Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a U.S. multicenter study of intermittent cyclical etidronate treatment for postmenopausal osteoporosis, approximately 20% of patients were nonresponders, defined as failure to increase spine bone mineral density. In contrast, essentially all patients who received 10 mg of alendronate daily in U.S. phase III trials showed some increase in spine bone mineral density. The current study was undertaken to determine the response to alendronate therapy in women with postmenopausal osteoporosis who were nonresponders to intermittent cyclical etidronate therapy. Twenty-five women with postmenopausal osteoporosis (mean +/- SD: 65.1+/-1.9 years of age), previously treated with intermittent cyclical etidronate with no increase of spine bone mineral density, and who agreed to be changed to alendronate, were recruited from a university out-patient clinic specializing in the treatment of osteoporosis for a prospective observational study. Measurements included bone mineral density of the lumbar spine and proximal femur (by dual-energy X-ray absorptiometry) and biochemical markers of bone remodeling (serum bone-specific alkaline phosphatase by immunoassay and urine deoxypyridinoline by high-pressure liquid chromatography). Patients had received intermittent cyclical etidronate for 3.3+/-0.4 years, during which time their bone density declined at spine and hip sites. They were then changed to alendronate 10 mg/day, which they received for 1.3+/-0.1 years; after treatment with alendronate, bone mineral density increased significantly at the lumbar spine (4.4+/-0.7% annualized,p < 0.0001) and at all hip sites. Bone markers also changed significantly after alendronate treatment: urine deoxypyridinoline fell from 6.8+/-0.8 to 5.5+/-0.6 micromol/mol creatinine (p < 0.0001) and serum bone-specific alkaline phosphatase rose from 4.6+/-0.5 to 11.9+/-1.0 ng/mL (p < 0.0001). Upper gastrointestinal side effects forced 4 of 25 patients (16%) to discontinue alendronate. Alendronate increases bone density at the spine and hip in patients who have not responded to intermittent cyclical etidronate therapy. Changes in bone markers suggest that alendronate causes more complete suppression of bone resorption and less inhibition (or stimulation) of bone formation.
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PMID:Alendronate increases spine and hip bone mineral density in women with postmenopausal osteoporosis who failed to respond to intermittent cyclical etidronate. 991 86

Alendronate is an antiresorptive therapy for osteoporosis and results in a decrease in bone turnover. To choose the optimal measurement for monitoring this therapy, the size of the change needs to be compared with the variability of the measurement. We studied 26 women with postmenopausal osteoporosis (bone mineral density [BMD] T score < -2.5), who were randomized in a 2:1 ratio to receive alendronate (10 mg/day) and calcium carbonate (500 mg/day) or calcium carbonate alone for 6 months. We measured serum markers of bone formation (osteocalcin [OC], bone isoform of alkaline phosphatase [BAP], and collagen type I C-terminal propeptide [CICP]) and urinary markers of bone resorption (cross-linked N-telopeptide [NTx], free deoxypyridinoline [iFDpd], and free pyridinolines). All subjects had two measurements 1 week apart at baseline to calculate the short-term variability. Biochemical measurements were then made at 4, 8, 12, 24, and 25 weeks. Measurements of bone mass were made by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and proximal femur twice at baseline and then at 24 and 25 weeks. The mean difference in change in BMD and markers between both groups at the end of the study that were significant were (short-term variability in brackets): DXA total hip 4.3% (2.5%), NTX 49% (10%), iFDpd 22% (12%), OC 28% (13%), BAP 31% (13%), and CICP 31% (11%). Five of the six markers showed significant responses to alendronate therapy, but they differed in the relationship between size of response and variability. These biochemical markers performed better than DXA for monitoring alendronate therapy over 6 months.
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PMID:Monitoring alendronate therapy for osteoporosis. 1023 82

