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Bone & Joint Research
Vol. 6, Issue 7 | Pages 399 - 404
1 Jul 2017
Sun X Liu W Cheng G Qu X Bi H Cao Z Yu Q

Objectives. The injured anterior cruciate ligament (ACL) is thought to exhibit an impaired healing response, and attempts at surgical repair have not been successful. Connective tissue growth factor (CTGF) is reported to be associated with wound healing, probably through transforming growth factor beta 1 (TGF-β1). Methods. A rabbit ACL injury model was used to study the effect of CTGF on ligament recovery. Quantitative real-time PCR (qRT-PCR) was performed for detection of changes in RNA levels of TGF-β1, type 1 collagen (COL1), type 2 collagen (COL2), SRY-related high mobility group-box gene9 (SOX9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase 13 (MMP-13). Expression of related proteins was detected by Western blotting. Results. The current study showed that CTGF could promote the recovery of an injured anterior cruciate ligament. It can upregulate mRNA and expression of TGF-β1, COL1, COL2, SOX9, and tissue inhibitor of TIMP-1, and downregulate mRNA and expression of MMP-13, suggesting that the curative effect of CTGF on injured rabbit ligaments is through regulation of these cellular factors. Conclusions. This finding revealed the healing role of CTGF in injured tissues and provides new possibilities of treating injured tissues and wound healing by using CTGF. Cite this article: X. Sun, W. Liu, G. Cheng, X. Qu, H. Bi, Z. Cao, Q. Yu. The influence of connective tissue growth factor on rabbit ligament injury repair. Bone Joint Res 2017;6:399–404. DOI: 10.1302/2046-3758.67.BJR.2016-0255.R1


Bone & Joint Research
Vol. 10, Issue 9 | Pages 558 - 570
1 Sep 2021
Li C Peng Z Zhou Y Su Y Bu P Meng X Li B Xu Y

Aims. Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH. Methods. High-throughput sequencing was used to identify genes that were differentially expressed in hip joint capsules between healthy controls and DDH patients. Biological assays including cell cycle, viability, apoptosis, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were performed to determine the roles of the differentially expressed genes in DDH pathology. Results. More than 1,000 genes were differentially expressed in hip joint capsules between healthy controls and DDH. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that extracellular matrix (ECM) modifications, muscle system processes, and cell proliferation were markedly influenced by the differentially expressed genes. Expression of Collagen Type I Alpha 1 Chain (COL1A1), COL3A1, matrix metalloproteinase-1 (MMP1), MMP3, MMP9, and MMP13 was downregulated in DDH, with the loss of collagen fibres in the joint capsule. Expression of transforming growth factor beta 1 (TGF-β1) was downregulated, while that of TGF-β2, Mothers against decapentaplegic homolog 3 (SMAD3), and WNT11 were upregulated in DDH, and alpha smooth muscle actin (αSMA), a key myofibroblast marker, showed marginal increase. In vitro studies showed that fibroblast proliferation was suppressed in DDH, which was associated with cell cycle arrest in G0/G1 and G2/M phases. Cell cycle regulators including Cyclin B1 (CCNB1), Cyclin E2 (CCNE2), Cyclin A2 (CCNA2), Cyclin-dependent kinase 1 (CDK1), E2F1, cell division cycle 6 (CDC6), and CDC7 were downregulated in DDH. Conclusion. DDH is associated with the loss of collagen fibres and fibroblasts, which may cause loose joint capsule formation. However, the degree of differentiation of fibroblasts to myofibroblasts needs further study. Cite this article: Bone Joint Res 2021;10(9):558–570


Greater trochanteric pain syndrome is a painful condition characterised by pain around the greater trochanter usually affecting middle-aged women. The majority of patients will improve with conservative management such as physiotherapy and non-steroidal anti-inflammatory drugs (NSAIDs); however, if this fails then more invasive treatments including corticosteroids and surgery may be required. Platelet-rich plasma (PRP) is an autologous blood product, which has a higher concentration of growth factors postulated to provide enhanced healing and anti-inflammatory properties. The Hip Injections PRP Vs Placebo (HIPPO) trial aims to assess the ability of ultrasound-guided PRP injections to improve symptoms and function in patients with GTPS. 64 patients were enrolled and randomised to either the PRP or placebo (normal saline) treatment arm. Two patients decided to drop out of the trial. Clinical outcomes in both groups were evaluated and compared using the International Hip Outcome Tool-12 (iHOT12), Visual Analogue Scale (VAS) of pain, the modified Harris Hip Score (mHHS) and the presence or absence of complications at 3 and six months. The level of significance was set at p<0.05. Both groups received physiotherapy after the injections. The mean age was 57.5. There were 6 males and 56 females with M:F ratio of 1:9.3. Both groups were similar in terms of demography and preoperative scores. The iHOT12 score improved from 28.23 to 45.42 at three-months and decreased slightly to 42.44 at six-months in the Placebo group. The iHOT12 in the PRP group improved from 35.51 to 44.47 at three-months and decreased to 39.78 at six-months. Both groups showed improved VAS and mHHS at three-months compared to the baseline with no statistically significant difference between the two groups (p >0.05). The scores decreased at six-months however remained above the baseline. No complications were reported. Gender and age had no effect on outcomes. Both groups similarly improved from baseline. Physiotherapy can be considered as an important factor in patients' treatment. Further research should be conducted to investigate the role of physiotherapy in the treatment of GTPS


