David C. Newitt

Bio: David C. Newitt is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Breast cancer & Bone mineral. The author has an hindex of 49, co-authored 118 publications receiving 7079 citations. Previous affiliations of David C. Newitt include Max Planck Society & University of Washington.

Correlation of trabecular bone structure with age, bone mineral density, and osteoporotic status: in vivo studies in the distal radius using high resolution magnetic resonance imaging.

Abstract: High resolution magnetic resonance (MR) images of the distal radius were obtained at 1.5 Tesla in premenopausal normal, postmenopausal normal, and postmenopausal osteoporotic women. The image resolution was 156 μm in plane and 700 μm in the slice direction; the total imaging time was ∼16 minutes. An intensity-based thresholding technique was used to segment the images into trabecular bone and marrow, respectively. Extensions of standard stereological techniques were used to derive measures of trabecular bone structure from these segmented images. The parameters calculated included apparent measures of trabecular bone volume fraction, trabecular thickness, trabecular spacing, and trabecular number. Fractal-based texture parameters, such as the box-counting dimension, were also derived. Trabecular bone mineral density (BMD) and cortical bone mineral content (BMC) were measured in the distal radius using peripheral quantitative computed tomography (pQCT). In a subset of patients, spinal trabecular BMD was measured using quantitative computed tomography (QCT). Correlations between the indices of trabecular bone structure measured from these high-resolution MR images, age, BMD, and osteoporotic fracture status were examined. Cortical BMC and trabecular BMD at the distal radius, spinal BMD, trabecular bone volume fraction, trabecular thickness, trabecular number, and fractal dimension all decreased with age. Trabecular spacing showed the greatest percentage change and increased with age. In addition, significant differences were evident in spinal BMD, radial trabecular BMD, trabecular bone volume fraction, trabecular spacing, and trabecular number between the postmenopausal nonfracture and the postmenopausal osteoporotic subjects. Trabecular spacing and trabecular number showed moderate correlation with radial trabecular BMD but correlated poorly with radial cortical BMC. High resolution MR imaging, a potentially useful tool for quantifying trabecular structure in vivo, may have applications for understanding and evaluating skeletal changes related to age and osteoporosis.

In Vivo High Resolution MRI of the Calcaneus: Differences in Trabecular Structure in Osteoporosis Patients

Abstract: The purpose of this study was to use high resolution (HR) magnetic resonance (MR) images of the calcaneus to investigate the trabecular structure of patients with and without osteoporotic hip fractures and to compare these techniques with bone mineral density (BMD) in differentiating fracture and nonfracture patients. Axial and sagittal HR MR images of the calcaneus were obtained in 50 female (23 postmenopausal patients with osteoporotic hip fractures and 27 postmenopausal controls). A three-dimensional gradient-echo sequence was used with a slice thickness of 500 micron and in plane resolution of 195 x 195 micron. Texture analysis was performed using morphological features, analogous to standard histomorphometry and fractal dimension. Additionally, BMd measurements of the hip (dual-energy X-ray absorptiometry) were obtained in all patients. Significant differences between both patient groups were obtained using morphological parameters and fractal dimension as well as hip BMD (p < 0.05). Odds ratios for the texture parameters apparent (app.) bone volume/total volume and app. trabecular separation were higher than for hip BMD. Receiver operator characteristic values of texture measures and hip BMD were comparable. In conclusion, trabecular structure measures derived from HR MR images of the calcaneus can differentiate between postmenopausal women with and without osteoporotic hip fractures.

Processing and analysis of in vivo high-resolution MR images of trabecular bone for longitudinal studies: reproducibility of structural measures and micro-finite element analysis derived mechanical properties.

Abstract: 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.

Guidelines for assessment of bone microstructure in rodents using micro–computed tomography

Abstract: Use of high-resolution micro-computed tomography (microCT) imaging to assess trabecular and cortical bone morphology has grown immensely. There are several commercially available microCT systems, each with different approaches to image acquisition, evaluation, and reporting of outcomes. This lack of consistency makes it difficult to interpret reported results and to compare findings across different studies. This article addresses this critical need for standardized terminology and consistent reporting of parameters related to image acquisition and analysis, and key outcome assessments, particularly with respect to ex vivo analysis of rodent specimens. Thus the guidelines herein provide recommendations regarding (1) standardized terminology and units, (2) information to be included in describing the methods for a given experiment, and (3) a minimal set of outcome variables that should be reported. Whereas the specific research objective will determine the experimental design, these guidelines are intended to ensure accurate and consistent reporting of microCT-derived bone morphometry and density measurements. In particular, the methods section for papers that present microCT-based outcomes must include details of the following scan aspects: (1) image acquisition, including the scanning medium, X-ray tube potential, and voxel size, as well as clear descriptions of the size and location of the volume of interest and the method used to delineate trabecular and cortical bone regions, and (2) image processing, including the algorithms used for image filtration and the approach used for image segmentation. Morphometric analyses should be based on 3D algorithms that do not rely on assumptions about the underlying structure whenever possible. When reporting microCT results, the minimal set of variables that should be used to describe trabecular bone morphometry includes bone volume fraction and trabecular number, thickness, and separation. The minimal set of variables that should be used to describe cortical bone morphometry includes total cross-sectional area, cortical bone area, cortical bone area fraction, and cortical thickness. Other variables also may be appropriate depending on the research question and technical quality of the scan. Standard nomenclature, outlined in this article, should be followed for reporting of results.

Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia

Abstract: Sarcopenia, the reduction of muscle mass and strength that occurs with aging, is widely considered one of the major causes of disability in older persons. Surprisingly, criteria that may help a clinician to identify persons with impaired muscle function are still lacking. Using data from a large representative sample of the general population, we examined how muscle function and calf muscle area change with aging and affect mobility in men and women free of neurological conditions. We tested several putative indicators of sarcopenia, including knee extension isometric torque, handgrip, lower extremity muscle power, and calf muscle area. For each indicator, sarcopenia was considered to be present when the measure was >2 SDs below the mean. For all four measures, the prevalence of sarcopenia increased with age, both in men and women. The age-associated gradient in prevalence was maximum for muscle power and minimum for calf-muscle area. However, lower extremity muscle power was no better than knee-extension torque or handgrip in the early identification of poor mobility, defined either as walking speed <0.8 m/s or inability to walk at least 1 km without difficulty and without developing symptoms. Optimal cutoff values that can be used in the clinical practice to identify older persons with poor mobility were developed. The findings of the study lay the basis for a cost-effective, clinical marker of sarcopenia based on a measure of isometric handgrip strength. Our findings should be verified in a longitudinal study.

Current Understanding of the Molecular Actions of Vitamin D

Abstract: The important reactions that occur to the vitamin D molecule and the important reactions involved in the expression of the final active form of vitamin D are reviewed in a critical manner. After an overview of the metabolism of vitamin D to its active form and to its metabolic degradation products, the molecular understanding of the 1alpha-hydroxylation reaction and the 24-hydroxylation reaction of the vitamin D hormone is presented. Furthermore, the role of vitamin D in maintenance of serum calcium is reviewed at the physiological level and at the molecular level whenever possible. Of particular importance is the regulation of the parathyroid gland by the vitamin D hormone. A third section describes the known molecular events involved in the action of 1alpha,25-dihydroxyvitamin D3 on its target cells. This includes reviewing what is now known concerning the overall mechanism of transcriptional regulation by vitamin D. It describes the vitamin D receptors that have been cloned and identified and describes the coactivators and retinoid X receptors required for the function of vitamin D in its genomic actions. The presence of receptor in previously uncharted target organs of vitamin D action has led to a study of the possible function of vitamin D in these organs. A good example of a new function described for 1alpha,25-dihydroxyvitamin D3 is that found in the parathyroid gland. This is also true for the role of vitamin D hormone in skin, the immune system, a possible role in the pancreas, i.e., in the islet cells, and a possible role in female reproduction. This review also raises the intriguing question of whether vitamin D plays an important role in embryonic development, since vitamin D deficiency does not prohibit development, nor does vitamin D receptor knockout. The final section reviews some interesting analogs of the vitamin D hormone and their possible uses. The review ends with possible ideas with regard to future directions of vitamin D drug design.

Bone's mechanostat: A 2003 update

Abstract: The still-evolving mechanostat hypothesis for bones inserts tissue-level realities into the former knowledge gap between bone's organ-level and cell-level realities. It concerns load-bearing bones in postnatal free-living bony vertebrates, physiologic bone loading, and how bones adapt their strength to the mechanical loads on them. Voluntary mechanical usage determines most of the postnatal strength of healthy bones in ways that minimize nontraumatic fractures and create a bone-strength safety factor. The mechanostat hypothesis predicts 32 things that occur, including the gross anatomical bone abnormalities in osteogenesis imperfecta; it distinguishes postnatal situations from baseline conditions at birth; it distinguishes bones that carry typical voluntary loads from bones that have other chief functions; and it distinguishes traumatic from nontraumatic fractures. It provides functional definitions of mechanical bone competence, bone quality, osteopenias, and osteoporoses. It includes permissive hormonal and other effects on bones, a marrow mediator mechanism, some limitations of clinical densitometry, a cause of bone "mass" plateaus during treatment, an "adaptational lag" in some children, and some vibration effects on bones. The mechanostat hypothesis may have analogs in nonosseous skeletal organs as well.