Biomedical subjects

G M Blake

Publications and source records attributed to G M Blake.

At least 19 recordsLinked to original sources

PubMed2005

Predicting the risk of fracture at any site in the skeleton: are all bone mineral density measurement sites equally effective?

The ability to assess a patient's risk of fracture is fundamental to the clinical role of bone densitometry. Fracture discrimination is quantified by the relative risk (RR), defined as the increased risk of fracture for a 1 standard deviation decrease in bone mineral density (BMD). The larger the value of RR, the more effective measurements are at identifying patients at risk of fracture. Epidemiological studies show that RR values for predicting the risk of any fracture are approximately the same for all BMD measurement sites. In this study, we show theoretically that this interesting observation is predictable and a consequence of two related observations: (1) that fracture prediction by BMD measurement sites distant from the fracture site is quantitatively explained by the correlation of BMD measurements and (2) that all correlation coefficients between distant BMD sites are comparable, with values in the range r = 0.55-0.65. The first of these conditions (referred to as the correlation hypothesis) is important because it sets a lower limit on the RR values at distant BMD sites on the assumption that measurements at these sites contain no independent information about fracture risk over and above that provided by their correlation with the fracture site BMD. If the correlation hypothesis is true, the present study points to the importance of the correlation coefficient between BMD sites as a key index that is indicative of the ability of different types of measurement to predict fracture risk. If, on the contrary, the correlation hypothesis is not valid, there is scope to improve bone densitometry by further studies to better identify those measurements that do provide independent information about fracture risk and how best to integrate this information with existing techniques to improve decision making.

Absorptiometry, Photon↗

PubMed2005

A list of device-specific thresholds for the clinical interpretation of peripheral x-ray absorptiometry examinations.

The UK National Osteoporosis Society (NOS) has recently issued new guidelines on the use of peripheral x-ray absorptiometry (pDXA) devices in managing osteoporosis. The NOS guidelines recommend a triage approach in which patients' bone mineral density (BMD) measurements are interpreted using upper and lower thresholds specific to each type of pDXA device. The thresholds are defined so that patients with osteoporosis at the hip or spine are identified with 90% sensitivity and 90% specificity. Patients with a pDXA result below the lower threshold are likely to have osteoporosis at the hip or spine, patients with a result above the upper threshold are unlikely to have osteoporosis, while those between the two thresholds require a hip and spine BMD examination for a definitive diagnosis. This report presents data from a multicenter study to establish the triage thresholds for a range of pDXA devices in use in the UK. The subjects were white female patients aged 55-70 years who met the normal referral criteria for a BMD examination. For each device, at least 70 women with osteoporosis at the hip or spine and 70 women without osteoporosis were enrolled. All women had hip and spine BMD measurements using axial DXA systems that were interpreted using the National Health and Nutrition Examination Survey (NHANES) reference range for the hip and the manufacturers' reference ranges for the spine. Data are presented for five different devices: the Osteometer DTX-200 (forearm BMD), the Schick AccuDEXA (hand BMD), the GE Lunar PIXI (heel BMD), the Alara MetriScan (hand BMD), and the Demetech Calscan (heel BMD). The clinical measurements were supplemented by theoretical modeling to estimate the age dependence of the triage thresholds and the effect of the correlation coefficient between pDXA and axial BMD on the percentage of women referred for an axial BMD examination. In summary, this study provides thresholds for implementing the new NOS guidelines for managing osteoporosis using pDXA devices. The figures reported apply to postmenopausal white women aged 55-70 years who meet the conventional criteria for a BMD examination. The results confirm that the thresholds are specific to each type of pDXA device and that the NOS triage algorithm requires 40% of women to have an axial DXA examination.

Absorptiometry, Photon↗

PubMed2005

Fractal analysis of trabecular bone in knee osteoarthritis (OA) is a more sensitive marker of disease status than bone mineral density (BMD).

