Denosumab and Osteoporotic Vertebral Compression Fracture

Denosumab Protects Bone Loss and Function in Patients With Osteoporotic Vertebral Compression Fracture After Percutaneous Vertebroplasty: a Randomized Placebo-controlled Clinical Trial

This study aimed to investigate the effect of denosumab on bone mineral density(BMD), bone turnover markers(BTMs), functional status, secondary fracture rate, and adverse effects in osteoporotic vertebral compression fracture (OVCF) patients after vertebroplasty during a 12-month follow-up period.

Study Overview

• Status: Completed
• Conditions: Osteoporotic Vertebral Compression Fracture
• Intervention / Treatment: Drug: Denosumab 60 mg/ml [Prolia]; Drug: Placebo

Detailed Description

We performed a single-center, placebo-controlled, randomized clinical trial in the Department of Spinal Surgery located at the First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital). All patients underwent vertebroplasty and randomly received denosumab treatment or placebo control after surgery. The BMDs (lumbar, total hip, and femoral neck) and BTMs were assessed at baseline, 6, and 12 months post-operation. The visual analog scale (VAS) score for back pain, and function status questionnaires, including EuroQol five-dimension (EQ-5D), the Quality of Life Questionnaire of the European Foundation for Osteoporosis-31 (QUALEFFO-31), and the Roland-Morris Disability Functioning Questionnaire (RMDQ),secondary fracture rate, and adverse effects in OVCF patients after vertebroplasty during a 12-month follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • ShenzhenPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be age between 50 and 90 years old
• X-ray diagnosis of 1 or 2 segment vertebral compression fractures from T4 to L5
• Bone mineral density T value less than -1 via dual-energy X-ray
• A recent fracture history less than 6 weeks
• MRI show bone marrow edema of fractured vertebrae
• low back pain, local paravertebral tenderness

Exclusion Criteria:

• Must be able to have no intervertebral fissure
• Must be able to have no infection
• Must be able to have no malignancy
• Must be able to have no neurological dysfunction
• Must be able to have no previous use of anti-osteoporosis drugs
• Must be able to have no inability to perform magnetic resonance imaging
• Must be able to have no prior back open surgery
• Must be able to have no other established contraindications for elective surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Denosumab; Denosumab 60 mg were injected subcutaneously every 6 months (Q6M)	Drug: Denosumab 60 mg/ml [Prolia]; denosumab subcutaneously every 6 months (Q6M); Other Names: Denosumab
Placebo Comparator: Placebo; Equal volume of saline (0.9%) as placebo were injected subcutaneously every 6 months (Q6M)	Drug: Placebo; placebo subcutaneously every 6 months (Q6M); Other Names: equal volume of saline (0.9%)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Femoral neck BMD	Femoral neck BMD were determined at baseline, 6 and 12 month via dual-energy X-ray	up to 12 months
C-terminal cross-linked type 1 collagen terminal peptide (CTX)	Bone resorption marker, CTX were determined at baseline, 6 and 12 months after surgery	up to 12 months
Visual analog scale (VAS) back	The VAS score for back pain were determined at baseline, 6 and 12 month. Use a ruler about 10cm long, one side is marked with "0" and the other "10" respectively. A score of 0 indicates no pain, 10 indicates the most unbearable pain.	up to 12 months
Total hip BMD	Total hip BMD were determined at baseline, 6 and 12 months via dual-energy X-ray.	up to 12 months
Procollagen type 1 n-terminal propeptide (P1NP)	Bone formation marker, P1NP were determined at baseline, 6 and 12 months after surgery.	up to 12 months
Lumbar bone mineral density(BMD)	Lumbar vertebral (L1 to L4, except the surgery segment) BMD were determined at baseline, 6 and 12 months via dual-energy X-ray.	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Roland-Morris Disability Questionnaire	The Roland-Morris Disability Questionnaire is scored by 24 adding up the number of items checked "yes" on different low back pain-related daily activity disabilities. Total scores range from 0 to 24, with higher scores 24 indicating a higher level of disability related to low back pain and lowest 0 represents no back pain.	up to 12 month
The QUALEFFO-31 Questionnaire	The Quality of Life Questionnaire of the European Foundation for Osteoporosis-31 (QUALEFFO-31), which contains three domains including pain, physical function, and mental function. This scale is assessed on a scale of 0 to 100, with 0 indicating the highest QoL and 100 the lowest.	up to 12 month
Adverse events	The main adverse events including deep venous thrombosis, pneumonia, acute renal failure, pulmonary embolism, myocardial infarction, influenza, transfer to intensive care unit, joint pain, headache, nausea, osteonecrosis of the jaw, atypical femoral fracture and rash.	up to 12 month
Secondary fracture rate	Secondary fracture rate containing vertebral fracture and non-vertebral fracture was assessed at 12 month after surgery. The lowest score was 0, the highest score was 100%. The lower score 0 represents no secondary fracture.	up to 12 month
The EQ-5D Questionnaire	The EQ-5D questionnaire evaluates health status consisting five dimensions: mobility, self-care, performance of usual activities, pain or discomfort, and anxiety or depression. After conversion, the index was between 0 and 1.0 (minimum score: 0, indicating worst health state; full score:1.0, indicating full health).	up to 12 month

Collaborators and Investigators

• Sponsor: Shenzhen People's Hospital
• Investigators: Principal Investigator: Xiao Xiao, Doctor, ShenZhen People's Hospital

Publications and helpful links

General Publications

• Chang R, Qian X, Xuan Z, Xu Y, Chen Y, Gu H, Fu C. Health related quality of life and its impacts by chronic diseases in urban community population, Shanghai, China in 2015. Psychol Health Med. 2021 Sep;26(8):931-939. doi: 10.1080/13548506.2020.1856896. Epub 2020 Dec 11.
• Zhou C, Li Q, Huang S, Fan L, Wang B, Dai J, Tang X. Validation of the simplified Chinese version of the quality of life questionnaire of the European foundation for osteoporosis (QUALEFFO-31). Eur Spine J. 2016 Jan;25(1):318-324. doi: 10.1007/s00586-015-4066-z. Epub 2015 Jun 14.
• Stevens ML, Lin CC, Maher CG. The Roland Morris Disability Questionnaire. J Physiother. 2016 Apr;62(2):116. doi: 10.1016/j.jphys.2015.10.003. Epub 2015 Dec 11. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2020
• Primary Completion (Actual): August 5, 2022
• Study Completion (Actual): August 10, 2022

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: September 16, 2021
• First Posted (Actual): September 27, 2021

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 18, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: denosumab; vertebroplasty
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Fractures, Compression; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: ShenzhenPH spine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No