Study on the structure and behaviour of cavitation bubbles generated in a high-intensity focused ultrasound (HIFU) field.

In this study, structures and behaviours of acoustic cavitation bubbles induced by a high-intensity focused ultrasound (HIFU) transducer, operating at its resonance frequency of 250kHz, are experimentally explored with corresponding observations captured by a high-speed video camera system. The experiments were conducted in an open-top Perspex water tank with deionized water, and illumination was provided by a LED spotlight which is placed beside the water tank throughout the whole experiment. Experimental results show that the structure of ultrasonically generated bubbles forms in a conical shape with several concentric bubble rings above the transducer. The distance between the adjacent rings with equal spacing as determined by the driving frequency of the HIFU transducer is experimentally measured and compared with the theoretical value. Then, the distribution of acoustic pressure in the acoustically driven liquid is further studied to investigate the behaviours of cavitation bubbles generated in a HIFU field. Additionally, the analysis of Bjerknes forces on the bubble surface which are induced by the gradient of acoustic pressure and the adjacent oscillating bubbles is quantitatively carried out, and the radius and velocity of a typical larger bubble are measured to characterize the behaviours of ultrasonically induced bubbles. Particularly, the physical phenomena of large bubbles including the coalescence, attraction or repulsion between adjacent bubbles, as well as the jumping of an acoustic bubble from the lower concentric ring level to the higher level, are analysed. The moving trajectory of the bubble is next obtained, and some conclusions are summarized to provide a greater understanding of the complex behaviours of the ultrasonically generated bubbles.

Ageing Effects on 3-Dimensional Femoral Neck Cross-Sectional Asymmetry: Implications for Age-Related Bone Fragility in Falling.

This paper explores the effects of aging on femoral neck (FN) anatomy in a study of women aged 20-90years in relation to implications for FN fracture propensity in buckling. Five hundred and four participants were scanned by Quantitative Computed Tomography and analyzed using Quantitative Computed Tomography Pro BIT (Mindways). FN cross-section was split through geometric center into superior and inferior sectors. Bone mass, structural measurements, and bone mineral density were analyzed. Buckling ratio was calculated as ratio of buckling radius to cortical thickness. Between 2nd decade and 8th decade, age-related integral bone mass reduction in superior sector was substantially larger than in inferior sector (33% compared to 21%), especially in cortical bone superiorly compared to inferiorly (53% vs 21%; p < 0.001), principally due to reduction in cortical thickness, averaged cortical thickness (56%) with little difference in density. Superior and inferior sector trabecular bone mineral density reduction was similar at 41% and 43% respectively. Differential cortical bone loss in superior sector resulted in a 59% inferior displacement (δ) of center-of-mass from geometric center. Differences in δ and averaged cortical thickness with age accounted for a 151% increase in mean superior buckling ratio from 9 to 23. Analysis confirms significant progressive age-related superior cortical bone loss as the major age effect on FN structure with relative preservation of inferior cortex probably related to maintenance of inferior sector by regular loading as a result of standing and walking. Computation of buckling ratio may allow prediction of fracture propensity in a sideways fall.

Metastatic efficiency of tumour cells can be impaired by intraoperative cell salvage process: truth or conjecture?

The use of salvaged blood in oncological surgery has been a matter of controversy over the years. This is due to the concern of systemic dissemination of reinfused tumour cells. Recent literature, across disciplines, has shed considerable light on its safety in terms of tumour recurrence, progression and overall survival rates. This clinical safety demonstrates the apparent metastatic inefficiency of reinfused tumour cells. The proof of this concept comes from various studies that have shown that salvaged blood has no tumour cells, or has a significantly lower count as compared to the patient's original circulatory tumour load. Recently, we took a step further and found that the tumour cells in the salvaged blood lose the capacity to replicate. In this review, we revisited the safety of salvaged blood from the point of view of metastatic potential. We have presented basic and applied science evidence regarding the innocuous nature of tumour cells that have been subjected to the cell salvage process. The understanding of the metastatic efficiency or the lack of it in tumour cells subjected to salvage process is key to allay the concerns conventionally associated with the use of salvaged blood in tumour surgery. Based on the available literature, we surmise that the prevalent apprehensions on the usage of salvaged blood are ill-founded and further substantiate why tumour cells in the salvaged blood could be regarded as cells with non-metastatic potential.

Evaluation of a simplified hip structure analysis method for the prediction of incident hip fracture events.

UNLABELLED: Many attempts have been made to improve the predictive ability of areal bone mineral density (aBMD) which integrates bone mass and area. The addition of an extra variable derived from the hip dual-energy X-ray (DXA) image TR_σ, which describes distribution of mass within the scanned area of the trochanter, improved prediction of 15-year hip fracture probability in elderly women. INTRODUCTION: Two-dimensional DXA imaging of the proximal femur to produce an aBMD is a clinically useful predictor of future fracture risk. Further analysis of the DXA image to produce an eight-variable hip structure analysis (Beck HSA) has been developed to improve understanding of structural factors determining hip bone strength at each of three proximal femur sites, the narrow femoral neck (NN), intertrochanter (TR) and shaft (S). Recently, data on four measurements derived from the currently used eight Beck HSA variables were used to capture population variation in bone structure at each site. These include two previously used variables, the localised aBMD and the sub-periosteal width (W) applying to 5-mm sections (at each sites), and two new variables, standard deviation of normalised mineral-mass projection profile distribution (σ), and displacement between centre-of-mineral mass and geometric centre-of-mineral mass of projection profile (δ). METHODS: Using a cohort of 1159 women, mean baseline age 75, who sustained 139 hip fractures over 15 years, we determined whether these measures significantly improved 15-year hip fracture prediction compared to current approach utilising age and total hip aBMD. To describe the most parsimonious model for hip fracture risk prediction, the 12 base measures (4 from each site), total hip aBMD and age were evaluated in stepwise logistic regression models. RESULTS: The final model included TR_σ, total hip aBMD and age and provided improved utility for hip fracture prediction compared to total hip aBMD and age alone (C-statistic 0.73 vs. 0.69, P = 0.009 and net reclassification improvement 0.164, P < 0.001, respectively). CONCLUSIONS: Addition of TR_σ to total hip aBMD and age substantially improved prediction of 15-year hip fracture risk in this cohort of elderly women.

Jitter reduction using native fiducials in rotating mirror ultra-fast microphotography.

Rotating mirror cameras represent a workhorse technology for high speed imaging in the MHz framing regime. The technique requires that the target image be swept across a series of juxtaposed CCD sensors, via reflection from a rapidly rotating mirror. Employing multiple sensors in this fashion can lead to spatial jitter in the resultant video file, due to component misalignments along the individual optical paths to each CCD. Here, we highlight that static and dynamic fiducials can be exploited as an effective software-borne countermeasure to jitter, suppressing the standard deviation of the corrected file relative to the raw data by up to 88.5% maximally, and 66.5% on average over the available range of framing rates. Direct comparison with industry-standard algorithms demonstrated that our fiducial-based strategy is as effective at jitter reduction, but typically also leads to an aesthetically superior final form in the post-processed video files.

Nasally located ectopic ACTH-secreting pituitary adenoma (EAPA) causing Nelson's syndrome: diagnostic challenges.

PURPOSE: We report the first case of an Ectopic adrenocorticotrophin (ACTH)-secreting pituitary adenoma (EAPA) located within the posterior nasal septum associated with Nelson's syndrome, which eluded diagnosis for over a decade. In this report, we explore the reasons for such diagnostic difficulty and suggest ways in which an earlier diagnosis may be made. METHODS AND RESULTS: A 19 years old Lebanese man presented in 2000, with overt Cushing's syndrome confirmed with markedly elevated urine free cortisols and failed dexamethasone suppression tests. An unsuppressed ACTH and a possible 5 mm adenoma on MRI (Magnetic Resonance Imaging) pituitary suggested Cushing's disease. The patient underwent trans-sphenoidal surgery (TSS), but histology revealed normal pituitary tissue and Cushing's syndrome persisted. A repeat MRI pituitary showed no anomaly, and extensive investigations failed to locate an ectopic lesion. Subsequently a bilateral adrenalectomy was performed. Over the ensuing years, the patient developed Nelson's syndrome with hyperpigmentation and markedly elevated ACTH levels. Repeated high dose dexamethasone suppression tests, corticotrophin releasing hormone (CRH) tests, and CRH stimulated inferior petrosal sinus samplings (IPSS) suggested a pituitary origin of the ACTH. Two further TSS were unsuccessful. The pituitary was irradiated. Subsequent review of his previous MRIs revealed an enlarging mass within the posterior nasal septum, which was excised in 2011. The histology confirmed the diagnosis of an EAPA within the nasal septum. CONCLUSION: Ectopic ACTH-secreting pituitary adenomas can occur not only along the developmental route of Rathke's pouch, but other aberrant locations giving a clinical and biochemical picture identical to Cushing's disease or Nelson's syndrome. Clinicians should suspect an EAPA, when a central ACTH source seems to be apparent with no obvious pituitary adenoma. A detailed MRI involving possible EAPA sites aids in locating these unusual lesions.

