Effects of Denosumab on Periprosthetic Bone After Total Hip Arthroplasty

Phase 2

Completed

• Conditions: Osteoarthritis, Hip; Ambulation Difficulty
• Interventions: Drug: denosumab

• Registration Number: NCT01630941
• Lead Sponsor: Hans Mallmin

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2012-06-26
• Study First Submitted QC: 2012-06-27
• Study First Posted: 2012-06-28
• Study Start: 2012-08-07
• Primary Completion: 2017-01-16
• Study Completion: 2017-03-30
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-04
• Last Update Posted: 2017-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1. male or female patient 35-65 years of age with an unilateral OAH requiring a THA and a healthy contralateral hip
2. body weight ≤110 kg or body mass index (BMI) ≤35 kg/m2
3. living in the Uppsala County
4. the eligible patients should have been given oral information, a written Patient Information and signed an Informed Consent

Exclusion Criteria

1. on or previously have had bone-specific treatment, e.g. bisphosphonates, raloxifene, parathyroid hormone, strontium ranelate, during the last five years
2. patients on systemical corticosteroid for more than 3 months should not be considered
3. patients with diagnosed malignant disease during the last five years or known to have metastasis from malignant disease should be excluded
4. patients with compromised general conditions and an American Society of Anesthesiologists, ASA-score >31 should not be regarded eligible
5. patients with known drug or alcohol abuse or regarded as socially dysfunctional, as judged by the investigator, should not be considered for the study
6. pregnant women or women planning for pregnancy or fertile women (premenopausal) without contraceptives should not be accepted for the study
7. 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.
8. 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
9. any condition or laboratory findings which in the opinion of the Investigator makes the patient unsuitable for inclusion (for example claustrophobia)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Denosumab	denosumab	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
saline	denosumab	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

Primary Outcome Measures

Name	Time	Method
Bone Mineral Density	12 months	Bone mineral density by DXA in Gruen Zone 7 and a sum of Gruen zone 1-7

Secondary Outcome Measures

Name	Time	Method
Standardised Uptake Value	6 months	Fluoride isotope uptake measured as SUV at the lumbar spine and at the contra lateral nonoperated hip after 3 and 6 months
Clinical outcome evaluation	24 months	to evaluate the patients Quality of Life, measured by Harris Hip score and EQ-5D questionnaires
Bone Mineral Density	24 months	BMD at the lumbar spine and at the contra lateral nonoperated hip 6, 12 and 24 months after surgery
Adverse events	24 months	incidence and severity of adverse events (AEs) during the study period
Standardised Uptake value	6 months	fluoride isotope uptake, measured as SUV adjacent to the acetabular cup 3 and 6 months after surgery
Bone Mineral density	24 months	BMD adjacent to the acetabular cup during the follow up period, i.e. after 3, 6, 12 and 24 months
Bone mineral Density	24 months	BMD, g/cm2, adjacent to the femur implant for Gruen Zone 1-7, 3, 6, and 24 months after surgery
Biochemical markers for bone metabolism	24 months	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
Biochemical markers for bone metabolism in relation to Bone Mineral Density and Standardised Uptake Value	24	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

Trial Locations

Locations (1)

Department of Orthopedics; 🇸🇪 Uppsala, Sweden