osteoarthritis
Conditions
Interventions
Experimental group:denosumab, 60 mg subcutaneous injection
Calcium/Vit D supplementation: Daily dosage Calcium 1000mg / Vit D 880 IU
Sponsors
Shanghai Sixth People's Hospital
Eligibility
Sex/Gender
All
Age
40 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. People >=40 years of age; 2. Knee OA as defined by the clinical and radiographic American College of Rheumatology (ACR) criteria; 3. Presence of pain in the study knee for at least half of the days in the previous month; 4. Pain intensity >= 40 and <90 on a 0-100 visual analogue scale (VAS); 5. Kellgren-Lawrence grade (KLG) 2 or 3 of the study knee based on the radiograph; 6. At least two bone marrow lesions (BMLs) in the study knee detected by knee MRI ; 7. High subchondral bone metabolic activity on baseline PET/MRI as defined by PET standardized uptake values (SUV) greater than 5 times the SUV in normal-appearing subchondral bone (45 minutes after injection); 8. Mild-to-moderate knee alignment (<=5° varus/valgus); 9. Willingness to undergo a new knee X-ray and PET/MRI.
Exclusion criteria
Exclusion criteria: 1. Patients with known hypersensitivities to mammalian-derived drug preparations; 2. Patients with clinically significant hypersensitivity to any of the components of denosumab; 3. Current and/or Prior treatment with any investigational agent within 90 days, or five half-lives of the product, whichever is longer 4. Previous administration of denosumab from clinical trials or others (e.g., commercial use); 5. Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (< 49.9 nmol/L)]. Possibility of replenishment and re-screening; 6. Subjects with current hypo- or hypercalcemia (normal serum calcium levels: 8.5-10.5 mg/dl or 2.12-2.62 mmol/L); 7. Patients currently under bisphosphonate (BP) treatment or any use of oral BPs within 12 months of study enrollment, or intravenous BPs or strontium ranelate within 5 years of study enrollment. 8. Knee surgery in the past three years; 9. Prior use of any chondroprotective drug within 90 days e.g. chondroitin sulfate, glucosamine, avocado-soybean unsaponifiables, tetracyclines; 10. Prior use of any immunomodulating drug with possible effects on proinflammatory cytokine metabolism within 90 days a.o. corticosteroids, methotrexate, sulfasalazine, leflunomide, D-Penicillin, anti-malarials, cytotoxic drugs, tumor necrosis factor (TNF) blocking agents; 11. Patients suffering from chronic inflammatory rheumatic disease (e.g. rheumatoid arthritis, spondylarthropathy, psoriatic arthritis, gout, chondrocalcinosis or other auto-immune diseases, e.g. systemic lupus erythematosus); 12. History of cancer or lymphoproliferative disease other than a successfully and completely treated squamous cell or basal cell carcinoma of the skin or cervical dysplasia, with no recurrence within the last two years; 13. History of any Solid Organ or Bone Marrow Transplant; 14. Comorbidities: significant renal function impairment (glomerular filtration < 30 ml/min/1.73m^2 or <50% of normal value), uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (NYHA III, IV), uncontrolled hypo or hyperparathyroidism, active inflammatory bowel disease, malabsorption, liver failure or chronic hepatic disease (serum aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) levels 3 times above normal), recent stroke (within three months), chronic leg ulcer and any other condition (e.g,. indwelling urinary catheter) which, in the opinion of the investigator, would put the subject at risk by participation in the protocol; 15. Female subjects who are breast-feeding; 16. Patient who is pregnant or planning pregnancy; 17. History of osteonecrosis of the jaw, and/or recent (within 3 months) tooth extraction or other unhealed dental surgery; or planned invasive dental work during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| WOMAC pain; | — |
Secondary
| Measure | Time frame |
|---|---|
| WOMAC pain;X-ray based knee joint structure change;PET/MRI based knee joint structure change;WOMAC function;EQ-5D-5L; | — |
Countries
China
Contacts
Public ContactXianyou Zheng
Shanghai Sixth People's Hospital
Outcome results
None listed