Prevention Of Postmenopausal Osteoporosis Research Articles

Ibandronate

Ibandronate (ibandronic acid; Bonviva, Boniva), a nitrogen-containing bisphosphonate available in once-monthly oral and quarterly intravenous formulations for intermittent administration, has been approved for the treatment of osteoporosis in postmenopausal women in the EU, the US and many other countries worldwide. The once-monthly oral formulation has also been approved for the prevention of postmenopausal osteoporosis in the US. Ibandronate is an effective and generally well tolerated bisphosphonate that offers an alternative to other bisphosphonates as a first-line treatment for postmenopausal osteoporosis. It occupies a similar position with respect to the prevention of osteoporosis in postmenopausal women at risk for the disease. The once-monthly oral and quarterly intravenous dosage regimens have the potential to improve treatment adherence and persistence, and hence clinical outcomes, compared with more frequently administered oral bisphosphonates. Intravenous ibandronate may be particularly useful for postmenopausal osteoporotic women who are noncompliant with, or are unable to tolerate or receive, oral bisphosphonates. Thus, intermittent ibandronate extends the range of pharmacological therapies for the treatment and prevention of postmenopausal osteoporosis.

Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis

Bazedoxifene acetate (WAY-140424; TSE-424) is an investigational non-steroidal indole-based selective estrogen receptor modulator (SERM) – also classified as an estrogen agonist/antagonist – that is being developed as a daily oral drug for the prevention and treatment of postmenopausal osteoporosis (PMO). Clinical studies have shown favorable effects on the skeleton, with prevention of bone loss in postmenopausal women without osteoporosis and reduction in vertebral fracture risk in women with PMO, without stimulation of endometrium or breast. Bazedoxifene combined with conjugated estrogens is an investigational tissue-selective estrogen complex, the first in a new class of therapeutic agents that pairs a selective estrogen receptor modulator with estrogens. Clinical trials with bazedoxifene/conjugated estrogens in postmenopausal women have shown skeletal benefit with improvement in menopausal vasomotor symptoms and little or no stimulation of endometrial or breast tissue. Bazedoxifene/conjugated estrogens is a potential agent for the prevention of PMO and control of menopausal symptoms.

Extraskeletal effects of the novel selective estrogen receptor modulator (SERM) bazedoxifene acetate (BZA): a 12-month study in ovariectomized rats

Bazedoxifene acetate (BZA) is a novel SERM currently in development as monotherapy for the prevention and treatment of postmenopausal osteoporosis and in pair with conjugated estrogens for the treatment of menopausal symptoms and prevention of postmenopausal osteoporosis. We examined effects of BZA on body, uterine, and pituitary weights, reproductive tract histology, and serum lipids to assess its safety in ovariectomized (OVX), 6-month-old female rats. In active treatment groups, 3 doses of BZA (0.15, 0.3, and 1.5 mg/kg/day) were administered to OVX animals by oral gavage for 12 months. Control groups included an untreated baseline group, untreated sham-operated animals, untreated OVX animals, and estrogen-treated (17α-ethinylestradiol [EST], 0.03 mg/kg/day) OVX group. Body, uterine, and pituitary weights were recorded as baseline and terminal procedures. The uterus and pituitary were examined macro- and microscopically. Laboratory investigations included serum cholesterol and triglycerides, with blood samples collected at baseline and throughout the study. Although animals in all groups had increased body weights, BZA-treated animals gained less weight than OVX controls and sham and EST-treated animals. Uterine weights were decreased in all BZA groups compared with the sham and EST groups and were slightly increased compared with the OVX control group. BZA-related uterus weight changes were correlated with decreased incidence of small uteri and decreased severity of uterine atrophy vs. OVX controls. Pituitary weights were decreased in all BZA groups compared with the OVX and sham control groups; these decreases were comparable to those in the EST group and were not correlated with macro- or microscopic findings. Total cholesterol levels in BZA-treated groups decreased from baseline at week 3 and remained lower compared to those in the sham-operated and OVX control groups and comparable to those in the EST group through the study's end. From week 25 through study end, animals in the 0.3 and 1.5 mg/kg/day BZA groups had triglyceride levels comparable to those in the sham-operated group and lower than in the EST group. We conclude that bazedoxifene, a novel SERM, has a promising therapeutic profile based on the safety outcomes observed in this animal model of accelerated bone loss: BZA prevented ovariectomy-associated increases in body weight, demonstrated minimal effects on uterine weight, and reduced serum cholesterol levels.

