technetium-tc-99m-medronate and Osteoporosis--Postmenopausal

Teriparatide (TPTD) increases skeletal mass, bone turnover markers, and bone strength, but in vivo effects at individual skeletal sites have not been characterized. Quantitative radionuclide imaging studies reflect bone blood flow and osteoblast activity to assess regional changes in bone metabolism. Changes in bone plasma clearance using technetium-99m methylene diphosphonate ((99m)Tc-MDP) were quantified and correlated with changes in bone turnover markers in 10 postmenopausal women with osteoporosis. Subjects underwent bone scintigraphy at baseline and 3 and 18 months after initiating TPTD 20 microg/day subcutaneously. Subjects were injected with 600 MBq (99m)Tc-MDP, and whole-body bone scan images were acquired at 10 minutes and 1, 2, 3, and 4 hours. Multiple blood samples were taken between 5 minutes and 4 hours after treatment, and free (99m)Tc-MDP was measured using ultrafiltration. The Patlak plot method was used to evaluate whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)) and derive regional bone clearance for the calvarium, mandible, spine, pelvis, and upper and lower extremities using gamma camera counts. Bone turnover markers were measured at baseline and 3, 12, and 18 months. Median increases from baseline in whole-skeleton K(bone) were 22.3% (p = .004) and 33.7% (p = .002) at 3 and 18 months, respectively. Regional K(bone) values were increased significantly in all six subregions at 3 months and in all subregions except the pelvis at 18 months. Bone markers were increased significantly from baseline at 3 and 18 months and correlated significantly with whole-skeleton K(bone). This is the first study showing a direct metabolic effect of TPTD at different skeletal sites in vivo, as measured by tracer kinetics.

Topics: Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Bone Density; Collagen Type I; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Peptide Fragments; Peptides; Procollagen; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate; Teriparatide

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.

Topics: Aged; Chromium Radioisotopes; Diagnostic Techniques, Radioisotope; Edetic Acid; Estrogen Replacement Therapy; Female; Glomerular Filtration Rate; Humans; Metabolic Clearance Rate; Middle Aged; Osteoporosis, Postmenopausal; Protein Binding; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate

Visual changes on radionuclide bone scans have been reported with teriparatide treatment. To assess this, serial studies were evaluated and quantified in ten postmenopausal women with osteoporosis treated with teriparatide (20 μg/day subcutaneous) who had (99m)Tc-methylene diphosphonate (MDP) bone scans (baseline, 3 and 18 months, then after 6 months off therapy).. Women were injected with 600 MBq (99m)Tc-MDP, and diagnostic bone scan images were assessed at 3.5 h. Additional whole-body scans (10 min, 1, 2, 3 and 4 h) were analysed for (99m)Tc-MDP skeletal plasma clearance (K(bone)). Regional K(bone) differences were obtained for the whole skeleton and six regions (calvarium, mandible, spine, pelvis, upper and lower extremities). Bone turnover markers (BTM) were also measured.. Most subjects showed visual changes on 3- and 18-month bone scan images that disappeared after 6 months off therapy. Enhanced uptake was seen predominantly in the calvarium and lower extremities. Whole skeleton K(bone) displayed a median increase of 22% (3 months, p = 0.004) and 34% (18 months, p = 0.002) decreasing to 0.7% (6 months off therapy). Calvarium K(bone) changes were three times larger than other sites. After 6 months off therapy, all K(bone) and BTM values returned towards baseline.. The increased (99m)Tc-MDP skeletal uptake with teriparatide indicated increased bone formation which was supported by BTM increases. After 6 months off therapy, metabolic activity diminished towards baseline. The modulation of (99m)Tc-MDP skeletal uptake during treatment was the result of teriparatide's metabolic activity. These findings may aid the radiological evaluation of similar teriparatide patients having radionuclide bone scans.

Topics: Aged; Bone and Bones; Bone Density; Bone Remodeling; Female; Humans; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Radionuclide Imaging; Technetium Tc 99m Medronate; Teriparatide; Time Factors; Whole Body Imaging

