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The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 632 - 638
1 Jun 2024
Hart CM Kelley BV Mamouei Z Turkmani A Ralston M Arnold M Bernthal NM Sassoon AA

Aims

Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation.

Methods

A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs.


The Bone & Joint Journal
Vol. 103-B, Issue 7 Supple B | Pages 135 - 144
1 Jul 2021
Kuyl E Shu F Sosa BR Lopez JD Qin D Pannellini T Ivashkiv LB Greenblatt MB Bostrom MPG Yang X

Aims. Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue. Methods. Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Pad4-/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure. Results. NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition (Pad4-/-) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice. Conclusion. This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury bone remodelling caused by implant loosening. By inhibiting or resolving NETs in an osseointegration failure murine model, fibrotic tissue encapsulation around an implant is reduced and osseointegration is enhanced, despite loose implant conditions. Cite this article: Bone Joint J 2021;103-B(7 Supple B):135–144


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 720 - 727
1 Jul 2024
Wu H Wang X Shen J Wei Z Wang S Xu T Luo F Xie Z

Aims

This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.

Methods

A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts.


The Bone & Joint Journal
Vol. 101-B, Issue 7_Supple_C | Pages 108 - 114
1 Jul 2019
Ji G Xu R Niu Y Li N Ivashkiv L Bostrom MPG Greenblatt MB Yang X

Aims. It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. Materials and Methods. An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium. RNA sequencing analysis was performed using sorted CD31. hi. EMCN. hi. endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. Results. Flow cytometry revealed that anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. Conclusion. VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31. hi. EMCN. hi. endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108–114


The Bone & Joint Journal
Vol. 104-B, Issue 1 | Pages 53 - 58
1 Jan 2022
Tai DBG Wengenack NL Patel R Berbari EF Abdel MP Tande AJ

Aims

Fungal and mycobacterial periprosthetic joint infections (PJI) are rare events. Clinicians are wary of missing these diagnoses, often leading to the routine ordering of fungal and mycobacterial cultures on periprosthetic specimens. Our goal was to examine the utility of these cultures and explore a modern bacterial culture technique using bacterial blood culture bottles (BCBs) as an alternative.

Methods

We performed a retrospective review of patients diagnosed with hip or knee PJI between 1 January 2010 and 31 December 2019, at the Mayo Clinic in Rochester, Minnesota, USA. We included patients aged 18 years or older who had fungal, mycobacterial, or both cultures performed together with bacterial cultures. Cases with positive fungal or mycobacterial cultures were reviewed using the electronic medical record to classify the microbiological findings as representing true infection or not.


The Bone & Joint Journal
Vol. 103-B, Issue 6 | Pages 1168 - 1172
1 Jun 2021
Iliadis AD Wright J Stoddart MT Goodier WD Calder P

Aims

The STRYDE nail is an evolution of the PRECICE Intramedullary Limb Lengthening System, with unique features regarding its composition. It is designed for load bearing throughout treatment in order to improve patient experience and outcomes and allow for simultaneous bilateral lower limb lengthening. The literature published to date is limited regarding outcomes and potential problems. We report on our early experience and raise awareness for the potential of adverse effects from this device.

Methods

This is a retrospective review of prospective data collected on all patients treated in our institution using this implant. We report the demographics, nail accuracy, reliability, consolidation index, and cases where concerning clinical and radiological findings were encountered. There were 14 STRYDE nails implanted in nine patients (three male and six female) between June 2019 and September 2020. Mean age at surgery was 33 years (14 to 65). Five patients underwent bilateral lengthening (two femoral and three tibial) and four patients unilateral femoral lengthening for multiple aetiologies.


The Bone & Joint Journal
Vol. 100-B, Issue 7 | Pages 882 - 890
1 Jul 2018
Bertrand J Delfosse D Mai V Awiszus F Harnisch K Lohmann CH

Aims. Early evidence has emerged suggesting that ceramic-on-ceramic articulations induce a different tissue reaction to ceramic-on-polyethylene and metal-on-metal bearings. Therefore, the aim of this study was to investigate the tissue reaction and cellular response to ceramic total hip arthroplasty (THA) materials in vitro, as well as the tissue reaction in capsular tissue after revision surgery of ceramic-on-ceramic THAs. Patients and Methods. We investigated tissue collected at revision surgery from nine ceramic-on-ceramic articulations. we compared our findings with tissue obtained from five metal-on-metal THA revisions, four ceramic-on-polyethylene THAs, and four primary osteoarthritis synovial membranes. The latter were analyzed to assess the amount of tissue fibrosis that might have been present at the time of implantation to enable evaluation, in relation to implantation time, of any subsequent response in the tissues. Results. There was a significant increase in tissue fibrosis with implantation time for all implant types tested. Interestingly, the tissue fibrosis in ceramic-on-ceramic THAs was significantly increased compared with metal-on-metal and ceramic-on-polyethylene. Additionally, we found ceramic wear particles in the periprosthetic tissue of ceramic implants. Fibroblasts responded with expression of cytokines when cultured on alumina-toughened zirconia (ATZ) and zirconia-toughened alumina (ZTA) ceramic surfaces. This response was more pronounced on ATZ ceramics compared with ZTA ceramics. The same inflammatory response was observed with peripheral blood mononuclear cells (PBMCs) cultured on ZTA and ATZ. Conclusion. Our findings therefore, corroborate the previous findings that ceramic-on-ceramic periprosthetic revision tissue is fibrous and offer an explanation for this observation. We detected a long-term inflammatory response of PBMCs and an inflammatory response of fibroblasts to ATZ and ZTA ceramic. These findings partially explain the fibrotic tissue change in periprosthetic tissue of ceramic-on-ceramic bearings. Cite this article: Bone Joint J 2018;100-B:882–90


