The Incidence of Pulmonary Embolism in Hospitalized Non-ICU Patients with COVID-19 during the First Wave: A Multicenter Retrospective Cohort Study in the Netherlands.

INTRODUCTION: During the first COVID-19 outbreak in 2020 in the Netherlands, the incidence of pulmonary embolism (PE) appeared to be high in COVID-19 patients admitted to the intensive care unit (ICU). This study was performed to evaluate the incidence of PE during hospital stay in COVID-19 patients not admitted to the ICU. METHODS: Data were retrospectively collected from 8 hospitals in the Netherlands. Patients admitted between February 27, 2020, and July 31, 2020, were included. Data extracted comprised clinical characteristics, medication use, first onset of COVID-19-related symptoms, admission date due to COVID-19, and date of PE diagnosis. Only polymerase chain reaction (PCR)-positive patients were included. All PEs were diagnosed with computed tomography pulmonary angiography (CTPA). RESULTS: Data from 1,852 patients who were admitted to the hospital ward were collected. Forty patients (2.2%) were diagnosed with PE within 28 days following hospital admission. The median time to PE since admission was 4.5 days (IQR 0.0-9.0). In all 40 patients, PE was diagnosed within the first 2 weeks after hospital admission and for 22 (55%) patients within 2 weeks after onset of symptoms. Patient characteristics, pre-existing comorbidities, anticoagulant use, and laboratory parameters at admission were not related to the development of PE. CONCLUSION: In this retrospective multicenter cohort study of 1,852 COVID-19 patients only admitted to the non-ICU wards, the incidence of CTPA-confirmed PE was 2.2% during the first 4 weeks after onset of symptoms and occurred exclusively within 2 weeks after hospital admission.

Trabecular, but not cortical, bone tissue protein synthesis rates are lower in the femoral head when compared to the proximal femur following an intracapsular hip fracture.

BACKGROUND: All musculoskeletal tissues are in a constant state of turnover, with a dynamic equilibrium between tissue protein synthesis and breakdown rates. The synthesis of protein allows musculoskeletal tissues to heal following injury. Yet, impaired tissue healing is observed following certain injuries, such as geriatric hip fractures. It is assumed that the regenerative properties of femoral head bone tissue are compromised following an intracapsular hip fracture and therefore hip replacement surgery is normally performed. However, the actual impact on in vivo bone protein synthesis rates has never been determined. DESIGN: In the present study, 10 patients (age: 79 ± 10 y, BMI: 24 ± 4 kg/m2) with an acute (<24 h) intracapsular hip fracture received a primed continuous intravenous infusion of L-[ring-13C6]-phenylalanine before and throughout their hip replacement surgery. Trabecular and cortical bone tissue from both the femoral head and proximal femur were sampled during surgery to assess protein synthesis rates of affected (femoral head) and unaffected (proximal femur) bone tissue, respectively. In addition, tissue samples of gluteus maximus muscle, synovium, ligamentum teres, and femoral head cartilage were collected. Tissue-specific protein synthesis rates were assessed by measuring L-[ring-13C6]-phenylalanine incorporation in tissue protein. RESULTS: Femoral head trabecular bone protein synthesis rates (0.056 [0.024-0.086] %/h) were lower when compared to proximal femur trabecular bone protein synthesis rates (0.081 [0.056-0.118] %/h; P = 0.043). Cortical bone protein synthesis rates did not differ between the femoral head and proximal femur (0.041 [0.021-0.078] and 0.045 [0.028-0.073] %/h, respectively; P > 0.05). Skeletal muscle, synovium, ligamentum teres, and femoral head cartilage protein synthesis rates averaged 0.080 [0.048-0.089], 0.093 [0.051-0.130], 0.121 [0.110-0.167], and 0.023 [0.015-0.039] %/h, respectively. CONCLUSION: In contrast to the general assumption that the femoral head is avital after an intracapsular displaced hip fracture in the elderly, our data show that bone protein synthesis is still ongoing in femoral head bone tissue during the early stages following an intracapsular hip fracture in older patients. Nonetheless, trabecular bone protein synthesis rates are lower in the femoral head when compared to the proximal femur in older patients following an acute intracapsular hip fracture. Trial register no: NL9036.

The incidence of fractures at various sites in newly treated patients with type 2 diabetes mellitus.