Quantitative radionuclide imaging using (18)F-fluoride positron emission tomography (18F-PET) or (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scans provides a novel tool for studying regional and whole skeleton bone turnover that complements the information provided by biochemical markers. Radionuclide bone scans can be quantified by measuring either tracer uptake or, if blood sampling is performed, bone plasma clearance. This study examines whether these two methods provide equivalent information about bone turnover. We examined data from two clinical trials of the bone anabolic agent teriparatide. In Study 1 twenty osteoporotic women had 18F-PET scans of the lumbar spine at baseline and after 6 months treatment with teriparatide. Bone uptake in the lumbar spine was expressed as standardised uptake values (SUV) and blood samples taken to evaluate plasma clearance. In Study 2 ten women had (99m)Tc-MDP scans at baseline, 3 and 18 months after starting teriparatide. Blood samples were taken and whole skeleton plasma clearance and bone uptake calculated. In Study 1 spine plasma clearance increased by 23.8% after 6-months treatment (P=0.0003), whilst SUV increased by only 3.0% (P=0.84). In Study 2 whole skeleton plasma clearance increased by 37.1% after 18-months treatment (P=0.0002), whilst the 4-hour whole skeleton uptake increased by only 25.5% (P=0.0001). During treatment the 18F- plasma concentration decrease by 20% and (99m)Tc-MDP concentration by 13%, and these latter changes were sufficient to explain the differences between the uptake and plasma clearance results. Measurements of response to treatment using bone uptake and plasma clearance gave different results because the effects of teriparatide on bone resulted in a sufficiently increased demand for radionuclide tracer from the skeleton that the concentration in the circulation decreased. Similar effects may occur with other therapies that have a large enough effect on bone metabolism. In these circumstances changes in bone plasma clearance give a truer impression of response to treatment than those in SUV or uptake.

Topics: Aged; Biomarkers; Bone and Bones; Bone Density Conservation Agents; Bone Remodeling; Female; Fluorine Radioisotopes; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Positron-Emission Tomography; Radiography; Radiopharmaceuticals; Technetium Tc 99m Medronate; Teriparatide

Quantitative studies of bone using (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) have a potentially valuable role in investigating the treatment of patients with metabolic bone disease. In this study we compared 3 different methods of measuring whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)) in 12 osteoporotic postmenopausal women (mean age, 67.3 y) before participation in a clinical trial of an osteoporosis therapy. The aim was to compare the consistency and accuracy of the 3 methods before their use in evaluating the subjects' response to treatment.. Subjects were injected with 600 MBq (99m)Tc-MDP and 3 MBq (51)Cr-ethylenediaminetetraacetic acid ((51)Cr-EDTA) and whole-body bone scan images were acquired at 10 min, 1, 2, 3, and 4 h. Two-minute static images of the thighs were acquired immediately after the 1- to 4-h whole-body scans. Six blood samples were taken between 5 min and 4 h, and free (99m)Tc-MDP was measured using ultrafiltration. The glomerular filtration rate (GFR) was estimated from the (51)Cr-EDTA plasma curve. The methods used to evaluate K(bone) were (a) the area-under-the-curve (AUC) method, in which the GFR measurement was subtracted from the total (bone plus renal) clearance (K(total)) measured from the free (99m)Tc-MDP plasma curve; (b) the modified Brenner method, in which (99m)Tc-MDP renal clearance estimated from the whole-body counts was subtracted from the total clearance measured from the rate of elimination of tracer from soft tissue; and (c) the Patlak plot method, which was also used to derive regional values of K(bone) for the skull, spine, pelvis, arms, and legs.. There was good agreement between the 3 methods of measuring K(bone). (mean K(bone) +/- SD: AUC method, 30.3 +/- 6.4 mL x min(-1); Brenner method, 31.1 +/- 5.8 mL x min(-1); Patlak method, 35.7 +/- 5.8 mL x min(-1)). The correlation coefficients between the methods varied from r = 0.767 (P = 0.004) to r = 0.805 (P = 0.002). Regional measurements of (99m)Tc-MDP clearance gave the following percentages of the whole-skeleton clearance: skull, 13.3%; spine, 16.6%; pelvis, 17.2%; arms, 11.1%; legs, 23.7%.. The 3 methods gave consistent and accurate measurements of K(bone). The Patlak method can be used to study regional as well as total-skeleton values of K(bone).

Topics: Aged; Bone Remodeling; Female; Humans; Image Interpretation, Computer-Assisted; Metabolic Clearance Rate; Osteoporosis, Postmenopausal; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Medronate

Osteoporosis is the most common of the metabolic bone diseases, and is an important cause of morbidity in the elderly. Bone scintigraphy is used to detect skeletal lesions at the earliest possible time, to monitor the course of the skeletal discase and to evaluate the metabolic activity of skeletal lesions. The aim of this study was to determine, by using the bone scan age of vertebral fractures in patients with severe osteoporosis, and make correlation between bone scintigraphy and mineral bone density. Material and methods 30 female patients were studied with bone scintigraphy after BMD.BMD was measurred with DEXA Hologic QDR 4500 Elite System. Correlation between T-score and uptake of radiofarmaceutical (Tc-99mMDP) was 0.849, and it was high. Intensity of uptake of Tc-99m MDP scintigraphy is an accurate method for the detection and ageing of fractures in osteoporotic patients.

