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

Table 2 Incidence of musculoskeletal symptoms 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, 12]	Anastrozole (5) versus Tamoxifen (5)	Arthralgia	35.6	29.4	< 0.0001
		Carpal tunnel syndrome	3	1	< 0.0001
ABCSG8/ARNO95 [16]	Tamoxifen (2-3) → Anastrozole (3) Versus Tamoxifen (5)	Bone pain	19	16	0.0546
ABCSG6a [17]	Tamoxifen (5) → Anastrozole (3) Versus Tamoxifen (5) → Placebo (3)	Bone pain including joint pain	24.5	18.3	0.009
ITA [20]	Tamoxifen (2-3) → Anastrozole (2-3) Versus Tamoxifen (5)	MSK disorders and bone fractures	9.9	6.7	0.2
BIG 1-98 [13]	Letrozole (5) versus Tamoxifen (5)	Arthralgia	20	13.5	< 0.001
		Myalgia	7.1	6.1	0.19
IES [14]	Tamoxifen (2-3) → Exemestane (2-3) versus Tamoxifen (5)	Arthritis	14.1	12.0	0.03
		Arthralgia	18.6	11.8	< 0.0001
		Carpal tunnel syndrome	2.8	0.3	< 0.0001
		MSK pain	21	16.1	< 0.0001
		Cramps	2.3	4.2	0.0002
		Joint stiffness	1.9	1	0.009
NSABP B33 [18]	Tamoxifen (5) → Exemestane (5) versus Tamoxifen (5) → Placebo (5)	Arthralgia	1	0.5	NA
MA17 [15]	Tamoxifen (5) → Letrozole (5) versus Tamoxifen (5) → Placebo (5)	Arthritis	6	5	0.07
		Arthralgia	25	21	< 0.001
		Myalgia	15	12	0.004
		Bone pain	5	6	0.67

ABCSG, Austrian Breast and Colorectal Cancer Study Group; ARNO, Arimidex-Nolvadex; ATAC, Arimidex, Tamoxifen, Alone or in Combination; BIG, Breast International Group; DFS, disease-free survival; IES, International Exemestane Study; ITA, Italian Trial of Anastrozole; MSK, musculoskeletal; NA, not available; NSABP, National Surgical Adjuvant Breast and Bowel Project.

ISSN: 1465-542X