Immunohistochemical markers of the hypoxic response can identify malignancy in phaeochromocytomas and paragangliomas and optimize the detection of tumours with VHL germline mutations.

BACKGROUND: There are no reliable markers of malignancy in phaeochromocytomas (PCC) and paragangliomas (PGL). We investigated the relevance of the mammalian target of rapamycin (mTOR)/AKT and hypoxic pathways as novel immunohistochemical markers of malignancy. METHODS: Tissue microarray blocks were constructed with a total of 100 tumours (10 metastatic) and 20 normal adrenomedullary samples. Sections were immunostained for hypoxia-inducible factor 1α (Hif-1α), vascular endothelial growth factor A (VEGF-A), mTOR, carbonic anhydrase IX (CaIX) and AKT. The predictive performance of these markers was studied using univariate, multivariate and receiver operating characteristic analyses. RESULTS: In all, 100 consecutive patients, 64% PCC, 29% familial with a median tumour size of 4.7 cm (range 1-14) were included. Univariate analyses showed Hif-1α overexpression, tumour necrosis, size >5 cm, capsular and vascular invasion to be predictors of metastasis. In multivariate analysis, Hif-1α, necrosis and vascular invasion remained as independent predictors of metastasis. Hif-1α was the most discriminatory biomarker for the presence of metastatic diffusion. Strong membranous CaIX expression was seen in von Hippel-Lindau (VHL) PCC as opposed to other subtypes. CONCLUSION: Lack of vascular invasion, tumour necrosis and low Hif-1α expression identify tumours with lower risk of malignancy. We propose membranous CaIX expression as a potential marker for VHL disease in patients presenting with PCC.

[Identification of endogenous control genes for gene expression studies in peripheral blood of patients with coronary artery disease].

The selection of stable endogenous control genes is critical for normalization of quantitative real-time PCR (qPCR) data. In this study, we aimed to identify a suitable set of control genes to be used as endogenous references for gene expression evaluation in human peripheral blood samples among coronary artery disease patients. The expression levels of 12 endogenous control genes procured from TATAA Biocenter (Goteborg, Sweden) were measured in five acute coronary syndrome patients and five chronic stable angina patients. Gene expression stability was analyzed using two different software applications i.e geNorm and NormFinder. Results suggested that beta-glucuronidase is the most stable endogenous control, followed by hypoxanthine-guanine phosphoribosyltransferase. The NormFinder analysis further confirmed that beta-glucuronidase and hypoxanthine-guanine phosphoribosyltransferase were on the first rank order with the most stable expression among endogenous control genes analyzed and 60S acidic ribosomal protein P0. Besides this, the expression levels of 18S rRNA were revealed to be highly variable between coronary heart disease patients. We thus recommend the use of beta-glucuronidase and hypoxanthine-guanine phosphoribosyltransferase as reference genes for accurate normalization of relative quantities of gene expression levels in coronary artery disease patients using qPCR. Also the use of 18S rRNA as a control gene should be avoided.

Differences in structural geometrical outcomes at the neck of the proximal femur using two-dimensional DXA-derived projection (APEX) and three-dimensional QCT-derived (BIT QCT) techniques.

