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Biomedical subjects

Harry K Genant

Publications and source records attributed to Harry K Genant.

At least 55 records · Page 3Linked to original sources
PubMed2003

Quantitative and qualitative assessment of closed fracture healing using computed tomography and conventional radiography.

RATIONALE AND OBJECTIVES: Development of new agents to induce fracture healing requires more sensitive methods to detect early changes in fracture repair. The aims of this study were to determine quantitative and qualitative features of fracture healing using volumetric computed tomography (CT) and to compare them with conventional radiography during the weeks following uncomplicated fractures of the appendicular skeleton. MATERIALS AND METHODS: 39 otherwise healthy men and women with acute, closed fractures of the distal radius, tibial and/or fibular malleoli, or tibial shaft, were enrolled and underwent CT and X-ray imaging at 1, 2, 4, 8, 12, and 16 (tibial shaft only) weeks post fracture. Qualitative assessment included fracture line/margins, fracture gap, external callus appearance, callus-to-cortex ratio, bridging, and radiologic union. Quantitative assessment of CT density changes (Hounsfield units [HU]) in the fracture gap was performed in a subset of 8 fracture patients using MEDx multimodality image analysis software (Sterling,VA). The analysis was performed by drawing free form regions of interest (ROI) covering the fracture gap on baseline (week 1) images and by automated registration of the follow-up images to the baseline co-ordinate system. RESULTS: The mean time to achieve radiologic union on CT was slightly shorter than on X-rays for radial and tibial shaft fractures (7.3 vs. 8.0 weeks, P = .1). Blurring of the fracture margins and reactive sclerosis were the earliest signs of healing in both modalities. External callus formation was evident in 11 cases and was detected earlier with CT technique. Overall, CT images allowed for more complete and detailed visualization of healing compared with conventional X-rays, which were limited by cast and fixation hardware superimposition, especially in subjects with malleolar and distal radial fractures. Quantitative evaluation showed good intraobserver and interobserver reproducibility and a statistically significant correlation to qualitative changes. CONCLUSION: Our methods of fracture healing assessment are reliable tools that are able to detect early changes in normal bone healing and may serve as useful additions to subjective image analysis in monitoring fracture healing in clinical trials. CT shows some advantages over conventional X-rays in evaluation of early fracture healing.

Adolescent↗
PubMed2003

Accuracy of CT-based thickness measurement of thin structures: modeling of limited spatial resolution in all three dimensions.

Measurement of the width of thin structures such as the cortical shell of the vertebral body or femoral neck with computed tomography (CT) is limited by the spatial resolution of the CT system. Limited spatial resolution exists both within the CT image plane and perpendicular to it and can be described by the in-plane point spread function (PSF) and the across-plane slice sensitivity profile (SSP), respectively. The goal of this study was to confirm that errors of thickness measurement of thin structures critically depend on the spatial positioning of the object and the spatial resolution limitations of CT in all three dimensions, and to assess the size of the errors themselves. We compared computer models that incorporated both effects to experimentally assessed cortical thicknesses of the European Spine Phantom. Analysis included varying CT slice width, the orientation of measurement and angle beta of misalignment of longitudinal scanner and phantom axes. Agreement of models with measurements was good in all configurations with an overall error of 0.17 mm. This showed that PSF and SSP are adequate system characteristics to predict deviation of measured values from true widths. Errors between measurements and true cortical thickness values delta(true) averaged to 1.5 mm were strongly positively correlated with slice width d and beta. When the across-plane partial volume effect was eliminated, limited in-plane resolution still accounted for overestimation of delta(true) by 0.68 (137%), 0.27 (27%), and 0.06 mm (4%) for delta(true)=0.5, 1.0, and 1.5 mm, respectively. For delta(true) of 1.0 mm and above, it was shown that although the absolute cortical thickness values might not be accurately measurable, relative differences between two values are reflected in measurement. Implications for cortical thickness measurement are that the spinal cortical shell is too thin, whereas accurate assessment at locations of the femoral neck exhibiting a thicker cortical shell of both difference and absolute values should be possible with CT even for larger misalignment angles, especially when a smaller CT slice width is chosen.