Topics: Absorptiometry, Photon; Bone and Bones; Bone Density; Female; Fractures, Spontaneous; Humans; Middle Aged; Osteoporosis, Postmenopausal; Radionuclide Imaging; Radiopharmaceuticals; Spinal Fractures; Technetium Tc 99m Medronate

Quantitative radionuclide studies of bone using the short-lived tracers (18)F-fluoride and (99m)Tc-methylene diphosphonate (MDP) are an alternative method to biochemical markers of bone turnover for investigating the dynamic state of the skeleton. In this study we evaluated their use to quantify bone turnover in women receiving antiresorptive therapy compared with that of untreated control subjects.. The patients were 69 healthy postmenopausal women. Twenty-six women were receiving hormone replacement therapy (HRT) and 43 were untreated age-matched control subjects. After bolus injection of (18)F-fluoride (1 MBq), (99m)Tc-MDP (1 MBq), (51)Cr-ethylenediaminetetraacetic acid (3 MBq), and (125)I-labeled human serum albumin (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h. The clearance to bone mineral K(bone) was first evaluated using the area under the plasma concentration curve (AUC) on the assumption that the rate constant k(4) for the outflow of tracer from bone was negligibly small. AUC values of K(bone) were then compared with those found using a compartmental model method that allowed k(4) to be fitted as a free parameter.. Using the AUC method the mean plus minus SD for K(bone) for the 2 tracers were: (18)F-fluoride, 61.8 plus minus 12.0 mL center dot min(-1) (HRT group) versus 67.2 plus minus 12.6 mL center dot min(-1) (control group) (P = 0.045); and (99m)Tc-MDP, 40.3 plus minus 8.2 mL center dot min(-1) (HRT group) versus 44.2 plus minus 7.6 mL center dot min(-1) (control group) (P = 0.024). Values for the 2 tracers in individual patients were moderately well correlated (r = 0.76; P < 0.001). Using the compartmental model method, k(4) for (18)F-fluoride was shown to lie in the range 0--0.0025 min(-1) with a best-fit value of 0.0018 min(-1). Values of K(bone) determined using k(4) = 0.0018 min(-1) were highly correlated with the AUC values (r = 0.989; SEE = 2.05 mL center dot min(-1)) with numeric values that were larger by a factor of 1.53. Analysis of the (99m)Tc-MDP data was more difficult because of uncertainties in protein binding in the extracellular fluid compartment space. The best fit for k(4) was in the range 0.0010--0.0014 min(-1) with values of K(bone) similar to those found using the AUC method.. Values of K(bone) determined using the AUC method were able to differentiate between HRT-treated women and postmenopausal women who were not treated and were highly correlated with those determined using a compartmental model method with nonzero values of k(4).

Topics: Aged; Area Under Curve; Bone and Bones; Bone Remodeling; Chromium Radioisotopes; Edetic Acid; Estrogen Replacement Therapy; Female; Fluorides; Fluorine Radioisotopes; Humans; Middle Aged; Osteoporosis, Postmenopausal; Radionuclide Imaging; Radiopharmaceuticals; Serum Albumin, Radio-Iodinated; Technetium Tc 99m Medronate

Bone turnover changes with age have been shown by both histomorphometric and scintimetric methods; fewer studies have been performed on the regional differences of bone remodeling in the aging skeleton. To noninvasively investigate this issue, we evaluated the age-related patterns of global and regional bone uptake of 99mTc-methylene diphosphonate (MDP) in a large sample of healthy women.. In a group of 84 healthy women (33 pre- and 51 postmenopausal), the uptake of 99mTcMDP was semiquantitatively measured in 5 regions of interest. Total-body digital scans (TBDSs) were acquired at 5 min and at 4 h. Five regions of interest were drawn on the skeleton as a whole, on the lumbar spine, on the iliac wing, on the femoral neck, and on the femoral diaphysis of the 4-h TBDS. Regional skeletal uptake of the lumbar spine (LS-RSU), of the iliac wing (IL-RSU), of the femoral neck (FN-RSU), and of the femoral diaphysis (FD-RSU) was calculated as percentage injected dose retained in these skeletal segments at 4 h.. As expected, in postmenopausal women the global skeletal uptake (GSU) values were higher than those in premenopausal women (40.7 +/- 5.9 percentage injected dose [%ID] versus 35.1 +/- 4.2 %ID; P < 0.0001). GSU correlated positively with age (r = 0.70; P < 0.001), but the addition of years since menopause to the regression model did not ameliorate the regression. On the other hand, LS-RSU (r = -0.55; P < 0.0001), IL-RSU (r = -0.45; P < 0.0001), and FN-RSU (r = -0.22; P < 0.005) decreased significantly, whereas FD-RSU increased significantly (r = 0.39; P < 0.001) with age; the same regressions were not influenced significantly by the addition of menopausal duration to the regression model. The strongest correlation among the different RSUs was that found between LS-RSU and IL-RSU (r = 0.63; P < 0.001). Moreover, the linear regression coefficients of the various RSUs with age were all significantly different from each other (P < 0.001).. Our data show that the GSU of 99mTc-MDP increases with age, whereas different skeletal segments display a variable degree of turnover activation at different ages. This could ultimately induce the different rates of bone loss of different skeletal segments at various ages and, consequently, their variable propensity to fracture.