The purpose of this study was to determine whether fractal analysis (FSA) of macroradiographs or bone mineral density (BMD) is more sensitive in detecting disease-related cancellous bone alterations in knee osteoarthritis (OA). Differences in BMD between 11 OA (6 females) and 11 non-OA reference (7 females) tibiae were compared with differences in trabecular organization measured by computerized method of fractal signature analysis (FSA) of digitized macroradiographs (x3.5 to x5). OA knees had anatomic and radiographic evidence of medial compartment disease. FSA measured cancellous bone organization at 4 regions of interest (ROI): medial and lateral subchondral (Sc) and subarticular (Sa) sites, dual X-ray absorptiometry (DXA) measured BMD at the same ROIs. Compared to non-OA, OA tibiae had significant increased (P < 0.05) in FSA of vertical trabeculae in the medial Sa region (trabecular size range: 0.42-0.54; 0.90-1.98 mm) and significant decrease (P < 0.05) in FSA for some horizontal trabeculae in the Sc region (trabecular size range: medial side 0.12-0.18 mm; lateral side 0.12-0.24 mm). Compared to non-OA, BMD of OA tibiae was not significantly different at any ROI. BMD was not sensitive to changes in trabecular organization detected by FSA. The increase in FSA of vertical trabeculae in the medial Sa region was consistent with trabecular fenestration and thinning, which may have been detected as decreased BMD in a larger sample. For studies involving small sample sizes, quantifying changes in trabecular organization is more sensitive than BMD for detecting bone alterations in knee OA.

Absorptiometry, Photon↗

PubMed2005

Dual X-ray absorptiometry: clinical evaluation of a new cone-beam system.

The DMS Lexxos is the first cone-beam dual X-ray absorptiometry (DXA) system capable of performing bone mineral density (BMD) measurements of the spine and hip. By using a two-dimensional (2-D) detector array rather than the linear array used with conventional fan-beam DXA systems, image acquisition time on Lexxos is only 1.5 s. However, the need to correct for the large signal from scattered radiation reaching the detector is a potential source of error in cone-beam DXA. The aim of this clinical evaluation of the Lexxos bone densitometer was to investigate the relative accuracy of cone-beam BMD measurements compared with conventional DXA by performing an in vivo cross-calibration study with an established fan-beam system, the Hologic QDR-4500. Spine (L1-L4) and hip BMD measurements were performed in 135 patients (111 women, 24 men) referred for a bone densitometry examination. Duplicate Lexxos measurements were performed in 27 female patients to evaluate precision. On average, Lexxos spine and femoral neck BMD measurements were 2% lower than those on the QDR-4500, whereas total hip BMD was 5% higher. Larger differences were found for the trochanter and Ward's triangle regions. For all sites, Lexxos BMD measurements showed a strong linear relationship with those measured on the QDR-4500 with correlation coefficients in the range r = 0.95 to 0.97 for the clinically important spine, femoral neck, and total hip regions. The root mean standard error (RMSE) between Lexxos and QDR-4500 BMDs ranged from 0.037 g/cm(2) for the femoral neck to 0.060 g/cm(2) for the spine, whereas Lexxos precision was 1.3% for total hip, 2.0% for femoral neck, and 2.3% for spine BMD. Although for the hip BMD sites the RMSE and precision of Lexxos measurements were similar to studies of pencil-beam and fan-beam DXA systems, the results for the spine were poorer than expected. The findings of this study suggest that Lexxos corrects accurately for the effects of scattered radiation at the detector, but that the precision of spine BMD measurements may be limited by involuntary patient movement between the high and low energy X-ray exposures.

Absorptiometry, Photon↗

PubMed2004

Dual X-ray absorptiometry: cross-calibration of a new fan-beam system.

