Associations of Iron Intake, Serum Iron and Serum Ferritin with Bone Mineral Density in Women: The National Health and Nutrition Examination Survey, 2005-2010.

The relationship between iron and bone mineral density (BMD) is still poorly understood. We investigated the associations of iron intake, serum iron and serum ferritin with BMD. This cross-sectional study identified 4000 females aged 12 to 49 years with complete and valid data on iron intake, serum iron, serum ferritin, and femoral neck and lumbar spine BMD from the National Health and Nutrition Examination Survey 2005-2010. Daily iron intake was the mean intake of iron nutrient ascertained from two consecutive 24-h dietary recalls; serum iron and serum ferritin were directly measured with established methods. Femoral neck and lumbar spine BMD were measured by Dual-energy X-ray absorptiometry (DXA). After adjusting for multiple covariates (i.e., age, body mass index and race), we used linear regression and generalized additive models (GAMs) to test the linear and non-linear associations of iron intake, serum iron and serum ferritin with BMD. The mean age of this study was 27.70 years (SD = 11.88 years). Higher serum ferritin was associated with lower femoral neck and lumbar spine BMD (all adjusted P < 0.05); iron intake and serum iron were not associated with femoral neck and lumbar spine BMD. Similar results were found when iron levels were classified as iron deficiency, normal iron and iron overload. There were no obvious non-linear relationships between the above three iron variables and BMD in the GAM analyses. There was a negative and linear association between serum ferritin and BMD; iron intake and serum iron were not associated with BMD. Serum ferritin appeared to be a better iron variable than iron intake and serum iron in relation to BMD.

An analysis of factors affecting the mercury content in the human femoral bone.

The study was carried out to determine the content of mercury in bone tissue of the proximal femur (head and neck bone) of 95 patients undergoing total hip replacement due to osteoarthritis, using CF-AFS analytical technique. Furthermore, the investigations were aimed at assessing the impact of selected factors, such as age, gender, tobacco smoking, alcohol consumption, exposure to chemical substance at work, type of degenerative changes, clinical evaluation and radiological parameters, type of medications, on the concentration of mercury in the head and neck of the femur, resected in situ. Mercury was obtained in all samples of the head and neck of the femur (n = 190) in patients aged 25-91 years. The mean content of mercury for the whole group of patients was as follows: 37.1 ± 35.0 ng/g for the femoral neck and 24.2 ± 19.5 ng/g for the femoral head. The highest Hg contents were found in femoral neck samples, both in women and men, and they amounted to 169.6 and 176.5 ng/g, respectively. The research showed that the mercury content of bones can be associated with body mass index, differences in body anatomy, and gender. The uses of statistical analysis gave the possibility to define the influence of factors on mercury content in human femoral bones.

Blood Cadmium Is Associated with Osteoporosis in Obese Males but Not in Non-Obese Males: The Korea National Health and Nutrition Examination Survey 2008-2011.

Osteoporosis in males is becoming an important health concern in an aging society. The aim of this study was to investigate the associations between cadmium exposure and osteoporosis by considering the effect of obesity in aged males using a representative sample of the Korean population. Using the fourth and fifth Korea National Health and Nutrition Examination Survey data, 1098 males over 50 years of age were analyzed. The blood cadmium concentration was measured. The bone mineral density in the total hip, femur neck, and lumbar spine was measured using dual-energy X-ray absorptiometry. T-scores to determine the presence of osteoporosis were calculated using a Korean reference. Subjects were stratified into two groups according to obesity status (body mass index <25 kg/m² and ≥25 kg/m²). In comparison with obese subjects with blood cadmium <1.00 µg/L, those with blood cadmium >1.50 µg/L had odds ratios of 4.57 (95% confidence interval [CI] 1.49-14.01) and 5.71 (95% CI 1.99-16.38) at the femur neck and any site, respectively, after adjusting for potential confounders such as age, serum creatinine, vitamin D deficiency, smoking, alcohol drinking, and physical activity level. However, this association was not significant in non-obese males. In conclusion, the effect of cadmium on osteoporosis was different by obesity status in aged males.

Association between Sleep Duration, Insomnia Symptoms and Bone Mineral Density in Older Boston Puerto Rican Adults.

