Postmenopausal Osteoporotic Women Research Articles

Association of farnesyl diphosphate synthase polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis

Background Genetic factors are important in the pathogenesis of osteoporosis, but less is known about the genetic determinants of osteoporosis treatment. We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase (FDPS) in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China. Methods The study group comprised 639 postmenopausal women aged (62.2±7.0) years with osteoporosis or osteopenia who had been randomly assigned to low dose group (70 mg/2w) or standard dose group (70 mg/w) of alendronate in this 1-year study. We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul. Before and after treatment, serum levels of calcium, phosphate, alkaline phosphatase (ALP), cross linked C-telopeptide of type I collagen (β-CTX) were detected. Bone mineral density (BMD) at lumbar spine and proximal femur was measured. The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD, bone turnover biomarkers after the treatment. Results The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck, and patients with CC genotype had significantly higher baseline femoral neck BMD ((733.6±84.1) mg/cm2) than those with AC genotypes ((703.0±86.9) mg/cm2) and AA genotypes ((649.8±62.4) mg/cm2) (P <0.01). No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS. The percentage change of serum ALP level was significantly lower in patients with CC genotype (-22.9%) than that in those with AC genotype (-24.1%) and AA genotype (-29.8%) of FDPS after 12 months of alendronate treatment (P <0.05). Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype. Conclusions FDPS gene was probably a candidate gene to predict femoral neck BMD at baseline. FDPS gene alleles could predict change percentage of ALP after treatment of alendronate, but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.

Effects of intravenous zoledronate and ibandronate on carotid intima-media thickness, lipids and FGF-23 in postmenopausal osteoporotic women

ObjectiveOsteoporosis and atherosclerosis are interconnected entities and share also some pathophysiological mechanisms. Moreover, recent literature data have supported the hypothesis that bisphosphonates (BPs) may have some antiatherogenic actions. This study aimed to evaluate the effects of one year with zoledronate or ibandronate given intravenously on lipid profile and on carotid artery intima-media thickness (CA-IMT). MethodsSixty postmenopausal osteoporotic women (mean age: 66.6±7.8years) were randomly assigned to 1-year treatment with zoledronate 5mg i.v. annually or ibandronate 3mg i.v. every 3 months. In all patients at baseline and after 12months we measured CA-IMT, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), 25-hydroxyvitamin D (25OHD), bone alkaline phosphatase (B-ALP), type I collagen β carboxy telopeptide (βCTX), osteocalcin (OC), fibroblast growth factor 23 (FGF-23) and sclerostin. ResultsThe osteoporotic women treated with zoledronate showed a greater reduction in CA-IMT than those treated with ibandronate. HDL-C and HDL-C/LDL-C ratio showed a significant (p<0.01) increase in the 2 groups, whereas, LDL-C showed a reduction in the two groups which, however, reached statistical significance (p<0.05) only in the zoledronate group. FGF-23 serum levels showed a similar and significant decrease in both the women treated with zoledronate and in those treated with ibandronate. At the end of the study period sclerostin serum levels showed a higher increase in the patients treated with zoledronate than in those treated with ibandronate. ConclusionIn osteoporotic women both zoledronate and ibandronate given intravenously resulted in an increase in HDL-C/LDL-C ratio and a reduction of CA-IMT which was significant only for zoledronate. Further prospective studies are needed to clarify whether the change in FGF-23 and sclerostin levels is a marker or a potential mechanism of the action of BPs at a vascular level.

Nutritional status and its relationship with bone mass density in postmenopausal women admitted in osteodensitometry center, Isfahan-Iran.

Introduction:Osteoporosis is a multifactorial disease and one of the most important modifiable factors in the development and maintenance of bone mass are nutrition nutritional status and its relationship with Bone Mass Density (BMD) in postmenopausal women admitted in osteodensitometry Center, Isfahan, Iran.Materials and Methods:Seventy-two postmenopausal osteoporotic women were studied. BMD of the lumbar spine and total hip were measured using dual-energy X-ray absorptiometry. Demographic and dietary intakes were collected by interview and using a validated food frequency questionnaires. T-scores, Pearson correlation and one way analysis of variance tests were conducted to analyze the data.Results:Mean of age and duration of menopause was nearly 57.5 ± 7.2 and 10.6 ± 7.1 years, respectively. The mean t-scores for BMD of spine and hip were 0.877 ± 0.179 and 0.997 ± 0.21, respectively. The mean of calcium (Ca), phosphorous (P), fluoride (F), Vitamin D, K and Zn were less than DRI and Na more than it (all P value less than 0.0001). BMD of hip was significantly correlated with dietary Ca, animal protein, Zn (P < 0.05), but BMD of spine did not show any significant correlation with nutrients (P > 0.05).Conclusion:Most of the postmenopausal osteoporotic women in this study had a considerable deficiency in terms of micronutrients such as Ca, vitamin D and P, which can be deleterious for bone health.

