Denosumab Discontinuation and the Rebound Phenomenon: A Case Report

Document Type

Conference Proceeding

Publication Date

9-27-2024

Publication Title

J Bone Miner Res

Abstract

Antiresorptive therapy with Denosumab increases bone mineral density (BMD) and lowers fracture risks across all skeletal sites. Progressive increase in BMD with long term use is thought to be due to preservation of modelling and intermittent increases in parathyroid hormone secretion. Nevertheless, upon discontinuation of therapy, there is a heightened likelihood of experiencing a rebound surge in bone turnover markers, potentially resulting in bone loss, and in individuals at high risk, possibly culminating in fractures. Prolonged use increases the risk of this rebound phenomenon in addition to other factors. We present the case of a 65-year-old woman diagnosed with osteoporosis at age 45 when she was diagnosed with breast cancer. BMD improved after treatment with Tamoxifen and Alendronate for 5 years. She then received Denosumab for 11 years with improvement in BMD: lumbar spine T-score of -1.7 with 11.2 % increase in BMD and femoral neck T-score of -1.9 with 20.3% increase in BMD. Denosumab was discontinued and bone markers were followed closely: Serum C-Telopeptide (CTx) at that time of discontinuation was 55 pg/mL (104-1008 pg/ mL). She received IV Zolendronic acid (ZDN) 6 months after cessation of Denosumab when her CTx was 163. There was a marked increase in bone remodeling 12 months after discontinuation of Denosumab despite IV ZDN given 6 months after discontinuation of Denosumab. BMD showed a mild decrease in spine BMD and a marked 14.5% decrease in femoral neck BMD. Oral weekly alendronate 70 mg was started, additional second dose of IV ZDN was administered, and oral bisphosphonate continued. Bone markers are showing a gradual decline. The expected 50-60% reduction of bone remodeling did not occur with IV ZDN suggesting some resistance to the antiresorptive effect of the most potent bisphosphonate. The rebound increase in bone remodeling following the cessation of Denosumab is believed to stem from the emergence of new osteoclasts from precursors, and/or the transition of osteoclasts into more aggressive osteomorphs. To safely discontinue Denosumab, clinicians should monitor bone markers closely and administer IV ZDN coinciding with activation of remodeling. Additional IV ZDN in combination with oral alendronate may be necessary if there is persistent increase in bone remodeling.

Volume

39

First Page

165

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