Aromatase inhibitor-associated bone loss and its management with bisphosphonates in patients with breast cancer

Figures & data

Figure 1 Cancer treatment-induced bone loss.^{44,45,88–90}

Abbreviations: AI, aromatase inhibitor; BMD, bone mineral density; GnRH, gonadotropin-releasing hormone; PMw, postmenopausal women.

Table 1 Bone-related and fracture-related adverse events from aromatase inhibitor (AI) trials^{5,18,22,31,62}

Trial (follow-up)	Adjuvant therapy type	AI	Comparator	Definition of adverse event	AI versus comparator	P value
ATAC (68 months)	Initial adjuvant	ANA	TAM	Overall fracture rate Osteopenia or osteoporosis	11.0% versus 7.7% 11.0% versus 7.0%	<0.0001 <0.0001
BIG 1-98 (60.3 months)	Initial adjuvant	LET	TAM	Overall fracture rate	9.3% versus 6.5%	<0.001
IES (55.7 months)	Switch adjuvant	EXE	TAM	Overall fracture rate Osteoporosis	7.0% versus 4.9% 9.2% versus 7.2%	0.003 0.01
TEAM (32 months)	Initial adjuvant	EXE	TAM	Overall fracture rate Osteoporosis	2.7% versus 2.3% 4.7% versus 2.1%	NS ≤0.001

© 2010 Reprinted with permission from Elsevier. Janni W, Hepp P. Adjuvant aromatase inhibitor therapy: Outcomes and safety. Cancer Treat Rev. 2010;36:249–261.⁵

Abbreviations: ANA, anastrozole; ATAC, Arimidex Tamoxifen Alone or in Combination; BIG, Breast International Group; EXE, exemestane; IES, Intergroup Exemestane Study; LET, letrozole; NR, not reported; NS, not significant; TAM, tamoxifen; TEAM, Tamoxifen, Exemestane Adjuvant Multicenter.

Figure 2 Left femur bone mass density over time. (A) At baseline, (B) at 12 months, and (C) at 24 months.

Note: Bone scans provided by authors.

Figure 3 Right femur bone mass density over time. (A) At baseline, (B) at 12 months, and (C) at 24 months.

Note: Bone scans provided by authors.

Figure 4 Lumbar spine bone mass density over time. (A) At baseline, (B) at 12 months, and (C) at 24 months.

Table 2 Dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) results

DXA LS baseline	DXA femur baseline	QUS baseline
BMD L1–L4: 1.059	Right/left	Right/left
T score L1–L4: −1.0	Neck BMD 0.826/0.791	T score −0.6/−1.8
	Neck t score −1.3/−1.6	Stiffness index
	Neck total BMD 0.867/0.899	92/77
	Neck total t score −1.1/−0.8
DXA LS 12 months	DXA femur 12 months	QUS 12 months
BMD L1–L4: 0.965	Right/left	Right/left
T score L1–L4: −1.8	Neck BMD 0.778/0.767	T score −2.2/−3.3
	Neck t score −1.7/−1.8	Stiffness index
	Neck total BMD 0.796/0.809	72/58
	Neck total t score −1.7/−1.6
DXA LS 2 years	DXA femur 24 months	QUS 24 months
BMD L1–L4: 1.916	Right/left	Right/left
T score L1–L4: −2.2	Neck BMD 0.733/0.749	T score −1.3/−3.1
	Neck t score −2.1/−1.9	Stiffness index
	Neck total BMD 0.764/0.792	84/59
	Neck total t score −2.0/−1.7

Abbreviations: BMD, bone mineral density; LS, lumbar spine.

Table 3 Disease-free survival (DFS) events and deathsa

Median follow-up, months	ZO-FAST^Citation81		Z-FAST^Citation72		E-ZO-FAST^Citation81
	48		61		36
	Upfront (n = 532)	Delayed (n = 533)	Upfront (n = 301)	Delayed (n = 301)	Upfront (n = 263)	Delayed (n = 264)
DFS events	32	53	–	–	19	11
Patients with disease recurrence for Z-FAST (n)	–	–	16	21	–	–
Deaths (any cause)	16	26	7	4	9	2

Note:

a Z-FAST, ZO-FAST, and E-ZO-FAST are studies in the series of the Zometa-Femara Adjuvant Synergy Trials.

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