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On new opportunities for absorptiometry.

Mechanical loads cause bone strains; and muscle forces, not body weight, cause the largest strains. The strains help to control the effects of bone modeling and remodeling on bone strength and "mass." When strains exceed a threshold range, modeling increases bone strength and "mass." When strains stay below a smaller threshold range, remodeling begins removing bone next to marrow. As a result, increasing muscle strength increases bone strength and "mass," and decreasing muscle strength decreases bone strength and "mass." Estrogen apparently lowers the remodeling threshold, which reduces bone losses. Loss of estrogen raises that threshold to cause losses of bone next to marrow. Such facts help to explain: 1. Bone loss in aging adults. 2. An increase in bone "mass" in girls at menarche. 3. The loss of bone during menopause. 4. The greater bone "mass" in obese than in slender subjects, and in weightlifters than in marathon runners. 5. And the pathogenesis of physiologic osteopenias and true osteoporoses. Thus new standards are needed for the relationships between bone and muscle strengths, and as functions of sex, age, race, disease, endocrine status, nutrition, vitamin and mineral intakes, medications, puberty, and menopause. Obtaining those standards and studying such relationships provide many new opportunities for studies that involve dual energy X-ray absorptiometry (DXA) and peripheral quantitative computer tomography (pQCT) and, perhaps some day, ultrasound and magnetic resonance imaging (MRI) techniques.

Journal Article↗

pQCT measurement of bone parameters in young children: validation of technique.

Dual-energy X-ray absorptiometry (DXA) measures areal bone mineral density (BMD) and is affected by bone size. Peripheral quantitative computed tomography (pQCT) measures volumetric density and should not be affected by bone size. We hypothesized that pQCT could be used to measure geometric parameters in the tibia and that bone size, not density, would correlate with weight and height in 3 and 4 yr olds. Phantom measurements indicate that accurate results for cortical volumetric bone mineral density can be obtained at cortical thickness > 2 mm with voxel/speed sizes of 0.40/20 mm/s. Correlations between pQCT measured geometric bone parameters and phantom calculations were observed (all r > 0.96). Baseline data from an ongoing trial of 101 preschool children (53 male) were used to correlate bone parameters and anthropometrics. Total cross-sectional area, cortical area, and cortical thickness correlated with weight (r = 0.54, p < 0.001; r = 0.52, p < 0. 001; r = 0.30, p = 0.002) and height (r = 0.41, p < 0.001; r = 0.55, p < 0.001; r = 0.41, p < 0.001). Because of the small cortical thickness at this age (mean = 1.2 mm) cortical density was not analyzed. In a regression model including height and weight, weight was the only predictor of total cross-sectional area (p < 0.001); cortical thickness was predicted by height (p = 0.006). Both height (p = 0.005) and weight (p = 0.05) predicted the cortical area. In summary, pQCT accurately measures total cross-sectional area, cortical area, and cortical thickness in children age 3-4 yr.

Absorptiometry, Photon↗

Centile curves for bone densitometry measurements in healthy males and females ages 5-22 yr.

Normative pediatric bone measurement data are necessary for defining osteopenia in children and for identifying factors associated with normal bone growth. The LMS statistical method is used to produce centile curves plotting a growth characteristic as a function of age. The purpose of this study was to provide centile curves of bone measurements using peripheral quantitative computed tomography (pQCT) and dual X-ray absorptiometry (DXA) in 231 (107 male) healthy individuals ages 5 22 yr using the LMS method. pQCT (Norland XCT 2000; Norland, Ft. Atkinson, WI) was used to image a single slice at the 20% distal tibia. Periosteal circumference, endosteal circumference, and cortical density measurements were used to obtain centile curves. Whole-body DXA (Hologic QDR 4500; Hologic, Bedford, MA) was obtained and scans were analyzed using adult whole-body software for total body bone mineral content (BMC) and total body bone area. pQCT measurements showed prepubertal expansion of the tibia that plateaued in females at age 14 and continued in males until age 18. Tibia cortical density increased during the age of puberty more gradually in females than in males. DXA measurement curves showed that total body BMC and total body bone area plateaued in females at approximately age 15, whereas male curves of the same measurements showed a continued increase.

