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1.
The biochemical responses to salmon calcitonin (SCT: 100 MRC units thrice weekly) and disodium etidronate (EHDP: 400 mg daily) alone and in combination for 6 months were compared in 72 patients with symptomatic Paget's disease of bone unresponsive to simple analgesic agents. SCT produced a 53% reduction in alkaline phosphatase (AP) and a 38% reduction in 24 h urinary hydroxyproline excretion (HYPRO). The response to EHDP was not significantly different--56% reduction in AP and 48% reduction in HYPRO. Their use in combination produced a significantly greater reduction of 71% in AP (P less than 0.002) and 69% reduction in HYPRO (P less than 0.0001). In those that remained symptomatic with increased disease activity treatment for longer than 6 months had a unpredictable effect and normal bone turnover was rarely achieved. Once therapy was withdrawn AP and HYPRO increased rapidly in those given SCT alone, returning to initial levels within 6 months. More sustained control of disease activity was achieved in those given EHDP either alone or with SCT but the combination retained the advantage obtained during treatment. Combinations of SCT + EHDP may find a place in the treatment of very active Paget's disease. 相似文献
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The use of agents that decrease bone resorption, notably the calcitonins, diphosphonates and mithramycin, has been shown to result in symptomatic and/or biochemical improvement in patients with Paget's disease of bone (osteitis deformans). The effects of short-term (6 months), low-dose (5 mg/kg body mass/d) etidronate disodium, a diphosphonate compound at present subject to registration in this country, on the clinical and laboratory manifestations of this disorder were examined. Marked symptomatic improvement was noted in 70% of patients, while biochemical parameters of bone turnover, namely serum alkaline phosphatase level (44%) and urine hydroxyproline excretion (56%), decreased significantly (P less than 0.001). A technetium-99m bone scan revealed an impressive reduction in uptake of isotope in 50% of patients. The drug was well tolerated and no adverse reactions (clinical, biochemical or haematological) were evident. It is concluded that short-term low-dose etidronate disodium affords a convenient and effective therapeutic alternative in patients with symptomatic Paget's disease. 相似文献
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Parathyroid hormone (PTH) increases the conversion of 25-hydroxyvitamin D [25(OH)D] to 1,25 dihydroxyvitamin D [1,25(OH)(2)D]. The purpose of this study was to assess the changes in serum concentration of vitamin D metabolites 1,25 dihydroxyvitamin D [1,25(OH)(2)D] and 25-hydroxyvitamin D [25(OH)D] during teriparatide 20 μg/day (teriparatide) therapy in the double-blind Fracture Prevention Trial of postmenopausal women with osteoporosis and in the male study of men with osteoporosis. Patients were randomized to teriparatide or placebo and received daily supplements of calcium 1000 mg and vitamin D 400-1200 IU. Serum concentrations of 1,25(OH)(2)D and 25(OH)D were measured. In women (N=336), median 1,25(OH)(2)D concentrations at 1 month increased from baseline by 27% (P<0.0001) in the teriparatide group versus -3% (P=0.87) in the placebo group (between group P<0.0001). At 12 months, the increase was 19% (P<0.0001) in the teriparatide group versus -2% (P=0.23) in the placebo group (P<0.0001). Median 25(OH)D concentrations at 12 months decreased by 19% (P<0.0001) in the teriparatide group versus 0% (P=0.13) in the placebo group (P<0.0001). In men (N=287), median 1,25(OH)(2)D concentrations at 1 month increased by 22% (P<0.0001) in the teriparatide group versus 0% (P=0.99) in the placebo group (P<0.0001). At 12 months, the increase was 14% (P<0.0001) in the teriparatide group versus 5% (P=0.004) in the placebo group (P=0.17). Median 25(OH)D concentrations at 12 months decreased by 11% (P=0.001) in the teriparatide group versus an increase of 1% (P=0.20) in the placebo group (P=0.003). Therefore, treatment with teriparatide increases 1,25(OH)(2)D concentrations and decreases 25(OH)D concentrations. 相似文献
6.