Endometrial and ovarian safety of bazedoxifene (BZA) in the prevention of postmenopausal osteoporosis

Endometrial safety is a key concern with selective estrogen receptor modulators (SERMs). BZA is a novel SERM that showed no significant uterotropic effects in preclinical and small clinical studies. This study assessed the efficacy and endometrial/ovarian safety of BZA for the prevention of osteoporosis. A randomized, double-blind, placebo- and raloxifene (RLX)-controlled phase III clinical trial conducted at 101 sites in the United States and globally. Generally healthy, postmenopausal (≥1 year) women ≥45 years of age were randomized to receive BZA 10, 20, or 40 mg; RLX 60 mg; or placebo daily for 2 years. Exclusion criteria included endometrial hyperplasia or endometrial thickness >5 mm. The primary efficacy endpoint was change from baseline in lumbar spine (LS) bone mineral density (BMD) at 24 months. Endometrial and ovarian safety were evaluated based on double-wall endometrial thickness and ovarian volume assessed by transvaginal ultrasound (TVUS) at Months 6, 12, 18, and 24, and endometrial biopsies performed at Months 12 and 24. The presence of, or changes in, ovarian cysts compared to baseline was assessed. Of the 1583 women (mean age ± standard deviation [SE], 57.6 ± 6.5 years) who received ≥1 dose of study medication, 1014 (70.7%) had an intact uterus, and 963 (60.8%) had TVUS at baseline and ≥1 on-therapy timepoint. LS BMD was preserved with BZA 10, 20 and 40 mg relative to placebo (P<0.001). Endometrial thickness with BZA 10, 20, and 40 mg remained stable over 24 months (mean change from baseline [mm] ± SE, 0.05 ± 0.11, −0.01 ± 0.10, and −0.16 ± 0.11, respectively), and was not different from baseline, placebo (−0.23 ± 0.10 mm), or RLX (−0.05 ± 0.11). There were no cases of endometrial hyperplasia or malignancy with any dose of BZA (n = 414) or RLX (n = 147), and 1 case of endometrial malignancy with placebo (n = 139). The incidence of endometrial polyps at 24 months was similar among BZA 10, 20, and 40 mg (2.2%, 3.4%, and 2.3%, respectively), and not different from placebo (3.5%); a slightly higher incidence of polyps was reported with RLX (4.7%). There were no clinically important changes from baseline or differences between treatment groups in the number or size of ovarian cysts or ovarian volume. BZA exhibits an excellent endometrial and ovarian safety profile, preserves BMD, and is an important addition to the therapeutic armamentarium for the prevention of postmenopausal osteoporosis.

Hormone replacement as the first-line prevention for postmenopausal osteoporosis

For more than two decades, HRT was the treatment of choice for the prevention of postmenopausal osteoporosis. HRT is known to be efficacious in preventing postmenopausal bone loss and fractures that occur as a result of postmenopausal estrogen deficiency. Nevertheless, with the publication of the results from the Women’s Health Initiative (WHI) in 2002, the world’s largest randomized placebo-controlled study of HRT in seemingly healthy, yet elderly, women, the political climate surrounding HRT use in postmenopausal women in general changed suddenly and dramatically. The WHI results indicated a lack of prevention of cardiovascular disease (CVD) in this population, and reported a small but significantly increased risk of CVD among women in the HRT arm, which was in clear contrast to the results from the abundant animal and large epidemiological studies. The WHI study has been criticized regarding the study population and HRT regimen used. Very recent reanalysis of the WHI data suggested that HRT in early me...

Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-tumor Activity of Resveratrol

Osteoporosis is a major public health problem and the most obvious preventive strategy, hormone replacement therapy, has lost favor due to recent findings of the Women's Health Initiative regarding increased risks of breast cancer and cardiovascular disease. Resveratrol, a naturally occurring compound possessing estrogenic activity, is thought to have considerable potential for therapy of osteoporosis. In the present study, resveratrol was found to exhibit bone-protective effects equivalent to those exerted by hormone replacement therapy and decrease the risk of breast cancer in the in vivo and in vitro models. Forkhead proteins were found to be essential for both effects of resveratrol. The bone-protective effect was attributable to induction of bone morphogenetic protein-2 through Src kinase-dependent estrogen receptor activation and FOXA1 is required for resveratrol-induced estrogen receptor-dependent bone morphogenetic protein-2 expression. The tumor-suppressive effects of resveratrol were the consequence of Akt inactivation-mediated FOXO3a nuclear accumulation and activation. Resveratrol is therefore anticipated to be highly effective in management of postmenopausal osteoporosis without an increased risk of breast cancer.

Bazedoxifene: A Third-Generation Selective Estrogen Receptor Modulator for Treatment of Postmenopausal Osteoporosis

To review clinical studies and other available literature regarding the development, pharmacology, toxicology, pharmacokinetics/pharmacodynamics, adverse effects, and place in therapy of bazedoxifene, a selective estrogen receptor modulator (SERM), currently in Phase III clinical trials for the treatment and prevention of postmenopausal osteoporosis. A literature search was performed of PubMed (1966-February 2007), International Pharmaceutical Abstracts (1970-February 2007), Web of Science (1975-February 2007), Biological Abstracts (1926-2007), and Google Scholar (2001-February 2007) databases, using the search terms bazedoxifene, TSE-424, Indole-33, WAY-140424, selective estrogen receptor modulator, and SERM. In addition, product information was requested from the manufacturer, and www.clinicaltrials.gov was searched for unpublished Phase III clinical trials in progress. Articles on Phase I and II trials were selected for review, as well as articles discussing preclinical development of bazedoxifene. At the time of writing, no articles on Phase III trials were available for review. Abstracts of unpublished data were reviewed, as was information provided by the manufacturer. Bazedoxifene is a third-generation SERM currently in Phase III clinical trials. It has been found to act as an agonist on skeletal tissue, with bone turnover reduced by 20-25% with doses of 20 or 40 mg daily. In addition, bazedoxifene has been found to be an antagonist on breast tissue and uterine tissue, demonstrating inhibition of breast tissue proliferation and decreased endometrial stimulation as the dose is increased. Current literature suggests that bazedoxifene will likely be safe and effective when used in the treatment of postmenopausal osteoporosis. Completion of Phase III clinical trials will more fully elucidate the safety and efficacy profile of bazedoxifene, as well as more clearly define its place in therapy.

Calcium and vitamin D – for whom and when

The basis of 'nutritional' interventions for the prevention of postmenopausal osteoporosis and osteoporotic fracture is a large topic with much genetic and biochemical evidence, as well as the results of randomized controlled trials, to guide the investigator and clinician. The efficacy of treatment with calcium and vitamin D was once controversial, but with the advent of controlled clinical trials using bone mineral density as an endpoint it has become clear that calcium with or without vitamin D therapy can lead to reductions in the rate of bone loss in postmenopausal women of all ages. Furthermore, with certain caveats, calcium with vitamin D therapy in the older postmenopausal woman can lead to useful reductions in fracture rates and falls, especially in populations with reduced exposure to sunlight, which is potentially the majority of postmenopausal women in both developed and developing countries. However, estrogen, selective estrogen receptor modulators (SERMs) and bisphosphonates (especially when given in combination with calcium and vitamin D) are more efficacious in preventing fracture, particularly in postmenopausal patients with impaired bone structure.

