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Background Spinal rotation couples with lateral flexion as a composite movement. Few data report the in vivo mechanical deformation of the nucleus pulposus following sustained rotation. MRI provides a non-invasive method of examining nucleus pulposus deformation by mapping the hydration signal distribution within the intervertebral disc. Methods T1 weighted coronal and sagittal lumbar images and T2 weighted axial images at L1–2 and L4–5 were obtained from 10 asymptomatic subjects (mean age 29, range: 24–34 years) in sustained flexed and extended positions plus combined positions of left rotation with flexion and extension. Nucleus pulposus deformation was tracked by mapping the change in hydration profiles from coronal and sagittal pixel measurements. Findings An average sagittal change in position of 44° (SD 14.5°) from flexion to extension was recorded between L1 and S1 (range: 18°– 60°) resulting in a mean anterior nucleus pulposus deformation of 16% of disc hydration profile (range: 3.5%–19%) in 19/20 discs. When rotation was combined with either flexion or extension, mean coronal deformation was 4.8% (SD—5.1%; range: 0.4%–15%). Lateral nucleus pulposus deformation direction varied in rotation (44% deformed left and 56% deformed right). Intersegmental lateral flexion direction more strongly predicted nucleus pulposus deformation direction with 75% deforming contralaterally. Interpretation Nucleus pulposus deformation direction in young subjects was more predictable following sagittal position change than in rotation combined with flexion or extension. Deformation magnitude was reduced in rotated positions. Intersegmental lateral flexion was a stronger predictor of nucleus pulposus deformation direction.

Copper-61 (61Cu) shares with 64Cu certain advantages for PET diagnostic imaging, but has a shorter half-life (3.4hr vs. 12.7hr) and a greater probability of positron production per disintegration (61% vs. 17.9%). One important application is for in vivo imaging of hypoxic tissue. In this study 61Cu was produced using the 64Zn(p,α)61Cu reaction on natural Zn or enriched 64Zn targets. The enriched 64Zn (99.82%) was electroplated onto high purity gold or silver foils or onto thin Al discs. A typical target bombardment used 30μA; at 11.7, 14.5 or 17.6MeV over 30-60min. The 61Cu (radiochemical purity of >95%) was separated using a combination of cation and anion exchange columns. The 64Zn target material was recovered after each run, for re-use. In a direct comparison with enriched 64Zn-target results, 61Cu production using the cheaper natZn target proved to be an effective alternative.

A semi-automated, in-house external beamline, ≤40 μA at 11.7 MeV for 120 min (degraded from 18 MeV to suppress 88Y & 88Zr co-production) produced 89Zr from 89Y(p,n)89Zr. EOB activity (by HPGe γ-spectr.) of 89Zr in target discs, derived from multiple runs, was 1.42 GBq (±0.45 GBq [SD], n=4) which was 67% (±21%, n=4) of the theoretical activity, with a maximum of 1.84 GBq (87% of theory) achieved. Recovery was 88% (±9%, n=4), radionuclidic purity >99% (n=4) and chemical purity 0.2 ppm Zr (±0.3 ppm, n=3, ICP-MS). The Zr:Y ratio improved from 1:10000 in the pre-filtered solution to 1:10 in the product purified by hydroxamate column. Efficiency of radiolabeling to monoclonal antibody (mAb; trastuzumab) was 100% and purified 89Zr did not bind non-specifically to mAb. Chelator:mAb ratio was 1.3:1. No-carrier-added specific activity of purified 89Zr was 408 MBq/μg (±26 MBq/μg, n=2) via the titration-by-chelator method. Minimum ligand concentration for which 100% labeling occurred was 302 nmol/L. Small animal PET imaging (Philips Mosaic; scan acquisition time 10 min; decay & randoms corrected; image reconstructed using a 3-D RAMLA algorithm) demonstrated marked tumor-specific uptake of 89Zr-labeled mAb but nil 'free' 89Zr (as chloride) tumor uptake.

Reliable production of copper-64 ({sup 64}Cu) was achieved by irradiating enriched nickel-64 ({sup 64}Ni, >94.8%) in an IBA 18/9 cyclotron. Nickel-64 (19.1 {+-} 3.0 mg) was electroplated onto an Au disc (125{mu}m Multiplication-Sign 15mm). Targets were irradiated with 11.7 MeV protons for 2 hours at 40{mu}A. Copper isotopes ({sup 60,61,62,64}Cu) were separated from target nickel and cobalt isotopes ({sup 55,57,61}Co) using a single ion exchange column, eluted with varying concentration of low HCl alcohol solutions. The {sup 64}Ni target material was recovered and reused. The {sup 64}Cu production rate was 1.46{+-}0.3MBq/{mu}A.hr/mg{sup 64}Ni(n = 10) (with a maximum of 2.6GBq of {sup 64}Cu isolated after 2hr irradiation at 40uA. Radionuclidic purity of the {sup 64}Cu was 98.7 {+-} 1.6 % at end of separation. Cu content was < 6mg/L (n = 21). The specific activity of {sup 64}Cu was determined by ICP-MS and by titration with Diamsar to be 28.9{+-}13.0GBq/{mu}mol[0.70{+-}0.35Ci/{mu}mol]/({mu}A.hr/mg{sup 64}Ni)(n = 10) and 13.1{+-}12.0GBq/{mu}mol[0.35{+-}0.32Ci/{mu}mol]/({mu}A.hr/mg{sup 64}Ni)(n 9), respectively; which are in agreement, however, further work is required.

Average dietary calcium intake and energy intake of 113 18-year-old university students in Western Australia was examined. Four-day, weighted diet records, including 1 weekend day, were completed by the subjects. A large proportion of the students (68%) had an average daily calcium consumption below the 800 mg recommended by the National Health and Medical Research Council of Australia. A strong positive association was also found between dietary calcium and dietary energy intakes. Many young women on self-imposed energy reduction diets are at risk of a dietary calcium intake deficit at a time when it should be enhanced. These findings are significant for nursing practice as they indicate the need for further health education concerning the importance of dietary calcium in young women.

Segmental variations in vertebral body cancellous bone architecture throughout the thoracolumbar spine were examined using histomorphometry and microradiography, and compared to bone mass measured using dual energy X-ray absorptiometry. In six human vertebral columns (T1 to L5) bone mineral content (BMC) and bone mineral density (BMD) of each vertebral body was determined in the lateral projection. Sagittal plane cancellous bone architecture was assessed from two-dimensional surface stained images and microradiographs of two 1 mm thick sections at each vertebral level. Computer-assisted image analysis was used to measure the total bone area (TBA), mean trabecular width (MTW) and trabecular number (TbN) from the stained images, and the skeletonized network length (SNL) from the radiographic images. Consistent segmental trends were observed for all structural parameters across the six columns examined. Higher TBA and TbN values were observed in the upper thoracic segments and decreased caudally. The MTW was relatively constant in the thoracic vertebrae before increasing in the lumbar spine. Pooled correlations between TBA and the bone density measurements were poor (BMC: r = 0.17, BMD: r = 0.25), while the TBA and SNL were only moderately correlated (r = 0.42). In conclusion, histomorphometric and radiological measurements appear to provide different information about cancellous bone structure. Bone structure is poorly correlated to integral measurements of bone mass. The consistent segmental variations in bone architecture appear to reflect a skeletal response to the relative extent of habitually applied loads in different regions of the spine.

Some previously immunodeficient HIV patients responding to antiretroviral therapy display poor recovery of CD4⁺ T cells. Evaluation of the contribution of thymic function requires sensitive detection and quantitation of metabolically active thymic tissue. We describe patients with low but detectable thymopoiesis assessed as circulating CD4⁺ naive T cells expressing CD31. High-resolution computed tomography and PET scans found no residual thymic tissue even though metabolic activity was demonstrable by PET in lymph nodes.