Association of Serum Adiponectin with Serum Insulin and Body mass density (BMD) in postmenopausal Osteoporotic women with and without T2DM

Background: Osteoporosis is a systemic disease of the skeleton, characterized by low bone mass and alteration in the micro-architecture of the bone tissue that lead to an increase in brittleness with the ensuing predisposition to bone fracture. Global statistics show that women are more exposed to this disease than men and in particular at menopause. Like osteoporosis, type 2 diabetes mellitus (T2DM) is also greatly prevalent in aging populations, causing substantial morbidity and mortality. Diabetes mellitus affects skeletal system and bone metabolism through multiple pathways and it has been standard as a major risk factor for osteoporosis. Objective: To evaluate the level of serum ostocalcin, adiponectin, insulin levels of osteoporotic menopausal women with and without T2DM. Subjects& Methods: Blood samples were collected from 90 postmenopausal women; 60 women were patients with osteoporosis who have been divided into 2 groups; group A included 30 postmenopausal patients with osteoporosis without T2DM; group B included 30 postmenopausal patients with osteoporosis and T2DM while the third group included 30 apparently healthy postmenopausal women as a control group . Serum were separated for the estimation of ostocalcin ,adiponectin and insulin by an enzyme-linked immunosorbent assay (ELISA) Kits. Insulin resistance (IR) was calculated in term of homeostatic model assessment (HOMA) Results: Body mass density (BMD) were significantly lower in osteoporotic menopausal women without T2DM than healthy group; while it is significantly higher in osteoporotic menopausal women with T2DM than the healthy group(p < 0.001) . The levels of osteocalcin and adiponectin were significantly higher in patients of group A compared with control group (P <0.01) , and group B (P <0.001). While serum insulin, fasting serum glucose (FSG), insulin resistance (HOMA-IR) were significantly higher in patients of group B comparedwith the controls and group A. There was a significant negative correlation between adiponectin level and insulin in patients of group A(r = - 0.370,p = 0.044) And a positive significantly correlation between adiponectin level and BMD in patients of group B(r = 0.419,p = 0.021).

The Consumption Effect of Garlic Tablet on Proteins Oxidation Biomarker (SH-group) in Postmenopausal Osteoporotic Women

The Consumption Effect of Garlic Tablet on Proteins Oxidation Biomarker (SH-group) in Postmenopausal Osteoporotic Women

Eldecalcitol improves chair-rising time in postmenopausal osteoporotic women treated with bisphosphonates

An open-label randomized controlled trial was conducted to clarify the effect of eldecalcitol (ED) on body balance and muscle power in postmenopausal osteoporotic women treated with bisphosphonates. A total of 106 postmenopausal women with osteoporosis (mean age 70.8 years) were randomly divided into two groups (n=53 in each group): a bisphosphonate group (control group) and a bisphosphonate plus ED group (ED group). Biochemical markers, unipedal standing time (body balance), and five-repetition chair-rising time (muscle power) were evaluated. The duration of the study was 6 months. Ninety-six women who completed the trial were included in the subsequent analyses. At baseline, the age, body mass index, bone mass indices, bone turnover markers, unipedal standing time, and chair-rising time did not differ significantly between the two groups. During the 6-month treatment period, bone turnover markers decreased significantly from the baseline values similarly in the two groups. Although no significant improvement in the unipedal standing time was seen in the ED group, compared with the control group, the chair-rising time decreased significantly in the ED group compared with the control group. The present study showed that ED improved the chair-rising time in terms of muscle power in postmenopausal osteoporotic women treated with bisphosphonates.

