Prevention of osteoporosis-related fractures among postmenopausal women and older men.
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ABSTRACT:
SUBMITTER: Rahmani P
PROVIDER: S-EPMC2780487 | biostudies-literature | 2009 Nov
REPOSITORIES: biostudies-literature
Publications
Prevention of osteoporosis-related fractures among postmenopausal women and older men.
Rahmani Poupak P Morin Suzanne S
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20091019 11
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Project description:The glycoprotein sclerostin inhibits activation of the canonical Wnt pathway and thereby suppresses bone formation by inhibiting the osteoblasts. Additionally, sclerostin increases bone resorption by stimulating the production of receptor activator of nuclear factor kappa-?-ligand (RANKL). Romosozumab (ROMO) is a monoclonal antibody against sclerostin. Phase III clinical trials in postmenopausal women with osteoporosis have shown that ROMO increases bone mineral density at the lumbar spine and hip and reduces the risk of vertebral and clinical fractures in comparison with placebo. In women with severe osteoporosis, ROMO reduces the risk of vertebral, nonvertebral and clinical fractures in comparison with alendronate. ROMO is the first treatment for osteoporosis with dual action, and may become a valuable tool for improving the treatment of osteoporosis. At present, the approval of ROMO by the authorities is awaiting further investigations of a potential increased risk of cardiovascular events associated with ROMO treatment.
| S-EPMC6009094 | biostudies-literature
Project description:BackgroundAlthough a number of studies have examined the association between alcohol intake and hip fractures, few have considered specific alcoholic beverages separately.ObjectivesWe prospectively assessed total alcohol and specific alcoholic beverage consumption and risk of hip fractures in US men and women.MethodsHealth, lifestyle information, and hip fractures were self-reported on biennial questionnaires between 1980 and 2014 in 75,180 postmenopausal women from the Nurses' Health Study, and between 1986 and 2014 in 38,398 men aged ≥50 y from the Health Professionals Follow-Up Study. Diet was assessed approximately every 4 y with a semiquantitative FFQ. RRs were computed for hip fracture using Cox proportional hazards models, adjusting for potential confounders.ResultsWe ascertained 2360 incident low trauma hip fractures in women and 709 in men. Among women, RRs for low trauma hip fractures compared with nondrinkers were 0.89 (95% CI: 0.80, 0.99) for an average daily consumption of <5.0 g, 0.81 (95% CI: 0.70, 0.94) for 5.0 to <10.0 g, 0.83 (95% CI: 0.71, 0.96) for 10.0 to <20.0 g, and 0.93 (95% CI: 0.78, 1.10) for ≥20.0 g. Among men, risk declined linearly with higher alcohol consumption (P-trend = 0.002). Multivariable RR compared with nondrinkers was 0.77 (95% CI: 0.59, 1.01), 0.69 (0.49, 0.96), and 0.67 (0.48, 0.95) for an average intake of 10 g/d to <20 g/d, 20 g/d to <30 g/d, and 30.0 g/d or more, respectively. In women, the alcoholic beverage most significantly associated with hip fracture risk was red wine (RR per serving = 0.59; 95% CI: 0.45, 0.79). In men, there was no clear association with specific alcoholic beverages.ConclusionIn these 2 US cohorts, low to moderate alcohol consumption, when compared with no consumption, was associated with a lower risk of hip fractures, particularly with red wine consumption among women.
| S-EPMC6736105 | biostudies-literature
Project description:Serum miRNAs could be powerful classifiers for the detection of patients with postmenopausal osteoporosis.
