Some articles are only available as abstracts. Other are available in full text at Pub Med or Pub Med Central. If you go to the publishers you may have to pay. But sometimes if you write to an author they will send you full text (just don't ask authors for medical advice). I've include author information and you can generally Google them to get more info.
Please note that it was never my intention to "discontinue" Prolia. However, nowhere that I can find in Amgen's information about Prolia is the word "delay." As I learned too late, the concept of "delay" appears to be subsumed under the heading of "discontinuing" (or "stopping.") While this might make sense to medical professionals, most lay people would not interpret "delay" as being the same as "stopping" or "discontinuation."
Since the topic of this blog is what happened when my Prolia shot was delayed by the prescribing entities, it seems appropriate to include articles about "stopping" or "discontinuing" herein. Again, these are in no way intended as medical advice. Medical advice should come from your qualified medical advisor.
Here are just a few citations, followed by abstracts in some instances, and one link to full text.
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Current Osteoporosis Reports
https://doi.org/10.1007/s11914-019-00502-4THERAPEUTICS AND MEDICAL MANAGEMENT (S JAN DE BEUR AND B CLARKE, SECTION
EDITORS)
Stopping Denosumab
Olivier Lamy1,2 & Delphine Stoll1 & Bérengère Aubry-Rozier1,3 & Elena Gonzalez Rodriguez1,4
# Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract
Purpose of Review Denosumab discontinuation is associated with a rebound effect manifesting by an increased risk of multiple
spontaneous vertebral fractures. The purpose of this review is to (1) better characterize this risk and (2) find solutions to avoid it.
Recent Findings In the absence of a potent bisphosphonate prescription at denosumab discontinuation, the frequency of multiple
vertebral fractures is common or frequent (≥ 1/100 and < 1/10). In five recent case series, the median number of vertebral
fractures was 5 within 7 to 20 months (median 11) after the last denosumab injection. Prescribing bisphosphonate before starting
denosumab and/or after stopping denosumab may reduce this risk. However, only small case series have evaluated these
strategies.
Summary After the second denosumab dose, there is a rebound effect with an increased risk of multiple vertebral fractures. A
potent bisphosphonate prescribed at denosumab discontinuation could reduce this risk. As denosumab discontinuation is characterized
by many uncertainties, denosumab is a second-line treatment for osteoporosis. Studies are urgently needed to define the
management of denosumab discontinuation.
Keywords Denosumab discontinuation . Osteoporosis . Rebound effect . Spontaneousmultiple vertebral fractures
Other Publications:
Editorial:
This appeared in: Osteoporosis International
, Volume 27, Issue 5, pp 1677–1682| McClung MR
Cancel the denosumab holiday
E-pub 2016 Mar 1
Denosumab is the generic name for Prolia.
This is one of many related articles by McClung which you may find by clicking on his name.
Please note my own "denosumab holiday" was totally unintentional, as noted elsewhere in this blog, and the result of an entirely avoidable medical clerical error.
But the painful and disabling results were the same!
Author McClung's given address is:
- Oregon Osteoporosis Center, 2881 NW Cumberland Road, Portland, OR, 97210, USA. mmcclung@orost.com.
Review Articles:
1. Bone. 2017 Dec;105:11-17. doi: 10.1016/j.bone.2017.08.003. Epub 2017 Aug 5.
Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS.
Tsourdi E1, Langdahl B2, Cohen-Solal M3, Aubry-Rozier B4, Eriksen EF5, Guañabens N6, Obermayer-Pietsch B7, Ralston SH8, Eastell R9, Zillikens MC10.
(*See abstract of the above article below.)
2. Consult Pharm. 2018 Mar 1;33(3):142-151. doi: 10.4140/TCP.n.2018.142.
Effects of Denosumab After Treatment Discontinuation : A Review of the Literature.
Case Studies:
- J Clin Endocrinol Metab. 2017 Feb 1;102(2):354-358. doi: 10.1210/jc.2016-3170.
Severe Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: 9 Clinical Cases Report.
Lamy O1, Gonzalez-Rodriguez E1, Stoll D1, Hans D1, Aubry-Rozier B1.
Osteoporos Int. 2016 May;27(5):1923-5. doi: 10.1007/s00198-015-3380-y. Epub 2015 Oct 28.
Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports.
Osteoporos Int. 2016 May;27(5):1917-21. doi: 10.1007/s00198-015-3458-6. Epub 2015 Dec 22.
Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics.
Popp AW1, Zysset PK2, Lippuner K3.
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*Abstract and more of the first review article above:
Bone. 2017 Dec;105:11-17. doi: 10.1016/j.bone.2017.08.003. Epub 2017 Aug 5.
Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS.
Tsourdi E1, Langdahl B2, Cohen-Solal M3, Aubry-Rozier B4, Eriksen EF5, Guañabens N6, Obermayer-Pietsch B7, Ralston SH8, Eastell R9, Zillikens MC10.