Purpose: In this descriptive study, we examined the incidence of fractures in patients with newly treated type 2 diabetes mellitus (T2D) compared to matched reference population. Methods: Participants from the UK Clinical Practice research datalink (CPRD) GOLD (1987-2017), aged ≥30 years, with a T2D diagnosis code and a first prescription for a non-insulin anti-diabetic drug (n = 124,328) were included. Cases with T2D were matched by year of birth, sex and practice to a reference population (n = 124,328), the mean follow-up was 7.7 years. Crude fracture incidence rates (IRs) and incidence rate ratios (IRRs) were calculated. Analyses were stratified by fracture site and sex and additionally adjusted for BMI, smoking status, alcohol use and history of any fracture at index date. Results: The IR of all fractures and major osteoporotic fractures was lower in T2D compared to the reference population (IRR 0.97; 95%CI 0.94-0.99). The IRs were lower for clavicle (IRR 0.67; 0.56-0.80), radius/ulna (IRR 0.81; 0.75-0.86) and vertebral fractures (0.83; 0.75-0.92) and higher for ankle (IRR 1.16; 95%CI 1.06-1.28), foot (1.11; 1.01-1.22), tibia/fibula (1.17; 1.03-1.32) and humerus fractures (1.11; 1.03-1.20). Differences in IRs at various fracture sites between T2D and the reference population were more pronounced in women than in men. In contrast, BMI adjusted IRs for all fractures (IRR 1.07; 1.04-1.10) and most individual fracture sites were significantly higher in T2D, especially in women. Conclusion: The crude incidence of all fractures was marginally lower in patients with newly treated T2D compared to the matched reference population but differed according to fracture site, especially in women. BMI adjusted analyses resulted in higher incidence rates in T2D at almost all fracture sites compared to crude incidence rates and this was more pronounced in women than in men. This implies that BMI may have a protective impact on the crude incidence of fractures, especially in women with newly treated T2D.

Effectiveness and cost-effectiveness of dynamic bracing versus standard care alone in patients suffering from osteoporotic vertebral compression fractures: protocol for a multicentre, two-armed, parallel-group randomised controlled trial with 12 months of follow-up.

INTRODUCTION: Patients with osteoporosis may suffer from a fracture after minimal trauma. Osteoporotic vertebral compression fractures (OVCFs) are among the most common fractures, often leading to substantial pain. There is a need for evidence-based conservative treatment to aid in the management of OVCFs. The objective of this randomised controlled trial (RCT) is to evaluate the effectiveness and cost-effectiveness of dynamic bracing in addition to standard care for improving quality of life (QoL) in patients suffering from an OVCF. METHODS AND ANALYSIS: Ninety-eight postmenopausal women from two academic and four community hospitals with a recent symptomatic thoracolumbar OVCF will be randomised into either the standard care or dynamic bracing group. In the dynamic bracing group, the Spinova Osteo orthosis will be used in addition to standard care. Standard care comprises pain control with analgesics, physical therapy and osteoporosis medication. The primary outcome parameter is QoL 1 year after inclusion, as measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41). Secondary outcome parameters are pain, pain medication used, functional disability, sagittal spinal alignment, recurrence rate of OVCFs and physical activity in daily life. A trial-based economic evaluation consisting of both cost-effectiveness analysis and cost-utility analysis will be performed based on empirical data obtained in the RCT. A process evaluation will assess the feasibility of dynamic bracing. All outcomes will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee, University Hospital Maastricht and Maastricht University (METC azM/UM) (NL74552.068.20/METC 20-055). Patients will be included only after verification of eligibility and obtaining written informed consent. Results will be disseminated via the Dutch National Osteoporosis Patient Society and via publications and conferences. TRIAL REGISTRATION NUMBER: NL8746.

Health burden in type 2 diabetes and prediabetes in The Maastricht Study.