Structural geometric parameters at neck of the proximal femur were obtained using DXA-derived hip structural analysis (APEX 3) and quantitative computed tomography-derived (BIT QCT) techniques in 237 elderly females. Linear correlations for parameters ranged from 0.45 to 0.90. The average value of the subperiosteal width, as determined by the two techniques, was the same; variables dependent on mass measurements were different. There has been increasing interest in using bone structural geometry to assess bone fragility to complement bone mineral mass. The objective of this study is to compare structural geometrical differences between “2D” DXA-derived and “3D” QCT-derived techniques in unselected clinical cases. All 237 females had both DXA and QCT assessments of femoral neck structural geometry. Variables compared were areal bone mineral density, cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), averaged cortical thickness (Ct), endosteal width (ESW), subperiosteal width (W), and buckling ratio (BR). Correlation of femoral neck variables ranged from 0.45 for ESW to 0.90 for CSA. APEX 3 and BIT QCT-derived femoral neck W values were numerically similar. However CSA, CSMI, Z and Ct values measured by APEX 3 were higher and ESW and BR values were lower than corresponding BIT QCT. 2D DXA structural analysis of neck of femur is related to but different from same parameters calculated from true 3D images obtained by CT. Femoral neck size values are similar for DXA and QCT, but structural geometrical variables dependent on mass calibration standards, location of neck ROI and mathematical derivation techniques are different.

Lateral scanning with dual energy X-ray absorptiometry (DXA) was undertaken on 153 thoracic and lumbar vertebral bodies from nine individuals (mean age 67; range 34–92 years) to establish their bone mineral content (BMC). All specimens were subsequently de-fatted and ashed to compare ash weight with BMC of the Tl to L5 segments. Linear regression analysis indicated a higher correlation between BMC and measured ash weights for each vertebral column (range: r = 0.97 0.99), with error analysis for all vertebrae tested showing a standard error of 0.40 g, or 10.8%. For the L2 4 segments the accuracy error was 0.50 g or 7.9%. In both cases there was a mean trend towards underestimation of ash weight. Mean BMC values of the T1 to T5 segments were similar before a progressive increase caudally. These data affirm the utility of DXA for determining bone mineral content in the vertebral column across wide ranges of age, and segmental and bone density.

International audience; The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, a participant of the worldwide Alzheimer's Disease Neuroimaging Initiative (ADNI), performed (11)C-Pittsburgh Compound B (PiB) scans in 177 healthy controls (HC), 57 mild cognitive impairment (MCI) subjects, and 53 mild Alzheimer's disease (AD) patients. High PiB binding was present in 33% of HC (49% in ApoE-epsilon4 carriers vs 21% in noncarriers) and increased with age, most strongly in epsilon4 carriers. 18% of HC aged 60-69 had high PiB binding rising to 65% in those over 80 years. Subjective memory complaint was only associated with elevated PiB binding in epsilon4 carriers. There was no correlation with cognition in HC or MCI. PiB binding in AD was unrelated to age, hippocampal volume or memory. Beta-amyloid (Abeta) deposition seems almost inevitable with advanced age, amyloid burden is similar at all ages in AD, and secondary factors or downstream events appear to play a more direct role than total beta amyloid burden in hippocampal atrophy and cognitive decline.

Human lactation is associated with transient decreases in bone mineral density (BMD). Bone strength is related to both mass and structural geometry. This study investigated longitudinal changes of hip bone strength during lactation using hip structural analysis (HSA), which determines hip structural geometry (including areal BMD, BMDa) from dual-energy X-ray absorptiometry scans (DXA). Forty-eight lactating women were studied longitudinally at the proximal femur using DXA at approximately 2 weeks postpartum, peak-lactation and post-lactation. Nonpregnant, nonlactating women (NPNL, n = 23) were studied concurrently at baseline and after 1 year. Hip scans were analysed using HSA at the narrow neck, intertrochanter and proximal shaft. No significant change (> 0.05) was observed in NPNL women for any measurement. In contrast, for lactating women BMDa decreased significantly from 2 weeks postpartum to peak-lactation at narrow neck (−2.8%), intertrochanter (−3.2%) and shaft (−1.4%). Cross-sectional area (CSA) decreased at narrow neck (−3.4%) and intertrochanter (−2.7%). There were no significant changes in bone width. Section modulus decreased at intertrochanter (−2.1%). At shaft, cortical thickness decreased (−1.7%) and buckling ratio increased (2.3%). By post-lactation, measurements were not significantly different from 2 weeks postpartum except for decrements in BMDa (−1.1%) and CSA (− 1.2%) at the shaft. During the study, lactating women lost 5% of their body weight. Adjusting for weight changes decreased the magnitude and significance of HSA changes at peak-lactation and by post-lactation there were no significant differences from 2 weeks postpartum. Calcium intake was not a significant predictor of changes in HSA variables. In conclusion, lactation is associated with significant but transient changes in hip BMD and structural geometry. Changes in body weight but not calcium intake were associated with these changes. These small changes at the hip during lactation occurred mainly at internal surfaces and had minimal impact on bending or compressive strength., Research highlights ►Lactation is associated with transient changes in hip BMD and structural geometry. ►Body weight, but not calcium intake, is associated with changes in bone. ►Lactation associated changes occur mainly at endosteal surfaces of hip. ►Changes have minimal impact on hip bending and compressive strength.

Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6×10−8), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6×10−13; SOX6, p = 6.4×10−10) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation., Author Summary BMD and hip geometry are two major predictors of osteoporotic fractures, the most severe consequence of osteoporosis in elderly persons. We performed sex-specific genome-wide association studies (GWAS) for BMD at the lumbar spine and femor neck skeletal sites as well as hip geometric indices (NSA, NL, and NW) in the Framingham Osteoporosis Study and then replicated the top findings in two independent studies. Three novel loci were significant: in women, including chromosome 1p13.2 (RAP1A) for NW; in men, 2q11.2 (TBC1D8) for NSA and 18q11.2 (OSBPL1A) for NW. We confirmed a previously reported region on 8q24.12 (TNFRSF11B/OPG) for lumbar spine BMD in women. In addition, we integrated GWAS signals with eQTL in several tissues and publicly available expression signature profiling in cellular and whole-animal models, and prioritized 16 candidate genes/loci based on their potential involvement in skeletal metabolism. Among three prioritized loci (GPR177, SOX6, and CASR genes) associated with BMD in women, GPR177 and SOX6 have been successfully replicated later in a large-scale meta-analysis, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of using expression profiling to support the candidacy of suggestive GWAS signals that may contain important genes of interest.

A simple and rapid technique to measure the proton beam energy in the external beam line of a medical cyclotron has been examined. A stack of 0.1 mm thick high purity copper (Cu) foils was bombarded and the relative activity of 65Zn produced in each foil was compared to a computational model that predicted activity, based on proton stopping power, reaction cross-sectional data, and beam energy. In the model, the beam energy was altered iteratively until the best match between computed and measured relative activities of the stack of disks was obtained. The main advantage of this method is that it does not require the comparison of the activities of different isotopes of zinc arising from (p, xn) reactions in the Cu, which would require the gamma photon detector being calibrated for different energy responses. Using this technique the proton beam energy of a nominally 18 MeV standard isochronous medical cyclotron was measured as 17.49 +/- 0.04 (SD) MeV, with a precision of 0.2% CV.

Hip structural analysis (HSA) has been developed over 20 yr, applied extensively in research, and has demonstrated useful outcomes associating bone structural geometry with bone fragility (research-HSA or r-HSA). In 2007, Hologic Inc. (Bedford, MA) incorporated HSA with some modifications as an option for Hologic dual-energy X-ray absorptiometry (DXA) scanners (clinical HSA or c-HSA). This brought HSA from the research environment into the clinical environment. This article reports a comparison of r-HSA and c-HSA implementations using DXA scans from a group of 191 females. Bland-Altman plots at the narrow-neck (NN) HSA region indicated higher r-HSA areal bone mineral density (mean difference: 0.27 g/cm(2); 21.7% [of mean]); cross-sectional area (0.63 cm(2); 18.7%); cross-sectional moment of inertia (0.26 cm(4); 11.1%), and section modulus (0.22 cm(3); 14.5%) compared with c-HSA. The converse was observed for NN subperiosteal width (-0.09 cm; 3.1%). High linear correlations (r(2) > 0.81) were found between r-HSA and c-HSA NN structural geometric outcomes, with the exception of neck shaft angle (r(2) > 0.47). As differences were significant (p < 0.001), slopes and intercepts are provided to enable linear transformations from r-HSA to corresponding c-HSA structural geometric data.

Osteoporosis among older women is a major public health problem. We studied the effects of three approaches to the prevention of osteoporosis in women with low bone density.One hundred twenty postmenopausal women (mean [+/- SD] age, 56 +/- 4) who were selected because they had low forearm bone density were enrolled in a double-blind, placebo-controlled, randomized study comparing the effects of an exercise regimen (exercise group, n = 41), exercise plus dietary calcium supplementation (exercise-calcium group, n = 39), and exercise plus continuous replacement of estrogen and progesterone (exercise-estrogen group, n = 40). Periodically during the two-year study period, we measured the women's bone density at three forearm sites, measured indexes of calcium metabolism, and recorded symptom scores. A comparison group of 42 women (mean age, 55.5 +/- 3.1) with normal bone density was also followed for two years.Significant bone loss in the distal forearm occurred in the group with normal bone density (control group) and the exercise group (change, -2.7 percent and -2.6 percent of the base-line value per year, respectively). Bone loss at the distal forearm site was significantly lower in the exercise-calcium group (-0.5 percent of the base-line value per year), and bone density increased at this site in the exercise-estrogen group (+2.7 percent of the base-line value per year). Bone loss at the median forearm site was significantly lower in the exercise-calcium group (-1.3 percent of the base-line value per year) than in the exercise group (-2.4 percent), and bone density at this site increased significantly in the exercise-estrogen group (+0.8 percent of the base-line value per year). Breast tenderness occurred in 47 percent of the women in the exercise-estrogen group but in only 20 percent in the other two treatment groups. Vaginal bleeding occurred at some time in 52 percent of the women who had not had a hysterectomy in the exercise-estrogen group, as compared with 11 percent and 12.5 percent, respectively, in the exercise and exercise-calcium groups.In postmenopausal women with low bone density, bone loss can be slowed or prevented by exercise plus calcium supplementation or estrogen-progesterone replacement. Although the exercise-estrogen regimen was more effective than exercise and calcium supplementation in increasing bone mass, it also caused more side effects.

Kathryn A. Ellis, Victor L. Villemagne, David Ames, Nat Lenzo, Kerryn E. Pike, Graeme O’Keefe, Henri Tochon-Danguy, Roger Price, Gareth Jones, Mira Rimajova, Pierrick Bourgeat, Parnesh Raniga, Jurgen Fripp, Oscar Acosta, Olivier Salvado, Ralph Martins, Colin L. Masters, Christopher C. Rowe, University of Melbourne, Melbourne, VIC, Australia; Austin Hospital, Melbourne, VIC, Australia; The Mental Health Research Institute of Victoria, Melbourne, VIC, Australia; National Ageing Research Institute, Melbourne, VIC, Australia; WA PET Centre, Perth, WA, Australia; Edith Cowan University, Perth, WA, Australia; Sir Charles Gairdner Hospital, Perth, WA, Australia; CSIRO ICT Centre, Brisbane, QLD, Australia. Contact e-mail: kellis@unimelb.edu.au

The healthcare cost of managing osteoporotic fractures is projected to rise because of the change in population demographics. To reduce the fracture epidemic, strategies are needed to identify those at risk early to allow preventative intervention to be implemented. The aim of this study was to investigate if low-cost community-based assessments, such as calcaneal ultrasound and falls risk assessments, can discriminate a group of elderly women at risk of osteoporotic fracture from those at lower risk. Over the period of 2002-2003, 104 community-dwelling women (mean age 71.3, standard deviation 5.8) were recruited via various modes including advertisements in community newspaper and community centres. These women underwent dual-energy X-ray absorptiometry bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) measurements; spinal radiography; and performance-based assessment of strength, mobility and balance. The women were classified into a 'high risk' (osteoporotic) group, based on low BMD (T-score of/= -2.5) and/or a history of a fragility fracture, or a 'low risk' (non-osteoporotic) group. Multiple stepwise logistic regression identified decreased speed of sound (SOS), a QUS variable, and poor mobility [slower performance in the timed 'up and go' (TUG) task], as significant discriminators, adjusted for age [SOS: adjusted odds ratio (OR) = 2.96, 95% confidence interval (CI) = 1.64-5.12, P0.001; TUG: adjusted OR = 1.69, 95% CI = 1.04-2.73, P = 0.031]. This result suggests that there may be a potential role for primary healthcare practitioners to use calcaneal QUS and functional mobility assessment (TUG) to screen for post-menopausal women at risk of osteoporotic fracture in community settings.

Individuals with existing vertebral fractures may not be aware that they are at high risk of subsequent fractures. We investigated if calcaneal quantitative ultrasonometry (QUS) and assessment of thoracic kyphosis could discriminate a group of older women with prevalent vertebral fracture from those without.One hundred four women (mean age 71.3 +/- 5.8 yrs) underwent dual-energy x-ray absorptiometry (DEXA) bone mineral density (BMD; lumbar spine and hip), calcaneal QUS, and video rasterstereographic thoracic kyphosis measurements. They were dichotomized into a group with prevalent vertebral fracture (VF, n = 24) or without vertebral fracture (NVF, n = 80).Univariate variables associated with the VF group included broadband ultrasound attenuation (BUA; age-adjusted OR 1.96, 95% CI 1.12-3.42, p = 0.018); speed of sound (SOS; age-adjusted OR 2.01, 95% CI 1.09-3.70, p = 0.026); and thoracic kyphosis (age-adjusted OR 1.72, 95% CI 1.01-2.92, p = 0.049). A composite model (BUA and thoracic kyphosis) had higher area under the receiver-operating characteristic curve (AUC = 0.75) compared to lumbar spine DEXA BMD (AUC = 0.50, p = 0.0004) and total hip DEXA BMD (AUC = 0.60, p = 0.057).Reduced calcaneal QUS values and greater thoracic kyphosis were found to be significantly associated with the group of women with prevalent vertebral fractures. A composite risk score (BUA and thoracic kyphosis) had better discriminatory power than the individual risk factor of (low) DEXA BMD.

Oral (44Ca: 0.13-0.20 mmol) and intravenous (42Ca: 0.02-0.037 mmol) isotopically enriched stable calcium (Ca) tracers were given together with an oral dose of 2.5 mmol of natural Ca to normal subjects. Blood and urine samples were collected up to 24 h after the tracer doses and atom fractions (AFs) of these tracers (relative to natural Ca) were measured by high-precision thermal ionization mass spectrometry (TIMS). The time-dependent fractional rate of oral dose absorbed and true fractional intestinal Ca absorption (alpha) were derived from the Afs by mathematical deconvolution. After 6 h, the ratio AF oral tracer/AF intravenous tracer in blood equalled that in urine and did not change thereafter. Reproducibility of the combination of chemical precipitation of Ca (from a urine standard) and subsequent TIMS measurements, in nine runs over 13 months, was 1.2% (coefficient of variation). This was in accord with the within-run reproducibility. An estimate of alpha derived from a single blood or urine measurement was 6-10% higher than the reference value obtained by deconvolution. This discrepancy could be explained by a correction factor depending, in part, on the elapsed time for peak Ca intestinal absorption rate. Instrumentally induced mass fractionation, as well as contributions from radiogenic Ca, had a significant effect on the accuracy and reproducibility of the ratio of AFs of tracers in blood and urine.