OBJECTIVE: To examine the association between sleep patterns (sleep duration and insomnia symptoms) and total and regional bone mineral density (BMD) among older Boston Puerto Rican adults. MATERIALS/METHODS: We conducted a cross-sectional study including 750 Puerto Rican adults, aged 47-79 y living in Massachusetts. BMD at 3 hip sites and the lumbar spine were measured using dual-energy X-ray absorptiometry. Sleep duration (≤5 h, 6 h, 7 h, 8 h, or ≥9 h/d) and insomnia symptoms (difficulty initiating sleep, difficulty maintaining sleep, early-morning awaking, and non-restorative sleep) were assessed by a questionnaire. Multivariable regression was used to examine sex-specific associations between sleep duration, insomnia symptoms and BMD adjusting for standard confounders and covariates. RESULTS: Men who slept ≥9h/d had significantly lower femoral neck BMD, relative to those reporting 8 h/d sleep, after adjusting for age, education level, smoking, physical activity, depressive symptomatology, comorbidity and serum vitamin D concentration. This association was attenuated and lost significance after further adjustment for urinary cortisol and serum inflammation biomarkers. In contrast, the association between sleep duration and BMD was not significant in women. Further, we did not find any significant associations between insomnia symptoms and BMD in men or women. CONCLUSIONS: Our study does not support the hypothesis that shorter sleep duration and insomnia symptoms are associated with lower BMD levels in older adults. However, our results should be interpreted with caution. Future studies with larger sample size, objective assessment of sleep pattern, and prospective design are needed before a conclusion regarding sleep and BMD can be reached.

Association of IL-6 G-174C polymorphism with bone mineral density.

Functional polymorphisms in the promoter region of interleukin-6 (IL-6) are known to be involved in bone mineral density (BMD) and the development of osteoporosis, but the reported results have been inconsistent. Using the meta-analysis approach, the present study is designed to provide a relatively comprehensive picture of the relationship between bone mineral density (BMD) or osteoporosis and polymorphisms in the promoter region of IL-6 (rs1800795 and rs1800796). The difference of bone mineral density (BMD) values between genotypes was examined by mean difference and 95 % confidence intervals (CIs). Association between IL-6 polymorphism and clinical osteoporosis was evaluated by pooled odds ratios (ORs) and 95 % CIs. A total of 13 articles with 11,499 subjects were included in the present study. For -174 (rs1800795), we found that individuals with the G/G genotype had a significantly lower BMD value than those with C/C genotype at femoral neck (0.02 g/cm(2), 95 % CI 0.00-0.03) (p = 0.04) and distal radius (0.01 g/cm(2), 95 %CI 0.01-0.01) (p < 0.0001). However, we did not find a statistically significant difference of BMD at the spine. When analysis was limited to postmenopausal women, similar results were obtained. We further found that the C/C genotype was associated with a reduced risk of osteoporosis compared to G/G genotype, and the pooled OR was 0.72 (95 % CI 0.54-0.95, p = 0.02). In addition, a significant relationship was found between G-634C (rs1800796) polymorphism and distal radius BMD (CC vs. GG: 0.02 g/cm(2), 95 % CI 0.01-0.03; GC vs. GG: 0.02 g/cm(2), 95 % CI 0.00-0.03) in the Asian population. These findings suggest that the CC genotype of IL-6 G-174C polymorphism may be associated with high BMD at femoral neck and distal radius and decreased risk of osteoporosis in the Caucasian population whereas G-634C polymorphism was associated with distal radius BMD in Asians.

Total and femoral neck bone mineral density and physical activity in a sample of men and women.

Physical activity (PA), total body fat (TBF), and lean body mass (LBM) are associated with bone mineral density (BMD). However, the independent influence of PA on BMD, while controlling for body composition is not understood as well and is the purpose of the current study. Whole-body BMD (g·cm⁻²), femoral neck BMD (g·cm⁻²), TBF (kg), and LBM (kg) were measured with dual-energy X-ray absorptiometry. PA levels (total, work, sport, non-sport) were estimated using the Baecke questionnaire. General linear models determined the independent effects of PA on BMD (whole-body and femoral neck), with adjustment for age, sex, ethnicity, smoking, menopausal status (as appropriate), LBM, and TBF. These associations were also examined by sex and age group (20-34, 35-49, and 50-64 years). The sample included 802 adults (65% women; 13% African American) from the Pennington Center Longitudinal Study that were 20 to 64 years of age (mean ± SD: 46.9 ± 11.0 years). Higher sports scores were associated with higher femoral neck BMD in the total group, men and women, and in 20- to 34-year-olds and 35- to 49-year-olds, but not significant in those 50-64 years of age. Similar significant associations were found for sports score with total body BMD; however, this relationship was not significant for women or for those 50-64 years of age. Total PA had inconsistent relationships with both femoral neck BMD and total body BMD. Higher levels of sport-related PA are associated with higher femoral neck BMD; however, these relationships vary by PA domain and site of BMD measurement.

