Pantoprazole, a Proton Pump Inhibitor, Delays Fracture Healing in Mice

Proton pump inhibitors (PPIs), which are widely used in the treatment of dyspeptic problems, have been shown to reduce osteoclast activity. There is no information, however, on whether PPIs affect fracture healing. We therefore studied the effect of the PPI pantoprazole on callus formation and biomechanics during fracture repair. Bone healing was analyzed in a murine fracture model using radiological, biomechanical, histomorphometric, and protein biochemical analyses at 2 and 5 weeks after fracture. Twenty-one mice received 100 mg/kg body weight pantoprazole i.p. daily. Controls (n = 21) received equivalent amounts of vehicle. In pantoprazole-treated animals biomechanical analysis revealed a significantly reduced bending stiffness at 5 weeks after fracture compared to controls. This was associated with a significantly lower amount of bony tissue within the callus and higher amounts of cartilaginous and fibrous tissue. Western blot analysis showed reduced expression of the bone formation markers bone morphogenetic protein (BMP)-2, BMP-4, and cysteine-rich protein (CYR61). In addition, significantly lower expression of proliferating cell nuclear antigen indicated reduced cell proliferation after pantoprazole treatment. Of interest, the reduced expression of bone formation markers was associated with a significantly diminished expression of RANKL, indicating osteoclast inhibition. Pantoprazole delays fracture healing by affecting both bone formation and bone remodeling.     

Long‐Term Proton Pump Inhibitor Therapy and Falls and Fractures in Elderly Women: A Prospective Cohort Study

Proton pump inhibitors (PPIs) are widely used in the elderly. Recent studies have suggested that long‐term PPI therapy is associated with fractures in the elderly, however the mechanism remains unknown. We investigated the association between long‐term PPI therapy ≥1 year and fracture risk factors including bone structure, falls, and balance‐related function in a post hoc analysis of a longitudinal population‐based prospective cohort of elderly postmenopausal women and replicated the findings in a second prospective study of falling in elderly postmenopausal women. Long‐term PPI therapy was associated with increased risk of falls and fracture‐related hospitalizations; adjusted odds ratio (AOR) 2.17; 95% CI, 1.25–3.77; p = 0.006 and 1.95; 95% CI, 1.20–3.16; p = 0.007, respectively. In the replication study, long‐term PPI use was associated with an increased risk of self‐reported falling; AOR, 1.51; 95% CI, 1.00–2.27; p = 0.049. No association of long‐term PPI therapy with bone structure was observed; however, questionnaire‐assessed falls‐associated metrics such as limiting outdoor activity (p = 0.002) and indoor activity (p = 0.001) due to fear of falling, dizziness (p < 0.001) and numbness of feet (p = 0.017) and objective clinical measurement such as Timed Up and Go (p = 0.002) and Romberg eyes closed (p = 0.025) tests were all significantly impaired in long‐term PPI users. Long‐term PPI users were also more likely to have low vitamin B12 levels than non‐users (50% versus 21%, p = 0.003). In conclusion, similar to previous studies, we identified an increased fracture risk in subjects on long‐term PPI therapy. This increase in fracture risk in elderly women, already at high risk of fracture, appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long‐term PPI therapy. © 2014 American Society for Bone and Mineral Research.     

Proton Pump Inhibitors, Histamine H2 Receptor Antagonists, and Other Antacid Medications and the Risk of Fracture

We studied the effect of proton pump inhibitors, histamine H₂ receptor antagonists, and other types of antacid drugs on fracture risk. All cases were subjects with any fracture sustained during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of proton pump inhibitors, histamine H₂ antagonists, and other antacid drugs. Adjustments were made for several confounders, including diagnosis of an ulcer, nonsteroidal anti-inflammatory drug use, use of histamine H₁ antagonists, stomach resection, previous fracture, and use of corticosteroids. The effect of dose was examined by stratifying for cumulated dose (defined daily dose). Use of proton pump inhibitors was associated with an increase in fracture risk for use within the last year [odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.12–1.43 for overall fracture risk; OR = 1.45, 95% CI 1.28–1.65 for hip fractures; and OR = 1.60, 95% CI 1.25–2.04 for spine fractures). Histamine H₂ antagonists were associated with a decreased fracture risk if they had been used within the last year (OR = 0.88, 95% CI 0.82–0.95 for any fracture, OR = 0.69, 95% CI 0.57–0.84 for hip fractures). Other antacids were not associated with overall fracture risk but were associated with hip and spine fractures. Proton pump inhibitors appeared to be associated with a limited increase in fracture risk, in contrast to histamine H ₂ antagonists, which seemed to be associated with a small decrease in fracture risk. In all cases, the changes in risk estimates were small and the clinical significance was limited.     