UNLABELLED: Structural geometric parameters at neck of the proximal femur were obtained using DXA-derived hip structural analysis (APEX 3) and quantitative computed tomography-derived (BIT QCT) techniques in 237 elderly females. Linear correlations for parameters ranged from 0.45 to 0.90. The average value of the subperiosteal width, as determined by the two techniques, was the same; variables dependent on mass measurements were different. INTRODUCTION: There has been increasing interest in using bone structural geometry to assess bone fragility to complement bone mineral mass. The objective of this study is to compare structural geometrical differences between "2D" DXA-derived and "3D" QCT-derived techniques in unselected clinical cases. METHODS: All 237 females had both DXA and QCT assessments of femoral neck structural geometry. Variables compared were areal bone mineral density, cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), averaged cortical thickness (Ct), endosteal width (ESW), subperiosteal width (W), and buckling ratio (BR). RESULTS: Correlation of femoral neck variables ranged from 0.45 for ESW to 0.90 for CSA. APEX 3 and BIT QCT-derived femoral neck W values were numerically similar. However CSA, CSMI, Z and Ct values measured by APEX 3 were higher and ESW and BR values were lower than corresponding BIT QCT. CONCLUSIONS: 2D DXA structural analysis of neck of femur is related to but different from same parameters calculated from true 3D images obtained by CT. Femoral neck size values are similar for DXA and QCT, but structural geometrical variables dependent on mass calibration standards, location of neck ROI and mathematical derivation techniques are different.

Performance of a third-generation TSH-receptor antibody in a UK clinic.

BACKGROUND: UK national guidelines recommend the measurement of TSH receptor antibodies (TRAb) in certain clinical scenarios. A commercial third-generation TRAb autoantibody M22-biotin ELISA assay was introduced in May 2008 in our centre. OBJECTIVE: To evaluate the diagnostic performance of a TRAb assay in a retrospective and subsequently a prospective cohort in a UK centre. DESIGN: A retrospective review of patients with thyroid disease followed by a prospective observational study in consecutive patients with newly found suppressed serum thyrotrophin (TSH). PATIENTS AND MEASUREMENTS: Medical records of 200 consecutive patients with thyroid disorders who had TRAb measured since the introduction of the assay. In a prospective study 44 patients with newly identified hyperthyroidism (TSH < 0·02 mIU/l) had sera assayed for TRAb prior to their clinic appointment at which a final diagnosis was sought. RESULTS: In the retrospective cohort, the manufacturer's cut-off point of TRAb ≥0·4 U/l resulted in a positive predictive value (PPV) of 95%, sensitivity 85%, specificity 94% and negative predictive value (NVP) 79% to diagnose Graves' disease using defined criteria. Receiver operating characteristic (ROC) analysis determined an optimal cut-off point of TRAb ≥3·5 U/l with a 100% specificity to exclude patients without Graves' disease at the cost though of a lower sensitivity (43%). In the prospective study, the sensitivity, PPV, specificity and NPV were all 96% using the ≥0·4 U/l cut-off. When combining hyperthyroid patients from both cohorts the assay sensitivity and specificity at ≥0·4 U/l cut-off were 95% and 92% respectively. A positive TRAb result increased the probability of Graves' disease for a particular patient by 25-35% and only six (2·5%) patients had a diagnosis of hyperthyroidism of uncertain aetiology after TRAb testing. CONCLUSIONS: The assay studied specifically identifies patients with Graves' disease. It is a reliable tool in the initial clinical assessment to determine the aetiology of hyperthyroidism and has the potential for cost-savings.

Outcomes in 125 individuals with adrenal incidentalomas from a single centre. a retrospective assessment of the 1 mg overnight and low dose dexamethasone suppression tests.

