Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration

Study Overview
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Brief Summary
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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.

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

Conditions
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Postmenopausal Osteoporosis

Intervention / Treatment
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* Drug: Teriparatide
* Drug: Denosumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Teriparatide only<br>daily subcutaneous injection teriparatide for 3 months | Drug: Teriparatide<br>* teriparatide daily subcutaneous injection<br>* Other names: Forteo;|
| Active Comparator: Denosumab only<br>one dose of subcutaneous injection denosumab | Drug: Denosumab<br>* denosumab subcutaneous injection<br>* Other names: Prolia;|
| Active Comparator: Denosumab and teriparatide<br>daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab | Drug: Teriparatide<br>* teriparatide daily subcutaneous injection<br>* Other names: Forteo;Drug: Denosumab<br>* denosumab subcutaneous injection<br>* Other names: Prolia;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoporosis, histomorphometry, bone density, teriparatide, denosumab