In vivo and in vitro activity of genistein in osteoporosis

<b>Background</b> : Osteoporosis is conventionally treated with synthetic estrogens. However, the serious side effects of hormone replacement therapy (HRT) hampers the clinical use of estrogens. Hence, alternatives for estrogens are being explored, one of which is the isoflavone, genistein. Many studies show that genistein may exert positive effects on bone. However, there are also studies which report no overall association between genistein intake and bone marrow density (BMD) and fracture rates. The effect of genistein on bone loss is still controversial. <br><b>Aims</b> : In this study, we evaluated both in vivo and in vitro pharmacological effects of genistein in osteoporosis. <br><b>Materials and Methods</b> : MTT and ALP activity assays were performed to evaluate genistein's in vitro activity on MC3T3-E1 cells. The OVX rat model was used to test genistein's in vivo effects by determination of BMD and bone calcium and phosphorus content after treatment for 12 weeks. <br><b>Results and Conclusions</b> : The data showed that 10^-6 M genistein both increased the number of MC3T3-E1 cells and elevated ALP activity significantly. In vivo, 9 or 18 mg/kg doses of genistein were found to prevent osteoporosis after 12 weeks treatment. Thus, our results indicated that genistein may be an alternative for HRT in prevention of postmenopausal osteoporosis.

β-Blocker and Other Analogous Treatments that Affect Bone Mass and Sympathetic Nerve Activity in Ovariectomized Rats

We investigated whether treatments with beta-blockers or other administrations that have similar actions to beta-blockers, such as Chinese herbs or needling, were effective in treating osteoporosis induced by ovariectomy (OVX). Female Wister rats were divided into five groups: a sham-operated control group treated with vehicle (Sham, n = 8), an ovariectomized (OVX) group treated with vehicle (Model, n = 8), an OVX group administered with propranolol (Pro, n = 10), an OVX group administered an ethanol extract of Fructus Citri Sarcodactylis (Fcs, n = 9), and an OVX punctured at Sanyinjiao (SP-6) and Neiguan (PC-6) (Needling, n = 8). The treatment started when rats were 12 weeks old and continued for 24 weeks. Serum osteocalcin and urinary deoxypyridinoline (Dpd) levels were upregulated in rats in response to OVX, together with a significantly decreased BMD and trabecular bone area. The Pro, Fcs and Needling treatment improved the decreased BMD and the trabecular area, increased the trabecular number, lowered the trabecular separation to some extent as well as significantly depressed the urinary Dpd levels (p < 0.05). The bone formation markers, such as the mineralizing surface, mineral apposition rate and bone formation rate were not significantly changed, along with a slightly higher trend of osteocalcin levels when compared with the Model rats. The slower heart rate and lower plasma NE levels in these therapeutic groups were also found. Our results suggested that propranolol, Fcs and needling on Sanyinjiao (SP-6) and Neiguan (PC-6) may improve the bone mass of OVX rats, and it provides an alternative and potential therapy for the prevention of postmenopausal osteoporosis.

Effect of vitamin D-containing plant extracts on osteoporotic bone

Adequate supply of vitamin D3 is not sufficient for the prevention of post-menopausal osteoporosis, because of a tightly regulated critical step in formation of the most active vitamin D metabolite 1,25-dihydroxyvitamin D3. Direct application of 1,25(OH)2D3, however, was effective in reducing fracture rate and increasing bone mineral density as has been shown in large clinical studies.Extracts from Solanum glaucophyllum and Trisetum flavescens plants containing 1,25(OH)2D3-glycosides were characterized by their vitamin D-activity in a quail eggshell bioassay and applied in an osteoporosis model in ovariectomized rats.An extract from the grass T. flavescens and a purified extract from S. glaucophyllum were characterized by the absence of alkaloids and the analytically determined content of 1,25(OH)2D3. In the ovariectomized rat model after 6 months duration, the bone metabolism relevant markers serum calcium, 1,25(OH)2D3, urinary crosslinks and calcium were measured. At termination tibial mineral content was determined and as imaging procedure micro-computerized tomography was applied. The bisphosphonate alendronate was used as a positive standard.While alendronate reduced bone resorption, as seen in a reduced urinary crosslink excretion, both vitamin D metabolite-containing extracts were able to improve bone mineral density by an enhanced calcium turnover.

Place du traitement hormonal substitutif dans la prise en charge de l’ostéoporose postménopausique et la prévention du risque fracturaire

The consequences to the bone of estrogen deficiency are early and irreversible. Effective prevention of postmenopausal osteoporosis at the individual level requires early screening of women at risk of fractures and their early treatment. Hormone treatment prevents bone loss and has been proven effective in preventing fractures, even in situations of low risk. The benefit/risk ratio of hormone treatment can be optimized by the choice of the 'right moment' and the 'right treatment'. HRT, administered early and for a limited period, must be integrated into a strategy of long-term osteoporosis prevention that includes using the (drug and nondrug) means most appropriate to the patient's age and clinical condition and choosing the 'right moment' and 'right treatment.'