The high precision and stable calibration of dual X-ray absorptiometry (DXA) scanners have led to their widespread use in longitudinal studies for research and the follow-up of individual patients who are receiving treatment for osteoporosis. However, difficulties in maintaining the continuity of the bone mineral density (BMD) calibration scale can arise when an old DXA system is replaced by a newer model. We report the results of an in vivo cross-calibration study performed when a GE-Lunar Prodigy fan-beam system replaced a DPX-L pencil-beam scanner. Lumbar spine and hip DXA scans were performed in 133 patients (104 female, 29 male) attending long-term BMD monitoring. On average, lumbar spine BMD measurements on the two systems agreed closely, with Prodigy values 1% lower than those on the DPX-L. However, after allowing for this difference, the root mean square error (RMSE) of 0.037 g/cm2 was larger than in previous cross-calibration studies reported in the literature, and was 3 times the value expected from the precision of the BMD measurements. Mean femoral neck BMD also agreed closely between the two systems, although for Prodigy, the spread of measurements was 10% smaller than that for the DPX-L. For the trochanter and Ward's triangle regions, mean BMD was 4% and 6% lower, respectively, on the Prodigy system, and the results were affected by a similar compression of the range of values. RMSE values were 0.037 g/cm2, 0.044 g/cm2, and 0.044 g/cm2, respectively, for the femoral neck, trochanter, and Ward's triangle sites. When the high value of the RMSE was investigated, it was found that for lumbar spine BMD, patient body weight and the difference between the two systems in the percentage fat reported in the soft tissue reference region explained 40% of the variance. This enabled equations to be developed that significantly improved the agreement between scans performed on the two systems. Smaller improvements were obtained for the femur BMD measurements.

Absorptiometry, Photon↗

PubMed2004

Evaluation of the Cockroft-Gault, Jelliffe and Wright formulae in estimating renal function in elderly cancer patients.

BACKGROUND: More elderly patients are being treated with chemotherapy. Reliable and accurate measures of renal function are needed to obtain predictable, safe and effective exposure to renally excreted drugs. The Jelliffe, Cockroft-Gault and Wright formulae have been used to evaluate renal function, although they have not been validated in elderly oncology patients. We performed a retrospective evaluation of these formulae using the [51Cr]-ethylenediamine tetraacetic acid ([51Cr]-EDTA) method of measuring glomerular filtration rate (GFR) as the 'gold standard'. PATIENTS AND METHODS: Inclusion criteria were age > or = 70 years and serum creatinine <250 micromol/l, performed within 4 weeks of glomerular filtration rate (GFR) measurement. Creatinine clearance was calculated using the Cockroft-Gault, Jelliffe and Wright formulae. The precision and accuracy of the three formulae were compared with the gold standard. RESULTS: Two hundred and twenty-five patients were evaluated: median age, 74 years (range 70-89); males, 108; females, 117; median creatinine, 84 micromol/l (range 44-186). Correlation coefficients of the Jelliffe, Cockroft-Gault and Wright formulae were similar. In the specific GFR ranges of 50-70, 70-90 and 90-120 ml/min, the bias [mean percentage error (MPE)] was +8%, -4% and -13%, respectively. The degree of bias was greater with the Cockroft-Gault and Jelliffe formulae across the same range of GFR with the MPE being -15%, -25%, -32% and -12%, -19% and -23%, respectively. All three formulae have reduced precision and greater bias at the extremes of GFR. CONCLUSIONS: The Wright formula is the most accurate, precise and least biased formula for the calculation of GFR in elderly patients with a GFR >50 ml/min. These results allow the physician to make a decision regarding the use of the formula based on an expected degree of bias.

Aged↗

PubMed2004

16-detector multislice CT: dosimetry estimation by TLD measurement compared with Monte Carlo simulation.

Computer simulations are widely used to estimate effective doses from CT examinations. The raw data often used in their estimations were obtained some years ago and made certain assumptions regarding CT unit design. At that time multidetector CT units were unavailable. Changes in design will limit the accuracy of computer simulated dosimetry on these machines. We therefore estimated CT dose on a 16-detector unit directly using thermoluminescent dosemeters (TLDs) and an anthropomorphic phantom. We found that the dose measured directly was 18% higher than the computer simulated dosimetry, in keeping with the previously recognised underestimation by computer simulation techniques compared with TLD measurements.

Computer Simulation↗

PubMed2003

Can the WHO definition of osteoporosis be applied to multi-site axial transmission quantitative ultrasound?

