Effects of Denosumab After Treatment Discontinuation : A Review of the Literature.

Objective: To review and summarize studies on the effects of denosumab on bone mineral density following the discontinuation of therapy.

Data sources: A search of PubMed (1966-July 2017) and International Pharmaceutical Abstracts (1970-July 2017) was conducted using the Medical Subject Headings (MeSH) terms denosumab, osteoporosis, and withholding treatment in combination with free term searches including the words drug holiday, discontinue, discontin*, and drug discontinuation.

Study selection and data extraction: An initial review yielded 10 articles. Four articles that addressed the effects of denosumab discontinuation on markers of overall bone health, fracture risk, or bone histology were included in the final review.

Data synthesis: Denosumab is a monoclonal antibody indicated for the treatment of osteoporosis in men and postmenopausal women. Denosumab has proven beneficial effects on bone remodeling and bone mineral density, and these effects have been noted to be reversed upon treatment discontinuation because of the agent's lack of incorporation into bone matrix. After 12 to 24 months off denosumab therapy, BMD, BTMs levels, as well as histologic and histomorphometric analyses, were reflective of baseline values. The number of studies evaluating the residual skeletal effects of denosumab is limited, and the sample sizes in the articles reviewed were relatively small.

Conclusion: An evaluation of studies showed that the discontinuation of denosumab results in loss of bone mineral density and a decline to near baseline values within 12 months of discontinuing therapy. Larger extension studies in a more diverse population need to be conducted to extrapolate the data to other patient groups.