The foramen ovale is usually obliterated following establishment of the adult circulation but remains patent in 25% of individuals. This potential communication between the venous and arterial circulations can allow thromboembolic material to bypass the lungs and enter the systemic circulation. We report two cases of paradoxical embolization through a patent foramen ovale following acute large pulmonary embolism (PE) and discuss the factors that predispose to paradoxical embolization following PE.

Background The nucleus pulposus deforms towards an area of least compression in response to offset loading, however, there is a lack of data reporting the deformation patterns of nuclear material in rotated positions of the lumbar spine. Our purpose was to assess a novel methodology using MRI to track nuclear deformation in response to flexion and extension positions, and the combined positions of flexion with left rotation and extension with left rotation, at L1–2 and L4–5. Methods Three asymptomatic female subjects, mean age 27 years, underwent T2 weighted MRI sequences in flexed, extended, and left rotated positions combined with flexion and extension. A pixel profile technique was employed to determine direction and magnitude of nuclear deformation. Results In 5 of 6 discs examined, deformation of the nucleus occurred anteriorly in extension and posteriorly in flexion. Left rotation resulted in migration of nuclear material to the right in 9 of 12 discs. Of the three discs that demonstrated a right nuclear migration, two occurred at L4–5 and one at L1–2. Interpretation This methodology demonstrated that nucleus pulposus deformation can be measured reliably in various positions achieved within the confines of the MRI. The consistent migration of nuclear material following sagittal plane movement and the less consistent response to rotation positions suggest other asymmetrical loading on the intervertebral disc may accompany rotation.

Musculoskeletal allografts are used widely in tumour and reconstructive surgery. Gamma irradiation has been used to sterilise allograft bone but its effect on the biomechanical properties of osseous tissue is not fully elucidated. In this study, we have examined the effect of gamma irradiation on the mechanical properties of human cortical bone. An examination was carried out of the three-point bending, compressive strength, and fracture toughness of human femoral cortical bone irradiated at doses of 15, 25, and 50 kGy, in comparison with non-irradiated control bone. We found that gamma irradiation degrades the mechanical properties of bone as evidenced by three-point bending and toughness assays. A 6% reduction in ultimate three-point bending stress was observed at 15 kGy, 23% at 25 kGy and 30% at 50 kGy. There was a 12% reduction in toughness at 15 kGy, 13% at 25 kGy and 22% at 50 kGy. The effect on ultimate compressive stress was less marked, with no significant effect seen below a 50 kGy radiation dose. In summary, given the low incidence of disease transmission from allograft bone, it is believed that where large structural allografts are concerned, the possible benefits of gamma irradiation need to be balanced against its detrimental effects on the resistance of the bone to catastrophic mechanical failure.

The effects of dietary calcium intake and physical activity on longitudinal changes in BMD over a mean of 9.4 years were examined in 62 healthy young women. Proximal femur BMD declined, lumbar spine BMD increased, and physical activity was associated with BMD change at intertrochanter and total hip sites. Introduction: Maximizing premenopausal BMD is an important strategy for the prevention of osteoporosis and resultant fractures later in life. Materials and Methods: Young women who previously participated in a placebo-controlled 2-year calcium intervention study at a mean age of 18.5 ± 0.3 years were remeasured at 27.8 ± 1.0 years of age. DXA (Hologic QDR 1000W) was used to measure changes in BMD, and lifestyle factors were ascertained by questionnaire. Results and Conclusions: Early decline in BMD at the neck of femur (−3.3%/decade) and the converse gain in BMD at the lumbar spine (+4.3%/decade) and intertrochanter (+1.9%/decade) suggest site-specific changes in BMD in young premenopausal women. No effect of previous calcium supplementation was seen on current BMD or changes in BMD (p > 0.10). Lifestyle predictors of change in BMD were determined using hierarchical regression analysis after forced correction for the covariates baseline BMD and previous calcium supplementation. Physical activity was positively associated with change in BMD at total hip and intertrochanter sites (β-coefficients, β = 0.26 and 0.26 respectively; p < 0.05). Calcium intake was negatively associated with change in BMD at the lumbar spine (β = −0.27, p < 0.05). Parity was negatively associated with change in BMD at all sites (β = −0.40 to −0.26, p < 0.05). These data show that BMD is already declining at the proximal femur in these healthy young women. Physical activity assists in maintenance of BMD at some sites and thus may contribute to lifelong fracture prevention. There was no positive association between calcium intake and change in BMD.

There are uncertainties concerning the optimal threshold value of bone mineral density (BMD) for the diagnosis of osteoporosis using dual-energy X-ray absorptiometry (DXA). The most widely accepted clinical criteria are based on T- and Z-scores, derived statistically from an age-dependent BMD reference range that includes healthy young adults. This study has compared different analyses of BMD data of healthy, nonfractured, adult white females aged 18–90 years, consisting of 953 studied with DXA in the L1–L4 spine and 1018 measured at the hip. Four regression curves were applied to each reference data set; mean peak BMD (PBMD R ) and the age-independent standard deviation (SD R ) were calculated. These data, plus derived T-score thresholds, were compared with equivalent values (PBMD YN , SD YN ) determined from BMDs of a subgroup of young normals. Choice of regression curve caused a variation of 0.044 g/cm 2 in spinal PBMD R and 0.015–0.022 g/cm 2 in the hip. The variation in calculated SD R between the regressions was minimal (maximum variation, 0.03 SD unit in the spine). A split-linear model was chosen as the best overall fit for both the spine and the hip on the basis of goodness-of-fit and biological plausibility. PBMD R and PBMD YN varied by less than 1% at the spine or hip. Although the difference between SD R and SD YN was ≤7% for the hip sites, SD R was 0.022 g/cm 2 > SD YN for the spine (17% difference). At each hip site, BMD T-score thresholds, derived from regression analysis of the entire reference range (T R ) or from young normals only (T YN ), were not significantly different; however, equivalent spinal values differed by 0.062 g/cm 2 for T=–2.5. The percentage of the Australian female population (AFP) aged 50 yr or older and classified as osteoporotic, using population census data and the split-line-based T-score threshold of T R = –2.5, was 23% for spinal BMD and 17% for the total hip. For T YN = –2.5, the values were 36% (spine) and 17% (total hip). The hip BMDs of this study were greater than those of NHANES III in the third, seventh and eighth decades by as much as 0.6 SD. This produced a difference of 0.049–0.077 g/cm 2 for T YN = –2.5 between the two reference ranges. However, this study is in broad agreement with an Eastern Australian and the U.S. DXA manufacturer's reference range. It is concluded that (i) derivation of peak BMD and its standard deviation are critical for calculation of T-scores in the spine but not in the hip; (ii) there are significant differences between the hip peak BMDs of young normals, as derived from studies of similar populations in different regions, significantly affecting the impact of the subsequent clinical application of the calculated T-score.

Patients attending a routine bone densitometry clinic were scanned on two different densitometers on the same day using a pencil-beam (Hologic QDR1000W) and fan-beam (Hologic QDR4500W) machine. Subjects were scanned at the lumbar spine site and or the proximal femur. The differences in bone mineral density (BMD) between the fan-beam and pencil-beam (QDR4500W–QDR1000W) were determined for all pairs of scans. The mean difference in BMD was also calculated to see if there was a systematic bias between the machines. The mean difference in BMD was –8 mg/cm 2 and 25 mg/cm 2 at the spine and total hip, respectively. The individual differences in BMD between the two machines were examined to assess if they were significantly greater than measurement error. The percentage of scans classified as significantly different was calculated for the difference in BMD before and after adjusting for the mean difference in BMD. The percentage of individuals classified as significantly different ranged from 17.1–45.0% before adjustment, at the spine and total hip, respectively, and 16.1–22.6% after adjustment. From a clinical perspective, this degree of misclassification is probably unacceptable. These results suggest that scans obtained from a QDR4500W fan-beam system and QDR1000W pencil-beam system should not be compared, with or without adjustment for systematic bias.