IL-17A-mediated sRANK ligand elevation involved in postmenopausal osteoporosis

The role of proinflammatory IL-17 cytokine was studied in postmenopausal bone loss between 31 osteopenic and 41 osteoporotic women. The effect of serum IL-17A, soluble receptor activator of NF-κB (sRANK) ligand, and osteoprotegerin (OPG) levels on lumbar bone mineral densities was measured. The results demonstrated an increased IL-17A-mediated sRANK ligand elevation in postmenopausal osteoporotic bone loss. IL-17 proinflammatory cytokine is a new inducer of bone loss. Postmenopausal osteoporosis represents a cross talk between estrogen deprivation and increased immune reactivity. The role of IL-17 was studied in the bone loss of postmenopausal osteoporosis. Serum IL-17A, sRANK ligand, and OPG levels were investigated on bone mineral densities (BMDs) in the total lumbar (L1-L4) region in 18 pre- and 72 postmenopausal women. IL-17A, sRANK ligand, OPG levels, and BMDs were measured with enzyme-linked immunosorbent assay (ELISA) and dual-energy X-ray absorptiometry (DXA). Increased serum IL-17A, sRANK ligand, and OPG levels were demonstrated in postmenopausal osteoporotic women compared to osteopenic women (3.65 ± 0.61 vs 3.31 ± 0.43 ng/ml for IL-17A, P < 0.007; 2.88 ± 0.84 vs 2.49 ± 0.61 ng/ml for sRANK ligand, P < 0.027; and 1.43 ± 0.07 vs 1.39 ± 0.07 ng/ml for OPG, P < 0.038). In postmenopausal women, IL-17A levels correlated inversely with total lumbar BMDs (P < 0.008, r = -0.279) and positively with sRANK ligand levels (P < 0.0001, r = 0.387) or the ratio of sRANK ligand and OPG (P < 0.013, r = 0.261), but did not with OPG levels alone. Increased IL-17A levels are involved in postmenopausal osteoporosis, playing a role in the bone-resorpting processes.

Cardiovascular safety of strontium ranelate: real-life assessment in clinical practice

Cardiovascular safety of strontium ranelate: real-life assessment in clinical practice

Denosumab: A cost-effective alternative for older men with osteoporosis from a Swedish payer perspective

ObjectiveTo assess the cost-effectiveness of denosumab versus other treatments in men with osteoporosis who are ≥75years old from a payer perspective in Sweden. MethodsA lifetime cohort Markov model was developed with seven health states: well, hip fracture, vertebral fracture, other osteoporotic fracture, post-hip fracture, post-vertebral fracture, and dead. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Background fracture risks, mortality rates, persistence rates, utilities, medical and drug costs were derived using published sources. Estimates of fracture efficacy were drawn from available studies in post-menopausal osteoporotic (PMO) women as BMD improvements have been shown to be similar across male osteoporosis (MOP) and PMO populations, and a recent clinical trial suggested that the fracture risk reduction from bisphosphonate therapy in men is similar to that seen in women in comparable studies. Lifetime expected costs and quality-adjusted life-years (QALYs) were estimated for denosumab, generic alendronate, generic risedronate, ibandronate, zoledronate, strontium ranelate and teriparatide. On average, patients in the model were 78years old, with bone mineral density T-score at the femoral neck of −2.12. Prevalent vertebral fractures were present in 23% of patients. In the base-case, the model assumed that patients would experience treatment-related effects up to 2years after discontinuation. Costs and QALYs were discounted at 3% annually. Extensive sensitivity analyses were conducted. ResultsTotal lifetime costs for denosumab, alendronate, strontium ranelate, zoledronate, risedronate, ibandronate and teriparatide were €31,004, €33,731, €34,788, €34,796, €34,826, €35,983 and €37,461, respectively. Total QALYs were 5.23, 5.15, 5.15, 5.17, 5.13, 5.12 and 5.22, respectively. Compared to other treatments, denosumab had the lowest costs and highest QALYs. In the one-way sensitivity analyses, when compared to alendronate (next least expensive strategy), the ICER for denosumab was most sensitive to the relative risk of hip fracture on denosumab. The probability of denosumab being cost-effective compared to the other treatments at a threshold of €66,000/QALY was 96.1%. ConclusionDenosumab dominated all comparators, including generic bisphosphonates, in the treatment of osteoporosis in men who were ≥75years old in Sweden.