Computer Simulation↗
PubMed2003

Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure.

UNLABELLED: Histomorphometry and microCT of 51 paired iliac crest biopsy specimens from women treated with teriparatide revealed significant increases in cancellous bone volume, cancellous bone connectivity density, cancellous bone plate-like structure, and cortical thickness, and a reduction in marrow star volume. INTRODUCTION: We studied the ability of teriparatide (rDNA origin) injection [rhPTH(1-34), TPTD] to improve both cancellous and cortical bone in a subset of women enrolled in the Fracture Prevention Trial of postmenopausal women with osteoporosis after a mean treatment time of 19 months. This is the first report of a biopsy study after treatment with teriparatide having a sufficient number of paired biopsy samples to provide quantitative structural data. METHODS: Fifty-one paired iliac crest bone biopsy specimens (placebo [n = 19], 20 microg teriparatide [n = 18], and 40 microg teriparatide [n = 14]) were analyzed using both two-dimensional (2D) histomorphometry and three-dimensional (3D) microcomputed tomography (microCT). Data for both teriparatide treatment groups were pooled for analysis. RESULTS AND CONCLUSIONS: By 2D histomorphometric analyses, teriparatide significantly increased cancellous bone volume (median percent change: teriparatide, 14%; placebo, -24%; p = 0.001) and reduced marrow star volume (teriparatide, -16%; placebo, 112%; p = 0.004). Teriparatide administration was not associated with osteomalacia or woven bone, and there were no significant changes in mineral appositional rate or wall thickness. By 3D cancellous and cortical bone structural analyses, teriparatide significantly decreased the cancellous structure model index (teriparatide, -12%; placebo, 7%; p = 0.025), increased cancellous connectivity density (teriparatide, 19%; placebo, - 14%; p = 0.034), and increased cortical thickness (teriparatide, 22%; placebo, 3%; p = 0.012). These data show that teriparatide treatment of postmenopausal women with osteoporosis significantly increased cancellous bone volume and connectivity, improved trabecular morphology with a shift toward a more plate-like structure, and increased cortical bone thickness. These changes in cancellous and cortical bone morphology should improve biomechanical competence and are consistent with the substantially reduced incidences of vertebral and nonvertebral fractures during administration of teriparatide.

Aged↗
PubMed2003

Clinical applications of body composition measurements using DXA.

Dual-energy X-ray absorptiometry (DXA) scanning was primarily developed for the diagnosis of osteoporosis and was initially applied to studies of the clinically important sites of the lumbar spine, femoral neck, and forearm. The rapid adoption of DXA has led to the development of different, competing generations of equipment. Improvements have been achieved through advances in X-ray generation and detection technology, modification of data acquisition protocols, and implementation of more sophisticated image analysis algorithms. As a result, DXA has been extended to allow the study of the total skeleton and its regional parts, as well as soft-tissue composition measurement. The three major components of the body: fat mass, lean mass, and bone mineral mass, can now be easily measured using a single whole body DXA scan with high precision and low scanning time. The comprehensive view of body composition provided by DXA makes it an attractive technique for a variety of clinical applications such as the prevention of cardiovascular and metabolic diseases, clinical management of different chronic diseases, and monitoring of the impact of treatment regimens on body tissues. In this article we review the contribution DXA has made to the understanding of body composition in clinical studies in adults.

Absorptiometry, Photon↗
PubMed2003

Repair of erosions in rheumatoid arthritis does occur. Results from 2 studies by the OMERACT Subcommittee on Healing of Erosions.

The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.

Arthritis, Rheumatoid↗
PubMed2002

Impingement syndrome of the ankle following supination external rotation trauma: MR imaging findings with arthroscopic correlation.