An Electron Gamma Shower version 4 (EGS4) based user code was developed to simulate the absorbed dose in humans during routine diagnostic radiological procedures. Measurements of absorbed dose using thermoluminescent dosimeters (TLDs) were compared directly with EGS4 simulations of absorbed dose in homogeneous, heterogeneous and anthropomorphic phantoms. Realistic voxel-based models characterizing the geometry of the phantoms were used as input to the EGS4 code. The voxel geometry of the anthropomorphic Rando phantom was derived from a CT scan of Rando. The 100 kVp diagnostic energy x-ray spectra of the apparatus used to irradiate the phantoms were measured, and provided as input to the EGS4 code. The TLDs were placed at evenly spaced points symmetrically about the central beam axis, which was perpendicular to the cathode-anode x-ray axis at a number of depths. The TLD measurements in the homogeneous and heterogenous phantoms were on average within 7% of the values calculated by EGS4. Estimates of effective dose with errors less than 10% required fewer numbers of photon histories (1 x 10(7)) than required for the calculation of dose profiles (1 x 10(9)). The EGS4 code was able to satisfactorily predict and thereby provide an instrument for reducing patient and staff effective dose imparted during radiological investigations.

Objectives. To compare the Cobb technique for measuring kyphosis with an alternative Cobb method and a computer-assisted curve assessment technique, and to examine the influence of vertebral body and disc shape on kyphosis. Methods. Kyphosis measurements were derived from 93 lateral spinal radiographs or sagittal computed tomography images of cadaveric spines, using: (i) a computer-assisted method for estimating radius of curvature; (ii) the traditional Cobb method; and (iii) an alternative Cobb method. Regression models were applied for agreement analyses, and to examine the relative contribution of vertebral body and disc shape on the extent of curvature. Results and conclusions. Strong associations existed between curvature and angle data derived from the three methods, confirming the clinical utility of these techniques for the quantification of thoracic kyphosis. However, the traditional Cobb method tended to overestimate kyphosis in the presence of vertebral body end-plate deformation. The degree of kyphosis was strongly reflective of the extent of deformity of the vertebral bodies, and to a lesser extent the shape of the thoracic discs.

The fractional absorption of calcium (FA-Ca) was measured using a dual non-radioactive Ca isotope technique in 26 control women, 49 women in the last triimester (36 weeks) of pregnancy and 31 of these women in established (20 weeks) lactation. The ratio of the two non-radioactive Ca isotopes was measured, by high precision thermal ionisation mass spectrometry, in urine 12–24 hours after administration and was used to calculate Fa-Ca. This is the first study to clearly show that FA-Ca is significantly elevated in late pregnancy but not in established lactation, when compared with control women.

Objective. The aim of this study was to quantify the morphology or shape of thoracic vertebral bodies and intervertebral discs, and to examine the ex vivo association of thoracic kyphosis with these shape parameters. Design. A quantitative, retrospective study design was applied to define vertebral body and disc influences on thoracic kyphosis. Background. Age-related progression of thoracic kyphosis is a well-defined process that is influenced by the morphology of vertebral bodies. However, little is known about the contribution of intervertebral disc shape to the thoracic curvature. Methods. Vertebral and disc morphology, as represented by antero-posterior height ratios, were quantified in 93 lateral spine radiographs and midsagittal computed tomography films of ex vivo spines. Kyphosis was indicated by the Cobb angle. Linear and stepwise regression were applied to examine relationships for cumulative (T1–T12) and regional (T4–T9) analyses. Results. Vertebral morphology was highly predictive of thoracic curvature, while a poorer association was noted for disc morphology. The combined influence of both accounted for >85% of the variability in kyphosis. There was a trend for a more pronounced anterior wedge configuration of the midthoracic vertebral bodies and discs. Higher associations between variables were also noted in this region. Conclusions. The normal kyphosis of the thoracic spine reflects the morphological adaptation of both the vertebral bodies and intervertebral discs. Relevance This study contributes new data on the thoracic spine, particularly the characteristics of thoracic discs and their contribution to kyphosis genesis. Future directions for morphology studies should encompass more detailed examination of the thoracic discs and greater emphasis on the midthoracic segments, considering the prevalence of osteoporosis related fractures and subsequent deformity at these levels.

The estimation of vertebral fracture risk in individuals with suspected osteopenia is commonly based on measurements of lumbar spine bone density. The efficacy of vertebral size and deformity, as assessed by vertebral morphometry, in the prediction of fractures has been less studied. In an ex vivo investigation the regional relationships between vertebral size, vertebral deformity, bone density and compressive strength throughout the thoracolumbar spine were examined. In 16 vertebral columns (T1-L5) the bone mineral content (BMC) and bone mineral density (BMD) of each segment were measured using lateral projection dual-energy X-ray absorptiometry, and the vertebral cancellous density (VCD) and mid-vertebral cross-sectional area (CSA) measured using quantitative computed tomography. Vertebral body heights were determined from mid-sagittal CT scans, and vertical height ratios calculated for each segment. The failure load and failure stress of the isolated vertebral bodies were determined using a material testing device. Separate analyses were performed for the upper (T1-4), middle (T5-8) and lower (T9-12) thoracic, and lumbar (L1-5) segments. In all regions, failure load was strongly correlated with BMD (r = 0.82-0.86), moderately correlated with VCD (r = 0.60-0.71) and vertebral height (r = 0.22-0.49), and poorly correlated with the height ratios (r = 0.04-0.33). Failure stress was best predicted by BMD (r = 0.73-0.78) and VCD (r = 0.70-0.78) but was poorly correlated with all morphometric variables (r = 0.01-0.33). The segmental correlations between BMD and VCD ranged form r = 0.49 to r = 0.79. For all regions, BMD and VCD were included in the stepwise regression models for predicting failure load and failure stress. Either the mid-vertebral height or CSA were included in all the failure load models, while mid-vertebral height was included in only one of the failure stress models. The results suggest that vertebral deformity and size (as assessed by vertebral morphometry) make only a minor contribution to the prediction of vertebral strength additional to that provided by bone densitometry alone. The consistent regional relationships between variables appear to support the practice of global fracture risk assessment based on lumbar spine densitometry.

An intravenous dosage schedule using pamidronate disodium, based on biochemical severity, was used to treat 71 patients with Paget's disease who had had no previous bisphosphonate treatment. Disease severity was stratified by fasting hydroxyproline excretion (Hyp(E)): Group (Gp) I (mild disease; Hyp(E) < 5.0 μmol/LGF) received a total dose of 120 mg; Gp II (moderate; Hyp(E), 5.00-9.99) received 180 mg; and Gp III (severe; Hyp(E) ≤ 10) received 240 mg. Within each group patients were randomly allocated to receive daily 30 mg or 60 mg infusions. Observations for 2 years included pain scores, indices of bone turnover, and radiology of lytic lesions. There was no difference in biochemical responses, or in the percentage of patients with early fever, between the 30 mg and 60 mg daily subgroups; for convenience, 60 mg infusions are recommended. Neutrophils and total white cell counts were both significantly below baseline 4 days after the first infusion; lymphocytes were significantly reduced by day 2; and all three measures had returned to within the reference range by day 6. Remission was assessed at 6 months, when both plasma alkaline phosphatase (ALP) and Hyp(E), had reached stable nadirs. Increasing severity was associated with increasing resistance to suppression of Hyp(E) at 6 months to within the reference range: Gp I, 87%; Gp II, 44%; and Gp III, O% (p < 0.0001 by chi-square test). Biochemical relapse at 2 years (defined as ALP 50% above the 6 month level) was also dependent on initial disease severity (Gp I, 6%; GpII, 39%; Gp III, 62%;p < 0.0005 by chi-square test). There was no association between time to relapse and either initial dose or log dose. Radiologic lytic lesions (in 22 patients) were all in remission at 3 months; however, relapse rates at 2 years appeared to be severity-dependent: Gp I, 13%; Gp II, 43%; and Gp III, 57% (n.s. by chi-square test). Remission rates based on a fall to < 50% of pretreatment of either Hyp(E) or ALP were more in accord with lytic lesion remission rates than were rates based on Hyp(E) falling to within the reference range. Pamidronate produced a significant reduction from baseline in Pagetic bone, Pagetic joint, and unrelated musculoskeletal pain in the first 6 months (p < 0.0001). From 0 months to 2 years the maintenance of improvement in bone pain (p < 0.005) and joint pain (p < 0.05) was significantly better than in unrelated pain. Pamidronate is a safe, well-tolerated, and effective treatment for Paget's disease. In spite of larger dosage in severe disease, increasing severity was associated with resistance to normalization of biochemistry and a higher incidence of biochemical and radiological relapse at 2 years. Our current dosage recommendation would be for two 60 mg infusions for mild disease (Gp I); and four 60 mg infusions for moderate disease (Gp II). Severe disease (Gp III) remains a challenge; regardless of dosage, the majority of patients will be in relapse 2 years after a single course of treatment.

