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

We have investigated whether the presence of polyethylene (PE) alone is sufficient to cause an aggressive periprosthetic tissue response, or whether certain mechanical interface conditions can allow bone to grow while in the presence of PE. An experimental implant was loaded in the presence and absence of particulate PE under stable and unstable conditions. Bone with a thin, discontinuous fibrous membrane formed in both groups of stable implants, either in the presence or absence of PE. By contrast, a continuous fibrous membrane consistently formed in both groups of unstable implants. The membrane consisted of loose fibrous connective tissue when PE was absent, and dense connective tissue with macrophages and a synovial lining when PE was present. In this model, if the interface was stable, the presence of PE was not sufficient to prevent the formation of bone or to produce a phagocytic tissue response. Only when the interface was unstable did a fibrous membrane form, and only then in the presence of PE

The pathogenesis of aseptic loosening of total joint prostheses is not clearly understood. Two features are associated with loosened prostheses, namely, particulate debris and movement of the implant. While numerous studies have evaluated the cellular response to particulate biomaterials, few have investigated the influence of movement of the implant on the biological response to particles. Our aim was therefore to test the hypothesis that excessive mechanical stimulation of the periprosthetic tissues induces an inflammatory response and that the addition of particulate biomaterials intensifies this. We allocated 66 adult Beagle dogs to four groups as follows: stable implants with (I) and without (II) particulate polymethylmethacrylate (PMMA) and moving implants with (III) and without (IV) particulate PMMA. They were then evaluated at 2, 4, 6, 12 and 24 weeks. The stable implants were well tolerated and a thin, fibrous membrane of connective tissue was observed. There was evidence of positive staining in some cells for interleukin-6 (IL-6). Addition of particulate PMMA around the stable implants resulted in an increase in the fibroblastic response and positive staining for IL-6 and tumour necrosis factor-alpha (TNF-α). By contrast, movement of the implant resulted in an immediate inflammatory response characterised by large numbers of histiocytes and cytokine staining for IL-1ß, TNF-α and IL-6. Introduction of particulate PMMA aggravated this response. Animals with particulate PMMA and movement of the implant have an intense inflammatory response associated with accelerated bone loss. Our results indicate that the initiation of the inflammatory response to biomaterial particles was much slower than that to gross mechanical instability. Furthermore, when there was both particulate debris and movement, there was an amplification of the adverse tissue response as evidenced by the presence of osteolysis and increases in the presence of inflammatory cells and their associated cytokines

This study evaluated the effect on movement under load of three different techniques for re-attachment of the tuberosities of the humerus using test sawbones. In the first, the tuberosities were attached both to the shaft and to each other, with one cerclage suture through the anterior hole in the prosthesis. The second technique was identical except for omission of the cerclage suture and in the third the tuberosities were attached to the prosthesis and to the shaft. An orthogonal photogrammetric system allowed all segments to be tracked in a 3D axis system. The humeri were incrementally-loaded in abduction, and the 3D linear and angular movements of all segments were calculated. Displacement between the tuberosities and the shaft was measured. The first and second techniques were the most stable constructs, with the third allowing greater separation of fragments and angular movement. Separation at the midpoint of the tuberosities was significantly greater using the latter technique (p < 0.05). The cerclage suture added no further stability to the fixation

We developed an in vivo model of the attachment of a patellar tendon to a metal implant to simulate the reconstruction of an extensor mechanism after replacement of the proximal tibia. In 24 ewes, the patellar tendon was attached to a hydroxyapatite (HA)-coated titanium prosthesis. In 12, the interface was augmented with autograft containing cancellous bone and marrow. In the remaining ewes, the interface was not grafted. Kinematic gait analysis showed nearly normal function of the joint by 12 weeks. Force-plate assessment showed a significant increase in functional weight-bearing in the grafted animals (p = 0.043). The tendon-implant interface showed that without graft, encapsulation of fibrous tissue occurred. With autograft, a developing tendon-bone-HA-implant interface was observed at six weeks and by 12 weeks a layered tendon-fibrocartilage-bone interface was seen which was similar to a direct-type enthesis. With stable mechanical fixation, an appropriate bioactive surface and biological augmentation the development of a functional tendon-implant interface can be achieved

