Denosumab Effect on Bone Quality and Function After Lumbar Fusion Surgery

Denosumab Protects Bone Loss and Function in Osteopenia Patients With Lumbar Degenerative Diseases After Lumbar Fusion Surgery, a Randomized, Placebo Controlled Trial.

Degenerative lumbar spinal diseases have become a common health problem and the most frequent indication for spinal surgery in elderly individuals. It mainly contain lumbar spinal stenosis and spondylolisthesis, occurs in most people over 60 years of age, and patients primarily diagnosed with lumbar degenerative disease are more likely to have osteoporosis. Our study was to explore denosumab effect on bone quality and functional status in osteopenia patients with lumbar degenerative diseases after lumbar fusion surgery.

Study Overview

• Status: Completed
• Conditions: Osteopenia; Spine Fusion; Denosumab Allergy
• Intervention / Treatment: Drug: Denosumab; Drug: Placebo

Detailed Description

However, It was still unknown for denosumab effect on osteopenia patients after lumbar fusion. Bone mineral density(BMD), bone turnover marker, lumbar functional status Roland-Morris Disability Functioning Questionnaire (RMDQ) and quality of life EuroQol Five-Dimension (EQ-5D), and Quality of Life Questionnaire of the European Foundation for Osteoporosis-31 (QUALEFFO-31) score, rate of new fracture, re-operation, lumbar fusion, complications or adverse events were still unknown. Our study will explore the effect of denosumab on lumbar, total hip, femoral neck BMD and bone turnover markers, functional status EQ-5D, QUALEFFO-31 and RMDQ score of participants after lumbar fusion at 12 months follow-up.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants aged 40 to 85 years
• who diagnosed with lumbar spinal stenosis or lumbar spondylolisthesis
• osteopenia with BMD T score between -1.0 and -2.5 via dual-energy X-ray
• low back pain or leg numbness or weakness
• MRI demonstrated signs of nerve compression

Exclusion Criteria:

• cauda equina syndrome
• progressive neurologic deficit
• history of cancer
• scoliosis greater than 15°
• back open surgery history
• have contraindications for surgery
• who had anti-osteoporosis medication within 6 weeks

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Denosumab; Denosumab 60 mg were injected subcutaneously Q6M on the same day after lumbar fusion surgery, and all patients received calcium supplementation 1200 mg/D and vitamin D 800 IU/D.	Drug: Denosumab; Denosumab 60 mg per 6 month were injected subcutaneously on the same day after lumbar fusion surgery, and all participants received calcium supplementation 1200 mg/D and vitamin D 800 IU/D.; Other Names: Denosumab 6 month/subcutaneous
Placebo Comparator: Placebo; Equal volume of saline (0.9%) as placebo were injected subcutaneously Q6M on the same day after lumbar fusion surgery, and all patients received calcium supplementation 1200 mg/D and vitamin D 800 IU/D.	Drug: Placebo; Equal volume of saline (0.9%) as placebo Q6M were injected subcutaneously on the same day after lumbar fusion surgery, and all participants received calcium supplementation 1200 mg/D and vitamin D 800 IU/D.; Other Names: Placebo 6 month/subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Total hip BMD	Total hip BMD were determined at baseline, 6 and 12 months via Dual-energy X-ray.	up to 12 months
Femoral neck BMD	Femoral neck BMD were determined at baseline, 6 and 12 months via Dual-energy X-ray.	up to 12 months
Type 1 n-terminal propeptide P1NP	Bone formation marker, type 1 n-terminal propeptide P1NP were determined at baseline, 6 and 12 months after surgery.	up to 12 months
C-terminal crosslinking type 1 collagen terminal peptide CTX	Bone resorption marker, C-terminal crosslinked type 1 collagen terminal peptide, CTX were assessed at baseline, 6 and 12 months after surgery.	up to 12 months
Visual analog scale (VAS) back	VAS score for back pain were assessed at baseline, 6 and 12 months. 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
VAS leg	VAS score for leg pain were assessed at baseline, 6 and 12 months. 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EQ-5D quality of life questionnaire	EQ-5D descriptive system is a preference-based quality of life measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. From this, a quality of life score can be calculated ranging from -0.594, indicating a health state worse than death where 0 is death, to 1, indicating full health	up to 12 month
Roland-Morris Disability Questionnaire	The Roland-Morris Disability Questionnaire is a health status measure designed to be completed by patients to assess physical disability due to low back pain. The lowest score is 0, the highest 24. The higher the score, the more severe the dysfunction.	up to 12 month
QUALEFFO-31 Questionnaire	QUALEFFO-31, which contains three domains including pain, physical function, and mental function. The worse the health related quality of life condition, the higher the score. 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
Lumbar Fusion rate	We determined lumbar fusion rate via CT at 12 month after surgery.The lowest rate is 0, the highest 100%. The higher the score represents higher fusion rate.	up to 12 month
New fracture rate	New fracture rate including new 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 represents no fracture.	up to 12 month
Reoperation rate	Reoperation rate was assessed at 12 month after surgery. The lowest reoperation rate was 0, the highest score was 100%.	up to 12 month
Complications	Complications such as cage subsidence, pedicle screw loosening, infection, peripheral nerve injury, recurrent symptoms were assessed at 12 months follow-up.	up to 12 month
Adverse effect	The main adverse effect including deep vein thrombosis, rash, joint pain, headache, nausea, pneumonia, necrosis of jaw, atypical femoral fracture, pulmonary embolism, transfer to intensive care unit (ICU), stroke, acute renal failure, myocardial infarction and so on.	up to 12 month

Collaborators and Investigators

• Sponsor: Shenzhen People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2020
• Primary Completion (Actual): January 5, 2023
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: June 8, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 13, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 15, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: ShenzhenPH spine01

Drug and device information, study documents

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