CER1gene variations associated with bone mineral density, bone markers, and early menopause in postmenopausal women

BackgroundOsteoporosis has a multifactorial pathogenesis characterized by a combination of low bone mass and increased fragility. In our study, we focused on the effects of polymorphisms in CER1 and DKK1 genes, recently reported as important susceptibility genes for osteoporosis, on bone mineral density (BMD) and bone markers in osteoporotic women. Our objective was to evaluate the effect of CER1 and DKK1 variations in 607 postmenopausal women. The entire DKK1 gene sequence and five selected CER1 SNPs were amplified and resequenced to assess whether there is a correlation between these genes and BMD, early menopause, and bone turnover markers in osteoporotic patients.ResultsOsteoporotic women seem to suffer menopause 2 years earlier than the control group. The entire DKK1 gene sequence analysis revealed six variations. There was no correlation between the six DKK1 variations and osteoporosis, in contrast to the five common CER1 variations that were significantly associated with BMD. Additionally, osteoporotic patients with rs3747532 and rs7022304 CER1 variations had significantly higher serum levels of parathyroid hormone and calcitonin and lower serum levels of osteocalcin and IGF-1.ConclusionsNo significant association between the studied DKK1 variations and osteoporosis was found, while CER1 variations seem to play a significant role in the determination of osteoporosis and a potential predictive role, combined with bone markers, in postmenopausal osteoporotic women.

Comparative cost-effectiveness of bazedoxifene and raloxifene in the treatment of postmenopausal osteoporosis in Europe, using the FRAX algorithm

Bazedoxifene and raloxifene were evaluated in the treatment of postmenopausal osteoporosis from health economic perspective in Europe. Based on a computer-based algorithm calculating efficacy of the treatments, bazedoxifene appears to be a cost-effective strategy compared to raloxifene, particularly in patients at high fracture risk. The purpose of this study was to compare cost-effectiveness of bazedoxifene and raloxifene in eight European countries: Belgium, France, Germany, Ireland, Italy, Spain, Sweden, and the UK. The Fracture Risk Assessment Tool, which is a computer-based algorithm to calculate fracture probability using clinical risk factors alone or with bone mineral density, was incorporated in a Markov Tunnel model to evaluate cost-effectiveness of bazedoxifene 20 or 40 mg vs. raloxifene 60 mg in postmenopausal osteoporotic women. The efficacy of bazedoxifene and raloxifene for vertebral and non-vertebral fractures was measured as a function of the 10-year probability of a major osteoporotic fracture. The model estimated the incremental cost-effectiveness ratio and net monetary benefit (NMB) from a healthcare perspective, given the willingness to pay <euro>30,000. In postmenopausal osteoporotic women, bazedoxifene was a cost saving strategy compared to raloxifene in the countries studied. The median NMB of bazedoxifene compared to raloxifene increased monotonically with the 10-year fracture probability. In general, the median NMB became greater than 0 in women with 10-year probabilities of a major osteoporotic fracture between 5 and 10% or above. The impact on results by varying the assumptions in the model was examined in sensitivity analysis. Bazedoxifene appears to be a cost-effective strategy compared to raloxifene for the treatment of postmenopausal osteoporotic women in Europe, particularly in patients at high fracture risk.

The Relationship between Serum Leptin Level and Bone Mineral Denisty in Postmenopausal Osteoporotic Women

Postmenopausal osteoporosis is a heterogeneous disorder characterized by a progressive loss of bone tissue that begins after menopause and leads to fracture within 15-20 years from the cessation of the ovarian function.Human leptin is a protein of 167 amino acids. It is manufactured primarily in the adipocytes of white adipose tissue, and the level of circulating leptin is proportional to the total amount of fat in the body.Leptin’s effects on bone are mediated via a central neuroendocrine signaling pathway, as well as directly on bone marrow stem cells to enhance their differentiation to osteoblasts and inhibit their differentiation to adipocytes. Aim of the Study: to detect the relation between serum leptin level, total lipid profile and bone mineral denisty in postmenopausal osteoporotic women. Subjects and Methods: The study was carried on 40 postmenopausalfemales. According to Dual Emergy X-ray absorptiometry (DEXA), the subjects were divided into group A, Tt-score <-2.5, group B, t-score <-1, leptin and lipid profile were measured for all subjects. Conclusion:The current study has provided evidence that bone mineral density is influced by serum leptin level in postmenopausal osteoporotic women and positive correlation between serum leptin level and bone mineral density was found. Recommendation: Serum leptin level measurement could be used as a simple and non invasive method for screening programs for osteoporosis in postmenopausal women but the accuracy of this test still needs furtherer studies. Abbreviation: Ob gene : Obese gene; BMD : Bone Mineral Density; NOF: National Osteoporosis Foundation; M-CSF : Monocyte colony stimulating factor; BMI: Body mass index; DEXA: Dual-energy X-ray absorptiometry

