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Glen M Blake

Publications and source records attributed to Glen M Blake.

At least 19 recordsLinked to original sources
PubMed2006

Theoretical model for the interpretation of BMD scans in patients stopping strontium ranelate treatment.

UNLABELLED: Strontium ranelate is a new treatment for osteoporosis that results in large increases in BMD, much of which is an artefact caused by high bone strontium content. We used clinical trial data and a model of long-term strontium kinetics to estimate the effect of past strontium treatment on future BMD measurements. INTRODUCTION: The oral administration of strontium ranelate causes a clinically significant overestimation of BMD because of the high attenuation of X-rays by strontium atoms in bone. As more patients are treated with strontium ranelate, questions will arise about the correct interpretation of their future BMD measurements. We performed a theoretical study to calculate the long-term effect of strontium treatment on BMD and establish the duration of past treatment for which the remaining bone strontium content (BSC) has a negligible effect on BMD. MATERIALS AND METHODS: The BMD changes measured at the spine and hip during strontium ranelate treatment were interpolated from clinical trial data. The long-term retention of strontium in bone was estimated using the International Commission on Radiological Protection (ICRP) strontium retention function modified for use in postmenopausal women. Estimates of the strontium BMD artefact after treatment has stopped were performed on the assumption that the BSC effect accounts for 75% of the total measured BMD change at 3 years. RESULTS: If 75% of the BMD changes are explained by BSC, in the average patient, 3-year treatment leads to a spine BMD artefact of 11.2%, decreasing to 3.8% 10 years after stopping treatment. The BMD artefacts at the total hip and femoral neck sites are smaller by factors of 0.65 and 0.53, respectively. If pre- and post-therapy BMD measurements are available, these predictions can be tailored to the individual patient. On average, 6-month treatment is required for the spine BMD artefact to exceed 3%, the figure adopted as the maximum BMD change caused by bone strontium that has a negligible effect on scan interpretation. Ten years after stopping treatment, 28 months of treatment are required for the residual BMD artefact to still exceed the 3% threshold. CONCLUSIONS: Strontium ranelate treatment lasting for >6 months can affect BMD measurements for many years afterward.

Bone Density↗
PubMed2006

Validation of a blood-sampling method for the measurement of 99mTc-methylene diphosphonate skeletal plasma clearance.

UNLABELLED: Quantitative studies of bone using (99m)Tc-methylene diphosphonate (MDP) reflect bone remodeling. The simplest method of evaluating (99m)Tc-MDP kinetics involves taking multiple blood samples and measuring total clearance (K(total)) from the area under the plasma curve (AUC) and deriving bone clearance (K(bone)) by subtracting glomerular filtration rate (GFR) from K(total). However, the accuracy of the AUC method is uncertain because of assumptions that the terminal exponential is reached by 2 h and that the rate constant k(4), representing the backflow of tracer from bone to plasma, is negligibly small. The aim of this study was to validate the accuracy of the AUC method by comparing K(bone) values obtained by that method with those obtained by gamma-camera imaging. METHODS: Seventy-one patients were injected with 600 MBq of (99m)Tc-MDP. For the first 22 patients, whole-body images were acquired at 15 min and at 1, 2, 3, and 4 h after injection, whereas the remaining 49 were imaged at 15 min and at 1 and 3 h. Two-minute static images of the thighs were acquired immediately before each whole-body scan. Multiple blood samples were taken between 5 min and 4 h, and free (99m)Tc-MDP was measured using ultrafiltration. Two gamma-camera methods were used to evaluate K(bone): the Patlak plot method and the Brenner method, which is based on measuring soft-tissue uptake in the thighs. The soft-tissue data were also used to measure k(4). RESULTS: The soft-tissue data gave a k(4) value of 0.0003 min(-1) (95% confidence interval, 0-0.0008 min(-1)). The mean (+/-SD) (99m)Tc-MDP K(bone) was 56.0 +/- 32.4 mL x min(-1) with the AUC method, 49.5 +/- 32.1 mL x min(-1) with the Patlak method, and 42.8 +/- 32.0 mL x min(-1) with the Brenner method. Correcting the AUC values of K(total) by factors of 0.95 and 0.90 gave K(bone) values in agreement with the Patlak and Brenner methods, respectively. CONCLUSION: Values of k(4) are too small to affect values of K(bone) measured using the AUC method. Correcting K(total) by factors in the range of 0.90-0.95 corrects for the error in the terminal exponential and brings K(bone) values measured using the AUC method into agreement with the gamma-camera results.

Adult↗
PubMed2005

Comparison of effective dose to children and adults from dual X-ray absorptiometry examinations.

Dual X-ray absorptiometry (DXA) is increasingly used to measure bone density in children. If the system software does not include pediatric scan modes, then child examinations must be performed using adult scan modes that give a higher radiation dose to children than adults. This report describes a study to compare the effective dose to children and adults from DXA scans performed on the Hologic Discovery and QDR4500 models. Depth dose measurements were made using thermoluminescent dosimeters in a Rando phantom and were mapped onto the Cristy mathematical phantoms representing a 5-, 10- and 15-year-old child and an adult, and effective dose (ED) was calculated using the ICRP Publication-60 tissue weighting factors. The ED for spine (hip) examinations performed with the Express mode using the default adult scan lengths were 16.1 (9.8), 11.1 (6.7), 5.6 (3.9) and 4.4 (3.1) microSv for a 5-, 10- and 15-year-old child and adult respectively. However, if care is taken to adjust scan lengths appropriately, the child doses were reduced to 9.1 (7.4), 7.1 (5.9) and 5.0 (3.7) microSv. ED figures for the Fast and Array modes were larger by factors of 1.5 and 3 respectively. EDs for whole body scans for a 5-, 10- and 15-year-old child and adult performed on the A-model (W-model) were 5.2 (10.5), 4.8 (9.6), 4.2 (8.4) and 4.2 (8.4) microSv. Using the infant whole body mode (only available on the A-model), they were 7.5 microSv for a 1-year-old and 8.9 microSv for a neonate. Although doses from child DXA examinations are low, it is still important to keep them as small as possible. DXA operators using Discovery systems can do this by using the Express scan mode, by setting appropriate values of the scan length before scan acquisition and by avoiding mistakes that lead to scans having to be unnecessarily repeated.

Absorptiometry, Photon↗
PubMed2005

Fracture prediction by bone density measurements at sites other than the fracture site: the contribution of BMD correlation.

It is widely believed that the most reliable BMD measurement for predicting fracture risk at any given skeletal site is one made at the fracture site itself. This study examines the hypothesis that the ability of BMD measurements at other distant sites in the skeleton remote from the fracture site to predict fracture risk is due to their correlation with the BMD measurements at the fracture site. We refer to this assumption as the correlation hypothesis. We show that the correlation hypothesis predicts the relationship betadist = rbetafrac, where beta is the gradient of the exponential relationship between fracture risk and Z-score, betafrac is the beta-value for the fracture site, betadist the beta-value for the distant BMD site, and r is the correlation coefficient between the Z-scores at the two sites. In practice it is important to consider the effect of BMD measurement errors on the (r, beta) relationship. We show that the effect of errors at the distant site is to reduce betadist and r in a way that preserves their original relationship. When errors at the fracture site are taken into account the effect on the (r, beta) plot is for the point representing the fracture site to fall below the extrapolation of the straight-line relationship predicted for the points representing the distant BMD sites. We tested the correlation hypothesis by using data from the Study of Osteoporotic Fractures to examine the (r, beta) plots for hip, spine and forearm fractures. For the hip the data are consistent with a straight-line relationship and suggest that measurements made at other sites provide no additional information about fracture risk over and above that provided by hip BMD itself. For spine and forearm fractures the data show that distant sites do provide additional information about fracture risk in a way that is quantitatively consistent with the BMD measurement errors reported in cadaver studies. It is clear that random BMD errors at the fracture site cause loss of information about fracture risk and that some of this lost information is recoverable from measurements made at other sites in the skeleton. Overall, this study points to BMD correlation as an important factor in explaining the ability of measurements made at distant sites to predict fracture risk.

