Table 2.

Antiresorptives in women with early breast cancer

	Prevention of CTIBL in women with early breast cancer treated with aromatase inhibitors		Prevention of metastases and improving diseases outcomes in women with early breast cancer
Who?	When? (according to different expert groups)	Which agents are recommended?	Which agents?	Level of evidence and grade of recommendationa
Premenopausal women receiving adjuvant ovarian suppression	Z-score <2.0 [41] T-score <1.0 [42] 10-year fracture risk (FRAX) [43] ≥3% for hip fracture ≥20% for major fracture	Zoledronic acid 4 mg i.v. q6mo [44]  Other BP do not have a sustained effect on BMD [44]	Clodronate 1600 mg daily [38, 44]  Zoledronic acid 4 mg i.v. q6mo [38, 44]  Zoledronic acid 4 mg i.v. q3-4w for 6 doses, then q3mo for 8 doses, then q6mo for 5 doses [45]	BP reduce the frequency of bone metastases and improve breast cancer survival: I, A [38, 44]
Postmenopausal women	T-score < −2.0 or ≥ 2 clinical risk factors for fracturesb [38, 39, 42, 44, 46] I, A [39] 10-year fracture risk (FRAX) [43] ≥3% for hip fracture ≥20% for major fracture	BP prevent bone loss: I, A [44] Alendronate 70 mg p.o. weekly [38, 42, 44, 46] Risedronate 35 mg p.o. weekly [38, 39, 42, 44] Clodronate 1600 mg p.o. daily [39, 44] Ibandronate 150 mg p.o. monthly [38, 39, 42, 44] Zoledronic acid 4 mg i.v. q6mo [38, 39, 42, 44] Pamidronate 90 mg i.v. q3mo [38]  Denosumab prevents bone loss (I, A) and fractures [40] Denosumab 60 mg s.c. q6mo [38–40, 44]	In women at intermediate or high risk of recurrence  Clodronate 1600 mg daily [38, 44]  Zoledronic acid 4 mg i.v. q6mo [38, 44]  Zoledronic acid 4 mg i.v. q3-4w for 6 doses, then q3mo for 8 doses, then q6mo for 5 doses [45]	BP reduce the frequency of bone metastases and improve breast cancer survival: I, A [38, 44, 47]
	Guidelines for AI-induced bone loss are currently reviewed in the light of the anti-tumoral effects of antiresorptive treatment (see right side of table) [46]		Recommended by expert groups (joint effort of various societies, including IOF [44])
			Data on Denosumab pending – Denosumab 60 mg s.c. q6mo improved disease-free survival in high-risk patients (ABCSG-18 [48])

^aMarked in bold: level of evidence (I-V), grade of recommendation (A-E)

^bClinical risk factors for fracture include: age > 65 years, T-score <1.5, smoking (current or history of), BMI < 24 kg/m², family history of hip fracture, personal history of fragility fracture above age 50, oral glucocorticoid use for >6 months [38, 39]