Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management

Table 1 Incidence of bone fractures and osteoporosis in patients treated with aromatase inhibitors versus tamoxifen or placebo in randomized phase III trials

Study	Treatment arms (years of treatment)	Symptom	Aromatase inhibitor (%)	Tamoxifen/placebo (%)	P-value
ATAC [11, 21]	Anastrozole (5) versus Tamoxifen (5)	Fractures	2.93	1.9	< 0.0001
		Osteopenia or osteoporosis	11	7	< 0.0001
ABCSG8/ARNO95 [16]	Tamoxifen (2-3) → Anastrozole (3) versus Tamoxifen (5)	Fractures	2	1	0.015
ABCSG6a [17]	Tamoxifen (5) → Anastrozole (3) versus Tamoxifen (5) → Placebo (3)	Fractures	0.8	1.1	NA
BIG 1-98 [13]	Letrozole (5) versus Tamoxifen (5)	Fractures	8.6	5.8	< 0.001
IES [14]	Tamoxifen (2-3) → Exemestane (2-3) versus Tamoxifen (5)	Fracture^a	4.3	3.1	0.03
		Osteoporosis	7.3	5.5	0.01
MA.17 [15]	Tamoxifen (5) → Letrozole (5) versus Tamoxifen (5) → Placebo (5)	Fracture	5.3	4.6	0.25
		Osteoporosis	8.1	6	0.003

^aFracture risk increased with exemestane versus tamoxifen (7 versus 4.9, respectively; P-value 0.003) after completion of therapy. ABCSG, Austrian Breast and Colorectal Cancer Study Group; ARNO, Arimidex-Nolvadex; ATAC, Arimidex, Tamoxifen, Alone or in Combination; BIG, Breast International Group; IES, International Exemestane Study; NA, not available.

ISSN: 1465-542X