Author information
- 1
- Department of Medicine III, Technische Universität Dresden, Dresden, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany.
- 2
- Medical Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark.
- 3
- Inserm U1132 and University Paris-Diderot, Department of Rheumatology, Lariboisière Hospital, Paris, France.
- 4
- Centre of bone diseases, Lausanne University Hospital, Lausanne, Switzerland.
- 5
- Department of Clinical Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Institute of Clinical Medicine, Oslo University, Oslo, Norway.
- 6
- Department of Rheumatology, Metabolic Bone Diseases Unit, Hospital Clínic, Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.
- 7
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria.
- 8
- Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK.
- 9
- Mellanby Centre for Bone Research, University of Sheffield, UK.
- 10
- Bone Center, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. Electronic address: m.c.zillikens@erasmusmc.nl.
Abstract
INTRODUCTION:
The optimal duration of osteoporosis treatment is controversial. As opposed to bisphosphonates, denosumab does not incorporate into bone matrix and bone turnover is not suppressed after its cessation. Recent reports imply that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures.
METHODS:
The European Calcified Tissue Society (ECTS) formed a working group to perform a systematic review of existing literature on the effects of stopping denosumab and provide advice on management.
RESULTS:
Data from phase 2 and 3 clinical trials underscore a rapid decrease of bone mineral density (BMD) and a steep increase in bone turnover markers (BTMs) after discontinuation of denosumab. Clinical case series report multiple vertebral fractures after discontinuation of denosumab and a renewed analysis of FREEDOM and FREEDOM Extension Trial suggests, albeit does not prove, that the risk of multiple vertebral fractures may be increased when denosumab is stopped due to a rebound increase in bone resorption.
CONCLUSION:
There appears to be an increased risk of multiple vertebral fractures after discontinuation of denosumab although strong evidence for such an effect and for measures to prevent the occurring bone loss is lacking. Clinicians and patients should be aware of this potential risk. Based on available data, a re-evaluation should be performed after 5years of denosumab treatment. Patients considered at high fracture risk should either continue denosumab therapy for up to 10years or be switched to an alternative treatment. For patients at low risk, a decision to discontinue denosumab could be made after 5years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover. However, since the optimal bisphosphonate regimen post-denosumab is currently unknown continuation of denosumab can also be considered until results from ongoing trials become available. Based on current data, denosumab should not be stopped without considering alternative treatment in order to prevent rapid BMD loss and a potential rebound in vertebral fracture risk.
Copyright © 2017 Elsevier Inc. All rights reserved.
KEYWORDS:
Denosumab; Discontinuation; Fractures; Osteoporosis treatment; Position paper
PMID: 28789921 DOI: 10.1016/j.bone.2017.08.003
[Indexed for MEDLINE]
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
(Note: The following article received financial support from Amgen.
Osteoporos Int. 2017; 28(5): 1723–1732.
Published online 2017 Jan 31. doi: [10.1007/s00198-017-3919-1]
PMCID: PMC5391373
PMID: 28144701
Observations following discontinuation of long-term denosumab therapy
1,2 R. B. Wagman,3 P. D. Miller,4 A. Wang,3 and E. M. Lewiecki5
Author information Article notes Copyright and License information Disclaimer
Summary
Stopping denosumab after 8 years of continued treatment was associated with bone loss during a 1-year observation study in patients who were not prescribed osteoporosis treatment. Bone loss was attenuated in patients who began another osteoporosis therapy. Treatment to prevent bone loss upon stopping denosumab should be considered.
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Contributor Information
M. R. McClung, Phone: 1-503-929-9633, Email: moc.liamg@coo.gnulccmm.
R. B. Wagman, Email: moc.negma@namgawr.
P. D. Miller, Email: moc.loa@RBCCrelliM.
A. Wang, Email: moc.negma@gnawa.
E. M. Lewiecki, Email: moc.liamg@ikceiwelm.
Conflicts of interest
MRM is a consultant for Amgen Inc., Merck, and Radius Health and receives honoraria from Amgen Inc. and Merck. RBW and AW are employees of and holders of stock and/or stock options in Amgen Inc. PDM receives research grants from Alexion, Eli Lilly, Amgen Inc., Novartis, National Bone Health Alliance, Pfizer, University of Alabama, Boehringer Ingelheim, Merck, Merck Serono, and Radius Health and is a consultant for Grunenthal, Shionogi, Radius Health, Amgen Inc., and Eli Lilly. EML receives research grants from Amgen Inc., Eli Lilly, and Merck and is a consultant for Amgen Inc., Eli Lilly, Merck, and Radius Health.
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Financial support
This study was sponsored by Amgen Inc., Thousand Oaks, CA, USA.
And here's an article about Prolia issues in the FDA reporting system published in a Legal database, Lawyers and Settlements:
Prolia LInked to Serious Adverse Events in FDA Reporting System