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 456 - 461
1 Mar 2021
Sasaki G Watanabe Y Yasui Y Nishizawa M Saka N Kawano H Miyamoto W

Aims

To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (β-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes.

Methods

A review of the medical records was conducted of consecutive 35 lower limbs (30 males and five females; median age 46 years (interquartile range (IQR) 40 to 61)) treated with IMT using β-TCP between 2014 and 2018. Lower Extremity Functional Score (LEFS) was examined preoperatively and at final follow-up to clarify patient-centered outcomes. Bone healing was assessed radiologically, and time from the second stage to bone healing was also evaluated. Patients were divided into ≥ 50 mm and < 50 mm defect groups and into femoral reconstruction, tibial reconstruction, and ankle arthrodesis groups.


The Bone & Joint Journal
Vol. 102-B, Issue 7 Supple B | Pages 3 - 10
1 Jul 2020
Sosa BR Niu Y Turajane K Staats K Suhardi V Carli A Fischetti V Bostrom M Yang X

Aims

Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment.

Methods

The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load.


The Bone & Joint Journal
Vol. 102-B, Issue 8 | Pages 1082 - 1087
1 Aug 2020
Yiğit Ş Arslan H Akar MS Şahin MA

Aims

Osteopetrosis (OP) is a rare hereditary disease that causes reduced bone resorption and increased bone density as a result of osteoclastic function defect. Our aim is to review the difficulties, mid-term follow-up results, and literature encountered during the treatment of OP.

Methods

This is a retrospective and observational study containing data from nine patients with a mean age of 14.1 years (9 to 25; three female, six male) with OP who were treated in our hospital between April 2008 and October 2018 with 20 surgical procedures due to 17 different fractures. Patient data included age, sex, operating time, length of stay, genetic type of the disease, previous surgery, fractures, complications, and comorbidity.


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1375 - 1383
3 Oct 2020
Zhang T Sze KY Peng ZW Cheung KMC Lui YF Wong YW Kwan KYH Cheung JPY

Aims

To investigate metallosis in patients with magnetically controlled growing rods (MCGRs) and characterize the metal particle profile of the tissues surrounding the rod.

Methods

This was a prospective observational study of patients with early onset scoliosis (EOS) treated with MCGRs and undergoing rod exchange who were consecutively recruited between February 2019 and January 2020. Ten patients were recruited (mean age 12 years (SD 1.3); 2 M:8 F). The configurations of the MCGR were studied to reveal the distraction mechanisms, with crucial rod parts being the distractable piston rod and the magnetically driven rotor inside the barrel of the MCGR. Metal-on-metal contact in the form of ring-like wear marks on the piston was found on the distracted portion of the piston immediately outside the barrel opening (BO) through which the piston rod distracts. Biopsies of paraspinal muscles and control tissue samples were taken over and away from the wear marks, respectively. Spectral analyses of the rod alloy and biopsies were performed to reveal the metal constituents and concentrations. Histological analyses of the biopsies were performed with haematoxylin and eosin staining.


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 899 - 903
1 Jul 2020
Bürger J Palmowski Y Strube P Perka C Putzier M Pumberger M

Aims

To evaluate the histopathological examination of peri-implant tissue samples as a technique in the diagnosis of postoperative spinal implant infection (PSII).

Methods

This was a retrospective analysis. Patients who underwent revision spinal surgery at our institution were recruited for this study. PSII was diagnosed by clinical signs, histopathology, and microbiological examination of intraoperatively collected samples. Histopathology was defined as the gold standard. The sensitivity for histopathology was calculated. A total of 47 patients with PSII and at least one microbiological and histopathological sample were included in the study.


Aims. The Intraosseous Transcutaneous Amputation Prosthesis (ITAP) may improve quality of life for amputees by avoiding soft-tissue complications associated with socket prostheses and by improving sensory feedback and function. It relies on the formation of a seal between the soft tissues and the implant and currently has a flange with drilled holes to promote dermal attachment. Despite this, infection remains a significant risk. This study explored alternative strategies to enhance soft-tissue integration. Materials and Methods. The effect of ITAP pins with a fully porous titanium alloy flange with interconnected pores on soft-tissue integration was investigated. The flanges were coated with fibronectin-functionalised hydroxyapatite and silver coatings, which have been shown to have an antibacterial effect, while also promoting viable fibroblast growth in vitro. The ITAP pins were implanted along the length of ovine tibias, and histological assessment was undertaken four weeks post-operatively. Results. The porous titanium alloy flange reduced epithelial downgrowth and increased soft-tissue integration compared with the current drilled flange. The addition of coatings did not enhance these effects. Conclusion. These results indicate that a fully porous titanium alloy flange has the potential to increase the soft-tissue seal around ITAP and reduce susceptibility to infection compared with the current design. Cite this article: Bone Joint J 2017;99-B:393–400


The Bone & Joint Journal
Vol. 102-B, Issue 7 Supple B | Pages 116 - 121
1 Jul 2020
Heise G Black CM Smith R Morrow BR Mihalko WM

Aims

This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys.

Methods

Murine peritoneal macrophages were cultured and placed on stainless steel, CoCrMo, and Ti6Al4V discs into a 96-well plate. Cells were activated with interferon gamma and lipopolysaccharide. Macrophages on stainless steel discs produced significantly more nitric oxide (NO) compared to their control counterparts after eight to ten days and remained elevated for the duration of the experiment.


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 904 - 911
1 Jul 2020
Sigmund IK Dudareva M Watts D Morgenstern M Athanasou NA McNally MA

Aims

The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition.

Methods

A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree.


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 5 | Pages 888 - 893
1 Sep 1998
Overgaard L Danielsen N Bjursten LM

Little is known about the tissue reactions to various implant materials which coincide with an inflammatory reaction. We used the avridine arthritis rat model to evaluate the tissue response in the synovial, interstitial and subcutaneous tissues after implant insertion. Quantitative immunohistochemistry showed that normal joint synovial tissue is dominated by ED2-positive resident macrophages. Polyethylene implants induced a much stronger foreign-body reaction than titanium implants, as measured by the number of interfacial ED1-positive macrophages. The tissue response to titanium and polyethylene was also vastly different in arthritic synovial tissue compared with control tissue. It is likely that these biomaterials interact differently with inflammatory cells or intermediary compounds. It may be that arthritic synovial tissue produces reactive oxygen intermediates (free radicals) with which titanium has a unique anti-inflammatory interaction in vitro


The Journal of Bone & Joint Surgery British Volume
Vol. 57-B, Issue 1 | Pages 36 - 45
1 Feb 1975
Chalmers J Gray DH Rush J

Using bone decalcilied with 0.6 N hydrochloric acid as an inducing agent, the inductive capacity of different soft tissue sites was investigated. Muscle and fascia regularly permitted the induction of bone, while spleen, liver and kidney suppressed bone induction. Bone formation could be induced in these organs if living autologous fascia was implanted together with the inducing agent; while bone formation was inhibited when living autologous spleen tissue was implanted with the inducing agent to normally favourable sites. The administration of systemic heparin and the diphosphonate ethane-1-hydroxyl, 1-diphosphonic acid (EHDP) suppressed bone induction. It is suggested that for bone induction to occur in soft tissues, three conditions must be present: 1) an inducing agent; 2) an osteogenic precursor cell; and 3) an environment which is permissive to osteogenesis. The presence of osteogenic inhibitors in spleen, liver and kidney is postulated


The Bone & Joint Journal
Vol. 100-B, Issue 12 | Pages 1618 - 1625
1 Dec 2018
Gill JR Kiliyanpilakkill B Parker MJ

Aims

This study describes and compares the operative management and outcomes in a consecutive case series of patients with dislocated hemiarthroplasties of the hip, and compares outcomes with those of patients not sustaining a dislocation.

Patients and Methods

Of 3326 consecutive patients treated with hemiarthroplasty for fractured neck of femur, 46 (1.4%) sustained dislocations. Of the 46 dislocations, there were 37 female patients (80.4%) and nine male patients (19.6%) with a mean age of 83.8 years (66 to 100). Operative intervention for each, and subsequent dislocations, were recorded. The following outcome measures were recorded: dislocation; mortality up to one-year post-injury; additional surgery; residential status; mobility; and pain score at one year.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1011 - 1016
1 Aug 2011
Langton DJ Jameson SS Joyce TJ Gandhi JN Sidaginamale R Mereddy P Lord J Nargol AVF

There is widespread concern regarding the incidence of adverse soft-tissue reactions after metal-on-metal (MoM) hip replacement. Recent National Joint Registry data have shown clear differences in the rates of failure of different designs of hip resurfacing. Our aim was to update the failure rates related to metal debris for the Articular Surface Replacement (ASR). A total of 505 of these were implanted. Kaplan-Meier analysis showed a failure rate of 25% at six years for the ASR resurfacing and of 48.8% for the ASR total hip replacement (THR). Of 257 patients with a minimum follow-up of two years, 67 (26.1%) had a serum cobalt concentration which was greater than 7 μg/l. Co-ordinate measuring machine analysis of revised components showed that all patients suffering adverse tissue reactions in the resurfacing group had abnormal wear of the bearing surfaces. Six THR patients had relatively low rates of articular wear, but were found to have considerable damage at the trunion-taper interface. Our results suggest that wear at the modular junction is an important factor in the development of adverse tissue reactions after implantation of a large-diameter MoM THR