[Bone mineral density in patients with type 2 diabetes]. / Densidad mineral ósea en pacientes con diabetes tipo 2.

OBJECTIVE: To establish whether type 2 diabetes (T2D) is associated with changes in the bone mineral density (BMD) of femoral neck, total hip and lumbar spine. MATERIAL AND METHODS: Comparative cross-sectional study that included 450 patients aged 30 years or more; 245 with, and 205 without T2D. Groups were matched by age. Degenerative joint disease, rheumatoid arthritis, neoplasia, renal failure, chronic liver disease, alcohol intake, prior treatment with drugs that modulate the BMD, Diabetes Mellitus Type 1 and other endocrinopathies were exclusion criteria. RESULTS: In the overall group, the presence of menopause was associated with osteoporosis in the hip (odds ratio -OR-4.2; CI95% 1.4-6.1), whereas T2D was a protective factor (OR 0.8; CI95% 0.4-0.9). Among premenopausal women, central obesity and total adiposity were associated with osteoporosis in the hip (OR 1.9; CI95% 1.1-3.9 and OR 2.1; CI95% 1.2-8.7) and femoral areas (OR 2.1; CI95% 1.2-4.1 and OR 2.3; CI95% 1.3-7.1); T2D remained as protective factor (OR 0.7; CI95% 0.5-0.9 and OR 0.6; CI95% 0.4-0.9). The adjusted analysis by BMI, waist circumference, and total adiposity showed that T2D remained as a protective factor for osteoporosis in the hip (OR 0.8; CI95% 0.6-0.9) and femoral areas (OR 0.7; CI95% 0.5-0.9). CONCLUSIONS: Our results suggest that T2D is an independent protective factor for osteoporosis.

The relationship between Receptor Activator of Nuclear Factor-kappaB Ligand (RANKL) gene polymorphism and aortic calcification in Korean women.

The aim of this study was to investigate the relationship between RANKL gene polymorphisms and aortic calcification in Korean women. In 237 healthy Korean women, aortic calcification in thoracic and abdominal aorta was examined in simple radiologic method and lumbar spine and femoral neck BMD were examined by dual energy X-ray absorptiometry. Serum OPG levels, bone turnover markers, such as ALP levels and urine deoxypyridinoline levels, and urine calcium excretion were measured. Genotyping of two RANKL gene polymorphisms, rs2277438 and rs9594782, was performed by allelic discrimination using the 5' nuclease polymerase chain reaction assay. The subjects with CT/CC genotypes of the rs9594782 polymorphism had a 3.9 times higher risk of aortic calcification compared with TT genotype. This significance was significant even after adjustment for age, BMI, blood pressure, fasting plasma glucose, serum high and low-density lipoprotein cholesterol levels. Mean levels of urine deoxypyridinoline were significantly higher in the subjects with AG/GG genotypes of the rs2277438 polymorphism compared with AA genotype, and this significance was persistent even after adjustment for age and BMI. There were no associations of mean values for age, BMI, serum OPG and ALP levels, urine calcium excretion, and BMD with RANKL gene polymorphisms. The RANKL gene rs9594782 polymorphism was associated with aortic calcification in Korean women. Rs2277438 polymorphism showed significant association with urine deoxypyridinoline levels, a bone resorption marker. These results suggest its role on vascular calcification and bone metabolism in humans.

Common polymorphisms rather than rare genetic variants of the Runx2 gene are associated with femoral neck BMD in Spanish women.

