绝经后骨质疏松性腰椎骨折骨代谢指标的变化

目的了解雌二醇和白细胞介素-6等骨代谢指标在骨质疏松症发病中的作用。方法选择女性腰椎骨折患者120例,绝经后有骨质疏松者60例(OP组),绝经后无骨质疏松者30例(NOP组),另外选择绝经前妇女30例为对照组。对120名妇女雌二醇、骨密度、白细胞介素-6、血清总碱性磷酸酶、骨钙素、尿羟脯氨酸肌酐比值、尿钙肌酐比值等指标进行了测定。结果绝经后妇女骨形成指标骨钙素及碱性磷酸酶明显高于对照组妇女,其中碱性磷酸酶在OP组和NOP组间有差异,而骨钙素在OP组和NOP组间无差异;绝经后妇女骨吸收指标尿羟脯氨酸肌酐比值及尿钙肌酐比值明显高于对照组妇女,OP组又明显高于NOP组;绝经后妇女的血清雌二醇的含量明显低于对照组(绝经前妇女),OP组又明显低于NOP组;绝经后妇女血清白细胞介素-6的含量明显高于对照组妇女,而OP组又明显高于NOP组。结论雌二醇、白细胞介素-6等骨代谢指标与骨质疏松关系密切。这充分说明雌激素水平的下降,IL-6分泌增多,导致骨吸收加速。     

Comparative Effects of Teriparatide and Strontium Ranelate on Bone Biopsies and Biochemical Markers of Bone Turnover in Postmenopausal Women With Osteoporosis

We assessed the effects on bone remodeling and histomorphometry after daily subcutaneous injections of teriparatide (n = 39, 20 μg/d) or oral strontium ranelate (SrR, n = 40, 2 g/d) in postmenopausal women with osteoporosis. Evaluable biopsies were obtained from 29 patients in the teriparatide group and 22 in the SrR group after 6 mo of treatment. The mean ± SD mineralization surfaces as a percent of bone surfaces (MS/BS, %) at the trabecular level were 7.73 ± 1.48% for teriparatide and 5.25 ± 1.15% for SrR (p = 0.219) and at the endocortical level were 17.22 ± 3.06% and 9.70 ± 2.07%, respectively (p = 0.052). Cortical porosity was 5.40 ± 0.41% in the teriparatide and 4.14 ± 0.40% in the SrR group (p = 0.037). Teriparatide induced significant increases from baseline in bone formation and resorption markers, reaching statistical significance for amino‐terminal propeptide of type I collagen (PINP) after 1 mo (+57%, p < 0.001). SrR induced small, but statistically significant, reductions from baseline in PINP at 3 (?14%, p = 0.005) and 6 mo (?19%, p < 0.001) and in serum β‐C‐terminal telopeptide of type I collagen (β‐CTX) at 1 and 3 mo (?11%, for both, p < 0.05). There were more patients with adverse events after SrR (70%) than teriparatide (41%) treatment (p = 0.013). In conclusion, the changes in biochemical markers of bone formation confirmed bone‐forming activity of teriparatide but not of SrR treatment. The effects of SrR on bone remodeling and cell activity were modest, indicating that its effects on fracture reduction may be predominantly mediated through a different mechanism than that observed with anabolic or more potent antiresorptive agents.     

Role of APOE Gene in Bone Mineral Density and Incidence of Bone Fractures in Brazilian Postmenopausal Women