In summary, the clinical efficacy studies provide clear evidence that treatment with oral alendronate markedly suppresses bone turnover and produces clinical improvement in pagetic patients. Serum alkaline phosphatase was greatly decreased by treatment, and the response to alendronate was superior to that observed for currently available therapies such as etidronate and calcitonin, which usually reduce alkaline phosphatase, on average, by 40%-50%. Alendronate also markedly reduced urinary resorption markers and induced radiologic improvement of pagetic osteolysis. A majority of alendronate-treated patients normalized their serum alkaline phosphatase by month 6. This observation is likely to be relevant to the duration of response to treatment, as previous studies have shown that the degree of suppression of alkaline phosphatase after antiresorptive treatment correlates with the duration of remission. Therefore, patients who responded to treatment with alendronate, especially those who normalized their alkaline phosphatase levels, are likely to maintain the biochemical remission for several years. Indeed, preliminary unpublished data seem to indicate that alendronate is capable of producing long-term biochemical remission in the majority of patients. In addition to its efficacy, the safety and tolerability profile of alendronate 40 mg/day was very favorable and, overall, comparable to that of placebo.
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PMID:Treatment of Paget's disease of bone with alendronate. 1032 31

Alendronate and estrogen are effective therapies for postmenopausal osteoporosis, but their efficacy and safety as combined therapy are unknown. The objective of this study was to evaluate the addition of alendronate to ongoing hormone replacement therapy (HRT) in the treatment of postmenopausal women with osteoporosis. A total of 428 postmenopausal women with osteoporosis, who had been receiving HRT for at least 1 yr, were randomized to receive either alendronate (10 mg/day) or placebo. HRT was continued in both groups. Changes in bone mineral density (BMD) and biochemical markers of bone turnover were assessed. Compared with HRT alone, at 12 months, alendronate plus HRT produced significantly greater increases in BMD of the lumbar spine (3.6% vs. 1.0%, P < 0.001) and hip trochanter (2.7% vs. 0.5%, P < 0.001); however, the between-group difference in BMD at the femoral neck was not significant (1.7% vs. 0.8%, P = 0.072). Biochemical markers of bone turnover (serum bone-specific alkaline phosphatase and urine N-telopeptide) decreased significantly at 6 and 12 months with alendronate plus HRT, and they remained within premenopausal levels. Addition of alendronate to ongoing HRT was generally well tolerated, with no significant between-group differences in upper gastrointestinal adverse events or fractures. This study demonstrated that, in postmenopausal women with low bone density despite ongoing treatment with estrogen, alendronate added to HRT significantly increased bone mass at both spine and hip trochanter and was generally well tolerated.
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PMID:Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a randomized, controlled clinical trial. 1048 68

To evaluate the efficacy and safety of alendronate, a double-masked, active (alfacalcidol) controlled comparative study for 48 weeks was carried out in a total of 210 Japanese patients with osteoporosis. The doses of alendronate and alfacalcidol were 5 mg/day and 1 microgram/day, respectively. The lumbar bone mineral density (LBMD) values observed at 12, 24, 36 and 48 weeks after the initiation of alendronate treatment were 3.53 +/- 0.53%, 5.37 +/- 0.62%, 5.87 +/- 0.74% and 6.21 +/- 0.59% (mean +/- SE), respectively, higher than the baseline value. Corresponding values in the alfacalcidol group were 1.50 +/- 0.43%, 0.69 +/- 0.63%, 1.12 +/- 0.60% and 1.36 +/- 0. 63%, respectively. There was a significant difference between the two groups at each time point (p<0.05 or p<0.001). The bone turnover markers were depressed during treatment in the alendronate group: -32.2% for alkaline phosphatase, -53.7% for N-terminal osteocalcin and -45.0% for urinary deoxypyridinoline compared with the corresponding baseline values. On the contrary, no notable changes in these parameters were observed in the alfacalcidol group. Treatment with alendronate caused a transient decrease in serum calcium concentrations associated with an increase in the serum level of intact parathyroid hormone. In contrast, treatment with alfacalcidol resulted in a tendency of these parameters to change in the opposite direction. No difference in fracture incidence between the two groups was observed. The overall safety of alendronate was comparable to that of alfacalcidol. In conclusion, although it was a relatively short-term study of 48 weeks, the results of the present study indicate that alendronate at the daily dose of 5 mg was effective in increasing LBMD and that no serious drug-related adverse events were observed in the alendronate-treated patients. Alendronate is more efficacious than alfacalcidol in increasing bone mineral density, although the mechanisms of the actions of the two drugs are apparently different.
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PMID:A double-masked multicenter comparative study between alendronate and alfacalcidol in Japanese patients with osteoporosis. The Alendronate Phase III Osteoporosis Treatment Research Group. 1052 9

Serum calcitriol levels decrease with advancing age in relation to reduced dietary intake or poor intestinal absorption of vitamin D. These decreased levels affect the development of senile osteopenia, which can be effectively prevented by the administration of alendronate and calcium. To evaluate the effect of a combined treatment with alendronate and calcitriol on bone mineral density (BMD), we followed 152 osteopenic postmenopausal women, aged 55-75 years, for 9 months. They were divided into three groups. The first group was treated every other day with 0.25 microgram of synthetic 1,25-dihydroxyvitamin D3 plus 10 mg alendronate. The second group received the same dose of alendronate plus calcium (500 mg/day). The third group received only calcium (500 mg/day). BMD measurements were made at the level of the lumbar spine and the femoral neck. At the beginning and at the end of the period of treatment the same biochemical analyses of bone metabolism were made. There were no significant differences in the baseline values of the three groups in the biological parameters. Alendronate plus calcium treatment led to a significant reduction in total alkaline phosphatase and hydroxy prolinuria as well as to a significant increase in lumbar and femoral bone density. The same changes were observed in the group treated with alendronate plus calcitriol except that femoral BMD did not significantly improve. These results show that continuous treatment for 9 months with calcitriol or calcium in combination with alendronate significantly increases both vertebral and femoral neck density (from 3.8% to 4.5% and from 0.61% to 2.36% respectively) in osteopenic postmenopausal women. The effects of both combinations on bone mass are clearly greater than those achieved by calcium monotherapy.
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PMID:Calcitriol and alendronate combination treatment in menopausal women with low bone mass. 1056 24

The FOSIT (Fosamax International Trial) was a placebo-controlled, double blind trial, to determine the effects of daily oral dose of 10 mg alendronate-sodium (Fosamax) or placebo, for one year in postmenopausal osteoporotic women. It was an international, multicenter study; the 153 centers distributed over 34 countries. The number of patients was 1908. Authors report the data of the only Hungarian study site, Debrecen. Twenty women [age (mean +/- SD) 62 +/- 8 years with bone mineral density--BMD--< or = 0.98 g/cm2 at the lumbar spine by LUNAR DPX densitometer] were enrolled into the study and randomly assigned to oral alendronate 10 mg daily or placebo (10 patients in each group). Patients in both groups received 500 mg of calcium. Bone density measurements were performed by dual x-ray absorptiometry (DXA) at months 0, 3, 6, and 12 at the lumbar spine and at the femoral neck. Biochemical indices of bone turnover [bone specific alkaline phosphatase (bAP) and urinary N-telopeptide/creatinine ratio (NTx/crea] were also measured every three months. Percent change of the BMD measurements from baseline at one-year in the alendronate group was +6% and in the placebo group -0.7% on the lumbar spine (p < 0.001). Alendronate treatment increased the bone mineral density in the femoral neck, the trochanter, the Ward's triangle and the total hip by +3.2, +1.6, +3.5, +2.2% respectively, meanwhile the changes in the placebo group were -1.2%; -0.7%; -0.9%; -0.8%, respectively, the difference was not significant. Urinary NTx/crea decreased by 70.6% in the alendronate group and by 9.4% in the placebo group, while bAP decreased by 47.4% in the alendronate group and 15.2% in the placebo group (p < 0.001). In conclusion, after one year of treatment with alendronate induced increase of bone mineral density at the lumbar spine and decreased the bone turnover as compared to the placebo group.
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PMID:[The effect of a one-year alendronate therapy on postmenopausal osteoporosis. (Results in Hungary of an international multicenter clinical study)]. 1064 67

