Effects of Denosumab on Periprosthetic Bone After Total Hip Arthroplasty

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Hip; Ambulation Difficulty
• Intervention / Treatment: Drug: denosumab

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 Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden
    • Department of orthopedics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Drug: denosumab; Two doses of 60 mg in a solution of 1 ml, given as an subcutaneous injection with a 6 month interval; Other Names: Prolia
Placebo Comparator: saline; 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; Two doses of 60 mg in a solution of 1 ml, given as an subcutaneous injection with a 6 month interval; Other Names: Prolia

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hans Mallmin
• Investigators: Principal Investigator: Hans Mallmin, MD, PhD, Uppsala University; Study Chair: Nils Hailer, MD, PhD, Uppsala University

Publications and helpful links

General Publications

• Nystrom A, Kiritopoulos D, Ullmark G, Sorensen J, Petren-Mallmin M, Milbrink J, Hailer NP, Mallmin H. Denosumab Prevents Early Periprosthetic Bone Loss After Uncemented Total Hip Arthroplasty: Results from a Randomized Placebo-Controlled Clinical Trial. J Bone Miner Res. 2020 Feb;35(2):239-247. doi: 10.1002/jbmr.3883. Epub 2019 Nov 4.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2012
• Primary Completion (Actual): January 16, 2017
• Study Completion (Actual): March 30, 2017

Study Registration Dates

• First Submitted: June 26, 2012
• First Submitted That Met QC Criteria: June 27, 2012
• First Posted (Estimate): June 28, 2012

Study Record Updates

• Last Update Posted (Actual): April 5, 2017
• Last Update Submitted That Met QC Criteria: April 4, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: PET; CT; DXA; BMD; Osteoarthritis of the hip; Uncemented Total Hip Arthroplasty; Biochemical bone markers
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Hip; Mobility Limitation; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: 2011-001481-18