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  • 1
    ISSN: 1433-2965
    Keywords: Anti-resorptive therapy ; Bone repletion ; Fluoride therapy ; Osteoporosis ; Spinal bone density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 44 osteoporotic subjects who had been treated with fluoride for 37±16 months, the fluoride was discontinued because they had shown fluoride-dependent increases in trabecular spinal bone densities from low initial levels (below the fracture threshold) to values that were equivalent to normal peak bone densities in the spines of young adults. During the subsequent period, after discontinuation of the fluoride therapy (i.e. 19±9 months), spinal bone density decreased in 73% of the subjects (i.e. 32 of 44,p〈0.03), at a rate that was comparable to the rate of the previous gain that had occurred during the treatment with fluoride (i.e. −3.23±2.39 mg/cm3 per month, compared with +3.91±1.96 mg/cm3 per month in this subgroup of patients,p〈0.001). Although 9 of the 44 subjects showed continuing increases in spinal bone density after discontinuation of the fluoride therapy, spinal bone density decreased in the entire group of 44 at an average rate of −1.02±4.72 mg/cm3 per month (p〈0.001, compared with the rate of the previous gain during the treatment with fluoride; i.e. +3.83±1.82 mg/cm3 per month). Surprisingly, our data showed that the rate of decrease in spinal bone density during the post-fluoride period was not affected by concurrent (undesigned) treatment with calcium, calcium plus estrogen, or calcium plus calcitriol. The cessation of fluoride therapy was also associated with a decrease in serum alkaline phosphatase activity (i.e. a decrease from the elevated levels that were observed during the period of fluoride therapy, back to the original, pre-treatment levels;p〈0.001), and that the rate of spinal bone loss after cessation of fluoride could be correlated with the prior rate of increase in serum alkaline phosphatase activity that had occurred during the treatment with fluoride (n=44,r=0.312,p=0.039). Together, the observations from this retrospective analysis of data obtained from our clinical subjects suggest that fluoride-treated osteoporotic subjects who have exhibited increases in trabecular spinal bone density are at risk for bone loss after discontinuation of the fluoride therapy.
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  • 2
    ISSN: 1433-2965
    Keywords: Bone formation ; Monofluorophosphate ; Osteocalcin ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a previous study we found that sustained-release monofluorophosphate (MFP-SR), a novel, sustained-release MFP preparation, acutely maintained the basal therapeutic serum fluoride levels without causing the high serum peak levels associated with plain MFP administration. The objective of the present study was to determine (a) whether chronic MFP-SR administration would provide therapeutic serum fluoride levels, and (b) whether treatment with this new preparation would result in an increase in bone formation similar to that achieved with plain MFP. Bone formation was assessed by serum osteocalcin (OC) determination. We studied 17 postmenopausal women older than 60 years and suffering from primary osteoporosis. All had received a minimum of 6 months of continuous treatment with plain MFP at a dose of 152 mg/day (76 mg b.i.d.). Upon entering the study, the subjects were randomized, in a double-masked protocol, to receive either MFP-SR (76 mg b.i.d.) (n=9) or placebo (n=8) for 2 months, after which all subjects returned to the original plain MFP regimen. Serum fluoride and serum OC levels were determined monthly for 3 months. At the beginning of the study serum fluoride levels were in the accepted therapeutic range (5–10 µM) in all patients. Serum fluoride levels were maintained in the patients switched to MFP-SR. In contrast, serum fluoride levels decreased significantly (p〈0.005) in the placebo-treated control subjects and returned to therapeutic levels upon switching back to plain MFP. Similarly, serum OC levels remained elevated in the subjects switched to MFP-SR but dropped significantly (p〈0.001) in the placebo-treated group. Our results demonstrate that chronic MFP-SR administration, at a dose of 152 mg/day, results in maintenance of therapeutic serum fluoride levels and in stimulation of bone formation. Because we have previously reported that high, supratherapeutic post-absorptive serum fluoride levels are avoided by MFP-SR administration, this novel preparation may prevent side effects associated with plain MFP by reducing the amount of fluoride deposited in bone.
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  • 3
    ISSN: 1433-2965
    Keywords: Cross-calibration ; Dual X-ray absorptiometry (DXA) ; European Spine Phantom (ESP) ; Osteoporosis ; Quantitative computed tomography (QCT)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Up to now it has not been possible to reliably cross-calibrate dual-energy X-ray absorptiometry (DXA) densitometry equipment made by different manufacturers so that a measurement made on an individual subject can be expressed in the units used with a different type of machine. Manufacturers have adopted various procedures for edge detection and calibration, producing various normal ranges which are specific to each individual manufacturer's brand of machine. In this study we have used the recently described European Spine Phantom (ESP, prototype version), which contains three semi-anthropomorphic “vertebrae” of different densities made of simulated cortical and trabecular bone, to calibrate a range of DXA densitometers and quantitative computed tomography (QCT) equipment used in the measurement of trabecular bone density of the lumbar vertebrae. Three brands of QCT equipment and three brands of DXA equipment were assessed. Repeat measurements were made to assess machine stability. With the large majority of machines which proved stable, mean values were obtained for the measured low, medium and high density vertebrae respectively. In the case of the QCT equipment these means were for the trabecular bone density, and in the case of the DXA equipment for vertebral body bone density in the posteroanterior projection. All DXA machines overestimated the projected area of the vertebral bodies by incorporating variable amounts of transverse process. In general, the QCT equipment gave measured values which were close to the specified values for trabecular density, but there were substantial differences from the specified values in the results provided by the three DXA brands. For the QCT and Norland DXA machines (posteroanterior view), the relationships between specified densities and observed densities were found to be linear, whereas for the other DXA equipment (posteroanterior view), slightly curvilinear, exponential fits were found to be necessary to fit the plots of observed versus specified densities. From these plots, individual calibration equations were derived for each machine studied. For optimal cross-calibration, it was found to be necessary to use an individual calibration equation for each machine. This study has shown that it is possible to cross-calibrate DXA as well as QCT equipment for the measurement of axial bone density. This will be of considerable benefit for large-scale epidemiological studies as well as for multi-site clinical studies depending on bone densitometry.
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