The effect of compressive loading on intraosseous pressure in the femoral head in vitro.

The severe and life-threatening nature of the COVID-19 infection, the ARDS (acute respiratory distress syndrome) as well as the cytokine storm induced by the infection, commands lifesaving high doses of steroid therapy. As in all pharmacological therapies adverse effects are present. One such adverse effect which is being reported is corticosteroid induced avascular necrosis of the femoral head/ osteonecrosis of the femoral head. It must be noted that AVN principally affects the femoral head and most commonly the anterolateral aspect thereof as it is the crux of weight bearing. Corticosteroids induce fat mobilization and this thus innately enhances the likelihood of fat emboli developing from the liver to occlude minor blood vessels in the femur, this thereby compromises the microvascular environment. Superadded to this the steroid therapy disrupts calcium metabolism and homeostasis which induces hypertrophy in the intramedullary fat cells, Gaucher cells and inflammatory cells; whilst increasing the activity of osteoclasts, thus increasing bone resorption and decreasing calcium uptake and deposition; ultimately leading to an insufficiency in the trabecular and cortical bone. This insufficiency thus equates to an increased intraosseous pressure which impedes intramedullary circulation and results in avascular necrosis. It is evident that avascular necrosis is directly caused by high dose steroid therapy, however the case reports have very clearly indicated that the rapid onset of AVN post recovery from the COVID-19 infection cannot be solely attributed to steroid therapy and that another benefactor induced by the COVID-19 infection is at play. It is thus vital for treating physicians to take cognisance of this adverse effect post recovery and therefore should ensure that prophylactic bisphosphonate therapy is initiated timeously and congruently.

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Induction of PI3K/Akt-Mediated Apoptosis in Osteoclasts Is a Key Approach for Buxue Tongluo Pills to Treat Osteonecrosis of the Femoral Head

Frontiers in Pharmacology ◽

10.3389/fphar.2021.729909 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dan Wang ◽

Yicheng Liu ◽

Dandan Tang ◽

Shujun Wei ◽

Jiayi Sun ◽

...

Keyword(s):

Femoral Head ◽

Functional Annotation ◽

Caspase 3 ◽

Differentially Expressed Gene ◽

Pathway Enrichment Analysis ◽

Therapeutic Effects ◽

Dependent Manner ◽

Clinical Practices ◽

Key Genes

The Buxue Tongluo pill (BTP) is a self-made pill with the functions of nourishing blood, promoting blood circulation, dredging collaterals, and relieving pain. It consists of Angelica sinensis (Oliv.) Diels, Pheretima aspergillum (E.Perrier), Panax notoginseng (Burk.) F. H. Chen, Astragalus membranaceus (Fisch.) Bge, and Glycyrrhiza uralensis Fisch. Various clinical practices have confirmed the therapeutic effect of BTP on osteonecrosis of the femoral head (ONFH), but little attention has been paid to the study of its bioactive ingredients and related mechanisms of action. In this study, UPLC/MS-MS combined with GEO data mining was used to construct a bioactive ingredient library of BTP and a differentially expressed gene (DEG) library for ONFH. Subsequently, Cytoscape (3.7.2) software was used to analyze the protein–protein interaction between BTP and DEGs of ONFH to screen the key targets, and functional annotation analysis and pathway enrichment analysis were carried out. Finally, 34 bioactive compounds were screened, which acted on 1,232 targets. A total of 178 DEGs were collected, and 17 key genes were obtained after two screenings. By bioinformatics annotation on these key genes, a total of 354 gene ontology (GO) functional annotation analyses and 42 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. The present study found that GO and KEGG enrichment were mainly related to apoptosis, suggesting that BTP may exert an anti-ONFH effect by promoting osteoclast apoptosis. Experiments in vitro demonstrated that BTP could increase the mitochondrial membrane potential (MMP) and induce remarkable apoptosis in osteoclasts. Furthermore, we determined the apoptosis marker of cleaved(C)-caspase-3, bcl-2, and bax and found that BTP could upregulate the C-caspase-3 and bax expression in osteoclasts and decrease the expression of bcl-2, p-Akt, and p-PI3K in a dose-dependent manner, indicating that BTP could induce PI3K/Akt-mediated apoptosis in osteoclasts to treat ONFH. This study explored the pharmacodynamic basis and mechanism of BTP against ONFH from the perspective of systemic pharmacology, laying a foundation for further elucidating the therapeutic effects of BTP against ONFH.

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EVALUATION OF THE RANGE OF MOTION OF A HIP ARTHROPLASTY SYSTEM: A COMPUTER SIMULATION STUDY

Acta Ortopédica Brasileira ◽

10.1590/1413-785220212905240525 ◽

2021 ◽

Vol 29 (5) ◽

pp. 246-248

Author(s):

GUILHERME GUADAGNINI FALOTICO ◽

VALÉRIA ROMERO ◽

RICARDO BASILE ◽

EDMILSON TAKEHIRO TAKATA

Keyword(s):

Femoral Head ◽

Range Of Motion ◽

Hip Arthroplasty ◽

External Rotation ◽

Angular Displacement ◽

Computational Method ◽

Technical Standards ◽

Level Of Evidence ◽

Mean Values

ABSTRACT Objective: To date, the literature lacks consensus on the most efficient method to measure the range of motion of an in vitro prosthetic system. In this study, we propose the use of a relatively low-cost online software to measure the range of motion of hip prosthetic implants manufactured in Brazil and compare its results with the current technical standards for hip arthroplasty. Methods: Three different diameters of femoral heads were evaluated (28 mm, 32 mm, and 36 mm). The mean values of the angular displacement of the prosthesis in each motion axis were obtained by computer simulations. Results: The range of motion with each femoral head was 28mm (extension/flexion: 148°, internal/external rotation: 179°, adduction/abduction: 107°), 32 mm (152°/185°/114°), and 36 mm (158°/193°/120°). Conclusion: The computational method showed that the larger the femoral head, the greater the range of motion of the hip joint prosthetic system. Additional clinical studies are necessary to compare the physical results obtained with the values found in this study by computational modeling. Level of evidence V, Experimental study.