Osteoporosis is one of the major diseases that affects mostly postmenopausal women. Despite being a multifactorial disease, some genes have been shown to play an important role in osteoporosis. Bone mineral density (BMD) is still largely used to diagnose it, although many other biomarkers are used to better follow the disease onset. It has been shown that the apolipoprotein E (APOE) gene could be a biomarker for risk of fractures as well as to predict lower BMD in patients with osteoporosis. The human APOE gene encodes 3 protein isoforms called ApoE2, ApoE3, and ApoE4, resulting in 4 possible genotypes, because they are a product of a single nucleotide polymorphism found in this gene. So far, the APOE4 allele has been associated with low BMD in postmenopausal women and to incidence of bone breaking in older women. This study aimed to investigate the role of ApoE isoforms in a cohort of 413 postmenopausal Brazilian women. These patients were randomly recruited, clinically examined, and subjected to dual-energy X-ray absorptiometry to measure their BMD. Patients were further grouped as normal BMD (T-score?<?0.5) or low BMD (T-score?>?1.0, osteopenic or osteoporotic). Patients with osteopenia or osteoporosis were further genotyped for APOE alleles as well as tested for many serum bone turnover biomarkers. Our data showed that presence of the APOE3 allele was associated with both higher BMDs and higher serum concentrations of osteocalcin and alkaline phosphatase, biomarkers for bone formation. On the other hand, the APOE2 and APOE4 alleles were associated with lower BMD as well as higher levels of serum C-terminus collagen peptide and urinary deoxipyridinolines, biomarkers for bone resorption. However, these effects on lower BMD and bone resorption biomarkers observed in either APOE2 or APOE4 alleles were eliminated when patients' genotype carried the APOE3 allele. Codominance of the APOE3 allele was also associated with lesser cases of bone fractures in these patients within a 5-year follow-up. In conclusion, our data show that APOE4 may be associated with lower bone formation as well as increased risk of osteoporosis and bone fractures, whereas APOE3 seems to decrease lowering BMD in postmenopausal women, and its presence seemed to lower the incidence of bone breaking in patients with osteoporosis.     

Effects of Growth Hormone Administration on Bone Mineral Metabolism,PTH Sensitivity and PTH Secretory Rhythm in Postmenopausal Women With Established Osteoporosis

Introduction : Growth hormone (GH) replacement improves target organ sensitivity to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover, and BMD in adult GH‐deficient (AGHD) patients. In postmenopausal women with established osteoporosis, GH and insulin like growth factor‐1 (IGF‐1) concentrations are low, and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH administration on PTH sensitivity, PTH circadian rhythm, and bone mineral metabolism in postmenopausal women with established osteoporosis. Materials and Methods : Fourteen postmenopausal women with osteoporosis were compared with 14 healthy premenopausal controls at baseline that then received GH for a period of 12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH administration and half‐hourly blood and 3‐h urine samples were collected. PTH, calcium (Ca), phosphate (PO₄), nephrogenous cyclic AMP (NcAMP), β C‐telopeptide of type 1 collagen (βCTX), procollagen type I amino‐terminal propeptide (PINP), and 1,25‐dihydroxyvitamin D [1,25(OH)₂D] were measured. Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t‐test and general linear model ANOVAs for repeated measures were used where appropriate. Results : IGF‐1 concentration was significantly lower in the women with established osteoporosis compared with controls (101.5 ± 8.9 versus 140.9 ± 10.8 μg/liter; p < 0.05) and increased significantly after 1, 3, 6, and 12 mo of GH administration (p < 0.001). Twenty‐four‐hour mean PTH concentration was higher in the osteoporotic women (5.4 ± 0.1 pM) than in healthy controls (4.4 ± 0.1 pM, p < 0.001) and decreased after 1 (5.2 ± 0.1 pM, p < 0.001), 3 (5.0 ± 0.1 pM, p < 0.001), 6 (4.7 ± 0.1 pM, p < 0.001), and 12 mo (4.9 ± 0.1 pM, p < 0.05) of GH administration compared with baseline. NcAMP was significantly lower in osteoporotic women (17.2 ± 1.2 nM glomerular filtration rate [GFR]) compared with controls (21.4 ± 1.4 nM GFR, p < 0.05) and increased after 1 (24.2 ± 2.5 nM GFR, p < 0.05), 3 (27.3 ± 1.5 nM GFR, p < 0.001), and 6 mo (32.4 ± 2.5 nM GFR, p < 0.001) compared with baseline. PTH secretion was characterized by two peaks in premenopausal women and was altered in postmenopausal women with a sustained increase in PTH concentration. GH administration also restored a normal PTH secretory pattern in the osteoporotic women. The 24‐h mean adjusted serum calcium (ACa) concentration increased at 1 and 3 mo (p < 0.001) and PO₄ at 1, 3, 6, and 12 mo (p < 0.001). 1,25(OH)₂D concentration increased after 3, 6, and 12 mo of GH (p < 0.05). An increase in urine Ca excretion was observed at 3 and 6 mo (p < 0.05), and the renal threshold for maximum tubular phosphate reabsorption rate (TmPO4/GFR) increased after 1, 3, 6, and 12 mo (p < 0.05). βCTX concentration increased progressively from 0.74 ± 0.07 μg/liter at baseline to 0.83 ± 0.07 μg/liter (p < 0.05) at 1 mo and 1.07 ± 0.09 μg/liter (p < 0.01) at 3 mo, with no further increase at 6 or 12 mo. PINP concentration increased progressively from baseline (60 ± 5 μg/liter) to 6 mo (126 ± 11 μg/liter, p < 0.001), with no further increase at 12 mo. The percentage increase in PINP concentration was significantly higher than βCTX (p < 0.05). Conclusions : Our study shows that GH has a regulatory role in bone mineral metabolism. GH administration to postmenopausal osteoporotic women improves target organ sensitivity to PTH and bone mineral metabolism and alters PTH secretory pattern with greater increases in bone formation than resorption. These changes, resulting in a net positive bone balance, may partly explain the mechanism causing the increase in BMD after long‐term administration of GH in postmenopausal women with osteoporosis shown in previous studies and proposes a further component in the development of age‐related postmenopausal osteoporosis.     

