The Effect of NSAID Use in the Acute Phase of Skeletally Immature Bone Healing: A Prospective Study

NCT ID: NCT02076321

Last Updated: 2019-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2016-11-30

Brief Summary

Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are excellent medications for providing pain control in children with fractures or those who have surgery to correct bony deformity requiring the bone to be cut (osteotomy) and realigned. There is some data to suggest that these types of medications can adversely affect bone healing in adult patients with broken bones or those having spine fusion surgery. There is little data with regard to how these medications effect bone healing in children. With this project, the investigators' goal is to determine if NSAIDs delay or otherwise adversely effect bone healing and to demonstrate that these medications adequately control pain in children with broken bones or those who have had an osteotomy.

Detailed Description

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in controlling both post-operative pain and pain associated with orthopaedic injuries, particularly in the pediatric population. Additionally, use of NSAIDs for pain control in this setting avoids the use of narcotic pain medications, the adverse effects of which are well known.

Recent research has suggested a possible association between use of NSAIDs and impaired fracture healing in the skeletally mature, or adult, population. Several adult mammal studies have demonstrated inhibition of bony repair with administration of NSAIDs. Yet, other adult animal studies have failed to find the same effect. Clinical data in the adult population is similarly conflicted, with some studies showing an inhibition of bone healing after posterior spinal fusion, while a larger study found no correlation. The data investigating the effects of NSAID use in adults after fracture or osteotomy is even less clear with some studies demonstrating higher rates of non-union with NSAID administration and others finding no significant effect on bone healing.

The research investigating these outcomes in the skeletally immature population is limited; one study compared administration of ketorolac versus normal saline for 7, 14 and 21 days in a juvenile rat model with a stabilized tibia fracture. They found no significant difference in strength, stiffness or histological characteristics of fracture callus between the two groups. Clinical retrospective studies of the pediatric population with regard to use of NSAIDs after posterior spinal fusion have failed to reproduce findings of inhibitory effects on bone healing. Similarly, two retrospective studies found no cases of delayed union or non-union in pediatric patients who received perioperative ketorolac around the time of operative fixation of fractures, or osteotomy. Given these results, the way in which and the degree to which NSAIDs perturb the inflammatory mileu during the acute phase of healing is potentially distinct from the effects on bone healing in the skeletally mature.

There have been no clinical prospective, randomized studies to evaluate the effect, if any, that NSAIDs have on bone healing in the skeletally immature patient population. The investigators hypothesize that NSAID administration in the acute phase of bone healing, whether it be a fracture or osteotomy, will not result in delayed union or non-union as compared to patients who take acetaminophen for pain control during this same time period.

Conditions

Fractures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Acetaminophen

control group

Group Type: OTHER

Acetaminophen

Intervention Type: DRUG

acetaminophen for pain control with dose and frequency of 10-15mg/kg/dose, Maximum dose 1000mg. Maximum amount per day: 75mg/kg (not to exceed 4g/day).

NSAID (Ibuprofen)

Study group

Group Type: OTHER

Ibuprofen

Intervention Type: DRUG

ibuprofen for pain control with dose and frequency 4-10mg/kg/dose. Maximum of 40mg/kg/day, not to exceed 3,200mg/day. Maximum one-time dose of 800mg.

Interventions

Acetaminophen

acetaminophen for pain control with dose and frequency of 10-15mg/kg/dose, Maximum dose 1000mg. Maximum amount per day: 75mg/kg (not to exceed 4g/day).

Intervention Type: DRUG

Ibuprofen

ibuprofen for pain control with dose and frequency 4-10mg/kg/dose. Maximum of 40mg/kg/day, not to exceed 3,200mg/day. Maximum one-time dose of 800mg.

Intervention Type: DRUG

Other Intervention Names

Tylenol; Advil; Motrin

Eligibility Criteria

Inclusion Criteria

• • Male aged 16 years or less or female aged 14 years or less

• Open physis on radiographs
• Fracture undergoing closed treatment or operative treatment or patient undergoing elective osteotomy

Exclusion Criteria

• • Regular use of NSAIDs

• Allergy to NSAIDs
• Inability to take breakthrough medications due side effects or allergy
• Systemic illness
• Renal impairment
• Liver disease
• Polytrauma
• Uncontrolled diabetes
• Regular use of corticosteroids
• History of any skeletal dysplasia
• History of neuromuscular disorder
• History of bleeding disorder
• History of liver disorder
• Pathologic fracture
• Closed physes
• Male greater than 16 years old
• Female greater than 14 years old
• Pregnant or possibly pregnant females based on report and last menstrual period

• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Missouri-Columbia

OTHER

Sponsor Role: lead

Responsible Party

Daniel Hoernschemeyer

Orthopaedic Surgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel G Hoernschemeyer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Missouri-Columbia

Locations

University of Missouri Health System

Columbia, Missouri, United States

Countries

United States

Other Identifiers

1207111

Identifier Type: -

Identifier Source: org_study_id