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Richard R. Love, MD; Howard S. Barden, PhD; Richard B. Mazess, PhD; Sol Epstein, MD; Richard J. Chappell, PhD

Arch Intern Med. 1994;154(22):2585-2588.

Abstract
Background
Because adjuvant tamoxifen citrate is given to women with early-stage breast cancer for long periods, it is important to know how it affects risk factors for osteoporotic bone fractures, particularly since rates of bone fracture increase rapidly with age in postmenopausal women. In a 2-year randomized placebo-controlled toxicity study in 140 subjects, we demonstrated that tamoxifen was associated with preservation of bone mineral density (BMD), a major risk factor for fractures, in the lumbar spine.

Methods
Five years after entry on this study we reexamined 62 of the original subjects with lumbar spine BMD and serum osteocalcin measurements. These were women available for study because they had not suffered major illnesses and had continued to receive (1) tamoxifen or (2) the no-tamoxifen regimen that they had originally been randomized to receive for the entire 5 years.

Results
For lumbar spine BMD at baseline, the 30 subjects in the long-term tamoxifen group and the 32 subjects in the long-term no-tamoxifen group were not significantly different (P=.26). During the first 2 years of follow-up, the 30 subjects in the long-term tamoxifen group showed the same BMD pattern as the entire 70-patient tamoxifen cohort, and similarly the 32 subjects in the long-term no-tamoxifen group showed the same pattern as the entire 70-patient cohort who received placebo. Five-year mean BMD measurements for each long-term follow-up group showed no significant changes from their respective 2-year levels. However, 5-year BMD measurements between the two groups differed (tamoxifen group, +0.8%; placebo group, —0.7%) (P=.06), and the mean regression lines for the changes in BMD over 5 years differed significantly between the two groups (P=.0005). Adjustment for differences in body mass index, reported exercise, and calcium supplementation between these two groups did not change these results. Osteocalcin levels, also comparable at baseline in the two groups, were significantly lower in tamoxifen-treated subjects at 5 years (P=.0005).

Conclusions:

While remodeling of bone may be lower, resorption of lumbar spine bone mineral is also lower, and tamoxifen preserves BMD in the lumbar spine over 5 years of treatment in postmenopausal women. Over longer periods, this preservation of BMD might be expected to be associated with lower fracture rates.

(Arch Intern Med. 1994;154:2585-2588)

Author Affiliations
From the Cancer Prevention Program, University of Wisconsin Comprehensive Cancer Center and the Departments of Human Oncology (Dr Love), Medicine Physics (Drs Barden and Mazess), and Biostatistics (Dr Chappell), School of Medicine, University of Wisconsin, Madison; and the Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pa (Dr Epstein).

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