Teriparatide Reduces Bone Microdamage Accumulation in Postmenopausal Women Previously Treated With Alendronate

Suppression of bone turnover by bisphosphonates is associated with increased bone microdamage accumulation in animal models. Our objective was to study the effects of teriparatide treatment on changes in microdamage accumulation at the iliac crest in previously treatment‐naïve patients or in those switched from alendronate to teriparatide. Sixty‐six postmenopausal women with osteoporosis (mean age, 68.0 yr; and mean BMD T‐score of ?2.8 at lumbar spine and ?1.7 at total hip; 62% with prevalent fractures) entered this prospective, nonrandomized study and started with 24‐mo 20 μg/d subcutaneous teriparatide treatment in monotherapy: 38 patients stopped previous alendronate treatment (10 mg/d or 70 mg/wk for a mean duration of 63.6 mo) and switched to teriparatide, whereas 28 were previously treatment naïve. Thirty‐one paired biopsies with two intact cortices were collected and analyzed for microstructure and microdamage accumulation at baseline and after 24 mo of teriparatide administration. After 24 mo of teriparatide treatment, crack density (Cr.Dn), crack surface density (Cr.S.Dn), and crack length (Cr.Le) were decreased in previously alendronate‐treated patients, whereas only Cr.Le was reduced in former treatment‐naïve patients. Patients with lower initial femoral neck BMD also showed a higher reduction of microdamage accumulation. Better bone microarchitecture correlated positively, whereas bone turnover markers and age did not correlate with reduced microdamage accumulation on teriparatide. In conclusion, teriparatide reduces microdamage accumulation in the iliac crest of patients previously treated with alendronate. There is insufficient evidence to suggest that age or bone turnover would be associated with this change.     

Effects of Yearly Zoledronic Acid 5 mg on Bone Turnover Markers and Relation of PINP With Fracture Reduction in Postmenopausal Women With Osteoporosis

