Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study

Zanchetta, María Belén; Boailchuk, Juan A.; Massari, Fabio; Silveira, Fernando; Bogado, CE; Zanchetta, José R.

doi:10.1007/s00198-017-4242-6

Cited by 95 publications

(82 citation statements)

References 18 publications

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“…Of relevance to these tumoral considerations, we observed an escape from suppressed bone resorption, with a precipitous rise to above baseline in serum CTX by 5 months post‐denosumab initiation, while receiving monthly denosumab dosing. The notion of “rebound effect” is emerging for a number of clinical outcomes in the denosumab treatment setting, including rebound vertebral fractures and loss of bone mineral density after denosumab discontinuation in women with postmenopausal osteoporosis . Rebound hypercalcemia in young children with osteogenesis imperfecta while on active therapy and in two adolescents and one young adult with GCTB have also been described.…”

Section: Discussionmentioning

confidence: 99%

Local Tumor Recurrence and Escape from Suppression of Bone Resorption With Denosumab Treatment in Two Adolescents With Giant Cell Tumors of Bone

et al. 2019

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Giant cell tumors of bone (GCTB) may be difficult to resect because of size or location. We describe two adolescents who were treated with denosumab and followed for tumoral and biochemical responses. Denosumab was effective in achieving sufficient regression to allow surgical resection and in preserving peritumor cortical bone. Reactivation of bone resorption markers was noted while the patients were receiving monthly denosumab. One patient suffered a local tumor recurrence. Denosumab was safe in enabling surgical resection of GCTB. However, the effect was transient, with an escape of resorption markers and tumor recurrence. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Local Tumor Recurrence and Escape from Suppression of Bone Resorption With Denosumab Treatment in Two Adolescents With Giant Cell Tumors of Bone

et al. 2019

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“…In a phase II trial, within 6 to 12 months of treatment cessation, serum CTX levels rose to twice the placebo levels and lumbar spine BMD returning to baseline levels . Similar findings were demonstrated in a phase III prevention study and an extension of the FREEDOM (A Study to Evaluate Denosumab in the Treatment of Postmenopausal Osteoporosis) trial . Although these studies have not clearly demonstrated a subsequent increased risk of fracture, experts in the field are suggesting the cancellation of DMab holidays, or advising in the case treatment cessation is required, that bisphosphonate treatment is applied to prevent rebound bone loss .…”

Section: Therapeutic Opportunities To Prevent or Exploit Reactivationmentioning

confidence: 66%

Tumor Cell Dormancy and Reactivation in Bone: Skeletal Biology and Therapeutic Opportunities

2019

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In the advanced stages of many cancers, tumor cells disseminate from the primary site and colonize distant locations such as the skeleton. These disseminated tumor cells colonizing bone can evade treatments and survive for prolonged periods in a dormant state before becoming reactivated to form overt metastases. The precise interactions between tumor cells and the bone microenvironment that promote survival, dormancy, and reactivation are currently unknown; as a result, bone metastases remain incurable. In this review we discuss the unique cellular and microenvironmental features of endosteal bone that tumor cells engage with to persist and survive, and ultimately reactivate and proliferate. Specifically, we provide a detailed summary of current perspectives on the processes of tumor cell colonization of the skeleton, and the endosteal bone cells as critical controllers of the dormant cancer cell phenotype, as well as relevant microenvironmental effects such as hypoxia. Evidence for the role of the osteoclast in controlling dormant cancer cell reactivation in bone is highlighted, preceding a discussion of therapeutics targeting the bone microenvironment, including anti‐RANK ligand and bisphosphonate therapies and their potential utility in preventing tumor cell reactivation in addition to protecting bone from tumor‐induced destruction. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…More recently, denosumab was shown to increase BMD and reduce fractures into a great extent . However, discontinuation of denosumab in patients with osteoporosis or vertebral fractures is associated with a strong decrease in BMD, exceeding the initial increase in BMD shown over a period of 7–10 years, and an increased risk of vertebral fractures . Therefore, denosumab should not be stopped in these patients without considering alternative treatment.…”

Section: Discussionmentioning

confidence: 99%

Assessment and management of bone health in women with early breast cancer receiving endocrine treatment in the DATA study

Hellemond

Smorenburg

Peer³

et al. 2019

Intl Journal of Cancer

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The phase III DATA study investigates the efficacy of adjuvant anastrozole (6 vs. 3 year) in postmenopausal women with breast cancer previously treated with 2–3 years of tamoxifen. This planned side‐study assessed patterns of care regarding detection and treatment of osteopenia/osteoporosis, and trends in bone mineral density (BMD) during and after therapy. We registered all BMD measurements and bisphosphonate‐use. Time to osteopenia/osteoporosis was analysed by Kaplan Meier methodology. For the trend in T‐scores we used linear mixed models with random patients effects. Of 1860 eligible DATA patients, 910 (48.9%) had a baseline BMD measurement. Among patients with a normal baseline BMD (n = 417), osteopenia was observed in 53.5% and 55.4% in the 6‐ and 3‐year group respectively (p = 0.18), during follow‐up. Only two patients (3‐year group) developed osteoporosis. Of the patients with osteopenia at baseline (n = 408), 24.4% and 20.4% developed osteoporosis respectively (p = 0.89). Three years after randomisation 18.3% and 18.2% used bisphosphonates in the 6‐ and 3‐year groups respectively and 6 years after randomisation this was 23.7% and 20.9% respectively (p = 0.90) of which the majority used oral bisphosphonates. The yearly mean BMD‐change during anastrozole in the lumbar spine showed a T‐score decline of 0.075. After bisphosphonate addition the decline became less prominent (0.047 (p < 0.001)) and after anastrozole cessation, while continuing bisphosphonates, the mean BMD yearly increased (0.047 (p < 0.001)). In conclusion, extended anastrozole therapy was not associated with a higher incidence of osteoporosis. Anastrozole‐use was associated with a BMD decrease; however, the decline was modest and partially reversible after anastrozole cessation.

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Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study

Cited by 95 publications

References 18 publications

Local Tumor Recurrence and Escape from Suppression of Bone Resorption With Denosumab Treatment in Two Adolescents With Giant Cell Tumors of Bone

Local Tumor Recurrence and Escape from Suppression of Bone Resorption With Denosumab Treatment in Two Adolescents With Giant Cell Tumors of Bone

Tumor Cell Dormancy and Reactivation in Bone: Skeletal Biology and Therapeutic Opportunities

Assessment and management of bone health in women with early breast cancer receiving endocrine treatment in the DATA study

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