Long-term effects of tibolone on ocular functions in postmenopausal women

Hormone replacement therapy has been widely used for the prevention of postmenopausal osteoporosis and treatment of climacteric symptoms for many years, but its effect on ocular functions remains unclear. The aim of the study was to evaluate the long-term effects of tibolone on ocular functions in postmenopausal women. A total of 77 healthy women with at least 1 year of spontaneous menopause were enrolled in the study. Forty women were treated with tibolone for 6 months and 37 women were left untreated. All these patients underwent ophthalmic examination including visual acuity, intraocular pressure (IOP), tear functions, blue-on-yellow and white-on-white Humphrey visual field (HVF), visual evoked potentials (VEP) and electroretinography (ERG). There were significant differences in mean deviation of blue-on-yellow HVF, and oscillatory potentials (O1, O2, and O4) in the ERGs of the chronic tibolone users and the control (P < 0.0001, P = 0.001, P < 0.0001 and 0.05, respectively). However, no significant differences were observed in visual acuity, IOP, tear functions, white-on-white HVF and VEP. We concluded that, although tibolone had no effects on visual acuity, IOP, tear functions and VEP, it might cause some early adverse effects on the electrophysiologic and structural characteristics of the retina, which are detected by these sensitive assays. Randomized placebo-controlled studies with larger groups are needed in future research.

Once-monthly Ibandronate for postmenopausal Osteoporosis: Review of a new dosing regimen

Background: Ibandronate, a nitrogen-containing bisphosphonate, was approved by the US Food and Drug Administration (FDA) in May 2003 as a daily oral regimen for the treatment and prevention of post-menopausal osteoporosis. In March 2005, the FDA approved once-monthly dosing with ibandronate for the same indications. Objective: The purpose of this article was to review the efficacy and tolerability of ibandronate 150 mg once monthly in the treatment and prevention of post-menopausal osteoporosis. Methods: A search of MEDLINE (1966-September 2005) and International Pharmaceutical Abstracts (1971-September 2005) for articles relating to the efficacy and tolerability of once-monthly ibandronate in the treatment of postmenopausal osteoporosis was conducted using the terms ibandronate and ibandronic acid. Additional searches were conducted to identify publications relevant to compliance and pharmacoeconomic considerations using the terms bispbospbonate, compliance, cost, and pharmacoeconomics. The reference lists of identified articles and presentations from recent scientific meetings also were reviewed. Selected safety information from the manufacturer was incorporated. Results: Ibandronate 2.5 mg/d and intermittent ibandronate (20 mg QOD for 12 doses every 3 months) have been shown to effectively reduce the incidence of vertebral fractures; after 3 years of therapy in a placebo-controlled clinical trial, the relative risk reductions for new vertebral fractures with daily and intermittent ibandronate were 62% and 50%, respectively (both, P < 0.001 vs placebo). Once-monthly ibandronate has been evaluated in 2 clinical trials: a Phase I dose-ranging trial in 144 healthy postmenopausal women and a Phase III noninferiority trial in 1609 women with postmenopausal osteoporosis who were randomized to receive ibandronate 2.5 mg/d or 1 of 3 monthly ibandronate regimens: 50/50 mg (50 mg given on 2 consecutive days) once monthly; 100 mg once monthly; and 150 mg once monthly. The primary end point of the Phase III trial was the change from baseline in lumbar spine bone mineral density (BMD). After 1 year of therapy, patients who received ibandronate 150 mg once monthly had a significantly greater increase from baseline in lumbar spine BMD compared with those who received ibandronate 2.5 mg/d (4.9% vs 3.9%, respectively; P = 0.002). The overall adverse-event profile was similar between the daily and monthly regimens. Drug-related adverse events were reported in 32.4% of patients receiving ibandronate 2.5 mg/d and 36.9% of patients receiving ibandronate 150 mg monthly. Upper gastrointestinal adverse events occurred in a respective 22.8% and 22.5% of the 2 groups. After 1 year of therapy, patients receiving ibandronate 150 mg monthly reported more flulike symptoms (8.3%) compared with those receiving ibandronate 2.5 mg/d (2.8%). In a crossover study comparing preference for and convenience of monthly ibandronate and weekly alendronate in 342 ambulatory women with postmenopausal osteoporosis, significantly more patients preferred the monthly ibandronate regimen to the weekly alendronate regimen (71.4% vs 28.5%, respectively; P < 0.001). Conclusion: Once-monthly ibandronate is an effective and well-tolerated treatment option for postmenopausal osteoporosis.

