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Aims

To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs).

Methods

Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 106 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed.


The Bone & Joint Journal
Vol. 104-B, Issue 8 | Pages 963 - 971
1 Aug 2022
Sun Z Liu W Liu H Li J Hu Y Tu B Wang W Fan C

Aims

Heterotopic ossification (HO) is a common complication after elbow trauma and can cause severe upper limb disability. Although multiple prognostic factors have been reported to be associated with the development of post-traumatic HO, no model has yet been able to combine these predictors more succinctly to convey prognostic information and medical measures to patients. Therefore, this study aimed to identify prognostic factors leading to the formation of HO after surgery for elbow trauma, and to establish and validate a nomogram to predict the probability of HO formation in such particular injuries.

Methods

This multicentre case-control study comprised 200 patients with post-traumatic elbow HO and 229 patients who had elbow trauma but without HO formation between July 2019 and December 2020. Features possibly associated with HO formation were obtained. The least absolute shrinkage and selection operator regression model was used to optimize feature selection. Multivariable logistic regression analysis was applied to build the new nomogram: the Shanghai post-Traumatic Elbow Heterotopic Ossification Prediction model (STEHOP). STEHOP was validated by concordance index (C-index) and calibration plot. Internal validation was conducted using bootstrapping validation.


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 10 | Pages 668 - 676
1 Oct 2021
Liu L Li Z Chen S Cui H Li X Dai G Zhong F Hao W Zhang K Liu H

Aims

Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy.

Methods

Achilles tendon puncture (ATP) mouse model was performed on ten-week-old male C57BL/6J mice. One week after ATP procedure, the mice were given different treatments (e.g. JQ1, shMancr). Achilles tendon samples were collected five weeks after treatment for RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) analysis; the legs were removed for micro-CT imaging and subsequent histology. Human bone marrow mesenchymal stem cells (hBMSCs) were isolated and purified bone marrow collected during surgeries by using density gradient centrifugation. After a series of interventions such as knockdown or overexpressing BRD4, Alizarin red staining, RT-qPCR, and Western Blot (Runx2, alkaline phosphatase (ALP), Osx) were performed on hBMSCs.


Bone & Joint 360
Vol. 9, Issue 6 | Pages 5 - 11
1 Dec 2020
Sharma V Turmezei T Wain J McNamara I


Bone & Joint Open
Vol. 1, Issue 9 | Pages 576 - 584
18 Sep 2020
Sun Z Liu W Li J Fan C

Post-traumatic elbow stiffness is a disabling condition that remains challenging for upper limb surgeons. Open elbow arthrolysis is commonly used for the treatment of stiff elbow when conservative therapy has failed. Multiple questions commonly arise from surgeons who deal with this disease. These include whether the patient has post-traumatic stiff elbow, how to evaluate the problem, when surgery is appropriate, how to perform an excellent arthrolysis, what the optimal postoperative rehabilitation is, and how to prevent or reduce the incidence of complications. Following these questions, this review provides an update and overview of post-traumatic elbow stiffness with respect to the diagnosis, preoperative evaluation, arthrolysis strategies, postoperative rehabilitation, and prevention of complications, aiming to provide a complete diagnosis and treatment path.

Cite this article: Bone Joint Open 2020;1-9:576–584.


The Bone & Joint Journal
Vol. 102-B, Issue 4 | Pages 539 - 544
1 Apr 2020
Cirino CM Chan JJ Patterson DC Jia R Poeran J Parsons BO Cagle PJ

Aims

Heterotopic ossification (HO) is a potentially devastating complication of the surgical treatment of a proximal humeral fracture. The literature on the rate and risk factors for the development of HO under these circumstances is lacking. The aim of this study was to determine the incidence and risk factors for the development of HO in these patients.

Methods

A retrospective analysis of 170 patients who underwent operative treatment for a proximal humeral fracture between 2005 and 2016, in a single institution, was undertaken. The mean follow-up was 18.2 months (1.5 to 140). The presence of HO was identified on follow-up radiographs.