The bisphosphonate alendronate and conjugated equine estrogens are both widely used for the treatment of postmenopausal osteoporosis. Acting by different mechanisms, these two agents decrease bone resorption and thereby increase or preserve bone mineral density (BMD). The comparative and combined effects of these medications have not been rigorously studied. This prospective, double blind, placebo-controlled, randomized clinical trial examined the effects of oral alendronate and conjugated estrogen, in combination and separately, on BMD, biochemical markers of bone turnover, safety, and tolerability in 425 hysterectomized postmenopausal women with low bone mass. In addition, bone biopsy with histomorphometry was performed in a subset of subjects. Treatment included placebo, alendronate (10 mg daily), conjugated equine estrogen (CEE; 0.625 mg daily), or alendronate (10 mg daily) plus CEE (0.625 mg daily) for 2 yr. All of the women received a supplement of 500 mg calcium daily. At 2 yr, placebo-treated patients showed a mean 0.6% loss in lumbar spine BMD, compared with mean increases in women receiving alendronate, CEE, and alendronate plus CEE of 6.0% (P < 0.001 vs. placebo), 6.0% (P < 0.001 vs. placebo), and 8.3% (P < 0.001 vs. placebo and CEE; P = 0.022 vs. alendronate), respectively. The corresponding changes in total proximal femur bone mineral density were +4.0%, +3.4%, +4.7%, and +0.3% for the alendronate, estrogen, alendronate plus estrogen, and placebo groups, respectively. Both alendronate and CEE significantly decreased biochemical markers of bone turnover, specifically urinary N-telopeptide of type I collagen and serum bone-specific alkaline phosphatase. The alendronate plus CEE combination produced slightly greater decreases in these markers than either treatment alone, but the mean absolute values remained within the normal premenopausal range. Alendronate, alone or in combination with CEE, was well tolerated. In the subset of patients who underwent bone biopsies, histomorphometry showed normal bone histology with the expected decrease in bone turnover, which was somewhat more pronounced in the combination group. Thus, alendronate and estrogen produced favorable effects on BMD. Combined use of alendronate and estrogen produced somewhat larger increases in BMD than either agent alone and was well tolerated.
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PMID:Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group. 1069 Aug 82

Chronic idiopathic hyperphosphatasia (CIH), also known as juvenile Paget's disease, is characterized by increased bone turnover, persistently elevated serum alkaline phosphatase concentrations and progressive bone deformities. The pathogenesis of the disease is unknown. Currently, there is no specific treatment and agents that reduce bone turnover have been tried in some cases with limited success. In this report, we present our experience with alendronate treatment in a 17 year-old boy with CIH. Ten weeks of treatment with alendronate resulted in marked clinical improvement and normalization of serum alkaline phosphatase activity. Serum osteocalcin and urinary deoxypyridinoline levels were decreased approximately 50% compared to pretreatment values, indicating decreased bone turnover rate. Alendronate seems to be a promising and safe agent for treatment of CIH.
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PMID:Effect of alendronate treatment on the clinical picture and bone turnover markers in chronic idiopathic hyperphosphatasia. 1071 70

Nowadays, bisphosphonates are considered the drugs of choice for the treatment of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit cholesterol biosynthesis and that this might be relevant for their actions on bone osteoclasts. The study includes 87 postmenopausal women with moderate to severe osteoporosis. The patients were randomly assigned to intravenous (iv) infusion of 50 mg of the aminobisphosphonate Neridronate dissolved in 100 ml of saline solution every 2 months for a year (44 patients). The remaining 43 served as controls. At the time of each infusion blood samples were obtained for the evaluation of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and total and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was measured in fasting urine specimens. In the control group no significant changes were observed throughout the study period for any of the biochemical variables. In the Neridronate-treated patients both bone AP and f-DPD excretion fell significantly by 15-20%. In these patients serum total cholesterol and serum triglycerides showed marginal decreases, which were occasionally significant. LDL-C and Apo B fell by 5-6% and these changes were statistically significant at most time points. Apo A-I and HDL-C rose progressively with time. At the 12th month, HDL-C rose 17-18% (p < 0.0001) above the baseline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisphophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant.
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PMID:Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol. 1075 May 76


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