Changes in Knee Articular Cartilage Volume in Women on Aromatase Inhibitors

Arthralgia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00111241
• Other study ID #: 2004/949
• Status: Completed
• Start date: May 2005
• Est. completion date: December 2011

Study information

• Verified date: November 2018
• Source: Monash University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: December 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthralgia

Intervention

Drug:
• aromatase inhibitors (letrozole, anastrozole)
Women prescribed an aromatase inhibitor by their clinician were compared with healthy controls in the community who had been recruited to a prior study

Locations

Country	Name	City	State
Australia	Women's Health Research Program, Monash University, The Alfred Hospital	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Monash University

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Knee Cartilage Volume	change in medial and lateral articular tibial cartilage volume over two years	Baseline, two years
Secondary	Knee Subchondral Bone Expansion	change in subchondral bone expansion area over two years	Baseline, Two years