Frederick R. Singer 《Calcified tissue international》1991,49(Z2):S7-S8
Clinical interest in salmon calcitonin began in 1972 when this peptide was shown to be effective in the treatment of Paget's
disease. Salmon calcitonin is more potent than porcine calcitonin, with human calcitonin intermediate in potency. Salmon calcitonin
is a highly effective therapeutic agent in the treatment of Paget's disease. During chronic treatment with salmon calcitonin,
alkaline phosphatase activity and urinary hydroxyproline excretion decrease on an average of 50% in patients with Paget's
disease. Patients may experience a variety of clinical benefits during chronic treatment, including relief of bone pain, a
reversal of neurological deficits, stabilization or improvement of hearing loss, and improvement of vascularity of bone. Radiologic
healing of osteolytic lesions is particularly striking with calcitonin treatment. Paget's disease patients prefer treatment
with salmon calcitonin administered by means of a nasal spray. Salmon calcitonin has an excellent safety profile and produces
mild side effects in a small percentage of patients. The most common side effects associated with salmon calcitonin administration
are nausea and facial flushing. It is unusual to observe severe side effects. In about 20% of patients, production of antibodies
may neutralize the effects of the exogenously administered calcitonin; these patients respond to human calcitonin. At this
time salmon calcitonin should still be considered a valuable therapeutic agent in the treatment of Paget's disease, particularly
in patients with osteolytic lesions. 相似文献
7.
H R D'Agostino C A Barnett X J Zielinski G S Gordan 《Clinical orthopaedics and related research》1988,(230):223-228
To ascertain whether salmon calcitonin, usually given parenterally, could control active Paget's disease when given by nasal insufflation, intranasal salmon calcitonin (INSC) was given to nine men with Paget's disease whose serum alkaline phosphatase (SAP) levels were elevated twofold or more. Treatment with 100, 200, and 400 IU/day for three to nine months was well tolerated. SAP fell 31%-51% in three patients and more than 20% in two others. Three of four men who had previously received salmon calcitonin (SC) by injection had no response of SAP but had a rise in antibodies to SC. INSC is mildly effective and more convenient than parenteral SC, but dose response and efficacy relative to parenteral SC have not been established, thereby raising questions of cost-effectiveness. 相似文献
8.
Four cases of spinal cord compression stemming from Paget's disease of bone tissue are reported. Sarcomatous degeneration was proved in one case and in another one malignancy was deduced by computed tomography (CT) scanning. Clinical and radiologic manifestations as well as surgical management are discussed. The value of CT scanning of the spine as an aid in the evaluation of structural changes and the size of the soft tissue mass in sarcomatous degeneration of the lesion is stressed. After calcitonin administration, alleviation of pain and improvement in neurological status have occurred in two treated patients. 相似文献
9.
J Foldes S Shamir G Kidroni J Menczel 《Clinical orthopaedics and related research》1989,(243):275-279
The role of vitamin D metabolism in Paget's disease of bone has not been well defined. Serum levels of the main, circulating vitamin D metabolites were measured in 23 patients with Paget's disease. Values of 25(OH)D3 and 24,25(OH)2D3 were within the normal range in most (more than 90%) of the subjects. 1,25(OH)2D3 was increased in 11 (48%) patients. Markedly elevated levels (93-298 pg/ml) were found in five patients. In a subgroup of patients with high 1,25(OH)2D3, the mean serum alkaline phosphatase activity was insignificantly higher, while serum calcium, phosphorous, and kidney function were the same as in a subgroup with normal 1,25(OH)2D3. 1,25(OH)2D3 levels were not affected by treatment with either calcitonin or etidronate disodium. Serum 1,25(OH)2D3 levels may be increased in a subset of patients with Paget's disease of bone. 相似文献
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C Mautalen D Gonzalez E L Blumenfeld E Santini Araujo F Schajowicz 《Clinical orthopaedics and related research》1986,(207):150-155
Three patients with Paget's disease of bone were treated by disodium etidronate (EHDP) without interruption during periods of 18 to 30 months. In one case the daily dose was also unduly high (approximately equal to 18 mg/kg/day). A moderate to conspicuous diminution of the renal function was observed in all cases. The three patients developed skeletal pain in a gradual but progressively severe pattern. Seven nontraumatic fractures in nonpagetic bones were encountered. EHDP produces blockage of bone mineralization and excessive suppression of bone remodeling, therefore increasing the risks of fracture. EHDP affects not only pagetic bones but normal skeleton. A baseline evaluation of the renal function might help to identify those patients with greater risk to develop skeletal side effects during EHDP treatment. 相似文献
12.