In patients with osteoporosis treated with antiresorptive agents, reduction in bone turnover explains much of the observed fracture risk reduction. Lower levels of bone turnover markers (BTMs) appear to be associated with a lower risk of fracture in bisphosphonate‐treated patients. BTMs were measured in a subset of subjects in the HORIZON Pivotal Fracture Trial. Annual infusions of zoledronic acid 5 mg significantly reduced BTMs: median decrease of 50% for β‐C‐terminal telopeptides of type 1 collagen (β‐CTX), 30% for bone alkaline phosphatase (ALP), and 56% for procollagen type 1 amino‐terminal propeptide (PINP). The mean level of BTMs decreased in treated patients but remained within the premenopausal range before the next injection. The percentage of zoledronic acid–treated patients with values below the premenopausal reference range at all time points was 1.7%, 17.8%, and 19% for bone ALP, CTX, and PINP, respectively. The third injection of zoledronic acid resulted in 60% reduction of β‐CTX within 9–11 days, followed by a gradual increase, indicating the persistence of osteoclastic bone resorption. The association between changes in BTMs and fracture incidence was assessed in 1132 patients who had PINP measurements at baseline and 1 yr. There was no association between low PINP levels at 1 yr and increased fracture incidence. In summary, (1) annual injections of zoledronic acid reduced BTMs in the premenopausal range, with a significant response persisting after the third infusion; and (2) low levels of PINP were not associated with increased fracture risk.     

Sclerostin Antibody Treatment Increases Bone Formation,Bone Mass,and Bone Strength in a Rat Model of Postmenopausal Osteoporosis

The development of bone‐rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long‐standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl‐AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six‐month‐old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency‐induced bone loss, at which point Scl‐AbII was administered for 5 wk. Scl‐AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency‐induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non‐ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody‐mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone‐related disorders, such as postmenopausal osteoporosis.     

Histomorphometric and μCT Analysis of Bone Biopsies From Postmenopausal Osteoporotic Women Treated With Strontium Ranelate

Strontium ranelate is a new anti‐osteoporotic treatment. On bone biopsies collected from humans receiving long‐term treatment over 5 yr, it has been shown that strontium ranelate has good bone safety and better results than placebo on 3D microarchitecture. Hence, these effects may explain the decreased fracture rate. Introduction: Strontium ranelate's mode of action involving dissociation of bone formation and resorption was shown in preclinical studies and could explain its antifracture efficacy in humans. Materials and Methods: One hundred forty‐one transiliac bone biopsies were obtained from 133 postmenopausal osteoporotic women: 49 biopsies after 1–5 yr of 2 g/d strontium ranelate and 92 biopsies at baseline or after 1–5 yr of placebo. Results and Conclusions: Histomorphometry provided a 2D demonstration of the bone safety of strontium ranelate, with significantly higher mineral apposition rate (MAR) in cancellous bone (+9% versus control, p = 0.019) and borderline higher in cortical bone (+10%, p = 0.056). Osteoblast surfaces were significantly higher (+38% versus control, p = 0.047). 3D analysis of 3‐yr biopsies with treatment (20 biopsies) and placebo (21 biopsies) using μCT showed significant changes in microarchitecture with, in the strontium ranelate group, higher cortical thickness (+18%, p = 0.008) and trabecular number (+14%, p = 0.05), and lower structure model index (?22%, p = 0.01) and trabecular separation (?16%, p = 0.04), with no change in cortical porosity. The changes in 3D microarchitecture may enhance bone biomechanical competence and explain the decreased fracture rate with strontium ranelate.     

Effects of Two Years of Daily Teriparatide Treatment on BMD in Postmenopausal Women With Severe Osteoporosis With and Without Prior Antiresorptive Treatment