Mortality in type 2 diabetes, is determined not only by classical complications, but also by comorbidities, and is linked to hyperglycaemia and apparent even in prediabetes. We aimed to comprehensively investigate, in a population-based cohort, health burden defined as the presence of comorbidities in addition to classical complications and cardiometabolic risk factors, in not only type 2 diabetes but also prediabetes. Such population-based study has not been performed previously. Extensive phenotyping was performed in 3,410 participants of the population-based Maastricht Study (15.0% prediabetes and 28.6% type 2 diabetes) to assess presence of 17 comorbidities, six classical complications, and ten cardiometabolic risk factors. These were added up into individual and combined sum scores and categorized. Group differences were studied with multinomial regression analyses adjusted for age and sex. Individuals with type 2 diabetes and prediabetes, as compared to normal glucose metabolism (NGM), had greater comorbidities, classical complications, cardiometabolic risk factors and combined sum scores (comorbidities sum score ≥ 3: frequencies (95% CI) 61.5% (57.6;65.4) and 41.2% (36.5;45.9) vs. 25.4% (23.5;27.4), p-trend < 0.001; classical complications ≥ 2 (26.6% (23.1;30.1; P < 0.001 vs. NGM) and 10.1% (7.8;12.7; P = 0.065 vs NGM) vs. 8.0% (6.9;9.3)); cardiometabolic risk factors ≥ 6 (39.7% (35.9;43.4) and 28.5% (24.5;32.6) vs. 14.0% (12.5;15.6); p-trend < 0.001); combined ≥ 8 (66.6% (62.7;70.5) and 48.4% (43.7;53.1) vs. 26.0%(24.1;28.0), p-trend < 0.001). Type 2 diabetes and prediabetes health burden was comparable to respectively 32 and 14 years of ageing. Our population-based study shows, independently of age and sex, a considerable health burden in both type 2 diabetes and prediabetes, which to a substantial extent can be attributed to comorbidities in addition to classical complications and cardiometabolic risk factors. Our findings emphasize the necessity of comorbidities' awareness in (pre)diabetes and for determining the exact role of hyperglycaemia in the occurrence of comorbidities.

Adaptive local thresholding can enhance the accuracy of HR-pQCT-based trabecular bone morphology assessment.

High-resolution peripheral quantitative computed tomography (HR-pQCT) devices can scan extremities at bone microstructural level in vivo and are used mainly in research of bone diseases. Two HR-pQCT scanners are commercially available to date: XtremeCT (first generation) and XtremeCT-II (second generation) from Scanco Medical AG (Switzerland). Recently, we have proposed an adaptive local thresholding (AT) technique and showed that it can improve quantification accuracy of bone microstructural parameters, with visually less sharp cone-beam CT (CBCT) images providing a similar accuracy than XtremeCT. The aim of this study was to evaluate whether the AT segmentation technique could enhance the accuracy of HR-pQCT in quantifying bone microstructural images and to assess whether the agreement between XtremeCT and XtremeCT-II could be improved. Nineteen radii were scanned with three scanners from Scanco Medical AG: (1) XtremeCT at 82 µm, (2) XtremeCT-II at 60.7 µm and (3) the small animal microCT scanner VivaCT40 at 19 µm voxel size. The scans were segmented applying two different methods, once following the manufacturer standard technique (ST), and once by means of AT. Three-dimensional (3D) morphological analysis was performed on the trabecular volume of the segmented images using the manufacturer's standard software to calculate bone volume fraction (BV/TV), trabecular thickness (Tb.Th), separation (Tb.Sp) and number (Tb.N). The average accuracy of XtremeCT improved from R2 = 0.76 (ST) to 0.85 (AT) and reached the same level of accuracy as XtremeCT-II with ST (R2 = 0.86). The largest improvements were obtained for BV/TV and Tb.Th. For XtremeCT-II, mean accuracy improved slightly from R2 = 0.86 (ST) to 0.89 (AT). For both segmentations and both scanners, the standard section was quantified slightly more accurate than the subchondral section. The agreement between the scanners was enhanced from R2 = 0.89 (ST) to 0.98 (AT). In conclusion, AT can enhance the accuracy of XtremeCT to quantify distal radius bone microstructural parameters close to XtremeCT-II level and increases the agreement between the two HR-pQCT scanners. High-resolution peripheral quantitative computed tomography, segmentation, bone microstructural parameters.

Incidence, hospitalization and mortality and their changes over time in people with a first ever diabetic foot ulcer.

AIMS: A diabetic foot ulcer (DFU) is a severe condition associated with morbidity and mortality. Population-based studies are rare and limited by access to reliable data. Without this data, efforts in primary prevention cannot be evaluated. Therefore, we examined the incidence and changes over time for the first DFU in people with diabetes. We also examined hospitalization and all-cause mortality and their changes over time. METHODS: From the UK primary care CPRD GOLD database (2007-2017), we identified 129,624 people with diabetes by a prescription for insulin or a non-insulin anti-diabetic drug. DFUs were identified using Read codes and expressed as incidence rates (IRs). Changes over time were described using Poisson and logistic regression and expressed as incidence rate ratios (IRRs) and odds ratios (ORs) respectively. RESULTS: The mean IR of first registered DFUs was 2.5 [95% CI: 2.1-2.9] per 1000 person-years for people with type 2 diabetes and 1.6 [1.3-1.9] per 1000 person-years for people with type 1. The IRs declined for people with type 2 diabetes (IRR per year: 0.97 [0.96-0.99]), while no changes were observed for people with type 1 diabetes (IRR per year: 0.96 [0.89-1.04]). Average hospitalization and 1-year mortality risk for people with type 2 diabetes were 8.2% [SD: 4.7] and 11.7% [SD: 2.2] respectively. Both declined over time (OR: 0.89 [0.84, 0.94] and 0.94 [0.89, 0.99]). CONCLUSION: The decline in all IRs, hospitalizations and mortality in people with type 2 diabetes suggests that prevention and care of the first DFU has improved for this group in primary care in the UK.

