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)

This review reports the results of 2 recently completed long-term, randomised, double-blind, multicentre, controlled studies in which men and women with moderate to severe Paget's disease received oral alendronate 40 mg daily for 6 months One study conducted in the United States, compared the effects of alendronate 60 mg/day (n=41) with those of oral etidronate 400 mg/day (n=47); the other, conducted in the United Kingdom, Australia, and New Zealand, compared the effects of alendronate (n=27) with those of placebo (n=28). In both studies alendronate significantly reduced serum concentrations of alkaline phosphatase by more than 70%, which was significant in comparison with baseline (P < 0.001) and the comparator regimens (P < 0.001). Response to treatment (i.e. a > 60% decrease in or normalisation of serum alkaline phosphatase) was seen in more than three-quarters of patients treated with alendronate in both trials, compared with less than one-third of patients treated with etidronate and no patients treated with placebo. Radiologic scores, reflecting the status of osteolytic lesions, improved in a greater proportion of patients receiving alendronate than in those receiving etidronate or placebo. Histomorphometric analysis performed at 6 months showed that bone formed during alendronate treatment was of normal quality, without evidence of impaired mineralisation or other abnormalities. Alendronate was well tolerated, with an adverse event profile comparable with those of etidronate and placebo. These studies therefore showed that 6 months of treatment with oral alendronate suppresses disease activity in patients with Paget's disease of bone, with beneficial effects on biochemical, radiologic, and histomorphometric indices superior to those of etidronate and placebo.
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PMID:Alendronate in the treatment of Paget's disease of bone. 1266 42

Male osteoporosis is an important disease, with 25-30% of all hip fractures occurring in men. In a recent randomized, placebo-controlled study of osteoporotic males, alendronate 10 mg daily for 2 yr led to significant increments in bone mineral density (BMD), of a similar magnitude to those observed in postmenopausal women. In this study, specimens collected at intervals during the recent trial of alendronate in male osteoporosis, from 197 of the original 241 participants, were assayed for testosterone, estradiol, IGF-I, IGF binding protein 3 (IGFBP-3), bone-specific alkaline phosphatase [BSAP (serum)], and N-telopeptide of type I collagen corrected for creatinine [NTx (urine)]. Together with fracture and densitometry data from the original study, relationships were examined between BMD and serum IGF-I, IGFBP-3, testosterone, estradiol, BSAP, and urine NTx, both at baseline and during treatment with alendronate, to gain possible insights into the pathogenesis of male osteoporosis. Statistically significant (P <or= 0.05) associations were documented, at baseline, between the presence of vertebral fracture and each of serum IGF-I, serum IGFBP-3, serum free testosterone, total spine BMD, and total body BMD. No statistically significant correlations were observed between any of the baseline variables (IGF-I, IGFBP-3, estradiol, testosterone, and presence of vertebral fracture) and the BMD response to alendronate at any site. In a multivariate analysis, used to identify possible combinations of factors capable of predicting baseline BMD or response to alendronate, statistically significant (P <or= 0.01) relationships were seen, at baseline, between BMD and body mass index, age, and prior fracture. However, no statistically significant relationships were seen between any of the baseline variables (age, body mass index, testosterone, estradiol, IGF-I, IGFBP-3, and prior fracture) and change in BMD at any site. These data suggest that among men with osteoporosis it is not possible to identify patients who would be particularly good candidates for therapy with alendronate on the basis of biochemical or hormonal markers. Alendronate therapy appears to benefit osteoporotic males equally, irrespective of baseline serum testosterone, estradiol, IGF-I, or markers of bone turnover.
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PMID:An investigation of the predictors of bone mineral density and response to therapy with alendronate in osteoporotic men. 1467 Nov 65

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.
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PMID:Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial. 1524 Jun 9

The purpose of this study was to determine factors that could predict the one-year response of the lumbar bone mineral density (BMD) to alendronate treatment in elderly Japanese women with osteoporosis. Eighty-five postmenopausal women with osteoporosis, all of whom were between 55-88 years of age, were treated with alendronate (5 mg daily) for 12 months. Serum calcium, phosphorus, and alkaline phosphatase (ALP) and urinary NTX levels were measured at the baseline and 6 months, and lumbar (L1-L4) BMD was measured by dual energy X-ray absorptiometry at the baseline and 12 months. Multiple regression analysis was used to determine factors that were correlated with the percent change in lumbar BMD at 12 months. Lumbar BMD increased by 8.1 % at 12 months with a reduction in the urinary NTX level by 51.0 % at 6 months. Baseline lumbar BMD (R2=0.226, p < 0.0001) and percent changes in serum ALP and urinary NTX levels (R2=0.044, p < 0.05 and R2=0.103, p < 0.001, respectively) had a negative correlation with the percent change in lumbar BMD at month 12, while the baseline number of prevalent vertebral fractures (R2=0.163, p < 0.001), serum ALP level, and urinary NTX level (R2=0.074, p < 0.05 and R2=0.160, p < 0.001, respectively) had a positive correlation with it. However, baseline age, height, body weight, body mass index, years since menopause, serum calcium and phosphorus levels, and percent changes in serum calcium and phosphorus levels at 6 months did not have any significant correlation with the percent change in lumbar BMD at 12 months. These results suggest that lumbar BMD was more responsive to one-year of alendronate treatment in elderly osteoporotic Japanese women with lower lumbar BMD, more prevalent vertebral fractures, and higher bone turnover, who showed a greater decrease in bone turnover at 6 months, regardless of age, years since menopause, and physique. Alendronate may be efficacious in elderly Japanese women with evident osteoporosis that is associated with high bone turnover, and the percent changes in serum ALP and urinary NTX levels at 6 months could predict the one-year response of lumbar BMD to alendronate treatment.
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PMID:Determinants of one-year response of lumbar bone mineral density to alendronate treatment in elderly Japanese women with osteoporosis. 1534 10

Structural and functional impairment of skeletal system is a relevant cause of morbidity and disability in patients with Cushing's syndrome (CS). Approximately 30-50% of patients with CS experience fractures (particularly at the spinal level) consistent with the 50% incidence of osteoporosis. Growth failure, pubertal arrest are the hallmarks of CS in children and growing adolescents leading to reduced final adult height and peak bone mass. The decrease in osteoblast number and function, through different mechanisms, seems to play a central role in the bone loss in CS. Patients with CS have decreased serum levels of osteocalcin and alkaline phosphatase. Considering the preferential bone loss in the cancellous skeleton it is reasonable to measure BMD, possibly with Dual X-rays absorptiometry (DEXA) at lumbar spine, in all patients with CS. Patients cured from CS have increased prevalence of spine damage: therefore, a radiological follow-up of the skeleton should be included in the management of patients with CS not only during the active phase but also after cure. Glucocorticoid-induced osteoporosis is reversible. The recovery of bone loss in CS is slow, taking approximately ten years to become complete. In the meanwhile, patients with severe osteopenia are exposed to a high risk of fracture. Alendronate may induce a more rapid improvement in BMD than cortisol normalization alone and it could be useful in patients with persistent postsurgical hypercortisolism to prevent further bone loss. The decision to discontinue antiresorptive therapy should be based on clinical monitoring and DEXA measurements.
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PMID:Cushing's syndrome and bone. 1601 Apr 58

The purpose of the present study was to compare the effect of alendronate treatment on lumbar bone mineral density (BMD) and bone turnover in men and postmenopausal women with osteoporosis. Sixty men with primary or secondary osteoporosis and 318 women with postmenopausal osteoporosis were treated with alendronate. The primary end points were lumbar BMD and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels. The secondary end point was the incidence of vertebral and nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could complete the 12-month trial were analyzed. The mean ages of men and postmenopausal women were 69.1 and 70.4 years, respectively. Both men and postmenopausal women showed higher levels of urinary NTX as compared with normal range of premenopausal women. Alendronate treatment decreased urinary NTX level by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal women, respectively, at 12 months. Reduction in urinary NTX level and increase in lumbar BMD were smaller in men than in postmenopausal women. The incidence of vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and 8.3 and 7.5%, respectively, in postmenopausal women, with no significant difference in these incidences between them. These results suggested that alendronate treatment effectively increased lumbar BMD from baseline in men with primary or secondary osteoporosis following reduction in bone turnover, although its efficacy did not appear to be greater than in postmenopausal women with osteoporosis.
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PMID:Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis. 1656 94

Alendronate is an aminobisphosphonate, a selective inhibitor of osteoclast-mediated bone resorption. Due to its influence a decline of markers of bone turnover occurs. The latter react much sooner than it is possible to detect significant changes of bone density. In the submitted trial the authors investigated changes of selected markers: total alkaline phosphatase (ALP), osteocalcin (OC), N-terminal telopeptide fragment of collagen type I (NTx) after 3 months' treatment with alendronate, the influence on bone density after one year's treatment in 50 postmenopausal women with densitometrically verified osteoporosis. After one-year treatment in the whole group a significant increase of bone density occurred in the area L2-L4 by 4.52% (SD = 3.9), neck of the femur by 2.24% (SD = 3.6), trochanter by 2.81% (SD = 3.0) and total by 1.89% (SD = 2.7). Total ALP and OC in serum, similarly as NTx in urine declined significantly already after 3 months treatment and the decline persisted also after one year of treatment. With the change of bone density after one year correlated significantly only NTx. A decline of NTx after 3 months by more than 30% as compared with the baseline value was recorded in 81% patients and this change predicted a significant rise of the bone density in the area of the neck of the femur, on average by 30. Urinary NTx is a promising predictor of the effect of alendronate treatment. Its drop by more than 30% after 3 months justifies the assumption that bone density increased after one year's treatment.
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PMID:[Prediction of changes in bone density during alendronate treatment in postmenopausal women]. 1673 41

Bisphosphonates are nonhydrolysable pyrophosphate analogues that prevent bone loss in several types of cancer. However, the mechanisms of anticancer action of bisphosphonates are not completely known. We have previously shown that nitrogen-containing bisphosphonates directly inhibit alkaline phosphatase of UMR106 rat osteosarcoma cells. In this study, we evaluated the effects of alendronate on the migration of UMR106 osteosarcoma using a model of multicellular cell spheroids, as well as the alendronate effect on neutral phosphatases. Alendronate significantly inhibited the migration of osteoblasts in a dose-dependent manner (10(-6)-10(-4) M). This effect was also dependent on calcium availability. The spheroid morphology and distribution of actin fibers were also affected by alendronate treatment. Alendronate dose-dependently inhibited neutral phosphatase activity in cell-free osteoblastic extracts as well as in osteoblasts in culture. Our results show that alendronate inhibits cell migration through mechanisms dependent on calcium, and that seem to involve inhibition of phosphotyrosine-neutral-phosphatases and disassembly of actin stress fibers.
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PMID:Alendronate induces anti-migratory effects and inhibition of neutral phosphatases in UMR106 osteosarcoma cells. 1734 19

To elucidate the mechanism of the effect of bisphosphonates on bone metabolism, we investigated the effect of alendronate, a widely used bisphosphonate, on osteogenic and adipogenic differentiation in bone marrow stromal cells (BMSCs) derived from ovariectomized SD rats. Alendronate treatment not only increased the mRNA level of bone morphogenetic protein-2, runt-related transcription factor 2, osteopontin, bone sialoprotein, and alkaline phosphatase activity after osteogenic induction, but also decreased the mRNA level of peroxisome proliferator activated receptor gamma 2 and total droplet number indicated by Oil Red O staining after adipogenic induction. The effect of alendronate treatment was dose-dependent, and the difference of the osteogenic or the adipogenic potential between the treated group and the non-treated group was statistically significant (p<0.001). The MAPK-specific inhibitors, PD98059 and SP600125, but not the p38-specific inhibitor, blocked the alendronate-induced regulation of BMSC differentiation. Analysis of BMSCs induced in the presence of alendronate revealed an immediate increase in ERK and JNK phosphorylation. Taken together, these data suggest that alendronate acts on BMSCs to stimulate osteogenic differentiation and inhibit adipogenic differentiation in a dose-dependent manner; this effect is mediated via activating ERK and JNK.
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PMID:Stimulation of osteogenic differentiation and inhibition of adipogenic differentiation in bone marrow stromal cells by alendronate via ERK and JNK activation. 1848 85

Alendronate inhibits osteoclastic activity. However, some studies suggest alendronate also has effects on osteoblast activity. We hypothesized alendronate would enhance osteoblastic differentiation without causing cytotoxicity of the osteoblasts. We evaluated the effect of alendronate on the osteogenic differentiation of mouse mesenchymal stem cells. D1 cells (multipotent mouse mesenchymal stem cells) were cultured in osteogenic differentiation medium for 7 days and then treated with alendronate for 2 days before being subjected to various tests using MTT assays, Alizarin Red, enzyme-linked immunosorbent assay, energy-dispersive xray spectrophotometry, reverse transcriptase-polymerase chain reaction, confocal microscopy, and flow cytometric analysis. D1 cells differentiated into osteoblasts in the presence of osteogenic differentiation medium as confirmed by positive Alizarin Red S staining, increased alkaline phosphatase activity and osteocalcin mRNA expression, a calcium peak by energy-dispersive xray spectrophotometry, and by positive immunofluorescence staining against CD44. Osteogenic differentiation was enhanced after treatment with alendronate as confirmed by Alizarin Red S staining, elevated alkaline phosphatase activity and osteocalcin mRNA expression, a greater calcium peak by energy-dispersive xray spectrophotometry, and by immunofluorescence staining against CD44 by flow cytometric analysis. These data suggest alendronate enhances osteogenic differentiation when treated with mouse mesenchymal stem cells in osteogenic differentiation medium.
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PMID:Alendronate enhances osteogenic differentiation of bone marrow stromal cells: a preliminary study. 1866 32


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