Kidney Clearance of Secretory Solutes Is Associated with Progression of CKD: The CRIC Study

BackgroundThe secretion of organic solutes by the proximal tubules is an essential intrinsic kidney function. However, the clinical significance of the kidney’s clearance of tubular secretory solutes is uncertain.MethodsIn this prospective cohort study, we evaluated 3416 participants with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study. We measured plasma and 24-hour urine concentrations of endogenous candidate secretory solutes at baseline, using targeted liquid chromatography–tandem mass spectrometry. The study defined CKD progression by a ≥50% decline in the eGFR, initiation of maintenance dialysis, or kidney transplantation. We used Cox proportional hazards regression to test associations of secretory-solute clearances with CKD progression and mortality, adjusting for eGFR, albuminuria, and other confounding characteristics.ResultsParticipants in this ancillary study had a mean age of 58 years and 41% were black; the median eGFR was 43 ml/min per 1.73 m2. After adjustment, lower kidney clearances of six solutes—kynurenic acid, pyridoxic acid, indoxyl sulfate, xanthosine, isovalerylglycine, and cinnamoylglycine—were associated with significantly greater risks of CKD progression, with clearance of kynurenic acid, a highly protein-bound solute, having the strongest association. Lower clearances of isovalerylglycine, tiglylglycine, hippurate, and trimethyluric acid were significantly associated with all-cause mortality after adjustment.ConclusionsWe found lower kidney clearances of endogenous secretory solutes to be associated with CKD progression and all-cause mortality, independent of eGFR and albuminuria. This suggests that tubular clearance of secretory solutes provides additional information about kidney health beyond measurements of glomerular function alone.

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Determining the Joint Effect of Obesity and Diabetes on All-Cause Mortality and Cardiovascular-Related Mortality following an Ischemic Stroke

Stroke Research and Treatment ◽

10.1155/2018/4812712 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Colleen Bauza ◽

Renee’ Martin ◽

Sharon D. Yeatts ◽

Keith Borg ◽

Gayenell Magwood ◽

...

Keyword(s):

Ischemic Stroke ◽

Proportional Hazards ◽

Joint Effect ◽

Normal Weight ◽

Cox Proportional Hazards ◽

Proportional Hazards Regression ◽

Obesity And Diabetes ◽

All Cause Mortality ◽

Obese Subjects ◽

Related Mortality

Although obesity and diabetes mellitus, or diabetes, are independently associated with mortality-related events (e.g., all-cause mortality and cardiovascular-related mortality) following an ischemic stroke, little is known about the joint effect of obesity and diabetes on mortality-related events following an ischemic stroke. The aim of this study is to evaluate the joint effect of obesity and diabetes on mortality-related events in subjects with a recent ischemic stroke. Data from the multicenter Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial was analyzed for this study. The joint effect of obesity and diabetes on mortality-related events was estimated via Cox proportional hazards regression models. No difference in the hazard of all-cause mortality following an ischemic stroke was observed between obese subjects with diabetes and underweight/normal-weight subjects without diabetes. In contrast, obese subjects with diabetes had an increased hazard of cardiovascular-related mortality following an ischemic stroke compared with underweight/normal-weight subjects without diabetes. Additionally, there was evidence of an attributable proportion due to interaction as well as evidence of a highly statistically significant interaction on the multiplicative scale for cardiovascular-related mortality. In this clinical trial cohort of ischemic stroke survivors, obesity and diabetes synergistically interacted to increase the hazard of cardiovascular-related mortality.

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Effects of Low-density Lipoprotein Cholesterol on Cardiovascular Disease and All-cause Mortality in Elderly Patients (≥75 years old)

10.21203/rs.3.rs-549837/v1 ◽

2021 ◽

Author(s):

Jiaxin Yu ◽

xiaokun liu ◽

shuohua chen ◽

yan liu ◽

hongmin liu ◽

...

