Mechanisms Underlying the Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration
Overview
- Phase
- Phase 4
- Intervention
- Teriparatide
- Conditions
- Postmenopausal Osteoporosis
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Cancellous Bone Formation Rate at Month 3
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Benjamin Leder, MD
Principal Investigator
Massachusetts General Hospital
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
Arms & Interventions
Teriparatide only
daily subcutaneous injection teriparatide for 3 months
Intervention: Teriparatide
Denosumab only
one dose of subcutaneous injection denosumab
Intervention: Denosumab
Denosumab and teriparatide
daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab
Intervention: Teriparatide
Denosumab and teriparatide
daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab
Intervention: Denosumab
Outcomes
Primary Outcomes
Cancellous Bone Formation Rate at Month 3
Time Frame: 3 months after first dose of study drug
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.