A Grauer F Raue H G Schneider K Frank-Raue R Ziegler 《Journal of bone and mineral research》1990,5(4):387-391
To elucidate the biologic relevance of circulating sCT antibodies, an in vitro bioassay system for the detection of neutralizing antibodies was developed utilizing the human breast carcinoma cell line T47D. We reasoned that the inhibition of the dose-dependent cAMP response to sCT in the T47D assay system by anti-sCT antibodies could be used to determine the in vivo relevance of these antibodies. In this report the clinical course of nine patients with Paget's disease of bone treated with intranasal sCT was correlated with the presence of 125I-sCT binding and neutralizing antibodies. Of these seven patients, four were found to have neutralizing antibodies; the appearance of the antibodies coincided with the development of resistance. One of these patients was subsequently treated with human calcitonin and revealed a good response to the treatment. There was no clinical resistance observed in the three patients with 125I-sCT binding antibodies but no neutralizing antibodies; no resistance was observed in two patients without 125I-sCT binding or neutralizing antibodies. We conclude that this new technique to determine the biologic relevance of circulating anti-sCT antibodies may be an useful adjunct for determining the cause of resistance in patients treated with sCT. 相似文献
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Calcified Tissue International - 相似文献
14.
Y Meller R S Kestenbaum S Shany D Galinsky I Zuili N Yankovitch J Giat A Conforti G Torok 《Clinical orthopaedics and related research》1985,(199):272-279
In order to study the role of calcium-regulating hormones during callus formation in elderly patients, serum levels of parathormone (PTH), calcitonin (CT), 25-hydroxyvitamin D [25-OH-D], 1,25-dihydroxyvitamin D [1,25(OH)2D], 24,25-dihydroxyvitamin D [24,25(OH)2D], and calcium (Ca) were determined in 41 patients with fractures of long bones, primarily hip fractures. The parameters were measured on admission and after eight weeks. There were almost no changes in hormone serum levels during bone repair, except for a decrease in serum levels of 1,25(OH)2D from 25.3 +/- 2.3 pg/ml on admission to 21.0 +/- 2.0 pg/ml eight weeks later (p less than .001). Patients with fractures compared to normal elderly humans have lower serum levels of PTH (0.99 +/- 0.06 ng/ml versus 1.88 +/- 0.34 ng/ml; p less than .001), 25-OH-D (10.7 +/- 1.0 ng/ml versus 17.1 +/- 1.8 ng/ml; p less than .001), and Ca (9.1 +/- 0.1 mg% versus 9.7 +/- 0.1 mg%; p less than .001) and higher serum levels of 1,25(OH)2D (25.3 +/- 2.3 pg/ml versus 17.1 +/- 2.3 pg/ml; p less than .001). Female patients have lower serum levels of 24,25(OH)2D compared to males (1.65 +/- 0.15 ng/ml versus 2.06 +/- 0.29 ng/ml; p less than .05). A similar trend was noted in serum CT levels during callus formation (0.12 +/- 0.02 ng/ml versus 0.16 +/- 0.02 ng/ml; p less than .05). Patients with subcapital fractures of the femur have significantly lower serum levels of all vitamin D metabolites on admission, compared with patients suffering from extracapsular fractures.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
15.
Reduction of skeletal blood flow in Paget's disease with disodium etidronate therapy 总被引:2,自引:0,他引:2
Fourteen patients with Paget's disease of bone were treated with disodium etidronate in doses of 5 to 7 mg/kg per day. Skeletal blood flow (SBF), was measured by the modified 18F clearance technique of Wootton et al. (1976) before treatment and again during treatment. In 10 patients restudied 3-4 months after the start of therapy, SBF had fallen by a mean of 21% of the initial value, and the individual differences correlated well with the individual reductions in serum alkaline phosphatase (r = 0.77, P less than 0.01). The results were similar to those seen in an earlier study in patients treated with calcitonin. However, no early reduction in SBF was seen in six repeat studies performed at the end of the second week of treatment, in contrast with our previous findings with calcitonin. 相似文献
16.
