N-3 PUFA ameliorated bone loss induced by postmenopausal depression following exposure to chronic mild stress and maternal separation by regulating neuronal processes.

Depression induced by chronic mild stress (CMS) reduced bone mass in ovariectomized (OVX) rats, and maternal separation (MS) during early life aggravated depression-induced bone mass destruction. N-3 polyunsaturated fatty acids (PUFA) have been shown to improve bone mass and depression, but the bone-protecting effects of n-3 PUFA were unclear in CMS+MS-induced depression models. The purpose of this study was to determine whether n-3 PUFA improved CMS+MS-induced postmenopausal bone loss via its antidepressant-like action. Rats were fed diets containing 0% of total energy intake (en %) of n-3 PUFA during lifetime or 1 en % n-3 PUFA during pre-weaning or post-weaning periods, or their entire lifetimes and were allocated to CMS or CMS+MS groups after OVX. Lifetime supply of n-3 PUFA enhanced bone mass and microarchitecture, and expression of runt-related transcription factor 2, while decreasing blood levels of amino-terminal cross-linked telopeptide of type 1 collagen and the expression of receptor activator of nuclear factor kappa Β ligand/osteoprotegerin, activating transcription factor 4, and adrenergic receptor ß2. Lifetime supply of n-3 PUFA decreased levels of adrenocorticotropic hormone and corticosterone and the expression of corticotropin-releasing factor in the brain but increased expression of the glucocorticoid receptor, serotonin-2C receptor, cAMP response element-binding protein (CREB), and calmodulin kinase IV and serotonin levels. Supply of n-3 PUFA during the pre-and post-weaning periods had beneficial effects on the brain but not on the bones. Lifetime supply of n-3 PUFA ameliorated bone loss induced by chronic stress by regulating hypothalamic-pituitary-adrenal axis activity and serotonin-CREB signaling.

Calcium-Enriched Pumpkin Affects Serum Leptin Levels and Fat Content in a Rat Model of Postmenopausal Osteoporosis.

Because the world's population is deficient in dietary calcium, it is important to search for new sources of this essential mineral for the bones and the entire body. One of the innovative foods that could act as such a source is pumpkin enriched with calcium lactate by means of osmotic dehydration. Providing the body with easily absorbable calcium may have beneficial effects on the reconstruction of bone tissue. Postmenopausal osteoporosis is associated with body weight and fat mass gain, and the aim of the present study was to evaluate the effect of consuming enriched pumpkin on the levels of adipokines and cytokines produced by the adipose tissue. This study was conducted on 12-month-old female Wistar rats that received nutritional intervention for 12 weeks. After termination of the rats, the levels of leptin, adiponectin, interleukin 31 and interleukin 33 in serum and adipose tissue were determined, and the femurs were examined histopathologically. It was demonstrated that calcium-enriched pumpkin reduced bone marrow femoral adipocytes and also markedly decreased serum leptin levels in groups of rats after ovariectomy, which was associated with a decrease of fat content. Additionally, it seems that calcium-enriched pumpkin may reduce body weight gain often observed after menopause.

Nutritional considerations for the prevention and treatment of postmenopausal osteoporosis.

Osteoporosis commonly affects postmenopausal women and accounts for 300,000 hip fractures in the United States each year. More women are deferring or discontinuing pharmacologic treatment because of intolerable adverse reactions or fear of long-term safety. Supplementing dietary intake of certain vitamins and minerals can have positive effects on bone parameters. Calcium is frequently recommended for osteoporotic patients but many not confer much benefit toward bone density. Certain forms of vitamins A and K have been shown to increase bone density. Isoflavones and phytates are phytochemicals found in soy foods that are comparable to bisphosphonates when consumed at certain levels. Lastly, increasing certain daily fruit and vegetable servings can improve bone health. Nutritional interventions are typically safe alternatives that should be considered for postmenopausal women who are seeking nonpharmacologic treatment options for osteoporosis.

[Osteoprotective effect of bread enriched with protein, dietary fiber, calcium, iron and iodine in hypoestrogen-induced osteoporosis among rats].

