Recombinant Human Bone Morphogenetic Protein-2(rhBMP-2) in Patients With Osteoporosis After Lumbar Fusion

Effect of rhBMP-2 on Early Bone Formation in Patients With Osteoporosis After Lumbar Fusion

rhBMP-2 has been used to promote spinal fusion. Despite potential risk of complications, satisfied results could be obtained with low dose of rhBMP-2. Effect of early bone formation has been validated using rat ovariectomy osteoporosis model. However, whether it functioned in patients with osteoporosis remained unknown. In this study, the investigators intend to investigate whether rhBMP-2 promotes early bone formation in patients with osteoporosis after transforaminal lumbar interbody fusion (TLIF).

Study Overview

• Status: Not yet recruiting
• Conditions: Osteoporosis; Spinal Fusion
• Intervention / Treatment: Drug: RhBMP-2

Detailed Description

Pseudoarthrosis and many complications associated with iliac crest bone graft (ICBG) has prompted the spine surgeons to seek alternative methods to promote rate of spinal fusion. The rhBMP-2 received FDA approval in 2002 for use as an alternative to autograft for single-level anterior lumbar interbody fusion (ALIF). Many studies reported equivalent or better fusion rates. Recent studies, however, identified complications related to rhBMP-2 use such as osteolysis, graft subsidence, and retrograde ejaculation and other urological complications. Overdose of rhBMP-2 in patients may lead to complications mentioned above. A recent randomized controlled trial in 2022 confirmed a low dose usage of rhBMP-2 promoted fusion after TLIF (21.mg per fusion level) without increase in complications.

Current fusion methods achieve interbody fusion by filling the cage in the central region of the intervertebral space with bone graft material. However, the early fusion rates (at 3 and 6 months postoperatively) are often unsatisfactory. According to present literatures, the 3-month and 6-month fusion rates have ranged from 2.9% to 43.1% and 30% to 68.8%, respectively. Although a lack of fusion may be asymptomatic, it may potentially lead to complications, even a reoperation. In addition, failure to achieve early fusion may result in a delayed return to work, and reduced patient satisfaction, especially in patients with osteoporosis. Whether rhBMP-2 may lead to higher and early fusion rate in osteoporosis patient remains unknown.

In this study, the investigators intend to compare the time it takes to achieve osseous union/fusion and the clinical efficacy of using rhBMP-2 to control group in TLIF. The rhBMP-2 in the study is produced by a domestic enterprise (HANGZHOU JIUYUAN GENE ENGINEERING CO .,LTD., Hangzhou, China).

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients diagnosed with degenerative lumbar diseases.
• patients underwent one-level TLIF
• osteoporosis (DXA T≤-2.5)
• complete preoperative and follow-up data (imaging and health-related quality of life)

Exclusion Criteria:

• history of previous spinal surgery
• inflammatory and neoplastic diseases

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: rhBMP-2 group	Drug: RhBMP-2; 1mg RhBMP-2 for one fusion-level
No Intervention: No rhBMP-2 group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fusion rate at 6 months	<5°of angular motion, ≤3 mm of translation from lumbar spine dynamic radiographs; Bridging bone connecting the adjacent vertebral bodies either through the implants or around the implants, and an absence of radiolucent lines around >50% of either implant from computed tomography (CT) scans of lumbar	6 months follow-up
Fusion rate at 3 months	<5°of angular motion, ≤3 mm of translation from lumbar spine dynamic radiographs of radiolucent lines around >50% of either implant	3 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Score for low back pain (VAS-B)	range from 0-10, a higher score means a worse outcome.Short Form Survey (SF-36)	pre- and post-operative immediately, 3- and 6- months follow-up
Visual Analog Score for leg pain (VAS-L)	range from 0-10, a higher score means a worse outcome.	pre- and post-operative immediately, 3- and 6- months follow-up
Oswestry disability index (ODI)	range from 0-100%, a higher score means a worse outcome.	pre-operatively, 3- and 6-months follow-up
36-Item Short Form Survey (SF-36)	As part of the Medical Outcomes Study (MOS), a multi-year, multi-site study to explain variations in patient outcomes, RAND developed the 36-Item Short Form Health Survey (SF-36) in 1992. SF-36 is a set of generic, coherent, and easily administered quality-of-life measures.	pre-operatively, 3- and 6-months follow-up
Incidence of complications	infection, revision surgery, etc.	post-operative immediately, 3- and 6- months follow-up

Collaborators and Investigators

• Sponsor: Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: June 5, 2023
• First Submitted That Met QC Criteria: June 20, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: rhBMP-2, lumbar fusion, fusion rate, osteoporosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis
• Other Study ID Numbers: 20222249-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Other researchers should ask for permissions from the investigator.
• IPD Sharing Time Frame: one year after the study is finished.
• IPD Sharing Access Criteria: Through emails after Obtaining written permission from the investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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