Keyword(s):

Proportional Hazards ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cox Proportional Hazards ◽

Cvd Risk ◽

Proportional Hazards Regression ◽

All Cause Mortality ◽

Level Group ◽

The Ideal

Abstract Background: The associations of low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) and all-cause mortality are unclear in elderly(≥75 years) Chinese individuals.Methods: A total of 3674 individuals aged 75 or older underwent medical examinations at the Kailuan Group in 2006. Participants were divided into three groups by LDL_C values: the ideal level (LDL-C <2.6 mmol/l), appropriate level (2.6 mmol/l≤ LDL-C＜3.4 mmol/l) and elevated level (LDL-C≥3.4 mmol/l) groups. CVD and all-cause mortality events were recorded during the follow-up period. The Cox proportional hazards regression model was applied to evaluate the effect of LDL-C on CVD and all-cause mortality events.Results: The average follow-up time was 9.87±3.60 years.After adjustment for confounding factors, the multivariate Cox proportional hazards regression model showed that CVD risk in the elevated group was 1.46 (95% CI, 1.08-1.97), acute myocardial infarction risk was 2.08 (95% CI, 1.26-3.44), and all-cause mortality risk in the appropriate level group and elevated group was 1.12 (95% CI, 1.00-1.25) and 1.17 (95% CI, 1.00-1.36), respectively, compared with those in the ideal level group. For every standard deviation increase in LDL-C, CVD risk increased by 10%, acute myocardial infarction risk increased by 21%, and all-cause mortality event risk increased by 4%. No association was found between elevated LDL-C levels and the risk of stroke.Conclusions: In the elderly population, elevated LDL-C levels are a risk factor for CVD and all-cause mortality.

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Long-term survival in patients with coronary artery disease undergoing percutaneous coronary intervention with or without intracoronary pressure wire guidance: a report from SCAAR

European Heart Journal ◽

10.1093/ehjci/ehaa946.2507 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Volz ◽

B Redfors ◽

C Dworeck ◽

P Petursson ◽

M Gotberg ◽

...

Keyword(s):

Stable Angina ◽

Proportional Hazards ◽

Coronary Intervention ◽

Cox Proportional Hazards ◽

Funding Source ◽

Proportional Hazards Regression ◽

Pressure Wire ◽

Percutaneous Coronary ◽

All Cause Mortality

Abstract Background Intracoronary pressure wire measurements of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) provide decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the impact of FFR/iFR on long-term clinical outcomes in patients with stable angina, unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI), or STEMI. Methods We used data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) on all patients in Sweden undergoing PCI (with or without FFR/iFR guidance) for stable angina, UA/NSTEMI, or STEMI between January 2005 and March 2018. The primary endpoint was all-cause mortality and the secondary endpoints were stent thrombosis or restenosis and periprocedural complications. The primary model was multilevel Cox proportional-hazards regression using an instrumental variable (IV) to adjust for known and unknown confounders with treating hospital as a treatment-preference instrument. The following variables were entered into Cox proportional-hazards regression in addition to the IV: age, sex, diabetes, indication for PCI, severity of coronary disease, smoking status, hypertension, hyperlipidemia, previous myocardial infarction, previous PCI, previous coronary artery bypass graft, type of stent. Results In total, 151,001 patients underwent PCI: 31,514 (20.9%) for stable angina, 74,982 (49.6%) for UA/NSTEMI, and 44,505 (29.5%) for STEMI. Of these, FFR/iFR guidance was used in 11,433 patients (7.6%): 5029 (44.0%) with stable angina, 5989 (52.4%) with UA/NSTEMI, and 415 (3.6%) with STEMI; iFR was used in 1156 (10.1%) of these patients. After a median follow-up of 1784 (range 1–4824) days, the FFR/iFR group had lower adjusted risk estimates for all-cause mortality [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69–0.91; P=0.001] and stent thrombosis and restenosis (HR 0.13; 95% CI 0.09–0.19; P<0.001). The number of periprocedural complications did not differ significantly between the groups (odds ratio 0.69; 95% CI 0.30–1.55; P=0.368). There was no interaction between FFR/iFR and indication for PCI. We found no difference between FFR and iFR (HR 1.12; 95% CI 0.90–1.59; P=0.216). Conclusions In this observational study, the use of FFR/IFR was associated with a lower risk of long-term mortality in patients undergoing PCI for stable angina, UA/NSTEMI, or STEMI. Our study supports the current European and American guidelines for the use of FFR/iFR during PCI and shows that intracoronary pressure wire guidance has prognostic benefit in patients with stable angina as well as in patients with the acute coronary syndrome. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Heart and Lung Foundation, ALF Västra Götaland, Swedish Scientific Council

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Mediation of the Associations of Physical Activity With Cardiovascular Events and Mortality by Diabetes in Older Mexican Americans

American Journal of Epidemiology ◽

10.1093/aje/kwaa068 ◽

2020 ◽

Vol 189 (10) ◽

pp. 1124-1133

Author(s):

Kosuke Inoue ◽

Elizabeth R Mayeda ◽

Kimberly C Paul ◽

I-Fan Shih ◽

Qi Yan ◽

...