The Bone & Joint Journal
Vol. 97-B, Issue 7 | Pages 917 - 923
1 Jul 2015
Singh G Nuechtern JV Meyer H Fiedler GM Awiszus F Junk-Jantsch S Bruegel M Pflueger G Lohmann CH

The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the ‘biologically active area’ of all metal wear particles may predict the type of peri-prosthetic tissue response. . Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6). . The overall distribution of the size and area of the particles in both lymphocyte and non-lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles. . 14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß), and growth factors (granulocyte macrophage colony stimulating factor (GM-CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group. . Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri-prosthetic response compared with those without this response. . These results suggest that the ‘biologically active area’ predicts the type of peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA. Cite this article: Bone Joint J 2015;97-B:917–23


Bone & Joint Open
Vol. 3, Issue 12 | Pages 991 - 997
23 Dec 2022
McPherson EJ Stavrakis AI Chowdhry M Curtin NL Dipane MV Crawford BM

Aims

Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects.

Methods

We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_1 | Pages 67 - 67
1 Jan 2018
Karachalios T Venousiou A
Full Access

There are numerous studies in the current literature that have demonstrated altered levels of various biomarkers in the serum of patients with implant loosening. Despite increasing interest in the biology of implant incorporation there are no studies investigating the changes in biological marker (of either osteoblastic or osteoclastic activity) levels during the integration of the bone-implant interface. Such a study would provide data about the biological profile of normal integration and would be helpful for future monitoring of implant prosthetic performance (either normal or abnormal). We present data from a study performed on 100 osteoarthritic patients, who underwent cementless THA (Synergy, Reflexion Interfit, Smith & Nephew) and 100 non arthritic volunteers. Serial measurements of serum biochemical markers (bone formation and resorption), of cytokines and of other biological mediators and growth factors were evaluated at regular intervals over the course of six years. Curves of per cent changes from baseline and marker variability curves have been created for each marker which are indicative of the incorporation process. Evaluating markers of osteoblastic activity, a first response, with average values below baseline, was observed at the level of the seventh day (perhaps as a response to local trauma). A second osteo-productive response was observed between the third week and 9 months (peak average values at the level of the 6. th. month). At the 1st year time interval, average values reached baseline and remained at this level up to the 6th postoperative year. Evaluating markers of osteoclastic activity, a first response, with average values above baseline, was observed at the level of the seventh day (perhaps as a response to local trauma). A second osteoclastic response was observed between the third week and 3 months (perhaps a coupling response to enhanced osteoblastic activity). At 6 months, average values reached baseline and remained at this level up to the 6th postoperative year. It seems that bone implant interface in cementless total hip arthroplasty remains active up to the 9. th. postoperative month. Possible future deviation from such ‘individual normal’ curves will be indicative of the initiation of the osteolysis process and loss of fixation


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%.


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.


Bone & Joint Research
Vol. 8, Issue 10 | Pages 451 - 458
1 Oct 2019
Kuroda Y Tanaka T Miyagawa T Kawai T Goto K Tanaka S Matsuda S Akiyama H

Objectives

Using a simple classification method, we aimed to estimate the collapse rate due to osteonecrosis of the femoral head (ONFH) in order to develop treatment guidelines for joint-preserving surgeries.

Methods

We retrospectively analyzed 505 hips from 310 patients (141 men, 169 women; mean age 45.5 years (sd 14.9; 15 to 86)) diagnosed with ONFH and classified them using the Japanese Investigation Committee (JIC) classification. The JIC system includes four visualized types based on the location and size of osteonecrotic lesions on weightbearing surfaces (types A, B, C1, and C2) and the stage of ONFH. The collapse rate due to ONFH was calculated using Kaplan–Meier survival analysis, with radiological collapse/arthroplasty as endpoints.


The Bone & Joint Journal
Vol. 101-B, Issue 6_Supple_B | Pages 116 - 122
1 Jun 2019
Whiteside LA Roy ME

Aims

The aims of this study were to assess the exposure and preservation of the abductor mechanism during primary total hip arthroplasty (THA) using the posterior approach, and to evaluate gluteus maximus transfer to restore abductor function of chronically avulsed gluteus medius and minimus.

Patients and Methods

A total of 519 patients (525 hips) underwent primary THA using the posterior approach, between 2009 and 2013. The patients were reviewed preoperatively and at two and five years postoperatively. Three patients had mild acute laceration of the gluteus medius caused by retraction. A total of 54 patients had mild chronic damage to the tendon (not caused by exposure), which was repaired with sutures through drill holes in the greater trochanter. A total of 41 patients had severe damage with major avulsion of the gluteus medius and minimus muscles, which was repaired with sutures through bone and a gluteus maximus flap transfer to the greater trochanter.