A novel hexa aza cage, N(1)-(4-isothiocyanatobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane-1,8-diamine (SarAr-NCS) was synthesized in good yield and characterized by (1)H NMR and electrospray mass spectrometry. A new method for the synthesis of the related N(1)-(4-carboxybenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane-1,8-diamine (AmBaSar) using the p-carboxybenzaldehyde is reported. The complexation of Cu(2+), Co(2+) and Zn(2+) by the two ligands over a range of pHs was found to be similar to the parent derivative SarAr. SarAr-NCS was conjugated to both silica particles (≈90 nm diam.) and the model B72.3 murine antibody. The SarAr-NCSN-silica particles were radiolabeled with Cu(2+) doped (64)Cu and the number of ligands conjugated was calculated to be an average of 7020 ligands per particle. Conjugation of SarAr-NCS to the B72.3 antibody was optimized over a range of conditions. The SarAr-NCSN-B72.3 conjugate was stored in buffer and as a lyophilized powder at 4 °C over 38 days. Its radiolabeling efficiency, stability and immunoreactivity were maintained. The development of a high yielding synthesis of SarAr-NCS should provide an entry point for a wide range of Cu and Zn radiometal PET imaging agents and potentially radiotherapeutic agents with (67)Cu.

The bone density of thoracolumbar vertebral columns (T1 to L5) from 18 individuals was measured using quantitative computed tomography and dual energy x-ray absorptiometry. Three hundred six isolated vertebral bodies were tested in a materials test device to determine their compressive strength. Between T1 and L5 the mean segmental increase in bone mineral content was 0.3 g, while the corresponding mean decrease in trabecular density was 4.7 HU. Midvertebral body cross-sectional area increased by an average of 46 mm2 per segment and the mean segmental increase in compressive strength was 0.17 kN. Compressive strength was significantly correlated with bone mineral density measured with dual energy x-ray absorptiometry (r = 0.86). Vertebral trabecular density samples measured with quantitative computed tomography were poorly correlated with compressive strength (r = 0.28); however, this was improved when the trabecular density was multiplied by the midvertebral body cross-sectional area (r = 0.83). This study provides information concerning the relationships between density and mechanical properties of all thoracic and lumbar vertebral bodies across a wide age range. While the load-bearing capacity of the vertebral bodies is largely dependent on their geometry and bone density, this relationship has been only extensively tested for the lumbar spine. This study extends these observations over the lumbar and thoracic regions to provide a comprehensive analysis of the strength characteristics of each vertebral body. This is particularly important given the paucity of data on the thoracic spine where age-related vertebral fractures predominate. These data provide a basis for the development of models to predict the potential for thoracolumbar fractures in the elderly vertebral column.

Although women lose 30% of their skeletal mass after the menopause, the mechanism of this loss is uncertain. Clearly estrogen deficiency is important but whether this works only through direct effects on the skeleton is uncertain. To examine these mechanisms further we have evaluated calcium-related metabolic factors in 655 healthy women. Fasting blood samples were collected from all subjects who were up to 35 years past the menopause, and fasting urine and 24-h urine samples were collected in 365 women who were up to 25 years past the menopause. In the first 15 years postmenopause, there was a rise in total plasma calcium due to a rise in albumin. Bone resorption (hydroxyproline creatinine ratio), bone formation (alkaline phosphatase), and the urine calcium creatinine ratio all rose at menopause and remained elevated for the next 25 years. There was a transient further rise in bone resorption for the 10 years following menopause. Neither PTH nor the free calcitriol index changed for the first 10 years following menopause. Ten years past the menopause, although total calcitriol rose, the free calcitriol index fell due to a rise in vitamin D binding protein. PTH began to rise at 15 years past menopause. GFR fell gradually over the 25 years following menopause. Thus following menopause there is an increase in bone turnover and increased urine calcium loss independent of any effect of PTH or calcitriol, suggesting a direct effect of estrogen deficiency on bone and kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential determinants of bone mineral density (BMD) were studied cross-sectionally in 115 healthy, sexually mature Caucasian women aged 18 years. Bone mineral density (Hologic QDR1000W) of the lumbar spine, proximal femur (five sites), and distal tibia and fibula; fasting blood and urine calcium biochemistry; serum sex hormone levels (follicular phase); nutrient intakes; aerobic fitness; trunk muscle strength; and habitual activity levels were measured. The effects of heredity were considered by measuring the BMD of 107 of the subjects' mothers. Simple and stepwise regression analysis were used to identify significant determinants of BMD at each of the regions studied. The analysis indicated that significant bivariate correlations exist between BMD at all sites and body weight (r = 0.23-0.47, por = 0.01), lean body weight (r = 0.34-0.46), trunk strength (r = 0.27-0.47), physical activity score (r = 0.20-0.25), and aerobic fitness (r = 0.29-0.45). Dietary calcium intake correlated significantly with BMD at the trochanter site only (r = 0.19), and none of the biochemical or hormonal indices measured correlated consistently with BMD at any site. Significant correlations between the BMD of mothers and daughters ranged from r = 0.43 at lumbar spine to r = 0.34 at the intertrochanteric site. Paired t-tests showed the daughters had significantly (p0.03) lower BMD than their mothers at the lumbar spine (98 +/- 12% [mean +/- SD]) and significantly higher (p0.002) BMD at the femoral neck, trochanter, and total hip sites (110 +/- 16%, 108 +/- 17%, 103 +/- 14%, respectively). When stepwise regression analysis included weight-corrected strength of the trunk flexor muscles (Corr Flex), weight-corrected aerobic fitness (Corr VO2max), physical activity score, and body weight, body weight was the only significant determinant of BMD at all sites. Corr Flex made significant contributions at all sites except the femoral neck, while Corr VO2max made additional contribution at the femoral neck, trochanter, total hip, and shaft of femur sites. These variables accounted for 13-27% of the variance in BMD. The addition of mother's BMD to these independent variables, in stepwise regression analysis, improved the prediction to 18-31% of the variance.

Summary Topographical variation in the articular cartilage and subchondral bone of the normal ovine knee was examined using histological techniques. The articular cartilage was examined grossly, then histological sections were cut and the cartilage thickness and chondrocyte density were measured. Bone mineral density, thickness of the subchondral bone plate (SBP) and volume and surface histomorphometrical parameters and mineral apposition rate were calculated for the subchondral bone. It was found that the articular cartilage on the tibial plateaux was thicker, less cellular, and overlay a thicker SBP than that on the femoral condyles. Similarly, the cartilage in the medial joint compartments was thicker, less cellular and overlying a thicker less dense SBP than that in the lateral joint compartments. There was no variation in bone histomorphometric parameters or mineral apposition rate between regions. Biomechanical testing has shown that loading is not uniform throughout the normal human knee joint. The present results suggest that loading within the ovine knee is also nonuniform, with the central regions of the tibial plateaux bearing greater loads than the femoral condyles, and the medial joint compartment being loaded more than the lateral one. The articular cartilage and subchondral bone have adapted in order to best withstand these variations in loading. These histological findings, plus the topographical variations in cartilage biochemistry reported by Read et al. (Topographical variation in composition, PG-biosynthesis and swelling pressure of cartilages of loaded tibio-femoral joints (Abstract). Proceedings of the Combined Meeting of the Orthopaedic Research Societies of USA, Japan and Canada . Banff, Alberta, October 1991:1.), emphasize the need for focal analysis of tissues in animal models of joint diseases, and the dangers of pooling samples from different joint regions.

