Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration

Mechanisms Underlying the Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration

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.

Study Overview

• Status: Completed
• Conditions: Postmenopausal Osteoporosis
• Intervention / Treatment: Drug: Teriparatide; Drug: Denosumab

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Teriparatide only; daily subcutaneous injection teriparatide for 3 months	Drug: Teriparatide; teriparatide daily subcutaneous injection; Other Names: Forteo
Active Comparator: Denosumab only; one dose of subcutaneous injection denosumab	Drug: Denosumab; denosumab subcutaneous injection; Other Names: Prolia
Active Comparator: Denosumab and teriparatide; daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab	Drug: Teriparatide; teriparatide daily subcutaneous injection; Other Names: Forteo; Drug: Denosumab; denosumab subcutaneous injection; Other Names: Prolia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 months after first dose of study drug

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: Benjamin Leder, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2019
• Primary Completion (Actual): April 18, 2022
• Study Completion (Actual): April 18, 2022

Study Registration Dates

• First Submitted: July 17, 2019
• First Submitted That Met QC Criteria: July 17, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: bone density; osteoporosis; histomorphometry; teriparatide; denosumab
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Teriparatide; Denosumab
• Other Study ID Numbers: 2018P002537; 5R01AR073191-04 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No