Osteoporosis is a highly prevalent but preventable disease and, as such, it is important that there are appropriate diagnostic criteria to identify those at risk of low trauma fracture. In 1994 the World Health Organization (WHO) introduced definitions of osteoporosis and osteopenia using T-scores, which identified 30% of all Caucasian post-menopausal women as having osteoporosis. However, the use of the WHO T-score thresholds of -2.5 for osteoporosis and -1.0 for osteopenia may be inappropriate at skeletal sites other than the spine, hip and forearm or when other modalities, such as quantitative ultrasound (QUS) are used. The aim of this study was to evaluate the age-dependence of T-scores for speed of sound (SOS) measurements at the radius, tibia, phalanx and metatarsal by use of the Sunlight Omnisense, to evaluate the prevalence of osteoporosis and osteopenia at these sites by use of the WHO criteria, and calculate appropriate equivalent T-score thresholds. The study population consisted of 278 healthy pre-menopausal women, 194 healthy post-menopausal women and 115 women with atraumatic vertebral fractures. All women had SOS measurements at the radius, tibia, phalanx and metatarsal and bone mineral density (BMD) measurements at the lumbar spine and hip. A group of healthy pre-menopausal women aged 20-40 years from the pre-menopausal group were used to estimate the population mean and SD for each of the SOS and BMD measurement sites. Healthy post-menopausal women were classified into normal, osteopenic or osteoporotic, based upon the standard WHO definition of osteoporosis and expressed as a percentage. We investigated the age-related decline in T-scores from 20-79 by stratifying the healthy subjects into 10-year age groups and calculating the mean T-score for each of these groups. Finally, we estimated appropriate T-score thresholds, using five different approaches. The prevalence of osteoporosis in the post-menopausal women aged 50 years and over ranged from 1.4 to 12.7% for SOS and 1.3 to 5.2% for BMD. The age-related decline in T-scores ranged from -0.92 to -1.80 for SOS measurements in the 60 to 69-year age group and -0.60 to -1.19 for BMD measurements in the same age group. The WHO definition was not suitable for use with SOS measurements, and revised T-score thresholds for the diagnosis of osteoporosis of -2.6, -3.0, -3.0 and -2.2 and for osteopenia of -1.4, -1.6, -2.3, and -1.4, for the radius, tibia, phalanx and metatarsal, respectively, were recommended.

Adult↗

PubMed2003

Periprosthetic bone remodelling of two types of uncemented femoral implant with proximal hydroxyapatite coating: a 3-year follow-up study addressing the influence of prosthesis design and preoperative bone density on periprosthetic bone loss.

Periprosthetic bone loss is a major cause of concern in patients undergoing total hip arthroplasty (THA). Further studies are required to identify the factors determining the pattern of bone remodelling following THA and obtain improvements in the design and durability of prostheses. In this study, we monitored periprosthetic bone loss around two different types of hydroxyapatite coated femoral implant over a 3-year period to evaluate their design and investigate the relationship with the preoperative bone mineral density (BMD) at the spine, hip and forearm. Sixty patients (35 F, 25 M, mean age 63 years, range 46-75 years) undergoing THA were randomised to either the Anatomic Benoist Girard (ABG) or Mallory-Head (MH) femoral stem. Preoperative dual-energy X-ray absorptiometry (DXA) scans were acquired of the posteroanterior (PA) and lateral lumbar spine, the contralateral hip and the non-dominant forearm. Postoperative DXA scans were performed to measure periprosthetic BMD at 10 days (treated as baseline), 6 weeks, and 3, 6, 12, 24 and 36 months after THA using a standard Gruen zone analysis. Results were expressed as the percentage change from baseline and the data examined for the differences in bone loss between the different Gruen zones, between the ABG and MH stems, and the relationship with preoperative BMD. A total of 50 patients (24 ABG, 26 MH) completed the study. Three months after THA there was a statistically significant BMD decrease in every Gruen zone that varied between 5.6% and 13.8% for the ABG prosthesis and between 3.8% and 8.7% for the MH prosthesis. Subsequently, in most zones BMD reached a plateau or showed a small recovery. However, BMD continued to fall in Gruen zones 1 and 7 in ABG patients and Gruen zone 1 in MH patients. Bone loss was less in every Gruen zone in MH patients compared with ABG with the largest difference (10%, P=0.018) in Gruen zone 7. Highly significant relationships were found between periprosthetic bone loss and preoperative BMD measured at the PA spine ( P<0.001), total hip ( P=0.004) and total distal radius ( P<0.001). This study showed differences between two different designs of hydroxyapatite-coated implant that confirmed that prosthesis design influences periprosthetic bone loss. The study also showed that patients' bone density measured at the spine, hip or forearm at the time of operation was a major factor influencing bone loss around the femoral stem.