Adrenal masses discovered incidentally during imaging studies - adrenal incidentalomas (AIs) - are common and prompt investigations to exclude secretory lesions and malignancy. Their best management strategy is unknown. Our objectives were to identify all outcomes of AI investigation in a UK centre and to assess the performance of the 2 mg low dose (LDDST) and 1 mg overnight dexamethasone (ODST) suppression tests in this setting. Out of 125 patients referred to our centre between 2005 and 2009 with AIs, 16 (12.8%) were diagnosed with secretory adrenal adenomas. 24 patients (23%) failed to suppress on LDDST or ODST using a serum cortisol cut-off of 50 nmol/l for both tests; in 12 this was due to false positive results. 5 patients were diagnosed with adrenal Cushing's syndrome and 7 with subclinical hypercortisolism. The use of a higher post LDDST (83 nmol/l) or ODST (138 nmol/l) cortisol cut-off would have resulted in missing 1 patient with Cushing's syndrome and 4 with subclinical hypercortisolism or 2 patients with Cushing's syndrome and 1 with subclinical hypercortisolism, respectively. In patients who had both tests, the ODST systematically resulted in higher post-test cortisol values compared with the LDDST. The adenoma diameter correlated with and was predictive of the post LDDST cortisol. Our results indicate that altering the post dexamethasone cut-off in accordance to published guidelines changes the performance of the suppression tests. The ODST may result in higher post-test cortisol levels compared to LDDST when used in patients with AIs.

Characterizing bubble dynamics created by high-intensity focused ultrasound for the delivery of antibacterial nanoparticles into a dental hard tissue.

Hig hintensity focused ultrasound (HIFU) has been applied for drug delivery in various disease conditions. Delivery of antibacterial-nanoparticles into dental hard tissues may open up new avenues in the treatment of dental infections. However, the basic mechanism of bubble dynamics, its characterization, and working parameters for effective delivery of nanoparticles, warrants further understanding. This study was conducted to highlight the basic concept of HIFU and the associated bubble dynamics for the delivery of nanoparticles. Characterization experiments to deliver micro-scale particles into simulated tubular channels, activity of ultrasonic bubbles, and pressure measurement inside the HIFU system were conducted. Subsequently, experiments were carried out to test the ability of HIFU to deliver nanoparticles into human dentine using field emission scanning electron micrographs (FESEM) and elemental dispersive X-ray analysis (EDX). The characterization experiments showed that the bubbles collapsing at the opening of tubular channels were able to propel particles along their whole length. The pressure measured showed sufficient negative and positive pressure suggesting that the bubble grew to a certain size before collapsing, thus enabling the particles to be pushed. The FESEM and EDX analysis highlighted the ability of HIFU to deliver nanoparticles deep within the dentinal tubules. This study highlighted the characteristics and the mechanism involved of the bubbles generated by the HIFU and their capability to deliver nanoparticles.

Comparison of QCT-derived and DXA-derived areal bone mineral density and T scores.

UNLABELLED: Two-dimensional areal bone mineral density (aBMD) of the proximal femur measured by three-dimensional quantitative computed tomography (QCT) in 91 elderly women was compared to dual-energy X-ray absorptiometry (DXA) aBMD results measured in the same patients. The measurements were highly correlated, though QCT aBMD values were marginally lower in absolute units. Transformation of the QCT aBMD values to T score values using National Health and Nutrition Examination Survey (NHANES) DXA-derived reference data improved agreement and clinical utility. INTRODUCTION: World Health Organization guidelines promulgate aBMD (g cm(-2)) measurement of the proximal femur for the diagnosis of bone fragility. In recent years, there has been increasing interest in QCT to facilitate understanding of three-dimensional bone structure and strength. OBJECTIVE: To assist in comparison of QCT-derived data with DXA aBMD results, a technique for deriving aBMD from QCT measurements has been developed. METHODS: To test the validity of the QCT method, 91 elderly females were scanned on both DXA and CT scanners. QCT-derived DXA equivalent aBMD (QCT(DXA) aBMD) was calculated using CTXA Hip software (Mindways Software Inc., Austin, TX, USA) and compared to DXA-derived aBMD results. RESULTS: Test retest analysis indicated lower root mean square (RMS) errors for CTXA; F test between CTXA and DXA was significantly different at femoral neck (FN) and trochanter (TR) (p < 0.05). QCT underestimates DXA values by 0.02 +/- 0.05 g cm(-2) (total hip, TH), 0.01 +/- 0.04 g cm(-2) (FN), 0.03 +/- 0.07 g cm(-2) (inter-trochanter, IT), and 0.02 +/- 0.05 g cm(-2) (TR). The RMS errors (standard error of estimate) between QCT and DXA T scores for TH, FN, IT, and TR were 0.36, 0.40, 0.39, and 0.49, respectively. CONCLUSIONS: This study shows that results from QCT aBMD appropriately adjusted can be evaluated against NHANES reference data to diagnose osteoporosis.