Adolescent↗

Assessment of forearm volumetric bone mineral density from standard areal densitometry data.

The common bone density measurement procedures produce areal bone mineral density data (BMD) alone. Volumetric bone density is thought to offer a different diagnostic perspective and is usually measured by peripheral quantitative computed tomography. We developed a calculation procedure for radial and ulnar volumetric densities based on single X-ray absorptiometry. The study consisted of 418 healthy Bulgarian females (ages 20 83 yr). Forearm bone density was measured on a DTX-100 densitometer at the 8-mm distal site, and the total volumetric bone densities of radius and ulna were calculated. The accuracy error determined on cadaveric bones was 10 14%. The in vivo precision error was 1.0 1.1%. Age-matched reference curves for volumetric BMD (vBMD) were built. Peak values were registered in the age 30 34 group: 0.403 (radius) and 0.469 g/cm(3) (ulna). Ulnar volumetric density exceeded the radial one, representing an interesting finding to be further investigated. For the age 70 74 group, vBMD was reduced by approx 30% compared with the age 30 34 group. Our data confirmed the fact that volumetric density was much less affected by age and menopause. Correlations between forearm vBMD and axial BMD were moderate. The proposed calculation procedure could become an extra option in forearm bone densitometry to be applied in pediatric populations or adults of extremely large or small body size.

Absorptiometry, Photon↗

In vivo measurement of apparent trabecular bone structure of the radius in women with low bone density discriminates patients with recent wrist fracture from those without fracture.

The purpose of this cross-sectional case-control study was to determine whether indices of bone structure at the 4% site of the radius discriminate women who have sustained a recent low-energy fracture of the contralateral distal radius (n = 21) from women with similar bone density and no history of fracture (n = 21). Images of the distal forearm were acquired using peripheral quantitative computed tomography (pQCT) and were analyzed using in-house-developed software to determine indices of trabecular bone structure (average hole size [H(A)], maximum hole size, and connectivity index). The same images were analyzed using commercial software to determine bone density, mass, geometry, and torsional strength. The fracture group had significantly larger H(A) (p = 0.03). No other bone variable differed between groups. Individual H(A) values were compared to the mean value for young adult women (n = 42). The odds ratio (95% confidence interval) associated with an H(A) >2 SDs above the young adult mean was 5.4 (1.2-24.3). Thus, estimation of in vivo trabecular bone porosity by measuring the average diameter of the pQCT-imaged marrow spaces in the ultradistal radius identifies individuals with low bone mass most at risk for osteoporotic fracture.

Bone Density↗

Trabecular and integral bone density in adults with sickle cell disease.

Sickle cell disease (SCD) is a hereditary disorder of hemoglobin synthesis that can affect the skeletal system owing to accelerated hematopoiesis and/or bone infarction. Additionally, several studies have suggested that a low bone mass is associated with SCD, partly because of adverse effects on growth and development. The few previous studies of bone mineral density (BMD) in these patients have utilized dual-photon or dual-energy x-ray absorptiometric (DXA) techniques, which may have limited value in this population because it cannot correct for differences in bone size. We undertook a study of BMD in the forearm of patients with sickle cell disease using peripheral quantitative computed tomography (QCT), which provides a measure of volumetric bone density for the trabecular bone component as well as cortical and trabecular bone together. We studied 32 African-American SCD patients with no known history of bone infarction in the wrist, and compared them with data from healthy African-American volunteers. We found a 13% lower integral (cortical and trabecular) BMD in the SCD patients (p=0.001), but no difference in trabecular BMD (p=0.40 for males, 0.32 for females). We hypothesize that the maintenance of trabecular BMD in the wrist may be related to the persistence of metabolically active red marrow in this region in adults with SCD.

Adult↗

Precision and accuracy of DXA and pQCT for densitometry of the rat femur.

