Effect of Teriparatide on Fracture Healing in Patients With Incomplete Atypical Femur Fractures

Effect of Teriparatide on Fracture Healing in Patients With Incomplete Atypical Femur Fractures: a Randomized Controlled Trial

Atypical femur (thigh bone) fractures (AFFs) are uncommon low-trauma fractures which often occur without warning, are highly debilitating, and are slow to heal. As physicians learn more about them, AFFs are increasingly being identified prior to a total break. However, there's no evidence on the best way to treat these non-displaced AFFs. One option is teriparatide, an osteoporosis medication that can build new bone. Investigators will conduct a double blind randomized placebo controlled trial to examine whether teriparatide use in AFF patients with an incomplete break will help accelerate fracture healing and prevent surgical intervention. Co-primary outcomes include change in WOMAC scores from baseline to 12 months and number of participants requiring surgical intervention at 12 months. Investigators will recruit 60 women and men over the age of 30 who have experienced an incomplete AFF. Participants will be randomly assigned to either teriparatide (20 mcg/day) or placebo (using an identical injection pen) for up to 2 years. As AFFs are highly debilitating, a trial examining the use of Teriparatide in this population is urgently needed.

Study Overview

• Status: Completed
• Conditions: Non Displaced Atypical Femoral Fractures
• Intervention / Treatment: Biological: Teriparatide 20 mcg; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

i. Female or male; ii. Over the age of 30; iii. Experienced an incomplete AFF that satisfies the diagnostic criteria as set forth by the American Society for Bone and Mineral Research (ASBMR) International Task Force on AFFs:

1. Atraumatic or low trauma incomplete stress fractures, defined as fractures sustained with minimal force, such as a fall from standing height;
2. From distal to the lesser trochanter to proximal to the supracondylar flare along the femoral shaft.
3. Radiographic confirmation of AFF features is required for a definitive diagnosis. Incomplete AFF features include cortical thickening, cortical beaking, and lucency line. Patients with cortical beaking without lucency line can be included.

Exclusion Criteria:

i. Peri-prosthetic fractures, ii. High trauma fractures, iii. Pathological fractures secondary to metastases or metabolic bone diseases other than osteoporosis, iv. Fractures that are not confirmed by radiological investigations, v. Contraindication to use of teriparatide such as:

1. pregnant or nursing mothers, or women who are planning on pregnancy within 1 year of completing teriparatide therapy,
2. hypersensitivity to teriparatide,
3. severe renal impairment,
4. multiple myeloma,
5. active cancer in past 5 years (other than non-melanoma skin cancer),
6. primary hyperparathyroidism,
7. hypercalcemia,
8. Paget's disease or other conditions that may increase the risk for osteosarcoma,
9. Prior radiation therapy involving the skeleton, vi. Concomitant use of other osteoporosis therapies including bisphosphonates or denosumab (except calcitonin).

AFF patients with complete fractures on the contralateral side or patients with secondary osteoporosis will not be excluded.

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
Active Comparator: Teriparatide 20 mcg daily; Teriparatide (Forteo) 20 mcg daily by injection pen for 12-24 months	Biological: Teriparatide 20 mcg; Teriparatide 20 mcg injection pen; Other Names: Brand name Forteo
Placebo Comparator: Placebo; Placebo injection pen identical to active drug injection pen	Other: Placebo; Placebo 20 mcg injection pen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in the modified The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)of the affected limb (the femur that has the incomplete AFF)	baseline to 12 months
The proportion of patients requiring surgical intervention	baseline to 12 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Eli Lilly and Company; The Physicians' Services Incorporated Foundation
• Investigators: Study Director: Angela M Cheung, MD, PhD, University Health Network, Toronto; Principal Investigator: Lianne E Tile, Md, MEd, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: July 5, 2013
• First Submitted That Met QC Criteria: July 5, 2013
• First Posted (Estimated): July 11, 2013

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Femoral Fractures; Fractures, Bone; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Teriparatide
• Other Study ID Numbers: 12-0170; Control # 164050 (Registry Identifier: Health Canada BGTD)

Drug and device information, study documents

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