Differential regulation of RNA polymerases I, II, and III by the TBP-binding repressor Dr1.

RNA polymerases I, II, and III each use the TATA-binding protein (TBP). Regulators that target this shared factor may therefore provide a means to coordinate the activities of the three nuclear RNA polymerases. The repressor Dr1 binds to TBP and blocks the interaction of TBP with polymerase II- and polymerase III-specific factors. This enables Dr1 to coordinately regulate transcription by RNA polymerases II and III. Under the same conditions, Dr1 does not inhibit polymerase I transcription. By selectively repressing polymerases II and III, Dr1 may shift the physiological balance of transcriptional output in favor of polymerase I.

Antibiotic prophylaxis tailored to local organisms reduces percutaneous gastrostomy site infection.

BACKGROUND: Current recommendations for the choice of antibiotic prophylaxis prior to percutaneous endoscopic gastrostomy (PEG) insertion may not be suitable in all situations. AIMS: We sought to review the microbiology of PEG-wound infections at our institution locally and observe PEG infection rates following a change in antibiotic policy. METHODS: A retrospective clinical and microbiological review of all PEG-wound infections resulted in a change in the choice of antibiotic. A further review was conducted 2 years later to examine the effect of this change. RESULTS: PEG-wound infection was detected in 33/103 (32.0%) patients between January 2002 and May 2004 with either second generation cephalosporins or co-amoxiclav antibiotic prophylaxis, with the commonest organisms being Pseudomonas aeruginosa (16.7%), Klebsiella species (9.9%) and methicillin-resistant Staphylococcus aureus (5.3%). Microbiological data revealed high levels of resistance to cefuroxime (60.7%) and co-amoxiclav (51%). A change of prophylaxis to cefoperazone (during the period June 2004-May 2006) resulted in a reduction of PEG-wound infections to 17/90 (18.9%) patients that required PEG tube insertion (p = 0.04). Together with a reduction in P. aeruginosa infections (18.4-10%, p = 0.10), a lower incidence of pyrexia (10.7% vs. 3.3%, p = 0.05), lower antibiotic administration (20.4% vs. 11.1%, p = 0.08) and lower rate of PEG removal (23.2% vs. 10.2%, p = 0.018) were noted following prophylaxis change. CONCLUSIONS: Antibiotic prophylaxis for PEG should be tailored to local organisms as this approach reduces the incidence and severity of peri-stomal PEG infections.

A cortical-bone structural geometry phantom: dental plaster as a convenient and radiologically similar fabrication material.

Areal bone mineral density (aBMD), derived from dual-energy X-ray absorptiometry (DXA) scanners is used routinely to infer bone strength. With DXA hip scans there is growing acceptance of the advantages of also measuring bone structural geometric variables, that complement conventional aBMD to improve understanding of bone modelling, remodelling and processes of metabolic bone disease. However, phantoms for assessing structural geometric variables from DXA scans are not widely available, unlike those for aBMD. This study describes the development of such a phantom, simulating the cortical shell of the human femoral neck, using dental plaster as a material radiologically similar to cortical bone. The mass attenuation coefficient of the dental plaster differed by < 1% from cortical bone, over the relevant energy range. Performance testing was carried out with DXA, to determine accuracy and precision of the phantom structural geometry, using its dimensions and composition as 'gold standards'. Accuracy and precision of cortical structural geometry were poor when measured in a simulated 1 mm-thick osteoporotic cortex (5.5% precision and 50% accuracy errors), but improved with increasing cortical thickness. This study demonstrates the limitations of DXA-based Hip Structure Analysis when applied to femora with thin cortices, and indicates improvements in the design of a phantom to better simulate such cortical structures.

Intracranial monodermal teratoma presenting with growing teratoma syndrome.

Intracranial teratomas are rare. We report a case of a purely monodermal teratoma manifesting as intracranial growing teratoma syndrome. To the best of our knowledge, this is the first report of such nature in the literature.