Absorptiometry, Photon↗

PubMed2003

Measurements of bone mineral density of the radius in a medieval population.

The current morbidity in the elderly as a result of osteoporotic fractures has led to interest in the incidence of this condition in past populations. The purpose of this study was to evaluate the technique of scanning of the distal radius with DXA in archaeological bone. The radius is often better preserved in archaeological contexts than bone with higher trabecular content such as the femoral neck or vertebrae. Adult radii (101) from the deserted medieval village site of Wharram Percy were scanned. These skeletal remains represent an homogenous rural population. The scanned individuals were divided into 3 age groups; 18-29, 30-49, and 50+. In both males and females bone loss was statistically significant in the highly trabecular ultra-distal region and the more cortical mid-region after age 50. Only females lost bone in the largely cortical one-third site before age 50. This is in accordance with modern clinical studies in which this loss is attributed to the effects of menopause. In order to assess whether there were differences in bone loss between weight and non-weight-bearing bones, the results were also compared with those from an earlier study of the femoral neck. In both sexes trabecular bone was lost at both anatomical sites after age 50. However, scanning the radius also had the advantage of assessing cortical bone loss. Additionally, despite demonstrable bone loss, there were no Colles or hip fractures in this paleopopulation, suggesting that although an active lifestyle such as that spent in agricultural activity, does not prevent bone loss, it may protect against osteoporotic fracture.

Absorptiometry, Photon↗

PubMed2003

Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF).

The purpose of this study was to compare changes in bone mineral density (BMD) in premenopausal patients with node-positive early breast cancer treated with goserelin (Zoladex) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients ( n=1640) were randomized to goserelin (3.6 mg every 28 days for 2 years) or CMF (sixx28-day cycles) treatment. In a protocoled sub-study involving 96 patients from eight centers (goserelin: n=53; CMF: n=43), lumbar spine (L2-L4) and femoral neck BMD were assessed by dual X-ray absorptiometry at baseline and then annually for 3 years. At the end of the 2-year goserelin-treatment period, mean BMD losses for goserelin-treated and CMF-treated patients were -10.5% and -6.5% ( P=0.0005) for lumbar spine and -6.4% and -4.5% ( P=0.04) for femoral neck, respectively. At 3 years, partial recovery of BMD was observed in goserelin recipients. In contrast, mean BMD losses for the CMF group indicated persistent BMD loss. No significant differences in BMD were observed between groups at the 3-year assessment of the spine or femoral neck. In the CMF group, based on amenorrhea status at 48 weeks, BMD losses at the lumbar spine were greater for amenorrheic than non-amenorrheic patients. Ovarian suppression resulting in amenorrhea was closely related to BMD loss in both treatment groups. Overall, patients who received CMF did not show recovery of BMD throughout follow-up, whereas partial recovery was observed 1 year after cessation of goserelin therapy, associated with the return of ovarian function in the majority of patients.

Adult↗

PubMed2003

Differential effects of hormone replacement therapy on bone mineral density and axial transmission ultrasound measurements in cortical bone.

