&lt;p&gt;Inflammation, Bone Healing and Osteonecrosis: From Bedside to Bench&lt;/p&gt;

Goodman, Stuart B.; Maruyama, Masahiro

doi:10.2147/jir.s281941

Cited by 37 publications

(31 citation statements)

References 101 publications

(127 reference statements)

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“…Avascular necrosis, also known as osteonecrosis, is a generic term referring to the ischemic death of the constituents of bone [ 1 , 2 ]. Osteonecrosis has a wide variety of causes and can affect nearly any bone in the human body, counterpart individually each osteonecrosis-affected bone has unique clinical, etiologic, and prognostic factors.…”

Section: Introductionmentioning

confidence: 99%

Medication-Related Osteonecrosis of the Jaw: A Critical Narrative Review

Lorenzo-Pouso

Bagán

et al. 2021

JCM

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Background: Nearly two decades have passed since a paradoxical reaction in the orofacial region to some bone modifying agents and other drugs was recognized, namely medication-related osteonecrosis of the jaw (MRONJ). Purpose: The aim of this manuscript was to critically review published data on MRONJ to provide an update on key terminology, concepts, and current trends in terms of prevention and diagnosis. In addition, our objective was to examine and evaluate the therapeutic options available for MRONJ. Methods: The authors perused the most relevant literature relating to MRONJ through a search in textbooks and published articles included in several databases for the years 2003–2021. Results and conclusions: A comprehensive update of the current understanding of these matters was elaborated, addressing these topics and identifying relevant gaps of knowledge. This review describes our updated view of the previous thematic blocks, highlights our current clinical directions, and emphasizes controversial aspects and barriers that may lead to extending the accumulating body of evidence related to this severe treatment sequela.

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Section: Introductionmentioning

confidence: 99%

Medication-Related Osteonecrosis of the Jaw: A Critical Narrative Review

Lorenzo-Pouso

Bagán

et al. 2021

JCM

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“…Moreover, those affected by ONFH are typically young, active individuals between 20 and 40 years old [ 4 ]. Although the exact etiology and pathophysiology of ONFH is unknown, it has been well established that glucocorticoid use, increased alcohol intake, and chronic inflammation play important roles in the development of the disease [ 1 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits

et al. 2021

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Background Approximately one third of patients undergoing core decompression (CD) for early-stage osteonecrosis of the femoral head (ONFH) experience progression of the disease, and subsequently require total hip arthroplasty (THA). Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH. Methods In vitro studies: Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20 mg/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed. Results In vitro studies: PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (P < 0.001) and CMV-PDGF-BB-MSCs (P < 0.05) at days 3 and 7. CMV-PDGF-BB-MSCs demonstrated greater PDGF-BB expression than PGK-PDGF-BB-MSCs (P < 0.01). However, PGK-PDGF-BB-MSCs exhibited greater alkaline phosphatase staining at 14 days (P < 0.01), and osteogenic differentiation at 28 days (P = 0.07) than CMV-PDGF-BB-MSCs. In vivo: The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (P = 0.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (P < 0.001), greater osteoclast density (P < 0.01), and greater angiogenesis (P < 0.01) than the other treatment groups. Conclusion The use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.

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“…These cells also have essential differentiation capacities needed to repair damaged bone and cartilage tissues in ON [ 12 ]. More recently, their high proliferation and ability of suppression of immune response associated with tissue damage via the production of immunosuppressive factors, indoleamine 2,3 dioxygenase (IDO), Transforming growth factor-beta (TGF-β), prostaglandin E2 (PGE-2) and IL-10 have been considered equally important [ 13 , 14 , 15 ]. A controlled inflammatory reaction is required for the normal bone healing process and is deemed necessary for timely fracture repair and tissue regeneration in ON [ 14 ].…”

Section: Msc Therapy For Osteonecrosismentioning

confidence: 99%

Bone Marrow Multipotent Mesenchymal Stromal Cells as Autologous Therapy for Osteonecrosis: Effects of Age and Underlying Causes

et al. 2021

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Bone marrow (BM) is a reliable source of multipotent mesenchymal stromal cells (MSCs), which have been successfully used for treating osteonecrosis. Considering the functional advantages of BM-MSCs as bone and cartilage reparatory cells and supporting angiogenesis, several donor-related factors are also essential to consider when autologous BM-MSCs are used for such regenerative therapies. Aging is one of several factors contributing to the donor-related variability and found to be associated with a reduction of BM-MSC numbers. However, even within the same age group, other factors affecting MSC quantity and function remain incompletely understood. For patients with osteonecrosis, several underlying factors have been linked to the decrease of the proliferation of BM-MSCs as well as the impairment of their differentiation, migration, angiogenesis-support and immunoregulatory functions. This review discusses the quality and quantity of BM-MSCs in relation to the etiological conditions of osteonecrosis such as sickle cell disease, Gaucher disease, alcohol, corticosteroids, Systemic Lupus Erythematosus, diabetes, chronic renal disease and chemotherapy. A clear understanding of the regenerative potential of BM-MSCs is essential to optimize the cellular therapy of osteonecrosis and other bone damage conditions.

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<p>Inflammation, Bone Healing and Osteonecrosis: From Bedside to Bench</p>

Cited by 37 publications

References 101 publications

Medication-Related Osteonecrosis of the Jaw: A Critical Narrative Review

Medication-Related Osteonecrosis of the Jaw: A Critical Narrative Review

The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits

Bone Marrow Multipotent Mesenchymal Stromal Cells as Autologous Therapy for Osteonecrosis: Effects of Age and Underlying Causes

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