RUNX2 is a transcription factor essential for osteoblast differentiation and skeletal morphogenesis. Its mutation creates cleidocranial dysplasia (CCD), a disorder characterized by skeletal abnormalities and bone mineral density (BMD) alterations. The purpose of the present study has been to clarify whether polymorphisms affecting this gene could be associated with changes in BMD in women. To that end, we performed an association study of BMD values from 776 women with two single nucleotide polymorphisms (SNPs) located at P2 promoter (-1025 T>C) and at exon 2 (+198 G>A), and with a deletion polymorphism (17Ala>11Ala), also located at exon 2. We found an association of -1025 T>C SNP with femoral neck BMD (FN-BMD), being the women of TC/CC genotype who have higher BMD than women of TT genotype (P = 0.006). This association was independent of age, weight, menopausal status, or hormone replacement therapy (HRT) use as shown by regression analysis. When women of highest versus lowest quartile of BMD were compared, this association became more evident (P = 0.002), extending also to +198 G>A SNP (GA/AA women with higher FN-BMD; P < 0.05). In addition, we describe herein three novel rare variants in the polyglutamine domain of RUNX2 protein: an in-frame insertion and two deletions in exon 2, resulting in the insertions of 7 and deletions of 7 and 5 glutamines, respectively. These variants do not produce CCD, increased frequency of bone fracture, or BMD alterations. In conclusion, common polymorphisms in Runx2 are associated with FN-BMD. Nevertheless, rare variants that modify the polyglutamine domain of RUNX2 neither have any effect on BMD nor produce the CCD phenotype. These results underscore the significance of polymorphisms in the 5'-region of Runx2 in the determination of FN-BMD.

Long-term effects on bone mineral density of different therapeutic schemes for acute lymphoblastic leukemia or non-Hodgkin lymphoma during childhood.

BACKGROUND: Little is known regarding long-term bone deficit in relationship with the modalities of cancer therapy among survivors of childhood malignancy. METHODS: Bone mineral density (BMD) was evaluated at lumbar spine (LS), total hip and femoral neck in 89 patients (44 men) more than 5 years after remission of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). The patients had received chemotherapy (group I; n = 41), chemotherapy and cranial irradiation (group II; n = 32), or bone marrow transplantation (BMT) with total body irradiation (TBI) (group III; n = 16). All patients had received methylprednisolone and 47 additional dexamethasone treatment. RESULTS: A reduced BMD at any site was observed in 44 of the 89 patients, more frequently in men (66%) than women (33%) (p < 0.001). In comparison with group I, mean BMD was significantly lower at all sites in group II and at the total hip and femoral neck in group III. A multivariate analysis showed independent significant influences of male gender at LS (p < 0.001) and of type of treatment and dexamethasone at the hip (p < 0.05). CONCLUSIONS: A low bone mass is frequently observed in adult survivors of childhood ALL and NHL, and is associated with male gender at the LS and with dexamethasone treatment, cranial irradiation and BMT/TBI at the hip.

The relationships among bone health, insulin-like growth factor-1 and sex hormones in adolescent female athletes.

The aim of this study was to determine the relationships of bone mineral density (BMD) and content (BMC) with insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3) and estradiol in pubertal female athletes. The participants were 170 healthy adolescent girls (13-15 years) who participated in competitive extramural athletic programs, i.e., sports games (n = 49), track sprinting (n = 24), rhythmic gymnastics (n = 23), swimming (n = 24) and cross-country skiing (n = 17). The control group (n = 33) consisted of girls who took part only in compulsory physical education classes at school. The whole-body BMD and femoral neck and lumbar spine BMD and BMC were measured using DXA, and the volumetric BMD was calculated. Venous blood samples to determine the concentration of IGF-1, IGFBP-3 and estradiol were drawn after an overnight fasting. After adjusting for age, body height and body mass, the relationships among BMD variables, IGF-1 and the IGF-1/IGFBP-3 molar ratio remained significant only in the rhythmic gymnast group. BMDs at the femoral neck and lumbar spine were also related to estradiol levels (r = 0.45-0.60; p < 0.05) only in the rhythmic gymnast group. No relationships were found among the measured BMD, IGF axis and estradiol in other athletic groups. Only BMC at the femoral neck remained associated with the IGF-1/IGFBP-3 molar ratio in the rhythmic gymnast group after adjusting for age, body height and body mass. Stepwise multiple regression analysis indicated that IGF-1 and estradiol together explained 42.6% (R(2) x 100) of total variance in the femoral neck BMD and IGF-1 alone 35.4% (R(2) x 100) of the total variance in the femoral neck BMC only in the rhythmic gymnast group. We conclude that femoral neck and lumbar spine BMD correlated with IGF-1, IGF-1/IGFBP-3 molar ratio and estradiol in rhythmic gymnasts. No relationships were found between bone parameters and the hormones used in other athletic groups.

