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

Abstract

Abstract:Postmenopausal women have an increased risk of osteopenia and osteoporosis due to loss of the bone-protective effects of estrogen. Disease-related processes may also contribute to the risk of bone loss in postmenopausal women with breast cancer. One of the most common and severe safety issues associated with cancer therapy for patients with breast cancer is bone loss and the associated increase in risk of fractures. This paper reviews the recent literature pertaining to aromatase inhibitor (AI)-associated bone loss, and discusses suggested management and preventative approaches that may help patients remain on therapy to derive maximum clinical benefit. A case study is presented to illustrate the discussion. We observed that AIs are in widespread use for women with hormone receptor-positive breast cancer and are now recommended as adjuvant therapy, either as primary therapy or sequential to tamoxifen, for postmenopausal women. AIs target the estrogen biosynthetic pathway and deprive tumor cells of the growth-promoting effects of estrogen, and AI therapies provide benefits to patients in terms of improved disease-free survival. However, there is a concern regarding the increased risk of bone loss with prolonged AI therapy, which can be managed in many cases with the use of bisphosphonates and other interventions (eg, calcium, vitamin D supplementation, exercise).

Cancer Treatment and Bone Health

“…exemestane) irreversibly bind to the aromatase enzyme, while non-steroidal AIs (e.g. anastrozole, letrozole) are competitive inhibitors which bind to the heme moiety of the aromatase cytochrome P450 complex [ 55 ]. Table 1 summarises the most important studies investigating the effects of AIs on bone health.…”

Male Breast Cancer: Prognosis and Survivorship

“…Aromatase inhibitors are known to cause bone loss and fractures in women [23], contrasting tamoxifen which causes osteopenia in premeno¬pausal women and enhances bone density in postmenopausal women. The National Comprehensive Cancer Network (NCCN) guidelines recommend periodic bone mineral density testing in females on aromatase inhibitor therapy.…”

Recomendações multidisciplinares portuguesas sobre o pedido de DXA e indicação de tratamento de prevenção das fraturas de fragilidade

“…Fratura de fragilidade ≤ 50 59 Terapia de privação de androgénios [60][61][62] Imobilização prolongada e paralisia [63][64] Glucocorticoides 65 Historial de quedas [5][6]8,11,18 Anticonvulsantes 66 Anorexia nervosa [67][68] Análogos da hormona libertadora de gonadotropinas (GnRH) 69-71 Deficiência de cálcio e de vitamina D 5,8,[72][73] Inibidores de aromatase [74][75][76][77][78] Absorção intestinal 8,79 Terapia antirretroviral 73,80 Artrite reumatoide 81 Hiperparatireoidismo [82][83] QUADRO III. Condições/doenças e tratamentos com impacto na DMO, conforme estabelecido em revisões sistemáticas da literatura e/ou em meta-análises documentos inibidores seletivos de recaptação de serotonina; Tamoxifen®; tiazolidinedionas hiazolidinedionas T (como Actos®); hormonas da tiroide (em excesso).…”