Topics: Adult; Aged; Aged, 80 and over; Aging; Bone and Bones; Female; Humans; Italy; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Premenopause; Radionuclide Imaging; Radiopharmaceuticals; Reference Values; Regression Analysis; Technetium Tc 99m Medronate; White People

This study is based on the assumption that is bone turnover, shown by the uptake of 99mTc-MDP, indicates a high rate of bone loss in patients with osteoporosis, it could potentially predict bone loss in patients at risk before significant bone loss has occurred.. Quantitative bone SPECT (QBS) using 99mTc-MDP, expressed as the %ID/cc x 10(-3), was performed in 71 women who had osteoporosis in the lumbar vertebrae, the femoral neck or both, and in 54 age-matched normal female controls. Of the women with osteoporosis, 42 had postmenopausal osteoporosis and 29 had primary hyperparathyroidism (HPT) and osteoporosis.. QBS increased with age in the cortical bone and decreased in the trabecular bone of the normal women. Quantitative bone SPECT in the femoral neck was 3.18 +/- 1.20 and was 2.73 +/- 1.06 in the femoral shaft in 20 women with postmenopausal osteoporosis of the femoral neck. In 19 women with HPT and osteoporosis of the femoral neck, the QBS value in the femoral neck was 3.57 +/- 0.92 and in the femoral shaft 3.38 +/- 1.12. These values were also significantly higher for the femoral neck and for the femoral shaft than those of normals. Although QBS values were higher in the lumbar region in 39 women with postmenopausal osteoporosis (4.59 +/- 1.45) and in 27 women with HPT (4.30 +/- 1.52), as compared with the normal group (4.28 +/- 1.61), the difference was not statistically significant.. This study shows that bone turnover is significantly higher in the cortical bone of women with osteoporosis than in normal women.

Topics: Bone and Bones; Bone Density; Female; Femur Neck; Humans; Hyperparathyroidism; Lumbar Vertebrae; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Technetium Tc 99m Medronate; Tomography, Emission-Computed, Single-Photon

To determine the radiographic appearance of osteoporotic vertebral fracture.. Lateral thoracic and lumbar spine radiographs were examined in 58 patients (812 vertebra) with osteoporosis and evidence of vertebral collapse at bone scintigraphy. Scintigraphic activity was graded as faint, moderate, or intense. Anterior, middle, and posterior heights of the T-4 to L-5 vertebrae were measured. The degree of vertebral deformity was derived by comparing a ratio of heights with the normal mean.. At radiography, 378 of the 812 vertebrae (47%) were normal, 434 (53%) had deformities that were more than two standard deviations (SDs) below the normal mean, 304 (37%) had deformities that were more than three SDs below the normal mean, and 222 (27%) had deformities that were more than four SDs below the normal mean. Of 86 vertebrae that showed moderate or intense radionuclide uptake at scintigraphy, all had deformities that were more than two SDs below the normal mean, and 80 (93%) had deformities that were more than three SDs below the normal mean.. Only in vertebrae with deformities more than three SDs below the normal mean can fractures be confidently diagnosed.

Topics: Female; Fractures, Spontaneous; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Radiography; Radionuclide Imaging; Reference Values; Spinal Fractures; Technetium Tc 99m Medronate; Thoracic Vertebrae

This paper reports the measurement of whole body retention using fluoride (WBRF) as an estimator of skeletal turnover in a group of climacteric women that received an oral dose of 700 mumol of sodium fluoride. WBRF is defined as 100(1-(urinary fluoride/fluoride load)). WBRF was significantly correlated with whole body retention of 99m-Tc-methylene-diphosphonate, the serum levels of the bone alkaline phosphatase and the urinary excretion of hydroxyproline. WBRF values ranged from 20% to 95% and were affected by calcium intake and the urinary calcium excretion. In normal subjects with high turnover, the measurement of serum alkaline phosphatase activity and/or urinary hydroxyproline excretion helps to distinguish these cases from patients with metabolic bone diseases due to metastases, Paget disease, etc. The fact that the fraction of fluoride not incorporated into bone is not further metabolized plus the accuracy, preciseness and rapidity of fluoride measurements in urine are the main advantages of this technique.

Topics: Alkaline Phosphatase; Bone and Bones; Calcium; Climacteric; Female; Fluorides; Humans; Hydroxyproline; Isoenzymes; Osteoporosis, Postmenopausal; Radionuclide Imaging; Technetium Tc 99m Medronate