Bone Markers and Bone Density Changes in Hyperperparathyroid Dialysis Patients Under Cinacalcet Treatment
Status:
Completed
Trial end date:
2020-06-30
Target enrollment:
Participant gender:
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
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