The biology and treatment of acute long-bones diaphyseal fractures: Overview of the current options for bone healing enhancement

Marongiu, Giuseppe; Dolci, Andrea; Verona, Marco; Capone, Antonio

doi:10.1016/j.bonr.2020.100249

Cited by 55 publications

(54 citation statements)

References 135 publications

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“…To reduce such a risk of delayed union or non-union related to extensive dissection, we look for osteoinductive ed osteogenic properties as well [49,[80][81][82]. BMC is derived from autologous bone marrow, and it is composed of a variety of cells, including mesenchymal stem cells that can contribute to the regeneration of mesenchymal tissues, capable of self-renewal and differentiation into various cell types such as bone, muscle, tendon and ligament.…”

Section: Discussionmentioning

confidence: 99%

“…Physiological PTH actions include stimulation of osteogenesis by direct effects on cells responsible of bone formation (osteoblasts) and indirectly by increasing intestinal absorption of calcium and increasing the renal tubular reabsorption of calcium and elimination of phosphate. Evidence is present in the Literature that Teriparatide can be useful in the treatment of nonunions, delayed unions and AFFs [47][48][49][50][51][52]. Also, in an animal model a combined administration of subcutaneous Teriparatide and systemic human mesenchymal stem cells showed a synergic positive effect on bone healing [93].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, studies are present in the literature suggesting that Teriparatide can be usefull in fractures' and nonunions' management as well as for osteoporosis [47][48][49][50][51][52]. This drug works by stimulating osteoblasts and reducing osteoblast apoptosis, increasing callus formation, improving mechanical strength, and resulting in increased osteoblast life span.…”

Section: Introductionmentioning

confidence: 99%

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Combined Surgical And Medical Treatment For Periprosthetic Femoral Fractures Over A Stable Stem (Vancouver Type B1 And C): A Proposal Of A Therapeutic Algorithm To Reduce The Risk Of Nonunion.

Mondanelli

Colasanti

Cataldi

et al. 2020

Preprint

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Background: There is lack of consensus regarding best operative fixation strategy for periprosthetic femoral fractures (PFFs) around a stable stem. Based on our experience in the treatment of nonunions after PFFs and other challenging cases and on Literature, we propose an algorithm that can guide in choosing the ideal surgical technique even for first-time PFFs with a stable stem.Methods: We retrospectively reviewed data on patients who failed to heal after a surgically treated Vancouver type B1 or C PFF. All patients were treated with locking plate, double structural allograft and autologous bone marrow concentrate (BMC) over a platelet-rich plasma (PRP)-based membrane at fracture site. All patients were also pharmacologically treated with Teriparatide in the postoperative period. We studied patients with radiograms, histological evaluation of the nonunion area, and phosphocalcic metabolism. Patients were assessed subjectively, clinically and radiographically until healing and then annually.Results: All nonunions healed over a six months period, and functional recovery appeared to be good. Retrospective evaluation of the proposed algorithm showed that none of the patients met biological or mechanical criteria such as to make valid the treatment with locking plate alone.Conclusion: Mechanical factors are not the only issues that should be taken into account when choosing the surgical approach to PFFs over a stable stem. Systemic and local biological conditions are factors that should drive to a rigid fixation with absolute stability (using a plate and structural allograft) plus local biological support (structural allograft and autologous BMC in a PRP-based scaffold) and systemic anabolic treatment (Teriparatide) in the first instance. A therapeutic algorithm is proposed, given the prosthetic stem to be stable, taking into account mechanical and biological criteria.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Combined Surgical And Medical Treatment For Periprosthetic Femoral Fractures Over A Stable Stem (Vancouver Type B1 And C): A Proposal Of A Therapeutic Algorithm To Reduce The Risk Of Nonunion.

Mondanelli

Colasanti

Cataldi

et al. 2020

Preprint

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“…Fractures at high risk of impaired bone healing should be identified according to fracture characteristics and patients' related factors, in order to choose the best-suited treatment [3]. In the last decade, the so-called "Diamond Concept" proposed a new paradigm for complex fractures and impaired union management in which the main elements-mechanical environment, scaffolds, growth factors and cell therapies-could be applied together to enhance bone healing [4]. The primary goal of the treatment is to provide mechanical stability at the fracture site preserving the local vascular supply, therefore, diaphyseal fractures of long bones are mostly surgically treated.…”

Section: Introductionmentioning

confidence: 99%

The Treatment of Acute Diaphyseal Long-bones Fractures with Orthobiologics and Pharmacological Interventions for Bone Healing Enhancement: A Systematic Review of Clinical Evidence

et al. 2020

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Background: The healing of long bones diaphyseal fractures can be often impaired and eventually end into delayed union and non-union. A number of therapeutic strategies have been proposed in combination with surgical treatment in order to enhance the healing process, such as scaffolds, growth factors, cell therapies and systemic pharmacological treatments. Our aim was to investigate the current evidence of bone healing enhancement of acute long bone diaphyseal fractures. Methods: A systematic review was conducted by using Pubmed/MEDLINE; Embase and Ovid databases. The combination of the search terms “long-bones; diaphyseal fracture; bone healing; growth factors; cell therapies; scaffolds; graft; bone substitutes; orthobiologics; teriparatide”. Results: The initial search resulted in 4156 articles of which 37 papers fulfilled the inclusion criteria and were the subject of this review. The studies included 1350 patients (837 males and 513 females) with a mean age of 65.3 years old. Conclusions: General lack of high-quality studies exists on the use of adjuvant strategies for bone healing enhancement in acute shaft fractures. Strong evidence supports the use of bone grafts, while only moderate evidence demineralized bone matrix and synthetic ceramics. Conflicting results partially supported the use of growth factors and cell therapies in acute fractures. Teriparatide showed promising results, particularly for atypical femoral fractures and periprosthetic femoral fractures.