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Bone morphogenetic protein 2 controls steroid-induced osteonecrosis of the femoral head via directly inhibiting interleukin-34 expression

Journal of Molecular Endocrinology ◽

10.1530/jme-21-0163 ◽

2021 ◽

Author(s):

Meng Wang ◽

Hong Sung Min ◽

Haojie Shan ◽

Yiwei Lin ◽

Wenyang Xia ◽

...

Keyword(s):

Femoral Head ◽

Bone Morphogenetic Protein ◽

Inflammatory Responses ◽

Gene Knockout ◽

Osteoclast Differentiation ◽

Bone Morphogenetic Protein 2 ◽

Qrt Pcr ◽

Morphogenetic Protein ◽

Local Expression

Increased inflammatory responses is one of the major characteristics of osteonecrosis of the femoral head (ONFH). We aimed to investigate the function of bone morphogenetic protein 2 (BMP-2)/interleukin (IL)-34 axis in the inflammatory responses of ONFH. The systemic and local expression of BMPs in ONFH patients were detected by qRT-PCR and ELISA. In vitro osteoclast differentiation and ONFH mouse models, induced by 20 mg/kg methylprednisolone through intramuscular injection, were established using wild type and BMP-2-/- mice to explore the regulatory role of BMP-2 in pro-inflammatory responses and bone defects of ONFH. IL-34 expression and function were examined in vitro and in vivo through qRT-PCR, TRAP staining, and gene knockout. The systemic and local expression of BMPs were elevated in ONFH patients. BMP-2 reduced the production of pro-inflammatory cytokines and inhibited the differentiation of osteoclasts. Mechanistically, BMP-2 inhibited osteoclasts formation through suppressing IL-34 expression, and then promoted bone repair and alleviated ONFH. In conclusion, our study reveals that BMP-2 inhibits inflammatory responses and osteoclast formation through down-regulating IL-34.

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The Importance of Increased Intraosseous Pressure in the Development of Osteonecrosis of the Femoral Head: Implications for Treatment

Orthopedic Clinics of North America ◽

10.1016/s0030-5898(20)30432-6 ◽

1985 ◽

Vol 16 (4) ◽

pp. 635-654 ◽

Cited By ~ 19

Author(s):

David S. Hungerford ◽

Dennis W. Lennox

Keyword(s):

Femoral Head ◽

Intraosseous Pressure

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Elevated intraosseous pressure in the intertrochanteric region is associated with poorer results in osteonecrosis of the femoral head treated by multiple drilling

Journal of Bone and Joint Surgery - British Volume ◽

10.1302/0301-620x.90b7.20125 ◽

2008 ◽

Vol 90-B (7) ◽

pp. 852-857 ◽

Cited By ~ 17

Author(s):

M. S. Lee ◽

P.-H. Hsieh ◽

Y.-H. Chang ◽

Y.-S. Chan ◽

S. Agrawal ◽

...

Keyword(s):

Femoral Head ◽

Intraosseous Pressure

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Phenotypic Characterization of Bone Marrow Mononuclear Cells and Derived Stromal Cell Populations from Human Iliac Crest, Vertebral Body and Femoral Head

International Journal of Molecular Sciences ◽

10.3390/ijms20143454 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3454 ◽

Cited By ~ 11

Author(s):

Marietta Herrmann ◽

Maria Hildebrand ◽

Ursula Menzel ◽

Niamh Fahy ◽

Mauro Alini ◽

...

Keyword(s):

Bone Marrow ◽

Femoral Head ◽

Cell Surface ◽

Cell Cultures ◽

Vertebral Body ◽

Stromal Cells ◽

Stromal Cell ◽

Iliac Crest ◽

Surface Marker

(1) In vitro, bone marrow-derived stromal cells (BMSCs) demonstrate inter-donor phenotypic variability, which presents challenges for the development of regenerative therapies. Here, we investigated whether the frequency of putative BMSC sub-populations within the freshly isolated mononuclear cell fraction of bone marrow is phenotypically predictive for the in vitro derived stromal cell culture. (2) Vertebral body, iliac crest, and femoral head bone marrow were acquired from 33 patients (10 female and 23 male, age range 14–91). BMSC sub-populations were identified within freshly isolated mononuclear cell fractions based on cell-surface marker profiles. Stromal cells were expanded in monolayer on tissue culture plastic. Phenotypic assessment of in vitro derived cell cultures was performed by examining growth kinetics, chondrogenic, osteogenic, and adipogenic differentiation. (3) Gender, donor age, and anatomical site were neither predictive for the total yield nor the population doubling time of in vitro derived BMSC cultures. The abundance of freshly isolated progenitor sub-populations (CD45−CD34−CD73+, CD45−CD34−CD146+, NG2+CD146+) was not phenotypically predictive of derived stromal cell cultures in terms of growth kinetics nor plasticity. BMSCs derived from iliac crest and vertebral body bone marrow were more responsive to chondrogenic induction, forming superior cartilaginous tissue in vitro, compared to those isolated from femoral head. (4) The identification of discrete progenitor populations in bone marrow by current cell-surface marker profiling is not predictive for subsequently derived in vitro BMSC cultures. Overall, the iliac crest and the vertebral body offer a more reliable tissue source of stromal progenitor cells for cartilage repair strategies compared to femoral head.

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