Effect of Atorvastatin on Bone-vascular Axis
Primary Purpose
Osteoporosis, Hypercholesterolemia
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Atorvastatin
Sponsored by
About this trial
This is an interventional basic science trial for Osteoporosis
Eligibility Criteria
Inclusion Criteria:
- Newly diagnosed osteoporosis (T score ≤ -2.5 SD at either the lumbar spine or femoral neck)
- LDL-cholesterol ≥ 130 mg/dl
Exclusion Criteria:
- History of bone fractures,
- Clinical evidence of atherosclerotic disease
- CKD (stage III-V),
- Liver disease
- COPD
- Rheumatic disorders;
- Current or previous treatment with statins, steroids, hormonal replacement therapies, and antiosteoporotic drugs (including vitamin D and calcium supplementation)
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Atorvastatin
Arm Description
Atorvastatin 40 mg/day for three months
Outcomes
Primary Outcome Measures
Relative Change in OPG/RANK/RANKL mRNA Expression in Isolated T Cells and Monocytes
Isolated T cells and monocytes will be obtained at baseline and at the end of the treatment period. Gene expression analysis will be performed in each cell type to assess the expression level of OPG, RANK, and RANKL at baseline and after three months of treatment.
Change in Circulating Levels of Osteoprogenitor Cells (CD34+/OCN+/BAP+ Cells)
Circulating levels of osteoprogenitor cells (CD34+/OCN+/BAP+ cells) will be measured by FACS analysis in each patient at baseline and after three months of treatment with Atorvastatin.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02342015
Brief Title
Effect of Atorvastatin on Bone-vascular Axis
Official Title
Effect of Atorvastatin on OPG/RANK/RANKL Expression in Immune Cells and Circulating Levels of Osteoprogenitor Cells
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
November 2012 (Actual)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Padova
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Background: Circulating osteoprogenitors and RANKL expression in immune cells have been implicated in the pathogenesis of osteoporosis and vascular calcification. The role played by statin therapy in the bone-vascular axis is unknown.
Methods: Twenty naïve post-menopausal osteoporotic hypercholesterolemic women will be treated with Atorvastatin 40 mg/day for three months. Blood samples will be collected at baseline and at the end of the treatment. Gene expression analysis will be performed to assess modification in OPG/RANK/RANKL expression in isolated T-cells and monocytes. A flow cytometry analysis will be used to study changes in the levels of circulating osteoprogenitor cells.
Detailed Description
Background: A considerable number of clinical studies have shown that osteoporosis carries a significant increase in cardiovascular risk. Although the pathophysiological substrate of the so-called bone-vascular axis is still elusive, an important role is attributed to the OPG/RANK/RANKL triad, a master regulator of bone remodeling. In addition, circulating osteoprogenitors have been recently described as a new subset of immature cells harbouring pro-calcific potential in the vasculature and heart valves. Nevertheless, a number of studies indicated that the accumulation of lipid oxidation products within the skeleton may contribute to pathological bone resorption, mainly through the inhibition of osteoblast differentiation and the induction of osteoclast maturation/activation. Starting from these notions, we sought to investigate whether treatment with Atorvastatin can affect circulating levels of osteo-progenitor cells and OPG/RANK/RANKL expression in T cells and monocytes in hypercholesterolemic postmenopausal osteoporotic women.
Methods: We will enrol 20 consecutive hypercholesterolemic (LDL-C ≥130 mg/dL) women with newly diagnosed osteoporosis who refer to the Osteoporosis and Bone Metabolism Unit of the Cà Foncello Hospital in Treviso. Diagnosis of osteoporosis was based on T-score ≤2.5 SD at either the lumbar spine or femoral neck. All patients will receive Atorvastatin 40 mg/day for 3 months. Blood samplings will be performed at the time of enrolment and at the end of the treatment period. During the study, the patients will not be treated with calcium, vitamin D, and bisphosphonates. We will exclude women with clinical judgment of high risk of bone fracture. At the beginning of the study and after 3 months, serum samples will be collected to assess the lipid profile (total cholesterol [TC], LDL-C, HDL-C, triglycerides [TG]), level of hs-CRP, osteocalcin (OCN), bone alkaline phosphatase (BAP), cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I), and OPG. Blood samples at enrolment and after three months will be also obtained to quantify circulating osteoprogenitor cells (flow cytometry) and gene expression of OPG/RANK/RANKL in mononuclear cells (RT-PCR).
Flow cytometry analysis (FACS): identification and quantification of circulating osteoprogenitor cells will be performed using polychromatic flow cytometry. Briefly, after red blood cell lysis, peripheral blood progenitor cells will be analysed for the surface expression of CD34, OCN and BAP using Fitc-conjugated anti-human CD34, PE-conjugated anti-human OCN, and APC-conjugated anti-human BAP.
Gene expression analysis: pure and viable monocytes and T cells will be obtained from blood samples by negative isolation using Dynabeads Untouched Human Monocytes and Dynabeads Untouched Human T cells respectively. Total RNA from both cell types will be collected using and stored at -80°Cuntil analysis. The levels of RANK, RANKL, and OPG transcripts will be then quantified by real-time PCR .
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis, Hypercholesterolemia
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Atorvastatin
Arm Type
Experimental
Arm Description
Atorvastatin 40 mg/day for three months
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Other Intervention Name(s)
Lipitor
Intervention Description
Atorvastatin 40mg/day for three months
Primary Outcome Measure Information:
Title
Relative Change in OPG/RANK/RANKL mRNA Expression in Isolated T Cells and Monocytes
Description
Isolated T cells and monocytes will be obtained at baseline and at the end of the treatment period. Gene expression analysis will be performed in each cell type to assess the expression level of OPG, RANK, and RANKL at baseline and after three months of treatment.
Time Frame
3 months
Title
Change in Circulating Levels of Osteoprogenitor Cells (CD34+/OCN+/BAP+ Cells)
Description
Circulating levels of osteoprogenitor cells (CD34+/OCN+/BAP+ cells) will be measured by FACS analysis in each patient at baseline and after three months of treatment with Atorvastatin.
Time Frame
3 months
10. Eligibility
Sex
Female
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Newly diagnosed osteoporosis (T score ≤ -2.5 SD at either the lumbar spine or femoral neck)
LDL-cholesterol ≥ 130 mg/dl
Exclusion Criteria:
History of bone fractures,
Clinical evidence of atherosclerotic disease
CKD (stage III-V),
Liver disease
COPD
Rheumatic disorders;
Current or previous treatment with statins, steroids, hormonal replacement therapies, and antiosteoporotic drugs (including vitamin D and calcium supplementation)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcello Rattazzi, MD
Organizational Affiliation
University of Padova, Department of Medicine
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Effect of Atorvastatin on Bone-vascular Axis
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