Gene-gene interactions in RANK/RANKL/OPG system influence bone mineral density in postmenopausal women.

Receptor activator of nuclear factor kappaB (RANK) is one of the proteins in regulation of osteoclastogenesis via RANK/RANKL/OPG. Gene that codes for RANK protein (TNFRSF11A) was associated with osteoporotic fractures in a recent genome-wide association study. As variations in the RANK gene could alter its expression and activity, the aim of our study was to evaluate the influence of four RANK gene polymorphisms on bone mineral density (BMD) and biochemical markers. We evaluated 467 postmenopausal women and 117 elderly men. All subjects were genotyped for the presence of RANK polymorphisms -670G>C, +34694C>T, +34901G>A and +35966insdelC. BMD and biochemical markers were measured. Significant associations of +35966insdelC with BMD at lumbar spine (BMD-ls), total hip (BMD-th) and femoral neck (BMD-fn) were found in postmenopausal women (p=0.020, 0.024 and 0.034), but not in men. Significant gene-gene interaction was proved for two RANK polymorphisms in combination with OPG and RANKL polymorphisms studied previously in postmenopausal women. Firstly, RANK/RANKL (+34901G>A/-290C>T) combination was associated with BMD-fn, BMD-th and BMD-ls (p=0.034, 0.016 and 0.050), and secondly, RANK/OPG combination (+35966insdelC/K3N) showed influence on BMD-fn and BMD-ls (p=0.043 and 0.039). Our results suggest that gene-gene interactions between RANK and OPG, and RANK and RANKL influence BMD in postmenopausal women.

Infusion of ibandronate once every 3 months effectively decreases bone resorption markers and increases bone mineral density in Chinese postmenopausal osteoporotic women: a 1-year study.

The efficacy and safety of intravenous ibandronate were evaluated in postmenopausal osteoporosis women in China. In this multicenter, positive drug-controlled study, 158 postmenopausal osteoporotic women were randomized to receive 2 mg ibandronate given intravenously once every 3 months or 70 mg alendronate given orally once per week. All women also received supplemental calcium (500 mg) and vitamin D (200 IU) daily. One hundred fifty-one patients completed the 1-year study. Ibandronate produced mean increases in bone mineral density (BMD) by 4.27% at the lumbar spine, 3.48% at the femoral neck, and 2.03% at the trochanter. Mean increases in BMD by 4.24% at the lumbar spine, 2.72% at the femoral neck, and 2.99% at the trochanter were observed in the alendronate group. No significant difference was found between the two groups in BMD in all sites measured. Significant decreases in serum c-telopeptide of type I collagen (CTX) and alkaline phosphatase (ALP) were found in the two groups after 1 and 3 months of treatment, respectively; these serum CTX and ALP levels were then maintained at the decreased levels throughout the study period (12 months). No changes of stature were found in the patients of the two groups. Adverse events were similar in the two groups, except more mild muscle pain was observed in the first month after infusion of ibandronate than with oral alendronate (P < 0.001). The results observed in Chinese patients may support the observation that intravenous ibandronate significantly reduced bone resorption and increased BMD with good tolerance in Chinese postmenopausal osteoporotic women. Use of intravenous ibandronate possibly could potentially improve compliance as compared with other oral bisphosphonates because it may avoid the peptic side effects of oral bisphosphonate.

The efficacy and tolerability of once-weekly alendronate 70 mg on bone mineral density and bone turnover markers in postmenopausal Chinese women with osteoporosis.

