data into pathway association analysis for genetic studies of complex human diseases. Cite this article: W. Wang, S. Huang, W. Hou, Y. Liu, Q. Fan, A. He, Y. Wen, J. Hao, X. Guo, F. Zhang. Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density. Bone Joint Res 2017;6:572–576

Odontoid fracture of the second cervical vertebra (C2) is the most common spinal fracture type in elderly patients. However, very little is known about the biomechanical fracture mechanisms, but could play a role in fracture prevention and treatment. This study aimed to investigate the biomechanical competence and fracture characteristics of the odontoid process. A total of 42 human C2 specimens (14 female and 28 male, 71.5 ± 6.5 years) were scanned via quantitative computed tomography, divided in 6 groups (n = 7) and subjected to combined quasi-static loading at a rate of 0.1 mm/s until fracturing at inclinations of −15°, 0° and 15° in sagittal plane, and −50° and 0° in transverse plane. Bone mineral density (BMD), specimen height, fusion state of the ossification centers, stiffness, yield load, ultimate load, and fracture type according to Anderson and d'Alonzo were assessed. While the lowest values for stiffness, yield, and ultimate load were observed at load inclination of 15° in sagittal plane, no statistically significant differences could be observed among the six groups (p = 0.235, p = 0.646, and p = 0.505, respectively). Evaluating specimens with only clearly distinguishable fusion of the ossification centers (n = 26) reveled even less differences among the groups for all mechanical parameters. BMD was positively correlated with yield load (R² = 0.350, p < 0.001), and ultimate load (R² = 0.955, p < 0.001), but not with stiffness (p = 0.070). Type III was the most common fracture type (23.5%). These biomechanical outcomes indicate that load direction plays a subordinate role in traumatic fractures of the odontoid process in contrast to BMD which is a strong determinant of stiffness and strength. Thus, odontoid fractures appear to result from an interaction between load magnitude and bone quality

While knee osteoarthritis (OA) is now recognized as a complex disease affecting the whole joint, not just the cartilages, there remains a paucity of data regarding the interactions between knee components. One relationship of particular interest is between the spatial variations in cartilage thickness (CTh) and subchondral bone mineral density (BMD). Indeed, bone and cartilage are two mechanosensitive tissues that interact as a functional unit and there is evidence of a biomechanical coupling between both tissues. Particularly, a recent in vivo study has shown a positive relationship in non-OA knees with thicker cartilage where bone is denser, and an alteration of this relationship in OA knees. These observations support the concept of an osteochondral unit and warrant additional research to assess the influence of bone depth. Therefore, this study aimed to characterize the relationship between spatial variations in CTh and BMD measured at various depths below the bone surface. CT-arthrography of 20 non-OA tibias and 20 severe medial-compartment OA tibias were segmented to build 3D mesh models of the bones and cartilages. Each individual tibia model was registered to a reference tibia, allowing to calculate BMD maps at 1, 3, 5 and 10mm below the bone-cartilage interface in the medial compartment. Pearson correlations between CTh maps and the four BMD maps were then calculated for each knee. Lastly, differences in correlation coefficients between successive bone layers were assessed using Wilcoxon signed-rank tests. In both OA and non-OA tibias, the correlation coefficients were higher with the BMD measured in the 1mm layer, and followed a pattern of statistically significant decrease with bone layers of increasing depth (p < 0.021). In non-OA tibias, the median relationship was positive with a strong effect size in the 1, 3 and 5mm layers, while in OA tibias the median relationship was positive only in the 1mm layer and with a medium effect size. In the OA tibias, the median relationship was negative with a weak effect size in the 3 and 5mm layers, and it was negative with a medium effect size in the 10mm layer. In conclusion, the results of the present study support the value of considering bone and cartilage as a unit, and more generally support OA pathophysiology models based on relationships among knee properties

