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1.
Measurement of microstructural parameters of trabecular bone noninvasively in vivo is possible with high-resolution magnetic resonance (MR) imaging. These measurements may prove useful in the determination of bone strength and fracture risk, but must be related to other measures of bone properties. In this study in vivo MR imaging was used to derive trabecular bone structure measures and combined with micro-finite element analysis (μFE) to determine the effects of trabecular bone microarchitecture on bone mechanical properties in the distal radius. The subjects were studied in two groups: (I) postmenopausal women with normal bone mineral density (BMD) (n= 22, mean age 58 ± 7 years) and (II) postmenopausal women with spine or femur BMD −1 SD to −2.5 SD below young normal (n= 37, mean age 62 ± 11 years). MR images of the distal radius were obtained at 1.5 T, and measures such as apparent trabecular bone volume fraction (App BV/TV), spacing, number and thickness (App TbSp, TbN, TbTh) were derived in regions of interest extending from the joint line to the radial shaft. The high-resolution images were also used in a micro-finite element model to derive the directional Young’s moduli (E1, E2 and E3), shear moduli (G12, G23 and G13) and anisotropy ratios such as E1/E3. BMD at the distal radius, lumbar spine and hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed by serum osteocalcin and bone resorption by serum type I collagen C-terminal telopeptide breakdown products (serum CTX) and urinary CTX biochemical markers. The trabecular architecture displayed considerable anisotropy. Measures of BMD such as the ultradistal radial BMD were lower in the osteopenic group (p<0.01). Biochemical markers between the two groups were comparable in value and showed no significant difference between the two groups. App BV/TV, TbTh and TbN were higher, and App TbSp lower, in the normal group than the osteopenic group. All three directional measures of elastic and shear moduli were lower in the osteopenic group compared with the normal group. Anisotropy of trabecular bone microarchitecture, as measured by the ratios of the mean intercept length (MIL) values (MIL1/MIL3, etc.), and the anisotropy in elastic modulus (E1/E3, etc.), were greater in the osteopenic group compared with the normal group. The correlations between the measures of architecture and moduli are higher than those between elastic moduli and BMD. Stepwise multiple regression analysis showed that while App BV/TV is highly correlated with the mechanical properties, additional structural measures do contribute to the improved prediction of the mechanical measures. This study demonstrates the feasibility and potential of using MR imaging with μFE modeling in vivo in the study of osteoporosis. Received: 13 December 2000 / Accepted: 30 May 2001  相似文献   

2.
The goal of this study was to assess whether a high-resolution CT measure of trabecular bone structure can enhance the discrimination between subjects with or without a vertebral fracture and having overall low hip or spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Sixty-one women with low BMD by DXA (T-score <–2.5 at hip or spine) were examined. Twenty women had sustained a vertebral fracture. Quantitative CT (QCT) BMD and high-resolution CT spinal scans were performed on a whole-body CT scanner. For the high-resolution images (0.31 mm pixel, 1.5 mm thick slice), trabecular bone was segmented from marrow using an adaptive threshold, region growth and skeletonization step. From the processed image we measured the apparent trabecular bone fraction (BV/TV), apparent trabecular thickness (I.Th) and apparent trabecular spacing (I.Sp). We also assessed the connectivity of the marrow space using region growing to derive a mean (HA) and maximum (HM) hole size. Despite the fact that the study population was preselected to have a low BMD by DXA, QCT BMD was highly associated with (p <0.005) with fracture status. All structural parameters were correlated (r ~ 0.64 to 0.79) with BMD with p <0.003 and showed significant differences between the fracture and non-fracture group. However, except for HA, this difference did not remain significant after adjustment for BMD. When BMD and then HA was entered into a paired linear regression model to predict fracture outcome, HA contributed with p= 0.03 and BMD with p= 0.86. ROC analysis was applied and showed that HA, BMD, I.Th and I.Sp discriminated the two groups with areas of 0.76, 0.75, 0.71 and 0.68, respectively. These findings suggest that an assessment of vertebral trabecular structure from high-resolution CT images is useful in discriminating subjects with vertebral fractures and potentially useful for predicting future fractures. Received: 10 October 1997 / Accepted: 4 December 1997  相似文献   

