Effects of Denosumab on Periprosthetic Bone After Total Hip Arthroplasty

Study Overview
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Brief Summary
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The primary objective is to study the effect of Denosumab on Bone Mineral Density, Standardised Uptake Value and bone metabolism in patients with total hip arthroplasty. The primary hypothesis is to demonstrate that Denosumab is superior to placebo.

Detailed Description
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A clinical study with 64 patients, age 35-65 years, with unilateral osteoarthritis of the hip, randomised to two groups of patients, either receiving Denosumab or placebo The patients will operated with an uncemented total hip arthroplasty with a Continuum acetabular cup with trabecular surface (Tantalum) and longevity Highly Cross-linked Polyethylene liner, Zimmer, Warsaw, IN, USA, and a CFP femoral stem with Titanium surface and a chrome cobalt 28 mm head, Waldemar Link, Hamburg, Germany. Clinical outcome evaluated by Harris Hip Score and EQ-5D, Bone Mineral Density by DXA, Standardised Uptake Value of Fluoride tracer, by PET/CT and biochemical markers for bone formation and bone resorption will be analyzed together with conventional radiology for implant position and fixation.

Official Title
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Uncemented Total Hip Implant and Subcutaneous Injections of Denosumab for Patients With Osteoarthritis of the Hip. A Randomized Double Blind Placebo Controlled Study on the Effects on Bone Evaluated With DXA, PET/CT and Biochemical Markers

Conditions
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Osteoarthritis, Hip, Ambulation Difficulty

Intervention / Treatment
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* Drug: denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female patient 35-65 years of age with an unilateral OAH requiring a THA and a healthy contralateral hip body weight ≤110 kg or body mass index (BMI) ≤35 kg/m2 living in the Uppsala County the eligible patients should have been given oral information, a written Patient Information and signed an Informed Consent Exclusion Criteria: on or previously have had bone-specific treatment, e.g. bisphosphonates, raloxifene, parathyroid hormone, strontium ranelate, during the last five years patients on systemical corticosteroid for more than 3 months should not be considered patients with diagnosed malignant disease during the last five years or known to have metastasis from malignant disease should be excluded patients with compromised general conditions and an American Society of Anesthesiologists, ASA-score >31 should not be regarded eligible patients with known drug or alcohol abuse or regarded as socially dysfunctional, as judged by the investigator, should not be considered for the study pregnant women or women planning for pregnancy or fertile women (premenopausal) without contraceptives should not be accepted for the study patients that have been exposed frequently and/or have had large irradiation doses, as judged by the investigator, must not be included in the study. enrolled in either another investigational drug study, in another investigational device study, or in another investigational study of an approved drug within 30 days prior to Visit 1 of the current study any condition or laboratory findings which in the opinion of the Investigator makes the patient unsuitable for inclusion (for example claustrophobia)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Denosumab<br>1 ml (60 mg) subcutaneous injection Denosumab give in the posterior part of the upper arm after surgery followed by another injection 6 months later | Drug: denosumab<br>* Two doses of 60 mg in a solution of 1 ml, given as an subcutaneous injection with a 6 month interval<br>* Other names: Prolia;|
| Placebo Comparator: saline<br>1 ml subcutaneous injection 0.9% saline give in the posterior part of the upper arm after surgery followed by another injection 6 months later | Drug: denosumab<br>* Two doses of 60 mg in a solution of 1 ml, given as an subcutaneous injection with a 6 month interval<br>* Other names: Prolia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density | Bone mineral density by DXA in Gruen Zone 7 and a sum of Gruen zone 1-7 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral Density | BMD, g/cm2, adjacent to the femur implant for Gruen Zone 1-7, 3, 6, and 24 months after surgery | 24 months | 
| Standardised Uptake value | fluoride isotope uptake, measured as (SUV), adjacent to the femoral stem, 3 and 6 months after surgery. | 6 months | 
| Standardised Uptake value | fluoride isotope uptake, measured as SUV adjacent to the acetabular cup 3 and 6 months after surgery | 6 months | 
| Bone Mineral density | BMD adjacent to the acetabular cup during the follow up period, i.e. after 3, 6, 12 and 24 months | 24 months | 
| Bone Mineral Density | BMD at the lumbar spine and at the contra lateral nonoperated hip 6, 12 and 24 months after surgery | 24 months | 
| Standardised Uptake Value | Fluoride isotope uptake measured as SUV at the lumbar spine and at the contra lateral nonoperated hip after 3 and 6 months | 6 months | 
| Biochemical markers for bone metabolism | biochemical markers for bone turnover and the relation to SUV and BMD findings at the proximal femur and acetabulum during the follow up period, i.e. 3, 6, 12 and 24 months after surgery | 24 months | 
| Biochemical markers for bone metabolism in relation to Bone Mineral Density and Standardised Uptake Value | biochemical markers for bone turnover and the relation to SUV and BMD findings at anatomical sites not exposed to surgery, i.e. the lumbar spine and the contra lateral hip 3 and 6 months after surgery | 24 | 
| Biochemical markers for bone metabolism in relation to Bone Mineral Density and Standardised Uptake Value | to evaluate the natural course of an uncemented THA on BMD, i.e. the placebo group 3, 6, 12 and 24 months after surgery, SUV i.e. the placebo group 3 and 6 months after surgery and on biochemical markers, i.e. the placebo group 3, 6, 12 and 24 months after surgery | 24 | 
| Clinical outcome evaluation | to evaluate the patients Quality of Life, measured by Harris Hip score and EQ-5D questionnaires | 24 months | 
| Adverse events | incidence and severity of adverse events (AEs) during the study period | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis of the hip, Uncemented Total Hip Arthroplasty, DXA, BMD, PET, CT, Biochemical bone markers