Objectives. The aim of the current study was to assess whether calcaneal broadband ultrasound attenuation (BUA) can predict whole body and regional dual-energy x-ray absorptiometry (DXA)-derived bone mass in healthy, Australian children and adolescents at different stages of maturity. Methods. A total of 389 boys and girls across a wide age range (four to 18 years) volunteered to participate. The estimated age of peak height velocity (APHV) was used to classify children into pre-, peri-, and post-APHV groups. BUA was measured at the non-dominant heel with quantitative ultrasonometry (QUS) (Lunar Achilles Insight, GE), while bone mineral density (BMD) and bone mineral content (BMC) were examined at the femoral neck, lumbar spine and whole body (DXA, XR-800, Norland). Associations between BUA and DXA-derived measures were examined with Pearson correlations and linear regression. Participants were additionally ranked in quartiles for QUS and DXA measures in order to determine agreement in rankings. Results. For the whole sample, BUA predicted 29% of the study population variance in whole body BMC and BMD, 23% to 24% of the study population variance in lumbar spine BMC and BMD, and 21% to 24% of the variance in femoral neck BMC and BMD (p < 0.001). BUA predictions were strongest for the most mature participants (pre-APHV R. 2. = 0.03 to 0.19; peri-APHV R. 2. = 0.05 to 0.17; post-APHV R. 2. = 0.18 to 0.28) and marginally stronger for girls (R. 2. = 0.25-0.32, p < 0.001) than for boys (R. 2. = 0.21-0.27, p < 0.001). Agreement in quartile rankings between QUS and DXA measures of bone mass was generally poor (27.3% to 38.2%). Conclusion. Calcaneal BUA has a weak to moderate relationship with DXA measurements of bone mass in children, and has a tendency to misclassify children on the basis of quartile rankings. Cite this article: B. K. Weeks, R. Hirsch, R. C. Nogueira, B. R. Beck. Is calcaneal broadband ultrasound attenuation a valid index of dual-energy x-ray absorptiometry-derived bone mass in children? Bone Joint Res 2016;5:538–543. DOI: 10.1302/2046-3758.511.BJR-2016-0116.R1

The effect of high-fat diet and testosterone replacement therapy upon bone remodelling was investigated in orchiectomised male APOE-/- mice. Mice were split in to three groups: sham surgery + placebo treatment (control, n=9), orchiectomy plus placebo treatment (n=8) and orchiectomy plus testosterone treatment (n=10). Treatments were administered via intramuscular injection once a fortnight for 17 weeks before sacrifice at 25 weeks of age. Tibiae were scanned ex-vivo using µCT followed by post-analysis histology and immunohistochemistry. Previously presented µCT data demonstrated orchiectomised, placebo treated mice exhibited significantly reduced trabecular bone volume, number, thickness and BMD compared to control mice despite no significant differences in body weight. Trabecular parameters were rescued back to control levels in orchiectomised mice treated with testosterone. No significant differences were observed in the cortical bone. Assessment of TRAP stained FFPE sections revealed no significant differences in osteoclast or osteoblast number along the endocortical surface. IHC assessment of osteoprotegerin (OPG) expression in osteoblasts is to be quantified alongside markers of osteoclastogenesis including RANK and RANKL. Results support morphological analysis of cortical bone where no change in cortical bone volume or density between groups is in line with no significant change in osteoblast or osteoclast number and percentage across all three groups. Future work will include further IHC assessment of bone remodelling and adiposity, as well as utilisation of mechanical testing to establish the effects of observed morphological differences in bone upon mechanical properties. Additionally, the effects of hormone treatments upon murine-derived bone cells will be investigated to provide mechanistic insights

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

Quantitative ultrasound (QUS) is a promising tool to estimate bone structure characteristics and predict fragile fracture. The aim of this pilot cross-sectional study was to evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragile fractures retrospectively in postmenopausal women. Methods. RF signal and speed of sound (SOS) were obtained using an axial transmission QUS at one‐third distal radius for 246 postmenopausal women. Based on the involved RF signal, we conducted a MResNet, which combines multi-channel training with original ResNet, to classify the high risk of fragility fractures patients from all subjects. The bone mineral density (BMD) at lumber, hip and femoral neck acquired with DXA was recorded on the same day. The fracture history of all subjects in adulthood were collected. To assess the ability of the different methods in the discrimination of fragile fracture, the odds ratios (OR) calculated using binomial logistic regression analysis and the area under the receiver operator characteristic curves (AUC) were analyzed. Results. Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was discriminant for all fragile fractures (OR = 2.64; AUC = 0.74), for Vertebral fracture (OR = 3.02; AUC = 0.77), for non-vertebral fracture (OR = 2.01; AUC = 0.69). MResNet showed comparable performance to that of BMD of hip and lumbar with all types of fractures, and significantly better performance than SOS all types of fractures. Conclusions. the MResNet model based on the ultrasonic RF signal can significantly improve the ability of QUS device to recognize previous fragile fractures. Moreover, the performance of the proposed model modified by age, weight, and height is further optimized. These results open perspectives to evaluate the risk of fragile fracture applying a deep learning model to analyze ultrasonic RF signal

