ReviewJournal of orthopaedic research : official publication of the Orthopaedic Research Society2017
Fracture healing physiology and the quest for therapies for delayed healing and nonunion.
Review in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
94 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Platelet-Rich Plasma Combined With Autologous Grafting in the Treatment of Long Bone Delayed Union or Non-union: A Meta-Analysis.Frontiers in surgery · 2021Pooled it
- Effects of photobiomodulation in the treatment of fractures: a systematic review and meta-analysis of randomized clinical trials.Lasers in medical science · 2020Pooled it
- Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: a pilot study.Stem cell research & therapy · 2021Trial
- Soft-tissue reconstruction timing in ballistic lower extremity open fractures: impact on osteomyelitis and union.Journal of orthopaedic surgery and research · 2026Article
- Experimental study on the effect of warm acupuncture on the healing of bone nonunion in rats.Journal of the Chinese Medical Association : JCMA · 2026Article
- Exploring the mechanism of Dieda Qili Tablet on fracture healing based on network pharmacology combined with machine learning models.Scientific reports · 2026Article
- Recent Advancements in Non-surgical Approaches for the Management of Delayed Union and Nonunion in Long Bone Fractures of the Extremities: A Review.Advances in therapy · 2026Review
- RETROSPECTIVE ANALYSIS OF MALLET FINGER TREATED WITH EXTENSION BLOCK FIXATION USING THE ISHIGURO TECHNIQUE.Acta ortopedica brasileira · 2026Article
- Association between fibrinogen concentration and nonunion in fracture patients.Frontiers in surgery · 2026Article
- Engineering bone tissue with mRNA: from molecular design and delivery to clinical applications.Materials today (Kidlington, England) · 2025Article
- Functional mechanism and clinical implications of miR-455-5p in delayed fracture healing.Journal of orthopaedic surgery and research · 2025Article
- CGRP-releasing PLGA/nHA/GO composite microspheres enhance distraction osteogenesis via activation of the cAMP/PKA/CREB pathway.Materials today. Bio · 2025Article
- Article
- Time to consider fracture nonunion an orphan disease? An update into pathophysiology, epidemiology and therapeutic solutions.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025Review
- Enabling adenosine signaling to promote aged fracture healing.NPJ Regenerative medicine · 2025Article
- The influence of adrenoceptor blocker treatment on fracture healing in osteoporotic and non-osteoporotic bone.Frontiers in physiology · 2025Article
- Usefulness of non-surgical treatment without weight bearing restriction versus surgical treatment for maintaining activities of daily living in patients with peri-prosthetic femoral fractures.International orthopaedics · 2024Article
- Functional mechanism and clinical implications of mir-1271-5p in pilon fracture healing processes.Journal of orthopaedic surgery and research · 2024Article
- Double plating and iliac crest bone graft can safely fix femoral shaft nonunion.Scientific reports · 2024Article
- Evaluating the Anti-Osteoporotic Potential of Mediterranean Medicinal Plants: A Review of Current Evidence.Pharmaceuticals (Basel, Switzerland) · 2024Review
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Delayed healing and nonunion of fractures represent enormous burdens to patients and healthcare systems. There are currently no approved pharmacological agents for the treatment of established nonunions, or for the acceleration of fracture healing, and no pharmacological agents are approved for promoting the healing of closed fractures. Yet several pharmacologic agents have the potential to enhance some aspects of fracture healing. In preclinical studies, various agents working across a broad spectrum of molecular pathways can produce larger, denser and stronger fracture calluses. However, untreated control animals in most of these studies also demonstrate robust structural and biomechanical healing, leaving unclear how these interventions might alter the healing of recalcitrant fractures in humans. This review describes the physiology of fracture healing, with a focus on aspects of natural repair that may be pharmacologically augmented to prevent or treat delayed or nonunion fractures (collectively referred to as DNFs). The agents covered in this review include recombinant BMPs, PTH/PTHrP receptor agonists, activators of Wnt/β-catenin signaling, and recombinant FGF-2. Agents from these therapeutic classes have undergone extensive preclinical testing and progressed to clinical fracture healing trials. Each can promote bone formation, which is important for the stability of bridged calluses, and some but not all can also promote cartilage formation, which may be critical for the initial bridging and subsequent stabilization of fractures. Appropriately timed stimulation of chondrogenesis and osteogenesis in the fracture callus may be a more effective approach for preventing or treating DNFs compared with stimulation of osteogenesis alone. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:213-223, 2017.
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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.