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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Denosumab | Active Comparator | 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 | Placebo Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| denosumab | Drug | Two doses of 60 mg in a solution of 1 ml, given as an subcutaneous injection with a 6 month interval |
|
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hans Mallmin, MD, PhD | Uppsala University | Principal Investigator |
| Nils Hailer, MD, PhD | Uppsala University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Orthopedics | Uppsala | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41921101 | Derived | Skold C, Hailer NP, Mallmin H. Denosumab and bone loss in uncemented total hip arthroplasty: a secondary 5-year follow-up of a randomized controlled trial. Acta Orthop. 2026 Apr 1;97:217-224. doi: 10.2340/17453674.2026.45695. | |
| 40584156 | Derived | Kultima K, Ashtiani SH, Erngren I, Khoonsari PE, Carlsson H, Herman S, Freyhult E, Mallmin H, Hailer NP. Uncemented hip arthroplasty and denosumab: increased postoperative dipeptide concentrations and identification of potential new bone turnover biomarkers. JBMR Plus. 2025 May 19;9(7):ziaf091. doi: 10.1093/jbmrpl/ziaf091. eCollection 2025 Jul. |
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| ID | Term |
|---|---|
| D015207 | Osteoarthritis, Hip |
| D051346 | Mobility Limitation |
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D000069448 | Denosumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| 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 |
| 31589776 | Derived | 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. |
| D012216 |
| Rheumatic Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |