NCT02731040

Brief Summary

The purpose of this study is to determine whether women who have atypical subtrochanteric and diaphyseal femoral fractures after treatment with bisphosphonates for osteoporosis, have a genetic predisposition to these unusual fractures.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Apr 2016

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 28, 2016

Completed
4 days until next milestone

Study Start

First participant enrolled

April 1, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

April 7, 2016

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 29, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 29, 2018

Completed
Last Updated

December 31, 2018

Status Verified

December 1, 2018

Enrollment Period

2 years

First QC Date

March 28, 2016

Last Update Submit

December 27, 2018

Conditions

Atypical Femoral FracturesOsteoporosisBisphosphonate Therapy

Outcome Measures

Primary Outcomes (3)

  • Whole Exome Sequencing to identify mutations in genes that regulate pyrophosphate metabolism.

    Whole Exome Sequencing will be used to identify changes in DNA sequences of genes which regulate pyrophosphate metabolism. These changes could alter the amino acid sequence, and may include termination of translation, or affect mRNA splicing.

    Within the first year of study

  • Whole Exome Sequencing to identify mutations in genes that regulate phosphate metabolism.

    Whole Exome Sequencing will be used to identify changes in DNA sequences of genes which regulate phosphate metabolism. These changes could alter the amino acid sequence, and may include termination of translation, or affect mRNA splicing.

    Within the first year of study

  • Whole Exome Sequencing to identify mutations in genes that regulate bisphosphonate metabolism.

    Whole Exome Sequencing will be used to identify changes in DNA sequences of genes which regulate bisphosphonate metabolism. These changes could alter the amino acid sequence, and may include termination of translation, or affect mRNA splicing.

    Within the first year of study

Study Arms (2)

Controls

Women who are/have been on bisphosphonate therapy for osteoporosis who have not suffered an atypical femoral fracture

Drug: Bisphosphonate

Fracture Group

Women who are/have been on bisphosphonate therapy for osteoporosis who have suffered an atypical femoral fracture

Drug: Bisphosphonate

Interventions

BisphosphonateDRUG
Also known as: Aledronate (Fosamax), Zoledronate (Zometa and Reclast), Risendronate (Actonel and Atelvia), Etidronate (Didronel), Ibandronate (Boniva)
ControlsFracture Group

Eligibility Criteria

Sexfemale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Women who are or have been taking bisphosphonates for osteoporosis.

You may qualify if:

  • Female
  • Previous and/or current use of bisphosphonate therapy for the management of osteoporosis
  • sustained one or more atypical subtrochanteric or diaphyseal femoral shaft fracture(s) as defined by the the 2010 ASBMR task force.

You may not qualify if:

  • None

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (9)

  • Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster D, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Koval K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O'Keefe R, Papapoulos S, Sen HT, van der Meulen MC, Weinstein RS, Whyte M; American Society for Bone and Mineral Research. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010 Nov;25(11):2267-94. doi: 10.1002/jbmr.253.

    PMID: 20842676BACKGROUND

  • Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster DW, Ebeling PR, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O'Keefe R, Papapoulos S, Howe TS, van der Meulen MC, Weinstein RS, Whyte MP. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2014 Jan;29(1):1-23. doi: 10.1002/jbmr.1998. Epub 2013 Oct 1.

    PMID: 23712442BACKGROUND

  • 2013 Annual Meeting of the American Society for Bone and Mineral Research, October 4-7, 2013, Baltimore, MD. J Bone Miner Res. 2013 Feb;28 Suppl 1:S1. doi: 10.1002/jbmr.2201. No abstract available.

    PMID: 24585702BACKGROUND

  • Sutton RA, Mumm S, Coburn SP, Ericson KL, Whyte MP. "Atypical femoral fractures" during bisphosphonate exposure in adult hypophosphatasia. J Bone Miner Res. 2012 May;27(5):987-94. doi: 10.1002/jbmr.1565.

    PMID: 22322541BACKGROUND

  • Whyte MP. Hypophosphatasia. In Pediatric Bone: Biology & Diseases, 3rd ed. Glorieux FH, Jueppner H, Pettifor J, eds. San Diego, CA: Elsevier, 2012;771-794.

    BACKGROUND

  • Reid IR, Hardy DC, Murphy WA, Teitelbaum SL, Bergfeld MA, Whyte MP. X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults. Medicine (Baltimore). 1989 Nov;68(6):336-52.

    PMID: 2811660BACKGROUND

  • Duncan, E.L., Brown, M.A. Genome-wide association studies (2013) Genetics of Bone Biology and Skeletal Disease, pp. 93-100

    BACKGROUND

  • Nguyen, T.V., Eisman, J.A. Pharmacogenetics and pharmacogenomics of osteoporosis: personalized medicine outlook (2013) Genetics of Bone Biology and Skeletal Disease, pp. 151-167

    BACKGROUND

  • Rivadeneira, F., Uitterlinden, A.G. Osteoporosis Genes Identified by Genome-wide Association Studies (2013) Genetics of Bone Biology and Skeletal Disease, pp. 243-256.

    BACKGROUND

MeSH Terms

Conditions

Osteoporosis

Interventions

DiphosphonatesAlendronateZoledronic AcidRisedronic AcidEtidronic AcidIbandronic Acid

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

OrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyridines

Study Officials

  • Steven Mumm, PhD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
OTHER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Medicine

Study Record Dates

First Submitted

March 28, 2016

First Posted

April 7, 2016

Study Start

April 1, 2016

Primary Completion

March 29, 2018

Study Completion

March 29, 2018

Last Updated

December 31, 2018

Record last verified: 2018-12