2022-05-01 | GSE201543 | GEO
Project description:ImportanceThe clinical decision to initiate bisphosphonate therapy for the treatment of osteoporosis requires balancing shorter-term harms and burdens (eg, gastroesophageal irritation or severe musculoskeletal pain) with longer-term benefits in reducing potential fractures.ObjectiveTo assess the time to benefit (TTB) of bisphosphonate therapy for the prevention of nonvertebral and other fractures among postmenopausal women with osteoporosis.Data sourcesRandomized clinical trials (RCTs) were identified from systematic reviews commissioned by the US Preventive Services Task Force (1 review), the Agency for Healthcare Research and Quality (1 review), the Cochrane Library (2 reviews), and the Endocrine Society (1 review).Study selectionStudies selected were RCTs involving postmenopausal women with a diagnosis of osteoporosis based on existing vertebral fractures or bone mineral density T scores of -2.5 or lower. The selection process was focused on studies of alendronate, risedronate, and zoledronic acid because they are guideline-recommended first-line agents for reducing nonvertebral fractures. Studies were excluded if they did not focus on women with a primary diagnosis of osteoporosis, had no placebo arm, or had a lack of data on time to fracture.Data extraction and synthesisRandom-effects Weibull survival curves were fitted and Markov chain Monte Carlo methods were used to estimate the absolute risk reduction (ARR) and TTB for each study. These estimates were pooled using a random-effects meta-analysis model.Main outcomes and measuresThe primary outcome was the time to 3 different ARR thresholds (0.002, 0.005, and 0.010) for the first nonvertebral fracture. Secondary outcomes included the time to 4 ARR thresholds (0.001, 0.002, 0.005, and 0.010) for hip fracture, any clinical fracture, and clinical vertebral fracture.ResultsOf 67 full-text articles identified, 10 RCTs comprising 23 384 postmenopausal women with osteoporosis were included either as the original RCT or part of subsequently published pooled analyses. Among the studies, the number of participants ranged from 994 to 7765, with mean (SD) age ranging from 63 (7) years to 74 (3) years and follow-up duration ranging from 12 to 48 months. The pooled meta-analysis found that 12.4 months (95% CI, 6.3-18.4 months) were needed to avoid 1 nonvertebral fracture per 100 postmenopausal women receiving bisphosphonate therapy at an ARR of 0.010. To prevent 1 hip fracture, 200 postmenopausal women with osteoporosis would need to receive bisphosphonate therapy for 20.3 months (95% CI, 11.0-29.7 months) at an ARR of 0.005. In addition, 200 postmenopausal women with osteoporosis would need to receive bisphosphonate therapy for 12.1 months (95% CI, 6.4-17.8 months) to avoid 1 clinical vertebral fracture at an ARR of 0.005.Conclusions and relevanceThis meta-analysis found that the TTB of bisphosphonate therapy was 12.4 months to prevent 1 nonvertebral fracture per 100 postmenopausal women with osteoporosis. These results suggest that bisphosphonate therapy is most likely to benefit postmenopausal women with osteoporosis who have a life expectancy greater than 12.4 months.
| S-EPMC8609461 | biostudies-literature
Project description:As life expectancy increases, the prevalence of osteoporosis is increasing. In addition to vitamin D which is well established to have an association with osteoporosis, B vitamins, such as thiamine, folate (vitamin B9), and cobalamin (vitamin B12), could affect bone metabolism, bone quality, and fracture risk in humans by influencing homocysteine/folate metabolism. Despite the crucial role of B vitamins in bone metabolism, there are few studies regarding associations between B vitamin-related genes and osteoporosis. In this study, we investigated the genetic association of four single nucleotide polymorphisms (SNPs) within the 3'-untranslated regions of vitamin B-related genes, including TCN2 (encodes transcobalamin II), CD320 (encodes transcobalamin II receptor), SLC19A1 (encodes reduced folate carrier protein 1), and SLC19A2 (encodes thiamine carrier 1), with osteoporosis and osteoporotic vertebral compression fracture (OVCF). We recruited 301 postmenopausal women and performed genotyping of CD320 rs9426C>T,TCN2 rs10418C>T, SLC19A1 rs1051296G>T, and SLC19A2 rs16862199C>T using a polymerization chain reaction-restriction fragment length polymorphism assay. There was a significantly higher incidence of both osteoporosis (AOR 5.019; 95% CI, 1.533-16.430, p < 0.05) and OVCF (AOR, 5.760; 95% CI, 1.480-22.417, p < 0.05) in individuals with genotype CD320 CT+TT and high homocysteine concentrations. Allele combination analysis revealed that two combinations, namely CD320 C-TCN2 T-SLC19A1 T-SLC19A2 C (OR, 3.244; 95% CI, 1.478-7.120, p < 0.05) and CD320 T-TCN2 C-SLC19A1 G-SLC19A2 C (OR, 2.287; 95% CI, 1.094-4.782, p < 0.05), were significantly more frequent among the osteoporosis group. Our findings suggest that SNPs within the CD320 gene in 3´-UTR may contribute to osteoporosis and OVCF occurrences in some individuals. Furthermore, specific allele combinations of CD320, TCN2, SLC19A1, and SLC19A2 may contribute to increased susceptibility to osteoporosis and OVCF.