We stably transfected early passage chondrocytes with an anti-apoptotic Bcl-2 gene in vitro using a retrovirus vector. Samples of articular cartilage were obtained from 11 patients with a mean age of 69 years (61 to 75) who were undergoing total knee replacement for osteoarthritis. The Bcl-2-gene-transfected chondrocytes were compared with non-transfected and lac-Z-gene-transfected chondrocytes, both of which were used as controls. All three groups of cultured chondrocytes were incubated with nitric oxide (NO) for ten days. Using the Trypan Blue exclusion assay, an enzyme-linked immunosorbent assay and flow cytometric analysis, we found that the number of apoptotic chondrocytes was significantly higher in the non-transfected and lac-Z-transfected groups than in the Bcl-2-transfected group (p < 0.05). The Bcl-2-transfected chondrocytes were protected from NO-induced impairment of proteoglycan synthesis. We conclude that NO-induced chondrocyte death involves a mechanism which appears to be subject to regulation by an anti-apoptotic Bcl-2 gene. Therefore, Bcl-2 gene therapy may prove to be of therapeutic value in protecting human articular chondrocytes

We observed the healing process under rigid external fixation after Salter-Harris type-1 or type-2 physeal separation at the proximal tibia in immature rabbits. Metaphyseal vessels grew across the gap with little delay; the site of separation then came to lie in the metaphysis and was bridged by endochondral ossification. Union was achieved within two days in all rabbits. Progression of endochondral ossification repaired the separated physis, thus showing ‘primary healing of physeal separation’. This depends on accurate reduction and stable fixation to allow the survival of vessels across the gap

We have used in vivo microdialysis to monitor postoperative physiological events in the synovial membrane after arthroscopy. The levels of lactate were significantly higher in the synovial membrane than in the reference tissue (subcutaneous fat) and there was a significant increase in lactate after operation. Blood flow, measured as the ethanol ratio, was stable in both tissues. Our findings show that there was an increase in the local production of lactate since the levels of lactate in blood and the reference tissue were comparable and did not show a significant increase. There was also a consumption of glucose in the synovial membrane which was not observed in the reference tissue. The levels of pyruvate were higher in the synovial membrane. A state of reperfusion occurs in the synovial membrane after moderate trauma such as standard arthroscopy of the knee. Microdialysis should be further evaluated in studies of the in vivo physiology of the synovial membrane

We measured the levels of cobalt and chromium in the serum in three groups of patients after uncemented porous-coated arthroplasty. Group 1 consisted of 14 consecutive patients undergoing revision for aseptic loosening. Group 2 comprised 14 matched patients in whom the arthroplasty was stable and group 3 was 14 similarly matched patients with arthritis awaiting hip replacement. Specimens were analysed using atomic absorption spectrophotometry. Aseptic loosening of a component resulted in a significant elevation of serum cobalt (p < 0.05), but not of serum chromium. The relative risk of a component being loose, if the patient had a serum cobalt greater than 9.0 nmol/l, was 2.8

In ten male rats we inserted ceramic ‘drawing-pin’ implants in weight-bearing positions within the right proximal tibia. Two animals were killed 6 weeks after surgery and two more 14 weeks after surgery. The remaining six received intra-articular injections of either high-density polyethylene (4 rats) or saline (2 rats) at 8, 10 and 12 weeks after surgery. These animals were killed two weeks after the last injection. Histological examination of the bone-implant interface in the control animals showed appositional bone growth around the implant at both 6 and 14 weeks. Polyethylene, but not saline, caused a chronic inflammatory response with numerous foreign-body giant cells in periprosthetic tissues. Our model of a stable, weight-bearing bone-implant interface provides a simple and reliable system in which to study in vivo the effects of particulate materials used in orthopaedic surgery

We examined whether somatosensory evoked potentials (SEPs) were detectable after direct electrical stimulation of injured, reconstructed and normal anterior cruciate ligaments (ACL) during arthroscopy under general anaesthesia. We investigated the position sense of the knee before and after reconstruction and the correlation between the SEP and instability. We found detectable SEPs in all ligaments which had been reconstructed with autogenous semitendinosus and gracilis tendons over the past 18 months as well as in all cases of the normal group. The SEP was detectable in only 15 out of 32 cases in the injured group, although the voltages in the injured group were significantly lower than those of the controls. This was not the case in the reconstructed group. The postoperative position sense in 17 knees improved significantly, but there was no correlation between it and the voltage. The voltage of stable knees was significantly higher than that of the unstable joints. Our findings showed that sensory reinnervation occurred in the reconstructed human ACL and was closely related to the function of the knee

We used a rat model in vivo to study the effects of the concentration of polyethylene particles on the bone-implant interface around stable implants in the proximal tibia. Intra-articular injections of 10. 4. , 10. 6. or 10. 8. high-density polyethylene (HDPE) particles per joint were given 8, 10 and 12 weeks after surgery. The animals were killed after 14 and 26 weeks and the response at the interface determined. Fibrous tissue was seen at the bone-implant interface when the head of the implant was flush with the top of the tibia but not when it was sunk below the tibial plateau. In the latter case the implant was completely surrounded by a shell of bone. The area of fibrous tissue and that of the gap between the implant and bone was related to the concentration of particles in the 14-week group (p < 0.05). Foreign-body granulomas containing HDPE particles were seen at the bone-implant interface in animals given 10. 8. particles. The pathology resembles that seen around prostheses with aseptic loosening and we suggest that this is a useful model by which to study this process

