Endocrine Abstracts

Denosumab discontinuation leads to loss of bone mineral density (BMD) achieved with treatment and in some patients to multiple vertebral fractures (VFx). Beyond bone, antiresorptive agents such as denosumab may affect breast cancer biology. We report a 69-year-old woman treated with the aromatase inhibitor anastrazole for breast cancer who suffered from five spontaneous vertebral fractures after denosumab cessation. Initially, she received four years of ibandronate followed by three years of denosumab (6 injections) as antiosteoporotic treatment. On denosumab her BMD significantly improved (increase of 12% in lumbar spine and 4.8% in hip BMD); after attaining nonosteoporotic BMD the treatment was withdrawn. Six months after the last injection of denosumab peroral ibandronate was administered. Despite ibandronate treatment, 13 months after stopping denosumab, C-terminal collagen cross links (CTX) increased 14-fold in comparison with their values on denosumab, demonstrating accelerated bone resorption, and hip BMD fell by 7.5%. Furthermore, VFx occurred 11 and 13 months after stopping denosumab. At the same time local breast cancer recurrence was diagnosed after six years of remission. The patient underwent left mastectomy followed by trastuzumab treatment. Bone scintigraphy and spine magnetic resonance imaging ruled out bone metastasis and confirmed osteoporosis- related fragility vertebral compressions. Denosumab was resumed and after three injections BMD significantly increased (increase of 17.5% in lumbar spine and 7.4% in hip BMD). The patient postponed one injection to avoid the risk of osteonecrosis of the jaw linked to dental treatment. CTX increased and BMD dropped again significantly (decrease of 21% in lumbar spine and 8.5% in hip BMD). Denosumab was reinitiated for the third time and has been continued. This case illustrates a rebound effect after denosumab cessation in a postmenopausal woman treated for breast cancer. Neither pretreatment nor subsequent postdenosumab treatment with ibandronate prevented high bone turnover, bone loss, and VFx. Denosumab decreases the risk of fractures and, moreover, may provide an adjuvant survival benefit in breast cancer patients. Denosumab discontinuation is, however, associated with a rapid reversal of its effect in bones. Whether this rebound effect has also negative clinical implications for breast cancer recurrence remains to be elucidated. Supported by MZ ČR - RVO (Institute of Endocrinology - EU, 00023761).