3.
We determined the quantitative relationships between graded oral dosing with vitamin D3, 25(OH)D3, and 1,25(OH)2D3 for short treatment periods and changes in circulating levels of these substances. The subjects were 116 healthy men (mean age, 28 + 4 years, with usual milk consumption of 40.47 l/day and mean serum 25(OH)D of 67 + 25 nmol/l). They were distributed among nine open-label treatment groups: vitamin D3 (25, 250 or 1250 mg/day for 8 weeks), 25(OH)D3 (10, 20 or 50 mg/day for 4 weeks) and 1,25(OH)2D3 (0.5, 1.0 or 1.0 mg/day for 2 weeks). All treatment occurred between January 3 and April 3. We measured fasting serum calcium, parathyroid hormone, vitamin D3, 25(OH)D and 1,25(OH)2D immediately before and after treatment. In the three groups treated with vitamin D3, mean values for circulating vitamin D3 increased by 13, 137 and 883 nmol/l and serum 25(OH)D increased by 29, 146 and 643 nmol/l for the three dosage groups, respectively. Treatment with 25(OH)D3 increased circulating 25(OH)D by 40, 76 and 206 nmol/l, respectively. Neither compound changed serum 1,25(OH)2D levels. However, treatment with 1,25(OH)2D3 increased circulating 1,25(OH)2D by 10, 46 and 60 pmol/l, respectively. Slopes calculated from these data allow the following estimates of mean treatment effects for typical dosage units in healthy 70-kg adults: an 8-week course of vitamin D3 at 10 mg/day (400 IU/day) would raise serum vitamin D by 9 nmol/l and serum 25(OH)D by 11 nmol/l; a 4-week course of 25(OH)D3 at 20 mg/day would raise serum 25(OH)D by 94 nmol/l; and a 2-week course of 1,25(OH)2D3 at 0.5 mg/day would raise serum 1,25(OH)2D by 17 pmol/l. Received: 4 August 1997 / Accepted: 14 October 1997  相似文献   

4.
A high-resolution magnetic resonance imaging (MRI) protocol, together with specialized image processing techniques, was applied to the quantitative measurement of age-related changes in calcaneal trabecular structure. The reproducibility of the technique was assessed and the annual rates of change for several trabecular structure parameters were measured. The MR-derived trabecular parameters were compared with calcaneal bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) in the same subjects. Sagittal MR images were acquired at 1.5 T in 23 healthy women (mean age: 49.3 ± 16.6 [SD]), using a three-dimensional gradient echo sequence. Image analysis procedures included internal gray-scale calibration, bone and marrow segmentation, and run-length methods. Three trabecular structure parameters, apparent bone volume (ABV/TV), intercept thickness (I.Th), and intercept separation (I.Sp) were calculated from the MR images. The short- and long-term precision errors (mean %CV) of these measured parameters were in the ranges 1–2% and 3–6%, respectively. Linear regression of the trabecular structure parameters vs. age showed significant correlation: ABV/TV (r 2= 33.7%, P < 0.0037), I.Th (r 2= 26.6%, P < 0.0118), I.Sp (r 2= 28.9%, P < 0.0081). These trends with age were also expressed as annual rates of change: ABV/TV (− 0.52%/year), I.Th (−0.33%/year), and I.Sp (0.59%/year). Linear regression analysis also showed significant correlation between the MR-derived trabecular structure parameters and calcaneal BMD values. Although a larger group of subjects is needed to better define the age-related changes in trabecular structure parameters and their relation to BMD, these preliminary results demonstrate that high-resolution MRI may potentially be useful for the quantitative assessment of trabecular structure. Received: 11 March 1996 / Accepted: 9 July 1996  相似文献   

5.
The authors have developed a system for the characterization of trabecular bone structure from high-resolution MR images. It features largely automated coil inhomogeneity correction, trabecular bone region segmentation, serial image registration, bone/marrow binarization, and structural calculation steps. The system addresses problems of efficiency and inter- and intra-operator variability inherent in previous analyses. The system is evaluated on repetitive scans of 8 volunteers for both two-dimensional (2D) apparent structure calculations and three-dimensional (3D) mechanical calculations using micro-finite element analysis. Coil correction methods based on a priori knowledge of the coil sensitivity and on low-pass filtering of the high-resolution mages are compared and found to perform similarly. Image alignment is found to cause small but significant changes in some structural parameters. Overall the automated system provides on the order of a 3-fold decrease in trained operator time over previous manual methods. Reproducibility is found to be dependent on image quality for most parameters. For 7 subjects with good image quality, reproducibility of 2–4% is found for 2D structural parameters, while 3D mechanical parameters vary by 4–9%, with percent standardized coefficients of variation in the ranges of 15–34% and 20–38% respectively. Received: 11 June 2001 / Accepted: 6 November 2001  相似文献   