Absorptiometry, Photon↗
PubMed2005

Reference data for 51Cr-EDTA measurements of the glomerular filtration rate derived from live kidney donors.

BACKGROUND AND AIM: 51Cr-Ethylenediaminetetraacetic acid (51Cr-EDTA) is widely used to measure the glomerular filtration rate (GFR) for the assessment of renal function. The aims of this study were to assess the dependence of GFR on age and gender and to produce reference data for the interpretation of 51Cr-EDTA GFR measurements in adults. METHODS: This was a retrospective study of 428 subjects (218 females, 210 males; age range, 19-72 years) undergoing assessment as live kidney donors. GFR was evaluated from 51Cr-EDTA plasma clearance using blood samples taken at 2, 3 and 4 h. The slope-intercept GFR was corrected for body surface area using the Haycock formula and for the fast exponential using the Brochner-Mortensen equation. The data were analysed for the dependence on age and gender using multivariate regression analysis. Precision was evaluated from duplicate measurements in 22 subjects. RESULTS: For 187 subjects, aged 19-40 years, the dependence of GFR on age was not statistically significant (P = 0.51). The mean GFR was 103.4 ml x min(-1) x (1.73 m2)(-1) with a root mean standard error (RMSE) of 15.5 ml x min(-1) x (1.73 m2)(-1). GFR was 1.3 ml x min(-1) x (1.73 m2)(-1) higher in men than in women, although the difference was not significant (P = 0.56). In 241 subjects, aged 40-73 years, GFR decreased by 0.91 ml x min(-1) x (1.73 m2)(-1) per year [standard error, 0.06 ml x min(-1) x (1.73 m2)(-1) per year] with an RMSE of 13.6 ml x min(-1) x (1.73 m2)(-1). Over both age groups GFR was 0.4 ml x min(-1) x (1.73 m2)(-1) higher in men than in women [P=0.80; 95% confidence interval, -2.4 to +3.1 ml x min(-1) x (1.73 m2)(-1)]. For the 22 subjects with duplicate measurements, the root mean square coefficient of variation was 10.4%. CONCLUSIONS: A model for the decline of GFR with age was produced in which GFR remains constant at 103.4 ml x min(-1) x (1.73 m2)(-1) until the age of 40 years and then declines at a rate of 9.1 ml x min(-1) x (1.73 m2)(-1) per decade. The data can be used to report the results of adult 51Cr-EDTA GFR investigations.

Adult↗
PubMed2005

An evaluation of the body surface area correction for 51Cr-EDTA measurements of glomerular filtration rate.

BACKGROUND: To interpret 51Cr-EDTA measurements of glomerular filtration rate (GFR) it is usual to correct results for a patient's body size by scaling values to a standard body surface area (BSA) of 1.73 m(2). AIM: To use 51Cr-EDTA data for a large group of healthy subjects to derive the optimum mathematical function for the body size correction that minimized the variance of the corrected GFR values. This function was then compared with the widely used Du Bois and Haycock BSA formulas to determine which of these two equations provided the better correction. METHODS: GFR data for 428 healthy adults (218 female, 210 male) undergoing assessment as live kidney donors were evaluated. The body size correction was assumed to scale as the product of power laws of body mass index (BMI = weight/height(2)) and height. The corrected GFR figures were fitted to a model in which GFR was constant in subjects below 40 years of age and decreased linearly with age in older subjects. The scatter about the best fitting model was expressed as a percentage of the mean GFR in the younger group and the optimum power law indices derived from a least-squares fit were compared with the values for the Du Bois and Haycock formulas. RESULTS: The least-squares fit gave values of 0.444 (95% CI, 0.297-0.590) for the BMI power law index and 1.416 (95% CI, 1.027-1.802) for the height index with a 95% confidence error figure that included the points representing both the-Du Bois ([delta][chi]2 = 1.161, P = 0.560) and Haycock ([delta][chi]2 = 2.524, P = 0.283) formulas. For subjects of average height and a BMI in the middle of the normal range the Du Bois and Haycock equations agreed closely. Differences in BMI were found to explain 89% of the variance in the BSA estimates between the two formulas. Compared with the Du Bois formula the Haycock equation gave a 5% increase in corrected GFR in subjects with a BMI of 15 kg x m(-2) and a 10% decrease in subjects with a BMI of 40 kg x m(-2). CONCLUSION: Within the statistical errors both the Du Bois and Haycock BSA formulas were consistent with the optimum power law function that minimized the variance of the corrected GFR values for a group of 428 healthy adults.