Comparison of alendronate and raloxifene for the management of primary hyperparathyroidism.

To evaluate and compare the efficacy of alendronate sodium (ALN) and raloxifene (RLX) for the management of primary hyperparathyroidism (PHPT) in postmenopausal female patients (pts) with osteoporosis. Twenty-four postmenopausal women with osteoporosis who were diagnosed with PHPT, but refused the option of surgery, were enrolled. Participants were sequentially randomized into two groups: an ALN-group of 12 pts (70 mg/week) and a RLX-group of 12 pts (60 mg/day). The control group consisted of 10 pts with PHPT who did not have any indications for surgery. The decrease in ionized calcium levels was significantly more pronounced in the ALN group compared to the RLX and control groups (p<0.001). In terms of difference from baseline in bone mineral density (BMD) of the lumbar area in percentages over a period of 12 months, pts in the ALN and RLX groups both showed statistically significant improvements compared to pts in the control group (control vs ALN, p<0.001; control vs RLX, p<0.001). BMD measurements of the femoral and radial areas were comparable in all three groups. ALN and RLX may improve bone density in the lumbar area of osteoporotic post-menopausal women with PHPT. The more significant decrease in serum calcium levels which was observed in the ALN group compared to both RLX and control groups, suggests that ALN could be used for the short-term control of calcium levels in patients awaiting surgery.

18F-fluoride Positron Emission Tomography Measurements of Regional Bone Formation in Hemodialysis Patients with Suspected Adynamic Bone Disease

18F-fluoride positron emission tomography (18F-PET) allows the assessment of regional bone formation and could have a role in the diagnosis of adynamic bone disease (ABD) in patients with chronic kidney disease (CKD). The purpose of this study was to examine bone formation at multiple sites of the skeleton in hemodialysis patients (CKD5D) and assess the correlation with bone biopsy. Seven CKD5D patients with suspected ABD and 12 osteoporotic postmenopausal women underwent an 18F-PET scan, and bone plasma clearance, K i, was measured at ten skeletal regions of interest (ROI). Fifteen subjects had a transiliac bone biopsy following double tetracycline labeling. Two CKD5D patients had ABD confirmed by biopsy. There was significant heterogeneity in K i between skeletal sites, ranging from 0.008 at the forearm to 0.028 mL/min/mL at the spine in the CKD5D group. There were no significant differences in K i between the two study groups or between the two subjects with ABD and the other CKD5D subjects at any skeletal ROI. Five biopsies from the CKD5D patients had single tetracycline labels only, including the two with ABD. Using an imputed value of 0.3 μm/day for mineral apposition rate (MAR) for biopsies with single labels, no significant correlations were observed between lumbar spine K i corrected for BMAD (K i/BMAD) and bone formation rate (BFR/BS), or MAR. When biopsies with single labels were excluded, a significant correlation was observed between K i/BMAD and MAR (r = 0.81, p = 0.008) but not BFR/BS. Further studies are required to establish the sensitivity of 18F-PET as a diagnostic tool for identifying CKD patients with ABD.

Potential diagnostic role of the MRI-derived internal magnetic field gradient in calcaneus cancellous bone for evaluating postmenopausal osteoporosis at 3 T

IntroductionBone mineral density (BMD) result has a low predictive value on patients' risk for future fractures. Thus, new approaches for examining patients at risk for developing osteoporosis would be desirable. Magnetic resonance (MR) investigations in cancellous bone have been shown to yield useful quantitative information on both trabecular-bone microstructure and bone marrow composition.This work was undertaken to address the hypothesis that the effective internal magnetic field gradient (IMFG), a new MR parameter, discriminates between healthy, osteopenic and osteoporotic postmenopausal women, classified on the basis of bone mineral density (BMD) criteria. The work builds on preliminary results indicating that IMFG, measured in trabecular-bone pores and quantified by spin-echo decay and water diffusion MR near the bone–bone marrow interface depends on both the bone marrow water rate of diffusion and the magnetic susceptibility difference (ΔX) between water and bone. Materials and methodsMR relaxometry, MR spectroscopy and diffusion-weighted MR imaging of the heel was performed in fifty-five women (mean age, 62.9±6.6years) at 3T. Moreover, in order to study the reproducibility of IMFG measurement, five young women (mean age 31.0±3.2years; age range, 28–36years) were scanned and rescanned. The study protocol was approved by the local Ethics Committee. Quantitative Computer Tomography (QCT) of the L1–L3 vertebral segments was performed to classify the postmenopausal women into three groups according to QCT BMD: healthy (n=8); osteopenic (n=25); and osteoporotic (n=22). In all subjects, BMD T-scores, marrow fat content (Mfc), T2*, apparent diffusion coefficient (ADC) and IMFG (estimated from the additional spin-echo decay due to diffusion of water in local magnetic field gradients), were assessed in the whole calcaneus as well as in three calcaneal subregions: subtalar, tuber calcaneus, and cavum calcaneus. Between-group comparisons to assess group differences and Pearson correlation analysis were performed. Short and long-term coefficients of variation (CVS and CVL, respectively) were evaluated in young subjects. ResultsReproducibility of the IMFG measurement was satisfactory. No significant difference was found in the IMFG measurement performed in both calcaneus and subtalar calcaneal region between the two separate sessions comprised of five young women. Mfc did not significantly differ between groups. The IMFG in the subtalar region was significantly different between all three groups (P<0.01), being greatest in healthy women, intermediate in those with osteopenia, and lowest in osteoporotic subjects. Conversely neither T2* nor ADC is able to discriminate healthy subjects from those with osteopenia and osteoporosis. Increased inter-trabecular space, as it typically occurs in patients with osteoporosis, modifies water diffusion, conferring higher ADC values, thereby lowering the IMFG. ConclusionThe IMFG measured in the calcaneal subtalar region shows a high ability in identifying healthy subjects. The new quantitative MR method based on measurement of the IMFG may provide a new means for assessing patients with osteoporosis.

Cost Effectiveness of Denosumab versus Oral Bisphosphonates for Postmenopausal Osteoporosis in the US

In the US, 26 % of women aged ≥65 years, and over 50 % of women aged ≥85 years are affected with postmenopausal osteoporosis (PMO). Each year, the total direct health care costs are estimated to be $US12-18 billion. The cost effectiveness of denosumab versus oral bisphosphonates in postmenopausal osteoporotic women from a US third-party payer perspective was evaluated. A lifetime cohort Markov model was developed with seven health states: 'well', hip fracture, vertebral fracture, 'other' osteoporotic fracture, post-hip fracture, post-vertebral fracture, and dead. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Relative fracture risk reductions, background fracture risks, mortality rates, treatment-specific persistence rate, utilities, and medical and drug costs were derived using published sources. Expected costs and quality-adjusted life years (QALYs) were estimated for generic alendronate, denosumab, branded risedronate, and branded ibandronate in the overall PMO population and high-risk subgroups: (a) ≥2 of the following risks: >70 years of age, bone mineral density (BMD) T score less than or equal to -3.0, and prevalent vertebral fracture; and (b) ≥75 years of age. Costs and QALYs were discounted at 3 % annually, and all costs were inflated to 2012 US dollars. Sensitivity analyses were conducted by varying parameters e.g., efficacies of interventions, costs, utilities, and the medication persistence ratio. In the overall PMO population, total lifetime costs for alendronate, denosumab, risedronate, and ibandronate were $US64,400, $US67,400, $US67,600 and $US69,200, respectively. Total QALYs were 8.2804, 8.3155, 8.2735 and 8.2691, respectively. The incremental cost-effectiveness ratio (ICER) for denosumab versus generic alendronate was $US85,100/QALY. Risedronate and ibandronate were dominated by denosumab. In the high-risk subgroup (a), total costs for alendronate, denosumab, risedronate and ibandronate were $US70,400, $US70,800, $US74,000 and $US76,900, respectively. Total QALYs were 7.2006, 7.2497, 7.1969 and 7.1841, respectively. Denosumab had an ICER of $US7,900/QALY versus generic alendronate and dominated all other strategies. Denosumab dominated all strategies in women aged ≥75 years. Base-case results between denosumab and generic alendronate were most sensitive to the relative risk of hip fracture for both drugs and the cost of denosumab. In each PMO population examined, denosumab represented good value for money compared with branded bisphosphonates. Furthermore, denosumab was either cost effective or dominant compared with generic alendronate in the high-risk subgroups.

