摘要:

AbstractA cohort of 101 patients were treated with enteric‐coated sodium fluoride tablets and calcium supplements. Vitamin D was also given in supra‐physiologic doses in 70% of the cases. Lumbar bone mineral density (BMD), as measured by dual‐photon absorptiometry, increased in a linear fashion up to four years, irrespective of the value of initial BMD and of the underlying condition, be it involutional osteoporosis (the vast majority), glucocorticoid osteoporosis, or even osteogenesis imperfecta. Estrogen replacement therapy (ERT) seemed to promote the fluoride‐induced increase in lumbar BMD, as did the vitamin D supplements. Of these patients, 17% proved “resistant” to the therapy. There was no way of predicting who would be in this category. Compared with an age‐ and sex‐matched control group, women showed significantly different behavior of their bone mass. In the control group, the losses were highly significant at the lumbar spine and at all three scanning sites of the forearm, as measured by single‐photon absorptiometry. In contrast, the fluoride group had a significant gain of BMD at the lumbar spine and changes of BMC at the forearm were not significant. Fluoride thus preserved bone mass at the appendicular skeleton, while increasing it at the axial skeleton. When comparing the patients who received vitamin D supplements and those who did not, there was a significant difference in the appendicular skeleton. The distal forearm in the vitamin D‐supplemented group tended to gain, whereas the midforearm lost significant bone mass. The trend was reversed in the group without vitamin D‐supplementation, a more favorable pattern. Therefore, vitamin D supplements should not, as a rule, be provided to such patients. The biochemical hallmark of the fluoride‐induced changes is a slight rise of the alkaline phosphatase within the normal range. Alkaline phosphatase levels that exceed the upper limit of normal signal a warning that too much fluoride and/or too little calcium supplements are being administered, or that a fluoride‐related complication is impending or has occurred (e.g., a stress fracture). Osteosclerosis was achieved in 69% of the cases who had a radiological followup of at least four years (average period of appearance: 1.8 years). Stress fractures in the lower limbs occurred in 17 patients, almost exclusively in females, and appeared on average 2.2 years after initiation of therapy. In this group of stress fractures there was significant cortical bone loss at midforearm. Stress fractures tended to aggregate with further peripheral fractures, which, however, did not seem to occur at a higher than expected rate. The increase of the permanent vertebral‐deforming events was significantly reduced, while the decrease of the vertebral deformation score plateaued considerably. Fluoride, when given as enteric‐coated tablets, with high‐dose calcium supplements and little or no vitamin D, appears to be beneficial in the management of the ve

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051303

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1990

数据来源: WILEY

摘要:

AbstractWe report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric‐coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% ± 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r= 0.52,p<0.01), serum fluoride (r= 0.50,p<0.01), and age (0.39,p<0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%,p<0.01), associated with an age‐related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r= −0.52,p5 μmol/liter), histological effects of fluoride (or bone fluoride), and toxicity. The mean dose of enteric‐coated tablets required to achieve a histologic fluoride effect (hyperosteoidosis) in 88% of patients so treated was 42.6 mg/day (19.3 mg elemen

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051340

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1990

数据来源: WILEY

摘要:

AbstractSince osteoporosis is a disease of diminished bone density, and since osteoporotic fractures occur most commonly in the spine, the ideal therapeutic agent for osteoporosis is one which can increase spinal bone density and thereby reduce the risk for vertebral fractures. In the current study we sought to examine the effect of fluoride therapy on spinal bone density utilizing quantitative computed tomography to measure changes in vertebral trabecular bone density during treatment with fluoride. A group of 61 postmenopausal osteoporotic females, aged 70 ± 9 years, were treated with 34 ± 7 mg elemental fluoride/day (equivalent to 75 ± 15 mg NaF/day) and 1500 mg calcium/day for 19 ± 6 months. Spinal bone density was increased within the first 6 months of fluoride therapy by 42% or 10 ± 13 mg/cm3(p<0.001) and continued to increase throughout 2 years of observation. The skeletal response to fluoride therapy was also associated with an early increase in serum alkaline phosphatase activity (p<0.001), which was related to the increase in spinal bone density (r= .58,p<0.001). Large interpatient variation was observed in the spinal bone response to fluoride therapy, which was not explained by variations in the pretreatment spinal bone density (r= .04), age of the patient (r= .15), or dose of fluoride (r= .16). Results from these studies demonstrate (1) the therapeutic value of fluoride to increase trabecular bone density lineraly for 2 years in the osteoporotic spine and (2) the clinical value of measuring spinal bone density and/or serum alkaline phosphatase activity as indices of the skeletal response to fluo

