Denosumab in Enhancement of Bone Bonding of Hip Prosthesis in Postmenopausal Women

Study Overview
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Brief Summary
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This randomized clinical trial will evaluate the efficacy of an antiresorptive osteoporosis drug (denosumab) in prevention of periprosthetic bone loss and in promotion of implant osseointegration (bone bonding) in postmenopausal women after total hip replacement. The investigators assume that denosumab prevents periprosthetic bone loss and enhances bone bonding of the hip stem in postmenopausal women.

Detailed Description
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This is a randomized, double-blind and placebo-controlled trial to evaluate the efficacy of denosumab on the biologic incorporation of cementless hip prosthesis. The study population consists of sixty-eight postmenopausal female patients, who are scheduled to have cementless total hip replacement (THA) for primary hip osteoarthritis. The patients will be randomly assigned to receive a subcutaneous injection of denosumab 60 mg or placebo four weeks before surgery and 22 weeks after surgery. The primary hypothesis is that denosumab is effective in preventing periprosthetic bone loss in the proximal femur as measured by DXA. The secondary hypothesis is that denosumab is effective in enhancement of bone bonding (osseointegration) of cementless femoral stems, as measured by model-based radiostereometric analysis.

Official Title
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Denosumab in Enhancement of Bone Bonding of Hip Prosthesis in Postmenopausal Women: a Randomized, Double-blind, Placebo-controlled Study

Conditions
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Hip Osteoarthritis

Intervention / Treatment
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* Drug: Denosumb
* Drug: Placebo (for denosumab)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women, age: ≥ 60 years to ≤ 85 years at randomization Degenerative primary hip osteoarthritis as the indication of hip replacement Signed informed consent Exclusion Criteria: Presence of severe osteoporosis (T-score less than -4.0 and a previous fracture) Presence of Dorr C-type geometric change of the proximal femur Evidence of secondary osteoporosis Clinical or laboratory evidence of hepatic disease Laboratory evidence of hypocalcaemia Vitamin D deficiency (serum 25-OH(D) < 12 ng/mL) Disorders of parathyroid function Uncontrolled hyperthyroidism or hypothyroidism History of malignancy, radiotherapy or chemotherapy for malignancy (except basal cell carcinoma of the skin) within the last 5 years History of osteonecrosis of the jaw History of recent tooth extraction or other dental surgery and/or invasive dental work planned in the next 2 years Severe asthma or chronic obstructive pulmonary disease History of solid organ or bone marrow transplant Use within 12 months of drugs that affect bone metabolism such as ant-osteoporotic agents (including SERMS), estrogens, testosterone, and anti-epileptics: Cumulative dose of 500 mg prednisone or equivalent within the last 6 months Ever use of oral or iv bisphosphonates Ever use of strontium ranelate or fluoride Use of the following medications: chronic systemic ketoconazole androgens cinacalcet aluminum lithium protease inhibitors gonadotropin-releasing hormone agonists Rheumatoid arthritis or any other inflammatory arthritis History of skeletal disorder, such as Paget's disease or osteomalacia Alcohol abuse General Mental, neurological or other conditions that may affect the ability to perform functional or clinical assessments required by the protocol Subjects with known sensitivity or intolerance to any of the products to be administered (calcium and D-vitamin supplements, denosumab) Subject will not be available for protocol-required study visits, to the best of the subject's and investigator's knowledge Any other condition that, in the judgement of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab<br>Subcutaneous injection of denosumab 60 mg 4 weeks before surgery and 22 weeks after surgery | Drug: Denosumb<br>* Prefilled syringe of 1 mL denosumab solution<br>* Other names: Brand name: Prolia;|
| Placebo Comparator: Placebo<br>Subcutaneous injection of placebo 4 weeks before surgery and 22 weeks after surgery | Drug: Placebo (for denosumab)<br> <br> * Other names: Prefilled syringe of 1 mL placebo solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Periprosthetic bone mineral density (BMD) | Periprosthetic BMD of the proximal femur will be measured according to seven Gruen zones and compared with the baseline value | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiostereometric analysis (RSA) of prosthesis stem migration | The translatory and rotatory migration of the femoral stem will be measured by means of model-based RSA and compared with the position at the baseline | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Denosumab, Osteoporosis, Hip replacement, Osteoarthritis, Radiostereometric analysis (RSA), Dual energy X-ray absorptiometry (DXA)