Decreasing BMD and Increasing Fracture Risk

Aromatase inhibitor (AI) therapy has been shown to lead to a rapid and significant decrease in bone mineral density (BMD), which can increase the risk of fracture.^1,2 The greatest rate of bone loss, measured by BMD, occurs within the first 2 years of AI therapy and persists over time.¹

AI: Effects on BMD

Change in lumbar spine BMD in patients with breast cancer over 5 years of treatment with anastrozole¹

Data from subprotocol of pateints (n = 308) recruited from the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial (median follow-up, 68 months) designed to prospectively assess the effects of long-term treatment with anastrozole or tamoxifen on BMD and bone turnover in postmenopausal women with invasive primary breast cancer. Patients received either anastozole (1 mg/d), tamoxifen (20 mg/d), or combination treatment with both agents (discontinued). Treatment groups were compared to a small, untreated, nonrandomized control group for 5 years. Lumbar spine and total hip BMD were assessed at baseline and after 1, 2, and 5 years.

Change in total hip BMD in patients with breast cancer over 5 years of treatment with anastrozole¹

AI therapy and fracture risk

Women with breast cancer who are taking AI therapy have an increased fracture risk.

A large, retrospective longitudinal analysis of 12,368 patients with breast cancer showed that the prevalence of bone fracture increased in women receiving AI therapy (n = 1,354) compared with women who were not treated with AI therapy (n = 11,014), 13.5% vs 10.3%, respectively. In fact, the relative risk of fracture was 35% higher in women treated with an AI compared with controls (P = 0.001).³

After controlling for age, comorbidities, geographic region, and health plan type, the risk of bone loss and fractures remained significantly higher in women treated with AIs (27% and 21%, respectively) compared with women not receiving AI therapy (P = 0.02).³

In addition, a 100-month analysis of ATAC data (N = 5,216) showed that the use of AI therapy was associated with a 55% increase in the risk of all fractures compared with tamoxifen (2.93% vs 1.90%, respectively, P < 0.0001 for any serious adverse events in this study).⁴ This increase did not continue into the post-treatment follow-up period, where the rate on AI therapy was very similar to that with tamoxifen (1.56% vs 1.51%, respectively).⁴

• Breast cancer, bone metastases, and skeletal-related events
• Impact on patients with breast cancer
• Increased RANK Ligand signaling in patients with bone metastases

References:

1. Eastell R, Adams JE, Coleman RE, et al. Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol. 2008;26:1051-1058.
2. Eastell R, Hannon RA, Cuzick J, et al. Effect of an aromatase inhibitor on BMD and bone turnover markers: 2-year results of the anastrozole, tamoxifen, alone or in combination (ATAC) trial (18233230). J Bone Miner Res. 2006;21:1215-1223.
3. Mincey BA, Duh MS, Thomas SK, et al. Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors. Clin Breast Cancer. 2006;7:127-132.
4. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Onc. 2008;9:45-53.