Evidence map›Paper›PMID 32535678›Full record

SynthesisSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer2021

Long-term impact of bone-modifying agents for the treatment of bone metastases: a systematic review.

Terry L Ng, Megan M Tu, Mohammed F K Ibrahim, Bassam Basulaiman, Sharon F McGee, Amirrtha Srikanthan, Ricardo Fernandes, Lisa Vandermeer, Carol Stober, Marta Sienkiewicz and 5 more

Registry-linked trialAbstract readSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04549207 (A Randomised Trial Comparing Continuation or De-escalation of Bone Modifying Agents), which is not on this map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.3field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04549207 phase4active not recruitingnot on this map

A Randomised Trial Comparing Continuation or De-escalation of Bone Modifying Agents (BMA) in Patients Treated for Over 2 Years for Bone Metastases From Either Breast or Castration-resistant Prostate Cancer (REaCT-Hold BMA)

TypeinterventionalSponsorOttawa Hospital Research InstituteRan2020 to 2026Enrolled240ConditionsBreast Cancer, Castration-resistant Prostate CancerArmsBone modifying agent
3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 58 citations in OpenAlex.

  1. Symptomatic skeletal-related events in patients receiving longer term bone-modifying agents for bone metastases from breast and castration resistant prostate cancers.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022
    Trial
  2. Trial
  3. Review
  4. Review
  5. Article
  6. A qualitative analysis of dental challenges for oncology patients receiving bone-modifying agents.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
    Review
  7. Observational
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Long-Term Efficacy and Safety of Denosumab: Insights beyond 10 Years of Use.Endocrinology and metabolism (Seoul, Korea) · 2025
    Review
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Terry L NgDivision of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada. teng@toh.ca.ORCID https://orcid.org/0000-0001-6128-3137
Megan M TuOttawa Hospital Research Institute, Ottawa, ON, Canada.
Mohammed F K IbrahimDivision of Clinical Sciences, Medical Oncology, Northern Ontario School of Medicine, Thunder Bay, ON, P7B 5E1, Canada.
Bassam BasulaimanComprehensive Cancer Center -Medical Oncology, King Fahad Medical City, Riyadh, Saudi Arabia.
Sharon F McGeeDivision of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.
Amirrtha SrikanthanDivision of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.
Ricardo FernandesDivision of Medical Oncology, London Regional Cancer Program, London Health Sciences Centre, University of Western Ontario, London, ON, Canada.
Lisa VandermeerOttawa Hospital Research Institute, Ottawa, ON, Canada.
Carol StoberOttawa Hospital Research Institute, Ottawa, ON, Canada.
Marta SienkiewiczOttawa Hospital Research Institute, Ottawa, ON, Canada.
Ahwon JeongOttawa Hospital Research Institute, Ottawa, ON, Canada.
Deanna SaundersOttawa Hospital Research Institute, Ottawa, ON, Canada.
Arif A AwanDivision of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.
Brian HuttonOttawa Hospital Research Institute, Ottawa, ON, Canada.
Mark J ClemonsDivision of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.
Ottawa Hospital · CAUniversity of Ottawa · CAKing Fahd Medical City · SANOSM University · CAWestern University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeBone-modifying agents (BMAs) for bone metastases are commonly prescribed for many years even though randomized clinical trials are only 1-2 years in duration. A systematic review on the risk-benefit of BMA use for > 2 years in breast cancer or castrate-resistant prostate cancer was conducted.

methodsMEDLINE, Embase, and Cochrane databases were searched (1970-February 2019) for randomized and observational studies, and case series reporting on BMA efficacy (skeletal-related events and quality of life) and toxicity (osteonecrosis of the jaw, renal impairment, hypocalcemia, and atypical femoral fractures) beyond 2 years.

resultsOf 2107 citations, 64 studies were identified. Three prospective and 9 retrospective studies were eligible. Data beyond 2 years was limited to subgroup analyses in all studies. Only one study (n = 181) reported skeletal-related event rates based on bisphosphonate exposure, with decreased rates from 27.6% (0-24 months) to 15.5% (> 24 months). None reported on quality of life. All 12 studies (denosumab (n = 948), zoledronate (n = 1036), pamidronate (n = 163), pamidronate-zoledronate (n = 522), ibandronate (n = 118)) reported ≥ 1 toxicity outcome. Seven bisphosphonate studies (n = 1077) and one denosumab study (n = 948) reported on osteonecrosis of the jaw. Across three studies (n = 1236), osteonecrosis of the jaw incidence ranged from 1 to 4% in the first 2 years to 3.8-18% after 2 years. Clinically significant hypocalcemia ranged from 1 to 2%. Severe renal function decline was ≤ 3%. Atypical femoral fractures were rare.

conclusionsEvidence informing the use of BMA beyond 2 years is heterogeneous and based on retrospective analysis. Prospective randomized studies with greater emphasis on quality of life are needed. PROSPERO REGISTRATION NUMBER: CRD42019126813.

Indexed as

Bone Density Conservation AgentsBone NeoplasmsBreast NeoplasmsDiphosphonatesFemaleHumansMaleObservational Studies as TopicProspective StudiesProstatic NeoplasmsQuality of LifeRandomized Controlled Trials as TopicRetrospective StudiesBone Density Conservation AgentsDiphosphonatesBisphosphonatesBone metastasesDenosumabSkeletal-related eventsSystematic review

Identifiers

PMID32535678
OpenAlexW3035007021

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.