Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration
Primary Purpose
Postmenopausal Osteoporosis
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Teriparatide
Denosumab
Sponsored by
About this trial
This is an interventional other trial for Postmenopausal Osteoporosis focused on measuring osteoporosis, histomorphometry, bone density, teriparatide, denosumab
Eligibility Criteria
Inclusion Criteria:
- women aged 45+
- postmenopausal
- osteoporotic with high risk of fracture
Exclusion Criteria:
- significant previous use of bone health modifying treatments
- known congenital or acquired bone disease other than osteoporosis
- significant renal disease, liver disease, cardiopulmonary disease, or psychiatric disease
- abnormal calcium or parathyroid hormone level
- serum vitamin D <20 ng/mL or >60ng/mL
- serum alkaline phosphatase above upper normal limit with no explanation
- anemia (hematocrit <32%)
- history of malignancy (except non-melanoma skin carcinoma), radiation therapy, or gouty arthritis
- history of urolithiasis within the last one year
- excessive alcohol use or substance abuse
- use of oral or parenteral glucocorticoids for more than 14 days within the past 6 months
- extensive dental work involving extraction or dental implant within the past or upcoming 2 months
- known sensitivity to mammalian cell-derived drug products
- known contraindications to denosumab, teriparatide, or any of their excipients
- known contraindications to tetracycline, demeclocycline, or other antibiotics in this drug class
- continuous use of tetracycline for >1-month duration within the last 10 years
Sites / Locations
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Teriparatide only
Denosumab only
Denosumab and teriparatide
Arm Description
daily subcutaneous injection teriparatide for 3 months
one dose of subcutaneous injection denosumab
daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab
Outcomes
Primary Outcome Measures
Cancellous Bone Formation Rate at Month 3
Cancellous bone formation rate at month 3 is calculated from the cancellous (trabecular) compartment of the iliac crest bone biopsy specimens.
Bone formation rate (BFR/BS, mm3/mm2/day): amount of new bone formed in unit time per unit of bone surface. It is calculated by multiplying the mineralizing surface/bone surface (MS/BS) by the mineral apposition rate (MAR) - see below for how MS/BS and MAR are calculated.
Mineralizing surface (MS/BS, %): is the percent of bone surface that displays a tetracycline label reflecting active mineralization. It is calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface. It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling.
Mineral apposition rate (MAR mm/day): is the mean distance between the double labels, divided by the time interval between them.
Secondary Outcome Measures
Full Information
NCT ID
NCT04026256
First Posted
July 17, 2019
Last Updated
August 1, 2023
Sponsor
Massachusetts General Hospital
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
1. Study Identification
Unique Protocol Identification Number
NCT04026256
Brief Title
Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration
Official Title
Mechanisms Underlying the Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
September 2, 2019 (Actual)
Primary Completion Date
April 18, 2022 (Actual)
Study Completion Date
April 18, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to examine, via iliac crest bone biopsies, the mechanism of combined teriparatide and denosumab on the bone of postmenopausal osteoporotic women after 3 months of treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postmenopausal Osteoporosis
Keywords
osteoporosis, histomorphometry, bone density, teriparatide, denosumab
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Teriparatide only
Arm Type
Active Comparator
Arm Description
daily subcutaneous injection teriparatide for 3 months
Arm Title
Denosumab only
Arm Type
Active Comparator
Arm Description
one dose of subcutaneous injection denosumab
Arm Title
Denosumab and teriparatide
Arm Type
Active Comparator
Arm Description
daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab
Intervention Type
Drug
Intervention Name(s)
Teriparatide
Other Intervention Name(s)
Forteo
Intervention Description
teriparatide daily subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Denosumab
Other Intervention Name(s)
Prolia
Intervention Description
denosumab subcutaneous injection
Primary Outcome Measure Information:
Title
Cancellous Bone Formation Rate at Month 3
Description
Cancellous bone formation rate at month 3 is calculated from the cancellous (trabecular) compartment of the iliac crest bone biopsy specimens.
Bone formation rate (BFR/BS, mm3/mm2/day): amount of new bone formed in unit time per unit of bone surface. It is calculated by multiplying the mineralizing surface/bone surface (MS/BS) by the mineral apposition rate (MAR) - see below for how MS/BS and MAR are calculated.
Mineralizing surface (MS/BS, %): is the percent of bone surface that displays a tetracycline label reflecting active mineralization. It is calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface. It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling.
Mineral apposition rate (MAR mm/day): is the mean distance between the double labels, divided by the time interval between them.
Time Frame
3 months after first dose of study drug
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
women aged 45+
postmenopausal
osteoporotic with high risk of fracture
Exclusion Criteria:
significant previous use of bone health modifying treatments
known congenital or acquired bone disease other than osteoporosis
significant renal disease, liver disease, cardiopulmonary disease, or psychiatric disease
abnormal calcium or parathyroid hormone level
serum vitamin D <20 ng/mL or >60ng/mL
serum alkaline phosphatase above upper normal limit with no explanation
anemia (hematocrit <32%)
history of malignancy (except non-melanoma skin carcinoma), radiation therapy, or gouty arthritis
history of urolithiasis within the last one year
excessive alcohol use or substance abuse
use of oral or parenteral glucocorticoids for more than 14 days within the past 6 months
extensive dental work involving extraction or dental implant within the past or upcoming 2 months
known sensitivity to mammalian cell-derived drug products
known contraindications to denosumab, teriparatide, or any of their excipients
known contraindications to tetracycline, demeclocycline, or other antibiotics in this drug class
continuous use of tetracycline for >1-month duration within the last 10 years
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Leder, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration
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