Our objective was to identify MR imaging findings in patients with syndesmotic soft tissue impingement of the ankle and to investigate the reliability of these imaging characteristics to predict syndesmotic soft tissue impingement syndromes of the ankle. Twenty-one ankles with chronic pain ultimately proven to have anterior soft tissue impingement syndrome were examined by MR imaging during January 1996 to June 2001. The MR imaging protocol included sagittal and coronal short tau inversion recovery (STIR), sagittal T1-weighted spin echo, axial and coronal proton-density, and T2-weighted spin-echo sequences. Nineteen ankles that underwent MR imaging during the same period of time and that had arthroscopically proven diagnosis different than impingement syndrome served as a control group. Fibrovascular scar formations distinct from the syndesmotic ligaments possibly related to syndesmotic soft tissue impingement were recorded. Arthroscopy was performed subsequently in all patients and was considered the gold standard. The statistical analysis revealed an overall frequency of scarred syndesmotic ligaments of 70% in the group with ankle impingement. Fibrovascular scar formations distinct from the syndesmotic ligaments presented with low signal intensity on T1-weighted images and remained low to intermediate in signal intensity on T2-weighted MR imaging. Compared with arthroscopy, MR imaging revealed a sensitivity of 89%, a specificity of 100%, and a diagnostic accuracy of 93% for scarred syndesmotic ligaments. The frequency of scar formation distinct from the syndesmotic ligaments in patients with impingement syndrome of the ankle was not statistically significantly higher than in the control group. In contrast to that, anterior tibial osteophytes and talar osteophytes were statistically significantly higher in the group with anterior impingement than in the control group. Conventional MR imaging was found to be insensitive for the diagnosis of syndesmotic soft tissue impingement of the ankle. Fibrovascular scar tissue distinct from syndesmotic ligaments is suggestive for the diagnosis of soft tissue impingement, but the reliability of these findings is still questionable.

Adult↗
PubMed2002

SHIP-deficient mice are severely osteoporotic due to increased numbers of hyper-resorptive osteoclasts.

The hematopoietic-restricted protein Src homology 2-containing inositol-5-phosphatase (SHIP) blunts phosphatidylinositol-3-kinase-initiated signaling by dephosphorylating its major substrate, phosphatidylinositol-3,4,5-trisphosphate. As SHIP(-/-) mice contain increased numbers of osteoclast precursors, that is, macrophages, we examined bones from these animals and found that osteoclast number is increased two-fold. This increased number is due to the prolonged life span of these cells and to hypersensitivity of precursors to macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B ligand (RANKL). Similar to pagetic osteoclasts, SHIP(-/-) osteoclasts are enlarged, containing upwards of 100 nuclei, and exhibit enhanced resorptive activity. Moreover, as in Paget disease, serum levels of interleukin-6 are markedly increased in SHIP(-/-) mice. Consistent with accelerated resorptive activity, 3D trabecular volume fraction, trabecular thickness, number and connectivity density of SHIP(-/-) long bones are reduced, resulting in a 22% loss of bone-mineral density and a 49% decrease in fracture energy. Thus, SHIP negatively regulates osteoclast formation and function and the absence of this enzyme results in severe osteoporosis.

Animals↗
PubMed2002

Trabecular microstructure and surface changes in the greater tuberosity in rotator cuff tears.

OBJECTIVE: When planning surgery in patients with rotator cuff tear, strength of bone at the tendon insertion and trabecular bone structure in the greater tuberosity are usually taken into consideration. We investigated radiographic changes in bone structure of the greater tuberosity in rotator cuff tears. DESIGN: Twenty-two human cadaveric shoulders from subjects ranging from 55 to 75 years of age were obtained. The integrity of the rotator cuff was examined by sonography to determine if it is intact without any tear, or torn partially or completely. The humeral head was sectioned in 3 mm thick coronal slab sections and microradiographed. After digitization of the microradiographs and imaging processing with in-house semi-automated image processing software tools developed using software interfaces on a Sun workstation, the trabecular histomorphometrical structural parameters and connectivity in the greater tuberosity were quantified. The degenerative changes on the surface of the greater tuberosity were interpreted blindly by 2 independent readers. RESULTS: Among the 22 shoulder specimens, the rotator cuff was found intact in 10 shoulders, partially in 7 and fully torn in 5. Statistically significant loss in apparent trabecular bone volume fraction, number of trabecular nodes, and number of trabecular branches, and a statistically significant increase in apparent trabecular separation and number of trabecular free ends were found in the greater tuberosity of the shoulders with tears. The loss was greater in association with full tear than in partial tear. Thickening of the cortical margin of the enthesis, irregularity of its surface, and calcification beyond the tidemark were observed in 2 (20%) shoulders with intact rotator cuff, in 6 (86%) shoulders with partial tear, and in 5 (100%) shoulders with full tear. CONCLUSIONS: Rotator cuff tears are associated with degenerative changes on the bone surface and with disuse osteopenia of the greater tuberosity. Aging, degenerative enthesopathy of the supraspinatus tendon, and rotator cuff tears appear closely related.