Purpose: The device for intervertebral assisted motion (DIAM™) is an interspinous (ISP) implant used to augment surgical decompression of lumbar degenerative conditions: Lumbar spinal stenosis [LSS; foraminal (FS) or central canal (CS)], herniated and degenerated disc disease, facet joint pain syndrome (FJPS) and minor degenerative spondylolisthesis (DS). Limited evidence guides its use in defined clinical indications, while few studies demonstrate effect according to clinically meaningful change (MCID). This prospective longitudinal study examined the efficacy of DIAM-augmented decompression surgery in the broad application of a single-center clinical reality. Methods: Eighty-one consecutive cases [37F, 44M; 52 years (SD 13)] were examined for two years after DIAM-augmented decompression surgery. Patient-reported pain [back and leg; visual analogue scale (VAS)], function [Oswestry disability index (ODI)], and satisfaction (Likert scale) were serially examined and referenced to contemporary MCID thresholds. Subjects were classified into anatomical and diagnostic categories and analyzed according to subgroups to better inform clinical pathways. Serial change was assessed with Scheffe post-hoc test; change scores with unpaired t-tests and descriptive statistics (p < 0.05). Results: Subjects reported 20.4% (SD 29.5; p < 0.0001) mean improvement in back pain, 20.3% (SD 30.6; p < 0.0001) in leg pain, and 15.1% (SD 20.8; p < 0.0001) in function at two years postoperatively. Greatest improvement was seen at six weeks for back pain (by 30.5%; p < 0.0001) and leg pain (by 29.4%; p < 0.0001) and three months for function (by 18.7%; p < 0.0001). Leg pain deteriorated between six weeks and 18 months (p < 0.05). There were more responders at one compared to two years after surgery. FS cases showed superior improvement compared to DS subjects (p < 0.05). Cases receiving multiple adjunctive surgical decompressions in addition to their DIAM had superior improvement than those receiving a single procedure (p < 0.05). Conclusions: Clinical improvement in back pain, leg pain and function were achieved to two years in a single-center cohort of 81 cases with lumbar degenerative disease who received DIAM-augmented decompression surgery. Subsets of the sample had a superior sustained response including foraminal/lateral recess stenosis patients and cases treated with > 1 adjunctive decompression techniques. The need for assessing homogeneous cohorts in future studies is emphasized.

Purpose: To examine clinical outcomes after decompressive lumbar surgery for herniated nucleus pulposus (HNP) in two cohorts from a single surgeon: Microdiscectomy alone [MICRO] versus microdiscectomy augmented with the Device for Intervertebral Assisted Motion [DIAM™, Medtronic Sofamor Danek, Memphis, USA]. We hypothesized that DIAM-augmented microdiscectomy would provide superior outcomes to microdiscectomy alone given purported benefits for interspinous devices reported in the literature. Improvements would concur with clinically significant change. Methods: Two separate HNP patient groups were sourced from a single surgeon: MICRO [n = 47 (17F/30M); 45 years (SD 14.2; 22–75)] and DIAM [n = 29 (10F/19M); 42 years (SD 11.2; 20–64)]. Patient-reported outcomes for function [MICRO=Roland-Morris Questionnaire (RMQ); DIAM=Oswestry Disability Index (ODI)] and back and leg pain [visual analogue scale (VAS)] were serially examined at preoperative baseline, 4–6 weeks, 6 and 12 months postoperatively. Incidence of repeat surgery at the index segment was recorded. Data were reported using descriptive statistics, unpaired t-tests and repeated ANOVA (Scheffe's post-hoc test). Statistically meaningful differences were defined by p < 0.05. Results: MICRO cases had higher preoperative leg pain (by 19%; p < 0.01). Improvements in absolute function and leg pain at one year were better in the MICRO group (p < 0.01). Both groups showed clinically significant improvement for all variables at each time-point during the period of follow-up. MICRO cases had proportionally fewer repeat surgeries (3/47 versus 4/29). Conclusions: Significant improvements in function, back and leg pain were shown in both patient groups out to one year. Clinically important change to function, back and leg pain was achieved for the MICRO cases, while clinically important change to leg pain occurred in the DIAM group. MICRO cases required proportionally fewer repeat surgeries by one year postoperatively. Microdiscectomy augmented with DIAM did not result in superior outcomes in treatment of herniated nucleus pulposus compared with microdiscectomy alone.

Vertebral body geometry, defined by the anterior/posterior (A/P) and mid/posterior (M/P) vertebral body height ratios, was measured in 18 vertebral columns (T1-L5) from sagittal computed tomography scans. For each vertebra, the trabecular density (VTD) and bone mineral density (BMD) were measured using quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA), respectively. Lateral view radiographs were digitized to measure the thoracic curvature. The segmental correlations between vertebral shape and bone density were poor (r = 0.01-0.31). The mean thoracic BMD and VTD and the mean lumbar VTD were significantly correlated with the mean thoracic A/P ratio (r = 0.55-0.69). The thoracic curvature was significantly correlated with both the mean thoracic and the mean lumbar VTD and BMD (r = 0.55-0.73). In summary, the extent of vertebral wedging and thoracic curvature was moderately indicative of the mean BMD of the thoracic vertebrae, and lumbar spine densitometry is useful to assess the relative severity of osteopenia in individuals with thoracic vertebral deformities.

There is general agreement that bone density falls with age and is higher in heavy people than light people. We have studied a variety of potential correlates of vertebral, ankle, and hip bone density to evaluate other potential influences on the skeleton. We recruited 196 healthy women who were more than 10 years past the menopause and collected a diet and activity record, a 24 h urine, and a fasting blood and urine specimen. These blood and urine samples were analyzed for factors related to calcium homeostasis. We then measured bone density at lumbar vertebrae 1-4 and the hip and the ankle bone density of the nondominant leg. Correlations between vertebral, hip, and ankle bone density and other measured variables were explored using the statistical package SPSS PC. At the vertebral site, in addition to correlations with age and body mass index (BMI), a negative correlation with a measure of bone resorption, the hydroxyproline creatinine ratio (OHPCR), was noted. At the ankle site, in addition to correlation with age, BMI, and OHPCR, a positive correlation with activity and a negative correlation with serum calcitriol were noted. At the hip site, as well as age, BMI, and OHPCR, significant correlations with GFR and dietary calcium intake were noted. These data suggest that even in women 10 years past the menopause bone resorption has a significant effect on bone density, that renal function may account for some of the variance in bone density at the hip, and that activity effects are more marked at sites of greater loading, namely the ankle.

Because intestinal calcium absorption may be an important independent determinant of calcium balance and therefore bone mass, we have studied this factor and other potential predictors in 196 healthy postmenopausal women. Gut calcium absorption was measured in each subject by a stable strontium method and expressed as a fractional absorption. The fractional absorption was significantly negatively correlated with years since menopause (YSM) (r = -0.15 P0.05) and dietary calcium intake (r = -0.15 P0.05), and significantly positively correlated with 24-hour urine calcium excretion (r = 0.31 P0.001) and body mass index (r = 0.20 P0.01). Apart from YSM, these factors remained as correlates in multiple regression analysis; the standardized regression coefficient was largest for 24-hour urine calcium excretion (0.32). Fractional absorption of calcium was not correlated with vertebral bone density. Thus, intestinal calcium absorption, although falling with increasing menopausal age and increasing calcium intake, is best correlated with the urine calcium excretion. This indicates either that gut calcium absorption is regulated in response to the magnitude of the urine calcium excretion or that the kidney maintains calcium balance by excreting what is absorbed by the intestine. The mechanisms whereby gut and renal calcium handling are correlated are uncertain.