High-Resolution Cone-Beam Computed Tomography is a Fast and Promising Technique to Quantify Bone Microstructure and Mechanics of the Distal Radius.

Obtaining high-resolution scans of bones and joints for clinical applications is challenging. HR-pQCT is considered the best technology to acquire high-resolution images of the peripheral skeleton in vivo, but a breakthrough for widespread clinical applications is still lacking. Recently, we showed on trapezia that CBCT is a promising alternative providing a larger FOV at a shorter scanning time. The goals of this study were to evaluate the accuracy of CBCT in quantifying trabecular bone microstructural and predicted mechanical parameters of the distal radius, the most often investigated skeletal site with HR-pQCT, and to compare it with HR-pQCT. Nineteen radii were scanned with four scanners: (1) HR-pQCT (XtremeCT, Scanco Medical AG, @ (voxel size) 82 µm), (2) HR-pQCT (XtremeCT-II, Scanco, @60.7 µm), (3) CBCT (NewTom 5G, Cefla, @75 µm) reconstructed and segmented using in-house developed software and (4) microCT (VivaCT40, Scanco, @19 µm-gold standard). The following parameters were evaluated: predicted stiffness, strength, bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), separation (Tb.Sp) and number (Tb.N). The overall accuracy of CBCT with in-house optimized algorithms in quantifying bone microstructural parameters was comparable (R2 = 0.79) to XtremeCT (R2 = 0.76) and slightly worse than XtremeCT-II (R2 = 0.86) which were both processed with the standard manufacturer's technique. CBCT had higher accuracy for BV/TV and Tb.Th but lower for Tb.Sp and Tb.N compared to XtremeCT. Regarding the mechanical parameters, all scanners had high accuracy (R2 [Formula: see text] 0.96). While HR-pQCT is optimized for research, the fast scanning time and good accuracy renders CBCT a promising technique for high-resolution clinical scanning.

Quantification of 3D microstructural parameters of trabecular bone is affected by the analysis software.

Over the last decades, the use of high-resolution imaging systems to assess bone microstructural parameters has grown immensely. Yet, no standard defining the quantification of these parameters exists. It has been reported that different voxel size and/or segmentation techniques lead to different results. However, the effect of the evaluation software has not been investigated so far. Therefore, the aim of this study was to compare the bone microstructural parameters obtained with two commonly used commercial software packages, namely IPL (Scanco, Switzerland) and CTan (Bruker, Belgium). We hypothesized that even when starting from the same segmented scans, different software packages will report different results. Nineteen trapezia and nineteen distal radii were scanned at two resolutions (20 µm voxel size with microCT and HR-pQCT 60 µm). The scans were segmented using the scanners' default protocol. The segmented images were analyzed twice, once with IPL and once with CTan, to quantify bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N) and specific bone surface (BS/BV). Only small differences between IPL and CTan were found for BV/TV. For Tb.Th, Tb.Sp and BS/BV high correlations (R2 ≥ 0.99) were observed between the two software packages, but important relative offsets were observed. For microCT scans, the offsets were relative constant, e.g., around 15% for Tb.Th. However, for the HR-pQCT scans the mean relative offsets ranged over the different bone samples (e.g., for Tb.Th from 14.5% to 19.8%). For Tb.N, poor correlations (0.43 ≤ R2 ≤ 0.81) for all tested cases were observed. We conclude that trabecular bone microstructural parameters obtained with IPL and CTan cannot be directly compared except for BV/TV. For Tb.Th, Tb.Sp and BS/BV, correction factors can be determined, but these depend on both the image voxel size and specific anatomic location. The two software packages did not produce consistent data on Tb.N. The development of a universal standard seems desirable.

Use of Sodium-Glucose Co-Transporter-2-Inhibitors (SGLT2-Is) and Risk of Lower Limb Amputation.

