Epidemiology of osteoporotic fractures

Osteoporosis constitutes a major public health problem through its association with age-related fractures. These fractures typically occur at the hip, spine and distal forearm. It has been estimated that the lifetime risk of a hip fracture in white women is 17.5%, with a comparable risk in men of 6%. Hip fractures lead to an overall reduction in survival of about 15% (relative or observed/expected survival at 5 years of 0.83), and the majority of excess deaths occur within the first 6 months following the fracture. Such fractures are also associated with considerable morbidity. Although all vertebral deformities do not come to clinical attention, the lifetime risk of clinically diagnosed vertebral fractures is about 15% in white women. Vertebral fractures tend to be associated with back pain and kyphosis, and also with an impairment of survival, though this is likely to be due to clustering of comorbidity. About one-quarter of clinically diagnosed vertebral deformities result in hospitalization.     

骨水泥填充治疗桡骨远端骨质疏松骨折

目的:探讨骨水泥填充治疗桡骨远端骨质疏松骨折的方法。方法:对本科2000以来对8例桡骨远端骨质疏松骨行有限切开、关节面撬拨复位后注入骨水泥填充关节软骨下缺损治疗。结果:全部病例获得随访10-68月,平均22月。所有患者术后1周内肿胀消失,3～4周功能恢复接近正常。X线检查显示骨折愈合良好,无延迟愈合或不愈合。患者自我感觉5例表示满意,2例表示基本满意,1例表示不满意,满意率87.5%。结论:有限切开、关节面撬拨复位后注入骨水泥填充关节软骨下缺损是治疗桡骨远端骨质疏松骨折的有效方法。     

MTHFR C677T polymorphism and osteoporotic fractures.

The C677T (rs1801133) polymorphism of MTHFR (methylenetetrahydrofolate reductase) has been associated with the risk of cardiovascular events, and also with osteoporosis in some studies. However, the results are controversial. Our objective was to determine the relationship of the polymorphism with osteoporotic fractures by means of a case-control study. C677T was analyzed in 823 subjects (365 controls, 136 with vertebral fractures and 322 with hip fracture) by using a Taqman assay. The distribution of MTHFR genotypes was similar in patients and controls. In comparison with TC/CC genotypes, the age-adjusted OR for hip fractures of the TT genotype was 1.0 (95% confidence interval 0.6-1.7) in women and 0.7 (0.3-1.8) in men. The OR for vertebral fractures was 0.8 (0.4-1.7) in women and 1.7 (0.4-6.7) in men. A meta-analysis combining these data with previous reports confirmed the lack of association between MTHFR and fractures, with an OR of 1.1 (0.7-1.9, p=0.65) for vertebral fractures and 1.2 (0.7-2.0; p=0.45) for peripheral fractures, but there was significant heterogeneity among the results of individual studies, particularly about peripheral fractures. In conclusion, the C677T polymorphism of the MTHFR gene does not appear to be associated with the overall risk of osteoporotic fractures. However, given the heterogeneity of the results of published studies, further investigations are needed to evaluate its influence in specific population subgroups.     

Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures

Introduction

Hip OF carries the highest morbidity and mortality. Previous studies revealed that individual genes/loci in the Tumor Necrosis Factor (TNF) -Related Apoptosis-Inducing Ligand (TRAIL) pathway were associated with bone metabolism. This study aims to verify the potential association between hip OF and TRAIL pathway.

Methods

Using genome-wide genotype data from Affymetrix 500 K SNP arrays, we performed novel pathway-based association analyses for hip OF in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls).

Results

The TRAIL pathway achieved a significant p value (p = 0.01) for association with hip OF. Among the 38 genes in the TRAIL pathway, seven genes achieved nominally significant association with hip OF (p<0.05); the TNFSF10 (TRAIL) gene obtained the most significant p value (p = 1.70×10⁻⁴). SNPs (rs719126, rs6533015, rs9594738, rs1805034, rs11160706) from five genes (CFLAR, NFKB1, TNFSF11, TNFRSF11A, TRAF3) of the pathway had minor alleles that appear to be protective to hip OF. SNPs (rs6445063 and rs4259415) from two genes (TNFSF10 and TNFRSF10B) of the pathway had minor alleles (A) that are associated with an increased risk of hip OF, with the ORs (odds ratios) of 16.51 (95%CI:3.83–71.24) and 1.37 (95%CI:1.08–1.74), respectively.

Conclusions

Our study supports the potential role of the TRAIL pathway in the pathogenesis of hip OF in Chinese Han population. Further functional study of this pathway will be pursued to determine the mechanism by which it confers risk to hip OF.     

Prediction of osteoporotic fractures by postural instability and bone density.

OBJECTIVE--To investigate the utility of risk factors such as bone mineral density, lifestyle, and postural stability in the prediction of osteoporotic fractures. DESIGN--Longitudinal, epidemiological, and population based survey. SETTING--City of Dubbo, New South Wales. SUBJECTS--All residents of Dubbo aged > or = 60 on 1 January 1989. MAIN OUTCOME MEASURE--Incidence of fracture for individual subjects. RESULTS--The overall incidence of atraumatic fractures in men and women was 1.9% and 3.1% per annum respectively. The predominant sites of fracture were hip (18.9%), distal radius (18.5%), ribs and humerus (11.9% in each case), and ankle and foot (9.1% and 6.6% respectively). Major predictors of fractures in men and women were femoral neck bone mineral density, body sway, and quadriceps strength. Age, years since menopause, height, weight, and lifestyle factors were also correlated with bone mineral density and body sway and hence were indirect risk factors for fracture. Discriminant function analysis correctly identified 96% and 93% (sensitivities 88% and 81%) of men and women, respectively, who subsequently developed atraumatic fractures. Predictions based on this model indicated that a woman with a bone mineral density in the lowest quartile in the hip together with high body sway had a 8.4% probability of fracture per annum. This represented an almost 14-fold increase in risk of fracture compared with a woman in the highest bone mineral density quartile with low postural sway. An individual with all three predictors in the "highest risk" quartile had a 13.1% risk of fracture per annum. CONCLUSIONS--Bone mineral density, body sway, and muscle strength are independent and powerful synergistic predictors of fracture incidence.     

椎体后凸成形术治疗老年骨质疏松脊柱压缩骨折的临床分析

目的分析老年骨质疏松脊柱压缩骨折行椎体后凸成形术的治疗方法及临床效果,为临床提供依据。方法回顾性分析我院2014年10月~2015年10月收治的老年骨质疏松脊柱压缩骨折患者40例的临床资料,全部患者均为椎体后壁完整疼痛性骨质疏松脊柱压缩骨折,均接受椎体后凸成形术治疗,经双侧椎弓根、椎弓根旁置入可扩张球囊,将骨折塌陷椎体进行复位,采取骨水泥填充球囊扩张产生的椎体内空腔,术后观察患者症状改善和骨折复位情况。结果 40例患者手术均顺利完成,术后48h内患者疼痛显著缓解,骨折椎体前缘以及中部高度丢失,从手术前的(12.5±2.2)mm、(9.1±1.3)mm减少到手术后的(4.6±1.4)mm、(3.3±1.0)mm;后凸畸形Cobb角从手术前的(22.2±5.1)°矫正到手术后的(9.1±4.6)°,其中1例患者术后出现少量骨水泥渗漏,1例患者手术过程中一侧穿刺管中出现脑脊液,即停止该侧手术。结论老年骨质疏松脊柱压缩骨折行椎体后凸成形术治疗效果显著,可以快速缓解患者的疼痛,使患者脊柱序列得到恢复,值得临床推广使用。     

The prospective evaluation of the osteoporotic vertebral fractures incidence in a random population sample

Introduction Osteoporotic vertebral fractures are mostly incidental but in some patients may lead to clinical symptoms, characteristic deformations of the vertebral column and increase total mortality. The aim of the study was to evaluate the prevalence of osteoporotic vertebral fractures and risk factors for osteoporosis in a random sample of Szczecin inhabitants aged over 50 in the relation to the whole European population examined in the frame of EVOS (European Vertebral Osteoporosis Study) and its prospective phase - EPOS (European Prospective Osteoporosis Study). At the baseline, 607 persons were studied, including 301 women and 306 men. Material and methods The questionnaire on the risk factors for osteoporosis and the spine X-rays analysed by morphometry, were taken in all subjects. The incidence of osteoporotic vertebral deformity in the studied population was similar in both sexes (12.6% women and 10,3% men) but in men aged 50-64 fracture incidence was significantly higher in comparison with women. The prevalence of new vertebral fractures examined after 4 years was higher in women than in men (9.1 vs 6.4/1000 persons years). Among the risk factors for osteoporosis, low physical activity and prolonged immobilization in women significantly influenced the incidence of vertebral deformities. Conclusions: 1) The study shows the high incidence of risk factors and osteoporotic vertebral deformities in the population of Szczecin inhabitants aged over 50. 2) Visual assessment only with a combination with morphometry is an optimal tool for detection of incident vertebral fractures.     

Association of vascular endothelial growth factor gene polymorphisms with osteoporotic vertebral compression fractures in postmenopausal women

Vascular endothelial growth factor (VEGF) is involved in bone formation through its role in angiogenesis. VEGF is also known to promote the healing of fractures. Thus, we determined whether or not VEGF ?2578C>A, ?1154G>A, ?634G>C, and 936C>T polymorphisms and haplotypes are associated with osteoporotic vertebral compression fractures (OVCF) in postmenopausal Korean women. The study subjects consisted of 82 patients with osteoporotic vertebral compression fractures and 117 control postmenopausal Korean women. PCR-RFLP and real-time PCR were used to analyze the VEGF polymorphisms. Homocysteine levels were also measured to determine whether or not polymorphisms of the VEGFgene affect homocysteine/folate metabolism. The AA genotype of the ?2578C>A polymorphism was significantly different between the stroke and control groups; no significant differences in the ?1154G>A, ?634G>C, and 936C>T genotype frequencies existed. However, the A-G-G-C haplotype had a tendency to be associated with OVCF in postmenopausal Korean women. Associations between the VEGF ?2578C>A polymorphism and homocysteine levels were also noted. In summary, these results suggest that the VEGF ?2578C>A polymorphisms and VEGF haplotypes may play an important role in the etiology of OVCF in postmenopausal Korean women.     

Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures.

OBJECTIVE--To determine the ability of measurements of bone density in women to predict later fractures. DESIGN-- Meta-analysis of prospective cohort studies published between 1985 and end of 1994 with a baseline measurement of bone density in women and subsequent follow up for fractures. For comparative purposes, we also reviewed case control studies of hip fractures published between 1990 and 1994. SUBJECTS--Eleven separate study populations with about 90,000 person years of observation time and over 2000 fractures. MAIN OUTCOME MEASURES--Relative risk of fracture for a decrease in bone mineral density of one standard deviation below age adjusted mean. RESULTS--All measuring sites had similar predictive abilities (relative risk 1.5 (95% confidence interval 1.4 to 1.6)) for decrease in bone mineral density except for measurement at spine for predicting vertebral fractures (relative risk 2.3 (1.9 to 2.8)) and measurement at hip for hip fractures (2.6 (2.0 to 3.5)). These results are in accordance with results of case-control studies. Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease. CONCLUSIONS--Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture. We do not recommend a programme of screening menopausal women for osteoporosis by measuring bone density.     

Comparison between bipolar hemiarthroplasty and total hip arthroplasty for unstable intertrochanteric fractures in elderly osteoporotic patients

The present study was conducted to compare bipolar hemiarthroplasty (BA) with total hip arthroplasty (THA) in treatment of unstable intertrochanteric fractures in elderly osteoporotic patients. The THA group included 14 males and 26 females with a mean age of 73.4 years, and the BA group included 27 males and 45 females with a mean age of 76.5 years. Significant difference existed between the two groups in operation time, blood loss, transfusion volume and cost of hospitalization, while no remarkable difference was identified in hospitalization period, general complications, joint function, pain, rate of revision and mortality. No dislocation was observed in BA group while 3 occurred in THA group. The results indicated that for unstable intertrochanteric fractures in elderly osteoporotic patients, BA seems to be a better or more reasonable choice compared with THA for the reason of less blood loss, shorter operation time, lower cost and no dislocation.     

RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis

The OPG/RANKL/RANK system is important in the balance between bone formation and resorption.We used primary human osteoblasts (hOBs) cells to examine the impact of 17-β-estradiol (E2) or/and 1,25-dihydroxyvitamin D (1,25D) in OPG/RANKL system in 28 post-menopausal (PM) women; (a) with hip fracture (OP) or (b) with osteoarthritis (OA). The hOB from OP patients proliferated slower during the first stage, than the OA women (31.5 ± 2.6 and 21.4 ± 1.3 days, respectively, p < 0.05). The OP group secreted significantly higher OPG protein levels than the OA women (10.1 ± 2.6 and 4.4 ± 0.8 pmol/L, respectively, p < 0.05). The 1,25D and 1,25D+E2 induce an increase in RANKL and RANKL/OPG mRNA expression in OP patients above 200% (p < 0.05).HOBs from the osteoporotic hip initially proliferate slower but after reaching the first cellular confluence, the proliferation rate is equal in both groups. Furthermore, hOBs from hips with OP present a higher protein secretion of OPG, and higher RANKL and RANKL/OPG expression ratio in response to 1,25D and 1,25D+E2, than hOBs from OA women. All this could suggest that the greater bone loss that characterizes OP patients can be mediated due to differences in the secretion and expression of the RANKL/OPG system in response to different stimuli.     

A randomised sham controlled trial of vertebroplasty for painful acute osteoporotic vertebral fractures (VERTOS IV)

Background

Combination of erlotinib and bevacizumab is a promising regimen in advanced non-squamous non-small-cell lung cancer (NSCLC). We are conducting a single arm phase II trial which aims to evaluate the efficacy and safety of this regime as a second- or third-line chemotherapy.

Methods

Key eligibility criteria were histologically or cytologically confirmed non-squamous NSCLC, stage III/IV or recurrent NSCLC not indicated radical chemoradiation, prior one or two regimen of chemotherapy, age 20 years or more, and performance status of two or less. The primary endpoint is objective response rate. The secondary endpoints include overall survival, progression-free survival, disease control rate and incidence of adverse events. This trial plans to accrue 80 patients based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate of 35% and a null hypothesis threshold response rate of 20%. A subset analysis according to EGFR mutation status is planned.

Discussion

We have presented the design of a single arm phase II trial to evaluate the efficacy and safety of combination of bevacizumab and erlotinib in advanced non-squamous NSCLC patients. In particular we are interested in determining the merit of further development of this regimen and whether prospective patient selection using EGFR gene is necessary in future trials.

Trial registration

This trial was registered at the UMIN Clinical Trials Registry as UMIN000004255 (http://www.umin.ac.jp/ctr/index.htm).