Keyword(s):

Physical Activity ◽

Mexican Americans ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Total Effect ◽

Proportional Hazards Regression ◽

All Cause Mortality ◽

Causal Mediation Analysis

Abstract Low physical activity (PA) among older adults increases the risk of cardiovascular disease (CVD) and mortality through metabolic disorders such as type 2 diabetes. We aimed to elucidate the extent to which diabetes mediates the effect of nonoccupational PA levels on CVD and mortality among older Mexican Americans. This study included 1,676 adults from the Sacramento Area Latino Study on Aging (1998–2007). We employed Cox proportional hazards regression models to investigate associations of PA level with all-cause mortality, fatal CVD, and nonfatal CVD events. Utilizing causal mediation analysis within a counterfactual framework, we decomposed the total effect of PA into natural indirect and direct effects. Over a median of 8 years of follow-up, low PA (<25th percentile) was associated with increased risks of all-cause mortality (hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.06, 1.75), fatal CVD (HR = 2.05, 95% CI: 1.42, 2.97), and nonfatal CVD events (HR = 1.67, 95% CI: 1.18, 2.37) in comparison with high PA (>75th percentile). Diabetes mediated 11.0%, 7.4%, and 5.2% of the total effect of PA on all-cause mortality, fatal CVD, and nonfatal CVD events, respectively. Our findings indicate that public health interventions targeting diabetes prevention and management would be a worthwhile strategy for preventing CVD and mortality among older Mexican Americans with insufficient PA levels.

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The Association Between Triglyceride-Glucose Index, Cardio-Cerebrovascular Diseases, and Death in Korean Adults: A Longitudinal Study Based on the NHIS-HEALS Cohort

10.21203/rs.3.rs-663384/v1 ◽

2021 ◽

Author(s):

Joungyoun Kim ◽

Sang-jun Shin ◽

Hee-Taik Kang

Keyword(s):

Regression Models ◽

Proportional Hazards ◽

Cerebrovascular Diseases ◽

Cox Proportional Hazards ◽

Men And Women ◽

Tyg Index ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Triglyceride Glucose Index ◽

All Cause Mortality

Abstract Background: The triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance. We aimed to investigate the TyG index in relation to cardio-cerebrovascular diseases (CCVDs) and mortality.Methods: This retrospective study included 114,603 subjects. The TyG index was categorized into four quartile groups by sex: Q1, <8.249 and <8.063; Q2, 8.249 ‒ <8.614 and 8.063 ‒ <8.403; Q3, 8.614 ‒ < 8.998 and 8.403 ‒ <8.752; and Q4, ≥8.998 and ≥8.752, in men and women, respectively. To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the primary outcomes (CCVDs and all-cause mortality), Cox proportional hazards regression models were adopted.Results: Compared to Q1, fully adjusted HRs (95% CIs) for the primary outcomes of Q2, Q3, and Q4 were 1.063 (0.982‒1.152), 1.112 (1.026‒1.206), and 1.153 (1.060‒1.254) in men and 1.099 (0.986‒1.226), 1.049 (0.941‒1.169), and 1.069 (0.960‒1.190) in women, respectively. HRs (95% CIs) for cardiovascular diseases (CVDs) of Q2, Q3, and Q4 were 1.117 (0.971‒1.285), 1.191 (1.036‒1.369), and 1.237 (1.071‒1.427) in men and 1.239 (1.018‒1.509), 1.188 (0.976‒1.446), and 1.248 (1.027‒1.517) in women, respectively. Conclusions: The elevated TyG index were was positively associated with CCVDs and all-cause mortality in men and predicted the higher risk of CVDs in both sexes.

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Urine Alpha-1-Microglobulin Levels and Acute Kidney Injury, Mortality, and Cardiovascular Events following Cardiac Surgery

American Journal of Nephrology ◽

10.1159/000518240 ◽

2021 ◽

pp. 1-11

Author(s):

Jonathan G. Amatruda ◽

Michelle M. Estrella ◽

Amit X. Garg ◽

Heather Thiessen-Philbrook ◽

Eric McArthur ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cardiac Surgery ◽

Proportional Hazards ◽

Kidney Injury ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Ckd Progression ◽