SL-PLUS MIA stem (Smith & Nephew Orthopaedics AG) is a modified implant of Zweymuller type SL-PLUS standard stem (Smith & Nephew Orthopaedics AG). We constructed finite element (FE) models and analysed equivalent stresses in the femur. In addition, we measured bone mineral density (BMD) in the femur by dual-energy X-ray absorptiometry (DEXA) after THA. The purpose of this study was to investigate the equivalent stress and to compare the results of the FE analyses with changes in BMD after THA. Twenty-one patients (18 women and 3 men) who underwent primary cementless THA with SL-PLUS MIA or SL-PLUS formed the basis of this study. Eleven patients received SL-PLUS MIA and ten patients received SL-PLUS. Zones were defined according to Gruen's system (zones 1∼7). Computed-tomography (CT) images of the femur were taken before and at 1 week after THA. FE models of the femur and prosthesis were obtained from CT data by Mechanical Finder (Research Center of Computational Mechanics Inc., Tokyo, Japan), software that creates FE models showing individual bone shape and density distribution. Equivalent stresses were analysed in zones 1 to 7 and compared to the DEXA data. FE studies revealed that there was no significant difference in equivalent stress between SL-PLUS MIA and SL-PLUS. BMD was maintained after THA in zones 3, 4, and 5, whereas BMD decreased in zones 2, 6, and 7. In zone 1, BMD decreased in SL-PLUS MIA stem group by 14%, while BMD was maintained in SL-PLUS standard stem

Introduction and Objective. Individuals with type 2 diabetes (T2D) have a 3-fold increased risk of bone fracture compared to non-diabetics, with the majority of fractures occurring in the hip, vertebrae and wrists. However, unlike osteoporosis, in T2D, increased bone fragility is generally not accompanied by a reduction in bone mineral density (BMD). This implies that T2D is explained by poorer bone quality, whereby the intrinsic properties of the bone tissue itself are impaired, rather than bone mass. Yet, the mechanics remain unclear. The objective of this study is to (1) assess the fracture mechanics of bone at the structural and tissue level; and (2) investigate for changes in the composition of bone tissue along with measuring total fluorescent advanced glycation end products (fAGEs) from the skin, as T2D progresses with age in Zucker diabetic fatty (ZDF (fa/fa)) and lean Zucker (ZL (fa/+)) rats. Materials and Methods. Right ulnae and skin sections were harvested from ZDF (fa/fa) (T2D) and ZL (fa/+) (Control) rats at 12 and 46 weeks (wks) of age (n = 8, per strain and age) and frozen. Right ulnae were thawed for 12 hrs before micro-CT (μCT) scanning to assess the microstructure and measure BMD. After scanning, ulnae were loaded until failure via three-point bending. Fourier transform-infrared microspectroscopy (FTIR) was used to measure various bone mineral- and collagen-related parameters such as, mineral-to-matrix ratio and nonenzymatic cross-link ratio. Finally, fAGEs were measured from skin sections using fluorescence spectrometry and an absorbance assay, reported in units of ng quinine/ mg collagen. Results. At 12 and 46 wks bone size was significantly smaller in length (p < 0.01), cortical area (p < 0.001) and cross-sectional moment of inertia (p < 0.001) in T2D rats compared to age-matched controls. A slight reduction in BMD was observed in T2D rats compared to controls at both ages, however, this was not significant. Structural properties of T2D bone were significantly altered at 12 and 46 wks, with bending rigidity increasing approximately 2.5-fold and 1.5-fold in control and T2D rats with age, respectively (p < 0.0001). Similarly, yield and ultimate moment significantly reduced in T2D rats with age in comparison to controls (p < 0.0001). Energy absorbed to failure was significantly reduced in T2D rats at 46 weeks of age compared to controls (p < 0.01). The amount of energy absorbed to failure increased approximately 1.4-fold from 12 to 46 wks in control rats, however, in T2D rats a reduction was seen with age, although not significant. At 12 wks, there was no significant deficits in tissue material properties, whereas, at 46 wks a significant reduction in yield stress, yield strain and ultimate stress was observed for T2D rats in comparison to controls (p < 0.05). Conclusions. These findings show that longitudinal growth is impaired as early as 12 wks of age and by 46 wks bone size is significantly reduced in T2D rats compared to controls. The reduction in T2D structural properties is likely attributed to the bone geometry deficits. At 12 wks of age, the tissue material properties are not altered in T2D bone versus controls. However, at 46 wks, bone strength is reduced in T2D, leading to the conclusion that tissue properties are altered as the disease progresses