The Journal of Bone & Joint Surgery British Volume
Vol. 73-B, Issue 4 | Pages 559 - 563
1 Jul 1991
Witt J Swann M

Thirteen total hip replacements with titanium alloy femoral components required revision for loosening at an average of two years after implantation. At revision the soft tissues around the implant were darkly stained and a proliferative membrane had invaded the cement-bone interface. The femoral components showed polishing of parts of their shot-blasted surfaces. Histology showed a fibroblastic reaction with abundant titanium lying free and within histiocytes, and a scanty foreign-body giant-cell reaction. Surface analysis of the removed femoral components and chemical analysis of the excised tissues is described. Tissue reaction in response to the metal-wear debris may have contributed to the early failure of these implants


The Journal of Bone & Joint Surgery British Volume
Vol. 77-B, Issue 6 | Pages 962 - 966
1 Nov 1995
Shahgaldi B Heatley F Dewar A Corrin B

Tissue reaction to wear particles from metal implants may play a major role in the aseptic loosening of implants. We used electron microprobe elemental analysis to determine the chemical composition of wear particles embedded in the soft tissues around hip and knee implants from 11 patients at revision surgery for aseptic loosening. The implants were made of cobalt-chromium-molybdenum alloy or titanium-aluminium-vanadium alloy. Histological examination showed a widespread giant-cell reaction to the particles. Elemental analysis showed that the chemical composition of the particles was different from that of the implanted alloys: cobalt and titanium were reduced, often down to zero, whereas chromium and aluminium persisted. Our findings indicate that corrosion is continually changing the shape, size and chemical composition of the implanted alloy. This may alter the biochemical environment of the tissue surrounding an implant to favour bone resorption


The Journal of Bone & Joint Surgery British Volume
Vol. 63-B, Issue 3 | Pages 342 - 353
1 Aug 1981
Buchholz H Elson R Engelbrecht E Lodenkamper H Rottger J Siegel A

Exchange operation is recommended as the treatment of choice for most deep infections involving a total hip replacement. This revision arthroplasty comprises, in one stage, excision of soft tissue, removal of implant and cement, replacement with an appropriate implant using Palacos R acrylic cement loaded with an appropriate antibiotic and, more recently, systemic antibiotics. During our first 10 years without systemic antibiotics we have achieved an overall 77 per cent success rate from a first attempt in 583 patients and a 90 per cent success rate after subsequent exchange procedures. Morbidity is significant but acceptable. Success is defined as control of infection, no loosening, and useful function. The factors associated with failures include, in particular, specific infections (Pseudomonas group, Streptococcus group D, Proteus group, and Escherichia coli), delay in operation and inadequate antibiotic dosage in the cement


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 3 | Pages 440 - 447
1 Apr 2003
Røkkum M Reigstad A Johansson CB Albrektsson T

Ten acetabular cups coated with hydroxyapatite (HA) had originally been inserted in five primary and five revision total hip replacements. The thickness of the HA was 155 ± 35 μm. The cups, which were well-fixed, were retrieved, with their adherent tissue, at reoperation after 0.3 to 5.8 years because of infection (five hips), wear of polyethylene (three hips), and instability (two hips). Undecalcified sections showed a direct contact between bone and osteoid-like tissue which had formed directly onto the HA coating. The area within the threads and their mirror images, as well as the implant-tissue interfaces consisted of similar amounts of bone and soft tissue. Degradation of HA was seen in all hips. The mean thickness of the remaining HA coating was 97 μm (95% CI 94 to 101). The metal interface comprised 66% HA. The HA-tissue interface contained more bone than soft tissue (p = 0.001), whereas the metal-tissue interface included more soft tissue than bone (p = 0.019). Soft tissue at the implant interface and poor replacement of HA by bone may interfere with long-term fixation


The Bone & Joint Journal
Vol. 98-B, Issue 5 | Pages 634 - 640
1 May 2016
Pedowitz DI Kane JM Smith GM Saffel HL Comer C Raikin SM

Aims

Few reports compare the contribution of the talonavicular articulation to overall range of movement in the sagittal plane after total ankle arthroplasty (TAA) and tibiotalar arthrodesis. The purpose of this study was to assess changes in ROM and functional outcomes following tibiotalar arthrodesis and TAA.

Patients and Methods

Patients who underwent isolated tibiotalar arthrodesis or TAA with greater than two-year follow-up were enrolled in the study. Overall arc of movement and talonavicular movement in the sagittal plane were assessed with weight-bearing lateral maximum dorsiflexion and plantarflexion radiographs. All patients completed Short Form-12 version 2.0 questionnaires, visual analogue scale for pain (VAS) scores, and the Foot and Ankle Ability Measure (FAAM).


The Bone & Joint Journal
Vol. 98-B, Issue 4 | Pages 437 - 441
1 Apr 2016
Middleton S Toms A

We explored the literature surrounding whether allergy and hypersensitivity has a clinical basis for implant selection in total knee arthroplasty (TKA). In error, the terms hypersensitivity and allergy are often used synonymously. Although a relationship is present, we could not find any evidence of implant failure due to allergy. There is however increasing basic science that suggests a link between loosening and metal ion production. This is not an allergic response but is a potential problem. With a lack of evidence logically there can be no justification to use ‘hypoallergenic’ implants in patients who have pre-existing skin sensitivity to the metals used in TKA.

Cite this article: Bone Joint J 2016;98-B:437–41.


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 179 - 186
1 Feb 2016
Berber R Skinner J Board T Kendoff D Eskelinen A Kwon Y Padgett DE Hart A

Aims

There are many guidelines that help direct the management of patients with metal-on-metal (MOM) hip arthroplasties. We have undertaken a study to compare the management of patients with MOM hip arthroplasties in different countries.

Methods

Six international tertiary referral orthopaedic centres were invited to participate by organising a multi-disciplinary team (MDT) meeting, consisting of two or more revision hip arthroplasty surgeons and a musculoskeletal radiologist. A full clinical dataset including history, blood tests and imaging for ten patients was sent to each unit, for discussion and treatment planning. Differences in the interpretation of findings, management decisions and rationale for decisions were compared using quantitative and qualitative methods.


The Bone & Joint Journal
Vol. 97-B, Issue 6 | Pages 830 - 835
1 Jun 2015
Li SL Lu Y Wang MY

This study compares the outcomes of two methods of fixation of displaced fractures of the radial neck. The 58 patients with a mean age of 38.5 years (18 to 56), were treated in a non randomised study with screws (n = 29) or a plate and screws (n = 29) according to the surgeon’s preference.

The patients were reviewed at one year. Radiographs and functional evaluations were carried out up to one year post-operatively, using the Broberg and Morrey functional evaluation score, range of movement, and assessment of complications.

The mean functional scores did not differ significantly between groups (90 (55 to 100) vs 84; 50 to 100, p = 0.09), but the mean range of forearm rotation in screw group was significantly better than in the plate group (152°; 110° to 170° vs 134°; 80° to 170°, p = 0.001). Although not statistically significant, the screw group had a lower incidence of heterotopic ossification than the plate group (n = 1) than the plated group (n = 3) and the pathology was graded as less severe.

Cite this article: Bone Joint J 2015;97-B:830–5


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 83 - 88
1 Jan 2015
Kocsis G McCulloch TA Thyagarajan D Wallace WA

The LockDown device (previously called Surgilig) is a braided polyester mesh which is mostly used to reconstruct the dislocated acromioclavicular joint. More than 11 000 have been implanted worldwide. Little is known about the tissue reaction to the device nor to its wear products when implanted in an extra-articular site in humans. This is of importance as an adverse immunological reaction could result in osteolysis or damage to the local tissues, thereby affecting the longevity of the implant.

We analysed the histology of five LockDown implants retrieved from five patients over the last seven years by one of the senior authors. Routine analysis was carried out in all five cases and immunohistochemistry in one.

The LockDown device acts as a scaffold for connective tissue which forms an investing fibrous pseudoligament. The immunological response at the histological level seems favourable with a limited histiocytic and giant cell response to micron-sized wear particles. The connective tissue envelope around the implant is less organised than a native ligament.

Cite this article: Bone Joint J 2015;97-B:83–8.


The Bone & Joint Journal
Vol. 95-B, Issue 2 | Pages 244 - 249
1 Feb 2013
Puig-Verdié L Alentorn-Geli E González-Cuevas A Sorlí L Salvadó M Alier A Pelfort X Portillo ME Horcajada JP

The purpose of this study was to compare the diagnostic accuracy for the detection of infection between the culture of fluid obtained by sonication (SFC) and the culture of peri-implant tissues (PITC) in patients with early and delayed implant failure, and those with unsuspected and suspected septic failure. It was hypothesised that SFC increases the diagnostic accuracy for infection in delayed, but not early, implant failure, and in unsuspected septic failure. The diagnostic accuracy for infection of all consecutive implants (hardware or prostheses) that were removed for failure was compared between SFC and PITC. This prospective study included 317 patients with a mean age of 62.7 years (9 to 97). The sensitivity for detection of infection using SFC was higher than using PITC in an overall comparison (89.9% versus 67%, respectively; p < 0.001), in unsuspected septic failure (100% versus 48.5%, respectively; p < 0.001), and in delayed implant failure (88% versus 58%, respectively; p < 0.001). PITC sensitivity dropped significantly in unsuspected compared with suspected septic failure (p = 0.007), and in delayed compared with early failure (p = 0.013). There were no differences in specificity.

Sonication is mainly recommended when there is implant failure with no clear signs of infection and in patients with delayed implant failure. In early failure, SFC is not superior to PITC for the diagnosis of infection and, therefore, is not recommended as a routine diagnostic test in these patients.

Cite this article: Bone Joint J 2013;95-B:244–9.