The menopause has a large effect on bone density, and hormone replacement therapy (HRT) has been shown to be an effective treatment for preventing postmenopausal bone loss. The aim of this study was to compare the effects of HRT use on speed of sound (SOS) measurements at the radius, tibia, phalanx, and metatarsal with bone mineral density (BMD) measurements of the lumbar spine and proximal femur. The study population consisted of 278 healthy premenopausal women, 194 healthy postmenopausal women, and 126 healthy postmenopausal women currently receiving HRT for one or more years. SOS measurements were taken at the radius, tibia, phalanx, and metatarsal using the Sunlight Omnisense, and BMD measurements at the lumbar spine and proximal femur using Hologic QDR-4500 densitometers. Z-scores were calculated using the postmenopausal control group. Z-score differences between the postmenopausal controls and HRT group, for the entire group and with the HRT group subdivided into three groups based on duration of HRT usage, were calculated. Significant postmenopausal bone loss was found for all SOS and BMD measurements. A positive effect of HRT usage was found for all SOS measurement sites and lumbar spine BMD, although only the radius and tibia SOS and lumbar spine BMD reached statistical significance. The Z-score differences between the two groups were 0.44, 0.37, 0.15, and 0.26 for the radius, tibia, phalanx, and metatarsal SOS respectively, and 0.28, 0.00, and -0.03 for the lumbar spine, femoral neck, and total hip BMD respectively. A clear effect of the duration of HRT use was seen for the radius measurements, the differences being less marked elsewhere. In conclusion, these results demonstrate a positive effect of HRT on SOS measurements at the radius and tibia and BMD measurements of the lumbar spine.

Absorptiometry, Photon↗

PubMed2003

The non-steroidal antiandrogen, bicalutamide ('Casodex'), may preserve bone mineral density as compared with castration: results of a preliminary study.

The impact of bicalutamide (Casodex) monotherapy on bone mineral density (BMD) was investigated in patients with locally advanced prostate cancer. BMD was assessed after treatment with bicalutamide 150 mg daily ( n=21) or by medical castration (goserelin acetate 3.6 mg every 28 days) ( n=8) for a median of 287 weeks. In 38% of castration compared with 17% of bicalutamide patients, femoral neck Z-scores were < or =-1 SD of the reference value (accepted as a two to three times increased risk of fracture) and T-scores were < or =-2.5 SD (World Health Organization definition of osteoporosis in white females). Total hip Z-scores were < or =-1 in 43% of castration patients and 13% of bicalutamide patients. In 38% of patients, lumbar spine BMD was affected by degenerative disease. These preliminary data suggest that there may be an advantage in terms of BMD in using bicalutamide monotherapy compared with castration; a benefit confirmed in a recent prospective randomised study.

Aged↗

PubMed2003

A direct in vivo measurement of 99mTc-methylene diphosphonate protein binding.

Quantitative studies of the kinetics of 99mTc-methylene diphosphonate (99mTc-MDP) in metabolic and metastatic bone disease require the measurement of free tracer in plasma to derive the input function. We describe a simple method of determination of free 99mTc-MDP in vivo based on measurements of the ratio of the renal plasma clearances of total 99mTc-MDP and 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA). The method is based on evidence that free MDP is cleared through the kidneys by glomerular filtration. Measurements of the fraction of free 99mTc-MDP were made between 0 and 4 h after injection in 70 postmenopausal women enrolled in a study of the effect of hormone replacement therapy on the whole-skeleton plasma clearance of 99mTc-MDP (K(bone)). The glomerular filtration rate (GFR) was measured simultaneously from the plasma clearance of 51Cr-EDTA. The mean fractions (and SD) of free MDP measured were 0.757 (0.050), 0.663 (0.062), 0.550 (0.052) and 0.472 (0.053), respectively, at 17, 90, 150 and 210 min after injection. The results agreed closely with data using protein precipitation with trichloroacetic acid. Between 2 and 4 h after injection, the biological half-life of free 99mTc-MDP in plasma was 92 min, compared with 540 min for bound MDP. Highly significant relationships were found between the fraction of free MDP measured in each patient at each of the four time points and the total plasma clearance of free 99mTc-MDP (K(total)=GFR+K(bone)), such that a larger value of K(total) was associated with a smaller fraction of free MDP. Multivariate regression analysis confirmed that this relationship held individually for both GFR and K(bone). A strong inverse relationship was found between K(total) and the plasma concentration of free 99mTc-MDP, but a much weaker relationship with the bound MDP concentration, a finding that is consistent with the slow re-equilibration of bound MDP in the circulation. The results confirm that the fraction of free 99mTc-MDP varies with time and shows significant differences between individuals, which are dependent on GFR and K(bone) amongst other factors.

