Activity of Pre-Osteoclasts and Osteoclasts Over Time in Postmenopausal Women Treated With Denosumab or Zoledronic Acid

NCT03812367 | Withdrawn

• 1 other identifier: 1030286
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates how patients treated with denosumab or zoledronic acid for osteoporosis may change the number of peripheral osteoclast precursors and osteoclast activity, and how that may be associated with changes in bone mass.

Conditions

Osteoporosis, Postmenopausal

Outcome Measures

Primary Outcomes (5)

• Percent change in osteoclast circulation

  Percent change (%Δ) from baseline in number of circulating osteoclast precursor cells by FACS analysis

  1 month, 6 months, 12 months

• Percent change in osteoclast maturation and activity

  Percent change (%Δ) in osteoclast maturation and activity, as assessed by resorption on dentin slides and expression of genes critical for osteoclast differentiation

  1 month, 6 months, 12 months

• Percent change in number of TRAP cells

  Percent change (%Δ) from baseline in the number of tartrate-resistant acid phosphatase (TRAP)+cells with 3 or mor nuclei by in vitro maturation

  1 month, 6 months, 12 months

• Percent change in bone mass density

  Percent change (%Δ) from baseline in BMD at the total hip and lumbar spine

  1 month, 6 months, 12 months

• Percent change in bone turnover markers

  Percent change (% Δ) from baseline in bone turnover markers C-telopeptide of type 1 collagen (CTX) and procollagen type 1 propeptide (P1NP)

  1 month, 6 months, 12 months

Study Arms (4)

Group 1

The denosumab naïve group

Group 2

The zoledronic acid naïve group

Group 3

The chronic denosumab (\> 1 year with at least 3 biannual injections)

Group 4

The chronic zoledronic acid (≥2 years with at least 2 annual injections)

Eligibility Criteria

• Age: 50 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women aged \> 50 with diagnosis of osteoporosis.

You may qualify if:

• Women at least 50 years of age who are postmenopausal. Postmenopausal is defined as being amenorrheic for at a period of at least 12 months.
• Diagnosis of osteoporosis by T score of \< -2.5 at either lumbar spine or the hip/femoral neck, or osteopenia that qualifies for treatment by FRAX calculation (10-year risk of hip fracture \> 3% and/or major osteoporotic fracture of \> 20%).
• a. Subjects who have had chronic treatment of denosumab (as defined as \> 1 year \[at least 3 6-monthly injections\]) or zoledronic acid (defined as ≥ 2 years \[at least 2 annual injections\]) . Note: At the time of treatment initiation, subjects must have met criteria for on-label use (e.g. criterion 2 above).
• OR 3b. Subjects who are naïve to treatment with denosumab and/or zoledronic acid.

You may not qualify if:

• Renal insufficiency, with glomerular filtration rate (GFR) \< 35 ml/min.
• Hypocalcemia within 6 months of study initiation.
• Known hypersensitivity to denosumab or zoledronic acid.
• Medications that could alter bone turnover including prednisone, anti-rheumatic medications, anti-metabolites (Cytoxan). Subjects who have been on stable doses of thyroid replacement or diabetes medications for more than 3 months are eligible.
• Evidence of untreated oral cavities or oral infections. Preventative dental exams should be performed before starting denosumab or zoledronic acid. Subjects must avoid invasive dental procedures during treatment with denosumab or zoledronic acid.

Sponsors & Collaborators

• University of California, Davis: lead
• Amgen: collaborator

Study Sites (1)

UC Davis Health, Center for Musculoskeletal Health

Sacramento, California, 95817, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood specimens

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Nancy Lane, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: January 23, 2019
• Study Start: January 1, 2019
• Primary Completion: June 1, 2021
• Study Completion: December 31, 2021
• Last Updated: June 14, 2019

Record last verified: 2019-06

Locations

US (1)