The Bone & Joint Journal
Vol. 96-B, Issue 2 | Pages 263 - 269
1 Feb 2014
Batta V Coathup MJ Parratt MT Pollock RC Aston WJ Cannon SR Skinner JA Briggs TW Blunn GW

We reviewed the outcome of 69 uncemented, custom-made, distal femoral endoprosthetic replacements performed in 69 patients between 1994 and 2006. There were 31 women and 38 men with a mean age at implantation of 16.5 years (5 to 37). All procedures were performed for primary malignant bone tumours of the distal femur. At a mean follow-up of 124.2 months (4 to 212), 53 patients were alive, with one patient lost to follow-up. All nine implants (13.0%) were revised due to aseptic loosening at a mean of 52 months (8 to 91); three implants (4.3%) were revised due to fracture of the shaft of the prosthesis and three patients (4.3%) had a peri-prosthetic fracture. Bone remodelling associated with periosteal cortical thinning adjacent to the uncemented intramedullary stem was seen in 24 patients but this did not predispose to failure. All aseptically loose implants in this series were diagnosed to be loose within the first five years.

The results from this study suggest that custom-made uncemented distal femur replacements have a higher rate of aseptic loosening compared to published results for this design when used with cemented fixation. Loosening of uncemented replacements occurs early indicating that initial fixation of the implant is crucial.

Cite this article: Bone Joint J 2014;96-B:263–9.


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. 93-B, Issue 7 | Pages 886 - 889
1 Jul 2011
Bremer AK Kalberer F Pfirrmann CWA Dora C

The direct anterior approach in total hip replacement anatomically offers the chance to minimise soft-tissue trauma because an intermuscular and internervous plane is explored. This motivated us to abandon our previously used transgluteal approach and to adopt the direct anterior approach for total hip replacement. Using MRI, we performed a retrospective comparative study of the direct anterior approach with the transgluteal approach. There were 25 patients in each group. At one year post-operatively all the patients underwent MRI of their replaced hips. A radiologist graded the changes in the soft-tissue signals in the abductor muscles. The groups were similar in terms of age, gender, body mass index, complexity of the reconstruction and absence of symptoms.

Detachment of the abductor insertion, partial tears and tendonitis of gluteus medius and minimus, the presence of peri-trochanteric bursal fluid and fatty atrophy of gluteus medius and minimus were significantly less pronounced and less frequent when the direct anterior approach was used. There was no significant difference in the findings regarding tensor fascia lata between the two approaches.

We conclude that use of the direct anterior approach results in a better soft-tissue response as assessed by MRI after total hip replacement. However, the impact on outcome needs to be evaluated further.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 12 | Pages 1632 - 1636
1 Dec 2012
Wallace DF Emmett SR Kang KK Chahal GS Hiskens R Balasubramanian S McGuinness K Parsons H Achten J Costa ML

Intra-operative, peri-articular injection of local anaesthesia is an increasingly popular way of controlling pain following total knee replacement. At the same time, the problems associated with allogenic blood transfusion have led to interest in alternative methods for managing blood loss after total knee replacement, including the use of auto-transfusion of fluid from the patient’s surgical drain. It is safe to combine peri-articular infiltration with auto-transfusion from the drain. We performed a randomised clinical trial to compare the concentration of local anaesthetic in the blood and in the fluid collected in the knee drain in patients having either a peri-articular injection or a femoral nerve block. Clinically relevant concentrations of local anaesthetic were found in the fluid from the drains of patients having peri-articular injections (4.92 μg/ml (sd 3.151)). However, none of the patients having femoral nerve blockade had detectable levels. None of the patients in either group had clinically relevant concentrations of local anaesthetic in their blood after re-transfusion.

The evidence from this study suggests that it is safe to use peri-articular injection in combination with auto-transfusion of blood from peri-articular drains during knee replacement surgery.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 12 | Pages 1685 - 1689
1 Dec 2010
Gokaraju K Miles J Parratt MTR Blunn GW Pollock RC Skinner JA Cannon SR Briggs TWR

We have reviewed five adult patients treated with endoprosthetic reconstruction of the proximal radius following resection of non-traumatic lesions. The patients had a mean age of 33.4 years (20 to 60) at the time of surgery and the mean follow-up was 7.6 years (0.8 to 16).

Following surgery, all elbows were clinically stable and there was 100% survivorship of the prosthesis. Evaluation of function was assessed clinically and by the Mayo Elbow Performance Score, achieving a mean of 86% (70 to 100).

Results at medium-term follow-up are encouraging with regards to elbow stability, implant survivorship and functional outcome.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 2 | Pages 151 - 157
1 Feb 2011
El-Husseiny M Patel S MacFarlane RJ Haddad FS

Bacterial infection in orthopaedic surgery can be devastating, and is associated with significant morbidity and poor functional outcomes, which may be improved if high concentrations of antibiotics can be delivered locally over a prolonged period of time. The two most widely used methods of doing this involve antibiotic-loaded polymethylmethacrylate or collagen fleece. The former is not biodegradable and is a surface upon which secondary bacterial infection may occur. Consequently, it has to be removed once treatment has finished. The latter has been used successfully as an adjunct to systemic antibiotics, but cannot effect a sustained release that would allow it to be used on its own, thereby avoiding systemic toxicity.