Aged↗

PubMed2002

A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual X-ray absorptiometry in women with a history of fracture at sites other than the spine and hip.

The aim of this study was to determine whether calcaneal quantitative ultrasound can discriminate between women with and those without fragility fracture at (1) the wrist or (2) at sites other than the spine, hip, or forearm, as well as axial DXA measurements of BMD can. The study population consisted of 342 postmenopausal Caucasian women who were placed into one of three groups: (1) healthy women with no clinical risk factors for osteoporosis (n = 240); (2) women with a history of atraumatic fracture at the wrist (n = 50); (3) women with a history of atraumatic fracture at a skeletal site other than the spine, hip, or wrist (n = 52). Subjects had DXA measurements of the lumbar spine (LS), femoral neck (FN), and total hip (THIP), and calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements on the Hologic Sahara (s) and Osteometer DTUone (d). Z-scores were calculated using the mean and SD obtained from the healthy postmenopausal group. All the BMD and QUS variables were significantly reduced in women reporting a fracture of the wrist or at a site other than the spine, hip, or forearm. When the group of women with a history of wrist fracture were compared with the postmenopausal controls, age-adjusted logistic regression yielded odds ratios associated with a 1 SD decrease, that were significant for both BMD and QUS, averaging 2.2. The AUC values ranged from 0.65 for FN BMD to 0.75 for BUAd. BMD and QUS measurements were also significantly reduced in women reporting a skeletal fracture at a site other than the spine, hip, or wrist, and odds ratios for BMD and QUS were significant, averaging 1.7. BMD and QUS showed similar fracture discriminatory abilities that were not significantly different from one another. In conclusion, calcaneal QUS can discriminate between women with and those without fracture at the wrist or at sites other than the spine, hip, or forearm as well as axial DXA measurements of BMD can.

Absorptiometry, Photon↗

PubMed2002

COLIA1 Sp1 polymorphism predicts response of femoral neck bone density to cyclical etidronate therapy.

Genetic factors are important in the pathogenesis of osteoporosis but less is known about their possible role in predicting response to anti-osteoporotic therapy. Previous studies have shown that a polymorphic Sp1 binding site in the collagen type 1 alpha 1 gene (COLIA1) is associated with bone mineral density (BMD) and osteoporotic vertebral fracture. In this study we sought to determine if the COLIA1 Sp1 polymorphism might also act as a predictor of the response to treatment of osteoporosis with bisphosphonate therapy. The study group comprised 108 perimenopausal women with osteopenia who had been randomized to receive cyclical etidronate therapy for 2 years with a 1-year treatment-free follow-up as part of a randomized placebo controlled trial. Bone mineral density was measured at the lumbar spine and femoral neck by dual X-ray absorptiometry and genotyping performed on DNA extracted from peripheral blood leukocytes using standard techniques. The distribution of COLIA1 genotypes was similar to that previously reported in Caucasians with 69 (63.9%) "SS" homozygotes, 38 (35.2%) "Ss" heterozygotes, and 1 (0.9%) "ss" homozygote. There was no association between COLIA1 genotype and response of lumbar spine BMD during etidronate treatment or the follow-up phase. The response of femoral neck (FN) BMD, however, differed significantly between the genotype groups throughout the study period, such that FN BMD increased by 0.56%, 2.36%, 1.82%, and 1.32 % after 1, 2, 2.5, and 3 years, respectively in the "SS" genotype group, compared with -1.56%, -0.62%, -0.37%, and -0.66% in the "Ss/ss" genotype groups (P = 0.002). The data presented here show that site-specific heterogeneity exists in the response of BMD to cyclical etidronate therapy, which is related to COLIA1 genotype. Our data raise the possibility that COLIA1 genotyping could be used to target etidronate therapy to those most likely to respond in terms of FN BMD, with potential benefits in terms of economic cost and clinical outcome.