The Bone & Joint Journal
Vol. 101-B, Issue 5 | Pages 610 - 614
1 May 2019
Aibinder WR Bartels DW Sperling JW Sanchez-Sotelo J

Aims

Shoulder arthroplasty using short humeral components is becoming increasingly popular. Some such components have been associated with relatively high rates of adverse radiological findings. The aim of this retrospective review was to evaluate the radiological humeral bone changes and mechanical failure rates with implantation of a short cementless humeral component in anatomical (TSA) and reverse shoulder arthroplasty (RSA).

Patients and Methods

A total of 100 shoulder arthroplasties (35 TSA and 65 RSA) were evaluated at a mean of 3.8 years (3 to 8.3). The mean age at the time of surgery was 68 years (31 to 90). The mean body mass index was 32.7 kg/m2 (17.3 to 66.4).


The Bone & Joint Journal
Vol. 100-B, Issue 10 | Pages 1352 - 1358
1 Oct 2018
Clough TM Alvi F Majeed H

Aims

Total ankle arthroplasty (TAA) surgery is complex and attracts a wide variety of complications. The literature lacks consistency in reporting adverse events and complications. The aim of this article is to provide a comprehensive analysis of each of these complications from a literature review, and to compare them with rates from our Unit, to aid clinicians with the process of informed consent.

Patients and Methods

A total of 278 consecutive total ankle arthroplasties (251 patients), performed by four surgeons over a six-year period in Wrightington Hospital (Wigan, United Kingdom) were prospectively reviewed. There were 143 men and 108 women with a mean age of 64 years (41 to 86). The data were recorded on each follow-up visit. Any complications either during initial hospital stay or subsequently reported on follow-ups were recorded, investigated, monitored, and treated as warranted. Literature search included the studies reporting the outcomes and complications of TAA implants.


Bone & Joint Research
Vol. 7, Issue 10 | Pages 570 - 579
1 Oct 2018
Kallala R Harris WE Ibrahim M Dipane M McPherson E

Aims

Calcium sulphate has traditionally been used as a filler of dead space arising during surgery. Various complications have been described following the use of Stimulan bio-absorbable calcium sulphate beads. This study is a prospective observational study to assess the safety profile of these beads when used in revision arthroplasty, comparing the complication rates with those reported in the literature.

Methods

A total of 755 patients who underwent 456 revision total knee arthroplasties (TKA) and 299 revision total hip arthroplasties (THA), with a mean follow-up of 35 months (0 to 78) were included in the study.


The Bone & Joint Journal
Vol. 100-B, Issue 7 | Pages 915 - 922
1 Jul 2018
Joice M Vasileiadis GI Amanatullah DF

Aims

The aim of this study was to assess the efficacy of non-selective and selective non-steroidal anti-inflammatory drugs (NSAIDs) in preventing heterotopic ossification (HO) after total hip arthroplasty (THA).

Methods

A thorough and systematic literature search was conducted and 29 studies were found that met inclusion criteria. Data were extracted and statistical analysis was carried out generating forest plots.


The Bone & Joint Journal
Vol. 99-B, Issue 10 | Pages 1399 - 1408
1 Oct 2017
Scott CEH MacDonald D Moran M White TO Patton JT Keating JF

Aims

To evaluate the outcomes of cemented total hip arthroplasty (THA) following a fracture of the acetabulum, with evaluation of risk factors and comparison with a patient group with no history of fracture.

Patients and Methods

Between 1992 and 2016, 49 patients (33 male) with mean age of 57 years (25 to 87) underwent cemented THA at a mean of 6.5 years (0.1 to 25) following acetabular fracture. A total of 38 had undergone surgical fixation and 11 had been treated non-operatively; 13 patients died at a mean of 10.2 years after THA (0.6 to 19). Patients were assessed pre-operatively, at one year and at final follow-up (mean 9.1 years, 0.5 to 23) using the Oxford Hip Score (OHS). Implant survivorship was assessed. An age and gender-matched cohort of THAs performed for non-traumatic osteoarthritis (OA) or avascular necrosis (AVN) (n = 98) were used to compare complications and patient-reported outcome measures (PROMs).


The Bone & Joint Journal
Vol. 99-B, Issue 4 | Pages 465 - 474
1 Apr 2017
Kim YS Abrahams JM Callary SA De Ieso C Costi K Howie DW Solomon LB

Aims

The purpose of this study was to determine the sensitivity, specificity and predictive values of previously reported thresholds of proximal translation and sagittal rotation of cementless acetabular components used for revision total hip arthroplasty (THA) at various times during early follow-up.

Patients and Methods

Migration of cementless acetabular components was measured retrospectively in 84 patients (94 components) using Ein-Bild-Rontgen-Analyse (EBRA-Cup) in two groups of patients. In Group A, components were recorded as not being loose intra-operatively at re-revision THA (52 components/48 patients) and Group B components were recorded to be loose at re-revision (42 components/36 patients).


The Bone & Joint Journal
Vol. 96-B, Issue 12 | Pages 1681 - 1687
1 Dec 2014
Foruria AM Lawrence TM Augustin S Morrey BF Sanchez-Sotelo J

We retrospectively reviewed 89 consecutive patients (45 men and 44 women) with a mean age at the time of injury of 58 years (18 to 97) who had undergone external fixation after sustaining a unilateral fracture of the distal humerus. Our objectives were to determine the incidence of heterotopic ossification (HO); identify risk factors associated with the development of HO; and characterise the location, severity and resultant functional impairment attributable to the presence of HO.

HO was identified in 37 elbows (42%), mostly around the humerus and along the course of the medial collateral ligament. HO was hazy immature in five elbows (13.5%), mature discrete in 20 (54%), extensive mature in 10 (27%), and complete bone bridges were present in two elbows (5.5%). Mild functional impairment occurred in eight patients, moderate in 27 and severe in two. HO was associated with less extension (p = 0.032) and less overall flexion-to-extension movement (p = 0.022); the flexion-to-extension arc was < 100º in 21 elbows (57%) with HO compared with 18 elbows (35%) without HO (p = 0.03). HO was removed surgically in seven elbows.

The development of HO was significantly associated with sustaining a head injury (p = 0.015), delayed internal fixation (p = 0.027), the method of fracture fixation (p = 0.039) and the use of bone graft or substitute (p = 0.02).HO continues to be a substantial complication after internal fixation for distal humerus fractures.

Cite this article: Bone Joint J 2014;96-B:1681–7.


Bone & Joint Research
Vol. 2, Issue 3 | Pages 51 - 57
1 Mar 2013
Sullivan MP Torres SJ Mehta S Ahn J

Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones


Bone & Joint Research
Vol. 1, Issue 8 | Pages 174 - 179
1 Aug 2012
Alfieri KA Forsberg JA Potter BK

Heterotopic ossification (HO) is perhaps the single most significant obstacle to independence, functional mobility, and return to duty for combat-injured veterans of Operation Enduring Freedom and Operation Iraqi Freedom. Recent research into the cause(s) of HO has been driven by a markedly higher prevalence seen in these wounded warriors than encountered in previous wars or following civilian trauma. To that end, research in both civilian and military laboratories continues to shed light onto the complex mechanisms behind HO formation, including systemic and wound specific factors, cell lineage, and neurogenic inflammation. Of particular interest, non-invasive in vivo testing using Raman spectroscopy may become a feasible modality for early detection, and a wound-specific model designed to detect the early gene transcript signatures associated with HO is being tested. Through a combined effort, the goals of early detection, risk stratification, and development of novel systemic and local prophylaxis may soon be attainable.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 2 | Pages 298 - 303
1 Feb 2010
Toom A Suutre S Märtson A Haviko T Selstam G Arend A