The search for new strategies for the prevention and control of osteoporosis is an urgent task. Functional foodstuffs and their components are of particular interest in this regard. The aim was to study the effect of bread enriched with protein, dietary fiber, calcium, iron and iodine on the state of the bone tissue of rats in a model of postmenopausal osteoporosis. Material and methods. The experiment was performed on sexually mature female Wistar rats divided into groups: K - control (sham-operated rats, not ovariectomized); О30 - osteoporosis model (animals were sacrificed 30 days after ovariectomy); groups О120 and О120+ - a model of osteoporosis (rats were sacrificed 120 days after ovariectomy). All animals were fed a standard vivary diet. For rats of the О120+ group, from the 40th to the 120th day, enriched bread was included in the diet in an amount of 6 g per 100 g of body weight per day. The bread was fortified with protein (whey protein, blood plasma proteins from farm animals), dietary fiber, calcium (eggshell), iron (purified hemoglobin) and iodized whey protein. Animals of groups K and О120 received unfortified bread in the same amount. Blood levels of total calcium (by colorimetric method), gonadotropins, testosterone, and estradiol (by enzyme-linked immunosorbent assay) were analyzed. Microtomographic evaluation of the architecture and mineral density of the trabecular part of the femur and lumbar vertebrae was performed. Histomorphological analysis of the uterus and femur of animals was performed. Results and discussion. In animals of the О120+ group, in comparison with the О120 sample, there was a decrease in blood testosterone and a marked compensatory release of follicle-stimulating hormone, while no changes were detected in the concentration of estradiol and the state of the uterus atrophied against the background of ovariectomy. There was an increase in the trabecular mineral density of the femur and lumbar vertebrae. The proportion of bone trabeculae in the total volume of the femoral metaphysis (BV/TV) in animals of the О120+ sample was 12.5±0.66% compared to 10.4±0.52% in the О120 group. The values of the structural model index (SMI) reflecting the loss of bone strength and the trabecularity coefficient (TbPf) in О120+ rats (1.44±0.07 and 5.96±0.29 1/mm) were significantly lower than these parameters in the О120 group (1.74±0.08; 9.13±0.46 1/mm, р<0.05). The micro-architectural structure of the femur in the О120+ group of rats was close to that of the О30 sample, which serves as a model of the early stage of osteoporosis (SMI 1.42±0.07; TbPf 5.55±0.28 1/mm). The percentage of bone resorption perimeter and the number of osteoclasts in the О120+ femoral trabeculae were lower than in the О120 group. In the О120+ group, active osteoblasts were observed in a significant part of the resorption cavities. Cell differentiation more was observed in the osteogenic direction than in the adipogenic direction. Conclusion. Bread enriched with protein, fiber, calcium, iron and iodine, effectively weakens osteoporosis induced by ovariectomy in rats. Its inclusion in the diet may be beneficial for the prevention and treatment of systemic postmenopausal osteoporosis.

The effect of protein diets in postmenopausal women with osteoporosis: Systematic review of randomized controlled trials.

The main objective of this systematic review was to examine the effectiveness of protein supplementation through diet or dietary supplements on osteoporosis in postmenopausal women as evidenced by randomized controlled trials (RCTs). Five RCTs were included using dietary protein (N = 2), protein supplements (N = 2), and proteins through diet and supplements (N = 1). A total of 677 postmenopausal woman were included, all diagnosed with osteoporosis (T score < -2.5) and aged between 50 and 80 years. Results have found that combined protein administration through diet, mainly from animal sources and supplemental proteins (whey proteins, 86 g/d PRO including 6 g WPI), for a short period of time (up to 12 months) may positively affect osteoporosis in postmenopausal women. In addition, a positive effect can also be achieved by the single administration of a 250 mg/d supplement in which 10 g was WPI for a six-month period. In this review, it is shown that both combined administration of proteins through diet and supplements and single administration through protein supplements may reduce the risk of fracture in postmenopausal osteoporotic women. In contrast, dietary proteins alone, in doses similar to and/or higher than the RDA values, may not have any positive effect on treating osteoporosis.

