Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study

Abstract

Denosumab increased lumbar spine bone mineral density (BMD) versus placebo in a 2-year, randomized, placebo-controlled, phase 3 study of patients with hormone-receptor-positive, non-metastatic breast cancer and low bone mass who were receiving adjuvant aromatase inhibitor therapy. In subgroup analyses at 12 and 24 months, we evaluated factors (duration and type of aromatase inhibitor, tamoxifen use, age, time since menopause, body mass index, T-score) that might influence BMD at the lumbar spine, total hip, femoral neck, and 1/3 radius. Patients were randomized to receive placebo (n = 125) or 60 mg denosumab (n = 127) subcutaneously every 6 months. In all subgroups, 12 or 24 months' treatment with denosumab was associated with larger BMD gains than placebo across multiple skeletal sites. Most increases were statistically significant (P < 0.05). Twice-yearly administration of denosumab, regardless of patient subgroup or skeletal site, resulted in consistent increases in BMD versus placebo at 12 and 24 months.

Update on Medications With Adverse Skeletal Effects

“…Preliminary studies also show bone density benefits with denosumab. 13 No trials addressing fracture risk reduction with osteoporosis treatment in the setting of aromatase inhibitor therapy have been reported to date. Treatment recommendations for osteoporosis therapies in the setting of aromatase inhibitors should take into account the baseline fracture risk.…”

Breast Cancer Metastases to Bone: Role of the Microenvironment

“…Compared to the most potent osteoclasttargeting drug in the market, bisphosphonate zoledronic acid, Denosumab treatment further delayed the occurrence of the first skeletal related event (SRE), and provided a further reduction in bone turnover markers in breast cancer patients (174). In non-metastatic breast cancer patients additionally receiving adjuvant aromatase inhibitors, bone mineral density gains were greater with Denosumab treatment (175). Bisphosphonate-resistant patients with bone metastases from breast or prostate cancer also benefitted from Denosumab treatment, with most having normalized serum markers of bone resorption after 13 weeks of treatment (176).…”

Denosumab treatment in patients with different courses of osteoporosis

“…Препарат эффективен для предупреждения переломов тел позвонков, бедра и внепозвоночных переломов в течение 10 лет терапии у женщин с постменопаузальным ОП [4]. До-казана эффективность лечения ДМБ у мужчин с сенильным ОП [5].ДМБ препятствует потере МПК и повышает её у мужчин на фоне андроген-депривационной терапии рака предста-тельной железы [6], и у женщин, получающих ингибиторы ароматазы при раке молочной железы [7].Лечение ДМБ постменопаузального ОП приводит к большему приросту МПК, измеренной двухэнергетиче-ской рентгеновской остеоденситометрией, количествен-ной компьютерной томографией и высокоразрешающей количественной компьютерной томографией, по сравне-нию с алендронатом [8,9]. Назначение ДМБ после терапии алендронатом, ибандронатом и золедроновой кислотой (ЗК) приводит к дальнейшей прибавке МПК [10].…”