Coating titanium alloy implants with titanium nitride (TiN) by the method of Powder Immersion Reaction Assisted Coating (PIRAC) produces a stable layer on their surface. We have examined the ability of the new TiN coating to undergo osseointegration. We implanted TiN-coated and uncoated Ti6Al4V alloy pins into the femora of six-month-old female Wistar rats. SEM after two months showed a bone collar around both TiN-coated and uncoated implants. Morphometrical analysis revealed no significant differences between the percentage of the implant-bone contact and the area and volume of the bone around TiN-coated compared with uncoated implants. Electron-probe microanalysis indicated the presence of calcium and phosphorus at the implant-bone interface. Mineralisation around the implants was also confirmed by labelling with oxytetracycline. Strong activity of alkaline phosphatase and weak activity of tartrate-resistant acid phosphatase were shown histochemically. Very few macrophages were detected by the non-specific esterase reaction at the site of implantation. Our findings indicate good biocompatibility and bone-bonding properties of the new PIRAC TiN coatings which are comparable to those of uncoated Ti6Al4V alloy implants

We analysed synovial fluid from 88 hips, 38 with osteoarthritis and 12 with well-functioning and 38 with loose hip prostheses. The levels of TNF-α, IL-1ß (71 hips) and IL-6 (45 hips) were measured using the ELISA technique. Joints with well-functioning or loose prostheses had significantly increased levels of TNF-α compared with those with osteoarthritis. Hips with aseptic loosening also had higher levels of IL-1ß but not of IL-6 compared with those without an implant. The levels of TNF-α and IL-1ß did not differ between hips with stable and loose prostheses. Higher levels of TNF-α were found in hips with bone resorption of type II and type III (Gustilo-Pasternak) compared with those with type-I loosening. The level of cytokines in joint fluid was not influenced by the time in situ of the implants or the age, gender or area of the osteolysis as measured on conventional radiographs. Our findings support the theory that macrophages in the joint capsule increase the production of TNF-α at an early phase probably because of particle load and in the absence of clinical loosening. Since TNF-α has an important role in the osteolytic process, the interfaces should be protected from penetration of joint fluid

To investigate the effect of instability on the remodelling of a minor articular surface offset, we created a 0.5 mm coronal step-off of the medial femoral condyle in 12 New Zealand white rabbits and transected the anterior cruciate ligament (ACL). A control group of 12 rabbits had only ACL resection and the opposite knee was used as the non-operated control. The osteoarthritic changes at 6, 12 and 24 weeks after surgery were evaluated histologically. In addition, changes in the immunological detection of 3-B-3(-) and 7-D-4 chondroitin-6-sulphate epitopes were determined because of the previous association of such changes with repair of cartilage and early osteoarthritis. In the instability/step-off group there was rapidly progressing focal degeneration of cartilage on the high side of the defect, not seen in previous step-off studies in stable knees. The rest of the femoral condyles and the tibial plateaux of the instability/step-off group had moderate osteoarthritis similar to that of the instability group. 3-B-3(-) was detectable in the early and the intermediate stages of osteoarthritis but no staining was seen in the severely damaged cartilage zones. Immunoreactivity with 7-D-4 increased as degeneration progressed. Our findings have shown that even a minor surface offset may induce rapid degeneration of cartilage when the stability of the knee is compromised

The clinical use of hydroxyapatite (HA) coating is controversial especially in regard to the long-term performance of the coating and the effects of resorption. In each of 15 consenting patients we inserted two implants, coated with either HA or fluorapatite (FA) into the iliac crest. They were harvested at a mean of 13.6 ± 0.6 months after surgery. Histological examination showed that bone ongrowth on the HA-coated implants was significantly greater (29%) than that on the FA-coated implants. When bone was present on the coating surface the HA coating was significantly thicker than the FA coating. When bone marrow was present, the HA coating was significantly thinner than the FA coating. The reduction in coating thickness when covered by bone or bone marrow was 23.1 ± 9.7 μm for HA and 5.1 ± 1.7 μm for FA (p < 0.01) suggesting that FA is more stable than HA against resorption by bone marrow. The findings suggest that in man the osteoconductive properties of HA coating are superior to those of FA. Resorption rates for both coatings were approximately 20% of the coating thickness per year. Bone ongrowth appears to protect against resorption whereas bone marrow seems to accelerate resorption. No adverse reaction was seen in the surrounding bone