Osteoporosis has become an important health problem in postmenopausal Chinese women. Bisphosphonates currently are the preferred therapy for treating osteoporosis. However, the use of daily regimen of alendronate in women at risk for osteoporosis has been relatively low in China because of its dosing inconvenience. To determine the efficacy and tolerability of once-weekly alendronate 70 mg in Chinese, a multicenter, randomized, double blind, placebo controlled study was performed in China. Five hundred and sixty postmenopausal women (< or =85 years old) with osteoporosis were randomly assigned to receive either alendronate 70 mg or placebo once-weekly for 12 months. All women received calcium 500 mg daily and vitamin D 200 IU daily. A significant increase in lumbar spine BMD was already evident at 6 months of alendronate treatment (P < 0.001). The alendronate group showed significant increase (P < 0.001) in BMD at 12 months at both the spine and hip when compared with the placebo group (lumbar spine 4.87% vs. 0.4%, femoral neck 2.47% vs. 0.31%, trochanter 3.24% vs. 0.78%, total hip 2.56% vs. 0.28%, respectively). The percentage of women with > or =0% and > or =3% BMD increase in lumbar spine was significantly greater in women with alendronate than placebo (P < 0.001). Significant reduction in urine N-telopeptide (NTx) and serum bone-specific alkaline phosphatase were evident at 6 and 12 months, respectively, with alendronate treatment. No significant differences in the incidence of adverse experiences and upper gastrointestinal adverse experiences were seen. We conclude that once-weekly alendronate 70 mg is an effective and well-tolerated agent for the treatment of postmenopausal osteoporosis in Chinese women.

Sickle cell bone disease: response to vitamin D and calcium.

Bone disease with osteoporosis and osteomalacia are common in sickle cell disease (SCD). Some patients have vitamin D deficiency and low bone mineral density (BMD). The role of vitamin D and calcium supplementation to restore bone health in SCD has not been well studied. In 14 adults with SCD, we measured 25(OH)D (25-hydroxyvitamin D) and BMD at the femoral neck, lumbar spine, and distal third of the ulna plus radius, along with markers of bone resorption (CTx; C-terminal component of pro-collagen type I) and bone formation (osteocalcin) before and after 12 months of vitamin D(2) and calcium carbonate treatment. Pretreatment, all patients were vitamin D deficient with a mean 25(OH)D level of 11.6 [corrected] +/- 4 [corrected] ng/ml, had low BMD at the lumbar spine (L-spine), 0.87 +/- 0.11 g/cm(2) (mean Z-score of -2.6 3 +/- 0.71 SD and T score of -2.31 +/- 0.75 SD), femoral neck, 0.8 +/- 0.18 g/cm(2) (mean Z-score -1.36 +/- 0.84, T-score -1.14 +/- 0.75), and the distal radius and ulna, 0.6 +/- 0.17 g/cm(2) (mean Z-score -1.18 +/- 0.79, T-score -1.01 +/- 0.74) and had elevated CTx (0.87 +/- 0.5 ng/ml) and osteocalcin levels (12.3 +/- 3.7 ng/mul). After treatment, all patients corrected their 25(OH)D level (34.6 [corrected] +/- 11 [corrected] ng/ml) (P < 0.001) with a 3.6% +/- 3.9% increase in BMD at the L-spine (P = 0.009), 4.6% +/- 8.5% increase at the femoral neck (P = 0.05) and 6.5% +/- 12.6% increase at the distal radius plus ulna (P = 0.09). CTx, osteocalcin, and PTH(i) levels were unchanged. Treatment of adult SCD with vitamin D and calcium can restore 25(OH)D levels to normal and improve BMD, but, markers of bone resorption remained unchanged. Screening for vitamin D deficiency and BMD in SCD patients seems warranted.

Increased augmentation index and central aortic blood pressure in osteoporotic postmenopausal women.

UNLABELLED: Osteoporosis has been associated with cardiovascular disease. We found increased augmentation index, a measure of wave reflections and arterial stiffness, and central pressures in osteoporotic postmenopausal women. They also showed a higher estimated aortic pulse wave velocity, indicating a stiffer aorta. These changes may increase cardiovascular risk in postmenopausal osteoporosis. INTRODUCTION: Evidence suggests a link between osteoporosis and cardiovascular disease. We investigated whether augmentation index (AIx), a measure of pulse wave reflections and arterial stiffness, is increased and related to the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL) system in postmenopausal osteoporosis. METHODS: AIx and central aortic haemodynamics were assessed using pulse wave analysis in 182 cardiovascular disease-free osteoporotic postmenopausal women and in 160 controls. Statistical analysis was performed by unpaired t test, Mann-Whitney test, Spearman's correlation coefficient, and multivariate linear regression analysis. RESULTS: AIx (37.2 +/- 7.0 vs. 29.6 +/- 9.2 %, P < 0.0001) and central aortic systolic (117.5 +/- 12.1 vs. 111.4 +/- 12.2 mmHg, P < 0.0001) and pulse (40.5 +/- 10.3 vs. 36.4 +/- 8.1 mmHg, P = 0.0007) pressures were significantly higher in osteoporotic patients than in controls. The estimated aortic pulse wave velocity (PWV) was also significantly higher in the osteoporotic group. In multivariate analysis for osteoporotic patients, femoral neck and lumbar spine bone mineral density T scores were independent negative predictors of AIx (P < 0.0001). AIx was not correlated with serum levels of OPG and RANKL. CONCLUSIONS: Osteoporotic postmenopausal women show increased AIx and central aortic pressures, and a higher estimated aortic PWV, indicating a stiffer aorta. Such alterations may increase cardiovascular risk in postmenopausal osteoporosis.

A new selective estrogen receptor modulator, CHF 4227.01, preserves bone mass and microarchitecture in ovariectomized rats.

UNLABELLED: A new SERM, CHF 4227.01, given to 6-month-old female rats immediately after ovariectomy, preserved bone mass and bone microarchitecture without affecting uterus weight. It also decreased serum cholesterol and fat mass in estrogen-deficient rats. INTRODUCTION: We tested the effect of a new benzopyran derivative, CHF 4227.01, with selective estrogen receptor modulator (SERM) activity on bone mass and biomechanics in ovariectomized (OVX) female rats in comparison with 17alpha-ethinylestradiol (EST), raloxifene (RLX), and lasofoxifene (LFX). MATERIALS AND METHODS: Four doses of CHF 4227.01 (0.001, 0.01, 0.1, and 1 mg/kg body weight [bw]/day) were administered in OVX animals daily by gavage 5 days/week for 4 months. EST was administered at a dose of 0.1 mg/kg bw/day, whereas RLX and LSX were administered at doses of 1 and 0.1 mg/kg bw/day, respectively, by gavage. In one group (Sham), rats were operated but the ovaries not removed; another OVX group was treated only with placebo. RESULTS AND CONCLUSIONS: Treatment with CHF 4227.01 (1.0 and 0.1 mg/kg bw), EST (0.1 mg/kg bw), LFX (0.1 mg/kg bw), or RLX (1.0 mg/kg bw) prevented bone loss on the lumbar spine and the proximal femur assessed in vivo by DXA. Volumetric BMD obtained by pQCT ex vivo confirmed protection from bone loss in the spine and proximal femur among rats treated with CHF 4227.01. This effect was associated with strong inhibition of bone resorption both histologically and biochemically. Furthermore, CHF 4227.01 preserved trabecular microarchitecture, analyzed by muCT, and maintained biomechanical indices of bone strength in the spine and proximal femur, effects also observed for RLX, whereas LSX was less protective of microarchitecture. CHF 4227.01 treatment did not affect uterine weight, prevented the increase in body weight and fat mass seen in OVX animals, and decreased serum cholesterol to below the average of intact animals. In conclusion, CHF 4227.01 exhibits a promising therapeutic and safety profile as a new SERM on both skeletal and extraskeletal outcomes.

Interventions for preventing bone disease in kidney transplant recipients: a systematic review of randomized controlled trials.

BACKGROUND: Before renal transplantation complex abnormalities of bone metabolism exist and lead to increased risk for fracture after transplantation. This study was conducted to assess the evidence available to guide targeted treatment to reduce bone disease in transplant recipients. METHODS: The Cochrane CENTRAL Registry, MEDLINE, and EMBASE were searched for randomized trials of interventions for bone disease after renal transplantation. Data were extracted on fracture, bone mineral density (BMD) by means of dual-energy X-ray absorptiometry, acute graft rejection, and adverse events. Analysis was performed with a random-effects model, and all results are expressed as relative risk with 95% confidence intervals (CIs). RESULTS: Twenty-three eligible trials (1,209 patients) were identified. No trial found a reduction in risk for fracture. Bisphosphonates (7 trials; 268 patients; weighted mean difference [WMD], 7.66; 95% CI, 4.82 to 10.50), vitamin D analogues (2 trials; 51 patients; WMD, 6.13; 95% CI, 4.97 to 7.29), and calcitonin (1 trial; 31 patients; WMD, 5.00; 95% CI, 0.88 to 9.12) favorably affected the percentage of change in BMD at the lumbar spine compared with no treatment. Bisphosphonates (4 trials; 149 patients; WMD, 7.18; 95% CI, 6.22 to 8.13) and vitamin D analogues (2 trials; 51 patients; WMD, 3.73; 95% CI, 2.71 to 4.75), but not calcitonin (1 trial; 31 patients; WMD, -0.30; 95% CI, -5.00 to 4.40), had a favorable effect on BMD measured at the femoral neck compared with no treatment. The incidence of reported toxicity was low. CONCLUSION: The trials were inadequately powered to show a reduction in risk for fracture. Bisphosphonates and vitamin D have a beneficial effect on BMD at the lumbar spine and femoral neck. With increasing survival after renal transplantation, this study stresses the importance of randomized controlled trial evidence of interventions of bone disease after renal transplantation.