BACKGROUND: Treatment with sodium-glucose co-transporter-2-inhibitors (SGLT2-Is), such as canagliflozin, has been associated with an increased risk of lower limb amputations (LLAs) in type 2 diabetes mellitus (T2DM). However, conflicting results have been reported for different SGLT2-Is and the underlying mechanism is unclear. OBJECTIVE: To investigate the risk of LLA and diabetic foot ulcer with SGLT2-I use compared to other anti-diabetic drugs and to explore hypovolemia as a potential underlying mechanism. METHODS: A cohort study was conducted using data from the Clinical Practice Research Datalink GOLD (2013-2019). The study population (N=51,847) consisted of T2DM patients over 18 years of age with at least one prescription of a non-insulin anti-diabetic drug. Concomitant diuretic use and the presence of signs of hypovolemia were determined to assess the potential underlying mechanism. Cox proportional hazard models were used to estimate the hazard ratio (HR) for LLA in current SGLT2-I use versus current sulphonylurea (SU) use. Analyses were adjusted for lifestyle variables, comorbidities, and concomitant drug use. RESULTS: Current SGLT2-I use was not associated with an increased risk of LLA compared to current SU use (fully adjusted HR 0.70; 95% confidence interval 0.38-1.29). Concomitant use of diuretics and the presence of signs of hypovolemia were not associated with an increased risk of LLA. CONCLUSION: Use of SGLT2-Is, with or without signs of hypovolemia, was not associated with an increased risk of LLA or DFU versus current SU use. Future studies powered to detect potential differences between individual SGLT2-Is are required to rule out a canagliflozin-specific effect.

The Prevalence of Celiac Disease in a Fracture Liaison Service Population.

Celiac disease (CD) is a known risk factor for osteoporosis and fractures. The prevalence of CD in patients with a recent fracture is unknown. We therefore systematically screened patients at a fracture liaison service (FLS) to study the prevalence of CD. Patients with a recent fracture aged ≥ 50 years were invited to VieCuri Medical Center's FLS. In FLS attendees, bone mineral density (BMD) and laboratory evaluation for metabolic bone disorders and serological screening for CD was systematically evaluated. If serologic testing for CD was positive, duodenal biopsies were performed to confirm the diagnosis CD. Data were collected in 1042 consecutive FLS attendees. Median age was 66 years (Interquartile range (IQR) 15), 27.6% had a major and 6.9% a hip fracture, 26.4% had osteoporosis and 50.8% osteopenia. Prevalent vertebral fractures were found in 29.1%. CD was already diagnosed in two patients (0.19%), one still had a positive serology. Three other patients (0.29%) had a positive serology for CD (one with gastro-intestinal complaints). In two of them, CD was confirmed by duodenal histology (0.19%) and one refused further evaluation. The prevalence of biopsy-proven CD was therefore 0.38% (4/1042) of which 0.19% (2/1042) was newly diagnosed. The prevalence of CD in patients with a recent fracture at the FLS was 0.38% and within the range of reported prevalences in the Western-European population (0.33-1.5%). Newly diagnosed CD was only found in 0.19%. Therefore, standard screening for CD in FLS patients is not recommended.

No decrease in fracture risk despite 15 years of treatment evolution for multiple myeloma patients: A Danish nationwide case-control study.

RATIONALE: While treatment strategies for multiple myeloma have evolved radically over the last decades, little is known about the risk of fractures for symptomatic multiple myeloma patients over time. OBJECTIVE: To determine the effect of different treatment periods (1996-2000, 2001-2006 and 2007-2011) on the risk of fractures in patients with multiple myeloma. METHODS: This retrospective case-control study included patients with multiple myeloma in Denmark, using the Danish National Health Service. Cases were defined as patients who had sustained a fracture between 1996 and 2011, and controls were those without a fracture. Exposure was defined as an ICD code for multiple myeloma. Vertebral fractures, gender, and age were considered in secondary analyses. Conditional logistic regression was used to estimate odd ratios (ORs) of fracture risk, and the analyses were adjusted for comorbidities and recent drug use. RESULTS: The study population consisted of 925,341 cases, and the same number of matched controls, of whom 1334 patients with multiple myeloma. Among cases, the risk of any fracture was higher in multiple myeloma patients compared to patients without multiple myeloma (any fracture: ORadj[95% CI] 1996-2000: 1.7[1.3-2.3]; 2001-2006: 1.3[1.1-1.6]; 2007-2011: 1.7[1.4-2.2]). Although fractures were mainly non-vertebral, the risk of vertebral fractures in particular was higher in multiple myeloma patients (vertebral fracture: ORadj[95% CI] 1996-2000: 3.5[1.4-8.6]; 2001-2006: 4.0[1.9-8.2]; 2007-2011: 3.0[1.6-5.7]). CONCLUSIONS: Despite new treatment strategies and improved supportive care, this study showed no decreased fracture risk for multiple myeloma patients over time. New treatment strategies, even if they have a positive impact on overall survival, offer no guarantee for a corresponding reduction in bone lesions.