Differences in femoral neck structure between elderly Caucasian and Chinese populations: a cross-sectional study of Perth-Beijing cohorts.

Structural skeletal differences of the femoral neck of older Beijing-Chinese and Perth-Caucasian women were compared; adjusting for frame size-related differences, Beijing-Chinese have lower periosteal width; however, indices of internal bone distribution suggest that Beijing-Chinese may exhibit increased resistance to fracture that may relate to the reduced hip fracture incidence. INTRODUCTION: Ethnic differences in skeletal structure may relate to differences in hip fracture risk in Chinese and Caucasian populations. 2D mass, size, and structural biomechanics were compared in the two populations. METHODS: Quantitative computed tomography-derived geometric variables were compared in age-matched community-derived female populations, 196 Beijing-Chinese 76.5 ± 4.8 (mean ± SD) years and 237 Perth-Caucasians 77.1 ± 5.0 years. These included scanned area (A), periosteal width (W), bone mineral content (BMC), aBMD, bone cross-sectional area (bCSA), section modulus (Z) and buckling ratio (BR). Assumption-free measures included sigma (σ), related to the distribution of bone in the scanned image previously identified as a predictor of hip fracture, and delta (δ), the center-of-mass displacement from the geometric center. RESULTS: Compared to Beijing-Chinese, Perth-Caucasians were heavier (Beijing-Chinese 58.7 ± 11.8; Perth-Caucasians 66.1 ± 11.0 kg), taller (154.9 ± 16.7 vs 158.9 ± 6.0 cm), and had higher BMC, A, and W. After adjustment for frame size, BMC was not significantly different but W remained higher in Perth-Caucasians. Differences in variables aBMD, Z, BR, and σ favored higher resistance to failure with Beijing-Chinese before and after adjustment for frame size. δ was similar in both populations; bCSA was higher in Beijing-Chinese before adjustment for frame size but not after. CONCLUSIONS: Bone mass differences in two populations were related to frame size differences. However, femoral neck width remained smaller in Beijing-Chinese suggesting effects of local genetic and environmental factors. In Beijing-Chinese participants compared to Perth-Caucasians, internal bone distribution suggests increased resistance to deformation if exposed to same force that may, in-part, relate to reduced incidence of hip fracture in Beijing-Chinese.

Reconsideration of the Effects of Age on Proximal Femur Structure: Implications for Joint Replacement and Hip Fracture.

OBJECTIVES: In recent years quantitative computed tomography (QCT) has allowed precise non-invasive, three dimensional, in vivo measurement of hip structure in large numbers of individuals. The effects of ageing on proximal femur structure are reported and implications for the prevention of hip prosthesis loosening and hip fracture considered. DESIGN, SETTING AND PARTICIPANTS: An observational cross-sectional study of proximal femur QCT in 719 unselected female European descent aged 20 to 89 years recruited from US and Australian populations. MAIN OUTCOMES MEASURES: QCT scans were obtained using software that separates cortical and cancellous bone by a thresholding technique. Voxel based mineral volume and mass was computed for the integral (external), cancellous and cortical compartments of 1 mm wide sections through the femoral neck (FN), trochanter (TR) and intertrochanter (IT) regions. RESULTS: Over the adult life span total integral volumes at the FN, TR and IT sites expand linearly by between 18 and 37% at the same time as bone mass decreased by 22 to 25% resulting in massive reductions in true volumetric BMD (vBMD) of 40 to 50%. Cancellous volume expansion was larger at 65 to 79% at the three sites. Between the ages of 65 and 75 the average increase in cancellous volume at the IT site was 3.74 cm3 (12.1%). Voxel determined FN cortical volume decreased linearly by 43%, as did cortical bone mass so that vBMD did not change substantially. TR and IT cortical volumes decreased 54 and 28% respectively, small reductions in TR and IT cortical vBMD also occurred. CONCLUSIONS: Large endosteal expansion in the area in which hip replacement stem placement occurs may contribute to loosening. Regarding the propensity to hip fracture, periosteal expansion contributes to increased resistance to bending but cortical thinning contributes to loss of bone to resistance to bending forces. Understanding individual hip structure may contribute to individualisation of risk and subsequent targeting of management using pharmaceutical agents.