6.
To study the short- and long-term effects of estrogen deficiency on trabecular bone, three-dimensional measurements of proximal tibiae of ovariectomized rats were performed by micro-computed tomography (MicroCT). New three-dimensional (3D) techniques were employed to characterize the trabecular architecture from 0 to 110 days post-ovariectomy (OVX). These new methods no longer assume a plate or rod model of bone, but calculate trabecular thickness, separation, and number and their distribution by placing maximal spheres into the 3D representation of the structure. The model type of bone was quantified with the Structure Model Index (SMI). Utilizing these methods we found a rapid loss of trabecular bone in the first week after OVX. After the first week bone mass declined further, although the rate of loss was lower. In addition there was a complete change in model type from plate-like to rod-like within 7 days post-OVX, and then a very constant SMI after 12 days. After an initial thinning of trabecular structure, further bone loss seems to occur through removal of trabeculae, while the trabecular plate thickness remains constant. The heterogeneity of the network could be quantified by intra-individual standard deviation of local separations, which showed a stair-like progression, with a plateau between 12 and 60 days post-OVX. This study provides new insights into ovariectomy-related changes in cancellous bone structure evaluated by 3D MicroCT. In addition, these data suggest that the rapid change of model from plate-like to rod-like post-OVX may potentially introduce biases in the parameters that are determined using model-based algorithms, and these biases may modify the impact of age-related or therapeutic changes. Received: 19 December 2000 / Accepted: 16 April 2001  相似文献   

7.
Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people. Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures, as proved by Decalyos I. Decalyos II is a 2-year, multicenter, randomized, double-masked, placebo-controlled confirmatory study. The intention-to-treat population consisted of 583 ambulatory institutionalized women (mean age 85.2 years, SD = 7.1) randomized to the calcium–vitamin D3 fixed combination group (n= 199); the calcium plus vitamin D3 separate combination group (n= 190) and the placebo group (n= 194). Fixed and separate combination groups received the same daily amount of calcium (1200 mg) and vitamin D3 (800 IU), which had similar pharmacodynamic effects. Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent, with levels returning within the normal range after 6 months. In a subgroup of 114 patients, femoral neck bone mineral density (BMD) decreased in the placebo group (mean =–2.36% per year, SD = 4.92), while remaining unchanged in women treated with calcium-vitamin D3 (mean = 0.29% per year, SD = 8.63). The difference between the two groups was 2.65% (95% CI =–0.44, 5.75%) with a trend in favor of the active treatment group. No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis. The relative risk (RR) of HF in the placebo group compared with the active treatment group was 1.69 (95% CI = 0.96, 3.0), which is similar to that found in Decalyos I (RR = 1.7; 95% CI = 1.0, 2.8). Thus, these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women. Received: 23 March 2001 / Accepted: 28 October 2001  相似文献   

8.
To determine whether magnetic resonance (MR)-derived measures of trabecular bone architecture in the distal radius are predictive for prevalent hip fractures, 20 subjects with hip fractures and 19 age-matched postmenopausal controls were studied. Bone mineral density (BMD) measures at the hip (dual-energy X-ray absorptiometry, DXA) and the distal radius (peripheral quantitative computed tomography, pQCT) were also obtained. We compared the MR-based structural measures derived in the radius with those in the calcaneus of the same patients. In the radius, images were acquired at an in-plane resolution of 156 μm and a slice thickness of 0.5 mm. Stereologic measures such as the apparent trabecular thickness (app. Tb.Th), fractional trabecular bone volume (app. BV/TV), trabecular spacing (app. Tb.Sp) and trabecular number (app. Tb.N) were derived from the images. Measures of app. Tb.Sp and app. Tb.N in the distal radius showed significant (p<0.05) differences between the two groups, as did hip BMD measures. However, radial trabecular BMD measures showed only a marginal difference (p= 0.05). Receiver operating curve analysis was used to determine the diagnostic efficacy of BMD, structural measures and a combination of the two. The area under the curve (AUC) for total hip BMD was 0.73, and for radial trabecular BMD was 0.69. AUC for most of the measures of trabecular bone structure at the distal radius was lower than for hip BMD measures; however, AUC for app. Tb.N at the radius was 0.69, comparable to trabecular BMD using pQCT. The AUC for combined BMD (hip) and structure measures was higher (0.87) when radius and calcaneus structure was included. Measures of trabecular architecture derived from MR images combined with BMD measures improve the discrimination between subjects with hip fractures and normal age-matched controls. Received: 22 December 1998 / Accepted: 12 February 1999  相似文献   