Adult↗
PubMed2005

Reference ranges for 51Cr-EDTA measurements of glomerular filtration rate in children.

BACKGROUND: 51Cr-Ethylenediaminetetraacetic acid (51Cr-EDTA) is widely used to measure the glomerular filtration rate (GFR) in children and adults. AIM: To produce paediatric reference data for use with the British Nuclear Medicine Society (BNMS) GFR guidelines. METHODS: This was a retrospective study of children and adolescents, aged 0-17 years, undergoing combined 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scintigraphy and GFR examination. GFR was evaluated from Cr-EDTA plasma clearance using blood samples taken at 2, 3 and 4 h according to the methods set out in the BNMS GFR guidelines. 99mTc-DMSA images were reviewed to identify children with normal scans. RESULTS: Of the 45 children having a combined 99mTc-DMSA and GFR investigation, 27 (12 females, 15 males) had a normal scan result. The mean GFR (standard deviation) in the 24 subjects aged 2-17 years was 109.5 (16.8) ml . min(-1) . (1.73 m2)(-1). This compared with a predicted figure of 107.0 (17.0) ml . min(-1) . (1.73 m2)(-1) when the paediatric reference range published by Piepsz et al. was adjusted to be consistent with the BNMS GFR guidelines. When the GFR results in the present study were calculated according to the single-sample and two-sample methods used by Piepsz et al., there was close agreement with the results obtained in the latter study [116.7 (24.2) vs. 114.7 (25.8) ml . min(-1) . (1.73 m2)(-1)]. Children with abnormal 99mTc-DMSA scans had significantly lower GFR than those with normal scans (P=0.003). CONCLUSION: There is a consistent difference between the GFR results in children with normal 99mTc-DMSA scans obtained in the present study and the unadjusted results of Piepsz et al. that can be explained by the different methods of calculating GFR in the two studies. Given the larger number of children in the latter study, it is proposed that centres evaluating GFR according to the BNMS method should adopt the Piepsz et al. reference range adjusted for consistency with the BNMS guidelines. This gives a mean GFR (SD) in children of 2 years and over of 107 (17) ml . min(-1) . (1.73 m2)(-1).

Adolescent↗
PubMed2004

Dissociation between global markers of bone formation and direct measurement of spinal bone formation in osteoporosis.