Estudio comparativo de la absorción neta de calcio de dos formulaciones distintas de carbonato de calcio en mujeres posmenopáusicas / Comparative study of net calcium absorption of two different pharma¬ceutical formulations of calcium carbonate in posmenopausal women

La suplementación con calcio reduciría, sola o asociada a otra medicación para osteoporosis, la pérdida de masa ósea y el riesgo de fracturas. Sin embargo, su tasa de adherencia es baja debido a la poca tolerancia. Objetivo: comparar la tasa de absorción neta de calcio entre dos formulaciones distintas de carbonato de calcio (500 mg): comprimidos vs. mousse. Material y métodos: 11 pruebas fueron realizadas en mujeres posmenopáusicas de 58,9±3 años. El diseño fue exploratorio abierto, aleatorizado, prospectivo cruzado de fase 4. Intervención: las participantes fueron aleatorizadas en dos grupos para recibir las dos formulaciones previa suplementación con vitamina D3. La tasa de absorción neta de calcio fue estudiada por la prueba de inhibición de hormona paratiroidea (PTH). Se obtuvieron muestras de sangre: basal y en la 1a, 2a y 3a hora posadministración del calcio asignado, y de orina de 2 horas basal y al final de la prueba. Determinaciones bioquímicas: calcio, fósforo, albúmina, 25-hidroxivitamina D y hormona paratiroidea intacta y calciuria. Análisis estadístico: método de los trapecios para calcular el área bajo la curva (AUC) de la concentración de calcio en el tiempo (R Development Core Team (2008). http://www.Rp-project.org) y Anova con dos términos de error para evaluar el efecto secuencia, período y formulación. Resultados: la mayor inhibición de PTH se observó a dos horas de la toma de ambas formulaciones (comprimidos -39,2% vs. mousse -38,0%; p=ns), con similar AUC0-3 h (comprimidos 3,35; IC 95%: 3,32; 3,37 vs. mousse 3,36; IC 95%: 3,33; 3,38). Cuando analizamos tolerancia y preferencias no se observaron diferencias estadísticamente significativas entre ambas formulaciones. Conclusión: el carbonato de calcio en mousse mostró similar tasa de absorción intestinal, preferencia y tolerancia gastrointestinal que en comprimido. (AU)

Calcium supplementation, administered alone or in combination with a specific medication for osteoporosis, would reduce bone mass loss and fracture risk in postmenopausal women. However, the adherence rate to calcium supplements is low, mainly due to low tolerance. Objective: comparisson of net calcium absorption rate between two different pharmaceutical formulations of calcium carbonate (PFCa) in postmenopausal women. Materials and Methods: 11 tests were performed in postmenopausal women aged 58.9±3 yrs. Design: Comparative, randomized, prospective, open-label exploratory crossover study of calcium mousse versus calcium pills. Intervention: Participants were randomized in 2 groups to receive the 2 different PFCa (500mg): pills vs. mousse, with previous vitamin D3 supplementation. The parathyroid hormone (PTH) inhibition test and the area-under-thecurve (AUC) of calcium were analyzed. Blood samples were taken at baseline and 1, 2 and 3 hrs after intake of the assigned PFCa. Urine samples (2hs) were obtained at -baseline, after 2hs of PFCa intake and at the end of the test. Biochemical Determinations: Serum: calcium, phosphorus, albumin, 25-hydroxyvitamin D, and intact PTH. In urine: calcium. Statistical Analysis: The trapezoid rule was applied to assess AUC in time (R Development Core Team (2008). http://www.Rp-project.org). An ANOVA model with 2 error terms was used to assess the effect of sequence, period, and formulation. Results: The highest inhibition PTH rates were observed after 2 hrs of PFCa (pills -39.2% vs. mousse -38.0%; p=ns). The AUC0-3hrs for both PFCa was similar (pills 3.35; 95%CI: 3.32; 3.37 vs. mousse 3.36; 95%CI: 3.33; 3.38). No statistically significant differences were observed when we analyze tolerance and predilection. Conclusion: The calcium carbonate in mousse showed an adequate rate of intestinal absorption, similarly predilection and gastrointestinal tolerance than the pill presentation. (AU)

PUFAs, Bone Mineral Density, and Fragility Fracture: Findings from Human Studies.

Osteoporosis is a global health problem that leads to an increased incidence of fragility fracture. Recent dietary patterns of Western populations include higher than recommended intakes of n-6 (ω-6) polyunsaturated fatty acids (PUFAs) relative to n-3 (ω-3) PUFAs that may result in a chronic state of sterile whole body inflammation. Findings from human bone cell culture experiments have revealed both benefits and detriments to bone-related outcomes depending on the quantity and source of PUFAs. Findings from observational and randomized controlled trials suggest that higher fatty fish intake is strongly linked with reduced risk of fragility fracture. Moreover, human studies largely support a greater intake of total PUFAs, total n-6 (ω-6) fatty acid, and total n-3 (ω-3) fatty acid for higher bone mineral density and reduced risk of fragility fracture. Less consistent evidence has been observed when investigating the role of long chain n-3 (ω-3) PUFAs or the ratio of n-6 (ω-6) PUFAs to n-3 (ω-3) PUFAs. Aspects to consider when interpreting the current literature involve participant characteristics, study duration, diet assessment tools, and the primary outcome measure.

The effect of two doses of dried plum on bone density and bone biomarkers in osteopenic postmenopausal women: a randomized, controlled trial.

UNLABELLED: Daily consumption of 50 g of dried plum (equivalent to 5-6 dried plums) for 6 months may be as effective as 100 g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. To some extent, these results may be attributed to the inhibition of bone resorption with the concurrent maintenance of bone formation. INTRODUCTION: The objective of our current study was to examine the possible dose-dependent effects of dried plum in preventing bone loss in older osteopenic postmenopausal women. METHODS: Forty-eight osteopenic women (65-79 years old) were randomly assigned into one of three treatment groups for 6 months: (1) 50 g of dried plum; (2) 100 g of dried plum; and (3) control. Total body, hip, and lumbar bone mineral density (BMD) were evaluated at baseline and 6 months using dual-energy X-ray absorptiometry. Blood biomarkers including bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRAP-5b), high-sensitivity C-reactive protein (hs-CRP), insulin-like growth factor-1 (IGF-1), and sclerostin were measured at baseline, 3 months, and 6 months. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), calcium, phosphorous, and vitamin D were measured at baseline and 6 months. RESULTS: Both doses of dried plum were able to prevent the loss of total body BMD compared with that of the control group (P < 0.05). TRAP-5b, a marker of bone resorption, decreased at 3 months and this was sustained at 6 months in both 50 and 100 g dried plum groups (P < 0.01 and P < 0.04, respectively). Although there were no significant changes in BAP for either of the dried plum groups, the BAP/TRAP-5b ratio was significantly (P < 0.05) greater at 6 months in both dried plum groups whereas there were no changes in the control group. CONCLUSIONS: These results confirm the ability of dried plum to prevent the loss of total body BMD in older osteopenic postmenopausal women and suggest that a lower dose of dried plum (i.e., 50 g) may be as effective as 100 g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. This may be due, in part, to the ability of dried plums to inhibit bone resorption. This clinical trial was registered at ClinicalTrials.gov: NCT02325895 .

Effect of Milk Powder Supplementation with Different Calcium Contents on Bone Mineral Density of Postmenopausal Women in Northern China: A Randomized Controlled Double-Blind Trial.

The objective of this study is to examine the effect of milk powder supplementation with different calcium contents on bone mineral density (BMD) in postmenopausal Chinese women, and to determine a more appropriate dose of calcium supplementation. A 2-year, randomized controlled double-blind trial. Postmenopausal women (n = 210) aged 50-65 years were recruited and assigned randomly into three calcium supplementation groups. All participants received milk powder supplementation with different calcium contents (300, 600, and 900 mg per day for groups A, B, and C, respectively) and all groups received 800 IU of vitamin D per day. During the follow-up period, BMD of the left hip and lumbar spine (as the main indicator) was measured using dual-energy X-ray absorptiometry at the baseline, 1 and 2 years. Both three BMD measures and the changes of BMD over 2 years were used to analyze. Before adjusting for covariates, BMD in group A of the lumbar spine and groups A and B of greater trochanter decreased significantly from the baseline over time but increased significantly in the rest groups of the lumbar spine and greater trochanter and in three groups of Ward's triangle. There were significant differences across the three groups for changes of BMD in the greater trochanter and Ward's triangle. When adjusting for covariates, there were significant decreases with time in group A of the spine (P = 0.001), groups A and B of greater trochanter (P = 0.0002 and P = 0.04, respectively) and increases in groups B and C of Ward's triangle (P = 0.03 and P = 0.004, respectively). BMD change in the greater trochanter was significantly different among three groups. For healthy postmenopausal women, high calcium milk powder supplementation was better in retarding bone loss than medium and low calcium in the greater trochanter. Considering the dietary calcium intake of postmenopausal women in north of China, a dose of 900 mg/day is considered as the most appropriate calcium supplementation for greater trochanter but not for other sites.

Cost-effectiveness of personalized supplementation with vitamin D-rich dairy products in the prevention of osteoporotic fractures.

UNLABELLED: Titrated supplementations with vitamin D-fortified yogurt, based on spontaneous calcium and vitamin D intakes, can be cost-effective in postmenopausal women with or without increased risk of osteoporotic fractures. INTRODUCTION: The objective of this study is to assess the cost-effectiveness of the vitamin D-fortified yogurt given to women with and without an increased risk of osteoporotic fracture. METHODS: A validated cost-effectiveness microsimulation Markov model of osteoporosis management was used. Three personalized supplementation scenarios to reflect the Ca/Vit D needs taking into account the well-known variations in dietary habits and a possible pharmacological supplementation in Ca/Vit D, given above or in combination with anti-osteoporosis medications: one yogurt per day, i.e., 400 mg of Ca + 200 IU of Vit D (scenario 1 U), two yogurts per day, i.e., 800 mg of Ca + 400 IU of Vit D (scenario 2 U), or three yogurts per day, i.e., 1,200 mg of Ca + 600 IU of Vit D (scenario 3 U). RESULTS: One yogurt is cost-effective in the general population above the age of 70 years and in all age groups in women with low bone mineral density (BMD) or prevalent vertebral fracture (PVF). The daily intake of two yogurts is cost-effective above 80 years in the general population and above 70 years in the two groups of women at increased risk of fractures. However, an intake of three yogurts per day is only cost-effective above 80 years old in the general population, as well as in women with low BMD or PVF. CONCLUSIONS: Our study is the first economic analysis supporting the cost-effectiveness of dairy products, fortified with vitamin D, in the armamentarium against osteoporotic fractures.

Plum and soy aglycon extracts superior at increasing bone calcium retention in ovariectomized Sprague Dawley rats.

Plant-derived polyphenols have been shown to influence bone turnover and bone properties in the estrogen-depleted state. We used a crossover design in ovariectomized rats (n = 16 rats for each diet) to investigate the effect of supplementation of two doses each of blueberry, plum, grape, grape seed extract, and resveratrol on bone. We tested the aglycon and glucoside forms of genistein to quantify differences in efficacy on bone calcium retention. Rats were given an intravenous dose of 45Ca to prelabel bone, and bone calcium retention was assessed by urinary excretion of 45Ca:Ca ratio during an intervention period compared with nonintervention. Genistein aglycon increased bone calcium retention significantly (p<0.05) more than the glucoside (22% vs 13%, respectively). Plum extract (0.45% w/w total dietary polyphenols) and resveratrol (0.2% w/w total dietary polyphenols) were also effective, increasing bone calcium retention by 20% (p=0.0153) and 14% (p=0.0012), respectively. Several polyphenolic-rich diets improved bone calcium retention.

The effect of dried plum on serum levels of receptor activator of NF-κB ligand, osteoprotegerin and sclerostin in osteopenic postmenopausal women: a randomised controlled trial.

Although several studies have confirmed the bone-protective properties of dried plum, its exact mechanisms of action remain unclear. Recent research has shown that osteocytes may control bone formation via the production of sclerostin and bone resorption via the receptor activator of NF-κB ligand (RANKL) and its inhibitor osteoprotegerin (OPG). To investigate the mechanism of action of dried plum in reversing bone loss, we measured serum levels of RANKL, OPG and sclerostin in osteopenic postmenopausal women (n 160). Participants were randomly assigned to the treatment group of either 100 g dried plum/d or 75 g dried apple/d (comparative control) for 1 year. All participants received 500 mg Ca plus 400 IU (10 µg) vitamin D daily. Bone mineral densities (BMD) of the lumbar spine, forearm, hip and whole body were assessed at baseline and at the end of the study using dual-energy X-ray absorptiometry. Blood samples were collected at baseline and after 12 months to assess bone biomarkers. Dried plum significantly increased the BMD of the ulna and spine in comparison with the control group. In comparison with corresponding baseline values, dried plum increased the RANKL levels by only +1·99 v. +18·33% and increased the OPG levels by +4·87 v. - 2·15% in the control group. Serum sclerostin levels were reduced by - 1·12% in the dried plum group v. +3·78% in the control group. Although percentage changes did not reach statistical significance (P≤ 0·05), these preliminary data may indicate that the positive effects of dried plum on bone are in part due to the suppression of RANKL production, the promotion of OPG and the inhibition of sclerostin.

Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational Study.

BACKGROUND: Magnesium is a necessary component of bone, but its relation to osteoporotic fractures is unclear. OBJECTIVE: We examined magnesium intake as a risk factor for osteoporotic fractures and altered bone mineral density (BMD). DESIGN: This prospective cohort study included 73,684 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Total daily magnesium intake was estimated from baseline food-frequency questionnaires plus supplements. Hip fractures were confirmed by a medical record review; other fractures were identified by self-report. A baseline BMD analysis was performed in 4778 participants. RESULTS: Baseline hip BMD was 3% higher (P < 0.001), and whole-body BMD was 2% higher (P < 0.001), in women who consumed >422.5 compared with <206.5 mg Mg/d. However, the incidence and RR of hip and total fractures did not differ across quintiles of magnesium. In contrast, risk of lower-arm or wrist fractures increased with higher magnesium intake [multivariate-adjusted HRs of 1.15 (95% CI: 1.01, 1.32) and 1.23 (95% CI: 1.07, 1.42) for quintiles 4 and 5, respectively, compared with quintile 1; P-trend = 0.002]. In addition, women with the highest magnesium intakes were more physically active and at increased risk of falls [HR for quintile 4: 1.11 (95% CI: 1.06, 1.16); HR for quintile 5: 1.15 (95% CI: 1.10, 1.20); P-trend < 0.001]. CONCLUSIONS: Lower magnesium intake is associated with lower BMD of the hip and whole body, but this result does not translate into increased risk of fractures. A magnesium consumption slightly greater than the Recommended Dietary Allowance is associated with increased lower-arm and wrist fractures that are possibly related to more physical activity and falls.

Effects of odanacatib on BMD and safety in the treatment of osteoporosis in postmenopausal women previously treated with alendronate: a randomized placebo-controlled trial.

CONTEXT: Odanacatib (ODN) is a selective cathepsin K inhibitor being developed to treat osteoporosis. OBJECTIVE: The effects of ODN were evaluated on bone mineral density (BMD), biochemical markers of bone turnover, and safety in patients previously treated with alendronate. DESIGN: This was a randomized, double-blind, placebo-controlled, 24-month study. SETTING: The study was conducted at private or institutional practices. PARTICIPANTS: Postmenopausal women (n = 243) ≥ 60 years of age with low BMD at the total hip, femoral neck, or trochanter (T-score ≤-2.5 but >-3.5 without prior fracture or ≤-1.5 but >-3.5 with prior fracture) on alendronate for ≥ 3 years. INTERVENTION: The intervention included ODN 50 mg or placebo weekly. MAIN OUTCOME MEASURES: The primary end point was percentage change from baseline of femoral neck BMD at month 24. BMD was assessed by dual-energy x-ray absorptiometry at baseline and 6, 12, and 24 months. Biochemical markers of bone turnover (serum C-telopeptides of type 1 collagen, urinary N-telopeptides of type 1 collagen, serum bone specific alkaline phosphatase, and serum N-terminal propeptide of type 1 collagen) were measured at baseline and 3, 6, 12, 18, and 24 months. RESULTS: In the ODN group, BMD changes from baseline at the femoral neck, trochanter, total hip, and lumbar spine at 24 months (1.7%, 1.8%, 0.8%, and 2.3%, respectively) were significantly different from the placebo group. ODN significantly decreased urinary N-telopeptides of type 1 collagen to creatinine ratio and significantly increased serum N-terminal propeptide of type 1 collagen compared with placebo. Serum C-telopeptides of type 1 collagen was unexpectedly increased with ODN treatment. The safety profile appeared similar between groups. CONCLUSIONS: ODN provided incremental BMD gains in osteoporotic women after alendronate treatment.

Consumption of yogurts fortified in vitamin D and calcium reduces serum parathyroid hormone and markers of bone resorption: a double-blind randomized controlled trial in institutionalized elderly women.

CONTEXT: Nutritional prevention of bone deterioration with fortified foods seems particularly suitable in institutionalized elderly women at risk of vitamin D deficiency, secondary hyperparathyroidism, increased bone resorption, and osteoporotic fracture. OBJECTIVE: The objective was to evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum PTH and bone resorption markers as compared with isocaloric and isoprotein dairy products in elderly women. DESIGN: A randomized double-blind controlled-trial, 56-day intervention was conducted in institutionalized women (mean age 85.5 years) consuming 2 125-g servings of either vitamin D- and calcium-fortified yogurt (FY) at supplemental levels of 10 µg/d vitamin D3 and 800 mg/d calcium or nonfortified control yogurt (CY) providing 280 mg/d calcium. MAIN OUTCOMES: The endpoints were serum changes from baseline (day 0) to day 28 and day 56 in 25-hydroxyvitamin-D (25OHD), PTH, and bone resorption markers tartrate-resistant acid phosphatase isoform-5b (TRAP5b), the primary outcome, and carboxyl-terminal cross-linked telopeptide of type I collagen (CTX). RESULTS: At day 56, serum 25OHD increased (mean ± SEM) by 25.3 ± 1.8 vs 5.2 ± 2.5 nmol/L in FY (n = 29) and CY (n = 27), respectively (P < .0001). The corresponding changes in PTH were -28.6% ± 7.2% vs -8.0% ± 4.3% (P = .0003); in TRAP5b, -21.9% ± 4.3% vs 3.0% ± 3.2% (P < .0001); and in CTX, -11.0% ± 9.7% vs -3.0% ± 4.1% (P = .0146), in FY and CY, respectively. At day 28, these differences were less pronounced but already significant for 25OHD, PTH, and TRAP5b. CONCLUSIONS: This study in institutionalized elderly at high risk for osteoporotic fracture suggests that fortification of dairy products with vitamin D3 and calcium provides a greater prevention of accelerated bone resorption as compared with nonfortified equivalent foods.

Dried plum's unique capacity to reverse bone loss and alter bone metabolism in postmenopausal osteoporosis model.

