Effects of Denosumab on Bone Fusion in Osteoporotic Patients After Lumbar Fusion

The Effects of Denosumab on Bone Fusion and Bone Metabolism in Osteoporotic Patients With Lumbar Degenerative Disease After Lumbar Interbody Fusion

Lumbar fusion is an accepted and effective technique for the treatment of lumbar degenerative disease. As the population ages, disability associated with spinal pathology and spinal surgery is rapidly increasing and there is a concomitant increase in prevalence of osteoporosis which is a detrimental factor for Lumbar fusion and instrumentation. Osteoporosis-related bone fragility is a primary reason for spinal fusion failure, implant fixation failure, and vertebral compression fractures above or below the fusion sites.

Denosumab is a human monoclonal antibody against RANKL, it inhibits osteoclast mediated bone destruction and has been found to be effective in treating osteoporosis, including reducing bone turnover markers, increasing bone mineral density (BMD), and reducing fractures. But few studies focus on the effects of Denosumab on lumbar fusion. In this study, we include osteoporotic patients with lumbar degenerative disease who have had lumbar interbody fusion surgery. The patients were randomized to either treatment of Denosumab or no treatment. All these patients are followed at 3, 6, 9, 12 months postoperation. During these periods, we detect bone metabolism and bone fusion of these patients. Finally, we would report whether Denosumab can improve bone metabolism and promote bone fusion or not.

Study Overview

• Status: Recruiting
• Conditions: Osteoporosis; Fusion of Spine, Lumbar Region
• Intervention / Treatment: Drug: Denosumab 60 mg/ml Injectable Solution [Prolia]; Drug: calcium and vitamin D

• Study Type: Interventional
• Enrollment (Anticipated): 116
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lvping Sun; Phone Number: 021-81885070; Email: shczkykxs@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200003
      • Recruiting
      • Shanghai Changzheng Hospital
      • Contact: Lvping Sun; Phone Number: 021-81885070; Email: shczkykxs@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of degenerative lumbar diseases with symptoms of low-back pain and/or leg pain for at least 3 months, which was not be adequately controlled by nonoperative treatments.
2. Diagnosis of osteoporosis, defined as a bone mineral density (BMD) at lumbar or femoral neck with 2.5 standard deviations or more below the mean peak bone mass (T scores <-2.5 SD) measured by dual-energy X-ray absorptiometry (DXA).
3. Patients will be underwent single-level or two-level lumbar interbody fusion.

Exclusion Criteria:

1. Paget disease of bone,
2. Low laboratory tests for calcium,
3. Previous radiation treatment or fusion surgery to lumbar spine,
4. Bone tumors,
5. Bone infection,
6. Acute vertebral fractures
7. Severe spinal deformities such as degenerative scoliosis,
8. Other metabolic bone disease,
9. History of a anti-osteoporosis medication
10. Combined with severe morbidities,
11. Uncorrected bleeding diatheses
12. Application of steroids.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Patients in this group are received denosumab (60 mg) subcutaneously at one week and 26 weeks after the lumbar fusion surgery, combined with receiving daily calcium (≥1·0 g) and vitamin D (≥400 IU).	Drug: Denosumab 60 mg/ml Injectable Solution [Prolia]; Denosumab, 60mg(1ml), subcutaneously, totally two times, with one time at 1-week postoperatively and another time at 26-week postoperatively.; Drug: calcium and vitamin D; calcium (≥1·0 g) and vitamin D (≥400 IU).
Sham Comparator: Control group; Patients in this group are only received daily calcium (≥1·0 g) and vitamin D (≥400 IU) after the lumbar fusion surgery.	Drug: calcium and vitamin D; calcium (≥1·0 g) and vitamin D (≥400 IU).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lumbar fusion rate	Fusion rate assessed by CT scan and dynamic radiograph	3-month post-operation
lumbar fusion rate	Fusion rate assessed by CT scan and dynamic radiograph	6-month post-operation
lumbar fusion rate	Fusion rate assessed by CT scan and dynamic radiograph	9-month post-operation
lumbar fusion rate	Fusion rate assessed by CT scan and dynamic radiograph	12-month post-operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone metabolic markers including serum carboxy terminal cross-linked telopeptide of type I collagen (β-CTX) and osteocalcin (OCN)	To assess bone metabolism, serum samples will be collected under nonfasting conditions, and the concentrations of β-CTX) and osteocalcin (OCN) will be measured using ELISA as biomarkers of bone resorption and formation, respectively.	pre-operation
Bone metabolic markers including serum carboxy terminal cross-linked telopeptide of type I collagen (β-CTX) and osteocalcin (OCN)	To assess bone metabolism, serum samples will be collected before and after surgery under nonfasting conditions, and the concentrations of β-CTX) and osteocalcin (OCN) will be measured using ELISA as biomarkers of bone resorption and formation, respectively.	3-month post-operation
Bone metabolic markers including serum carboxy terminal cross-linked telopeptide of type I collagen (β-CTX) and osteocalcin (OCN)	To assess bone metabolism, serum samples will be collected before and after surgery under nonfasting conditions, and the concentrations of β-CTX) and osteocalcin (OCN) will be measured using ELISA as biomarkers of bone resorption and formation, respectively.	6-month post-operation
Bone metabolic markers including serum carboxy terminal cross-linked telopeptide of type I collagen (β-CTX) and osteocalcin (OCN)	To assess bone metabolism, serum samples will be collected before and after surgery under nonfasting conditions, and the concentrations of β-CTX) and osteocalcin (OCN) will be measured using ELISA as biomarkers of bone resorption and formation, respectively.	9-month post-operation
Bone metabolic markers including serum carboxy terminal cross-linked telopeptide of type I collagen (β-CTX) and osteocalcin (OCN)	To assess bone metabolism, serum samples will be collected before and after surgery under nonfasting conditions, and the concentrations of β-CTX) and osteocalcin (OCN) will be measured using ELISA as biomarkers of bone resorption and formation, respectively.	12-month post-operation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineral density (BMD)	BMD will be measured at the lumbar spine or femoral neck by DXA before surgery.	Pre-operation
Bone mineral density (BMD)	Due to instrumentation at the lumbar site, BMD will be measured only at the femoral neck by DXA after surgery.	6-month post-operation
Bone mineral density (BMD)	Due to instrumentation at the lumbar site, BMD will be measured only at the femoral neck by DXA after surgery.	12-month post-operation

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital
• Investigators: Principal Investigator: Changgui Shi, M.D., Shanghai Changzheng Hospital, Naval Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2021
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: December 8, 2021
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Calcium; Denosumab
• Other Study ID Numbers: 2021SL031

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes