Bone Resorption In Postmenopausal Women Research Articles

Alendronate reduces osteoclast precursors in osteoporosis

This study evaluates the effect of alendronate on osteoclastogenesis, cytokine production, and bone resorption in postmenopausal women. We suggest that it acts on mature bone resorbing osteoclasts after 3 months of treatment, whereas, after 1 year, it diminishes their formation by reducing their precursors and serum RANKL. Osteoclasts are the target cells of bisphosphonates, though the most drug-sensitive steps of their formation and activity have not been determined. The present study evaluates the effect of alendronate on osteoclastogenesis, cytokine production, and bone resorption in postmenopausal women. The study was conducted on 35 osteoporotic women; 15 were pretreated with alendronate 70 mg/week, whereas, 20 were treated with calcium 1 g/day and vitamin D 800 IU/day. After 3 months, 30 received alendonate 70/mg, vitamin D 2800 IU/week, and calcium 1 g/day for 12 months (combined therapy), whereas, the other five patients remained on calcium 1 g/day and vitamin D 800 IU/day. The following parameters were assessed before and after therapy: changes in bone resorption markers, circulating osteoclast precursors, formation of osteoclasts in peripheral blood mononuclear cell cultures, their viability, and variations in cytokines production. After 3 months of alendronate, there was no significant reduction in the number of osteoclast precursors, osteoclast formation and viability, and cytokine levels, whereas, there was a significant reduction of bone resorption markers. One year of the combined therapy, on the other hand, reduced osteoclast precursors, osteoclast formation, and serum RANKL, whereas, calcium plus vitamin D alone had no effect. We suggest that alendronate mainly acts on mature bone resorbing osteoclasts in the short term, whereas, its long-term administration diminishes their formation by reducing their precursors and serum RANKL.

Antiresorptive Effects of Phytoestrogen Supplements Compared with Estradiol or Risedronate in Postmenopausal Women Using 41Ca Methodology

Reduction of ovarian estrogen secretion at menopause increases net bone resorption and leads to bone loss. Isoflavones have been reported to protect bone from estrogen deficiency, but their modest effects on bone resorption have been difficult to measure with traditional analytical methods. In this randomized-order, crossover, blinded trial in 11 healthy postmenopausal women, we compared four commercial sources of isoflavones from soy cotyledon, soy germ, kudzu, and red clover and a positive control of oral 1 mg estradiol combined with 2.5 mg medroxyprogesterone or 5 mg/d oral risedronate (Actonel) for their antiresorptive effects on bone using novel (41)Ca methodology. Risedronate and estrogen plus progesterone decreased net bone resorption measured by urinary (41)Ca by 22 and 24%, respectively (P < 0.0001). Despite serum isoflavone profiles indicating bioavailability of the phytoestrogens, only soy isoflavones from the cotyledon and germ significantly decreased net bone resorption by 9% (P = 0.0002) and 5% (P = 0.03), respectively. Calcium absorption and biochemical markers of bone turnover were not influenced by interventions. Dietary supplements containing genistein-like isoflavones demonstrated a significant but modest ability to suppress net bone resorption in postmenopausal women at the doses supplied in this study over a 50-d intervention period.

The effect of l‐arginine administration on muscle force and power in postmenopausal women

Previously published data (J Bone Miner Res (2005); 20: 471) did not give evidence that the administration of the nitric oxide precursor L-arginine increases bone formation and decreases bone resorption in postmenopausal women. Data of this trial were reanalysed for putative effects of L-arginine on muscle mass and muscular function. Therefore, 11 females of the former study group (n=15; age 54.5+/-4.1 years; daily oral administration of 18 g L-arginine hydrochloride (equivalent of 14.2 g L-arginine) over 6 months) and 12 females of the control group (n=15; age 55.3+/-4.4 years; daily administration of 18 g dextrose over 6 months) were analysed for biomechanical parameters (MIGF, maximal isometric grip force; PJF, peak jump force; PJP, peak jump power) and for the cross-sectional muscle area (MA) and fat area (FA) at forearm and leg (calf) measured by peripheral quantitative computed tomography. The study was performed in a double-blind design. The assessment of muscular and biomechanical parameters was undertaken before and after 6 months of L-arginine versus placebo administration. L-arginine-supplemented females had a significant increase of PJF/kg in comparison with the control group. PJP/kg, MIGF, MA and FA were not significantly influenced by the administration of L-arginine. In conclusion, the administration of L-arginine increased maximal force in mechanographic analyses and may prevent a decline of muscle force in postmenopausal women.

Subantimicrobial‐Dose Doxycycline Modulates Gingival Crevicular Fluid Biomarkers of Periodontitis in Postmenopausal Osteopenic Women

We recently demonstrated that a 2-year subantimicrobial-dose doxycycline (SDD) regimen (double-masked, placebo-controlled clinical trial) in postmenopausal (PM) women exhibiting mild systemic bone loss (osteopenia) and local bone loss (periodontitis) reduced the progression of periodontal attachment loss (intent-to-treat analysis) and the severity of gingival inflammation and alveolar bone loss (subgroups) without producing antibiotic side effects. We now describe SDD effects on biomarkers of collagen degradation and bone resorption in the gingival crevicular fluid (GCF) of the same vulnerable subjects. GCF was collected from SDD- and placebo-treated PM subjects (n=64 each) at the baseline and 1- and 2-year appointments; the volume was determined; and the samples were analyzed for collagenase activity (using a synthetic peptide as substrate), relative levels of three genetically distinct collagenases (Western blot), a type-1 collagen breakdown product/bone resorption marker (a carboxyterminal telopeptide cross-link fragment of type I collagen [ICTP]; radioimmunoassay), and interleukin-1beta (enzyme-linked immunosorbent assay). Statistical analyses were performed using generalized estimating equations; primary analyses were intent-to-treat. Collagenase activity was significantly reduced by SDD treatment relative to placebo based on intent-to-treat (P=0.01). ICTP showed a similar pattern of change during SDD treatment, and GCF collagenase activity and ICTP were positively correlated at all time periods (P<0.001). Matrix metalloproteinase (MMP)-8 accounted for approximately 80% of total collagenase in GCF, with much less MMP-1 and -13, and SDD reduced the odds of elevated MMP-8 by 60% compared to placebo (P=0.006). These observations support the therapeutic potential of long-term SDD therapy to reduce periodontal collagen breakdown and alveolar bone resorption in PM women; effects on serum biomarkers of systemic bone loss in these subjects are being analyzed.

Bone mass and bone resorption in postmenopausal women with type 2 diabetes mellitus

The aim of the present study was to examine the relationships between bone mass or bone resorption evaluated by urinary cross-linked N-telopeptides of type I collagen (NTx) concentration and known and potential contributors to bone mass or bone resorption such as sex hormones, age, duration of diabetes, glycemic control (hemoglobin A 1c [HbA 1c]), body mass index (BMI), severity of diabetic complications, smoking status, and current treatment of diabetes in postmenopausal women with type 2 diabetes mellitus (n = 196). In addition, the relationship of bone mass to pulse wave velocity, which is an earlier indicator of cardiovascular disease, was investigated in a subgroup of patients (n = 120). Bone mass was evaluated by the quantitative ultrasound method. A higher stiffness index indicates higher bone mass. Inverse correlations were found between the stiffness index and age ( r = −0.374, P < .0001) and between the stiffness index and log (urinary albumin excretion) ( r = −0.170, P = .0398), and a positive correlation was found between the stiffness index and serum dehydroepiandrosterone sulfate (DHEA-S) concentration ( r = 0.201, P = .0136). No significant correlations were found between the stiffness index and duration of diabetes, HbA 1c, BMI, or serum estradiol concentration. No significant correlations were found between urinary NTx concentration and age, duration of diabetes, HbA 1c, BMI, serum estradiol concentration, or serum DHEA-S concentration. The stiffness index correlated inversely with urinary NTx concentration ( r = −0.262, P = .0002). No significant correlation was found between the stiffness index and pulse wave velocity ( r = −0.165, P = .0714). Multiple regression analysis demonstrated that serum DHEA-S concentration was an independent determinant of the stiffness index ( β = .207, P = .0428). In conclusion, serum DHEA-S concentration correlated positively with bone mass, whereas glycemic control, BMI, or duration of diabetes did not correlate with bone mass or urinary NTx concentration in postmenopausal women with type 2 diabetes mellitus.

Effect of risedronate on biochemical marker of bone resorption in postmenopausal women with osteoporosis or osteopenia

Objective. The primary objective of the present study was to evaluate the effectiveness and adverse events of risedronate use in postmenopausal woman by measuring its effects on urinary crosslinked C-terminal telopeptides of type I collagen (CTx), a biochemical marker of bone resorption.Methods. One hundred osteoporotic (control and treatment) and 111 osteopenic (control and treatment) postmenopausal women, selected according to World Health Organization criteria, were included in the study. The treatment groups (osteopenic and osteoporotic) were given risedronate 35 mg once a week. The primary endpoint was mean percentage change in CTx from baseline to 6 months. The secondary endpoints included evaluation of the incidence of clinical or laboratory adverse events occurring during the 6-month study period. The least significant change (LSC), calculated from the within-subject variability in the two control groups, was used to define response.Results. Of the 211 women enrolled, 157 (74.4%) completed the study. After 6 months, urinary CTx levels were −54.7% (range −67% to −48%) below baseline in the osteoporotic treatment group and −66.7% (range −74% to −59%) below baseline in the osteopenic treatment group. Analysis of LSC showed that 89% of risedronate treatment groups were categorized as responders after 6 months of treatment.Conclusion. The study shows that osteoporotic and osteopenic women on risedronate treatment have statistically significant suppressed bone turnover and CTx can be useful to confirm this observation. The low withdrawal rate and adverse effects rate show that risedronate was well tolerated by the study population.

Reduction in bone resorption by exogenous glucagon-like peptide-2 administration requires an intact gastrointestinal tract

Objective. Biochemical markers for bone resorption (s-CTX) are reduced by food intake, whereas markers for bone formation seem to be unaffected by meal status. Glucagon-like peptide-2 (GLP-2) is a peptide secreted from endocrine L cells in the intestinal mucosa in relation to food-intake. Subcutaneous GLP-2 treatment has been shown to reduce bone resorption in postmenopausal women. The objective of this study was to investigate the ability of exogenous GLP-2 to reduce bone resorption in patients with jejunostomy or ileostomy and to elucidate whether an intact gastrointestinal tract and the ability to secrete GLP-2 are required for meal-induced inhibition of bone resorption. Material and methods. Fifteen control subjects, 13 colectomized patients with an ileostomy and 12 colectomized patients with a jejunostomy (remnant small bowel 89±53 cm) were given: a) a subcutaneous injection of 1600 µg GLP-2, b) placebo and c) 3.8 MJ of a breakfast meal. Blood was sampled for measurements of s-CTX, s-osteocalcin and GLP-2 for 4 h after each intervention. Results. After the GLP-2 injection, only control subjects showed a significant reduction in s-CTX (24%±13%, p=0.05, 120 min) compared with baseline values. Patients with an ileostomy had a preserved endogenous postprandial GLP-2 secretion, which was absent in patients with a jejunostomy. Consumption of a meal reduced s-CTX in all groups but significantly less so in the jejunostomy group. Conclusions. Reductions in bone resorption by exogenous GLP-2 require an intact gastrointestinal tract. The decreased meal-induced inhibition of bone resorption in the jejunostomy patients, who lack a GLP-2 response, supports the view that GLP-2 plays a role in postprandial reduction in bone resorption.

Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis

Although bisphosphonates do inhibit bone resorption in postmenopausal women and lessen the risk of vertebral and hip fractures, as many as half of patients no longer adhere to prescribed oral treatment after 12 months. A single intravenous infusion of zoledronic acid reportedly decreases bone turnover and improves bone mineral density (BMD) for at least a year. In the HORIZON (Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly) Pivotal Fracture Trial, an international, randomized, double-blind, placebo-controlled study, postmenopausal women ranging in age from 65 to 89 years were assigned to receive either a 15-minute IV infusion of 5 mg of zoledronic acid or placebo at yearly intervals up to 24 months. All women received a daily supplement of 1000-1500 mg of calcium and 400-1200 IU of vitamin D. Participants had a bone mineral density (BMD) T score of -2.5 or less at the femoral neck or a score of -1.5 or less with 1 or more vertebral fractures. The efficacy analysis included 7736 patients, and the safety analysis, 7714 patients. The 3-year incidence of vertebral fracture was 10.9% in the placebo group and 3.3% in women given zoledronic acid, a 70% reduction (relative risk, 0.30; 95% confidence interval [CI], 0.24-0.38). Similar effects were noted after 1 and 2 years. Hip fractures were reduced 41% in actively treated women (hazard ratio, 0.59; 95% CI, 0.42-0.83). Nonvertebral fractures, all clinical fractures, and clinical vertebral fractures all were significantly less frequent in women given zoledronic acid-by 25%, 33%, and 77%, respectively. Actively treated women lost significantly less height than placebo recipients (-4.2 mm vs. -7.0 mm). BMD rose significantly at all measurement sites in the active treatment group compared to placebo recipients. Biochemical markers of bone turnover-including serum C-telopeptide of type I collagen, bone-specific alkaline phosphatase, and N-terminal propeptide of type I collagen-all decreased significantly with active treatment. Postdose symptoms were more frequent in actively treated women, but there were no significant group differences in numbers of deaths. Renal function was not compromised by zoledronic acid therapy. Serious atrial fibrillation was more frequent in actively treated women than in placebo patients (1.3% vs. 0.5%), as was the prevalence of inflammatory ocular disorders, mainly conjunctivitis. One patient in each group had potential osteonecrosis of the jaw. In this large-scale trial, once-a-year infusion of zoledronic acid was associated with a sustained decrease in vertebral, hip, and other fractures in postmenopausal women with osteoporosis over a 3-year period. Treatment was generally well tolerated and had a favorable safety profile.

Soy Isoflavones Do Not Affect Bone Resorption in Postmenopausal Women: A Dose-Response Study Using a Novel Approach with 41Ca

The purpose of this 3-way crossover study was to identify the effective dose of soy protein isolate enriched with isoflavones for suppressing bone resorption in postmenopausal women using a novel, rapid assessment of antibone resorbing treatments. Thirteen postmenopausal women (>or=6 yr since menopause) were predosed with 41Ca iv. After a 200-d baseline period, subjects were given 43 g soy protein/d that contained 0, 97.5, or 135.5 mg total isoflavones in randomized order. The soy protein isolate powder was incorporated into baked products and beverages. Each 50-d intervention phase was preceded by a 50-d pretreatment phase for comparison. Serum isoflavone levels and biochemical markers were measured at the end of each phase. Twenty-four-hour urine samples were collected approximately every 10 d during each phase for 41Ca/Ca analysis by accelerator mass spectrometry. Serum isoflavone levels reflected the amount of isoflavones consumed in a dose-dependent manner. None of the isoflavone levels had a significant effect on biochemical markers of bone turnover, urinary cross-linked N teleopeptides of type I collagen and serum osteocalcin, or bone turnover as assessed by urinary 41Ca/Ca ratios. Soy protein with isoflavone doses of up to 135.5 mg/d did not suppress bone resorption in postmenopausal women. This is the first efficacy trial using the novel technique of urinary 41Ca excretion from prelabeled bone.

Dietary isoflavones differentially induce gene expression changes in lymphocytes from postmenopausal women who form equol as compared with those who do not

Human and animal studies suggest that dietary soy isoflavones reduce cancer risk, ameliorate postmenopausal syndrome and decrease bone resorption in postmenopausal women. The capacity to form the metabolite equol from daidzein is suggested as an important modulator of response to isoflavones; this capacity depends on gut colonization with appropriate bacteria. We administered a dietary supplement containing high-dose purified soy isoflavones (genistein, 558 mg/day; daidzein, 296 mg/day; and glycitein, 44 mg/day) to 30 postmenopausal women for 84 days and collected peripheral lymphocytes at timed intervals. Using microarray analysis, we determined whether changes in gene expression associated with this treatment support existing hypotheses as to isoflavones' mechanisms of action. Expression of a large number of genes was altered by isoflavone treatment, including induction of genes associated with cyclic adenosine 3′,5′-monophosphate (cAMP) signaling and cell differentiation and decreased expression of genes associated with cyclin-dependent kinase activity and cell division. We report that isoflavone treatment in subjects who have the capacity to produce equol differentially affects gene expression as compared with nonproducers, supporting the plausibility of the importance of equol production. In general, isoflavones had a stronger effect on some putative estrogen-responsive genes in equol producers than in nonproducers. Our study suggests that, in humans, isoflavone changes are related to increased cell differentiation, increased cAMP signaling and G-protein-coupled protein metabolism and increased steroid hormone receptor activity and have some estrogen agonist effects; equol-production status is likely to be an important modulator of responses to isoflavones.

Soy Protein, Isoflavones, and Cardiovascular Health

This editorial summarizes the recent American Heart Association (AHA) Science Advisory on soy protein and isoflavones (phytoestrogens) published in the February 21, 2006, issue of Circulation .1 Soy protein and isoflavones have gained considerable attention for their potential role in improving risk factors for cardiovascular disease. This scientific advisory report assesses the more recent work published on soy protein and its component isoflavones. In 22 randomized trials, isolated soy protein with isoflavones compared with milk or other proteins decreased LDL cholesterol concentrations in most studies; the average effect was approximately 3%. This reduction is very small compared with the large amount of soy protein tested in these studies, averaging 50 g, approximately half the usual total daily protein intake. No significant effects were evident on HDL cholesterol, triglycerides, lipoprotein(a), or blood pressure. Among 19 studies of soy isoflavones, the average effect on LDL cholesterol and other lipid risk factors was nil. Soy protein or isoflavones have not been shown to lessen vasomotor symptoms of menopause, and results are mixed regarding slowing of postmenopausal bone loss. The efficacy and safety of soy isoflavones for preventing or treating cancer of the breast, endometrium, and prostate are not established; evidence from clinical trials is meager and cautionary as regards a possible adverse effect. For this reason, use of isoflavone supplements in food or pills is not recommended. Thus, earlier research indicating that soy protein compared with other proteins has clinically important favorable effects has not enjoyed confirmation. In contrast, many soy products should be beneficial to cardiovascular and overall health because of their high content of polyunsaturated fats, fiber, vitamins, and minerals and low content of saturated fat. In October 1999, the US Food and Drug Administration (FDA) approved labeling for foods containing soy protein as protective against coronary heart disease.2 …

Nutrition-Related Peptides and Bone Homeostasis

THE SKELETON SERVES two main functions. First, it has a structural role, to support, protect, and facilitate the function of the soft tissues. Second, it is a mineral reservoir, which can be drawn on when dietary intake is inadequate to meet the body’s needs. Optimal function in each of these roles requires regulation of skeletal mass and function in relation to the demands being placed on it. From the structural perspective, the size and strength of the skeleton should be proportional to the mass of soft tissue that it supports, so that the skeleton is structurally adequate without being larger or heavier than necessary. To function as an effective mineral reservoir, there must be a mechanism by which mineral release from the skeleton can occur during times of privation and its replacement be affected when there is dietary abundance. Both the structural and reservoir roles of the skeleton suggest that skeletal homeostasis should be regulated by factors that reflect soft tissue mass on the one hand and nutritional status on the other. Because soft tissue mass and nutrition are themselves linked, there is the possibility of a complex interaction of regulatory factors that act across these two dimensions. Recent research indicates that this is the case, and this Perspective will review our current understanding of this relatively new area of bone science.

Isoflavone‐induced gene expression changes in lymphocytes from postmenopausal women

Soy isoflavones may have various beneficial effects, including decreased cancer risk in women and men, amelioration of hot flashes and a decrease in bone resorption in postmenopausal women. It has been suggested that the metabolite equol formed from the soy isoflavone daidzein, is the active component, and that equol producers have a better response to diets containing isoflavones. In addition, there has been concern that isoflavone-mediated activation of estrogen receptors could enhance breast cancer proliferation in postmenopausal women. Using microarray analysis, we investigated changes in peripheral lymphocyte gene expression induced by oral treatment with high-doses of purified soy isoflavones for 84 days. The samples were stratified based on the equol-producer status of the subjects. From 30 postmenopausal women that successfully completed this Phase I clinical trial, 26 arrays were available for analysis; 16 from the treated group (11 equol producers and 5 non-equol producers), and 10 from the placebo group. We report that isoflavones change gene expression profiles in both equol and non–equol producers, and these changes were related to, among others, cell differentiations, cAMP metabolism and genes that are estrogen responsive. This work was funded by a grant from National Cancer Institute (NCI-N01-CN-75035).

Raloxifene increases serum leptin levels in postmenopausal women: A prospective study

The purpose of this study was to investigate the effect of raloxifene on leptin and insulin-like growth factor-I levels and their relation with the biochemical markers of bone metabolism in postmenopausal women. Sixty-four women were given 60 mg/d raloxifene for 6 months. Serum leptin, insulin-like growth factor-I, alkaline phosphatase, calcium, osteocalcin, and collagen type I cross-link C-telopeptide levels were measured before and after the treatment. The patients were grouped as obese (body mass index, > or =25 kg/m2) or non-obese (body mass index, <25 kg/m2). The mean basal leptin level was significantly higher (P < .001), and the mean cross-link C-telopeptide level was significantly lower (P = .001) in obese patients. Raloxifene therapy increased leptin levels (P < .001) and decreased insulin-like growth factor-I, alkaline phosphatase, and cross-link C-telopeptide levels significantly (P < .001). There was a strong negative correlation between leptin and cross-link C-telopeptide (r = -0.703; P < .001). Insulin-like growth factor-I was not correlated with any parameter. Raloxifene increases serum leptin levels while decreasing bone resorption in postmenopausal women.

Effects of Low-Dose Prednisone on Bone Metabolism

Prednisone 5 mg/day suppresses multiple indices of bone formation in a randomized placebo-controlled trial in healthy postmenopausal females. This suggests that even low doses of prednisone may reduce bone repair or renewal and may have adverse effects on bone mass and/or bone strength. High doses of chronic glucocorticoids are known to have adverse effects on bone, and measures to prevent bone loss are well established for doses >7.5 mg daily, because these doses can cause premature or exaggerated osteoporosis. However, it is unclear if chronic prednisone doses of 5 mg daily have the same effects on bone. There are no established recommendations for preventing glucocorticoid-induced osteoporosis in people taking prednisone 5 mg daily, a dose used frequently in medical practice to treat diseases of the lungs, joints, skin, muscles, eyes, nerves, etc. Our primary objective was to test whether prednisone 5 mg daily affects serum and urine indices of bone metabolism in healthy postmenopausal women. Our secondary objectives were to determine if prednisone 5 mg affected systolic or diastolic blood pressure or causes side effects. A double-blinded randomized placebo-controlled 8-week trial in 50 healthy postmenopausal women was conducted at the Massachusetts General Hospital Outpatient General Clinical Research Center. Patients were randomly assigned to prednisone 5 mg daily or matching placebo for 6 weeks, followed by a 2-week recovery phase. Markers of bone formation and resorption were determined at weeks 0, 2, 4, 6, and 8. Indices of osteoblast activity included serum propeptide of type I N-terminal procollagen (PINP), propeptide of type I C-terminal procollagen (PICP), osteocalcin, and bone-specific alkaline phosphatase (BSALP). Indices of osteoclast activity included urine and serum type I collagen N-telopeptide (NTX) and free urinary deoxypyridinoline (DPD). Prednisone rapidly and significantly decreased serum PINP (p < 0.01), PICP (p < 0.01), and osteocalcin (p < 0.01) and free urinary deoxypyridinoline (p = 0.017). These changes were largely reversed during the recovery period. Side effects were indistinguishable in the two groups. Neither systolic nor diastolic blood pressure changed significantly throughout the study between the two groups. In conclusion, low-dose prednisone significantly decreases indices of bone formation and may decrease indices of bone resorption in postmenopausal women. Further studies are needed to assess the effects of low-dose prednisone on BMD and fracture risk.

Effects of alendronate on the markers of bone metabolic activity in postmenopausal women with osteoporosis

Bisphosphonates are synthetic compounds used in treatment of osteoporosis and inhibition of bone resorption. The research included a group of 30 postmenopausal women with osteoporosis, treated with alendronate (70 mg per week--Fosamax tablets in combination with calcium and active vitamin D--Alpha D3 0.25mcg). The control group included 20 women with osteoporosis treated with hormone substitution therapy (HST), calcitonin and deca duraboline. Bone metabolic activity, was evaluated using osteocalcin for bone formation and cross-laps for bone resorption. Blood samples were taken before therapy and 6-8 weeks after. The serum levels of osteocalcin and cross-laps during application of alendronate were statistically significantly lower comparing to those in pre-therapy. The serum levels of osteocalcin and cross-laps during the therapy applied in the control group were statistically insignificantly lower than values in pre-therapy. Osteocalcin has a tendency of decreasing in both groups, and it was slightly more evident in alendronate group. Cross-laps demontrated the same tendency of decreasing in both groups, and it was more evident in alendronate group. Our results have shown the efficacy of alendronate in preventing bone loss, which was highly statistically significant. They have also shown its suppressive effect on bone formation and resorption, but the effects were statistically less significant. Alendronate significantly reduces the level of bone resorption in postmenopausal women with osteoporosis. Its effects on bone formation are less expressed Alendronate's effects on bone metabolism become evident not later than 6-8 weeks after therapy application. Parameters of bone metabolic activity are very useful diagnostic means in evaluation of alendronate effect on bone metabolic activity and in the prognosis of bone mass loss.

Increased RANKL/OPG mRNA Ratio in Iliac Bone Biopsies From Women with Hip Fractures

RANKL (receptor activator of NF-kappaB) is a potent physiological inducer of osteoclastogenesis. Its actions are blocked by the decoy receptor osteoprotegerin (OPG), and treatment with OPG blocks bone resorption in postmenopausal women. Both positive and negative associations between serum OPG and bone mineral density (BMD) have been reported in the literature. We hypothesized that decreased OPG production relative to RANKL within bone itself could lead to increased risk of osteoporotic fracture. We included ten women with hip fracture (age 76.3 +/- 8.0 years, N.S, : hip BMD 0.686 +/- 1.3 g/cm2, P < 0.05) and 24 women with osteoarthrosis of the hip (age 72.8 +/- 7.2 years, hip BMD 0.832 +/- 1.1 g/cm(2)). Transiliac biopsies were obtained at the time of surgery. Total RNA was extracted from biopsies and reverse-transcribed. Real-time quantification of mRNA was performed with a SYBR Green I real time PCR assay, calculating relative gene expression with normalization of results for beta actin mRNA. Actin normalized mRNA levels for OPG and interleukin (IL)-6 were significantly lower in fracture patients, with a significantly higher RANKL/OPG ratio in patients with fractures. There was no significant difference in tumor necrosis factor (TNF), IL-1, IL-1ra, or IL-7 expression. IL-6 mRNA levels were lower in fracture patients (P < 0.05). The effect of increased RANKL/OPG ratio (Z = 2.08, P < 0.05) on fracture risk was additive to that of hip BMD T score (Z = -1.95, P < 0.05) when assessed using logistic regression. Elderly women with hip fractures exhibit an increased RANKL/OPG mRNA content of iliac bone. This is associated with increased fracture susceptibility, which is not in itself explained by low BMD.

Decreased Bone Resorption with Soy Isoflavone Supplementation in Postmenopausal Women

To investigate the effect of soy isoflavone supplementation on bone mineral density (BMD) and markers of bone turnover in postmenopausal women. In this randomized, placebo-controlled clinical trial, we used a crossover design to test the effect of soy isoflavone (110 mg/day) (1.3:1.0:0.22 ratio of genistein/daidzein/ glycitein) on bone formation, bone resorption, bone mineral content (BMC), and BMD for 6 months. Postmenopausal women (n = 19), mean age 70.6 +/- 6.3 years and mean time since menopause 19.1 +/- 5.5 years, were given isoflavone supplements for 6 months. There was a 37% decrease in urinary concentrations of type 1 collagen alpha1-chain helical peptide (HP), a marker of bone resorption, during the isoflavone supplementation compared with baseline (p < 0.05) and a significant difference in mean (SE) HP excretion levels when isoflavone was compared with placebo (43.4 +/- 5.2 vs. 56.3 +/- 7.2 microg/mmol creatinine [cr], p < 0.05). With isoflavone supplementation, mean spine BMD at L2 and L3 was significantly greater when treatment was compared with control, with a difference between means of 0.03 +/- 0.04 g and 0.03 +/- 0.04 g (p < 0.05), respectively. There were nonsignificant increases from baseline for total spine BMC (3.5%), total spine BMD (1%), total hip BMC (3.6%), and total hip BMD (1.3%) with the isoflavone treatment. Soy isoflavone, in isolated form, was effective in this study to significantly decrease bone resorption in postmenopausal women. Further investigation needs to be done to evaluate the long-term effects of soy isoflavone on bone mass and fracture risk.

Effects of cyclical etidronate with alfacalcidol on lumbar bone mineral density, bone resorption, and back pain in postmenopausal women with osteoporosis

AbstractThe purpose of the present open-labeled, randomized, prospective study was to compare the effects of cyclical etidronate combined with alfacalcidol with those of cyclical etidronate alone on lumbar bone mineral density (BMD), bone resorption, and back pain in postmenopausal women with osteoporosis. Forty postmenopausal women with osteoporosis, 60–86 years of age, without any vertebral fractures in the lumbar spine, were randomly divided into two groups with 20 patients in each group. One group was treated with cyclical etidronate (oral etidronate 200mg daily for 2 weeks every 3 months) and the other was given cyclical etidronate combined with alfacalcidol (cyclical etidronate plus alfacalcidol 1μg daily continuously). The BMD of the lumbar spine (L1–L4) measured by dual-energy X-ray absorptiometry, urinary crosslinked N-terminal telopeptides of type I collagen (NTX) measured by an enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Both treatments significantly reduced the urinary NTX level and back pain. Cyclical etidronate combined with alfacalcidol significantly increased the lumbar BMD with a more significant reduction in the urinary NTX level than cyclical etidronate alone, but cyclical etidronate alone did not significantly increase the lumbar BMD. Alleviation of back pain was similar in the two groups. These results suggest that cyclical etidronate combined with alfacalcidol appears to be more useful than cyclical etidronate alone for increasing the lumbar BMD by more markedly suppressing bone resorption in postmenopausal women with osteoporosis.

High salt intake appears to increase bone resorption in postmenopausal women but high potassium intake ameliorates this adverse effect.

A high-salt diet increases urinary calcium excretion. Its effect on bone, however, is less clear. Recent research suggests that a high-salt diet increases the rate of bone resorption in postmenopausal women over a 4-week period, but increased potassium intake (as potassium citrate) ameliorates this adverse effect. These findings may have implications for the development of dietary guidelines for osteoporosis prevention.