Postmenopausal Osteoporosis Prevention

Postmenopausal Osteoporosis Prevention

Retracted: A randomized clinical trial of the effects of isosorbide mononitrate on bone formation and resorption in post-menopausal women: a pilot study

Nitric oxide (NO) stimulates bone formation and inhibits bone resorption in vitro. NO donors (nitrates) are inexpensive and widely available, but their value for post-menopausal osteoporosis has never been evaluated in a randomized trial. The objective of this study was to compare the effects of 5 and 20 mg of isosorbide mononitrate (ISMO) on markers of bone turnover in post-menopausal women. A prospective randomized trial was carried out in the Department of Obstetrics & Gynecology, Ain Shams University, Egypt. The study included 50 healthy post-menopausal women with a hip bone mineral density T score between 0 and -2.5. Participants were randomly assigned to 5 or 20 mg/day of ISMO for 12 weeks. Urine N-telopeptide (NTx), a marker of bone resorption, and serum bone-specific alkaline phosphatase (BSALP), a marker of bone formation, were measured. Markers were measured immediately before randomization and after 12 weeks of treatment. The percent change in NTx and BSALP for each of the treatment groups (5 mg ISMO and 20 mg ISMO) was calculated. The main outcome measures were serum NTx and BSALP in the 5 and 20 mg ISMO groups after 12 weeks of treatment. Women adhering to 20 mg of ISMO had a 42.03% (95% confidence interval (CI), 20.1-73.7) reduction in NTx and a 29.05% (95% CI, 10.8-48.4) increase in BSALP, and women adhering to 5 mg of ISMO had a 31.12% (95% CI, 8.3-68.2) reduction in NTx and a 28.4% (95% CI, 4.6-52.1) increase in BSALP. ISMO, as a NO donor, may be useful for the prevention of post-menopausal osteoporosis.

Ibandronate: A New Oral Bisphosphonate for Postmenopausal Osteoporosis

To review a new oral bisphosphonate, ibandronate, recently approved by the U.S. Food and Drug Administration for the treatment and prevention of postmenopausal osteoporosis. A MEDLINE/PUBMED search was conducted to identify pertinent studies in the English language. Additional references were obtained from the bibliographies of these studies. Data over the time period of 1986 through July 2005 were reviewed. All studies evaluating any aspect of ibandronate in animals and humans. Studies in humans focused on the oral drug formulation. Preclinical studies established that ibandronate was an extremely potent bisphosphonate compared with its predecessors and that it was active in all animal models of human postmenopausal and corticosteroid-associated osteoporosis. Similar to other selected bisphosphonates, preclinical studies also showed that ibandronate exhibits antitumor activity and prevents and/or reduces bone metastases. As with other oral bisphosphonates, oral bioavailability is very poor (less than 1%) and substantially reduced by administration with or proximal to cations (e.g., food, antacids, mineral supplements). Clinical trials have demonstrated the efficacy and tolerability of oral ibandronate in the treatment and prevention of postmenopausal osteoporosis when administered once daily, once weekly, and even once monthly. Ibandronate also reduces the skeletal complications of bone metastases in patients with cancer, including pain, although the dosage used is much higher than that used in osteoporosis. As with other bisphosphonates, the major tolerability issue with ibandronate is upper gastrointestinal (GI) distress (dyspepsia, pain, esophagitis, esophageal and gastric ulcers). The dosage regimen for the treatment or prevention of postmenopausal osteoporosis (the only currently approved use in the United States) is 2.5 mg once a day or 150 mg once monthly (on the same date each month). Ibandronate should not be used in the presence of severe renal impairment (creatinine clearance below 30 mL/min). The usual complex administration instructions for other oral bisphosphonates apply to ibandronate as well. Oral ibandronate is an interesting addition to the therapeutic armamentarium for osteoporosis and cancer metastatic to bone. In fact, studies of ibandronate as an adjunctive treatment for cancers with a predilection to metastasize to bone are under way. Ibandronate has taken advantage of a complex pharmacodynamic profile in which its antiresorptive activity is independent of the frequency of dosing provided that a minimum dose-per-unit time is exceeded. Studies with every three-month dosing (and even less frequently) are under way. Whether or not the less frequent dosing of oral ibandronate will translate into a therapeutic advantage over older oral agents such as alendronate and risedronate is open to speculation. This is a difficult question to answer in the absence of head-to-head randomized controlled trials (RCTs). Older agents are still preferred until RCTs demonstrate that ibandronate is as safe and effective as these older agents.