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“…Bone defects or fracture nonunion, which is still no e cacious way for the treatment, being one of the most intractable clinical diseases for orthopedic surgeons [1,2]. Severe fracture, bone tumor ablation, debridement of a wide range of bone infections and congenital defects can lead to the failure of fracture healing [3].…”

Section: Introductionmentioning

confidence: 99%

Low-Dose IL-34 Has No Effect on Osteoclastogenesis But Promotes Osteogenesis of Hbmscs Partly Via Activation of The PI3K/AKT And ERK Signaling Pathways 

Bai

Zhong

et al. 2020

Preprint

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Background: Inflammatory microenvironment is significant to the differentiation and function of mesenchymal stem cells(MSCs). It evidentially influences the osteoblastogenesis of MSCs. IL-34, a newly discovered cytokine, playing a key role in metabolism. However, the research on its functional role in the osteogenesis of MSCs was rarely reported. Here, we described the regulatory effects of low-dose IL-34 on both osteoblastogenesis and osteoclastogenesis.Methods: We performed the osteogenic effects of hBMSCs by exogenous and overexpressed IL-34 in vitro, so was the osteoclastogenesis effects of mBMMs by extracellular IL-34. CCK-8 was used to assess the effect of IL-34 on the viability of hBMSCs and mBMMs. ALP staining, ARS and TRAP staining were used to evaluate ALP activity, mineral deposition and osteoclastogenesis, respectively. qRT-PCR and Western blotting analysis were performed to detect the expression of target genes and proteins. ELISA was used to evaluate the concentrations of IL-34. In vivo, a rat tibial osteotomy model and an OVX model were established. Radiographic analysis and histological evaluation were performed to confirm the therapeutic effects of IL-34 in fracture healing and osteoporosis. Statistical differences were evaluated by two-tailed Student’s t-test, one-way ANOVA with Bonferroni’s post hoc test and two-way ANOVA with Bonferroni multiple comparisons post hoc test in the comparison of 2 groups, more than 2 groups and different time points of treated groups, respectively. Results: Promoted osteoblastogenesis of hBMSCs was observed after treated by exogenous or overexpressed IL-34 in vitro, confirmed by increased mineral deposits and ALP activity. Furthermore, exogenous or overexpressed IL-34 enhanced the expression of p-AKT and p-ERK. The specific AKT and ERK signaling pathway inhibitors suppressed the enhancement of osteoblastogenesis induced by IL-34. In a rat tibial osteotomy model, imaging and histological analyses testified the local injection of exogenous IL-34 improved bone healing. However, the additional IL-34 has no influence on both osteoclastogenesis of mBMMs in vitro and osteoporosis of OVX model of rat in vivo. Conclusions: Collectively, our study demonstrate that low-dose IL-34 regulates osteogenesis of hBMSCs partly via the PIK/AKT and ERK signaling pathway and enhances fracture healing, with neither promoting nor preventing osteoclastogenesis in vitro and osteoporosis in vivo.

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The biology and treatment of acute long-bones diaphyseal fractures: Overview of the current options for bone healing enhancement

Cited by 55 publications

References 135 publications

Combined Surgical And Medical Treatment For Periprosthetic Femoral Fractures Over A Stable Stem (Vancouver Type B1 And C): A Proposal Of A Therapeutic Algorithm To Reduce The Risk Of Nonunion.

Combined Surgical And Medical Treatment For Periprosthetic Femoral Fractures Over A Stable Stem (Vancouver Type B1 And C): A Proposal Of A Therapeutic Algorithm To Reduce The Risk Of Nonunion.

The Treatment of Acute Diaphyseal Long-bones Fractures with Orthobiologics and Pharmacological Interventions for Bone Healing Enhancement: A Systematic Review of Clinical Evidence

Low-Dose IL-34 Has No Effect on Osteoclastogenesis But Promotes Osteogenesis of Hbmscs Partly Via Activation of The PI3K/AKT And ERK Signaling Pathways

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The biology and treatment of acute long-bones diaphyseal fractures: Overview of the current options for bone healing enhancement

Cited by 55 publications

References 135 publications

Combined Surgical And Medical Treatment For Periprosthetic Femoral Fractures Over A Stable Stem (Vancouver Type B1 And C): A Proposal Of A Therapeutic Algorithm To Reduce The Risk Of Nonunion.

Combined Surgical And Medical Treatment For Periprosthetic Femoral Fractures Over A Stable Stem (Vancouver Type B1 And C): A Proposal Of A Therapeutic Algorithm To Reduce The Risk Of Nonunion.

The Treatment of Acute Diaphyseal Long-bones Fractures with Orthobiologics and Pharmacological Interventions for Bone Healing Enhancement: A Systematic Review of Clinical Evidence

Low-Dose IL-34 Has No Effect on Osteoclastogenesis But Promotes Osteogenesis of Hbmscs Partly Via Activation of The PI3K/AKT And ERK Signaling Pathways&nbsp;

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Low-Dose IL-34 Has No Effect on Osteoclastogenesis But Promotes Osteogenesis of Hbmscs Partly Via Activation of The PI3K/AKT And ERK Signaling Pathways