Measurements of bone mineral density and bone mineral content are key data in the study of osteoporosis and pathologic skeletal disease. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography are used in human and small animal studies. The purpose of this study was to evaluate the precision, accuracy, and systematic bias of measurement of the rat femur. Comparing machine-measured parameters with standard, nonradiographic measurements, we assessed validation of relative and absolute accuracy. Regression analysis and calculations of percent difference from standard values were used to determine the accuracy of each densitometry technique. Machine-specific and subject-specific precision was evaluated for each densitometer using repeated scans to calculate coefficients of variation. Each of the methods of densitometry examined in this study produced comparable results and was sensitive to small changes following experimental stimuli. Further, our assessment of the precision and accuracy observed between methods of scanning excised rat femurs validates our data acquisition method and serves as a foundation for future densitometry studies.

Absorptiometry, Photon↗

Optimizing results from pQCT: reliability of operator-dependent pQCT variables in cadavers and humans with low bone mass.

Peripheral quantitative computed tomography (pQCT) can assess bone geometric properties and separate cortical from trabecular bone. Despite pQCT's potential benefits for research, most reliability and accuracy studies have used a constant acquisition and analysis protocol. There are, however, numerous steps in the pQCT scan acquisition and analysis that are operator dependent. Whether or not these influence the quality of the pQCT scans and, potentially, the precision and validity of the data collected has been little explored. We investigated how pQCT outputs changed when operator-dependent parameters were varied, particularly when the bone of interest was of low mineral density. We found that bone parameters and scan failure rate varied significantly depending on the acquisition resolution; only one scan slice at the 10 and 30% radius is required to maintain adequate precision, and reference lines for sites should use a reproducible landmark. These results provide a foundation for recommending scan acquisition and analysis options for patients with low bone mass.

Aged↗

CyberNews.

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American Dental Association↗

Alteration in serum leptin correlates with alterations in serum N-telopeptide of collagen type I and serum osteocalcin during the progression of osteoporosis in ovariectomized rats.

The role of leptin during the progression of osteoporosis was investigated in ovariectomized rats by correlation of serum leptin levels with N-telopeptide of collagen type I (NTx) and osteocalcin levels before ovariectomy and 20, 40 and 60 days after the operation. Furthermore, peripheral quantitative computed tomography was used to confirm the development of severe osteoporosis in rats on day 60. The levels of NTx and osteocalcin were significantly increased on day 20 [61.9+/-5.4 nM BCE (bone collagen equivalents) and 215.6+/-53.3 ng/mL, respectively] in comparison to those before ovariectomy (41.3+/-1.7 nM BCE and 60.4+/-10.9 ng/mL). Accordingly, leptin was significantly elevated on day 20 (3033+/-661 vs. 606+/-346 pg/mL before ovariectomy). Bone markers and leptin levels remained constant up to day 40, while a slight, but not statistically significant, decrease was noted for osteocalcin and leptin on day 60. Although leptin and bone markers did not correlate before ovariectomy (r=0.09 for NTx and r=-0.05 for osteocalcin), strong correlation was observed at all time points after ovariectomy. The data obtained suggest that the alterations in serum leptin levels during the progression of osteoporosis in ovariectomized rats follow the alterations in bone markers.

Animals↗

Effects of a split keyboard design and wrist rest on performance, posture, and comfort.

The purpose of this study was to examine differences in experienced typists' performance, posture, and musculoskeletal pain when using a split, adjustable (SA) computer keyboard and when using a standard flat keyboard. In addition, the use of a wrist rest was examined for performance, posture, and musculoskeletal pain effects. Eighteen participants were exposed to the SA keyboard and a flat keyboard in a laboratory study of text typing for four consecutive hours on five days. The results indicated that after just 2 h of orientation and practice, the participants could perform as well on the SA keyboard as on the flat keyboard. The SA keyboard provided advantages for reduced wrist/hand pronation. There was no difference between the keyboards in the level of musculoskeletal pain reported by participants after typing. However, they reported increased pain in the back, neck, shoulders, and wrists from the beginning to the end of each of the experimental periods for both keyboards.