This review explores the newer biodegradable carrier systems which are currently in the experimental phase of development and which may prove to be more effective in the treatment of osteomyelitis.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 1 | Pages 131 - 139
1 Jan 2011
Daugaard H Elmengaard B Andreassen TT Baas J Bechtold JE Soballe K

Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant.

Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseointegration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1–34) 5 μg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters.

These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 4 | Pages 564 - 569
1 Apr 2012
Pendegrass CJ El-Husseiny M Blunn GW

The success of long-term transcutaneous implants depends on dermal attachment to prevent downgrowth of the epithelium and infection. Hydroxyapatite (HA) coatings and fibronectin (Fn) have independently been shown to regulate fibroblast activity and improve attachment. In an attempt to enhance this phenomenon we adsorbed Fn onto HA-coated substrates. Our study was designed to test the hypothesis that adsorption of Fn onto HA produces a surface that will increase the attachment of dermal fibroblasts better than HA alone or titanium alloy controls.

Iodinated Fn was used to investigate the durability of the protein coating and a bioassay using human dermal fibroblasts was performed to assess the effects of the coating on cell attachment. Cell attachment data were compared with those for HA alone and titanium alloy controls at one, four and 24 hours. Protein attachment peaked within one hour of incubation and the maximum binding efficiency was achieved with an initial droplet of 1000 ng. We showed that after 24 hours one-fifth of the initial Fn coating remained on the substrates, and this resulted in a significant, three-, four-, and sevenfold increase in dermal fibroblast attachment strength compared to uncoated controls at one, four and 24 hours, respectively.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 11 | Pages 1575 - 1580
1 Nov 2005
Böstman OM Laitinen OM Tynninen O Salminen ST Pihlajamäki HK

Despite worldwide clinical use of bio-absorbable devices for internal fixation in orthopaedic surgery, the degradation behaviour and tissue replacement of these implants are not fully understood.

In a long-term experimental study, we have determined the patterns of tissue restoration 36 and 54 months after implantation of polyglycolic acid and poly-laevo-lactic acid screws in the distal femur of the rabbit.

After 36 months in the polyglycolic acid group the specimens showed no remaining polymer and loose connective tissue occupied 80% of the screw track. Tissue restoration remained poor at 54 months, the amounts of trabecular bone and haematopoietic elements being significantly lower than those in the intact control group. The amount of trabecular bone within the screw track at 54 months in the polyglycolic acid group was less than in the empty drill holes (p = 0.04). In the poly-laevo-lactic acid group, polymeric material was present in abundance after 54 months, occupying 60% of the cross-section of the core area of the screw track.

When using absorbable internal fixation implants we should recognise that the degradation of the devices will probably not be accompanied by the restoration of normal trabecular bone.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 11 | Pages 1515 - 1521
1 Nov 2010
Clauss M Ilchmann T Zimmermann P Ochsner PE

The aim of this study was to obtain detailed long-term data on the cement-bone interface in patients with cemented stems, implanted using the constrained fixation technique. A total of eight stems were removed together with adjacent bone during post-mortem examinations of patients with well-functioning prostheses. Specimens were cut at four defined levels, contact radiographs were obtained for each level, and slices were prepared for histological analysis. Clinical data, clinical radiographs, contact radiographs and histological samples were examined for signs of loosening and remodelling. The mean radiological follow-up was 9.6 years and all stems were well-fixed, based on clinical and radiological criteria. Contact radiographs revealed an incomplete cement mantle but a complete filling of the medullary canal for all implants. Various amounts of polyethylene particles were evident at the cement-bone interface of seven stems, with no accompanying inflammatory reaction. Cortical atrophy and the formation of an ‘inner cortex’ were confirmed in six of eight stems by contact radiographs and histology, but were only visible on two clinical radiographs.

Our results confirm that a complete cement mantle is not essential for the survival of Müller straight stems into the mid term, and support our hypothesis that no benefit to long-term survival can be expected from modern cementing techniques.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 114 - 121
1 Jan 2008
Pendegrass CJ Gordon D Middleton CA Sun SNM Blunn GW

Conventional amputation prostheses rely on the attachment of the socket to the stump, which may lead to soft-tissue complications. Intraosseous transcutaneous amputation prostheses (ITAPs) allow direct loading of the skeleton, but their success is limited by infection resulting from breaching of the skin at the interface with the implant. Keratinocytes provide the skin’s primary barrier function, while hemidesmosomes mediate their attachment to natural ITAP analogues. Keratinocytes must attach directly to the surface of the implant. We have assessed the proliferation, morphology and attachment of keratinocytes to four titaniumalloy surfaces in order to determine the optimal topography in vitro. We used immunolocalisation of adhesion complex components, scanning electron microscopy and transmission electron microscopy to assess cell parameters.

