Personalizing Osteoporosis Care: Clinical & Genetic Risk Factors for AFFs

Active, not recruiting

• Conditions: Atypical Femur Fracture
• Interventions: Other: No Intervention

• Registration Number: NCT04110795
• Lead Sponsor: University Health Network, Toronto

Brief Summary

The overall objective of this project is to identify clinical and genetic risk factors for Atypical Femur Fractures (AFFs) in Anti-resorptive therapy (ART) users by conducting a case control study of 330 cases of AFFs and 660 controls without AFFs matched for age, sex, race and duration of ART.

Detailed Description

Antiresorptive therapy (ART) drugs are effective osteoporosis treatment and help decrease osteoporosis-related fractures. However, their long-term use has been associated with rare but serious atypical femur fractures (AFFs). Fear of these side effects has caused a substantial decline in the use of these effective drugs and rising fracture rates. The investigators propose to compare 330 cases of people with AFFs to 660 matched controls to explore similarities and differences in (1) clinical findings, such as type of ART and length of use, prior fracture, bone density, femur geometry, etc., and (2) genetic variants, and then (3) to validate the top few genetic variants to see if they are indeed present in an additional group of 100 AFF patients and not present in 100 control subjects. This study will determine clinical and genetic risk factors for these debilitating atypical fractures such that at-risk patients in the future can be treated differently to avoid them.

Study Timeline

• Study Start: 2018-06-25
• Study First Submitted: 2019-09-25
• Study First Submitted QC: 2019-09-30
• Study First Posted: 2019-10-01
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-30
• Last Update Posted: 2023-06-01
• Primary Completion: 2025-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 1200

Inclusion Criteria

• Cases: Have experienced a confirmed, documented Atypical femur fracture
• Controls: currently on anti-resorptive therapy, matches AFF case by age, race and length of ART use

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Exclusion Criteria

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control	No Intervention	matched to AFF cases by race, age, length of ART use
Cases	No Intervention	Atypical Femur fracture cases

Primary Outcome Measures

Name	Time	Method
Associations between AFF and clinical Risk Factor	baseline	Associations between AFFs and clinical risk factors
Associations between AFF and common genetic variants	baseline	Associations of common genetic variants among patients with AFFs
Validation of top genetic variants	baseline	To validate the top few genetic variants identified in the above case-control study in a separate cohort of 100 cases and 100 controls.

Trial Locations

Locations (3)

Bone Research & Education Centre; 🇨🇦 Oakville, Ontario, Canada

Adachi Medical Centre; 🇨🇦 Hamilton, Ontario, Canada

University Health Network, TGH; 🇨🇦 Toronto, Ontario, Canada