Quantification of human bone microarchitecture damage in press-fit femoral knee implantation using HR-pQCT and digital volume correlation.

Primary press-fit fixation of femoral knee prostheses is obtained thanks to the inside dimensions of the implant being undersized with respect to the bone cuts created intra-operatively, dictated by a press-fit specified by the implant design. However, during prostheses press-fit implantation, high compressive and shear stresses at the implant-bone interface are generated, which causes permanent bone damage. The extent of this damage is unknown, but it may influence the implant stability and be a contributing factor to aseptic loosening, a main cause of revisions for knee arthroplasty. The aim of this ex-vivo study was to quantify, using high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging and Digital Volume Correlation (DVC), permanent bone deformation due to press-fit femoral knee implantation of a commonly used implant. Six human cadaveric distal femora were resected and imaged with HR-pQCT (60.7 µm/voxel, isotropic). Femurs were fitted with cementless femoral knee implants (Sigma PFC) and rescanned after implant removal. For each femur, permanent deformation was examined in the anterior, posterior-medial and posterior-lateral condyles for volumes of interest (VOIs) of 10 mm depth. The bone volume fraction (BV/TV) for the VOIs in pre- and post-implantation images was calculated, at increasing depth from the bone surface. DVC was applied on the VOIs pre- and post-implantation, to assess trabecular bone displacements and plastically accumulated strains. The "BV/TVpost/BV/TVpre ratio vs. depth" showed, consistently among the six femurs, three consecutive points of interest at increasing bone depth, indicating: bone removal (ratio<100%), compaction (ratio>100%) and no changes (ratio = 100%). Accordingly, the trabecular bone displacement computed by DVC suggested bone compaction up to 2.6 ±â€¯0.8 mm in depth, with peak third principal strains of -162,100 ±â€¯55,000 µÎµ (mean absolute error: 1,000-2,000 µÎµ, SD: 200-500 µÎµ), well above the yield strain of bone (7,000-10,000 µÎµ). Combining 3D-imaging, at spatial resolutions obtainable with clinical HR-pQCT, and DVC, determines the extent of plastic deformation and accumulated compressive strains occurring within the bone due to femoral press-fit implantation. The methods and data presented can be used to compare different implants, implant surface coatings and press-fit values. These can also be used to advance and validate computational models by providing information about the bone-implant interface obtained experimentally. Future studies using these methods can assist in determining the influence of bone damage on implant stability and the subsequent osseointegration.

Metformin use in type 2 diabetic patients is not associated with lower arterial stiffness: the Maastricht Study.

INTRODUCTION: Type 2 diabetes (T2D) is associated with cardiovascular disease complications such as myocardial infarction and stroke. These complications are at least partially the consequence of diabetes-associated increased arterial stiffness. Metformin, a first choice oral glucose-lowering drug, has been associated with potential cardio-protective effects. However, there are no data on the association between real-life metformin use and arterial stiffness. The objective of the current study is to investigate in a population-based sample of individuals with T2D the association between metformin use and aortic stiffness (i.e. carotid-femoral pulse wave velocity, cfPWV) and carotid stiffness [i.e. carotid distensibility coefficient and Young's elastic modulus (YEM)]. METHODS: We used data from The Maastricht Study, an ongoing observational prospective population-based cohort study (current N = 3451). All participants with T2D, based on pharmacy records (N = 672, 31.3% women, mean age 62.6 ±â€Š7.7), were included in the current study. Linear regression analyses were used to study the association between current metformin use and cfPWV, distensibility coefficient and YEM, as compared with no metformin use. Furthermore, metformin use was stratified by cumulative dose (in grams), continuous duration of use (in days), average daily dose (in grams) and time since first prescription (in years). Regression coefficients of distensibility coefficient were multiplied by -1, consequently, for all arterial stiffness indices, a positive regression coefficient signifies increasing arterial stiffness. RESULTS: Linear regression showed that neither current metformin use was associated with cfPWV [adjusted B: -0.04 (-0.11 to 0.02)] nor metformin use was as stratified by cumulative dose, by continuous duration of use, by average daily dose or by time since first prescription. Metformin use was statistically significantly associated with higher carotid stiffness as assessed by distensibility coefficient [0.12 (0.01 to 0.23)], but not with YEM [0.10 (-0.03 to 0.22)]. However, there was no consistent pattern with the different stratifications of metformin use when further investigating the association with distensibility coefficient. CONCLUSION: We showed that there is no significant association between current metformin use and aortic stiffness, regardless of how metformin use in itself was defined. In addition, metformin use was not associated with a lower carotid stiffness. The present results showed no beneficial effect of metformin use, dosage or duration on arterial stiffness in middle-aged patients with T2D. Alternatively, metformin may exerts its cardio-protective effects via other pathways.

