Clinical trial NCT01630941: Effects of Denosumab on Periprosthetic Bone After Total Hip Arthroplasty
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis, Hip
Ambulation Difficulty
Keywords: Osteoarthritis of the hip
Uncemented Total Hip Arthroplasty
DXA
BMD
PET
CT
Biochemical bone markers
Lead sponsor: Uppsala University Hospital
Sponsor class: OTHER
First posted: 2012-06-28
Enrollment: 64
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Bone Mineral Density
timeFrame: 12 months
Secondary outcomes:
measure: Bone mineral Density
timeFrame: 24 months
measure: Standardised Uptake value
timeFrame: 6 months
measure: Standardised Uptake value
timeFrame: 6 months
measure: Bone Mineral density
timeFrame: 24 months
measure: Bone Mineral Density
timeFrame: 24 months
measure: Standardised Uptake Value
timeFrame: 6 months
measure: Biochemical markers for bone metabolism
timeFrame: 24 months
measure: Biochemical markers for bone metabolism in relation to Bone Mineral Density and Standardised Uptake Value
timeFrame: 24
measure: Biochemical markers for bone metabolism in relation to Bone Mineral Density and Standardised Uptake Value
timeFrame: 24
measure: Clinical outcome evaluation
timeFrame: 24 months
measure: Adverse events
timeFrame: 24 months
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Department of Orthopedics
Study officials:
affiliation: Uppsala University
name: Hans Mallmin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Uppsala University
name: Nils Hailer, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.