Evidence map›Paper›PMID 18214569›Full record

ReviewOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2008

Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy.

R G G Russell, N B Watts, F H Ebetino, M J Rogers

Abstract readReview
PubMed Publisher
In one paragraph

Review in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 533 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
533citing papers in PubMed, 8 pooled it
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

533 citing papers in PubMed, 8 syntheses or guidelines pooled it.

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  6. Differences between bisphosphonate-related and denosumab-related osteonecrosis of the jaws: a systematic review.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021
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  10. Early changes in bone turnover and bone mineral density after discontinuation of long-term oral bisphosphonates: a post hoc analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021
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  12. Impact of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk: real-world evidence from a retrospective cohort study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
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473 more citing papers are in PubMed but not listed here.

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

4 authors.

R G G RussellNuffield Department of Orthopaedic Surgery, Oxford University Institute of Musculoskeletal Sciences (The Botnar Research Centre), Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, UK. graham.russell@ndos.ox.ac.uk
N B Watts
F H Ebetino
M J Rogers

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

unlabelledBisphosphonates (BPs) are well established as the leading drugs for the treatment of osteoporosis. There is new knowledge about how they work. The differences that exist among individual BPs in terms of mineral binding and biochemical actions may explain differences in their clinical behavior and effectiveness.

introductionThe classical pharmacological effects of bisphosphonates (BPs) appear to be the result of two key properties: their affinity for bone mineral and their inhibitory effects on osteoclasts. DISCUSSION: There is new information about both properties. Mineral binding affinities differ among the clinically used BPs and may influence their differential distribution within bone, their biological potency, and their duration of action. The antiresorptive effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) appear to result from their inhibition of the enzyme farnesyl pyrophosphate synthase (FPPS) in osteoclasts. FPPS is a key enzyme in the mevalonate pathway, which generates isoprenoid lipids utilized for the post-translational modification of small GTP-binding proteins that are essential for osteoclast function. Effects on other cellular targets, such as osteocytes, may also be important. BPs share several common properties as a drug class. However, as with other families of drugs, there are obvious chemical, biochemical, and pharmacological differences among the individual BPs. Each BP has a unique profile that may help to explain potential clinical differences among them, in terms of their speed and duration of action, and effects on fracture reduction.

Indexed as

AnimalsBone and BonesBone DensityBone Density Conservation AgentsBone ResorptionDiphosphonatesHumansOsteoclastsOsteocytesOsteoporosisStructure-Activity RelationshipBone Density Conservation AgentsDiphosphonates

Identifiers

PMID18214569

What OpenQuestion holds

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Registered trials

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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.