The role of the Fracture Liaison Service (FLS) in subsequent fracture prevention in the extreme elderly.

BACKGROUND: Several guidelines recommend a bone and fall-related osteoporosis risk assessment in all patients with fracture and age > 50 years. In practice, however, there is no consensus whether screening > 85 years is useful. AIM: To evaluate the subsequent fracture risk in all patient > 85 years, comparing the two populations of Fracture Liaison Service (FLS) attenders and non-attenders. METHODS: All patients > 85 years that presented at the FLS with a non-vertebral fracture were included in the study during a 5-year period (September 2004 and December 2009). Excluded were pathologic fractures, death < 30 days, or patients on osteoporosis treatment. in patients that attended the FLS, assessment of bone mineral density and fall-risk factors were screened. In both the attenders and non-attenders groups, mortality and subsequent fracture rates were scored during a follow-up of 2 years. RESULTS: 282 patients fulfilled inclusion criteria for screening, of which 160 (57%) patients did not attend the FLS. 122 patients were screened for osteoporosis and fall-related risk of whom 72 were diagnosed with osteoporosis. Subsequent fracture risk in both groups was 19%. Medical treatment was started in 51 patients, of which 15 patients developed a subsequent fracture. Cox-regression analysis indicated a significantly lower mortality rate, but not a diminished subsequent fracture rate in the FLS screened population compared to the non-attenders. CONCLUSION: The advantage of a FLS in reducing subsequent fracture risk in patients > 85 years seems to be limited. In practice a large proportion of these patients are not screened.

Reduced mortality and subsequent fracture risk associated with oral bisphosphonate recommendation in a fracture liaison service setting: A prospective cohort study.

OBJECTIVE: Osteoporotic fragility fractures, that are common in men and women, signal increased risk of future fractures and of premature mortality. Less than one-third of postmenopausal women and fewer men are prescribed active treatments to reduce fracture risk. Therefore, in this study the association of oral bisphosphonate recommendation with subsequent fracture and mortality over eight years in a fracture liaison service setting was analysed. MATERIALS AND METHODS: In this prospective cohort study, 5011 men and women aged >50 years, who sustained a clinical fracture, accepted the invitation to attend the fracture liaison service of the West Glasgow health service between 1999 and 2007. These patients were fully assessed and all were recommended calcium and vitamin D. Based on pre-defined fracture risk criteria, 2534 (50.7%) patients were additionally also recommended oral bisphosphonates. Mortality and subsequent fracture risk were the pre-defined outcomes analysed using Cox proportional hazard models. RESULTS: Those recommended bisphosphonates were more often female (82.9 vs. 72.4%), were older (73.4 vs. 64.4 years), had lower bone mineral density T-score (-3.1 vs. -1.5) and more had sustained hip fractures (21.7 vs. 6.2%; p < 0.001). After adjustments, patients recommended bisphosphonates had lower subsequent fracture risk (Hazard Ratio (HR): 0.60; 95% confidence interval (CI): 0.49-0.73) and lower mortality risk (HR: 0.79, 95%CI: 0.64-0.97). CONCLUSION: Of the patients, who are fully assessed after a fracture at the fracture liaison service, those with higher fracture risk and a recommendation for bisphosphonates had worse baseline characteristics. However, after adjusting for these differences, those recommended bisphosphonate treatment had a substantially lower risk for subsequent fragility fracture and lower risk for mortality. These community-based data indicate the adverse public health outcomes and mortality impacts of the current low treatment levels post fracture could be improved by bisphosphonate recommendation for both subsequent fracture and mortality.

Reliability of HR-pQCT Derived Cortical Bone Structural Parameters When Using Uncorrected Instead of Corrected Automatically Generated Endocortical Contours in a Cross-Sectional Study: The Maastricht Study.