Response to acute and chronic administration of calcitonin and calcium and of biphosphonates (EHDP) was evaluated in 14 patients with Paget's bone disease who were grouped on the basis of homogeneous disease activity, as appraised by bone involvement and alkaline phosphatase and hydroxyproline levels. At first, 100 MRC U of calcitonin followed 4 hours later by 500 mg of elemental calcium were given for 10 days; a significant (p less than 0.001; paired and unpaired Student t test) reduction in alkaline phosphatase (-25%) and hydroproline (-55%) was observed. Subsequently, 5 mg/kg/day of EHDP was given for 20 days. Both parameters increased to levels similar to basal values. These increases were significant (p less than 0.001 for the paired and unpaired Student test) compared with those obtained after calcitonin administration; alkaline phosphatase rose +27% and hydroxproline +135%. After this, patients were divided into 2 groups (A and B). Group A was treated with calcitonin and calcium, at the dosage indicated above, for 10 days a month during 6 months. Group B continued with the same protocol with the addition of EHDP for the 20 days during which calcitonin and calcium were not given. The results of 6 months of treatment showed that calcitonin was more active and suggested that EHDP diminishes hormonal effects. These results also demonstrate a short-term absence of EHDP activity. 相似文献
17.
Two metabolites of vitamin D3, 25-hydroxycholecalciferol (25-OHD3) and 1,25-dihydroxy-cholecalciferol (1,25-(OH)2D3) are potent stimulators of bone resorption in two test systems whereas vitamin D3 itself is inactive. These substances were tested (a) by directly comparing their action on bone explants of mouse half-calvariain vitro, and (b) by injecting them into young mice and measuring the degree of resorptionin vitro when explants were made 18 hours atter the injection. In both tests the 1,25-metabolite was about 100 times more potent than 25-OHD3. The dose-response curve for 1,25-(OH)2D3 indicates that doses above about 0.2 ng/g body weight are capable of inducing an increase in bone resorption in normal young mice. These data show that 1,25-(OH)2D3 is one of the most potent substances known that affects bone metabolism. The results are discussed in relation to the possible role of 1,25-(OH)2D3 in the normal mobilization of calcium from bone.
Zusammenfassung Bei Anwendung zweier verschiedener Versuchsanordnungen konnte gezeigt werden, daß die beiden Vitamin D3-Metaboliten 25-Hydroxycholecalciferol (25-OHD3) und 1,25-Dihydroxycholecalciferol (1,25-(OH)2D3) als starke Stimulatoren der Knochenresorption wirken, während sich Vitamin D3 selbst inaktiv verhält. Diese Substanzen wurden folgendermaßen geprüft: a) durch direkten Vergleich ihrer Wirkung auf Knochenexplantate (Hälften von Mäusecalvarien)in vitro und b) indem die Metaboliten jungen Mäusen injiziert wurden und der Resorptionsgrad an Explantaten 18 Std nach Injektionin vitro gemessen wurde. Bei beiden Versuchsanordnungen war der 1,25-Metabolit etwa 100mal wirksamer als der 25-OHD3-Metabolit. Aus der Dosiswirkungskurve für 1,25-(OH)2D3 geht hervor, daß es möglich ist, mit Dosen über ca. 0,2 ng/g Körpergewicht bei normalen jungen Mäusen bereits eine erhöhte Knochenresorption auszulösen. Diese Resultate zeigen, daß 1,25-(OH)2D3 eine der wirksamsten bisher bekannten Substanzen ist, die auf den Knochenmetabolismus einwirken können. Die Ergebnisse werden im Zusammenhang mit der Rolle, die das 1,25-(OH)2D3 bei der normalen Freisetzung von Calcium aus dem Knochen spielt, besprochen.
