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

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.

Conditions

• Hyperparathyroidism; Secondary, Renal

Interventions

DRUG

Cinacalcet Tablets

All study subjects were treated with a fixed dose of oral Cinacalcet (25 mg/day) from baseline to 6 months.

DRUG

calcitriol

All hyperparathyroidism were treated as traditional therapy with oral calcitriol 0.25 mcg(dosage according to IPTH serum level) from baseline to 6 months.

Sponsors & Collaborators

• Taipei Medical University Shuang Ho Hospital

  collaborator OTHER

• Taipei Medical University

  collaborator OTHER

• En Chu Kong Hospital

  collaborator OTHER

• National Taiwan University

  collaborator OTHER

• Taichung Tzu Chi Hospital

  collaborator OTHER

• Min-Sheng General Hospital

  lead OTHER

Principal Investigators

• Ren-Si Syu, Dr. · Min-Sheng General Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-01-01

Primary Completion

2018-12-31

Completion

2020-06-30

Countries

• Taiwan

Study Locations