Most HR-pQCT studies examining cortical bone use an automatically generated endocortical contour (AUTO), which is manually corrected if it visually deviates from the apparent endocortical margin (semi-automatic method, S-AUTO). This technique may be prone to operator-related variability and is time consuming. We examined whether the AUTO instead of the S-AUTO method can be used for cortical bone analysis. Fifty scans of the distal radius and tibia from participants of The Maastricht Study were evaluated with AUTO, and subsequently with S-AUTO by three independent operators. AUTO cortical bone parameters were compared to the average parameters obtained by the three operators (S-AUTOmean). All differences in mean cortical bone parameters between AUTO and S-AUTOmean were < 5%, except for lower AUTO cortical porosity of the radius (- 16%) and tibia (- 6%), and cortical pore volume (Ct.Po.V) of the radius (- 7%). The ICC of S-AUTOmean and AUTO was > 0.90 for all parameters, except for cortical pore diameter of the radius (0.79) and tibia (0.74) and Ct.Po.V of the tibia (0.89), without systematic errors on the Bland-Altman plots. The precision errors (RMS-CV%) of the radius parameters between S-AUTOmean and AUTO were comparable to those between the individual operators, whereas the tibia RMS-CV% between S-AUTOmean and AUTO were higher than those of the individual operators. Comparison of the three operators revealed clear inter-operator variability. This study suggests that the AUTO method can be used for cortical bone analysis in a cross-sectional study, but that the absolute values-particularly of the porosity-related parameters-will be lower.

Evaluation of interference fit and bone damage of an uncemented femoral knee implant.

BACKGROUND: During implantation of an uncemented femoral knee implant, press-fit interference fit provides the primary stability. It is assumed that during implantation a combination of elastic and plastic deformation and abrasion of the bone will occur, but little is known about what happens at the bone-implant interface and how much press-fit interference fit is eventually achieved. METHODS: Five cadaveric femora were prepared and implantation was performed by an experienced surgeon. Micro-CT- and conventional CT-scans were obtained pre- and post-implantation for geometrical measurements and to measure bone mineral density. Additionally, the position of the implant with respect to the bone was determined by optical scanning of the reconstructions. By measuring the differences in surface geometry, assessments were made of the cutting error, the actual interference fit, the amount of bone damage, and the effective interference fit. FINDINGS: Our analysis showed an average cutting error of 0.67mm (SD 0.17mm), which pointed mostly towards bone under-resections. We found an average actual AP interference fit of 1.48mm (SD 0.27mm), which was close to the nominal value of 1.5mm. INTERPRETATION: We observed combinations of bone damage and elastic deformation in all bone specimens, which showed a trend to be related with bone density. Higher bone density tended to lead to lower bone damage and higher elastic deformation. The results of the current study indicate different factors that interact while implanting an uncemented femoral knee component. This knowledge can be used to fine-tune design criteria of femoral components to achieve adequate primary stability for all patients.

Fracture liaison services: do they reduce fracture rates?

The fracture liaison service (FLS) care is considered the most appropriate organizational approach for secondary fracture prevention. We performed a literature search to evaluate to what extent the introduction of a FLS reduced subsequent fracture rates. We identified five studies that compared subsequent fracture rates. These studies varied in study design, proportion of women, baseline and subsequent fracture type [vertebral fracture (VF), non-VF (NVF) or hip fractures], duration of follow-up, response rates of attending the FLS, as well as variables included in adjusted analyses (age, sex, baseline fracture, time dependency). In two studies comparing hospitals with and without a FLS, the adjusted hazard ratio (HR) for subsequent fractures was significantly lower in the FLS hospitals (HR: 0.84 during the first year, 0.44 during the second year for subsequent NVFs after baseline NVF, and 0.67 during the third year for subsequent VFs + NVFs after baseline VFs + NVFs). When comparing fracture rates before (pre-FLS) and after (post-FLS) introduction of a FLS, the adjusted HR for subsequent NVFs after baseline NVF was significantly lower in the post-FLS group after 2 years in one study (HR = 0.65) and nonsignificant in another study for subsequent hip fractures after baseline hip fracture. One study comparing pre-FLS and post-FLS with a follow-up of less than a year did not demonstrate a significant difference in subsequent fracture risk. In conclusion, only five FLS studies with heterogeneous study designs are available, three of them reported a lower subsequent fracture rate related to FLS care. Larger and long-term studies will be needed to further quantify the effect of FLS care on subsequent fracture risk.