Résumé Deux métabolites de la vitamine D3, le 25-hydroxycholecalciferol (25-OHD3) et 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), stimulent la résorption osseuse dans deux systèmestests alors que la vitamine D3 est inactive. Ces substances sont testées a) en comparant directement leur action dans les explants osseux de calottes craniennes de sourisin vitro et b) en les injectant dans de jeunes souris et en mesurant le degré de résorptionin vitro, lorsque les explants sont réalisés 18 heures après l'injection. Dans les deux tests, le métabolite 1,25 est environ 100 fois plus puissant que 25-OHD3. La courbe dose-résponse de 1,25-(OH)2D3 indique que des doses au-dessus d'environ 0.2 ng/g de poids corporel sont capables d'induire une augmentation de la résorption osseuse chez de jeunes souris normales. Ces résultats montrent que 1,25-(OH)2D3 est une des substances connues les plus actives qui agit sur le métabolisme osseux. Le rôle possible de 1,25-(OH)2D3 sur la mobilisation normale du calcium osseux est envisagé.相似文献
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J Y Reginster A M Jeugmans-Huynen A Albert D Denis P Franchimont 《Journal of bone and mineral research》1988,3(3):249-252
The effectiveness of synthetic salmon calcitonin (SCT) administered as a nasal spray was assessed via clinical, biological, and radiological variables in 17 previously untreated Pagetic patients over a 1-year course of therapy. The results showed a highly significant decrease of serum alkaline phosphatase (S-ALP) (p less than 0.05 after 1 month of treatment) and of the urinary hydroxyproline/creatinine ratio (OH/Cr) (p less than 0.01 after 1 month of treatment). For the whole group, the mean decrease in S-ALP was 37 +/- 4% (SEM) after 6 months (p less than 0.01) and 31 +/- 5% after 1 year (p less than 0.01). The mean fall in OH/Cr was 35 +/- 6% (SEM) (p less than 0.01) and 37 +/- 7% (p less than 0.01) after 6 and 12 months, respectively. None of the usual side-effects of SCT were reported and local tolerance was excellent throughout the study. 相似文献
19.
B. Lund M.D. Ph.D. P. Charles C. Egsmose Bj. Lund F. Melsen L. Mosekilde T. Storm H. Søndergård J. Thode O. H. Sørensen 《Calcified tissue international》1985,37(5):478-483
Summary The relative roles of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D) and 24,25-dihydroxyvitamin D (24,25-(OH)2D) in bone mineralization are largely unknown. Young vitamin D depleted rats were fed increasing amounts of vitamin D and
grouped radiologically in accordance with the rat line test. They ranged from severely rachitic to normal. Radiology was correlated
with serum levels of 25-OHD, 1,25-(OH)2D, 24,25-(OH)2D, ionized calcium, magnesium, and phosphate, with bone histology, and with the total mineral content of the animals. Serum
1,25-(OH)2D rose in a linear fashion to supranormal values during bone healing and correlated with the radiological degree of rickets.
Serum 25-OHD was below detection limit in the most rachitic and low in the radiologicall normal rats, whereas 24,25-(OH)2D was low in all groups. These two metabolites showed no correlation with the radiologic, histologic or biochemical parameters.
In rachitic rats, 1,25-(OH)2D appears to play a major role in bone healing and possibly exerts a direct effect on bone cells. It cannot be ruled out,
however, that the effect is mediated through a rise in serum levels of calcium and phosphorus, although signs of bone healing
were seen in the presence of a subnormal calcium x phosphorus product. Initiation of mineralization can take place with unmeasurable
25-OHD, and 24,25-(OH)2D seems to be without importance. 相似文献
20.
Vitamin D deficiency is known to cause alterations in the lipid and mineral components of bone and cartilage. In this study, second generation, normal phosphatemic, vitamin D-deficient rats, treated with low and high doses of three different vitamin D metabolites were sacrificed 24 h after treatment and their bones analyzed in order to determine which metabolites were most effective in altering the lipid composition. In the untreated vitamin D-deficient rats, tissues undergoing endochondral ossification (epimetaphyses), periosteal and endosteal bone formation (diaphyseal bone), and intramembranous bone formation (calvaria) all contained lower amounts of complexed acidic phospholipids, as well as decreased amounts of mineral. Twenty-four hours following treatment, the complexed acidic phospholipid content was significantly increased relative to both untreated and normal (vitamin D-replete) animals, the greatest increases occurring in animals treated with 1,25-dihydroxyvitamin D. All metabolites tested altered histomorphometric and/or mineral parameters, but only 1,25-dihydroxyvitamin D, in low and high doses, significantly increased the content of the complexed acidic phospholipids in all tissues studied. High doses of other metabolites increased complexed acidic phospholipid content in some tissues, perhaps due to their conversion to 1,25-dihydroxyvitamin D. Linear relationships between serum 1,25-dihydroxyvitamin D levels and tissue complexed acidic phospholipid content are reported. It is suggested that one way in which this metabolite may directly contribute to calcification is by facilitating formation of lipids involved in this process. 相似文献