9.
Osteoblast deficit plays a principal role in the development of diabetic osteopenia. We have previously reported that high glucose conditions impair the function of osteoblast-like MG-63 cells. This study was performed to assess the sensitivity of osteoblasts to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in patients with type 2 diabetes without insulin deficiency or overt diabetic complications. During stimulation with 1,25(OH)2D3 at 2.0 mg/day for 6 consecutive days in 9 type 2 diabetic patients, serum levels of bone alkaline phosphatase (BALP), osteocalcin (OC) and the carboxyterminal propeptide of type 1 procollagen, and the urinary excretion of pyridinoline and deoxypyridinoline (DPYR), were monitored. As parameters of glycemic control, the mean level of fasting plasma glucose (mFPG) throughout the 1,25(OH)2D3 stimulation test and the level of HbA1C were used. 1,25(OH)2D3 increased serum 1,25(OH)2D significantly by day 2, which was followed by a significant reduction in the serum level of intact parathyroid hormone. The maximal increment of serum OC adjusted for that of 1,25(OH)2D was negatively correlated with both mFPG and HbA1C levels (p50.05). Furthermore, the magnitude of 1,25(OH)2D3-induced bone resorption, as reflected by the maximal increase in urinary DPYR excretion, was negatively correlated with the mFPG level (p50.05). Basal BALP tended to be negatively correlated with HbA1C, although not to a significant extent. In conclusion, our findings would indicate that poor glycemic control impairs the responses of osteoblasts and osteoclasts to 1,25(OH)2D3 in normo-insulinemic type 2 diabetic patients. Received: 9 February 1998 / Accepted: 10 November 1998  相似文献   

10.
Vitamin D metabolites can prevent estrogen depletion-induced bone loss in ovariectomized (OVX) rats. Our aim was to compare the bone-protective effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), 1α,25-dihydroxyvitamin D2 (1,25(OH)2D2), 1α-hydroxyvitamin D3 (1α(OH)D3), and 1α-hydroxyvitamin D2 (1α(OH)D2) in OVX rats. 1α(OH)D3 and 1α(OH)D2 are thought to be activated in the liver to form 1,25(OH)2D3 and 1,25(OH)2D2, respectively. Forty-four 12-week-old female Fischer-344 rats were either OVX or sham-operated (SHAM). Groups of OVX rats (n = 7 each) received vehicle alone, 1,25(OH)2D3, 1,25(OH)2D2, 1α(OH)D3, or 1α(OH)D2, starting 2 weeks after surgery. All vitamin D metabolites were administered orally at a dose of 15 ng/day/rat. Urine and blood samples were collected 6, 9, 12, and 16 weeks after surgery. Serum samples were analyzed for total calcium and phosphate. Calcium, phosphate, creatinine, and free collagen cross-links (ELISA) were determined in urine. After tetracycline double labeling, the rats were sacrificed 16 weeks postsurgery, and the proximal tibiae and the first lumbar vertebrae were processed undecalcified for static and dynamic bone histomorphometry. 1,25(OH)2D3 and, to a slightly lesser extent, 1,25(OH)2D2 elevated vertebral cancellous bone mass in OVX rats to a level beyond that observed in SHAM animals, and both compounds increased serum calcium and urinary calcium excretion to similar extents. 1α(OH)D3 and 1α(OH)D2 resulted in a 64% and 84%, respectively, inhibition of ovariectomy-induced vertebral cancellous bone loss. In the proximal tibial metaphysis, all vitamin D metabolites tested could only partially prevent post-OVX trabecular bone loss, with a tendency for 1α(OH)D3 to be the least active compound. The effects of 1α(OH)D3 and 1α(OH)D2 on calcium homeostasis differed markedly, however. The mean increase in urinary calcium excretion over the whole experiment was fivefold for 1α(OH)D3, whereas the corresponding increase for 1α(OH)D2 was only twofold. We conclude that, compared with 1α(OH)D3, 1α(OH)D2 combined at least equal or higher bone-protective activity in OVX rats with distinctly less pronounced effects on calcium homeostasis. This effect was not due to a differential action of the corresponding main activation products, 1,25(OH)2D3 and 1,25(OH)2D2. Received: 2 May 1996 / Accepted: 18 October 1996  相似文献   

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