Screening for the Prevention of Post-Menopausal Osteoporosis: A Meta-Analysis in Search of Cost-Effective Procedures

The incidence of all types of fractures in post-menopausal women is expected to rise because of the aging population. The estimated cost in Canada, stemming from fragility fractures, is expected to rise above $1.3 billion/year, yet these fractures are preventable. Appropriate cost-effective, patient and population wide screening procedures are required to identify women prone to high-risk fragility fractures and treat them accordingly. The purpose of this meta-analysis was: i) to define the limits of untreated spontaneous bone loss in post-menopausal women; ii) to identify the role of bone density and other risk factors in the occurrence of fragility fractures; iii) and to compare the sensitivity and specificity of various assessment tools which can help clinicians to identify women at high risk of fragility fractures.

Inulin-type fructans and bone health: state of the art and perspectives in the management of osteoporosis

If the primary role of diet is to provide sufficient nutrients to meet the metabolic requirements of an individual, there is an emerging rationale to support the hypothesis that, by modulating specific target functions in the body, it can help achieve optimal health. Regarding osteoporosis prevention, since Ca is most likely to be inadequate in terms of dietary intake, every strategy targeting an improvement in Ca absorption is very interesting. Actually, this process may be susceptible to manipulation by fermentable substrates. In this light, inulin-type fructans are very interesting, even if we need to gather more data targeting bone metabolism before health professionals can actively advocate their consumption to prevent senile osteoporosis. Besides targeting the prevention of postmenopausal osteoporosis, inulin-type fructans still remain a source for putative innovative dietary health intervention. Indeed, given in combination with isoflavones, they may have a potential for maintaining or improving the bone mass of human subjects, by modulating the bioavailability of phyto-oestrogens.

Biochanin A Stimulates Osteoblastic Differentiation and Inhibits Hydrogen Peroxide-Induced Production of Inflammatory Mediators in MC3T3-E1 Cells

Phytoestrogens are plant chemicals that are structurally analogous to estrogen and are known to affect estrogenic activity. Biochanin A, a naturally occurring isoflavone, has been identified and detected in various diets and plant species. We examined the effects of biochanin A on the differentiation of osteoblastic MC3T3-E1 cells and the production of local factors in osteoblasts. Biochanin A (1-50 microM) caused a significant elevation of cell growth, alkaline phosphatase (ALP) activity, collagen content, and osteocalcin secretion in osteoblastic MC3T3-E1 cells (p<0.05). The effect of biochanin A (10 microM) in increasing ALP activity and collagen content was completely prevented by the presence of 10(-6) M cycloheximide and 10(-6) M tamoxifen, suggesting that biochanin A's effect results from a newly synthesized protein component and might be partly involved in estrogen action. We then examined the effect of biochanin A on the H2O2-induced production of inflammatory mediators in osteoblasts. Biochanin A (1-10 microM) decreased the 0.2 mM H2O2-induced production of TNF-alpha, IL-6 and NO in osteoblasts. These results suggest that biochanin A may be useful as potential phytoestrogens, which play important physiological roles in the prevention of postmenopausal osteoporosis.