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Higher incidences of fractures are seen in people with type 1 diabetes (T1D), but knowledge on different fracture sites is sparse. We found a higher incidence mainly for distal fracture sites in people with T1D compared to controls. It must be further studied which fractures attributed to the higher incidence rates (IRs) at specific sites. Introduction People with T1D have a higher incidence of fractures compared to the general population. However, sparse knowledge exists on the incidence rates of individual fracture sites. Therefore, we examined the incidence of various fracture sites in people with newly treated T1D compared to matched controls. Methods All people from the UK Clinical Practice Research Datalink GOLD (1987-2017), of all ages with a T1D diagnosis code (n = 6381), were included. People with T1D were matched by year of birth, sex, and practice to controls (n = 6381). Fracture IRs and incidence rate ratios (IRRs) were calculated. Analyses were stratified by fracture site and sex. Results The IR of all fractures was significantly higher in people with T1D compared to controls (IRR: 1.39 (CI95%: 1.24-1.55)). Compared to controls, the IRR for people with T1D was higher for several fracture sites including carpal (IRR: 1.41 (CI95%: 1.14-1.75)), clavicle (IRR: 2.10 (CI95%: 1.18-3.74)), foot (IRR: 1.70 (CI95%: 1.23-2.36)), humerus (IRR: 1.46 (CI95%: 1.04-2.05)), and tibia/fibula (IRR: 1.67 CI95%: 1.08-2.59)). In women with T1D, higher IRs were seen at the ankle (IRR: 2.25 (CI95%: 1.10-4.56)) and foot (IRR: 2.11 (CI95%: 1.27-3.50)), whereas in men with T1D, higher IRs were seen for carpal (IRR: 1.45 (CI95%: 1.14-1.86)), clavicle (IRR: 2.13 (CI95%: 1.13-4.02)), and humerus (IRR: 1.77 (CI95%: 1.10-2.83)) fractures. Conclusion The incidence of carpal, clavicle, foot, humerus, and tibia/fibula fractures was higher in newly treated T1D, but there was no difference at other fracture sites compared to controls. Therefore, the higher incidence of fractures in newly t

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 mu m, (2) XtremeCT-II at 60.7 mu m and (3) the small animal microCT scanner VivaCT40 at 19 mu m 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 R-2 = 0.76 (ST) to 0.85 (AT) and reached the same level of accuracy as XtremeCT-II with ST (R-2 = 0.86). The largest improvements were obtained for BV/TV and Tb.Th. For XtremeCT-II, mean accuracy improved slightly from R-2 = 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 R-2 = 0.89 (ST) to 0.98 (AT).In conclusion, AT can enhance the accurac

Background Long-term use of antiseizure drugs is associated with a low bone mineral density (BMD) and an increased fracture risk. The literature regarding institutionalised children on chronic antiseizure drugs is limited. Therefore, the aim of this cross-sectional study is to evaluate the prevalence of low BMD and the history of fractures in institutionalised children with epilepsy and intellectual disability (ID). Methods A dual-energy X-ray absorptiometry of lumbar spine (L1-L4) and hip was performed in 24 children, residing in a long-stay care facility in the Netherlands. Additionally, serum concentrations of albumin, calcium and 25-hydroxyvitamin D were determined. Data on fractures were retrospectively extracted from the medical files. Results Ages of the children (14 male and 10 female) ranged from 5 to 17 years with a mean age of 13.0 (+/- 3.2). The criteria of the International Society for Clinical Densitometry (ISCD) were used for classification of bone mineral disorders. Eight (33.3%) children had a normal BMD (Z-score > - 2.0). Of the 16 children with a low BMD (Z-score <= - 2.0), three were diagnosed as osteoporotic, based on their fracture history. Ten children (41.7%) were reported to have at least one fracture in their medical history. Serum concentrations of albumin-corrected calcium (2.28-2.50 mmol/L) and (supplemented) vitamin D (16-137 nmol/L) were within the normal range. Conclusions This study demonstrated that 67% of institutionalised children with epilepsy and ID had low BMD and 42% had a history of at least one fracture, despite supplementation of calcium and vitamin D in accordance with the Dutch guidelines.

Objectives: To study the relationship between structural damage and inflammatory features on magnetic resonance imaging (MRI) or radiography and other risk factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) seropositivity, hand dominance, disease duration] and the presence or number of cortical interruptions in finger joints on high-resolution peripheral quantitative computed tomography (HR-pQCT). Method: Finger joints of 38 healthy subjects and 39 patients with rheumatoid arthritis (RA) were examined through radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical interruptions. Descriptive statistics were calculated and associations examined using generalized estimating equations. Results: Cortical interruptions were found in healthy subjects and patients with RA on HR-pQCT (mean ± sd 0.33 ± 0.63 vs 0.38 ± 0.64 per joint quadrant, respectively, p < 0.01). Structural damage on MRI (cortical interruptions) or radiographs (SvH ≥ 1) was associated with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95% confidence interval (CI) 7.5–21.4, p < 0.01 and OR 4.8, 95% CI 1.9–11.7, respectively, p < 0.01]. The presence of BMO or synovitis was associated with more cortical interruptions on HR-pQCT (β 0.47, 95% CI 0.4–0.6, p < 0.01 and β 1.9, 95% CI 0.6–3.1, p < 0.01). In patients with RA, ACPA, and/or RF seropositivity, hand dominance and disease duration were not associated with more cortical interruptions on HR-pQCT. Conclusion: Structural damage and inflammatory features on MRI and radiographs are associated with cortical interruptions on HR-pQCT. No association between other risk factors and cortical interruptions was demonstrated.

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.

OBJECTIVES: To develop a scoring method to visually score cortical interruptions in finger joints on High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), determine its intra- and inter-reader reliability and test its feasibility.METHODS: The scoring method was developed by integrating results from in-depth discussions with experts, consensus meetings, multiple reading experiments and the literature. Cortical interruptions were scored by two independent readers in an imaging dataset with finger joints from patients with rheumatoid arthritis (RA) and healthy controls and assessed for adjacent trabecular distortion. Reliability for the total number of cortical interruptions per joint and per quadrant was calculated using intraclass correlation coefficient (ICC). Feasibility was tested by recording the time to analyze one joint.RESULTS: In 98 joints we identified 252 cortical interruptions, 17% had trabecular distortion. Mean diameter of the interruptions was significantly larger in patients with RA compared with healthy controls (0.88 vs 0.47 mm, p = 0.03). Intra-reader reliability was ICC 0.88 (95% CI 0.83;0.92) per joint and ICC 0.69 (95% CI 0.65;0.73) per quadrant. Inter-reader reliability was ICC 0.48 (95% CI 0.20;0.67) per joint and ICC 0.56 (95% CI 0.49;0.62) per quadrant. The time to score one joint was mean 9.2 (SD 4.9) min.CONCLUSIONS: This scoring method allows detection of small cortical interruptions on HR-pQCT imaging of finger joints, which is promising for use in clinical studies.

Summary In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites. Introduction To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally—in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters. Methods Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history. Results After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (− 4%) in prediabetes and smaller cross-sectional area of the tibia (− 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (− 5%), cortical thickness (− 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (− 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters. Conclusions In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are wa

