Clinical Study of Desuzumab in the Treatment of Knee Osteoarthritis

Recruiting

• Conditions: Knee Osteoarthritis
• Interventions: Drug: Denosumab

• Registration Number: NCT06357741
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

As an activator of inhibiting nuclear factor kB receptor, denosumab affects osteoclast differentiation and development by inhibiting OPG/RANKL-RANK bone regulatory axis pathway. Therefore, denosumab is widely used in the treatment of bone diseases such as osteoporosis. Osteoporosis is closely related to knee osteoarthritis. RANKL-RANK pathway also plays a key role in the pathogenesis of knee osteoarthritis. Therefore, the investigators propose the hypothesis that denosumab can effectively treat knee osteoarthritis.

Detailed Description

basic overview at present, about 60% of the elderly over 60 years old in China suffer from knee osteoarthritis, and there are more than 100million patients with knee osteoarthritis in China. It is estimated that the world's elderly population will reach 2.02 billion in 2050, and China will reach 480million, accounting for almost 5% of the global elderly population, making it the country with the largest elderly population in the world . At present, the treatment of knee osteoarthritis is only analgesic drugs to alleviate symptoms, and there is no effective treatment to reverse the progress of knee osteoarthritis. Therefore, many patients with knee osteoarthritis eventually face knee replacement surgery. In 2019, there were nearly 400000 knee replacement operations in China, and the number will increase by 30% next year, which is undoubtedly a huge economic expenditure for patients. Denosumab is widely used in the treatment of osteoporosis by inhibiting nuclear factor kB activating factor (rank). Rank and RANKL are important molecular systems that regulate bone remodeling and the dynamic balance of bone metabolism. In osteoporosis, the combination of rank and RANKL will directly promote the differentiation and maturation of osteoblasts, enhance their bone resorption activity and prevent their apoptosis. The relative transcription of rank in osteoclasts and their precursor cells is significantly increased, which promotes bone loss and leads to osteoporosis. RANKL-RANK pathway also plays a key role in the pathogenesis of osteoarthritis . The chondrocytes and synovial cells of patients with knee osteoarthritis will produce interleukin-1 after being stimulated by trauma, wear and tear β （IL-1 β）、 TNF- α And prostaglandin E2 (PGE2) and other inflammatory factors promote osteoclasts to secrete metalloproteinases (MMPs) and matrix protease tissue inhibitors (TIMPs), and these inflammatory factors can directly stimulate RANKL to induce the production of osteoclasts, resulting in the destruction of cartilage matrix, the impairment of bone regeneration ability, the irreversible degradation of cartilage tissue, and even apoptosis . At the same time, it has been reported in the literature that osteoporosis and knee osteoarthritis are closely related, and the two promote each other, forming a vicious circle . The symptoms of knee osteoarthritis can be relieved by treating osteoporosis. However, there is no report about denosumab in the treatment of knee osteoarthritis. Therefore, this project plans to use a prospective, single center randomized controlled trial to study the clinical efficacy of denosumab in the treatment of patients with knee osteoarthritis and osteoporosis.

Study Timeline

• Study Start: 2021-08-01
• Study First Submitted: 2023-08-05
• Study First Submitted QC: 2024-04-04
• Study First Posted: 2024-04-10
• Status Verified: 2025-03
• Last Update Submitted: 2025-04-04
• Last Update Posted: 2025-04-09
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• patients with knee osteoarthritis whose inclusion criteria meet the "diagnostic criteria for arthritis" .
• no drug contraindications .
• aged between 45 and 75 .
• committed to follow the research procedures, And cooperate with the •implementation of the whole process study .
• the patient understands the relevant treatment process .
• the patient has the ability to give informed consent .
• The patient had not recently taken any medication that affected observation.
• the subjects must meet all the inclusion criteria to be eligible to participate in the study .

Exclusion Criteria

• mental illness .
• patients with malignant tumors.
• patients with other infectious diseases .
• patients with metabolic bone disease, diabetes and hyperthyroidism.
• patients who cannot actively cooperate in the treatment.
• hypocalcemia.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
desumumab1	Denosumab	60mg, single injection.
desumumab 3	Denosumab	60mg, single injection.
desumumab 13	Denosumab	60mg, single injection.
desumumab 14	Denosumab	60mg, single injection.
desumumab2	Denosumab	60mg, single injection.
desumumab 6	Denosumab	60mg, single injection.
desumumab 8	Denosumab	60mg, single injection.
desumumab 9	Denosumab	60mg, single injection.
desumumab 10	Denosumab	60mg, single injection.
desumumab4	Denosumab	60mg, single injection.
desumumab5	Denosumab	60mg, single injection.
desumumab7	Denosumab	60mg, single injection.
desumumab 11	Denosumab	60mg, single injection.
desumumab 12	Denosumab	60mg, single injection.
desumumab 15	Denosumab	60mg, single injection.

Primary Outcome Measures

Name	Time	Method
Knee pain relief	1,3,6 months	OKS function of knee joint at 1,3 and 6 months, VAS pain score at 1,3 and 6 months;

Secondary Outcome Measures

Name	Time	Method
Knee pain relief and incidence of adverse reactions	1,3,6 months	Knee joint WOMAC score（maximum：250 ，minimum：0） at 1,3 and 6 months；incidence of adverse reactions;EQ-5D quality of life score at 1,3 and 6 months；

Trial Locations

Locations (1)

Wuhan Union Hospital; 🇨🇳 Wuhan, Hubei, China