Advertisement for orthosearch.org.uk
Results 1 - 6 of 6
Results per page:
Bone & Joint Research
Vol. 10, Issue 8 | Pages 498 - 513
3 Aug 2021
Liu Z Lu C Shen P Chou S Shih C Chen J Tien YC

Aims. Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Methods. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. Results. Suramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. Conclusion. Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498–513


Bone & Joint Open
Vol. 3, Issue 4 | Pages 340 - 347
22 Apr 2022
Winkler T Costa ML Ofir R Parolini O Geissler S Volk H Eder C

Aims

The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

Methods

HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%.


The Bone & Joint Journal
Vol. 100-B, Issue 11 | Pages 1455 - 1462
1 Nov 2018
Munro JT Millar JS Fernandez JW Walker CG Howie DW Shim VB

Aims

Osteolysis, secondary to local and systemic physiological effects, is a major challenge in total hip arthroplasty (THA). While osteolytic defects are commonly observed in long-term follow-up, how such lesions alter the distribution of stress is unclear. The aim of this study was to quantitatively describe the biomechanical implication of such lesions by performing subject-specific finite-element (FE) analysis on patients with osteolysis after THA.

Patients and Methods

A total of 22 hemipelvis FE models were constructed in order to assess the transfer of load in 11 patients with osteolysis around the acetabular component of a THA during slow walking and a fall onto the side. There were nine men and two women. Their mean age was 69 years (55 to 81) at final follow-up. Changes in peak stress values and loads to fracture in the presence of the osteolytic defects were measured.


The Bone & Joint Journal
Vol. 99-B, Issue 3 | Pages 317 - 324
1 Mar 2017
Schilcher J Palm L Ivarsson I Aspenberg P

Aims

Post-operative migration of cemented acetabular components as measured by radiostereometric analysis (RSA) has a strong predictive power for late, aseptic loosening. Also, radiolucent lines predict late loosening. Migration has been reduced by systemic bisphosphonate treatment in randomised trials of hip and knee arthroplasty. Used as a local treatment, a higher local dose of bisphosphonate can be achieved without systemic exposure. We wished to see if this principle could be applied usefully in total hip arthroplasty (THA).

Patients and Methods

In this randomised placebo-controlled, double-blinded trial with 60 participants, we compressed gauze soaked in bisphosphonate solution (ibandronate) or saline against the acetabular bone bed immediately before cementing the acetabular component. RSA, classification of radiolucent lines, the Harris Hip Score (HHS) and the Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) were carried out at three-, six-, 12-, and 24-month follow-up.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 7 | Pages 994 - 997
1 Jul 2012
Cross MB Nam D van der Meulen MCH Bostrom MPG

An 81-year-old woman presented with a fracture in the left femur. She had well-fixed bilateral hip replacements and had received long-term bisphosphonate treatment. Prolonged bisphosphonate use has been recently linked with atypical subtrochanteric and diaphyseal femoral fractures. While the current definition of an atypical fracture of the femur excludes peri-prosthetic fractures, this case suggests that they do occur and should be considered in patients with severe osteopenia. Union of the fracture followed cessation of bisphosphonates and treatment with teriparatide. Thus, this case calls into question whether prophylactic intramedullary nailing is sufficient alone to treat early or completed atypical femoral fractures.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 4 | Pages 460 - 466
1 Apr 2006
Keizer SB Kock NB Dijkstra PDS Taminiau AHM Nelissen RGHH

This retrospective study describes the long-term results of core decompression and placement of a non-vascularised bone graft in the management of avascular necrosis of the femoral head. We treated 80 hips in 65 patients, 18 by a cortical tibial autograft and 62 by a fibular allograft. The mean age of the patients was 36 years (sd 13.2). A total of 78 hips were available for evaluation of which pre-operatively six were Ficat-Arlet stage 0, three stage I, 31 stage IIA, 16 stage IIB, 13 stage III and nine stage IV.

A total of 34 hips (44%) were revised at a mean of four years (sd 3.8). Survivorship analysis using a clinical end-point showed a survival rate of 59% five years after surgery. We found a significant difference (p = 0.002) in survivorship, when using a clinical and radiological end-point, between the two grafts, in favour of the tibial autograft. We considered this difference to be the result of the better quality and increased volume of tibial bone compared with that from the trochanteric region used with the fibular allograft.

This is a relatively simple, extra-articular and reproducible procedure. In our view core decompression, removal of the necrotic tissue and packing of the cancellous grafts into the core track are vital parts of the procedure.