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

被引：8
作者：
Iranikhah, Maryam [1 ]
Deas, Crystal [1 ]
Murphy, Pilar [1 ]
Freeman, Maisha Kelly [1 ,2 ]
机构：
[1] Samford Univ, Pharm Practice, Birmingham, AL 35229 USA
[2] Samford Univ, CHIPOR, Birmingham, AL USA
来源：
CONSULTANT PHARMACIST | 2018年 / 33卷 / 03期
关键词：
Bone mineral density; Denosumab; Discontinuation; Drug holiday; Fractures;
D O I：
10.4140/TCP.n.2018.142
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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.
引用
收藏
页码：142 / 151
页数：10
相关论文
共 18 条
  • [1] Miller P.D., Pannacciulli N., Brown J.P., Et al., Denosumab or zoledronic acid in postmenopausal women with osteoporosis previously treated with oral bisphosphonate, J Clin Endocrinol Metab, 101, pp. 3163-3170, (2009)
  • [2] Curtis E.M., Moon R., Harvey N.C., Et al., The impact of fragility fracture and approaches to osteoporosis risk assessment worldwide, Bone
  • [3] Cosman F., De Beur S.J., LeBoff M.S., Et al., Clinician’s guide to prevention and treatment of osteoporosis, Osteoporos Int, 25, pp. 2359-2381, (2014)
  • [4] Black D.M., Bauer D.C., Schwartz A.V., Et al., Continuing bisphosphonate treatment for osteoporosis—for whom and how long?, N Engl J Med, 366, pp. 2051-2053, (2012)
  • [5] Prolia® (Denosumab) Prescribing Information
  • [6] Baron R., Serge F., Graham R., Et al., Denosumab and bisphosphonates: Different mechanisms of action and effects, Bone, 48, pp. 677-692, (2011)
  • [7] Miller P.D., Bolognese M.A., Lewiecki M.E., Et al., Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: A randomized blinded phase 2 clinical trial, Bone, 43, pp. 222-229, (2008)
  • [8] Bone H., Bolognese M., Gallagher J., Et al., Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass, J Clin Endocrinol Metab, 96, pp. 972-980, (2011)
  • [9] Seeman E., Delmas P.D., Hanley D.A., Et al., Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate, J Bone Miner Res, 25, pp. 1886-1894, (2010)
  • [10] Brown J.P., Prince R.L., Deal C., Et al., Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: A randomized, blinded, phase 3 trial, J Bone Miner Res, 24, pp. 153-161, (2009)
12