Aged↗
PubMed2002

Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs.

PURPOSE: To estimate how much the improvement in bone mass accounts for the reduction in risk of vertebral fracture that has been observed in randomized trials of antiresorptive treatments for osteoporosis. METHODS: After a systematic search, we conducted a meta-analysis of 12 trials to describe the relation between improvement in spine bone mineral density and reduction in risk of vertebral fracture in postmenopausal women. We also used logistic models to estimate the proportion of the reduction in risk of vertebral fracture observed with alendronate in the Fracture Intervention Trial that was due to improvement in bone mineral density. RESULTS: Across the 12 trials, a 1% improvement in spine bone mineral density was associated with a 0.03 decrease (95% confidence interval [CI]: 0.02 to 0.05) in the relative risk (RR) of vertebral fracture. The reductions in risk were greater than predicted from improvement in bone mineral density; for example, the model estimated that treatments predicted to reduce fracture risk by 20% (RR = 0.80), based on improvement in bone mineral density, actually reduce the risk of fracture by about 45% (RR = 0.55). In the Fracture Intervention Trial, improvement in spine bone mineral density explained 16% (95% CI: 11% to 27%) of the reduction in the risk of vertebral fracture with alendronate. CONCLUSION: Improvement in spine bone mineral density during treatment with antiresorptive drugs accounts for a predictable but small part of the observed reduction in the risk of vertebral fracture.

Alendronate↗
PubMed2002

Identification of vertebral fractures in osteoporosis.

Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and microarchitectural deterioration. These lead to subsequent increase in bone fragility and susceptibility to low-trauma or atraumatic fractures, most commonly vertebral fractures but also fractures of hip and wrist. These have a significant impact on morbidity, mortality, and health care cost. Studies have demonstrated that the presence of vertebral fractures is an independent and significant predictor of the increased risk for further fractures. The occurrence of a vertebral fracture is often clinically asymptomatic, and many of these fractures, therefore, remain undiagnosed. Recently, a number of techniques have been developed that allow for reliable identification of vertebral fractures on radiographs. The two most widely used methods in clinical research are the semiquantitative assessment of vertebral deformities, which is based on visual evaluation, and the quantitative approach, which is based on different morphometric criteria. In our practice for osteoporosis evaluation we use the Genant semiquantitative approach-an accurate and reproducible method, tested and applied in many clinical studies. The newest generation of fan-beam dual energy X-ray absorptiometry (DXA) systems delivering "high-resolution" lateral spine images offer a potential practical alternative to radiographs for clinical vertebral fracture analysis. The advantages of using DXA over conventional X-ray devices are its minimal radiation exposure and high-speed image acquisition. It also allows combined evaluation of vertebral fracture status and bone mineral density, which could become a standard for patient assessment in osteoporosis.

Humans↗
PubMed2002

Measurement of breast density with dual X-ray absorptiometry: feasibility.

Dual x-ray absorptiometry (DXA) was used to quantify breast density with a phantom and with cadaveric breasts. With DXA, percentage of fat correlated with percentage of glandular density of the phantom (r > 0.998) and with density at mammography (r(adjusted) = 0.83). DXA precision (SD) was 0.5% without and 1.1% with breast repositioning. DXA devices can be used to accurately and precisely estimate breast tissue density.

Absorptiometry, Photon↗