Adolescent↗

Wrist and forearm posture from typing on split and vertically inclined computer keyboards.

A study was conducted on 90 experienced office workers to determine how commercially available alternative computer keyboards affected wrist and forearm posture. The alternative keyboards tested had the QWERTY layout of keys and were of three designs: split fixed angle, split adjustable angle, and vertically inclined (tilted or tented). When set up correctly, commercially available split keyboards reduced mean ulnar deviation of the right and left wrists from 12 degrees to within 5 degrees of a neutral position compared with a conventional keyboard. The finding that split keyboards place the wrist closer to a neutral posture in the radial/ulnar plane substantially reduces one occupational risk factor of work-related musculoskeletal disorders (WMSDs): ulnar deviation of the wrist. Applications of this research include commercially available computer keyboard designs that typists can use and ergonomists can recommend to their clients in order to minimize wrist ulnar deviation from typing.

Adult↗

Light pen use and practice minimize age and hand performance differences in pointing tasks.

We contrasted performance with mouse and light pen input devices for younger, middle-aged, and older adults (N = 72) who were experienced mouse users. Participants used both preferred and nonpreferred hands to perform a menu target selection task. The light pen minimized age differences in performance relative to the mouse. Older adults were more lateralized on a handedness test than young adults and were less efficient using their nonpreferred hand. With practice, older adults improved their response time more than other age groups did. The mouse was rated as more acceptable and easier to use than the light pen across trials, despite the performance advantage of the light pen for all age groups. Usability ratings correlated moderately with performance. A benefit-cost analysis indicated that the more efficient light pen might cover its greater initial cost within 11 months for an older adult and within 23 months for a younger adult. Actual or potential applications of this research include advising older adults to persist with practice for new input devices, advising those who must switch to their non-preferred hand to select a direct positioning device, and providing a methodology for determining the potential payback interval when switching to a faster, though more expensive, input device.

Adult↗

Analysis of the musculoskeletal system in children and adolescents receiving anticonvulsant monotherapy with valproic acid or carbamazepine.

OBJECTIVE: To examine bone development in children and adolescents who have uncomplicated idiopathic epilepsy and had received monotherapy with carbamazepine or valproic acid for at least 1 year. METHODS: Thirty-nine patients from 6 to 19 years of age (18 girls) were studied. Total bone mineral content (BMC) and trabecular volumetric bone mineral density were measured at the distal radius using peripheral quantitative computed tomography. Maximum isometric grip force was determined with a standard dynamometer. Alkaline phosphatase activity and deoxypyridinoline (a marker of bone resorption) were assessed in serum and urine, respectively. RESULTS: Trabecular volumetric bone mineral density was significantly decreased in the entire group (z score mean +/- standard deviation: -0.62 +/- 1.04) and in the subgroup using valproic acid (-0.75 +/- 1.18). In the carbamazepine subgroup, there was a similar but nonsignificant trend (-0.50 +/- 0.90). Total BMC and isometric maximum grip force were normal in the entire study population (0.10 +/- 1.22) and in the 2 subgroups. The relationship between BMC and grip force was similar between patients and healthy participants. Urinary levels of deoxypyridinoline were significantly elevated above normal in the whole study population (1.35 +/- 2.00) and in both the valproic acid and the carbamazepine subgroups. CONCLUSIONS: Bone turnover can be increased, but bone mass is adequate in children and adolescents who have uncomplicated idiopathic epilepsy and who receive monotherapy with carbamazepine or valproic acid.

Adolescent↗

Model-based testing with UML applied to a roaming algorithm for bluetooth devices.

In late 2001, the Object Management Group issued a Request for Proposal to develop a testing profile for UML 2.0. In June 2003, the work on the UML 2.0 Testing Profile was finally adopted by the OMG. Since March 2004, it has become an official standard of the OMG. The UML 2.0 Testing Profile provides support for UML based model-driven testing. This paper introduces a methodology on how to use the testing profile in order to modify and extend an existing UML design model for test issues. The application of the methodology will be explained by applying it to an existing UML Model for a Bluetooth device.