UNLABELLED: Regional bone metabolism measured using 18F-fluoride PET was assessed in 72 postmenopausal women classified as normal, osteopenic, or osteoporotic. Lower values of regional bone formation activity at the lumbar spine were seen in osteoporotic women, whereas global markers of bone formation were significantly increased. INTRODUCTION: Evaluations of global bone remodeling have revealed that increased bone turnover is a feature of patients with osteoporosis. The noninvasive functional imaging technique of 18F-fluoride positron emission tomography (PET) allows the direct quantitative assessment of bone metabolism at specific sites in the skeleton, including the clinically important site of the lumbar spine. MATERIALS AND METHODS: The aim of this study was to compare regional skeletal kinetics in 72 postmenopausal women (mean age, 61 years) classified as normal, osteopenic, or osteoporotic according to their BMD T score at the lumbar spine. Each woman had a dynamic PET scan of the lumbar spine after injection of 90 MBq 18F-fluoride ion and measurements of biochemical markers of bone formation and resorption. The arterial plasma input function was derived using aorta arterial activity from the PET image. Time-activity curves were obtained by placing regions of interest over the lumbar vertebrae. A three-compartmental model was used to calculate bone blood flow (K1) and the net plasma clearance of tracer to bone mineral (Ki), reflecting regional osteoblastic activity (ml/minutes/ml). Rate constants k2, k3, and k4, which describe transport between plasma, the extracellular fluid (ECF) compartment, and the bone mineral compartment, were also measured. RESULTS: The net uptake of fluoride to the bone mineral compartment (Ki) was significantly lower in the osteoporotic group compared with both the osteopenic and normal groups, with a mean difference of 0.005 ml/minutes/ml (16.7%). The fraction of the tracer in the extravascular tissue space that underwent specific binding to bone mineral (k3/k2 + k3) was also significantly reduced in the women classified as osteoporotic. In contrast, levels of bone-specific alkaline phosphatase (BSALP) were significantly higher in the osteoporotic group compared with the normal and osteopenic groups by 35% and 27%, respectively. A significant negative correlation (r = -0.41) was observed between levels of BSALP and the fraction of the tracer that underwent specific binding to bone mineral. CONCLUSION: Lower values of Ki, a measurement of regional bone formation activity, were seen in women classified as osteoporotic, whereas levels of BSALP, a measure of global bone formation, were significantly increased. These findings are suggestive of increased global skeletal bone turnover in women with postmenopausal osteoporosis but with relatively reduced regional bone formation at the predominantly trabecular site of the lumbar spine.

Absorptiometry, Photon↗
PubMed2004

An evaluation of the United Kingdom National Osteoporosis Society position statement on the use of peripheral dual-energy X-ray absorptiometry.

A recent position statement issued by the UK National Osteoporosis Society recommends a triage approach to the use of peripheral dual-energy X-ray absorptiometry (pDXA) devices. Patients with a forearm T-score greater than -1 or less than -2.5 are regarded as normal or osteoporotic, respectively, while those with a T-score between -1 and -2.5 are sent for further assessment with spine and hip DXA. We have evaluated the NOS pDXA algorithm by comparing it with the alternative strategies of relying on forearm BMD alone, or performing spine and hip DXA in every patient. The evaluation was carried out using a mathematical model, and the predictions were compared with in vivo data obtained in patients referred for investigation by their general practitioner. In the model the population distribution of spine, hip, and forearm BMD was described by a trivariant Gaussian function. Relative risks of fracture were taken from a meta-analysis. The three strategies were compared using receiver operating characteristic (ROC) curves in which the percentage of future fracture cases identified was plotted against the percentage of the whole population found to have osteoporosis. ROC curves plotted for the discrimination of hip, vertebral, and Colles fracture risk and the risk of a fracture at any skeletal site were similar for all three strategies, with the curves for the NOS pDXA algorithm nearly identical to those for spine and hip DXA. For the case of hip fracture, vertebral fracture, or a fracture at any site, forearm BMD was slightly inferior to the NOS algorithm, but the reverse was true for Colles fracture. The small difference between the ROC curves suggests that forearm BMD used alone can reproduce clinical decision-making with the NOS pDXA algorithm provided that a T-score threshold of T=-2.1 is used for the diagnosis of osteoporosis, instead of the conventional figure of T=-2.5. Results from the in vivo study were in good agreement with the predictions of the model, although some differences were observed that were explained by inaccuracies in the forearm reference data. We conclude that use of forearm BMD alone with a modified T-score threshold of -2.1 would save the need for spine and hip DXA scans and identify only slightly fewer fracture cases for treatment.

Absorptiometry, Photon↗
PubMed2003

Effects of dietary improvement on bone metabolism in elderly underweight women with osteoporosis: a randomised controlled trial.

Malnutrition in elderly people contributes to osteoporosis and fracture. The aim of the study was to investigate the effects of nutritional improvement on bone metabolism in elderly community-dwelling women. A 12-month randomized controlled trial of 71 ambulant women aged > or =70 years with BMI < or =21 kg/m(2 )and osteoporosis at the hip was undertaken. They received either calcium (1 g) and vitamin D (800 units of cholecalciferol) only (group 1: n=35) or calcium/vitamin D and one or two cartons of a nutritional supplement drink which provided 300 Kcal, 12 g protein, 11.6 g fat and 36.8 g carbohydrate per carton (group 2: n=36). Body composition and bone mineral density (BMD) were assessed at baseline and 12 months. Biochemical markers of bone turnover were measured at baseline and at 1, 3, 6, 9 and 12 months. Group 2 gained significantly more weight [mean (SD) group 1: 0.15 (2.45), group 2:2.66 (2.8) kg P<0.001] and fat mass [group 1: -0.26 (1.8), group 2:1.9 (1.7) kg P<0.001]. BMD at the spine, femoral neck and total hip did not change significantly, although there was a positive trend at the total hip in group 2 [group 1: -0.5 (5.2), group 2:1.25 (3.3)%, P=0.13]. In a subgroup analysis, irrespective of their treatment group, there was a significant difference in changes in BMD at the lumbar spine and total hip in those who lost body weight (A) compared to those who had maintained or increased their weight (B), [mean (SD) % change in BMD lumbar spine; A: -1.64 (3.75), B: 0.96 (2.75) P=0.013, total hip A: -2.09 (6.0), B: 1.04 (3.3), P=0.05)] A significant reduction in serum CTX, a marker of bone resorption, was seen in group 2 [% decrease at 3 months, group 1: 1 (8.7), Group 2: 32 (5.8), P<0.01]. Serum osteoprotegerin (OPG) increased significantly in group 2 with a maximal increase (27%) observed at 6 ( P<0.01) and 9 months ( P<0.05). A small increase in bone-specific alkaline phosphatase was seen at 12 months in group 2 [% increase group 1:5 (5), group 2: 17 (6), P=0.05]. Serum osteocalcin increased at 12 months in group 2 ( P=0.01). Dietary improvement in elderly women with low BMI is associated with a reduction in bone resorption with a small but "net" positive effect on bone formation.

Aged↗
PubMed2003

DXA scanning and its interpretation in osteoporosis.

The recent growth in the clinical use of bone densitometry began with the introduction of the first dual X-ray absorptiometry (DXA) scanning systems in the late 1980s. Today, scans to measure bone mineral density are seen as having an essential role in the evaluation of patients at risk of osteoporosis.

Absorptiometry, Photon↗
PubMed2003

Does the combination of two BMD measurements improve fracture discrimination?

UNLABELLED: Combining information from different types of BMD measurement should improve the evaluation of patients' risk of fracture. This study used a bivariate gaussian model to examine the effect of combining two different BMD measurements. The results show that, in practice, there is little benefit unless the measurements are completely unrelated. INTRODUCTION: Intuitively, the combination of information from two or more different types of bone densitometry investigation should improve our ability to identify patients at high risk of fracture. However, the best way to combine measurements and the resulting gain in fracture discrimination are not known. MATERIALS AND METHODS: In this study, we used a bivariate gaussian model to investigate the effect of combining two different types of bone densitometry measurements. The measurements had individual relative risk values RR1 and RR2 and a correlation coefficient r between their Z-scores. Different approaches to the combination of the two measurements were compared by calculating the area under the curve (AUC) for the receiver operating characteristic (ROC) curve, which was obtained by plotting the percentage of fracture patients against the percentage of the whole population with a Z-score below some chosen threshold. ROC curves were calculated for three cases: (1) one type of measurement only; (2) two different types of measurements combined using their mean Z-score weighted according to the theoretical optimum weighting factors predicted by the bivariate gaussian model; and (3) two different types of measurements combined using the conventional World Health Organization (WHO) approach, where one or other measurement is below a set threshold. The theoretical model was tested using measurements of speed of sound (SOS) in the radius, phalanx, and metatarsal in patients with vertebral and Colles' fractures. RESULTS: Results were calculated for RR values of 1.5, 2.0, and 2.5 and r = 0, 0.5, and 0.7. Although a significant improvement in fracture discrimination was obtained when r = 0 and RR1 = RR2, the improvements obtained when r > or = 0.5 or RR1 double dagger RR2 were relatively modest. Slightly better fracture discrimination was obtained using the weighted mean Z-score approach compared with the WHO approach, although the differences were small. The results of the in vivo study in Colles' and vertebral fracture patients showed close agreement with the predictions of the bivariate gaussian model. CONCLUSION: In practice, from a theoretical point of view, there is unlikely to be any benefit from combining information from different types of bone densitometry measurements unless they are completely unrelated.