Vertebral Fracture Risk in Diabetic Elderly Men: The MrOS Study

Type 2 diabetes (T2DM) is associated with a significant increase in risk of nonvertebral fractures, but information on risk of vertebral fractures (VFs) in subjects with T2DM, particularly among men, is lacking. Furthermore, it is not known whether spine bone mineral density (BMD) can predict the risk of VF in T2DM. We sought to examine the effect of diabetes status on prevalent and incident vertebral fracture, and to estimate the effect of lumbar spine BMD (areal and volumetric) as a risk factor for prevalent and incident morphometric vertebral fracture in T2DM (n = 875) and nondiabetic men (n = 4679). We used data from the Osteoporotic Fractures in Men (MrOS) Study, which enrolled men aged ≥65 years. Lumbar spine areal BMD (aBMD) was measured with dual‐energy X‐ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT). Prevalence (7.0% versus 7.7%) and incidence (4.4% versus 4.5%) of VFs were not higher in T2DM versus nondiabetic men. The risk of prevalent (OR, 1.05; 95% CI, 0.78 to 1.40) or incident vertebral‐fracture (OR, 1.28; 95% CI, 0.81 to 2.00) was not higher in T2DM versus nondiabetic men in models adjusted for age, clinic site, race, BMI, and aBMD. Higher spine aBMD was associated with lower risk of prevalent VF in T2DM (OR, 0.55; 95% CI, 0.48 to 0.63) and nondiabetic men (OR, 0.66; 95% CI, 0.5 to 0.88) (p for interaction = 0.24) and of incident VF in T2DM (OR, 0.50; 95% CI, 0.41 to 0.60) and nondiabetic men (OR, 0.54; 95% CI, 0.33 to 0.88) (p for interaction = 0.77). Results were similar for vBMD. In conclusion, T2DM was not associated with higher prevalent or incident VF in older men, even after adjustment for BMI and BMD. Higher spine aBMD and vBMD are associated with lower prevalence and incidence of VF in T2DM as well as nondiabetic men. © 2017 American Society for Bone and Mineral Research.     

The Relationship Between Vitamin A and Risk of Fracture: Meta‐Analysis of Prospective Studies

Osteoporotic fracture is a significant cause of morbidity and mortality and is a challenging global health problem. Previous reports of the relation between vitamin A intake or blood retinol and risk of fracture were inconsistent. We searched Medline and Embase to assess the effects of vitamin A (or retinol or beta‐carotene but not vitamin A metabolites) on risk of hip and total fracture. Only prospective studies were included. We pooled data with a random effects meta‐analysis with adjusted relative risk (adj.RR) and 95% confidence interval (CI). We used Q statistic and I² statistic to assess heterogeneity and Egger's test to assess publication bias. Eight vitamin A (or retinol or beta‐carotene) intake studies (283,930 participants) and four blood retinol level prospective studies (8725 participants) were included. High intake of vitamin A and retinol were shown to increase risk of hip fracture (adj.RR [95% CI] = 1.29 [1.07, 1.57] and 1.40 [1.03, 1.91], respectively), whereas beta‐carotene intake was not found to increase the risk of hip fracture (adj.RR [95% CI] = 0.82 [0.59, 1.14]). Both high or low level of blood retinol was shown to increase the risk of hip fracture (adj.RR [95% CI] = 1.87 [1.31, 2.65] and 1.56 [1.09, 2.22], respectively). The risk of total fracture does not differ significantly by level of vitamin A (or retinol) intake or by blood retinol level. Dose‐response meta‐analysis shows a U‐shaped relationship between serum retinol level and hip fracture risk. Our meta‐analysis suggests that blood retinol level is a double‐edged sword for risk of hip fracture. To avoid the risk of hip fracture caused by too low or too high a level of retinol concentration, we suggest that intake of beta‐carotene (a provitamin A), which should be converted to retinol in blood, may be better than intake of retinol from meat, which is directly absorbed into blood after intake. © 2014 American Society for Bone and Mineral Research.     

