The Treatment of Osteoporosis Using a Combination of Teriparatide (Forteo) and Denosumab

Study Overview
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Brief Summary
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This is a three-year study to evaluate the effect of sequential therapy of Forteo (teriparatide) and denosumab on bone density at the spine, hip, leg and forearm.

Detailed Description
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In order to maximize the early anabolic effect with teriparatide (TPTD), and to avoid the development of tachyphylaxis to the continued daily administration of TPTD beyond 6 months, cyclic therapy might be optimal. Since Denosumab (Prolia) is a potent antiresorptive agent with a rapid off-effect, it might be the optimal agent to help maximize bone gains with cyclic TPTD/antiresorptive therapy. Our primary hypothesis is that the increment in bone density of the spine by DXA will be greater in women randomized to receive the cyclic sequential regimen (three separate 6 month cycles of daily subcutaneous TPTD, each followed by one subcutaneous injection of Denosumab) compared with daily sequential therapy (18 months of daily subcutaneous TPTD followed by Denosumab therapy for 18 months).

Official Title
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The Treatment of Osteoporosis Using a Combination of Teriparatide (Forteo) and Denosumab

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Standard Clinical Practice Regimen
* Drug: Experimental Cyclic Regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Subjects should be postmenopausal >age 45, and of any racial origin. They must not be on any osteoporosis medication. They should be willing to participate for the duration of the study and have no physical or psychological illness that would prohibit them from participating. Pregnant women, protected individuals (institutionalized), and those unable to give informed consent will not be recruited. Exclusion criteria are detailed below. Subjects who meet initial pre-screening criteria will present for an on site screening visit and have a full medical history, brief physical exam, BMD and lab evaluation to confirm eligibility. Osteoporosis will be defined by DXA BMD T-Score < -2.5 at lumbar spine (at least 2 evaluable vertebrae between L1 and L4), or total hip or femoral neck. In addition, women with confirmed vertebral deformity on radiograph or lateral DXA image, or prior osteoporosis-related fracture at age >45 along with a DXA BMD T-Score < -1.5 at one or more skeletal sites will be eligible to participate. Exclusion Criteria: The use of drugs known to affect skeletal or calcium homeostasis. Multiple vertebral fractures or severe lumbar degenerative changes with fewer than 2 evaluable lumbar vertebrae Current use of anti-resorptive medicines Use of Hormone/Estrogen Therapy, raloxifene or calcitonin within the past 3 months Use of oral bisphosphonate for more than 4 months within the past 2 years or more than 5 years total cumulative bisphosphonate use in the past 10 years Use of intravenous ibandronate within the past 18 months Use of intravenous zoledronic acid within the past 4 years A history of a symptomatic renal stone within the past 3 years or history of multiple symptomatic renal stones Skeletal Disorders other than osteoporosis including: Hypercalcemia, hyperparathyroidism, Paget's Disease or osteomalacia Untreated or uncontrolled thyroid disease Elevated Bone Specific Alkaline Phosphatase level History of external or internal radiation therapy Renal insufficiency with estimated GFR below 30 ml/min Liver function tests (ALT/AST) more than 1.5 times the upper limit of normal Clinically significant hyperuricemia or active gout Any contraindications to receipt of Teriparatide or Denosumab (including hypocalcemia) History of an atypical fracture of the femoral shaft

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Clinical Practice Regimen<br>Standard Clinical Practice (Daily) Regimen: 18 months of daily subcutaneous Forteo followed by denosumab therapy for 18 months (18 months of Forteo then 3 injections of Prolia at 18, 24 and 30 months). | Drug: Standard Clinical Practice Regimen<br>* Standard Clinical Practice Regimen<br>* Other names: 18 months Forteo followed by 18 months Prolia;|
| Experimental: Experimental (cyclic) regimen<br>Experimental (Cyclic) Regimen: three separate 6-month cycles of daily subcutaneous Forteo, each followed by one subcutaneous injection of Prolia (Forteo from 0 to 6 months, and then from 12 to 18 months and then from 24 to 30 months, for a total dose of 18 months; 3 injections of Prolia at 6, 18 and 30 months). | Drug: Experimental Cyclic Regimen<br>* Experimental Cyclic Regimen<br>* Other names: three separate 6 month cycles of daily Forteo, each followed by one of Prolia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| spine bone density |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bone mineral density of the hip, wrist, total body and lateral spine and CT of arm and leg | Bone mineral density testing of multiple skeletal sites and peripheral QCT with high resolution of the leg and arm | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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teriparatide, Forteo, Denosumab, Prolia, bone density, treatment