Algorithms↗

The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats.

Growth hormone (GH) is of importance for normal bone remodelling. A recent clinical study demonstrated that MK-677, a member of a class of GH secretagogues (GHSs), increases serum concentrations of biochemical markers of bone formation and bone resorption. The aim of the present study was to investigate whether the GHSs, ipamorelin (IPA) and GH-releasing peptide-6 (GHRP-6), increase bone mineral content (BMC) in young adult female rats. Thirteen-week-old female Sprague-Dawley rats were given IPA (0.5 mg/kg per day; n=7), GHRP-6 (0.5 mg/kg per day; n=8), GH (3.5 mg/kg per day; n=7), or vehicle administered continuously s.c. via osmotic minipumps for 12 weeks. The animals were followed in vivo by dual X-ray absorptiometry (DXA) measurements every 4th week. After the animals were killed, femurs were analysed in vitro by mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. After this, excised femurs and vertebrae L6 were analysed by the use of Archimedes' principle and by determinations of ash weights. All treatments increased body weight and total tibial and vertebral BMC measured by DXA in vivo compared with vehicle-treated controls. However, total BMC corrected for the increase in body weight (total BMC:body weight ratio) was unaffected. Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged. The pQCT measurements in vitro revealed that the increase in the cortical BMC was due to an increased cross-sectional bone area, whereas the cortical volumetric BMD was unchanged. Femur and vertebra L6 volumes were increased but no effect was seen on the volumetric BMDs as measured by Archimedes' principle. Ash weight was increased by all treatments, but the mineral concentration was unchanged. We conclude that treatment of adult female rats with the GHSs ipamorelin and GHRP-6 increases BMC as measured by DXA in vivo. The results of in vitro measurements using pQCT and Archimedes' principle, in addition to ash weight determinations, show that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged.

Absorptiometry, Photon↗

Repeated in vivo determinations of bone mineral density during parathyroid hormone treatment in ovariectomized mice.

The recent development of different genetically modified mice with potentially interesting bone phenotypes has increased the demand for effective non-invasive methods to evaluate effects on bone of mice during growth and development, and for drug evaluation. In the present study, the skeleton was analyzed by repeated in vivo scans using dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Ovariectomized (ovx) mice treated with parathyroid hormone (PTH) were used as an animal model to evaluate these two techniques at different times after the onset of treatment. Female mice (6 weeks of age) were allocated randomly to four groups: (1) sham-operated+vehicle; (2) ovx+vehicle; (3) sham-operated+PTH(1-84) 150 microg/kg per day; (4) ovx+PTH. Six weeks after ovariectomy the drug treatment began and was continued for 8 weeks. The total body bone mineral content (BMC) and total body areal bone mineral density (BMD) were measured by DXA. Ovariectomy reduced total body BMC and total body areal BMD by 6.2+/-1.7% and 2.6+/-0.9% respectively. No effect of PTH on total body BMC was seen during the treatment period. The trabecular volumetric BMD was measured by pQCT. Ovariectomy reduced the trabecular volumetric BMD by 52+/-6.7%. The pQCT technique detected a clear effect on trabecular volumetric BMD after 2 weeks of PTH treatment (ovx 94+/-29% and sham-operated 46+/-10% more than vehicle-treated). The cortical bone was measured in a mid-diaphyseal pQCT scan of the tibia. Ovariectomy reduced the cortical BMC by 9+/-2%. PTH treatment for 8 weeks increased cortical BMC in ovx mice. In conclusion, the pQCT technique is more sensitive than the DXA technique in the detection of bone loss after ovariectomy and increased bone mass after PTH treatment in mice. Notably, the pQCT, but not the DXA, technique detected a dramatic effect as early as after 2 weeks of PTH treatment. Dynamic pQCT measurements will be useful for monitoring skeletal changes during growth and development, and for drug evaluation in mice.

Absorptiometry, Photon↗