Long-term raloxifene for postmenopausal osteoporosis

Abstract

Background:

Due to the chronic nature of osteoporosis and the risk of invasive breast cancer, raloxifene 60 mg/day (raloxifene) is intended to be used for long-term treatment (treatment >3 years).

Scope:

We review available information concerning long-term use of raloxifene, present several new analyses, and report new data from patients who underwent iliac crest bone biopsies after 8 years of raloxifene therapy. The most important studies were the Multiple Outcomes of Raloxifene Evaluation (MORE) followed by the Continued Outcomes of Raloxifene Evaluation (CORE).

Findings:

The primary endpoint in MORE was incidence of vertebral fracture, and the difference between the raloxifene and placebo groups for this endpoint widened during 4 years of therapy, with the relative risk reduction during the fourth year of the study being similar to the relative risk reduction during years 0 to 3 of the study. Continued raloxifene treatment is necessary to preserve bone mineral density (BMD). In MORE, raloxifene lowered markers of bone turnover to a premenopausal reference interval. Biopsies from three patients treated with raloxifene for 8 years showed normal bone and bone cells and double label in all specimens. Invasive breast cancer risk is a clinical consideration in postmenopausal women with osteoporosis, and invasive breast cancer risk reduction was the primary endpoint in CORE. In MORE and CORE, the benefit of raloxifene versus placebo in incidence of invasive breast cancer increased with greater duration of therapy up to 8 years.

Conclusions:

The long-term use of raloxifene has been evaluated through changes in fracture risk reduction, BMD, markers of bone turnover, iliac crest bone biopsies, and invasive breast cancer risk reduction.

Keywords::

• Breast neoplasms
• Clinical trials
• Osteoporosis
• Raloxifene
• SERMs

Transparency

Declaration of funding

This study was supported by Eli Lilly and Company, Indianapolis, IN, USA.

Declaration of financial/other relationships

R.R.R. is a paid consultant for Merck, Lilly, Pfizer, Procter & Gamble, Amgen, Roche, Glaxo Smith Kline, and Novartis; and has received grant/research support from Merck, Lilly, Wyeth, Procter & Gamble, Amgen, Roche, Glaxo Smith Kline, Novartis and Sanofi-Aventis through grants to his institution. B.H.M. is an employee of Eli Lilly and Company and owns stock in Eli Lilly, and X.N. and J.H.K. are employees of Lilly USA, LLC and own stock in Eli Lilly.

Acknowledgements

Editorial assistance was provided by Barbara Jackson of i3 statprobe.