老年人A型行为与心身疾病的关系

为探讨A型行为中各元素与老年人心身疾病之间的关系，对200例老年人作健康检查，分别统计所患心身疾病种类和数量，同时完成“A型行为问卷”。结果发现患几种常见的心身疾病如高血压、冠心病、心律失常、胃溃疡、糖尿病等病人的敌意性分值均分别高于无上述疾病者（P＜0．05或P＜0．01）。表明A型行为模式中敌意性行为元素与心身疾病的患病有密切的联系，提示在日常护理工作中，应注意干预和矫正不利于健康的敌意性行为，以减少心身疾病的发生。     

Relationship Between Body Mass Index and Fracture Risk Is Mediated by Bone Mineral Density

The relationship between body mass index (BMI) and fracture risk is controversial. We sought to investigate the effect of collinearity between BMI and bone mineral density (BMD) on fracture risk, and to estimate the direct and indirect effect of BMI on fracture with BMD being the mediator. The study involved 2199 women and 1351 men aged 60 years or older. BMI was derived from baseline weight and height. Femoral neck BMD was measured by dual‐energy X‐ray absorptiometry (DXA; GE‐LUNAR, Madison, WI, USA). The incidence of fragility fracture was ascertained by X‐ray reports from 1991 through 2012. Causal mediation analysis was used to assess the mediated effect of BMD on the BMI‐fracture relationship. Overall, 774 women (35% of total women) and 258 men (19%) had sustained a fracture. Approximately 21% of women and 20% of men were considered obese (BMI ≥ 30). In univariate analysis, greater BMI was associated with reduced fracture risk in women (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.85 to 0.99) and in men (HR 0.77; 95% CI, 0.67 to 0.88). After adjusting for femoral neck BMD, higher BMI was associated with greater risk of fracture in women (HR 1.21; 95% CI, 1.11 to 1.31) but not in men (HR 0.96; 95% CI, 0.83 to 1.11). Collinearity had minimal impact on the BMD‐adjusted results (variance inflation factor [VIF] = 1.2 for men and women). However, in mediation analysis, it was found that the majority of BMI effect on fracture risk was mediated by femoral neck BMD. The overall mediated effect estimates were ?0.048 (95% CI, ?0.059 to ?0.036; p < 0.001) in women and ?0.030 (95% CI, ?0.042 to ?0.018; p < 0.001) in men. These analyses suggest that there is no significant direct effect of BMI on fracture, and that the observed association between BMI and fracture risk is mediated by femoral neck BMD in both men and women. © 2014 American Society for Bone and Mineral Research.     

Characteristics of Falls and Risk of Hip Fracture in Elderly Men

The steep rise in hip fracture incidence rates with age is not fully explained by an increase in the frequency of falls or by reduction in bone mineral density, suggesting that circumstances of falls may also affect the risk of hip fracture. Previous studies conducted mainly among women have identified the importance of the orientation of a fall in the etiology of hip fracture. In this case–control study among men of 45 years and older, we evaluated how the circumstances of falls affect the risk of hip fracture. We compared 214 cases with hip fracture due to a fall with 86 controls who had fallen within the past year but did not sustain a hip fracture. As expected, in multivariable age-adjusted analyses men who reported hitting the hip/thigh in a fall had a markedly elevated risk of hip fracture (OR = 97.8; 95% CI = 31.7–302). Hitting the knee in a fall was associated with reduced risk (OR = 0.24; 95% CI = 0.09–0.67). Other factors that were associated with reduced risk of hip fracture among men who fell were more hours of physical activity in the past year (OR = 0.84; 95% CI = 0.73–0.97, for each additional 4 h per week), a greater body mass index (OR = 0.60; 95% CI = 0.40–0.90, for each additional 4 kg/m²), and a history of a fracture when age 45 years or older (OR = 0.26; 95% CI = 0.10–0.69). Reported lower limb dysfunction was associated with increased risk of hip fracture (OR = 6.41; 95% CI = 2.09–19.6) among fallers. The increased risk associated with hitting the hip/thigh in a fall and the reduced risk associated with high body mass index suggest that preventive efforts for older men at high risk might include protective hip pads to reduce the force on the hip in a fall. Exercise and strength training programs may also reduce the risk of hip fracture among men who fall. Received: 12 May 1997 / Accepted: 14 October 1997     

Association Between Physical Activity and Risk of Fracture

Prospective studies that have examined the association between physical activity and fracture risks have reported conflicting findings. We performed a meta‐analysis to evaluate this association. We searched MEDLINE (1966 to February 1, 2013), EMBASE (1980 to February 1, 2013), and OVID (1950 to February 1, 2013) for prospective cohort studies with no restrictions. Categorical, heterogeneity, publication bias, and subgroup analyses were performed. There were 22 cohort studies with 1,235,768 participants and 14,843 fractures, including 8874 hip, 690 wrist, and 927 vertebral fractures. The pooled relative risk (RR) of total fractures for the highest versus lowest category of physical activity was 0.71 (95% confidence interval [CI], 0.63–0.80). The analysis of fracture subtypes showed a statistically significant inverse relationship between a higher category of physical activity and risk of hip and wrist fracture. The risk of hip or wrist fracture was 39% and 28% lower, respectively, among individuals with the highest category of physical activity than among those with the lowest category (95% CI, 0.54–0.69 and 0.49–0.96, respectively). The association between physical activity and vertebral fracture risk was not statistically related (RR, 0.87; 95% CI, 0.72–1.03). There was no evidence of publication bias. There was a statistically significant inverse association between physical activity and total fracture risk, especially for hip and wrist fractures. Additional subject‐level meta‐analyses are required for a more reliable assessment of subgroups and types of physical activity. © 2014 American Society for Bone and Mineral Research.     

Relationship Between Pump Speed Design and Hemolysis in an Axial Flow Blood Pump

Abstract
In an attempt to reduce the hemolysis caused by axial flow blood pumps, we investigated whether the specific speed should be kept within the standard engineering range or whether pump speed should be minimized, thus making the specific speed beyond the standard range. Four pumps with 11.8 mm diameter impellers were designed to accommodate a flow of 5 L/min and a head of 100 mm Hg. The pumps were tested at 4 speeds: A, 14,000; B, 18,000; C, 22,000; and D, 26,000 rpm. Pump performance data were obtained, and the maximum point of total pump efficiency was found for each pump. The maximum efficiencies were A, 50%; B, 58%; C, 52%; and D, 53%. The specific speed of each pump recorded at the maximum efficiency point was calculated as A, 899; B, 954; C, 1,218; and D, 1,951 rpm. Hemolytic tests were performed with fresh goat blood in a closed, mock-loop circuit. Hemolytic indexes were A, 0.036; B, 0.22; C, 0.35; and D, 0.66. We have concluded that decreased hemolysis is correlated with a lower pump speed and that the specific speed for the lowest pump speed is less than the standard range. Having a specific speed outside the standard range was not correlated with reduced total pump efficiency.     

Relationship Between Obesity and Risk of Major Osteoporotic Fracture in Postmenopausal Women: Taking Frailty Into Consideration

The role of obesity in fracture risk remains uncertain and inconclusive in postmenopausal women. Our study aimed to assess the relationship between obesity and risk of major osteoporotic fracture (MOF; ie, a clinical fracture of upper arm or shoulder, hip, spine, or wrist) in postmenopausal women, after taking frailty into consideration. We used the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 5-year Hamilton cohort for this study. Frailty was measured by a frailty index (FI) of deficit accumulation at baseline. We incorporated an interaction term (obesity × FI) in the Cox proportional hazards regression model. We included 3985 women (mean age 69.4 years) for analyses, among which 29% were obese (n = 1118). There were 200 (5.02%) MOF events documented during follow-up: 48 (4.29%) in obese women and 152 (5.65%) in the nonobese group. Significant relationships between obesity, frailty, and MOF risk were found: hazard ratio (HR) = 0.72 (95% confidence interval [CI] 0.67–0.78) for those with an FI of zero regarding MOF risk among obese women, and HR = 1.34 (95% CI 1.11–1.62) per SD increase in the FI among nonobese women. The interaction term was also significant: HR = 1.16 (95% CI 1.02–1.34) per SD increase in the FI among obese women. Increased HRs were found with higher FIs regarding the relationship between obesity and MOF risk, indicating increasing frailty attenuated the protective effect of obesity. For example, although the HR for obesity and MOF risk among those who were not frail (FI = 0) was 0.72 (95% CI 0.67–0.78), among those who were very frail (FI = 0.70), the HR was 0.91 (95% CI 0.85–0.98). To conclude, after taking frailty into consideration, obesity was significantly associated with decreased risk of MOF in postmenopausal women among those who were not frail; however, increasing frailty attenuated this protective effect of obesity. Evaluating frailty status may aid in understanding of the complex relationship between obesity and fracture risk. © 2020 American Society for Bone and Mineral Research (ASBMR).     