We have shown that the proliferation, morphology and attachment of keratinocytes are affected by the surface topography of the biomaterials used to support their growth. Smoother surfaces improved adhesion. We postulate that a smooth topography at the point of epithelium-ITAP contact could increase attachment in vivo, producing an effective barrier of infection.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 2 | Pages 218 - 225
1 Feb 2005
Tsuchiya H Wan SL Sakayama K Yamamoto N Nishida H Tomita K

We describe a method of reconstruction using tumour-bearing autograft treated by liquid nitrogen in 28 patients. The operative technique consisted of en bloc excision of the tumour, removal of soft tissue, curettage of the tumour, drilling and preparation for internal fixation or prosthetic replacement before incubation for 20 minutes in liquid nitrogen, thawing at room temperature for 15 minutes, thawing in distilled water for ten minutes, and internal fixation with an intramedullary nail, plate or composite use of prosthetic replacement. Bone graft or cement was used to augment bone strength when necessary.

The limb function was rated as excellent in 20 patients (71.4%), good in three (10.7%), fair in three (10.7%), and poor in two (7.1%). At the final follow-up six patients had died at a mean of 19.8 months after the operation, while 21 remained free from disease with a mean follow-up of 28.1 months (10 to 54). One patient is alive with disease. Bony union was seen at a mean of 6.7 months after the operation in 26 patients. Complications were encountered in seven patients, including three deep infections, two fractures, and two local recurrences. All were managed successfully. Our results suggest that this is a simple and effective method of biological reconstruction.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1285 - 1291
1 Sep 2005
Whiteside RA Jakob RP Wyss UP Mainil-Varlet P

Surgical reconstruction of articular surfaces by transplantation of osteochondral autografts has shown considerable promise in the treatment of focal articular lesions. During mosaicplasty, each cylindrical osteochondral graft is centred over the recipient hole and delivered by impacting the articular surface. Impact loading of articular cartilage has been associated with structural damage, loss of the viability of chondrocytes and subsequent degeneration of the articular cartilage. We have examined the relationship between single-impact loading and chondrocyte death for the specific confined-compression boundary conditions of mosaicplasty and the effect of repetitive impact loading which occurs during implantation of the graft on the resulting viability of the chondrocytes.

Fresh bovine and porcine femoral condyles were used in this experiment. The percentage of chondrocyte death was found to vary logarithmically with single-impact energy and was predicted more strongly by the mean force of the impact rather than by the number of impacts required during placement of the graft. The significance of these results in regard to the surgical technique and design features of instruments for osteochondral transplantation is discussed.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 7 - 10
1 Jan 2008
Lidgren L

This paper considers the increased risk of the development of lymphoma in patients with chronic inflammatory disease who undergo metal-on-metal arthroplasty.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 8 | Pages 1106 - 1113
1 Aug 2008
Richards L Brown C Stone MH Fisher J Ingham E Tipper JL

Nanometre-sized particles of ultra-high molecular weight polyethylene have been identified in the lubricants retrieved from hip simulators. Tissue samples were taken from seven failed Charnley total hip replacements, digested using strong alkali and analysed using high-resolution field emission gun-scanning electron microscopy to determine whether nanometre-sized particles of polyethylene debris were generated in vivo. A randomised method of analysis was used to quantify and characterise all the polyethylene particles isolated.

We isolated nanometre-sized particles from the retrieved tissue samples. The smallest identified was 30 nm and the majority were in the 0.1 μm to 0.99 μm size range. Particles in the 1.0 μm to 9.99 μm size range represented the highest proportion of the wear volume of the tissue samples, with 35% to 98% of the total wear volume comprised of particles of this size. The number of nanometre-sized particles isolated from the tissues accounted for only a small proportion of the total wear volume. Further work is required to assess the biological response to nanometre-sized polyethylene particles.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 672 - 685
1 May 2007
Goodrich LR Hidaka C Robbins PD Evans CH Nixon AJ

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model.

A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 × 107 AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 107 naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated.

Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months.

Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model.

The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 4 | Pages 571 - 576
1 Apr 2005
Savarino L Granchi D Cenni E Baldini N Greco M Giunti A

There is no diagnostic, non-invasive method for the early detection of loosening after total hip arthroplasty. In a pilot study, we have analysed two serum markers of bone remodelling, procollagen I C-terminal extension peptide (PICP) and cross-linked N-terminal telopeptide (NTx), as well as the diagnostic performance of NTx for the assessment of osteolysis. We recruited 21 patients with loosening (group I), 18 with a well-fixed prosthesis (group II) and 17 at the time of primary arthroplasty for osteoarthritis (OA) (group III). Internal normal reference ranges were obtained from 30 healthy subjects (group IV).

The serum PICP level was found to be significantly lower in patients with OA and those with loosening, when compared with those with stable implants, while the NTx level was significantly increased only in the group with loosening, suggesting that collagen degradation depended on the altered bone turnover induced by the implant. This hypothesis was reinforced by the finding that the values in the pre-surgery patients and stable subjects were comparable with the reference range of younger healthy subjects.

A high specificity and positive predictive value for NTx provided good diagnostic evidence of agreement between the test and the clinical and radiological evaluations. The NTx level could be used to indicate stability of the implant. However, further prospective, larger studies are necessary.