Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro, strontium ranelate increases collagen and non-collagenic proteins synthesis by mature osteoblast enriched cells. The effects of strontium ranelate on bone formation were confirmed as the drug enhanced preosteoblastic cell replication. In the isolated rat osteoclast, a preincubation of bone slices with strontium ranelate induced a dose-dependent inhibition of the bone resorbing activity of treated rat osteoclast. Strontium ranelate dose-dependently inhibited preosteoclast differentiation. In a phase II dose ranging trial Strontium ranelate (500 mg, 1000 mg, 2000 mg/day) or placebo were given to 353 postmenopausal women with prevalent vertebral osteoporosis. At the conclusion of this 2-year study, the annual increase in lumbar BMD of the group receiving 2000 mg of strontium ranelate was + 7.3%, a significant increase in bone alkaline phosphatase, over a 6-month period and a significant decrease in N-telopeptide crosslinks throughout the 2-year period were seen. During the second year of treatment, the dose of 2000 mg was associated with a 44% reduction in the number of patients experiencing a new vertebral deformity. The primary analysis of the SOTI study, evaluating the effect of strontium ranelate 2000 mg on vertebral fracture rates, revealed a 41% reduction in the relative risk of patient experiencing a first new vertebral fracture with strontium ranelate throughout the 3-year study. The TROPOS study showed a significant reduction in the risk of experiencing a first non-vertebral fracture by 16% in the group treated with strontium ranelate throughout the 3-year study. A reduction in the risk of experiencing a hip fracture by 36% was also demonstrated in the patients at high risk of hip fracture (age > or =74 years and Femoral Neck T score < or = -2.4 according to NHANES normative value). All these results suggest that strontium ranelate is a new, effective and safe treatment of vertebral and non-vertebral osteoporosis, with a unique mode of action.
 ...
PMID:Comprehensive therapy in osteoporosis using a single drug: from ADFR to strontium ranelate. 1678 5

Osteoporosis is an important cause of morbidity in beta-thalassemia patients. Bisphosphonates have been recently used for the treatment of osteoporosis in beta-thalassemia. This study is a prospective quasi-experimental study to assess the efficacy and safety of zoledronic acid in thalassemics with osteoporosis. Eighteen thalassemia patients with osteoporosis were given zoledronic acid 4 mg intravenously every 3 months over a period of 12 months. The efficacy of treatment was assessed by measuring (BMD) at the lumbar spine, femoral neck, and hip at baseline, 6, and 12 months. Z-score was used to measure the BMD. Other medical assessments included markers of bone formation and resorption (bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline), and the assessment of pain score, analgesic score, and performance score. Ten thalassemic osteoporotic patients were followed up only with serial BMDs as controls. Both groups had no significant difference with respect to age, gender, and baseline BMD. Patients taking zoledronic acid had a significant increase in their lumbar spine, femoral neck, trochanter, and total hip BMD measurements over the 12-month period. Patients in the control group did not have any significant change in BMD measurements. There was a significant change in the levels of OC and BAP over the 12-month follow-up period. There was also a significant decrease in the number of painful sites experienced by the patients. Treatment of thalassemic osteoporotic patients with zoledronic acid is very effective in increasing BMD at the lumbar spine and hip and in reducing pain; it is also well-tolerated.
 ...
PMID:Intravenous zoledronic acid treatment in thalassemia-induced osteoporosis: results of a phase II clinical trial. 1683 Jan 43

The elevation of undercarboxylated osteocalcin (ucOC) means vitamin K insufficiency is significantly increased in elderly women, and is associated with high skeletal turnover, low BMD, and increased risk of osteoporotic fracture. The objective of the present study was to find out the level of ucOC and the prevalence of vitamin K deficiency in elderly Thai women. The upper limit of normal premenopausal ucOC level was 2.314 ng/ml, represented the cut-off level for vitamin K deficiency, 39.1% of elderly women had serum ucOC concentration above this level. Women with high serum ucOC level had a significantly lower BMD of ultradistal radius, distal 1/3 of radius and 25(OH)D level, higher serum PTH and alkaline phosphatase activity than women with a normal ucOC (p<0.05). Serum ucOC was correlated positively with PTH (r = 0.411, p< 0.001), modest negatively with serum 25(OH)D (r = -0.17, p= 0.013). The ucOC level of urbanized elderly was higher than that of rural elderly. It was concluded that vitamin K deficiency is one of the risks of osteoporosis with high prevalence in the Thai elderly especially urbanized ones, the supplement of vitamin K should be recommended in Thai osteoporotic patients especially the urbanized elderly.
 ...
PMID:Serum concentration of undercarboxylated osteocalcin and the risk of osteoporosis in thai elderly women. 1686 4

Four-and-a-half LIM 2 (FHL2) is a member of a family of LIM domain proteins which mediate protein-protein interactions. FHL2 acts as a coactivator and binds to important regulators of bone formation such as insulin-like growth factor binding protein (IGFBP)-5, androgen receptor, and beta-catenin. We hypothesized that FHL2 is an important regulator of bone formation. We evaluated growth and skeletal parameters in FHL2 knockout (KO) and wild-type (WT) mice at 4, 8, and 12 weeks of age. At 4 weeks of age, lack of FHL2 reduced femur, tibia, and total bone mineral content (BMC) and body weight in all mice. A gender-by-treatment interaction (P <or= 0.05) was observed for several parameters due to a greater reduction in females. Specifically, femur BMC was reduced 11-27% at 8 and 12 weeks of age and BMD was reduced 7-13% at all ages in female KO mice (P < 0.05). A similar reduction was observed in the tibias at 8 weeks of age. A 6% reduction (P = 0.07) in femur cortical thickness was observed at 12 weeks of age in female KO mice. Interestingly, a gender-specific reduction in IGFBP-5 expression was observed in the femurs of female KO mice. During differentiation of bone marrow stromal cells into osteoblasts, expression of osteocalcin, alkaline phosphatase, and bone sialoprotein was reduced 47-96% in FHL2 KO cells (P < 0.001). In conclusion, FHL2 is an important regulator of peak bone mass, lack of FHL2 produces gender- and site-specific effects on bone accretion and IGFBP-5 expression, and FHL2 is important for optimal osteoblast differentiation in vitro.
 ...
PMID:Disruption of four-and-a-half LIM 2 decreases bone mineral content and bone mineral density in femur and tibia bones of female mice. 1692 43

In this multicenter, randomized, double-blind controlled trial, the efficacy and safety of once-weekly dosing with 17.5 mg risedronate was compared with once-daily dosing with 2.5 mg risedronate in Japanese patients with involutional osteoporosis. A total of 496 patients were randomized to receive either once-weekly (n = 249) or once-daily (n = 247) treatment. All patients were supplemented with 200 mg/day calcium. Following 48 weeks of treatment, the mean (+/-SD) percent changes, from baseline, in the bone mineral density of the lumbar spine (L2-L4 BMD) in the once-weekly and once-daily treatment groups were 5.36 +/- 4.27% and 5.87 +/- 4.47%, respectively. The difference between the groups was -0.5% (95% confidence interval: -1.35% to 0.35%), demonstrating that the effect on BMD of once-weekly treatment was not inferior to that of once-daily treatment. The time-course reductions in biochemical markers of bone resorption (urinary N- and C-telopeptide of type I collagen) and bone formation (bone-specific alkaline phosphatase) were similar for the two dosing regimens. There were no differences in the incidence of new vertebral fractures or the worsening of existing fractures between the once-weekly (2.2%) and once-daily (2.7%) dosing regimens. No significant differences were observed between the two dosing regimens in the incidence or the type of adverse events. However, 10.1% of the patients in the once-daily group withdrew due to adverse events as compared to 5.2% in the once-weekly group. Moreover, drug-related adverse events, including upper gastrointestinal disorders and abnormal changes in laboratory parameters, tended to be less in the once-weekly dosing regimen than in the once-daily dosing regimen. In conclusion, once-weekly oral dosing with 17.5 mg risedronate was well tolerated in Japanese osteoporotic patients, and showed equivalent efficacy to once-daily oral dosing with 2.5 mg risedronate. This once-weekly regimen is expected to provide a more convenient therapeutic option as an alternative to daily dosing and to enhance patient compliance in long-term therapy for osteoporosis.
 ...
PMID:Efficacy and tolerability of once-weekly administration of 17.5 mg risedronate in Japanese patients with involutional osteoporosis: a comparison with 2.5-mg once-daily dosage regimen. 1693 74

To our knowledge anorexia nervosa (AN) adversely influences bone density, but whether qualitative characteristics of bone are also affected is not known. For this reason we investigated prospectively the changes in skeletal status in a population of 18 adolescent girls with AN aged 11.5-18.1 years (mean 15.9+/-1.9 years) using both dual-photon X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) measurements, bone turnover markers (osteocalcin, bone alkaline phosphatase - bALP, carboxy-terminal cross-linked telopeptide of type I collagen - ICTP), and laboratory investigations (serum total and ionised calcium, serum phosphate, urine calcium/creatinine ratio, luteinizing hormone - LH, follicle-stimulating hormone - FSH, estradiol). Measurements of bone mineral density at the spine (s-BMD) and total body (TB-BMD) and amplitude-dependent speed of sound (Ad-SOS) of the hand phalanges were performed at baseline, 7.8+/-2.4 and 19.4+/-5.6 months of follow-up. The mean values of TB-BMD, s-BMD and Ad-SOS measurements did not change during the period of observation. The mean Z-scores for TB-BMD and Ad-SOS were significantly lower after 19.4 months of observation vs. baseline (-1.06+/-1.00 vs. -0.67+/-0.98 vs. and -0.50+/-0.88 vs. 0.26+/-1.75, respectively). Z-scores for s-BMD decreased non-significantly (p=0.08). Among bone turnover markers, we observed a significant increase in bALP and a non-significant increase in osteocalcin serum concentrations which were below normal ranges for age, sex and Tanner stage at baseline. High baseline serum ICTP concentration decreased non-significantly, reaching normal ranges during the observation. We conclude that anorexia nervosa seriously affects skeletal status in adolescent girls. Bone turnover markers analysed together with densitometric parameters suggest that AN influences both bone formation and resorption processes. QUS measurements at hand phalanges may be an appropriate method in the evaluation of skeletal status in patients with AN.
 ...
PMID:Skeletal status and laboratory investigations in adolescent girls with anorexia nervosa. 1749 87

The aim of the present study is to investigate, based on the rat model of moderate and relatively high human exposure to cadmium (Cd), whether zinc (Zn) supplementation may prevent Cd-induced disorders in bone metabolism. For this purpose, male Wistar rats received Cd (5 and 50mg/l) or/and Zn (30 and 60mg/l) in drinking water for 6 and 12 months. Bone densitometry and biochemical markers of bone turnover were used to assess the effects of Cd or/and Zn. Bone mineral content (BMC) and density (BMD) were measured in the femur. Serum osteocalcin (OC) and alkaline phosphatase in trabecular (bT-ALP) and cortical (bC-ALP) bone were determined as bone formation markers, and carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in serum were measured as bone resorption marker. Serum concentration of calcium (Ca) and its renal handling, as well as Zn and Cd concentrations in the serum/blood, urine and femur were evaluated as well. The exposure to 5 and 50mg Cd/l (0.340+/-0.026 and 2.498+/-0.093mg Cd/kg body wt/24h, respectively), in a dose and duration dependent manner, affected bone turnover (inhibited bone formation and stimulated its resorption) and disturbed bone mineralization (decreased BMC, BMD and Zn concentration). Zn supply at the concentration of 30 and 60mg/l (1.904+/-0.123 and 3.699+/-0.213mg/kg body wt/24h, respectively) during Cd exposure influenced the Cd-induced disorders in bone metabolism. Zn administration to the Cd-exposed rats enhanced the bone ALP activity and prevented Cd-induced bone resorption, but had no statistically significant effect on BMC and BMD; however, mean values of the densitometric parameters in the rats receiving both Cd and Zn were higher than in those treated with Cd alone. Moreover, Zn supplementation at both levels of Cd exposure was found to prevent Cd accumulation in the femur and the Cd-induced decrease in bone Zn concentration. The results of the present study allow the conclusion that Zn supplementation during Cd exposure may partly protect from disorders in bone metabolism. The influence of Zn may be accompanied by its ability to prevent Cd-induced Zn deficiency and to decrease Cd accumulation in bone tissue. The findings seem to indicate that enhanced dietary intake of Zn in subjects chronically exposed to moderate and relatively high Cd levels may have a protective influence on the skeleton.
 ...
PMID:Effect of zinc supplementation on bone metabolism in male rats chronically exposed to cadmium. 1756 2

The aim of this study was to evaluate the short-term (1 year) changes of the lumbar spine (L2-L4) bone mineral density (LS-BMD) after parathyroidectomy (PTx) in pre- and postmenopausal women with primary hyperparathyroidism (PHPT). A series of 48 women (median age 56 years, range 23-82 years) with confirmed PHPT were prospectively enrolled in the study. Patients who received both oral contraceptives less than 2 years before the diagnosis and estrogen replacement therapy have previously been excluded. All patients underwent LS-BMD by dual energy x-ray absorptiometry before surgery. Patients were divided into two groups: group A (n = 12) premenopausal, and group B (n = 36) postmenopausal patients. The LS-BMD was repeated 12 months after successful PTx. Basal LS-BMD (0.852 +/- 0.061 vs. 0.748 +/- 0.142 g/cm(2)), serum calcium (2.95 +/- 0.23 vs. 2.94 +/- 0.26 mmol/L), creatinine (69.2 +/- 17.5 vs. 82.0 +/- 24.2 micromol/L), alkaline phosphatase (107.4 +/- 43.6 vs. 151.3 +/- 95.7 U/L), osteocalcin (28.6 +/- 9.3 vs. 28.2 +/- 8.3 microg/L), and PTH (192.7 +/- 133.2 vs. 175.2 +/- 132.1 ng/L) levels did not differ significantly (P = NS) between groups. The 1-year LS-BMD was 0.921 +/- 0.048 and 0.825 +/- 0.151 g/cm(2) in group A and B, respectively. In group B patients, the 1-year LS-BMD value did not improve significantly (P = NS), while in group A patients the difference between basal and postsurgical LS-BMD was significant (P < 0.01). In conclusion, PTx should be considered for all patients with PHPT and loss of bone density, but in premenopausal patients a greatest improvement of BMD may be found, suggesting the need of endogenous estrogens in complete lumbar bone recovery after surgery.
 ...
PMID:Bone mineral density improvement after successful parathyroidectomy in pre- and postmenopausal women with primary hyperparathyroidism: a prospective study. 1764 61

Renal osteodystrophy is a common complication of chronic renal failure and renal replacement therapy. The purpose of the study was to assess whether hemodialysis (HD) or hemodiafiltration (HDF) affects bone turnover. In all, 45 HD and 17 HDF patients were evaluated with respect to bone metabolism markers. We assessed PTH; markers of bone formation-alkaline phosphatase and its bone isoform, osteocalcin; markers of bone resorption- PICP, ICTP; Ctx; beta2-microglobulin; and urinary DPD. BMD were determined for femoral neck and lumbar spine (L2-L4) using DEXA. Hemodialyzed patients had lower calcidiol, calcitriol, and BMD in the femur neck, and higher phosphate, Kt/V, residual renal function, venous pH, osteocalcin, ALP, bALP, DPD, beta2-microglobulin, ICTP, Ctx, osteoprotegerin, and RANKL than patients on HDF. HDF seems to ameliorate bone metabolism in comparison with HD. Bone turnover in end-stage renal failure might be affected to some extent by the choice of renal replacement therapy.
 ...
PMID:Markers of bone metabolism in hemodialyses and hemodiafiltration. 1765 23

Peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand-activated transcription factor, is considered as an anti-osteoblastic factor associated with adiposity and the elderly osteoporosis due to a defect in osteoblastogenesis. We have found that oral administration of PPARgamma activator rosiglitazone decreased tibia BMD and serum ALP but left serum calcium and osteoclast marker C-terminal telopeptide unaffected. In addition, we examined the inhibitory mechanisms of PPARgamma on the bone formation by using PPARgamma activators ciglitazone and 15-deoxy-Delta(12,14)-prostaglandin-J2 (15d-PGJ2). Our data indicated that PPARgamma ligands decreased both mineralized bone nodules and alkaline phosphatase (ALP) activities in cultured primary osteoblasts. Reverse transcription polymerase chain reaction (RT-PCR) showed that the expression of bone morphogenetic protein-2 (BMP-2) and osteocalcin (OCN) was inhibited by ciglitizone and 15d-PGJ2. Furthermore, PPARgamma ligands inhibited NF-kappaB associated downstream COX-2 and iNOS osteogenic signaling. The ultrasound (US)-induced elevation of COX-2 and iNOS expression and nitric oxide (NO) production were attenuated in the presence of PPARgamma ligands. Furthermore, local administration of PPARgamma ligands into the metaphysis of rat tibia decreased the bone volume in secondary spongiosa. These results suggest that the activation of PPARgamma inhibits osteoblastic differentiation and the expression of several anabolic mediators involved in bone formation. These data may reflect osteoporosis and less bone formation in the aging people and patients treated with thiazolidinediones.
 ...
PMID:PPARgamma inhibits osteogenesis via the down-regulation of the expression of COX-2 and iNOS in rats. 1766 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>