Interest in dried plum has increased over the past decade due to its promise in restoring bone and preventing bone loss in animal models of osteoporosis. This study compared the effects of dried plum on bone to other dried fruits and further explored the potential mechanisms of action through which dried plum may exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX) C57BL/6 mice were fed either a control diet or a diet supplemented with 25% (w/w) dried plum, apple, apricot, grape or mango for 8 weeks. Whole body and spine bone mineral density improved in mice consuming the dried plum, apricot and grape diets compared to the OVX control mice, but dried plum was the only fruit to have an anabolic effect on trabecular bone in the vertebra and prevent bone loss in the tibia. Restoration of biomechanical properties occurred in conjunction with the changes in trabecular bone in the spine. Compared to other dried fruits in this study, dried plum was unique in its ability to down-regulate osteoclast differentiation coincident with up-regulating osteoblast and glutathione (GPx) activity. These alterations in bone metabolism and antioxidant status compared to other dried fruits provide insight into dried plum's unique effects on bone.

Zoledronic acid acutely increases sclerostin serum levels in women with postmenopausal osteoporosis.

CONTEXT: Sclerostin is a circulating inhibitor of the Wnt-signaling pathway produced by osteocytes, which acts as a negative regulator of bone formation. Effects of zoledronic acid on sclerostin serum levels in postmenopausal osteoporosis are unknown. OBJECTIVE: The purpose of this study was to evaluate sclerostin serum levels after zoledronic acid administration and correlate variations with bone turnover markers. DESIGN AND SETTING: We conducted a prospective intervention study in an ambulatory care setting. PARTICIPANTS AND INTERVENTION: Forty women (mean age 62.6 ± 4.9 years) with postmenopausal osteoporosis were enrolled in this study and randomized into 2 groups to receive zoledronic acid (5 mg) or placebo. MAIN OUTCOMES MEASURES: At baseline and then at 2, 7, 30, and 360 days after zoledronic acid or placebo administration, serum levels of sclerostin, bone-specific alkaline phosphatase (BSAP), as a bone formation marker, and serum C-telopeptide of type 1 collagen (CTX), as a bone resorption marker, were measured. RESULTS: Sclerostin serum levels increased by day 2, reached a peak at day 7 (3-fold baseline, P < .001), and then decreased at day 30 and returned near to baseline after 360 days in the zoledronic acid group. Both CTX and BSAP were reduced, and a significant negative correlation was observed between the percentage changes of sclerostin and the variation in BSAP and CTX at all time points in the zoledronic acid group (P < .05). No changes were observed in the placebo group. CONCLUSIONS: Our data demonstrate that zoledronic acid increases sclerostin serum levels and that sclerostin could play a role in coupling bone resorption to bone formation.

Assessment of OPG/RANK/RANKL gene expression levels in peripheral blood mononuclear cells (PBMC) after treatment with strontium ranelate and ibandronate in patients with postmenopausal osteoporosis.

CONTEXT: Recent research results have confirmed the high significance of the OPG/RANK/RANKL system in the development of bone diseases. AIM: The aim of the reported study was to assess gene expression levels of the OPG/RANK/RANKL system in peripheral blood mononuclear cells (PBMCs) after strontium ranelate (SR) and ibandronate administered to patients with postmenopausal osteoporosis. PATIENTS AND METHODS: A total of 89 postmenopausal women, aged 51 to 85 years, patients of the Outpatient Clinic of Osteoporosis of the Military Teaching Hospital in Lodz, were enrolled into the study. The patients were randomly assigned to different medical therapies: ibandronate and SR. Patients of the control group received only calcium and vitamin D3 supplements. Patient visits were repeated after 3 and 6 months. Measurements of serum alkaline phosphatase concentrations and of RNA expression in PBMCs as well as of total serum calcium and phosphate levels and of their 24-hour urine excretion rates were carried out in material, collected at baseline and after 3 and 6 months of the therapy. Densitometry of the left hip and of the lumbar spine was done at the baseline visit and after 6 months. RESULTS: The differences in gene expressions of RANKL and RANK were not significant during the study period and did not differ between the groups in a statistically significant manner. No OPG gene expression was observed in PBMCs of patients in any of the studied groups and at any time point. The tendency of correlation (P = .07) was observed between decreasing RANK gene expression and increasing bone mineral density in the patients treated with SR. CONCLUSIONS: Both ibandronate and SR do not seem to cause any significant changes in gene expression levels of OPG/RANK/RANKL in PBMCs during the first 6 months of treatment.