老年骨质疏松性骨折的危险因素及其护理干预

目的了解老年人骨质疏松性骨折的危险因素 ,提高其生活质量。方法对 132例老年骨质疏松性骨折患者按年龄段分成三组 ,根据X线摄片结果确定骨折部位 ,询问患者骨折发生时的状态和诱发因素。结果女性骨折占6 8.94 % ,男性占 31.0 6 % ,骨折发生频率高的部位依次为股骨颈、椎体、前臂远端。跌倒是导致老年人骨质疏松性骨折的主要危险因素。结论老年骨质疏松患者受轻微的外力撞击或震动即可发生骨折 ,护理人员应针对骨质疏松性骨折的危险因素 ,采取有效的干预措施和健康教育 ,降低骨质疏松性骨折的发生率。     

Relationship Between Bone Mineral Density T-Score and Nonvertebral Fracture Risk Over 10 Years of Denosumab Treatment

Although treat-to-target strategies are being discussed in osteoporosis, there is little evidence of what the target should be to reduce fracture risk maximally. We investigated the relationship between total hip BMD T-score and the incidence of nonvertebral fracture in women who received up to 10 years of continued denosumab therapy in the FREEDOM (3 years) study and its long-term Extension (up to 7 years) study. We report the percentages of women who achieved a range of T-scores at the total hip or femoral neck over 10 years of denosumab treatment (1343 women completed 10 years of treatment). The incidence of nonvertebral fractures was lower with higher total hip T-score. This relationship plateaued at a T-score between -2.0 and -1.5 and was independent of age and prevalent vertebral fractures, similar to observations in treatment-naïve subjects. Reaching a specific T-score during denosumab treatment was dependent on the baseline T-score, with higher T-scores at baseline more likely to result in higher T-scores at each time point during the study. Our findings highlight the importance of follow-up BMD measurements in patients receiving denosumab therapy because BMD remains a robust indicator of fracture risk. These data support the notion of a specific T-score threshold as a practical target for therapy in osteoporosis. © 2019 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)     

Clinical Risk Factors for Osteoporotic Hip Fracture in Elderly Women - Implications for Fracture Prevention

Of all fractures being linked with osteoporosis, those of the hip are the most important in terms of early death, functional dependence, and costs of care. Reduction of these adverse outcomes depends on preventing hip fractures caused by a fall on a biomechanically compromised proximal femur. In order to allow targeting of preventive care, there is considerable interest in predicting the risk of hip fracture. Bone densitometry is an established method to determine the risk of developing fractures. Recent studies, however, have identified additional factors which contribute to fracture risk independently of bone mass, suggesting that, in addition to taking measures that maintain bone density, risk factor modification may prove to be an effective strategy for preventing hip fracture. The aim of this article is to review current knowledge on clinical risk factors for hip fracture in elderly women.     

Clinical Risk Factors for Osteoporotic Hip Fracture in Elderly Women – Implications for Fracture Prevention

Of all fractures being linked with osteoporosis, those of the hip are the most important in terms of early death, functional dependence, and costs of care. Reduction of these adverse outcomes depends on preventing hip fractures caused by a fall on a biomechanically compromised proximal femur. In order to allow targeting of preventive care, there is considerable interest in predicting the risk of hip fracture. Bone densitometry is an established method to determine the risk of developing fractures. Recent studies, however, have identified additional factors which contribute to fracture risk independently of bone mass, suggesting that, in addition to taking measures that maintain bone density, risk factor modification may prove to be an effective strategy for preventing hip fracture. The aim of this article is to review current knowledge on clinical risk factors for hip fracture in elderly women.     

骨质疏松性椎体骨折部位与疼痛部位关系的研究

目的 探讨骨质疏松性椎体骨折部位与疼痛部位之间的一致性关系.方法 分析128例骨质疏松性椎体骨折(T8～L4)的临床和X线资料.记录外伤史、骨折部位,采用疼痛视觉模拟评分(VAS)评估初诊时疼痛程度,Kuorinka法标注疼痛部位,Kappa系数检验骨折部位与疼痛部位的一致性.结果 各组在性别、年龄、外伤史方面差异无统计学意义(P＞0.05).胸椎骨折VAS评分较腰椎骨折高,差异有统计学意义(P＜0.001).58例胸椎骨折仅15例主诉上背痛,骨折部位与疼痛部位之间一致性较差(Kappa值=0.031,P=0.290);47例中45例腰椎骨折主诉下背部痛,骨折部位与疼痛部位之间一致性较好(Kappa值=0.770,P＜0.001).结论 骨质疏松性椎体骨折疼痛部位与骨折部位不一致性较高,对疑似骨质疏松性骨折的老年腰背部疼痛患者,应行包括胸、腰椎的X线检查,以免误诊或漏诊.