The Bone & Joint Journal
Vol. 98-B, Issue 6 | Pages 761 - 766
1 Jun 2016
Davis G Patel RP Tan TL Alijanipour P Naik TU Parvizi J

Aims

We aimed to assess the influence of ethnicity on the incidence of heterotopic ossification (HO) after total hip arthroplasty (THA).

Patients and Methods

We studied the six-month post-operative anteroposterior radiographs of 1449 consecutive primary THAs (1324 patients) and retrospectively graded them for the presence of HO, using the Brooker Classification.


The Bone & Joint Journal
Vol. 96-B, Issue 11_Supple_A | Pages 70 - 72
1 Nov 2014
Callaghan JJ Liu SS Phruetthiphat O

A common situation presenting to the orthopaedic surgeon today is a worn acetabular liner with substantial acetabular and pelvic osteolysis. The surgeon has many options for dealing with osteolytic defects. These include allograft, calcium based substitutes, demineralised bone matrix, or combinations of these options with or without addition of platelet rich plasma. To date there are no clinical studies to determine the efficacy of using bone-stimulating materials in osteolytic defects at the time of revision surgery and there are surprisingly few studies demonstrating the clinical efficacy of these treatment options. Even when radiographs appear to demonstrate incorporation of graft material CT studies have shown that incorporation is incomplete. The surgeon, in choosing a graft material for a surgical procedure must take into account the efficacy, safety, cost and convenience of that material.

Cite this article: Bone Joint J 2014;96-B (11 Suppl A):70–2.


The Bone & Joint Journal
Vol. 96-B, Issue 1 | Pages 31 - 35
1 Jan 2014
Papanagiotou M Malizos KN Vlychou M Dailiana ZH

This preliminary study evaluates a combination of bone morphogenetic protein (BMP)-7 and non-vascularised autologous fibular grafting (AFG) for the treatment of osteonecrosis of the femoral head.

BMP-7/AFG combination was applied in seven pre-collapse femoral heads (five Steinberg stage II, two stage III) in six patients. Pre- and post-operative evaluation included clinical (Harris hip score (HHS), visual analogue scale (VAS) for pain) and radiological assessment (radiographs, quantitative CT) at a mean follow-up of 4 years (2 to 5.5).

A marked improvement of function (mean HHS increase of 49.2) and decrease of pain level (mean VAS decrease of 5) as well as retention of the sphericity of the femoral head was noted in five hips at the latest follow-up, while signs of consolidation were apparent from the third post-operative month. One patient (two hips) required bilateral total hip replacement at one year post-operatively. In the series as a whole, quantitative-CT evaluation revealed similar densities between affected and normal bone. Heterotopic ossification was observed in four hips, without compromise of the clinical outcome.

In this limited series AFG/BMP-7 combination proved a safe and effective method for the treatment of femoral head osteonecrosis, leading to early consolidation of the AFG and preventing collapse in five of seven hips, while the operative time and post-operative rehabilitation period were much shorter compared with free vascularised fibular grafts.

Cite this article: Bone Joint J 2014;96-B:31–5.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 8 | Pages 993 - 996
1 Aug 2006
Kesteris U Aspenberg P

During revision total hip replacement using morcellised compacted bone allograft, 16 patients were randomised to receive a graft which had been rinsed in either an ibandronate solution or in saline. Patients were assessed by dual energy x-ray absorptiometry after operation and at 3, 6, 12 and 24 months. A region of interest between the tip of the femoral stem and the distal plastic plug was chosen to measure the changes in bone density over time. The study was double-blinded. In all the control patients the bone density decreased during the first three months and then remained constant at this lower level. A large proportion of the mass of the bone graft was lost. In contrast, all patients with grafts treated with bisphosphonate showed a slight increase in bone density. The difference between the groups was highly significant at all points in time.

We conclude that rinsing the graft in a bisphosphonate solution prevents its resorption and may therefore reduce the risk of mechanical failure. The treatment is simple, inexpensive, and appears virtually free of risk.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 9 | Pages 1164 - 1171
1 Sep 2008
Ochs BG Schmid U Rieth J Ateschrang A Weise K Ochs U

Deficiencies of acetabular bone stock at revision hip replacement were reconstructed with two different types of allograft using impaction bone grafting and a Burch-Schneider reinforcement ring. We compared a standard frozen non-irradiated bone bank allograft (group A) with a freeze-dried irradiated bone allograft, vitalised with autologous marrow (group B). We studied 78 patients (79 hips), of whom 87% (69 hips) had type III acetabular defects according to the American Academy of Orthopaedic Surgeons classification at a mean of 31.4 months (14 to 51) after surgery. At the latest follow-up, the mean Harris hip score was 69.9 points (13.5 to 97.1) in group A and 71.0 points (11.5 to 96.5) in group B. Each hip showed evidence of trabeculation and incorporation of the allograft with no acetabular loosening.

These results suggest that the use of an acetabular reinforcement ring and a living composite of sterile allograft and autologous marrow appears to be a method of reconstructing acetabular deficiencies which gives comparable results to current forms of treatment.