We have developed an animal model to examine the formation of heterotopic ossification using standardised muscular damage and implantation of a beta-tricalcium phosphate block into a hip capsulotomy wound in Wistar rats. The aim was to investigate how cells originating from drilled femoral canals and damaged muscles influence the formation of heterotopic bone. The femoral canal was either drilled or left untouched and a tricalcium phosphate block, immersed either in saline or a rhBMP-2 solution, was implanted. These implants were removed at three and 21 days after the operation and examined histologically, histomorphometrically and immunohistochemically. Bone formation was seen in all implants in rhBMP-2-immersed, whereas in those immersed in saline the process was minimal, irrespective of drilling of the femoral canals. Bone mineralisation was somewhat greater in the absence of drilling with a mean mineralised volume to mean total volume of 18.2% (. sd. 4.5) versus 12.7% (. sd. 2.9, p < 0.019), respectively. Our findings suggest that osteoinductive signalling is an early event in the formation of ectopic bone. If applicable to man the results indicate that careful tissue handling is more important than the prevention of the dissemination of bone cells in order to avoid heterotopic ossification


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 11 | Pages 1493 - 1498
1 Nov 2009
Genet F Marmorat J Lautridou C Schnitzler A Mailhan L Denormandie P

Heterotopic ossification (HO) of the hip after injury to the central nervous system can lead to joint ankylosis. Surgery is usually delayed to avoid recurrence, even if the functional status is affected. We report a consecutive series of patients with HO of the hip after injury to the central nervous system who required surgery in a single, specialised tertiary referral unit. As was usual practice, they all underwent CT to determine the location of the HO and to evaluate the density of the femoral head and articular surface. The outcome of surgery was correlated with the pre-, peri- and post-operative findings.

In all, 183 hips (143 patients) were included of which 70 were ankylosed. A total of 25 peri-operative fractures of the femoral neck occurred, all of which arose in patients with ankylosed hips and were associated with intra-articular lesions in 18 and severe osteopenia of the femoral head in seven. All the intra-articular lesions were predicted by CT and strongly associated with post-operative complications.

The loss of the range of movement before ankylosis is a more important factor than the maturity of the HO in deciding the timing of surgery. Early surgical intervention minimises the development of intra-articular pathology, osteoporosis and the resultant complications without increasing the risk of recurrence of HO.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 8 | Pages 1007 - 1012
1 Aug 2009
Egermann M Döderlein L Schläger E Müller S Braatz F

In patients with severe quadriplegic cerebral palsy and painful hip dislocation proximal femoral resection arthroplasty can reduce pain, but the risk of heterotopic ossification is significant. We present a surgical technique of autologous capping of the femoral stump in order to reduce this risk, using the resected femoral head as the graft.

A retrospective study of 31 patients (43 hips) who had undergone proximal femoral resection arthroplasty with (29 hips) and without autologous capping (14 hips) was undertaken. Heterotopic ossification was less frequent in patients with autologous capping, and a more predictable pattern of bony overgrowth was found.

For a selected group of non-ambulatory patients with long-standing painful dislocation of the hip, we recommend femoral resection arthroplasty over more complicated reconstructive operations. The risk of heterotopic ossification, which is a major disadvantage of this operation, is reduced by autologous capping.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 5 | Pages 577 - 582
1 May 2009
Duncan WW Hubble MJW Howell JR Whitehouse SL Timperley AJ Gie GA

The removal of well-fixed bone cement from the femoral canal during revision of a total hip replacement (THR) can be difficult and risks the loss of excessive bone stock and perforation or fracture of the femoral shaft. Retaining the cement mantle is attractive, yet the technique of cement-in-cement revision is not widely practised. We have used this procedure at our hospital since 1989. The stems were removed to gain a better exposure for acetabular revision, to alter version or leg length, or for component incompatibility.

We studied 136 hips in 134 patients and followed them up for a mean of eight years (5 to 15). A further revision was required in 35 hips (25.7%), for acetabular loosening in 26 (19.1%), sepsis in four, instability in three, femoral fracture in one and stem fracture in one. No femoral stem needed to be re-revised for aseptic loosening.

A cement-in-cement revision of the femoral stem is a reliable technique in the medium term. It also reduces the risk of perforation or fracture of the femoral shaft.