Compressive fracture of osteoporotic vertebrae has been one of the most important health problems in aged societies because severely injured spin might be a reason of bedridden for elderly people. Osteoporosis has been widely assessed by averaged bone mineral density of vertebrae measured using DEXA, however, BMD sometimes does not reflect the strength of vertebrae. CT imaged based finite element method (CT-FEM) has been applied to evaluate the strength of vertebrae based on the biomechanics theory and approved by a part of the highly advanced medical treatment in Japan. In the present study, compressive strength of more than 100 vertebrae were evaluated using CT-FEM, and the correlation between BMD and the strength was thoroughly investigated. It was found that some vertebrae with high BMD could have low strength which may cause fracture easily. Thus, a controversial point of the BMD based diagnosis of osteoporosis was clearly indicated. In this invited talk, some basic theories of CT-FEM and fracture assessment and some key results from the recent study will be presented

Total Hip Replacement (THR) is one of the most successful operations in all of medicine, however surgeons just rely on their experience and expertise when choosing between cemented or cementless stem, without having any quantitative guidelines. The aim of this project is to provide clinicians with some tools to support in their decision making. A novel method based on bone mineral density (BMD) measurements and assessments was developed 1) to estimate the periprosthetic fracture risk (FR) while press-fitting cementless stem; 2) to evaluate post-operative bone remodeling in terms of BMD changes after primary THR. Data for 5 out of over 70 patients (already involved in a previous study. 1. ) that underwent primary THA in Iceland were selected for developing novel methods to assess intra-operative FR and bone mineral density (BMD) changes after the operation. For each patient three CT images were acquired (Philips Brilliance 64 Spiral-CT, 120 kVp, slice thickness: 1 mm, slice increment: 0.5 mm): pre-op, 24 hours and 1 year post-operative. Pre-op CT scan was used to create 3D finite element model (Materialise Mimics) of the proximal femur. The material properties were assigned based on Hounsfield Units. Different strategies were analyzed for simulating the press-fitting operation, developing what has already been done in prior study. 1. In the finite element simulation (Ansys Workbench), a pressure (related to the implant hammering force of 9.25 kN. 2. ) was applied around the femur's hollow for the stem and the distribution of maximum principal elastic strain over the bone was calculated. Assuming a critical failure value. 3. of 7300 με, the percentage of fractured elements was calculated (i.e. FR). Post 24 hours and Post 1 year CT images were co-registrated and compared (Materialise Mimics) in order to assess BMD changes. Successively, volumes of bone lost and bone gained were calculated and represented in a 3D model. Age and gender should not be taken as unique indicators to choose between implants typologies, since also three dimensional BMD distribution along with volume of cortical bone influence the risk of periprosthetic fractures. Highest FR values were experienced in the calcar-femorale zone and in similar location on the posterior side. BMD loss volume fractions after 1 year were usually higher than BMD gain ones. Consistently with prior studies. 4. , BMD loss was mainly concentrated around the proximal end (lesser trochanter area, outer bone). If present, BMD gain occurred at the distal end (below stem's tip) or proximally (lesser trochanter area, interface contact with the stem). The use of clinical data for BMD assessments serves as an important tool to develop a quantitative method which will support surgeons in their decisions, guiding them to the optimal implant for the patient. Knowing the risk of fracture if choosing a cementless stem and being aware of how the bone will remodel around the stem in one year's time can eventually lead to reduction in revisions and increased quality of life for the patient. Further work will target analysis of a larger cohort of patients and validate FE models