Absorptiometry, Photon↗

PubMed2002

Multisite quantitative ultrasound: Colles' fracture discrimination in postmenopausal women.

Distal forearm fractures are the most common perimenopausal fracture and are generally associated with osteoporosis. The aim of this study was to evaluate the capability of speed of sound (SOS) measurements in cortical bone at the phalanx, radius, tibia and metatarsal to discriminate Colles' fracture cases from controls in postmenopausal women and to compare this with bone mineral density (BMD) measurements obtained by dual-energy X-ray absorptiometry (DXA). Sixty-three postmenopausal Colles' fracture cases and 191 postmenopausal controls had SOS measurements of the radius, tibia, phalanx and metatarsal using a semi-reflection ultrasound technique and BMD measurements of the lumbar spine and proximal femur using DXA. The age-adjusted odds ratios (ORs) for fracture for the SOS measurement sites were 1.50 [95% CI 1.07-2.10] for the radius, 1.23 [0.86-1.76] for the tibia, 1.85 [1.06-3.23] for the phalanx and 1.74 [1.12-2.71] for the metatarsal site. For the BMD measurements the ORs were 1.95 [1.34-2.85] for the lumbar spine, 2.21 [1.43-3.40] for the femoral neck and 2.62 [1.69-4.08] for the total hip. The benefits of combining sites either by taking their average Z-score or by using the manufacturer's ORI algorithm were evaluated. The two methods yielded similar results and the ORs for the combination of the radius and phalanx were 2.00 [1.21-3.33], for the radius and metatarsal 1.67 [1.05-2.67], for the phalanx and metatarsal 1.86 [1.11-3.08] and for the radius, phalanx and metatarsal 1.81 [1.07-3.06]. Combinations of DXA sites gave 2.22 [1.44-3.41] for the lumbar spine and femoral neck and 2.41 [1.57-3.70] for the lumbar spine and total hip. In conclusion, semi-reflection ultrasound measurements at the radius, phalanx or metatarsal demonstrated an ability to discriminate fracture cases from controls in postmenopausal Colles' fracture patients, although the odds ratios were lower than with spine and femur BMD.

Absorptiometry, Photon↗

PubMed2002

Quantification of skeletal kinetic indices in Paget's disease using dynamic 18F-fluoride positron emission tomography.

The purpose of this study was to quantify indices of regional bone metabolism in Paget's disease and to compare these indices with normal bone using dynamic 18F-fluoride positron emission tomography (PET). Seven patients with vertebral Paget's disease had 1 h dynamic 18F-fluoride PET scans performed. The scans included a diseased vertebra and an adjacent normal vertebra. Arterial plasma input functions were also measured. A three-compartment, four-parameter model was used with nonlinear regression analysis to estimate bone kinetic variables. Compared with normal bone, pagetic bone demonstrated higher values of plasma clearance to bone mineral (Ki; 1.03 x 10(-1) vs. 0.36 x 10(-1) ml/min per milliliter; p = 0.018) and clearance to total bone tissue (K1; 2.38 x 10(-1) vs. 1.25 x 10(-1) ml/min per milliliter; p = 0.018), reflecting increased mineralization and blood flow, respectively. Release of 18F-fluoride from bone mineral (k4) was lower in pagetic bone (p = 0.022), suggesting tighter binding of 18F-fluoride to bone mineral. The notional volume of the extravascular bone compartment (K1/k2) was greater in pagetic bone (p = 0.018). Although the unidirectional extraction efficiency from the extravascular space to bone mineral (Ki/K1) was greater in pagetic bone (p = 0.018), a lower pagetic value of k2 (p = 0.028), describing the rate of transfer from the bone extravascular compartment to plasma, suggests that the 18F-fluoride that enters the relatively fibrotic marrow space of pagetic bone may be less accessible for return to plasma. These findings confirm some of the known pathophysiology of Paget's disease, introduce some new observations, and show how dynamic 18F-fluoride PET may be of value in the measurement of regional metabolic parameters in focal bone disorders.

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