Urine Albumin ◽

All Cause Mortality

Introduction: Urine alpha-1-microglobulin (Uα1m) elevations signal proximal tubule dysfunction. In ambulatory settings, higher Uα1m is associated with acute kidney injury (AKI), progressive chronic kidney disease (CKD), cardiovascular (CV) events, and mortality. We investigated the associations of pre- and postoperative Uα1m concentrations with adverse outcomes after cardiac surgery. Methods: In 1,464 adults undergoing cardiac surgery in the prospective multicenter Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury (TRIBE-AKI) cohort, we measured the pre-and postoperative Uα1m concentrations and calculated the changes from pre- to postoperative concentrations. Outcomes were postoperative AKI during index hospitalization and longitudinal risks for CKD incidence and progression, CV events, and all-cause mortality after discharge. We analyzed Uα1m continuously and categorically by tertiles using multivariable logistic regression and Cox proportional hazards regression adjusted for demographics, surgery characteristics, comorbidities, baseline estimated glomerular filtration rate, urine albumin, and urine creatinine. Results: There were 230 AKI events during cardiac surgery hospitalization; during median 6.7 years of follow-up, there were 212 cases of incident CKD, 54 cases of CKD progression, 269 CV events, and 459 deaths. Each 2-fold higher concentration of preoperative Uα1m was independently associated with AKI (adjusted odds ratio [aOR] = 1.36, 95% confidence interval 1.14–1.62), CKD progression (adjusted hazard ratio [aHR] = 1.46, 1.04–2.05), and all-cause mortality (aHR = 1.19, 1.06–1.33) but not with incident CKD (aHR = 1.21, 0.96–1.51) or CV events (aHR = 1.01, 0.86–1.19). Postoperative Uα1m was not associated with AKI (aOR per 2-fold higher = 1.07, 0.93–1.22), CKD incidence (aHR = 0.90, 0.79–1.03) or progression (aHR = 0.79, 0.56–1.11), CV events (aHR = 1.06, 0.94–1.19), and mortality (aHR = 1.01, 0.92–1.11). Conclusion: Preoperative Uα1m concentrations may identify patients at high risk of AKI and other adverse events after cardiac surgery, but postoperative Uα1m concentrations do not appear to be informative.

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Loneliness, Social Isolation and All-Cause Mortality in Older Adults

Innovation in Aging ◽

10.1093/geroni/igab046.3321 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 925-925

Author(s):

Timothy Barnes ◽

Rifky Tkatch ◽

Manik Ahuja ◽

Laurie Albright ◽

James Schaeffer ◽

...

Keyword(s):

Older Adults ◽

Social Isolation ◽

Regression Models ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Proportional Hazards Regression ◽

Risk Of Mortality ◽

The Social ◽

All Cause Mortality ◽

Using Data

Abstract As distinct constructs, loneliness and social isolation have both been associated with mortality in older adults. Many studies have examined each construct separately; however, few have examined their impact together, especially within the U.S. Using data from a large sample of U.S. adults age 65+ (N=7,982), the effect of loneliness and social isolation on all-cause mortality was examined considering their separate and joint effects. Measures were based on the UCLA-3 Loneliness Scale and the Social Network Index (SNI). Loneliness was categorized as: Severe, moderate, or no loneliness. Social isolation (defined by the SNI) was categorized as: Limited, medium, or diverse social networks (SN). Cox proportional hazards regression models were performed. Among participants, there were 328 deaths after data collection (4.1%). In separate, adjusted models, loneliness (severe, HR=1.86, 95% CI: 1.43-2.41 and moderate, HR=1.51, 95% CI: 1.16-1.98) and social isolation (limited SN, HR=2.37, 95% CI: 1.72-3.27 and moderate SN, HR=1.55, 95% CI: 1.12-2.14) were both associated with mortality. Modeled together, loneliness (severe, HR=1.55, 95% CI: 1.18-2.04 and moderate, HR=1.40, 95% CI: 1.07-1.83) and social isolation (limited SN, HR=2.08, 95% CI: 1.49-2.89 and moderate SN, HR=1.46, 95% CI: 1.05-2.02) both remained significantly associated with all-cause mortality with limited SN as the stronger indicator. Results demonstrate that both loneliness and social isolation contribute to greater risk of mortality among older adults. Furthermore, individuals with limited SN are at greatest risk. As the COVID-19 pandemic continues, loneliness and social isolation should be targeted safely in efforts to reduce mortality risk among older adults.

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PETCO2 gradient: a novel prognostic parameter in cardiopulmonary exercise testing

European Heart Journal ◽

10.1093/ehjci/ehaa946.1077 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

I.D Poveda Pinedo ◽

I Marco Clement ◽

O Gonzalez ◽

I Ponz ◽

A.M Iniesta ◽

...