Adrenomedullin is a peptide hormone that has attracted attention with its proliferative and anti-apoptotic effects on osteoblasts in recent years. We investigated the effect of adrenomedullin on healing of the segmental bone defect in a rat model. 36 Wistar rats were randomly divided in six groups based on follow-up periods and administered dose of adrenomedullin hormone. In each group, a 2 mm bone defect was created at the diaphysis of radius, bilaterally. NaCl solution was administered to sham groups three times a week for 4 and 8 weeks, intraperitoneally. Adrenomedullin was administered to study groups three times a week; 15 µg-4 weeks, 15 µg-8 weeks, 30 µg-4 weeks and 30 µg-8 weeks, respectively. After euthanasia, the segmental defects were evaluated by histomorphometric (new bone area (NBA)) and micro-tomographic (bone volume (BV), bone surface (BS), bone mineral density (BMD)) analysis. Although 4 and 8 weeks 15 μg administered study groups had higher NBA values than the other study and control groups, histomorphometric analysis did not reveal any statistical difference between the control and study groups in terms of new bone area (p > 0.05). In micro-tomographic analysis, BV was higher in 15 μg – 4 weeks group than 30 μg – 4 weeks group (296.9 vs 208.5, p = 0.003) and BS was lower in 30 μg – 4 weeks than 4 week - control group (695.5 vs 1334.7, p = 0.005) but in overall, no significant difference was found between the control and study groups (p > 0.05). Despite these minor differences in histomorphometric and micro-tomographic criteria indicating new bone formation, BMD values of 15 µg-4 and −8 weeks study groups showed significant increase comparing with the control group (p = 0.04, p = 0.001, respectively). Adrenomedullin seemed to have a positive effect on BMD at a certain dose (15 µg) but it alone is not considered sufficient for healing of the defect with new bone formation. Further studies are needed to assess its effects on bone tissue trauma. This study was funded by Hacettepe University Scientific Research Projects Coordination Unit

Introduction. DXA areal-bone-mineral-density (aBMD) is used clinically as a surrogate for true volumetric-BMD to assess bone fragility. Trabecular-Bone-Score (TBS) provides an assessment of bone quality based on the DXA-derived two-dimensional images. Calculated from bone area (BA), aBMD may under- or overestimate true BMD in individuals with relatively low and high BA respectively. This study investigated relationships between BA at the lumbar-spine (L1–L4) and measurements of BMD and TBS. Method. Lumbar spine scans were performed (GE Lunar Prodigy) on 114 women (mean 53 yrs). The study population was divided by L1–L4 BA using the 20th and 80th centiles, and BMD v TBS correlations calculated for the subgroups. BMD and TBS, converted to Z-scores, were correlated with BA. Results. For the whole group, r = 0.23 for BMD v BA, whereas r = −0.12 for TBS v. BA: the correlation between BMD and TBS was r=0.38. Correlations between BMD and TBS for BA subgroups were r = 0.23, r=0.44 and r=0.59 for the >20th, 20th −80th and >80th centile groups respectively. Conclusion. Low correlation between BMD and TBS for the entire group indicates that TBS reflects some bone quality properties unrelated to BMD. The correlation of BMD with BA suggests that it incorrectly estimates true BMD at BA extremes. Correlation for BMD v TBS in the lowest area-subgroup was substantially lower than for the middle and highest area subgroups suggesting that TBS may afford valuable complementary information on bone fragility at the lowest extreme of BA where distortions in BMD measurement potentially occur