For accurate analysis of bone formation and resorption during fracture healing, correct registration of follow-up onto baseline image is required. A per-fragment approach could improve alignment compared to standard registration based on the whole fractured region. In this exploratory study, we tested the effect of fragment size and displacement on a per-fragment registration, and compared the results of this per-fragment registration to the results of the standard registration in two stable fractures and one unstable fracture. To test the effect of fragment size and displacement, high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of three unfractured radii were divided into subvolumes. Different displacements in x-, y, or z-direction or rotations around each axis were applied, and each subvolume was registered onto the initial volume to realign it. Next, registration of follow-up onto baseline scan was performed in two stable and one unstable fracture. After coarsely aligning the follow-up onto the baseline scan, a more accurate registration was performed of the whole fracture, i.e. the standard registration, and of each fracture fragment separately, i.e. per-fragment registration. Alignment was checked using overlay images showing baseline, follow-up and overlap between these scans, and by comparing correlation coefficients between the standard and per-fragment registration. Generally, subvolumes as small as 300 mm3 that were displaced up to 0.82 mm in x- or y-, or up to 1.64 mm in z-direction could be realigned correctly. For the fragments of all fractures, correlation coefficients were higher after per-fragment registration compared to standard registration. Most improvement was found in the unstable fracture and one fragment of the unstable fracture did not align correctly. This exploratory study showed that image registration of individual subvolumes, such as fracture fragments, is feasible in both stable and unstable fra

We evaluated whether cortical interruptions classified as vascular channel (VC) on high-resolution peripheral quantitative computed tomography (HR-pQCT) could be confirmed by histology. We subsequently evaluated the image characteristics of histologically identified VCs on matched single and multiplane HR-pQCT images. Four 3-mm thick portions in three anatomic metacarpophalangeal joint specimens were selected for histologic sectioning. First, VCs identified with HR-pQCT were examined for confirmation on histology. Second and independently, VCs identified by histology were matched to single and multiplane HR-pQCT images to assess for presence of cortical interruptions. Only one out of five cortical interruptions suggestive for VC on HR-pQCT could be confirmed on histology. In contrast, 52 VCs were identified by histology of which 39 (75%) could be classified as cortical interruption or periosteal excavation on matched single HR-pQCT slices. On multiplane HR-pQCT images, 11 (21%) showed a cortical interruption in at least two consecutive slices in two planes, 36 (69%) in at least one slice in two planes and five (10%) showed no cortical interruption. Substantially more VCs were present in histology sections than initially suggested by HR-pQCT. The small size and heterogeneous presentation, limit the identification as VC on HR-pQCT.

We developed a semi-automated algorithm for the detection of cortical interruptions in finger joints using high-resolution peripheral quantitative computed tomography (HR-pQCT). Here, we tested its reliability compared to microCT (µCT) as gold standard. Nineteen joints of 10 female anatomic index fingers were imaged by HR-pQCT and µCT (82 and 18 µm isotropic voxel sizes, respectively). The algorithm was applied for detection of cortical interruptions of different minimum diameters (range >0.16 to >0.50 mm). Reliability was tested at the joint level with intra-class correlation coefficient (ICC) for the number of interruptions and interruption surface, and at the level of a single interruption for matching between HR-pQCT and µCT with a fixed interruption diameter (>0.10 mm) on µCT. The positive predictive value (PPV0.10mm) and sensitivity0.10mm were evaluated. The mean number of interruptions per joint depended on the diameter cut-off and ranged from 3.4 to 53.5 on HR-pQCT and from 1.8 to 45.1 on µCT for interruptions >0.50 to >0.16 mm, respectively. Reliability at the joint level was almost perfect (ICC ≥0.81) for both the number and surface of interruptions >0.16 and >0.33 mm. As expected, the PPV0.10mm increased with increasing interruption diameter from 84.9 to 100%, for interruptions >0.16 and >0.50 mm, respectively. However, the sensitivity0.10mm decreased with increasing interruption diameter from 62.4 to 4.7%. This semi-automated algorithm for HR-pQCT in finger joints performed best for the detection of cortical interruptions with a minimum diameter of >0.16 or >0.33 mm, showing almost perfect reliability at the joint level and interruptions matched with those on µCT.