Serum sclerostin levels associated with lumbar spine bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis

Background Sclerostin, expressed exclusively by osteocytes, is a negative regulator of bone formation. To gain insights into the action of sclerostin in postmenopausal osteoporosis, we evaluated serum sclerostin levels in postmenopausal women and investigated its possible associations with bone turnover markers in patients with postmenopausal osteoporosis. Methods We detected serum sclerostin, and measured lumbar spine bone mineral density in 650 Chinese postmenopausal women. We also assessed serum levels of β-isomerized C-terminal crosslinking of type I collagen, intact N-terminal propeptide of type I collagen, N-mid fragment of osteocalcin, 25-hydroxyvitamin D, and estradiol. Results Serum sclerostin levels were lower in postmenopausal osteoporotic women compared with non-osteoporotic postmenopausal women ((38.79±7.43) vs. (52.86±6.69) pmol/L, P &lt;0.001). Serum sclerostin was positively correlated with lumbar spine bone mineral density (r=0.391, P &lt;0.001) and weakly negatively correlated with β-isomerized C-terminal crosslinking of type I collagen, intact N-terminal propeptide of type I collagen, N-mid fragment of osteocalcin (r= −0.225, P &lt;0.001; r= −0.091, P=0.046; r= −0.108, P=0.018; respectively) in postmenopausal osteoporosis. There was no significant association of serum sclerostin with age, body mass index, 25-hydroxyvitamin D, and estradiol (r= −0.004, P=0.926; r=0.067, P=0.143; r=0.063, P=0.165; r= −0.045, P=0.324; respectively). Conclusion Sclerostin may be involved in the pathogenesis of postmenopausal osteoporosis and may play a role in bone turnover.

Cost-effectiveness of bazedoxifene versus raloxifene in the treatment of postmenopausal women in Spain.

BackgroundThe purpose of this study was to assess the cost-effectiveness of bazedoxifene and raloxifene for prevention of vertebral and nonvertebral fractures among postmenopausal Spanish women aged 55–82 years with established osteoporosis and a high fracture risk.MethodsA Markov model was developed to represent the transition of a cohort of postmenopausal osteoporotic women through different health states, ie, patients free of fractures, patients with vertebral or nonvertebral fractures, and patients recovered from a fracture. Efficacy data for bazedoxifene were obtained from the Osteoporosis Study. The perspective of the Spanish National Health Service was chosen with a time horizon of 27 years. Costs were reported in 2010 Euros. Deterministic results were presented as expected cost per quality-adjusted life-year (QALY), and probabilistic results were represented in cost-effectiveness planes.ResultsIn deterministic analysis, the expected cost per patient was higher in the raloxifene cohort (€13,881) than in the bazedoxifene cohort (€13,436). QALYs gained were slightly higher in the bazedoxifene cohort (14.56 versus 14.54). Results from probabilistic sensitivity analysis showed that bazedoxifene has a slightly higher probability of being cost-effective for all threshold values independent of the maximum that the National Health Service is willing to pay per additional QALY.ConclusionBazedoxifene was shown to be a cost-effective treatment option for the prevention of fractures in Spanish women with postmenopausal osteoporosis and a high fracture risk. When comparing bazedoxifene with raloxifene, it may be concluded that the former is the dominant strategy.