To prevent bone loss, OPG/RANK/RANKL signalling pathway is a key in keeping the balance between the action of osteoblasts and osteoclasts. Aim of this study is to assess the influence of long-term nicotine exposure on bone mineral density (BMD) scores, RANKL and OPG levels of plasma and RANKL and OPG immunoreactivities of tissue in rats. In this study, totally 36 Swiss Albino rats (70±10 g) were used in three groups. Whereas normal drinking water was given for the control group (n:12), 0.4 mg/kg/day and 6.0 mg/kg/day nicotine was added to drinking water for low-dose nicotine (LDN) group (n:12) and high-dose nicotine (HDN) group (n:12), respectively for 12 months. At the end of 12. th. month, BMD scores were measured via X-ray absorptiometry and then bone turnover was assessed via measuring both RANKL, OPG levels in plasma and RANKL, OPG immunoreactivities in tail vertebrae of all rats. Lumbar spine and femoral regions BMD scores of the control group and the nicotine groups were not significantly difference. In HDN group, OPG levels of plasma were found significantly higher when compared with the control and LDN groups (p=0.001) unlike RANKL levels of plasma. RANKL and OPG immunoreactivities of tissue were found significantly lower in both LDN and HDN groups (p<0.001, p=0.004, respectively) in comparison to control group. No correlation was found between plasma levels and tissue immunoreactivities of RANKL and OPG. As a result, this study indicates that nicotine is not primarily responsible for the decline of BMD frequently seen in smokers

The metal on metal implants was introduced without the proper stepwise introduction. The ASR resurfacing hip arthroplasty (RHA) withdrawn due to high clinical failure rates and the large diameter head THA (LDH-THA) are also widely abandoned. Early (2 year) radiostereometry studies does not support early instability as cause of failure but more likely metal wear products. A possible advantage may be maintenance of bone mineral density (BMD). We present 5 year prospective follow up from a randomized series, aiming to report changes from baseline and to investigate links between implant micromotion, Cr & Co ions and BMD. Patients eligible for an artificial hip were randomized to RHA, Biomet LDH-THA or standard Biometric THA. 19, 17 and 15 patients completed 5 year follow-up. All followed with BMD of the femur, acetabulum and for RHA the collum. RHA and THA with whole blood Co and Co. LDH-THA only at 5 year. RHA had marker based RSA of both components, cup only for LDH-THA. Translations were compiled to total translation (TT= √(x. 2. +y. 2. +z. 2. )). Data were collected at baseline, 8 weeks, 6 months, 1, 2 and 5 years. Statistical tests: ANCOVA for TT movement, Spearman's correlation for BMD, Cr, Co and BMI to TT at 5 years. RSA: The 5 year median (25%to75%) RHA cup translations were X=-0.00(−0.49 to 0.19) Y=0.15(−0.03 to 0.20), z=0.24(−0.42 to 0.37) and TT 0.58 (0.16 to 1.82) mm. For the LDH-THA X=−0.33(−0.90 to 0.20) Y=0.28(0.02 to 0.54), z=0.43(−1.12 to −0.19) and TT 1.06 (0.97 to 1.72) mm. The TT was statistically different (p<0.05) for the two cups. The RHA femoral component moved X=0.37(0.21 to 0.56) Y=0.02(−0.07 to 0.11), z=-0.01(−0.07 to 0.26) and TT 0.48 (0.29 to 0.60) mm at 5 years. There was no TT movement from year 2. The mean (SD) acetabular BMD was diminished to 93(90–97)% for RHA and 97(93–99.9)% for THA, but LDH-THA maintained 99(95–103)%. Overall femoral BMD was unchanged at 5 years for all interventions, but both stemmed implants lost 17% at the calcar. Median (25%to75%) whole-blood Cr peaked in the LDH-THA group with 1.7 (0.9 to 3.1) followed by RHA 1.2 (0.8 to 5.0) and THA with 0.5 (0.4 to 0.7)ppb. For Co the highest levels were found in RHA with 1.6(0.8 to 4.7) followed by LDH-THA 1.2 (0.7–1.7) and THA 0.2 (0.2 to 0.6) ppb. The only correlations above +/−0.3 for TT were the RHA femoral component with a correlation of 0.47 to BMI, 0.30 to Co and Cr. The ASR cup conversely had a negative correlation of −0.60 to BMI and again, the LDH-THA cup had a negative correlation of −0.37 to Cr. In contrast to registered revision rates, we found significantly larger movement for the Biomet cup than the ASR cup. The metal ion levels were similar. The LDH-THA cup maintained the acetabular BMD best at 5 years, but the difference was small, we are limited by small numbers and the correlations between TT and the covariates showed no clear pattern