BACKGROUND: Carbon-fiber-reinforced poly-ether-ether-ketone (CFR-PEEK) has superior radiolucency compared to other orthopedic implant materials, e.g. titanium or stainless steel, thus allowing metal-artifact-free postoperative monitoring by computed tomography (CT). Recently, high-resolution peripheral quantitative CT (HRpQCT) proved to be a promising technique to monitor the recovery of volumetric bone mineral density (vBMD), micro-architecture and biomechanical parameters in stable conservatively treated distal radius fractures. When using HRpQCT to monitor unstable distal radius fractures that require volar distal radius plating for fixation, radiolucent CFR-PEEK plates may be a better alternative to currently used titanium plates to allow for reliable assessment. In this pilot study, we assessed the effect of a volar distal radius plate made from CFR-PEEK on bone parameters obtained from HRpQCT in comparison to two titanium plates.METHODS: Plates were instrumented in separate cadaveric human fore-arms (n = 3). After instrumentation and after removal of the plates duplicate HRpQCT scans were made of the region covered by the plate. HRpQCT images were visually checked for artifacts. vBMD, micro-architectural and biomechanical parameters were calculated, and compared between the uninstrumented and instrumented radii.RESULTS: No visible image artifacts were observed in the CFR-PEEK plate instrumented radius, and errors in bone parameters ranged from -3.2 to 2.6%. In the radii instrumented with the titanium plates, severe image artifacts were observed and errors in bone parameters ranged between -30.2 and 67.0%.CONCLUSIONS: We recommend using CFR-PEEK plates in longitudinal in vivo studies that monitor the healing process of unstable distal radius fractures treated operatively by plating or bone graft ingrowth.

Type 2 diabetes mellitus has recently been linked to an increased Since bone mass seems to be normal to elevated in patient with type 2 the increased fracture risk is thought to be due to both an increased frequency and decreased bone quality. The increased falling frequency is result of complications of the disease such as a retinopathy and Bone quality is affected through changes in bone shape, bone micro- and in material properties such as bone mineralization and the quality collagen. Commonly used methods for predicting fracture risk such as X-ray absorptiometry and fracture risk assessment tools are helpful in with type 2 diabetes mellitus, but underestimate the absolute fracture given score. New imaging modalities such as high resolution peripheral quantitative computed tomography are promising for giving insight in the etiology underlying the fragility of the diabetic bone, as they can give insight into the microarchitecture and geometry of the bone. We present overview of the contributing mechanisms to the increased fracture risk usefulness of imaging modalities and risk assessment tools in predicting risk in patients with type 2 diabetes.

Background: Previously undetected contributors to secondary osteoporosis and metabolic bone diseases (SECOB) are frequently found in patients with osteoporosis, but the prevalence in patients at the time they present with a clinical fracture is unknown. Methods: All consecutive patients with a recent clinical vertebral or nonvertebral fracture, who were able and willing to be investigated (n = 626: 482 women, 144 men, age range 50-97 yr) had bone mineral density and laboratory investigations (serum calcium, inorganic phosphate, 25-hydroxyvitamin D, creatinine, intact PTH, TSH, free T-4, serum and urine protein electrophoresis, and in men also serum testosterone). Results: Known SECOB contributors were present in 23.0% of patients and newly diagnosed SECOB contributors in 26.5%: monoclonal proteinemia (14 of 626), renal insufficiency grade III or greater (54 of 626), primary (17 of 626) and secondary (64 of 626) hyperparathyroidism, hyperthyroidism (39 of 626), and hypogonadism in men (12 of 144). Newly diagnosed SECOBs, serum 25-hydroxyvitamin D less than 50 nmol/liter (in 63.9%), and dietary calcium intake less than 1200 mg/d (in 90.6%) were found at any age, in both sexes, after any fracture (except SECOB in men with finger and toe fractures) and at any level of bone mineral density. Conclusion: At presentation with a fracture, 26.5% of patients have previously unknown contributors to SECOB, which are treatable or need follow-up, and more than 90% of patients have an inadequate vitamin D status and/or calcium intake. Systematic screening of patients with a recent fracture identifies those in whom potentially reversible contributors to SECOB and calcium and vitamin D deficiency are present. (J Clin Endocrinol Metab 96: 1360-1367, 2011)