Previous antiresorptive (AR) treatment may influence the response to teriparatide. We examined BMD response and safety in a subgroup of 503 postmenopausal women with osteoporosis who received teriparatide for 24 mo. Patients were divided into three groups based on their prior AR treatment: treatment‐naïve (n = 84); pretreated with no evidence of inadequate treatment response (n = 134); and pretreated showing an inadequate response to AR treatment (n = 285), which was predefined based on the occurrence of fractures, persistent low BMD, and/or significant BMD loss while on therapy. Changes in BMD from baseline were analyzed using mixed model repeated measures. Lumbar spine BMD increased significantly from baseline at 6, 12, 18, and 24 mo in all three groups. The mean gain in spine BMD over 24 mo was greater in the treatment‐naïve group (0.095 g/cm²; 13.1%) than in the AR pretreated (0.074 g/cm²; 10.2%; p < 0.005) and inadequate AR responder (0.071 g/cm²; 9.8%; p < 0.001) groups. The corresponding increases in total hip BMD were 3.8%, 2.3%, and 2.3%, respectively. Early decreases in hip BMD in the inadequate AR responder group were reversed by 18 mo of treatment. Increases in BMD between 18 and 24 mo were highly significant. Nausea (13.3%) and arthralgia (11.7%) were the most commonly reported adverse events. Asymptomatic hypercalcemia was reported in 5.0% of patients. Teriparatide treatment for 24 mo is associated with a significant increase in BMD in patients with and without previous AR use. Prior AR treatment modestly blunted the BMD response to teriparatide. Safety was consistent with current prescribing label information.     

Calcium and Bone Metabolism During Pregnancy and Lactation

Pregnancy and lactation both place significant demands on the mother to provide sufficient calcium (among other minerals and nutrients) to the fetus and neonate. Despite facing similar demands for calcium during pregnancy and lactation, the maternal adaptations differ significantly between these two reproductive periods. Women lose 300 to 400 mg of calcium daily through breast milk, and this calcium demand is met by a 5–10% loss of skeletal mineral content during 6 months of exclusive lactation. Most importantly, the lost mineral is fully restored within a few months of weaning, such that women who have breastfed do not have a long-term deficit in skeletal mineral content. This article will review our present understanding of the adaptations in mineral metabolism that occur during pregnancy and lactation, and will focus on recent evidence that the breast itself plays a central role in regulating the adaptations during lactation.     

Five Years of Treatment with Risedronate and its Effects on Bone Safety in Women with Postmenopausal Osteoporosis

We have recently reported that risedronate preserves normal bone formation and decreases bone remodeling in women with postmenopausal osteoporosis after 3 years of treatment. We report now the results of a 2-year extension study. The primary objective of this study was to determine the effect of 5 years of risedronate treatment (5 mg daily) on bone quality and bone remodeling based on paired transiliac bone biopsies. There were additional measurements that included bone turnover markers and bone mineral density (BMD). Histologic evaluation of biopsy sections (placebo, n = 21; risedronate, n = 27) yielded no pathologic findings after 5 years in either treatment group. Histomorphometric assessment of paired biopsy specimens after 5 years (placebo, n =12; risedronate, n = 13) found no statistically significant differences between treatment groups in structural or resorption parameters. There was a significant reduction in osteoid (–27%) and mineralizing surfaces (–49%) from baseline values in the risedronate group that were also significantly different from placebo at 5 years. Similarly, activation frequency decreased significantly (–77%) in the risedronate group, although it was not significantly different from placebo at 5 years (0.09 vs. 0.21, respectively). Double tetracycline labels were identified in all biopsy specimens indicating continuous bone turnover. After 5 years of risedronate treatment, serum bone-specific alkaline phosphatase (bone ALP) and N-telopeptide (NTX) decreased significantly from baseline by 33.3% and 47.5%, respectively. In the placebo group, bone ALP decreased by 3.9% (P = NS), whereas NTX decreased by 27.0% (P < 0.005). Lumbar spine BMD increased significantly in the risedronate group (9.2%), whereas no significant change was seen in the placebo group (–0.26%). Risedronate was overall well tolerated; during the 2-year study extension nonvertebral fractures occurred in 7 patients in placebo and 2 patients in risedronate groups. The findings from this study are consistent with the antiremodeling effect of risedronate and support long-term bone safety and antifracture efficacy of risedronate treatment.This work was supported by grants from Procter & Gamble Pharmaceuticals, Inc., Mason, Ohio, and Aventis Pharmaceuticals, Bridgewater, New Jersey.     