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051350

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1990

数据来源: WILEY

摘要:

AbstractThe aim of the study was to investigate the usefulness of urinary fluoride excretion in evaluating fluoride therapy. In a prospective study, 35 patients with osteoporosis were treated for about 44 months with a mean dosage of 31.4 mg fluoride ion per day. Urinary fluoride excretion and serum alkaline phosphatase activity were measured at 3‐month intervals. Bone mineral content (BMC) was measured in L2–L4 with dual‐photon absorptiometer. The mean number of BMC measurements was 5.7 per patient. The interindividual reproducibility for measurements in 10 patients was 2.1%. For each individual, the regression coefficient of BMC for the period of treatment was calculated. Responders were defined as those who had a positive value and nonresponders had 0 or a negative value. The percentage responders was 83%. Between responders and nonresponders no differences were found for age, fluoride dosage, duration of treatment, or changes in serum alkaline phosphatase activity. Urinary fluoride excretion was higher in responders than in nonresponders (p<0.001) and a positive correlation (p8 mg/24 h. All nonresponders had a urinary fluoride excretion<8 mg/24 h. Urinary fluoride excretion is a valuable predictor of BMC response during fluoride therapy for osteopo

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051360

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1990

数据来源: WILEY

摘要:

AbstractIn this study, the relationship between fluoride pharmacokinetics and the response in spinal bone density to fluoride treatment was studied in 14 patients with primary osteoporosis treated with fluoride for at least 1 year. Serum concentrations and urinary excretion of fluoride were determined after ingestion of 10 mg fluoride as monofluorophosphate. The pharmacokinetic parameters were calculated according to a linear one‐compartment open model. The fasting serum fluoride level was 8.8 ± 0.98 μmol/liter. The peak serum fluoride level was 20.5 ± 1.4 μmol/liter and was reached within 2 h after ingestion of fluoride. When the patients were divided into good and poor responders, based on whether they did or did not exhibit a change in spinal bone density of 13 mg/cc per year or more, we found that good responders had decreased renal fluoride clearance (−62 ± 13%,p<.02), increased maximum change in serum fluoride (+38 ± 18%,p<.01), increased extrarenal clearance (+62 ± 57%,p<.05) and increased change in serum alkaline phosphatase (ALP) (+241 ± 169%,p<0.02) compared with poor responders. Our data suggest that one factor accounting for a good response is a relatively high serum level of fluoride. However, although the maximum change in serum fluoride was greater in good responders compared with poor responders, variations in fluoride levels could not explain all of the variation in spinal bone density. Therefore, we propose that in addition to differences in serum fluoride, other factors are also responsible for the go

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051370

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1990

数据来源: WILEY

摘要:

AbstractThis report reviews some aspects of fluoride pharmacokinetics in relation to the treatment of osteoporosis. The bioavailability of conventional plain NaF tablets has been shown to be close to 100, for sustained‐release NaF tablets close to 90%, and for enteric‐coated NaF tablets 65%. The simultaneous intake of food and/or calcium tablets reduces the bioavailability by 30 to 40%. Fluoride renal clearance is influenced by both urinary pH and flow and the clinical consequences of this is discussed. Studies on plasma kinetics of fluoride during chronic fluoride intake suggests that a plasma sample taken at mid‐dosage intervals will give reproducible “mean steady‐state” levels. It is suggested that improvements of the clinical benefit of fluoride therapy in osteoporosis might be achieved if the dosage regimen were based on the pharmacokinetic properties of the fluoride preparation used as well as plasma fluoride

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051380

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1990

数据来源: WILEY

摘要:

AbstractIn this study we investigated the possibility of the formation of a calcium fluoride surface film on the new bone matrix in patients undergoing fluoride treatment for osteoporosis. This calcium fluoride film could interfere with the normal mineralization process and lead to hyperosteoidosis (osteomalacia), a well‐documented complication seen in fluoride‐treated patients. During treatment, fluoride circulating in the blood and extracellular fluid of patients, could interact with the components of the serum, but particularly calcium and magnesium ions. The interrelationships among serum components in the presence of fluoride ion may result, at thermodynamic equilibrium, in deposition on the apatitic bone surface of phases such as calcium fluoride, fluorapatite, or fluorhydroxyapatite. Differences in the phase deposited among patients could result in differences in response to fluoride treatment. A computer program based on equilibrium thermodynamic data was utilized to study the physicochemical calcium, fluoride, and phosphate interrelationships in serum. In all the computer calculations, fluorhydroxyapatite (FHAP), alone or in combination with hydroxyapatite (HAP), was determined to be the thermodynamically stable precipitating surface phase. These data strongly suggest that calcium fluoride surface film is not the reason for the delay of mineralization of fluoride‐stimulated new bone. Based on these calculations, we now advance the hypothesis that the effect of fluoride to cause osteomalacia is due to an effect on osteoblasts and also on osteocytes. Consistent with this hypothesis was the finding in bone biopsies, that the excess of osteoid in fluoride‐treated patients was found not only at the mineralization front (which is transversed by osteoblast cell processes), but also around young osteocytes, two sites where FHAP or FAP is presumed to be formed. It is possible that an adsorption/desorption of the FHAP phase occurring at the osteoblastic canalicular and osteocytic lacunar surface leads to prolonged fluoride exposure of osteoblast processes in canaliculi and of young osteocytes to fluoride thereby disrupting the normal process of mineralization. The delay in mineralization (osteoid accumulation) may be further accentuated by acid equilibrium processes which occur during mineral deposition and which would enhance cellular fluoride uptake at the calcifying front and at the periphery of the os

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051390

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1990

数据来源: WILEY

摘要:

AbstractTo assess whether an interval of a few hours would be advisable between an intake of sodium fluoride (NaF) and that of calcium salts when treating osteoporotic patients with vertebral collapse, we carried out three pharmacokinetic studies in 12 healthy fasting volunteer subjects to compare the fluoride bioavailability provided by NaF alone and NaF combined with two calcium salts. The results were as follows: (1) When NaF is accompanied by calcium, the fluoride peak level is lower and delayed. (2) Fluoride absorption varied greatly among individuals in both experiments, but none of the 6 subjects proved to be nonabsorbers. (3) The areas under the curves obtained with each of the three preparations were not significantly different, but 24‐h urinary fluoride was significantly lower in volunteers receiving simultaneously NaF and calcium salts than in volunteers receiving only Na

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051310

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1990

数据来源: WILEY

摘要:

AbstractThe gastrointestinal absorption of enteric‐coated (EC) tablets of sodium fluoride (NaF) with respect to different time schedules of administration of calcium supplements in solution was tested. It was found that the simultaneous administration of these two medications under these formulations did not interfere with fluoride absorption. The calcium was also well absorbed as shown by the rise in serum ionized calcium concentration. Other schedules were studied as well, such as EC NaF tablets taken 1 hour after or 3 hours before the administration of calcium supplements. No superiority was shown, on the contrary, compared with the simultaneous administration of both medications. It was concluded that EC tablets of NaF and calcium supplements in solution can be provided simultaneously to enhance complianc

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051311

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1990

数据来源: WILEY

摘要:

AbstractThe effects of fluoride (F) on ectopic bone formation induced in rats by implants of demineralized cortical bone tissue were studied. Test rats received sodium fluoride (NaF), 6 mmol/liter in drinking water, and controls received fluoride‐free water. Implant accumulations of tracer hydroxyproline ([3H](OH)P),45Ca, and stable Ca were determined 24 h after injections of tritiated proline ([3H]P) and45Ca, to estimate rates of collagen synthesis, mineralization, and net mineral mass, respectively. Conventional histology on undemineralized implant sections was done. Mineralized bone was first observed by implant histology, 2 weeks after implantation and continued to increase up to 8 weeks. A few chondrocytes were observed. Prior to bone formation, dense fibrous tissue was observed within the marrow space of the original implant. The rate of collagen synthesis peaked at 1 week, again at 3 weeks, and then continued at a slower rate up to 8 weeks. The rates of mineralization paralleled the rates of collagen synthesis between 2 and 8 weeks, indicating bone mineralization over this period. During the first 2 weeks after implantation no mineral deposition was observed. The initial peak of collagen synthesis without mineralization (0‐2 weeks) indicates fibrous tissue formation and is in agreement with the histological analysis. Fluoride treatment increased rates of collagen synthesis during both the initial period of fibrous tissue formation and later bone formation. The ratio of mineralization rate to collagen synthesis rate (45Ca/[3H](OH)P) was decreased by fluoride throughout the 2‐8 week period, but net mineral mass was comparable to control rats by 8 weeks, indicating that fluoride delays, but does not prevent, bone mineralization. Fluoride stimulation of both fibrous tissue and bone suggests effects on precursor cells, possibly cells of the immune s

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051312

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1990

数据来源: WILEY