Bone growth into cementless prosthetic components is compromised by osteoporosis, by any gap between the implant and the bone, by micromotion, and after the revision of failed prostheses. Recombinant human transforming growth factor-β1 (rhTGF-β1) has recently been shown to be a potent stimulator of bone healing and bone formation in various models in vivo. We have investigated the potential of rhTGF-β1, adsorbed on to weight-loaded tricalcium phosphate (TCP) coated implants, to enhance bone ongrowth and mechanical fixation. We inserted cylindrical grit-blasted titanium alloy implants bilaterally into the weight-bearing part of the medial femoral condyles of ten skeletally mature dogs. The implants were mounted on special devices which ensured stable weight-loading during each gait cycle. All implants were initially surrounded by a 0.75 mm gap and were coated with TCP ceramic. Each animal received two implants, one with 0.3 μg rhTGF-β1 adsorbed on the ceramic surface and the other without growth factor. Histological analysis showed that bone ongrowth was significantly increased from 22 ± 5.6% bone-implant contact in the control group to 36 ± 2.9% in the rhTGF-β stimulated group, an increase of 59%. The volume of bone in the gap was increased by 16% in rhTGF-β1-stimulated TCP-coated implants, but this difference was not significant. Mechanical push-out tests showed no difference in fixation of the implant between the two groups. Our study suggests that rhTGF-β1 adsorbed on TCP-ceramic-coated implants can enhance bone ongrowth

We revised seven alumina-blasted cementless hip prostheses (Ti-alloy stems, cp Ti threaded sockets) with low- or high-carbon Co-alloy bearings at a mean of 20.1 months after implantation because of pain and loosening. Histological examination of the retrieved periprosthetic tissues from two cases in which the implant was stable and three in which the socket was loose showed macrophages with basophilic granules containing metal and alumina wear particles and lymph-cell infiltrates. In one of the two cases of stem loosening the thickened neocapsule also contained definite lymphatic follicles and gross lymphocyte/plasma-cell infiltrates. Spectrometric determination of the concentration of elements in periprosthetic tissues from six cases was compared with that of joint capsules from five control patients undergoing primary hip surgery. In the revisions the mean concentration of implant-relevant elements was 693.85 μg/g dry tissue. In addition to Cr (15.2%), Co (4.3%), and Ti (10.3%), Al was predominant (68.1%) and all concentrations were significantly higher (p < 0.001) than those in the control tissues. The annual rates of linear wear were calculated for six implants. The mean value was 11.1 μm (heads 6.25 μm, inserts 4.82 μm). SEM/EDXA showed numerous fine scratches and deep furrows containing alumina particles in loosened sockets, and stems showed contamination with adhering or impacted alumina particles of between 2 and 50 μm in size

High-intensity narrow-spectrum (HINS) light is a novel violet-blue light inactivation technology which kills bacteria through a photodynamic process, and has been shown to have bactericidal activity against a wide range of species. Specimens from patients with infected hip and knee arthroplasties were collected over a one-year period (1 May 2009 to 30 April 2010). A range of these microbial isolates were tested for sensitivity to HINS-light. During testing, suspensions of the pathogens were exposed to increasing doses of HINS-light (of 123mW/cm² irradiance). Non-light exposed control samples were also used. The samples were then plated onto agar plates and incubated at 37°C for 24 hours before enumeration. Complete inactivation (greater than 4-log₁₀ reduction) was achieved for all of the isolates. The typical inactivation curve showed a slow initial reaction followed by a rapid period of inactivation. The doses of HINS-light required ranged between 118 and 2214 J/cm². Gram-positive bacteria were generally found to be more susceptible than Gram-negative.

As HINS-light uses visible wavelengths, it can be safely used in the presence of patients and staff. This unique feature could lead to its possible use in the prevention of infection during surgery and post-operative dressing changes.

Cite this article: Bone Joint J 2015;97-B:283–8.

We used a biodegradable mesh to convert an acetabular defect into a contained defect in six patients at total hip replacement. Their mean age was 61 years (46 to 69). The mean follow-up was 32 months (19 to 50). Before clinical use, the strength retention and hydrolytic in vitro degradation properties of the implants were studied in the laboratory over a two-year period. A successful clinical outcome was determined by the radiological findings and the Harris hip score.

All the patients had a satisfactory outcome and no mechanical failures or other complications were observed. No protrusion of any of the impacted grafts was observed beyond the mesh. According to our preliminary laboratory and clinical results the biodegradable mesh is suitable for augmenting uncontained acetabular defects in which the primary stability of the implanted acetabular component is provided by the host bone. In the case of defects of the acetabular floor this new application provides a safe method of preventing graft material from protruding excessively into the pelvis and the mesh seems to tolerate bone-impaction grafting in selected patients with primary and revision total hip replacement.