Changes in Knee Articular Cartilage Volume in Women on Aromatase Inhibitors

November 26, 2018 updated by: Professor Susan Davis, Monash University

Assessment of Knee Joint Articular Cartilage Volume Change, Bone Loss and Change in Body Composition in Women Treated With Anastrozole or Letrozole and Comparison With Untreated Controls

Many women with breast cancer are treated with a class of drugs called aromatase inhibitors (mainly letrozole or anastrozole), which lowers the amount of estrogen being produced in the body. Women on aromatase inhibitors appear to experience joint pains and arthralgia. The aim of this study is to determine whether the joint pains experienced by some women on aromatase inhibitors is associated with more defects in their cartilage, compared to women not receiving this therapy. Using the magnetic resonance imaging (MRI) technique, the knee joint will be examined to assess changes in cartilage volume over time.

Study Overview

Status

Completed

Conditions

Arthralgia

Intervention / Treatment

Drug: aromatase inhibitors (letrozole, anastrozole)

Detailed Description

The mechanism of increased bone loss and fracture risk is clearly related to the depletion of estrogen production in the bone. But why there is a higher rate of reporting arthralgia, fracture and joint pain amongst women on aromatase inhibitors is not understood.

Using magnetic resonance imaging (MRI) to measure knee articular cartilage volume, we have demonstrated that post menopausal hormone therapy used for at least five years is associated with retention of articular cartilage in the knee, indicating that oestrogen may protect against the development of osteoarthritis in post menopausal women. Furthermore, we have recently observed that free testosterone is associated with loss of tibial cartilage, after taking into account age, body mass index, baseline tibial cartilage volume, tibial plateau area and total bone mineral content in healthy men. Whether an excess of testosterone to oestrogen as a consequence of aromatase inhibition has an adverse effect on articular cartilage volume warrants further investigation.

This study will include non-hysterectomised women aged 40 to 65 years who have undergone breast surgery and then commenced on aromatase inhibitors within the preceding 12 weeks. The control group (which has been fully recruited) included non-hysterectomised, healthy women aged 40 to 65 years. A MRI of the dominant knee will be used to compare changes in knee articular volume over time. A MRI will be done at baseline and again at 2 years. Changes in knee articular volume is the primary outcome. We will also use this opportunity to compare menopausal symptoms (assessed using the Menopause Quality of Life (MENQOL)questionnaire) between women treated with aromatase inhibitors and those who are not. Well-being will also be assessed using the Psychological General Well-Being index.

Study Type

Observational

Enrollment (Actual)

115

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Australia
- Victoria
  - Melbourne, Victoria, Australia, 3004
    - Women's Health Research Program, Monash University, The Alfred Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Participants will be informed of study by their treating physician and invited to participate and by community sample.

Description

Inclusion Criteria:

Group 1 :

Aged 40 - 65
Non-hysterectomised women who have undergone breast surgery
Women on aromatase inhibitors within preceding 12 weeks

Group 2 : control group

Healthy, non-hysterectomised women aged 40-65 .

Exclusion Criteria:

Previous knee injury requiring non-weight bearing treatment for > 24 hrs or surgery (including arthroscopy)
Inability to complete the study (eg proposed relocation)
Contraindication to undergoing an MRI including pacemaker, metal sutures, presence of shrapnel, iron filings in eye
Claustrophobia

Additional Exclusions for Group 1

Treatment with tamoxifen for > 8 weeks prior to commencement
Knee pain lasting for >24 hours in the last 5 years (prior to commencement on anastrozole or letrozole)
Anastrazole or Letrozole therapy for > 12 weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Cohort
Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee Cartilage Volume Time Frame: Baseline, two years	change in medial and lateral articular tibial cartilage volume over two years	Baseline, two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee Subchondral Bone Expansion Time Frame: Baseline, Two years	change in subchondral bone expansion area over two years	Baseline, Two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Monash University

Investigators

Principal Investigator: Susan Davis, MBBS PhD, Director Women's Health Program

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

May 18, 2005

First Submitted That Met QC Criteria