Intervention on Osteoporosis and Chronic Kidney Disease-mineral and Bone Disorder (CKD-MBD)

Study Overview
=================
Brief Summary
-----------------
Older adults having chronic kidney disease (CKD) have a higher rate of fracture than those without chronic kidney disease. Osteoporosis and chronic kidney disease mineral and bone disorder (CKD-MBD) are risk factors for skeletal fractures. In addition, CKD-MBD is also a risk factor for cardiovascular disease. Pharmacological and non-pharmacological therapy are both important to prevent complications of chronic kidney disease and osteoporosis. Therefore, a prospective intervention study is purposed to investigate the effect of a multifaceted intervention including exercise, diet modification, and pharmacological therapy on their outcomes. Patients who are older than 50 years old and have chronic kidney disease G3-G4 (estimated glomerular filtration rate > 20 ml/min per 1.73 m2) with a high risk of fracture (screening by Fracture Risk Assessment Tool (FRAX®)) are enrolled. Baseline questionnaire, clinical, laboratory and radiological examination are performed. If CKD-MBD or osteoporosis are revealed, the intervention will be given accordingly. All examinations will be repeated every 3 months, except bone mineral density and x-ray film for the spine to investigate the effect of the intervention. After one-year, primary outcomes including mortality, cardiovascular events, subsequent fracture, and fall rate will be examined. The secondary outcomes include changes in biochemistry laboratory data before and after interventions (pharmacological therapy and lifestyle modifications). The bivariate analysis will be performed using the t-test or Mann-Whitney U test for continuous variables with normal or non-normal distribution, respectively. Chi-squared test for categorical variables will be used to test correlations between baseline characteristics, change of laboratory results and outcomes. The paired t-test will be used to examine the difference between before and after the interventions. Stepwise multivariate logistic regression models will be used to identify the correlates of outcomes after adjusting for potential confounders.

Detailed Description
-----------------
Background: Older adults having chronic kidney disease (CKD) have a higher rate of fracture. Osteoporosis and chronic kidney disease mineral and bone disorder (CKD-MBD) are risk factors for skeletal fractures. However, most chronic kidney disease patients did not have data of bone mineral density before the recommendation of Kidney Disease: Improving Global Outcomes (KDIGO) guideline. The correlation of the CKD-MBD and osteoporosis was not fully elucidated. Also, the effect of a multifaceted intervention on those having both diseases was less studied. Aims: To observe the clinical outcomes and the trends of biochemistry laboratory data before and after the multifaceted intervention Method: Sixty subjects with chronic kidney disease stage 3-4, and estimated glomerular filtration rate >20 mL/min/1.73m2 and high risk of fracture (FRAX screening: risk of hip fracture (HF) and major osteoporotic fracture (MOF) (HF: men>6%, women >7%; MOF: men>15%, women>12.5%) are enrolled. Subjects received CKD-MBD and osteoporosis-related assessments, treatments, consultation on diet, medications, exercise. Followed assessments and interventions are conducted every 3 months. Primary outcomes include one-year mortality, cardiovascular events, subsequent fracture, and fall events during the one-year intervention. Secondary outcomes include trends of biochemistry laboratory data before and after interventions.

Official Title
-----------------
The Effect of Multi-faceted Intervention on Osteoporosis and Mineral and Bone Disorder (CKD-MBD)

Conditions
-----------------
Osteoporosis, Postmenopausal

Intervention / Treatment
-----------------
* Behavioral: diet and exercise suggestion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 50 years Chronic kidney disease stage 3-4, and estimated glomerular filtration rate > 20 mL/min/1.73m2 Fracture Risk Assessment Tool (FRAX®) screening: risk of hip fracture (HF) and major osteoporotic fracture (MOF) (HF: men > 6%, women > 7%; MOF: men > 15%, women > 12.5%). Have ability to sign inform consent and agree with being follow-up for one year. Exclusion Criteria: Have cancer under treatment. Have acute coronary syndrome (unstable angina, non ST-elevation myocardial infarction, ST-segment elevation myocardial infarction) or stroke in 3 months. (ST segment is the flat, isoelectric section of the ECG between the end of the S wave and the beginning of the T wave.) Limited cognitive or physical function for execute the intervention.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Behavior Intervention and Pharmacological Therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: behavior intervention and pharmacological therapy<br>For participants with abnormal biochemical markers, pharmacological therapy and diet modification are applied. Dietary education on phosphorus additives is applied specifically for retention of phosphorus or high serum phosphorus level. Exercise for bone and cardiovascular health. Osteoporosis medications are initiated according to the reimbursed criteria of National Health Insurance, otherwise medications are used with non-insurance payment. | Behavioral: diet and exercise suggestion<br>* diet and exercise suggestion according to blood biochemistry data and bone mineral density<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality, After Behavior Intervention and Pharmacological Therapy in Study Time Frame | A measure of the number of deaths in the participants with intervention during January 1, 2020 to December 31, 2020. The mortality rate was calculated in percentage by the number of deaths during study period/all participants. First participant was enrolled on February 14, 2020. The study was terminated in December 31, 2020. | Through study termination, up to 45 weeks | 
| Number of Participants With New-onset Cardiovascular Events After Behavior Intervention and Pharmacological Therapy in Study Time Frame | A measure of cardiovascular events of participants with intervention in January 1, 2020 to December 31, 2020. It included acute coronary syndrome and acute stroke. The cardiovascular event rate was calculated in percentage by the number of participants who had a new-onset of the cardiovascular event during study period/all participants. First participant was enrolled on February 14, 2020. The study was terminated in December 31, 2020. | Through study termination, up to 45 weeks | 
| Number of Participants With New-onset Fragility Fracture After Behavior Intervention and Pharmacological Therapy in Study Time Frame | New fracture was measured by participants' history and medical record of participants in January 1, 2020 to December 31, 2020. Subsequent fragility fracture rate was calculated in percentage by number of participants who had a new-onset of fragility fracture during study period/all participants. First participant was enrolled on February 14, 2020. The study was terminated in December 31, 2020. | Through study termination, up to 45 weeks | 
| Number of Fall Events After Behavior Intervention and Pharmacological Therapy in Study Time Frame | Fall episodes was measured by participants' history and medical record of participants in January 1, 2020 to December 31, 2020. Fall rate was calculated in percentage by number of participants who had a new-onset of fall events during study period/all participants. First participant was enrolled on February 14, 2020. The study was terminated in December 31, 2020. | Through study termination, up to 45 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
osteoporosis, chronic kidney disease, mineral-bone disorder