Comparison of Bone Mineral Density of the Phalanges, Lumbar Spine, Hip, and Forearm for Assessment of Osteoporosis in Postmenopausal Women

The objective of this study was to compare peripheral bone mineral density (BMD) of the phalanges with BMD of the lumbar spine, total hip, femoral neck, and forearm and to determine the clinical value of measuring a single peripheral site (phalanges) in identifying postmenopausal women with osteoporosis. BMD was measured by dual energy X-ray absorptiometry using the accuDEXA((R)) (ADXA-finger) (Schick, New York, NY) and the QDR-4500 (DXA-lumbar spine, hip, forearm) (Hologic, Waltham, MA). Correlation coefficients between ADXA and DXA of the lumbar spine, total hip, femoral neck and one third radial site ranged from 0.53 to 0.73. The sensitivity of an ADXA T-score of -2.5 in identifying patients with a DXA T-score of < or = -2.5 at the femoral neck was 35%. An ADXA T-score cut point of -1.0 improved the sensitivity of ADXA in identifying patients with a femoral neck T-score of < or = -2.5 (85%), but the specificity declined from 88 to 49%. There was substantial discordance in the diagnosis of osteoporosis when a single site was measured, regardless of technique. Within the limitations of single-site measurements, BMD measured by ADXA has adequate sensitivity to identify women with low BMD at the femoral neck, if an appropriate T-score criterion is used.     

Fibroblast Growth Factor 21 Is Associated With Bone Mineral Density,but not With Bone Turnover Markers and Fractures in Chinese Postmenopausal Women

Fibroblast growth factor 21 (FGF21) is a member of the endocrine FGF subfamily and an important metabolic regulator that has multiple beneficial effects on glucose homeostasis and lipid metabolism. However, it was unclear whether FGF21 would induce bone defects in humans. This study evaluated the associations of FGF21 levels, bone mineral density (BMD), osteoporotic fracture, and bone turnover marks (BTMs) in postmenopausal women. A total of 1342 postmenopausal Chinese Han women (511 cases of fragility fracture in the case group and 831 cases in nonfragility fracture group) were enrolled. Serum FGF21 concentration was measured by ELISA (Quantikine), serum calcium (Ca), phosphate (P), alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone, β-crosslinked C-telopeptide of type l collagen, were measured using an automated Roche electro-chemiluminescence system. BMD was measured using dual-energy X-ray absorptiometry. The association with age, BMD, 25-hydroxyvitamin D, parathyroid hormone, β-crosslinked C-telopeptide of type l collagen, and FGF21 levels were also evaluated in postmenopausal women. In nonfracture group and fragility fracture group, postmenopausal women's FGF21 level was 226.57pg/mL (149.11–354.43 pg/mL) and 219.43pg/mL (147.21–323.74 pg/mL), respectively. There is no significant difference in serum FGF21 levels between the fragility fracture group and the nonfracture group (p = 0.160). There was a significant statistical difference in BMD between the fragility fracture group and the nonfracture group (p?=?0.000). In multiple linear regression analysis, FGF21 levels were significantly positive associated with lumbar BMD in postmenopausal women (L1-4, p?=?0.007), independent of other factors, especially in fragility fracture group (L1-4, p?=?0.001). In addition, a significant positive association was also observed between serum FGF21 levels and age in postmenopausal women (p < 0.05). We reveal a positive correlation between serum FGF21 concentrations with lumbar BMD in Chinese Han postmenopausal women. No significant correlations are present between serum FGF21 and bone turnover marks or serum FGF21 and fragility fracture in our study.     

瘦素在骨与软骨代谢中的作用

肥胖对机体健康的不良影响已得到越来越多的重视,但人们在研究和防治肥胖的同时,也发现肥胖对骨骼有保护作用:肥胖者很少患有骨质疏松症,髋部骨折的发生率也较低[1]。体重或体重指数(BMI)与骨密度(BMD)的相关性已经得到公认,许多研究进一步证明体重的重要组成部分———体脂量(     

Sodium and Bone Health: Impact of Moderately High and Low Salt Intakes on Calcium Metabolism in Postmenopausal Women

High salt intake is a well‐recognized risk factor for osteoporosis because it induces calciuria, but the effects of salt on calcium metabolism and the potential impact on bone health in postmenopausal women have not been fully characterized. This study investigated adaptive mechanisms in response to changes in salt and calcium intake in postmenopausal women. Eleven women completed a randomized cross‐over trial consisting of four successive 5‐wk periods of controlled dietary intervention, each separated by a minimum 4‐wk washout. Moderately low and high calcium (518 versus 1284 mg) and salt (3.9 versus 11.2 g) diets, reflecting lower and upper intakes in postmenopausal women consuming a Western‐style diet, were provided. Stable isotope labeling techniques were used to measure calcium absorption and excretion, compartmental modeling was undertaken to estimate bone calcium balance, and biomarkers of bone formation and resorption were measured in blood and urine. Moderately high salt intake (11.2 g/d) elicited a significant increase in urinary calcium excretion (p = 0.0008) and significantly affected bone calcium balance with the high calcium diet (p = 0.024). Efficiency of calcium absorption was higher after a period of moderately low calcium intake (p < 0.05) but was unaffected by salt intake. Salt was responsible for a significant change in bone calcium balance, from positive to negative, when consumed as part of a high calcium diet, but with a low calcium intake, the bone calcium balance was negative on both high and low salt diets.     

Phytoestrogens in the Prevention of Postmenopausal Bone Loss

Postmenopausal osteoporosis is a condition associated with low bone mass resulting from the increased bone resorption that occurs following a decline in estrogen levels. Phytoestrogens are plant-derived compounds that have affinity to the estrogen receptor and are able to act as either estrogen agonists or antagonists. Because of their structural similarity to 17-beta-estradiol, they have been studied extensively for their role in the prevention of postmenopausal bone loss. An extensive number of studies employing different types of isoflavone preparations (including soy foods, soy-enriched foods, and soy isoflavone tablets) have been conducted in a wide range of populations, including Western and Asian women. Although there is considerable variability in study design and duration, study population, type of soy isoflavone employed in the intervention, and study outcomes, the evidence points to a lack of a protective role of soy isoflavones in the prevention of postmenopausal bone loss.     

Vitamin D Status,Parathyroid Function,Bone Turnover,and BMD in Postmenopausal Women With Osteoporosis: Global Perspective

Poor vitamin D status is common in the elderly and is associated with bone loss and fractures. The aim was to assess worldwide vitamin D status in postmenopausal women with osteoporosis according to latitude and economic status, in relation to parathyroid function, bone turnover markers, and BMD. The study was performed in 7441 postmenopausal women from 29 countries participating in a clinical trial on bazedoxifene (selective estrogen receptor modulator), with BMD T‐score at the femoral neck or lumbar spine ≤ ?2.5 or one to five mild or moderate vertebral fractures. Serum 25(OH)D, PTH, alkaline phosphatase (ALP), bone turnover markers osteocalcin (OC) and C‐terminal cross‐linked telopeptides of type I collagen (CTX), and BMD of the lumbar spine, total hip, femoral neck, and trochanter were measured. The mean serum 25(OH)D level was 61.2 ± 22.4 nM. The prevalence of 25(OH)D <25, 25–50, 50–75, and >75 nM was 5.9%, 29.4%, 43.5%, and 21.2%, respectively, in winter and 3.0%, 22.2%, 47.2%, and 27.5% in summer. Worldwide, a negative correlation between 25(OH)D and latitude was observed. With increasing 25(OH)D categories of <25, 25–50, 50–75, and >75 nM, mean PTH, OC, and CTX were decreasing (p < 0.001), whereas BMD of all sites was increasing (p < 0.001). A threshold in the positive relationship between 25(OH)D and different BMD parameters was visible at a 25(OH)D level of 50 nM. Our study showed a high prevalence of low 25(OH)D in postmenopausal women with osteoporosis worldwide. Along with latitude, affluence seems to be an important factor for serum 25(OH)D level, especially in Europe, where it is strongly correlated with latitude.