Bone Markers and Bone Density Changes in Hyperperparathyroid Dialysis Patients Under Cinacalcet Treatment

• Status: Completed
• Trial end date: 2020-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Chronic kidney disease related mineral and bone disorders (CKD-MBDs) and secondary hyperparathyroidism (SHPT) are observed in most patients with chronic kidney disease on dialysis (CKD-5D). The original use of the calcimimetic cinacalcet in these patients was to reduce the elevated parathyroid hormone (PTH) levels; however, subsequent clinical studies consistently confirmed its beneficial effects on mineral disturbances and bone disease. Although many mechanisms proposed, its specific mechanisms underlying the bone disease is still unclear. Recently, Wnt signaling and their inhibitors were proposed to involve in fine control of osteoclast-to-osteoblast cross-talk. In previous study, investigators explore the changes in Wnt 10b in bone microenvironment after addition of calcimimetic cinacalcet using in vitro osteoclasts. In vitro results were confirmed in 5/6 nephrectomy mice, which were grouped into control, with cinacalcet and without cinacalcet groups. From in-vitro study, investigators found cinacalcet increase mineralization; enhance osteoclast apoptosis, which probably work as osteoclast-osteoblast cross talk for bone formation. Similar results were found in-vivo animal study, and the micro-CT of cinacalcet treated CKD animals revealed a significantly decrease in cortical porosity. On the basis of our in-vitro and animal study, investigators propose that cinacalcet have definitive role on bone turnover marker and bone density changes among SHPT dialysis patients.

Methods: Our study includes 50 hyperparathyroid dialysis patients using cinacalcet from 1st Dec 2017 to 31 Oct 2018. Investigators will exclude post-menopausal female subjects. Enzyme-linked immunosorbent assay and Western blot analysis will be done for bone turnover markers (TRACP，Alk-P，S1P，BMP6，Wnt，10B，16，SOST，P1NP，PDGF BB，HGF and CTHRC1, etc.). Bone mineral density will be determined by dual-energy X-ray absorptiometry (DXA). Plasma fibroblast growth factor (FGF-23), Ca 2+ , P 3+ , calcium-phosphorus product and parathyroid hormone will also be measured. Data will be collected and analyzed the differences between baseline measures and 4 weekly and follow up for 6 months after the treatment. Control group that we enrolled 30 hyperparathyroid dialysis patients using traditional therapy active vitamin D without use cinacalcet.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Min-Sheng General Hospital
• Collaborators: En Chu Kong Hospital; National Taiwan University; Taichung Tzu Chi Hospital; Taipei Medical University; Taipei Medical University Shuang Ho Hospital
• Treatments: Calcitriol; Cinacalcet

Criteria

Inclusion Criteria:

1. 20 - 80 yrs of age and eligible for consent

2. Hyperparathyroid (iPTH>300 pg/mL) regular dialysis patients using cinacalcet and start the treatment during the study period.

Exclusion Criteria:

1. <20yrs or >80yrs patients

2. Post-menopausal female patients

3. Malignancies, inflammatory or infectious disease < 3 months

4. Pregnancy

5. Severe malnutrition

6. Surgical intervention < 3 months

7. Acute myocardial infarction, unstable angina, cerebrovascular disease or transient ischemic attack, deep vein thrombosis, pulmonary embolism, congestive heart failure < 3months.