Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG

Peyman Hadji, Matti S. Aapro, Jean Jacques Body, Michael Gnant, Maria Luisa Brandi, Jean Yves Reginster, M. Carola Zillikens, Claus C. Glüer, Tobie de Villiers, Rod Baber, G. David Roodman, Cyrus Cooper, Bente Langdahl, Santiago Palacios, John Kanis, Nasser Al-Daghri, Xavier Nogues, Erik Fink Eriksen, Andreas Kurth, Rene RizzoliRobert E. Coleman

Research output: Contribution to journalReview article

56 Citations (Scopus)

Abstract

Background Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL). Patients and methods A systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety. Results Several fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL. Conclusions In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<−2.0 or with a T-score of <–1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>−1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalJournal of Bone Oncology
Volume7
DOIs
StatePublished - Jun 1 2017

Fingerprint

Aromatase Inhibitors
Postmenopausal Osteoporosis
Joints
Hormones
Breast Neoplasms
Bone and Bones
Bone Neoplasms
Diphosphonates
Therapeutics
Compliance
Guidelines
Bone Density Conservation Agents
Safety
Recurrence
Mortality
Risk Reduction Behavior
Vitamin D
Meta-Analysis
Randomized Controlled Trials
Exercise

Keywords

  • Bisphosphonate
  • Breast cancer
  • Denosumab
  • Endocrine treatment
  • Fracture
  • Osteoporosis

ASJC Scopus subject areas

  • Oncology

Cite this

Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer : Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. / Hadji, Peyman; Aapro, Matti S.; Body, Jean Jacques; Gnant, Michael; Brandi, Maria Luisa; Reginster, Jean Yves; Zillikens, M. Carola; Glüer, Claus C.; de Villiers, Tobie; Baber, Rod; Roodman, G. David; Cooper, Cyrus; Langdahl, Bente; Palacios, Santiago; Kanis, John; Al-Daghri, Nasser; Nogues, Xavier; Eriksen, Erik Fink; Kurth, Andreas; Rizzoli, Rene; Coleman, Robert E.

In: Journal of Bone Oncology, Vol. 7, 01.06.2017, p. 1-12.

Research output: Contribution to journalReview article

Hadji, P, Aapro, MS, Body, JJ, Gnant, M, Brandi, ML, Reginster, JY, Zillikens, MC, Glüer, CC, de Villiers, T, Baber, R, Roodman, GD, Cooper, C, Langdahl, B, Palacios, S, Kanis, J, Al-Daghri, N, Nogues, X, Eriksen, EF, Kurth, A, Rizzoli, R & Coleman, RE 2017, 'Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG', Journal of Bone Oncology, vol. 7, pp. 1-12. https://doi.org/10.1016/j.jbo.2017.03.001
Hadji, Peyman ; Aapro, Matti S. ; Body, Jean Jacques ; Gnant, Michael ; Brandi, Maria Luisa ; Reginster, Jean Yves ; Zillikens, M. Carola ; Glüer, Claus C. ; de Villiers, Tobie ; Baber, Rod ; Roodman, G. David ; Cooper, Cyrus ; Langdahl, Bente ; Palacios, Santiago ; Kanis, John ; Al-Daghri, Nasser ; Nogues, Xavier ; Eriksen, Erik Fink ; Kurth, Andreas ; Rizzoli, Rene ; Coleman, Robert E. / Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer : Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. In: Journal of Bone Oncology. 2017 ; Vol. 7. pp. 1-12.
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abstract = "Background Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL). Patients and methods A systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety. Results Several fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34{\%} relative risk reduction in bone metastasis and 17{\%} relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL. Conclusions In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<−2.0 or with a T-score of <–1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>−1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.",
keywords = "Bisphosphonate, Breast cancer, Denosumab, Endocrine treatment, Fracture, Osteoporosis",
author = "Peyman Hadji and Aapro, {Matti S.} and Body, {Jean Jacques} and Michael Gnant and Brandi, {Maria Luisa} and Reginster, {Jean Yves} and Zillikens, {M. Carola} and Gl{\"u}er, {Claus C.} and {de Villiers}, Tobie and Rod Baber and Roodman, {G. David} and Cyrus Cooper and Bente Langdahl and Santiago Palacios and John Kanis and Nasser Al-Daghri and Xavier Nogues and Eriksen, {Erik Fink} and Andreas Kurth and Rene Rizzoli and Coleman, {Robert E.}",
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TY - JOUR

T1 - Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer

T2 - Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG

AU - Hadji, Peyman

AU - Aapro, Matti S.

AU - Body, Jean Jacques

AU - Gnant, Michael

AU - Brandi, Maria Luisa

AU - Reginster, Jean Yves

AU - Zillikens, M. Carola

AU - Glüer, Claus C.

AU - de Villiers, Tobie

AU - Baber, Rod

AU - Roodman, G. David

AU - Cooper, Cyrus

AU - Langdahl, Bente

AU - Palacios, Santiago

AU - Kanis, John

AU - Al-Daghri, Nasser

AU - Nogues, Xavier

AU - Eriksen, Erik Fink

AU - Kurth, Andreas

AU - Rizzoli, Rene

AU - Coleman, Robert E.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL). Patients and methods A systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety. Results Several fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL. Conclusions In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<−2.0 or with a T-score of <–1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>−1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.

AB - Background Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL). Patients and methods A systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety. Results Several fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL. Conclusions In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<−2.0 or with a T-score of <–1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>−1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.

KW - Bisphosphonate

KW - Breast cancer

KW - Denosumab

KW - Endocrine treatment

KW - Fracture

KW - Osteoporosis

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