Trial Information

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

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.