Pharmacokinetics of Oral Recombinant Human Parathyroid Hormone [rhPTH(1–31)NH2] in Postmenopausal Women with Osteoporosis

Teriparatide [rhPTH(1-34)OH] is a subcutaneously administered bone anabolic drug that increases bone mineral density (BMD) and reduces the risk of osteoporotic fracture. Because rhPTH(1-34)OH is administered by injection, oral delivery is a desirable alternative. However, the peroral delivery of peptides is challenging due to their susceptibility to protease digestion and low permeability through the intestinal layers. The objective of this study was to assess the pharmacokinetics of a PTH analog (rhPTH(1-31)NH2) in a novel oral tablet formulation and to compare them to subcutaneously administered teriparatide in postmenopausal osteoporotic women in a phase 2 proof-of-concept clinical study. This was a 24-week repeat-dose, randomized, double blind, parallel group phase 2 study with three once-daily treatment arms: oral rhPTH(1-31)NH2 tablets (5 mg), matching placebo tablets, and open-label teriparatide (20 μg daily subcutaneous injection). The primary endpoint of this study was to assess the change in lumbar spine BMD of orally administered rhPTH(1-31)NH2 tablets compared to baseline. This study was conducted at three sites in Denmark and at one site in Estonia. The patients included were women diagnosed with postmenopausal osteoporosis as detected by lumbar spine dual-energy X-ray absorptiometry, with exclusion of those with prior treatment with bone-active agents. The study treatment consisted of orally formulated recombinant human PTH(1-31)NH2, placebo, or subcutaneous teriparatide as an active comparator. The pharmacokinetic profile at first and last dose was evaluated and correlated with the primary endpoint, which was to characterize the percent change from baseline in BMD of the lumbar spine after 24 weeks of once daily treatment with rhPTH(1-31)NH2. The pharmacokinetic profile for the tablets showed a pulsatile peak with durations of at least 1 h but less than 5 h, which is consistent with the requirement for bone anabolic activity. The mean maximum (peak) plasma drug concentration (C max) values for patients receiving tablets at week 0 (n = 32) and week 24 (n = 28) were 295 and 207 pg/mL, respectively. The mean time to reach maximum (peak) plasma concentration following drug administration (t max) for both week 0 and week 24 was 3.25 h. The mean area under the concentration-time curve (AUC) for week 0 and week 24 was 178 and 141 pg·h/mL, respectively. No significant differences were observed between weeks 0 and 24 in any pharmacokinetic parameters tested, demonstrating good reproducibility, no time-dependent changes, and little or no accumulation of the study drug. The systemic exposure as measured by C max values was higher for the oral tablets formulation than for subcutaneous teriparatide. The observed data demonstrate that the enteric-coated tablet formulation technology was able to generate consistently robust and pulsatile levels of exposure of rhPTH(1-31)NH2. There was no apparent correlation between higher exposures and adverse events, even though the pharmacokinetic variability was somewhat higher with the tablets. These positive results recommend this orally delivered drug candidate for further clinical development.

Influence of local exposure to static magnetic field on pain perception and bone turnover of osteoporotic patients with vertebral deformity – a randomized controlled trial

Purpose: Static magnetic field (SMF) could improve pain sensation and bone turnover. In a single-center randomized double-blind placebo-controlled study we investigated the effects of SMF exposure on subjective pain and bone turnover.Materials and methods: Postmenopausal osteoporotic women (aged 50–70 years) with bone deformity and back pain were randomized to 10 weekly visits of 30-min SMF (n = 6) or treatment with non-magnetized pads (n = 5) on the back. Primary and secondary outcomes were changes in pain sensation on a visual analogue scale (VAS) during each visit and over 10 weeks, respectively. Tertiary outcomes were changes in osteocalcin and β-crosslaps. SMF was inhomogeneous with 192 millitesla peak-to-peak value by 19 tesla/meter gradient of the magnetic flux density at 3 mm.Results: Participants randomized to sham had higher VAS at baseline (mean difference: 2.8, 95% confidence interval (CI) 0.47–5.2 cm). Both SMF and sham similarly reduced short term pain (sham-SMF: 0.59, 95% CI − 0.31–1.49 cm, p = 0.195). VAS did not change in SMF, while it decreased in the sham group (between-group difference 0.27, 95% CI 0.04–0.50 cm/visit). Bone turnover markers remained stable.Conclusions: SMF as used in this investigation is not recommended for pain relief in postmenopausal women with vertebral deformity. The finding on long-term pain relief may relate to unbalanced randomization.