Keyword(s):

Exercise Testing ◽

Proportional Hazards ◽

Cardiopulmonary Exercise Testing ◽

Cox Proportional Hazards ◽

Prognostic Parameter ◽

Cardiopulmonary Exercise ◽

Proportional Hazards Regression ◽

Kaplan Meier ◽

Baseline Characteristics ◽

The Difference

Abstract Background Previous parameters such as peak VO2, VE/VCO2 slope and OUES have been described to be prognostic in heart failure (HF). The aim of this study was to identify further prognostic factors of cardiopulmonary exercise testing (CPET) in HF patients. Methods A retrospective analysis of HF patients who underwent CPET from January to November 2019 in a single centre was performed. PETCO2 gradient was defined by the difference between final PETCO2 and baseline PETCO2. HF events were defined as decompensated HF requiring hospital admission or IV diuretics, or decompensated HF resulting in death. Results A total of 64 HF patients were assessed by CPET, HF events occurred in 8 (12.5%) patients. Baseline characteristics are shown in table 1. Patients having HF events had a negative PETCO2 gradient while patients not having events showed a positive PETCO2 gradient (−1.5 [IQR −4.8, 2.3] vs 3 [IQR 1, 5] mmHg; p=0.004). A multivariate Cox proportional-hazards regression analysis revealed that PETCO2 gradient was an independent predictor of HF events (HR 0.74, 95% CI [0.61–0.89]; p=0.002). Kaplan-Meier curves showed a significantly higher incidence of HF events in patients having negative gradients, p=0.002 (figure 1). Conclusion PETCO2 gradient was demonstrated to be a prognostic parameter of CPET in HF patients in our study. Patients having negative gradients had worse outcomes by having more HF events. Time to first event, decompensated heart Funding Acknowledgement Type of funding source: None

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High School Quality and 56-Year All-Cause Mortality Risk Across Race and Ethnicity

Innovation in Aging ◽

10.1093/geroni/igaa057.1632 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 505-506

Author(s):

Dominika Seblova ◽

Kelly Peters ◽

Susan Lapham ◽

Laura Zahodne ◽

Tara Gruenewald ◽

...

Keyword(s):

High School ◽

Mortality Risk ◽

Race And Ethnicity ◽

Proportional Hazards ◽

School Quality ◽

Cox Proportional Hazards ◽

School Level ◽

Lower Mortality ◽

All Cause Mortality ◽

Race Ethnicity

Abstract Having more years of education is independently associated with lower mortality, but it is unclear whether other attributes of schooling matter. We examined the association of high school quality and all-cause mortality across race/ethnicity. In 1960, about 5% of US high schools participated in Project Talent (PT), which collected information about students and their schools. Over 21,000 PT respondents were followed for mortality into their eighth decade of life using the National Death Index. A school quality factor, capturing term length, class size, and teacher qualifications, was used as the main predictor. First, we estimated overall and sex-stratified Cox proportional hazards models with standard errors clustered at the school level, adjusting for age, sex, composite measure of parental socioeconomic status, and 1960 cognitive ability. Second, we added an interaction between school quality and race/ethnicity. Among this diverse cohort (60% non-Hispanic Whites, 23% non-Hispanic Blacks, 7% Hispanics, 10% classified as another race/s) there were 3,476 deaths (16.5%). School quality was highest for Hispanic respondents and lowest for non-Hispanic Blacks. Non-Hispanic Blacks also had the highest mortality risk. In the whole sample, school quality was not associated with mortality risk. However, higher school quality was associated with lower mortality among those classified as another race/s (HR 0.75, 95% CI: 0.56-0.99). For non-Hispanic Blacks and Whites, the HR point estimates were unreliable, but suggest that higher school quality is associated with increased mortality. Future work will disentangle these differences in association of school quality across race/ethnicity and examine cause-specific mortality.

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Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases

Supportive Care in Cancer ◽

10.1007/s00520-021-06018-x ◽

2021 ◽

Author(s):

Hiroaki Ikesue ◽

Moe Mouri ◽

Hideaki Tomita ◽

Masaki Hirabatake ◽

Mai Ikemura ◽

...

Keyword(s):

Zoledronic Acid ◽

Bone Metastases ◽

Tooth Extraction ◽

Proportional Hazards ◽

Osteonecrosis Of The Jaw ◽

Cox Proportional Hazards ◽

Patients With Cancer ◽

Proportional Hazards Regression ◽

Before And After ◽

Denosumab Treatment

Abstract Purpose This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. Methods The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. Results Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). Conclusion The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

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