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Comparative Effect of Zoledronic Acid Versus Denosumab on Serum Sclerostin of Postmenopausal Women With Low Bone Mass (DenoZol)

This study has been completed.
Sponsor:
Collaborators:
424 General Military Hospital
251 Hellenic Air Force Hospital
Information provided by (Responsible Party):
Stergios A. Polyzos, MD, MSc, PhD, Aristotle University Of Thessaloniki
ClinicalTrials.gov Identifier:
NCT01572545
First received: April 3, 2012
Last updated: January 15, 2013
Last verified: January 2013
History of Changes
  Purpose

The primary aim of the study is the comparative effect of zolendronic acid versus denosumab on serum sclerostin levels in postmenopausal women with low bone mass.

Secondary aims are their comparative effect on serum dickkopf-1, osteoprotegerin, receptor activator of nuclear factor kappaB ligand (RANKL) and bone turnover markers (procollagen type I N-terminal peptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]).


Condition Intervention
Postmenopausal Osteoporosis
 Drug: Denosumab
Drug: Zoledronic acid

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparative Effect of Zoledronic Acid Versus Denosumab on Serum Sclerostin Levels of Postmenopausal Women With Low Bone Mass: A Multicenter, Randomized, Head-to-head Clinical Trial

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Aristotle University Of Thessaloniki:

Primary Outcome Measures:
  • Sclerostin [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Serum sclerostin levels


Secondary Outcome Measures:
  • Dickkopf-1 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Serum dickkopf-1 (DKK-1) levels

  • OPG/RANKL [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Serum osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) levels

  • Calcium metabolism [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Serum calcium, phosphate, intact parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25OHD)

  • Bone turnover [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Serum bone turnover markers (total alkaline phosphatase [TSAP], type I N-terminal peptides [PINP] και C-terminal cross-linking telopeptide of type I collagen [CTX])


Enrollment: 91
Study Start Date: April 2012
Study Completion Date: January 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denosumab Drug: Denosumab
Denosumab (injection), 60 mg, administered as a single subcutaneous injection once
Other Name: Prolia
Experimental: Zoledronic Acid Drug: Zoledronic acid
Zoledronic acid (vial), 5 mg, administered once as a single 15- to 30-minute intravenous infusion
Other Name: Aclasta

Detailed Description:

Osteoporosis is the most common bone disease, caused by a relatively increased rate of bone resorption by the osteoclasts that exceeds the rate of bone formation by the osteoblasts, resulting in net loss of bone mass. To-date, antiresorptive agents, which inhibit osteoclast activity and induce their apoptosis, are considered as the cornerstone of osteoporosis prevention and treatment.

Bisphosphonates currently represent the first line antiresorptive agents for the management of postmenopausal osteoporosis. Zoledronic acid is considered to-date the most potent bisphosphonate. A once-yearly infusion of intravenous zoledronic acid decreases bone turnover, improves bone density and decreases the vertebral and non-vertebral fracture risk.

Most recently, denosumab (AMG-162) has been launched for the treatment of postmenopausal osteoporosis. Denosumab, a fully human monoclonal IgG2 antibody against human RANKL, specifically binds and neutralizes the receptor activator of nuclear factor kappaB ligand (RANKL) in order to decrease bone resorption and subsequent bone loss. Subcutaneous administration of denosumab every six months decreases bone turnover markers, increases bone mineral density and reduces the vertebral and non-vertebral fracture risk.

The role of sclerostin in bone metabolism is emerging. Sclerostin is the secreted expression of the SOST gene. In adult human bone, sclerostin is expressed only by osteocytes and inhibits bone formation by osteoblasts. It has been proposed that sclerostin expression by newly embedded osteocytes at the onset of osteoid mineralization may serve as a negative feedback signal on osteoblasts to prevent overfilling of the basic multicellular unit.

Although zoledronic acid and denosumab are currently regarded as the most potent antiresorptive agents, there is no head-to-head comparative study. This study primarily aims to the comparative effect of zoledronic acid and denosumab on serum sclerostin levels and secondarily on serum dickkopf-1, osteoprotegerin, RANKL and bone turnover markers (procollagen type I N-terminal peptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]).

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Caucasian postmenopausal women older than 40 years
  • Low bone mass at lumbar spine (L2-L4) or femoral neck (BMD T-score of ≤ -2.0) or BMD T-score of > -2.0 coexistent with low-energy fracture of vertebral, femoral neck or forearm
  • Patient's informed consent to participate

Exclusion Criteria:

  • Secondary osteoporosis
  • Any bone and mineral disorder other than osteoporosis, including primary or secondary hyperparathyroidism, Paget's disease of bone, osteogenesis imperfecta, rheumatologic diseases, paraplegia, chronic immobilization
  • Severe liver or kidney disease (creatinine clearance < 60ml/min/1.73m2) or liver or kidney transplantation
  • Premature ovarian failure
  • Uncontrolled thyroid disease
  • Any malignancy
  • Any musculoskeletal injury or surgical procedure 6 months prior to baseline
  • Dental surgery or teeth removed 3 months prior to baseline or plan to
  • History or concomitant medications that could affect bone metabolism, including immunosuppressive, anticonvulsant, antiviral and anti-tuberculosis agents, addictive drugs, corticosteroids, non-steroidal anti-inflammatory drugs, amiodarone, thiazolidinediones, interferon, metronidazole, and tamoxifen
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01572545

Locations
Greece
251 Hellenic Air Force Hospital
Athens, Attikis, Greece
Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital
Thessaloniki, Greece
424 General Military Hospital
Thessaloniki, Greece
Sponsors and Collaborators
Aristotle University Of Thessaloniki
424 General Military Hospital
251 Hellenic Air Force Hospital
Investigators
Principal Investigator: Stergios A Polyzos, MD, MSc, PhD Aristotle University Of Thessaloniki
Principal Investigator: Athanasios D Anastasilakis, MD, PhD 424 General Military Hospital
Principal Investigator: Polyzois Makras, MD, PhD 251 Hellenic Air Force Hospital
  More Information

Publications:

Responsible Party: Stergios A. Polyzos, MD, MSc, PhD, Principal Investigator, Aristotle University Of Thessaloniki
ClinicalTrials.gov Identifier: NCT01572545     History of Changes
Other Study ID Numbers: PolyzosAnastasilakis
Study First Received: April 3, 2012
Last Updated: January 15, 2013
Health Authority: Greece: Ethics Committee

Keywords provided by Aristotle University Of Thessaloniki:
bone turnover
denosumab
postmenopausal osteoporosis
sclerostin
zolendronic acid

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
 Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013