Intravenous disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate (pamidronate disodium) was used to treat 39 patients (22 males and 17 females, age range 48–85 years) with symptomatic Paget's disease. Patients were stratified into three groups based on the biochemical severity of the disease as assessed by fasting urinary hydroxyproline excretion (HypE, μmol/liter GF, glomerular filtrate): group I (n = 23), HypE 10.0, 240 mg over 4 or 8 days. Bone mineral density (BMD) was measured before and 3 and 6 months following treatment in the spine (LI-4) using dual-energy x-ray absorptiometry and in the forearm at an ultradistal and a shaft site using single-photon absorptiometry. When groups I-III were combined, nonpagetic and pagetic lumbar spinal BMD had both risen significantly at 3 months compared with the pretreatment values (p < 0.001). In each group, lumbar spinal BMD in pagetic vertebrae rose markedly by 3 months, with no further significant change at 6 months. The percentage rises in the three groups were not different from each other at 3 or 6 months. Nonpagetic lumbar spinal BMD followed a similar and significant trend but with a significantly smaller rise than for pagetic bone. (For the combined groups, nonpagetic BMD rose 5.1 ± 1.1% SEM, above pretreatment at 6 months; pagetic BMD rose 17.8 ± 1.6%: significance of comparison = p < 0.0001). In contrast, forearm BMD in group III had fallen at 6 months by 8.3 ± 2.5% (p < 0.01) and 7.0 ± 1.2% (p < 0.001) in the ultradistal and shaft sites, respectively. There were no significant changes in forearm BMD in groups I and II. When groups I-III were combined, the maximum observed changes within each individual in ultradistal forearm BMD (seen posttreatment) were correlated inversely with maximum intraindividual changes (seen posttreatment) in intact parathyroid hormone (Spearman's Q = −0.53, p < 0.001). A group of 18 control subjects with untreated Paget's disease were studied for 3–6 months. No changes were seen in nonpagetic or pagetic lumbar spinal BMD or in forearm BMD. Three mechanisms are proposed to explain these findings: (1) in nonpagetic bone, persistence of bone formation following acute reduction in resorption, with a more marked effect in the axial than in the appendicular skeleton; (2) in pagetic bone, magnification of mechanism 1, caused by the presence of abnormally active osteoclasts, leading to a marked divergence between bone resorption and formation, and (3) in cancellous and cortical distal forearm bone, the onset of acute secondary hyperparathyroidism following treatment, leading to resorption. These findings have implications for treatment of Paget's disease using pamidronate or other bisphosphonates in patients with preexisting appendicular osteopenia, particularly if the treatment-induced appendicular deficit is sustained.

We have performed computer modelling of the relationship between bone mass, age and hip fracture in a conditional probability model using a notional population of 100 000 postmenopausal women aged 50 who have their bone density measured once. The computer model very closely reproduced the actual number of fractures in a Western Australian population. Intervention to bone loss completely in subjects with the lowest bone density (below 1 SD below the mean) would prevent 0.42 of a hip fracture per patient treated if the whole population were treated. Halving the rate of bone loss in the whole population would reduce hip fracture by two-thirds. These data suggest that hormone replacement therapy, which is the most effective therapy for preventing bone loss but which has the most side effects, should be focused on subjects with bone mass below 1 SD below the mean. The remainder of the population could be targeted with a public health campaign based on the lifestyle factors of increased dietary calcium and exercise which have been shown to slow but not stop bone loss.

Vertebral bone density of two human vertebral specimens was evaluated using dual-anergy X-ray absorptiometry and single-energy quantitative computed tomography immediately before and after 4 weeks of fixation. The repeated QCT assessment of these segments produced a mean rate of change of 1.17 HU/month, while for DXA the mean rate of change was -0.002 g/month for BMC and -0.0004 g/cm(2)/month for BMD. Ten fresh and 10 fixed sheep lumbar spines underwent absorptiometry before being sectioned into units comprising a central vertebra and adjacent intervertebral discs, plus 1 cm of the flanking vertebral end-plate for embedding into bone cement. The fixed sheep spines underwent a repeat scan after 4 weeks in 10% formalin. Mechanical testing produced a significantly lower average failure load for unfixed specimens (9.3 kN) than for the fixed material (10.8 kN). Failure strain was not significantly different between groups. Linear regression showed a high correlation of BMC values before and after 4 weeks of formalin fixation, while the slopes of the regression for BMD and failure load of both fresh and fixed groups were not significantly different. While formalin fixation may result in a slight increase in compressive strength this does not appear to be associated with a systematic change in mineral density.

The bone density of thoracolumbar vertebral columns (T1-L2) from 12 individuals having a mean age of 73 years was examined using quantitative computed tomography and dual energy X-ray absorptiometry. Spinal units, comprising three vertebrae, from different regions were then tested for compressive strength in a materials test device. Results showed segmental variations in trabecular and integral bone density of the vertebral bodies and their capacity for load bearing. Failure strength increased craniocaudally, whereas failure stress (load/cross-sectional area) decreased. Vertebral compressive strength was moderately correlated with bone mineral density as assessed with dual energy X-ray absorptiometry. In contrast, trabecular bone density determined from quantitative computed tomography was a poor predictor of compressive strength, as was bone mineral content. Use of an integral measure of bone density may provide a more practical guide to bone fragility.

Summary Intravenous 3-amino-l-hydroxypropylidene-1, 1-blsphosphonic acid (APD) was used to treat 26 patients with Paget's disease. Three daily dosages were studied; 20–30 mg/day in 20 patients, 45 mg/day in three patients and 60 mg/day in three patients, by daily 4-hour Infusions for 2–10 days. The fasting urinary hydroxyprollne excretion (Hype) declined exponentially, reaching 50% of pretreatment values at 1·92±0·16 (mean±SEM) days. This initial rapid decline was complete by 4 days following treatment to a mean of 28·0±3·4% of pretreatment values. Thereafter, there was no significant decline in Hype. The Initial rate of decline of Hype was unchanged by Increasing the daily dose of APD. Transient non-symptomatic hypocalcaemia with secondary hyperparathyroidism occurred In all patients. No adverse changes In the renal handling of calcium or phosphate, as seen with high-dose 1-hydroxyethylldene-1,1-bisphosphonate (EHDP), were seen in any patient on any daily dose. Fever occurred In 73% of patients in the first 2 days of treatment. Overall, there was a significant fall In the lymphocyte count (P> 0·005 febrile group, n=19; P> 0·02 non-febrile group, n=7) and a fever-dependent rise in the neutrophil count (P> 0·005 febrile group only). The occurrence of fever was associated with a more rapid decline in Hype, compared to the non-febrile group, so that Hype was significantly lower in the febrile group by day 5 (P > 0·025). Seventy-two per cent of patients with bone and/or joint pain reported a reduction in pain. APD therapy resulted in repair or arrest of progression of Pagetic lytlc bone lesions in those seven patients with measurable lesions. Quantitative histomorphometry was performed in eight patients. Significant Improvement was seen in all Indices. In the six patients for whom a post-treatment calcification rate could be deter-mined, there was no evidence of a mineralization defect. All patients with mild-moderate disease (Hype > 10 μmol/IGF) achieved normal Hype and alkaline phosphatase values following a single course of APD. Provided that pretreatment Hype was · 10 μmol/IGF, an upper limit for the total dose of APD required to achieve normalization of Hype could be estimated. For those patients with ‘severe’ disease (defined as Hype > 10 μmot/1 GF), a reduction of > 50% In Hype could be achieved readily, but biochemical normalization was not possible with a single course of up to 315 mg of APD.