Bone Density↗
PubMed2003

A prospective study of risedronate on regional bone metabolism and blood flow at the lumbar spine measured by 18F-fluoride positron emission tomography.

UNLABELLED: The effect of risedronate on bone metabolism at the lumbar spine was assessed in 18 women who had a 18F-fluoride PET scan at baseline and after 6 months of therapy. The net plasma clearance of fluoride to bone mineral reflecting osteoblastic activity decreased significantly after therapy. INTRODUCTION: Quantitative radionuclide studies of bone reflect bone blood flow and regional osteoblastic activity, and the latter should change after treatment with a bisphosphonate, although this has not been previously demonstrated. The aim of this study was to examine regional 18F-fluoride kinetics in the lumbar spine measured by 18F-fluoride positron emission tomography (PET) before and after treatment with risedronate. MATERIALS AND METHODS: Eighteen women, with a mean age of 67.0 years and a T-score of less than -2 at the spine or hip, had a dynamic PET scan of the lumbar spine after the injection of 90 MBq 18F-fluoride ion at baseline and 6 months after commencing risedronate therapy. The arterial plasma input function was derived using aorta arterial activity from the PET image. Time-activity curves were measured by placing regions of interest over the lumbar vertebrae. A three-compartmental model was used to calculate bone blood flow (K(1)) and the net plasma clearance of tracer to bone mineral (K(i)). Rate constants k(2), k(3), and k(4), which describe transport between plasma, the extracellular fluid (ECF) compartment, and the bone mineral compartment, respectively, were also measured. RESULTS: Mean vertebral K(i) decreased significantly by 18.4% from baseline (3.32 x 10(-2) ml/min/ml) to 6 months post-treatment (2.71 x 10(-2) ml/min/ml; p = 0.04). This decrease was similar in magnitude to the decrease observed for bone-specific alkaline phosphatase, a marker of bone formation. There was no significant difference in K(1) from baseline (1.49 x 10(-1) ml/min/ml) to 6 months after treatment (1.38 x 10(-1) ml/min/ml; p > 0.05). There was a significant increase in k(2), reflecting the reverse transport of fluoride from the extravascular tissue compartment to plasma, after 6 months of treatment (2.90 x 10(-1)/min versus 4.43 x 10(-1)/min; p = 0.01). No significant changes were seen for k(3) or k(4). There was a significant decrease from baseline in the fraction of tracer in the extravascular tissue space that underwent specific binding to the bone matrix (k(3)/[k(2) + k(3)]), decreasing by 18.1% (p = 0.02). CONCLUSION: K(i), the net plasma clearance to bone mineral reflecting regional osteoblastic activity, displayed a significant decrease after 6 months of antiresorptive therapy. This is the first study to show a direct metabolic effect of antiresorptive therapy on skeletal kinetics at the clinically important site of the lumbar spine. The use of 18F-fluoride PET may provide a useful noninvasive tool to assess novel treatments currently being developed for osteoporosis.

Absorptiometry, Photon↗