| S-EPMC7349196 | biostudies-literature
Project description: Not available
| S-EPMC9062986 | biostudies-literature
Project description:ContextIn postmenopausal women, bone mineral density (BMD) declines after teriparatide therapy is stopped. The pattern of BMD loss after teriparatide therapy is stopped in men is less clear.ObjectiveThe aim of the study was to determine whether the pattern of teriparatide-induced bone accrual and post-teriparatide bone loss differs between postmenopausal women and eugonadal men.DesignWe conducted a prospective cohort substudy.PatientsThe study included 14 postmenopausal women and 17 eugonadal men, ages 46-85 yr, with lumbar spine or femoral neck BMD T-scores below -2.InterventionTeriparatide (37 microg sc daily) was administered for 24 months, followed by 12 months off therapy.Main outcome measuresWe measured BMD at various anatomic sites by dual-energy x-ray absorptiometry, trabecular spine BMD by quantitative computed tomography, and bone turnover markers during the treatment and observation periods. The response to teriparatide administration and discontinuation was compared between females and males.ResultsBMD of the spine, femoral neck, total hip, and trabecular spine increased similarly during the treatment period in men and women, whereas BMD at the radius was stable in men but decreased by 8.1 +/- 3.3% in women (P < 0.0001). After teriparatide was stopped, BMD at the posterior-anterior spine decreased by 7.1 +/- 3.8% in women and by 4.1 +/- 3.5% in men (P = 0.036). BMD at the total hip and femoral neck decreased by 3.8 +/- 3.9 and 3.1 +/- 4.3%, respectively, in women but remained stable in men (P < 0.05 for both sites). BMD at the distal radius remained stable in men but increased in women by 1.6 +/- 3.1% (P = 0.069).ConclusionsTeriparatide appears to increase BMD similarly in postmenopausal women and eugonadal men with osteoporosis. After teriparatide is stopped, the decline in BMD is greater in women than in men. If confirmed in larger cohorts, these findings would suggest that the indication for immediate antiresorptive therapy after teriparatide may not be as urgent in men as in women.
| S-EPMC2730878 | biostudies-literature
Project description:ObjectiveTo compare the efficacy of bazedoxifene and oral bisphosphonates for the prevention of nonvertebral fractures (NVFs) in women with higher risk of postmenopausal osteoporosis (i.e., the Fracture Risk Assessment Tool [FRAX] score ≥ 20%), based on currently available evidence from randomized controlled trials.MethodsRandomized controlled trials evaluating the NVF relative risk reduction (RRR) with oral bisphosphonates or bazedoxifene were identified by a systematic literature review and combined by means of a network meta-analysis. A subgroup of patients with a FRAX score of 20% or more in the bazedoxifene phase III osteoporosis study was selected as the population of interest on the basis of the bazedoxifene label. In one analysis (analysis 1), the placebo response of the subgroup with a FRAX score of 20% or more was the benchmark to select comparable bisphosphonate trials. Additional analyses incorporated the aggregate data from the bisphosphonate trials with all the FRAX subgroups (analysis 2) or with the individual patient data from the bazedoxifene trial (analysis 3).ResultsNine identified bisphosphonate trials (alendronate, ibandronate, risedronate; N = 23,440 patients) with a similar placebo response as observed for the subgroup of high risk patients in the bazedoxifene trial were included in analysis 1. The results of the network meta-analysis of this study set suggest that bazedoxifene is expected to have an RRR of 0.43 (95% credible interval [CrI] -0.19 to 0.72) versus alendronate, 0.58 (95% CrI 0.05-0.81) versus ibandronate, and 0.39 (95% CrI -0.29 to 0.70) versus risedronate. Analyses in which treatment effects with bisphosphonates were projected to a population with a FRAX score of 20% or more with meta-regression approaches (analysis 2 and analysis 3) provide similar findings.ConclusionBased on an indirect comparison of randomized trials, bazedoxifene is expected to have at least a comparable RRR of NVF as alendronate, ibandronate, and risedronate in women with higher risk of postmenopausal osteoporosis.
| S-EPMC5583519 | biostudies-literature
Project description:Bazedoxifene acetate is a novel, chemically distinct selective estrogen receptor modulator (SERM) that has been specifically developed after a stringent preclinical screening in order to obtain favorable effects on the skeleton and lipid metabolism with the additional improvement of a neutral effect on hot flushes and without stimulating the uterus or the breast. In both preclinical and clinical studies this SERM was shown to maintain BMD, prevent fractures, and reduce total cholesterol. Moreover, bazedoxifene also showed an improved uterine profile and demonstrated estrogen antagonistic activity on the endometrium. Importantly, this latter capacity has led to the development of a novel class of menopausal therapy called tissue selective estrogen complex (TSEC), in which bazedoxifene is combined with conjugated estrogen. The rationale for selecting bazedoxifene as the SERM in this TSEC combination is that it may offset estrogen stimulation of endometrial and breast tissue, without the necessity of using a progestin in women with an intact uterus, without aggravating menopausal vasomotor symptoms, but with an additive effect on bone. Preliminary data from phase 3 clinical trials appear to confirm this hypothesis, showing a greater effect of bazedoxifene on BMD with respect to raloxifene, coupled with efficacy on menopausal vasomotor symptoms not achieved by SERM alone. These properties and the safety profile of this combination, if confirmed long-term in ongoing phase 3 trials, might significantly affect the way women and physicians approach menopause and its related disorders.
| S-EPMC2643104 | biostudies-literature
Project description:BackgroundTo investigate whether thoracolumbar kyphosis (TLK) of the spine is related to the reduction of bone mineral density (BMD) in postmenopausal osteoporosis women, and whether BMD of postmenopausal osteoporosis women can predict the occurrence of TLK.MethodsThis retrospective cohort study included 224 postmenopausal female patients hospitalized for osteoporosis from December 2017 to December 2020, and the control group included 270 postmenopausal female patients hospitalized for thoracolumbar degenerative diseases. The age, body mass index (BMI), visual analogue scale (VAS), and BMD of the lumbar spine [BMD(L)] and femoral neck [BMD(F)] of all patients during admission were recorded. We measured and recorded the Cobb angle of thoracolumbar and the height of the thoracolumbar intervertebral space in the spinal X-ray lateral radiograph. The Pearson and Spearman correlation coefficients were used to calculate the correlation between each parameter in the group. The Chi-square test was used for categorical variables, the independent-sample t-test was used for normally distributed continuous variables, and two-sample non-parametric tests were used for non-normally distributed variables. Binary logistic regression analysis and receiver operating characteristic (ROC) curves were applied to determine independent risk factors and cut-off values, respectively.ResultsThere were significant differences in the BMD(L), BMD(F), thoracolumbar junction Cobb angle, lumbar spine Cobb angle, T11/12-L1/2 height difference of the posterior and anterior edge of intervertebral space (HDPAIS), single vertebra Cobb angle (SVC), procollagen type 1 N-terminal propeptide (PINP) and 25-hydroxyvitamin D [25-(OH)D] between the study and control groups. Through binary logistic regression analysis, we found that BMD(L), PINP, bone alkaline phosphatase, and 25-(OH)D were independent risk factors for future TLK in postmenopausal women. According to the ROC curve, the prediction accuracy of BMD(L) was the highest. By calculating the critical value, we found that when the BMD(L) T-score <-1.65, postmenopausal women were more likely to develop TLK.ConclusionsIn postmenopausal osteoporosis patients, TLK will occur even if there is no compression fracture, and when the BMD(L) T-score <-1.65, postmenopausal women are more likely to develop TLK in the future.
| S-EPMC8848406 | biostudies-literature