High resolution Ca/P maps of bone architecture in 3D synchrotron radiation microtomographic images.

The Ca/P ratio was measured in cortical bone samples from the femoral neck and tibia of different animal species, using synchrotron radiation microtomography. Use of a monoenergetic X-ray beam, as provided by the synchrotron facility, generates accurate 3D maps of the linear attenuation coefficient within the sample and hence gives the ability to map different chemical components. Also, by comparing normal and abnormal bones, i.e. osteoporotic (induced by inflammation), changes in the Ca/P ratio brought about by bone diseases can be detected. MicroCT data sets were collected at 20 and 28 keV for each bone sample and two calibration phantoms. From the 3D data sets, multiple 2D slices were reconstructed with a slice thickness of approximately 30 microm. Regions of interest were defined around suitable sites and were converted to Ca/P ratios using the data collected from the test phantoms. A significant difference (p<0.001) between osteoporotics and age-matched normals at both energies was detected. Differences between different bone sites from the same animal are not significant (p>0.5) while those between the same bone sites from different animals are highly significant (p<0.001). Differences between estimates made at 20 and 28 keV are not significant (p>0.5). An important aspect is the ability to map the spatial distribution of the Ca/P ratio.

Oral daily ibandronate prevents bone loss in early postmenopausal women without osteoporosis.

UNLABELLED: Oral daily ibandronate was investigated for the prevention of bone loss in postmenopausal women without osteoporosis (n = 653). BMD at the lumbar spine and hip were significantly increased (3.1% and 1.8%, respectively; p < or = 0.0001 versus placebo) with 2.5 mg ibandronate after 24 months. Oral ibandronate is a promising option for the prevention of postmenopausal bone loss. INTRODUCTION: Further strategies to manage patients most at risk from developing postmenopausal osteoporosis are required. The objectives of this multicenter, double-blind, randomized, placebo-controlled study were to examine the efficacy, tolerability, and optimal dose of oral daily ibandronate in the prevention of bone loss in postmenopausal women. MATERIALS AND METHODS: In total, 653 women (mean bone mineral density [BMD] T-score > -2.5 at the lumbar spine), who had been postmenopausal for at least 1 year, were allocated to one of four strata based on time since menopause and baseline lumbar spine BMD. Women were randomized to receive calcium (500 mg daily) plus either placebo (n = 162) or ibandronate 0.5 mg (n = 162), 1 mg (n = 166), or 2.5 mg (n = 163) as once-daily oral treatment for 2 years. The primary endpoint was the mean percent change in lumbar spine BMD with ibandronate versus placebo. RESULTS AND CONCLUSIONS: After 2 years, oral daily ibandronate produced a dose-related and sustained maintenance or increase in BMD at the lumbar spine and hip (total hip, femoral neck, trochanter), together with a dose-related reduction in the rate of bone turnover. The greatest nominal increases in spinal and hip BMD were observed with the 2.5-mg dose, which produced statistically significant BMD gains compared with placebo at 6 months and all subsequent time-points at the spine and hip (3.1% and 1.8% increase in lumbar spine and total hip BMD, respectively, versus placebo; p < or = 0.0001 after 24 months). Oral daily ibandronate was well tolerated with an incidence of upper gastrointestinal adverse events similar to placebo. No safety concerns were identified. In summary, oral daily ibandronate 2.5 mg decreases bone turnover, preserves or increases BMD in the spine and proximal femur, and is well tolerated. Oral ibandronate provides a promising option for the prevention of bone loss in postmenopausal women.