Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: CAS:66376-36-1 (Alendronate)
 536 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postmenopausal osteoporosis is preventable and treatable. Women need not lose bone mineral density (BMD) after the menopause. Without intervention, all women lose bone after menopause, regardless of the amount of calcium, vitamin D, and exercise they undertake. Postmenopausal women need estrogen replacement, a selective estrogen receptor modulator (SERM), or a bisphosphonate to prevent bone loss. Alendronate, risedronate (bisphosphonates) and raloxifene (SERM) are approved for the prevention of bone loss. The diagnosis of at-risk postmenopausal women can best be accomplished by measuring BMD in all postmenopausal women age 65 years and older regardless of their risk profile and in all postmenopausal women under 65 years with one or more risk factors. Treatment guidelines direct physicians to treat postmenopausal women with T-scores lower than -2.0 SD regardless of their risk profile and postmenopausal women with T-scores lower than -1.5 SD with one or more risk factors. The lower the BMD, the greater the fracture risk, particularly in individuals with increased age, existing fragility fractures, or high bone turnover. The best intervention for a patient should be individually selected, based on careful clinical assessment. Although calcitonin is not approved for prevention, it is approved for treatment. The labeling of estrogens has been modified to state that they may be used to "manage" osteoporosis. The lack of efficacy of calcitonin to prevent bone loss during the first 5 years after menopause, and the lack of prospective fracture reduction data for estrogen, have resulted in these labeling restrictions. Alendronate, risedronate, and raloxifene are currently approved for the treatment of osteoporosis. Both of these compounds have been shown to increase BMD and decrease fracture risk. Monitoring of a patient's response to treatment may be accomplished using serial BMD testing and biomarkers of bone turnover.
 ...
PMID:New possibilities for diagnosis and treatment of osteoporosis. 1156 32

The effects of calcitonin, alendronate and fluorophosphate preventive treatment on ovariectomized rat femur were studied by comparing densitometric, mechanical, mineralogical and histomorphometric data. Sixty retired breeder female Sprague-Dawley rats, aged 10 months, were randomly divided into six groups. A group (baseline) was euthanized at the beginning of the study as a baseline group; four groups were ovariectomized and one was sham-operated (sham) and considered as a sham-aged group. A group of ovariectomized rats was used as a sham-therapy control (OVX) and received only deionized drinking water, while the other three received: a) salmon calcitonin (SCN) at a dose of 2 IU/kg/d s.c. (OVX + SCN); b) alendronate sodium salt (ALN) at a dose of 6 microg/kg/d administered by gavage (OVX + ALN); and c) L-glutamine monofluorophosphate (G-MFP) and calcium at a rate of 1:30 F/Ca at a dose of 0.21 mg F/6.30 mg Ca per kg/d by gavage (OVX + MFP). Significant increases (P < 0.05) of about 15 and 27% in femoral proximal epiphysis bone mineral density (BMD) of the OVX + ALN group were observed versus healthy groups and the OVX group, respectively. The OVX + ALN group also showed significant increases in femoral mid-diaphysis BMD when compared to OVX (18%, P < 0.001), OVX + SCN (14%, P < 0.05) and OVX + MFP (18%, P < 0.001) groups. In the OVX + MFP group, the three-point bending test demonstrated significant increases (P < 0.05) in maximal load of 21 and 22% when compared to the OVX and OVX + SCN groups, respectively. Also, stiffness data showed significant increases of the OVX + MFP (17%) and sham (14%) groups in comparison with the OVX group. A decrease in Mg (42%, P < 0.05), and increases in Ca (15%, P < 0.0001) and PO4 (8%, P < 0.005) content were found by comparing OVX + MFP and OVX groups. Trabecular bone volume results showed significant increases by comparing OVX + ALN and OVX groups (12.20%, P < 0.0005), as well as control groups. Tested agents were able to reduce the bone loss due to estrogen deficiency, but this did not always produce an increase in strength of the treated bone. Alendronate treatment prevented a decrease in bone mineral density and maintained bone mechanical properties after ovariectomy without impairment of bone mineralization in aged rats.
 ...
PMID:Comparison of calcitonin, alendronate and fluorophosphate effects on ovariectomized rat bone. 1166 3

Osteoporosis is a major clinical problem in older women and men. Almost any bone can fracture as a result of the increased bone fragility of osteoporosis. These fractures are associated with higher health care costs, physical disability, impaired quality of life, and increased mortality. Because the incidence of osteoporotic fracture increases with advancing age, measures to diagnose and prevent osteoporosis and its complications assume a major public health concern. BMD is a valuable tool to identify patients at risk for fracture, to make therapeutic decisions, and to monitor therapy. Several other modifiable and nonmodifiable risk factors for osteoporosis have also been identified. Treatment of potentially modifiable risk factors along with exercise and calcium and vitamin D supplementation forms an important adjunct to pharmacologic management of osteoporosis. Improved household safety can reduce the risk of falls. Hip protectors have been found to be effective in nursing home population. The pharmacologic options include bisphosphonates, HRT, SERMs and calcitonin. PTH had received FDA advisory committee approval. Alendronate has been approved for treatment of osteoporosis in men, and other treatments for men are under evaluation.
 ...
PMID:Osteoporosis in elderly: prevention and treatment. 1242 71

Drugs used to treat osteoporosis act either by inhibiting bone resorption or stimulating bone formation. Osteoclast formation and bone resorption require cell-to-cell contact between osteoblasts and osteoclast precursors and osteoclasts in the marrow. Interaction between the receptor for activation of nuclear factor kappa B (RANK) on the surface of preosteoclasts and osteoclasts and RANK ligand on the surface of osteoblasts is required to stimulate osteoclast formation and activation. Binding of the RANK ligand to its receptor and osteoclastogenesis are prevented by osteoprotegerin (OPG), a decoy receptor produced by osteoblasts and marrow stromal cells. Thus, interference in binding of the RANK ligand to RANK by OPG determines the rate of bone resorption. Antiresorptive drugs such as estrogen, raloxifene, bisphosphonates, salmon calcitonin, and osteoprotegerin increase bone mass by inhibiting osteoclast function and bone resorption. Osteoprotegerin is more potent since it also inhibits osteoclast formation. Raloxifene, a selective estrogen receptor modulator (SERM), is a member of a class of compounds that act through estrogen receptors and are agonists for bone, antagonists for breast and uterine tissue and may be cardioprotective. The drug was shown to prevent vertebral fractures. Alendronate and bisphosphonates are the only antiresorptive drugs that have been shown to decrease fracture rates for the hip in addition to spine and other sites. Bone morphogenetic proteins stimulate bone formation at local sites and are being developed to stimulate fracture healing. Parathyroid hormone (1-34) stimulates osteoblastic bone formation, markedly increases bone mass, prevents vertebral fractures and is under development to treat osteoporosis.
 ...
PMID:Advances in the treatment of osteoporosis. 1247 84

The aim of this review is to assess the efficacy of treatments for postmenopausal osteoporosis in women with low bone mass or with an existing vertebral fracture. We searched the literature for studies (randomized, double-masked, placebo-controlled and prospective) that reported on drugs registered in Europe or North America. We included 41 reports on 12 agents. To assess the consistency among the studies for each drug, we plotted the percent change in bone mineral density (BMD) for the control group against the percent change in BMD for the treated group for lumbar spine and femoral neck. We used methods of cluster analysis to determine consistency among the studies. For each agent we summarized the relative risk for vertebral fracture (patients with new fracture) and for hip fractures. The duration of the studies ranged from 1 to 4.3 years. The proportion of patients who discontinued treatment ranged from 4% to 80%. Most of the studies reported on change in BMD. Twenty-six studies (10 drugs) provided data on new vertebral fractures and 12 (6 drugs) on hip fractures. Apart from fluoride effects on spine BMD, increases in BMD with bisphosphonates were greater than those seen with the remaining treatments. Generally, for each agent the changes in BMD (relative to placebo) were consistent among the studies. The exceptions were calcitriol and calcitonin for changes in BMD of the spine and of the femoral neck. Alendronate, calcitonin, risedronate and raloxifene caused significant reductions in the risk of vertebral fractures. Alendronate, risedronate or the combination of calcium plus vitamin D had a significant effect on the risk of hip fracture. Most therapies are effective in increasing BMD; some decrease the risk of vertebral fracture. For hip fracture, alendronate and risedronate reduce the risk in women with osteoporosis, and calcium and vitamin D reduce the risk in institutionalized patients.
 ...
PMID:A comprehensive review of treatments for postmenopausal osteoporosis. 1257 79

The management of oestrogen deficiency bone loss needs to include general measures to protect against osteoporosis, the identification and treatment of other reversible causes of bone loss, and the use of proven agents for the treatment of osteoporosis. The general measures include improved physical activity, adequate diet (paying particular attention to calcium and vitamin D), and avoidance of behaviours that promote bone loss, such as smoking and alcohol abuse. The diseases that should be identified, other than estrogen-deficiency, include primary hyperparathyroidism, thyrotoxicosis and celiac disease. The treatments that are proven to prevent fractures in women with estrogen deficiency, include hormone replacement therapy, raloxifene, nasal calcitonin, bisphosphonates, (alendronate and risedronate) and parathyroid hormone. The most appropriate therapy in the younger woman is HRT, although the trial-based evidence that HRT prevents fractures is not strong. There is a wide choice of preparations and the use of continuous combined preparations avoids regular menstrual periods, one of the limitations to the use of HRT. Raloxifene has less effect on bone mineral density than HRT, but a similar effect on vertebral fractures and does not result in menstrual bleeding or increased risk of breast cancer. There is recent evidence suggesting that the beneficial effects on lipids translate into reduced risk of cardiovascular disease. Bisphosphonates are the standard treatment for the older woman with osteoporosis. Alendronate has been found to reduce the risk of spine, hip, and wrist fractures and has approval for a once weekly regimen, an approach that appears to prevent GI side effects. Risedronate reduces the risk of spine and non-vertebral fractures within the first year of treatment and has been shown to reduce the risk of hip fracture. It has not been associated with an excess of GI side effects. Parathyroid hormone therapy results in increases in BMD that are even greater than estrogen and the bisphosphonates and to an even greater reduction in the risk of fractures, particularly non-vertebral fractures. It works by stimulation of bone formation rather than by inhibition of bone resorption. However, it has to be given by daily injection. Thus, we have a wide choice of therapies for the woman with osteoporosis due to ovarian failure.
 ...
PMID:Management of osteoporosis due to ovarian failure. 1286 23

Standard pharmacological antiresorptive therapy for the prevention and/or treatment of postmenopausal osteoporosis now consists of four categories of drugs: estrogens, a selective estrogen receptor modulator (SERM), bisphosponates, and calcitonin. All of these drugs have been studied in randomized controlled trials, but meaningful comparisons of the efficacy of drugs have been difficult due to differences in baseline risks for fracture and differences in study design, including calcium and vitamin D supplementation, definition of fracture, and discontinuation rates. The current paper reviews results from pivotal studies of antiresorptive therapies with fracture as a primary endpoint, as well as head-to-head trials comparing these therapies using surrogate markers of fracture risk, and introduces the first head-to-head trial with fracture as a primary endpoint. The Evista Alendronate Comparison (EVA) trial, a multi-center, double-blind, double-dummy, randomized trial with two active treatment arms is currently underway to compare directly the osteoporotic fracture risk reduction efficacy of raloxifene and alendronate in postmenopausal women with osteoporosis as defined by bone mineral density. The results from this trial will permit more informed judgment by practitioners and provider groups concerning the relative clinical utility of these two drugs.
 ...
PMID:Antiresorptive treatment of postmenopausal osteoporosis: review of randomized clinical studies and rationale for the Evista alendronate comparison (EVA) trial. 1502 44

Osteoporosis is a major public health burden. The most devastating outcome of osteoporosis is fracture, which results in increased morbidity and mortality. These fractures most often occur in the vertebrae and indicate an increased risk of future vertebral and hip fractures. Consequently, it is important to identify patients at risk for fracture and to intervene with pharmacologic therapies, lifestyle changes, or both to reduce the frequency of the first or subsequent fracture. Moreover, because osteoporosis is a chronic condition requiring long-term therapy, factors that increase compliance and improve safety and efficacy outcomes should be considered when treatment is selected. The bisphosphonates alendronate and risedronate can substantially reduce the risk of both hip and vertebral fractures. Furthermore, these agents are available in once-weekly formulations that provide patients with a convenient alternative to a daily dosage regimen. Alendronate and the selective estrogen-receptor modulator raloxifene provide considerable vertebral fracture protection after 1 year of treatment, and risedronate markedly reduces the rate of vertebral and nonvertebral fractures after 6 months of treatment. Data suggest that calcitonin-salmon nasal spray also reduces the risk of vertebral, but not nonvertebral, fractures. Raloxifene decreases the risk of nonvertebral fracture, but only in women with severe prevalent vertebral fractures. Although evidence supports the efficacy of hormone therapy, the risks should be carefully considered before treatment is begun. In addition to the antiresorptive therapies, teriparatide is a daily injectable anabolic treatment that is effective in reducing the risk of vertebral and nonvertebral fractures. Therefore, clinicians and patients have several options for reducing the risk of fracture and achieving optimal dosing convenience.
 ...
PMID:Treatment of postmenopausal osteoporosis. 1597 18

Significant progress has been achieved in osteoporosis treatment, in terms of agents with novel mechanisms of action, of new schedules of administration, and of long-term treatment safety demonstration. Alendronate, ibandronate, intranasal calcitonin, parathyroid hormones, raloxifene, risedronate, hormone replacement therapy, strontium ranelate and zoledronate decrease the risk of vertebral fracture. Alendronate, risedronate, strontium ranelate and zoledronate reduce the risk of hip fracture in women with osteoporosis, hormone replacement therapy in postmenopausal women, and calcium and vitamin D in institutionalized patients. In two meta-analyses, the combination of calcium and vitamin D was able to reduce the risk of falling, and hip fracture risk was decreased (>700 IU/day). Two subsequently published large trials were unable to detect any antifracture effect. PTH(1-84) reduces the risk of new vertebral fracture. There is no indication that combining PTH with a bone resorption inhibitor has any additional benefit to either drug alone. Strontium ranelate is a new agent for the treatment of osteoporosis, with antifracture efficacy whatever the severity of osteoporosis. An extension of the phase 3 trials up to 5 years has shown sustained antifracture efficacy. The humanized monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL) denosumab causes a rapid, high-magnitude, dose-dependent inhibition of bone resorption. Spine, hip and forearm bone mineral density increased, to an extent slightly higher than with the weekly administration of 70 mg alendronate.
 ...
PMID:Osteoporosis: non-hormonal treatment. 1788 78

We investigated the effect of eel calcitonin (elcatonin) on the process of fracture repair in the osteotomized femur of cynomolgus monkeys, since they possess a Haversian remodeling system similar to that of humans. Alendronate was used for comparison. Twenty female cynomolgus monkeys (Macaca fascicularis), aged 18-22 years, were allocated into five groups: control (CNT, n = 4), low-dose elcatonin group (0.5 U/kg; ELL, n = 4), high-dose elcatonin group (5 U/kg; ELH, n = 4), low-dose alendronate group (10 microg/kg; ALL, n = 4) and high-dose alendronate group (100 microg/kg; ALH, n = 4). All animals were given subcutaneous injections twice a week for 3 weeks. Then fracture was produced surgically by transversely cutting the midshaft of the right femur and fixing with stainless steel plate. After fracture, treatments were continued until sacrifice at 26 weeks after surgery. The femora were assessed by micro CT, contact microradiograph, three-point bending mechanical test and histomorphometry. Micro CT showed that callus sizes in elcatonin-treated groups were similar to CNT, whereas alendronate-treated groups had larger calluses than those in the CNT and elcatonin-treated groups. Fracture lines almost disappeared in the CNT and elcatonin-treated groups but remained clear in the alendronate-treated groups. Total area did not differ significantly between the elcatonin-treated groups and the CNT but was significantly greater in the ALH compared to the CNT and elcatonin-treated groups, due to increased callus area in the ALH group. Callus remodeling was less suppressed in the elcatonin-treated groups than in the alendronate-treated groups when compared with callus remodeling in the CNT. Although no significant differences in structural mechanical properties such as ultimate load, stiffness and work to failure were found among all groups, ultimate stress was significantly reduced in the ALH group compared with CNT and ELL groups. In conclusion, mild suppression of callus remodeling by elcatonin did not impair overall fracture healing process. In contrast, alendronate delayed structural fracture healing process by strongly suppressing callus remodeling.
 ...
PMID:Eel calcitonin (elcatonin) suppressed callus remodeling but did not interfere with fracture healing in the femoral fracture model of cynomolgus monkeys. 1934 73


<< Previous 1 2 3 Next >>