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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.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 9 | Pages 1217 - 1223
1 Sep 2006
Wiig O Terjesen T Svenningsen S Lie SA

A nationwide study of Perthes’ disease in Norway was undertaken over a five-year period from January 1996. There were 425 patients registered, which represents a mean annual incidence of 9.2 per 100 000 in subjects under 15 years of age, and an occurrence rate of 1:714 for the country as a whole. There were marked regional variations. The lowest incidence was found in the northern region (5.4 per 100 000 per year) and the highest in the central and western regions (10.8 and 11.3 per 100 000 per year, respectively). There was a trend towards a higher incidence in urban (9.5 per 100 000 per year) compared with rural areas (8.9 per 100 000 per year). The mean age at onset was 5.8 years (1.3 to 15.2) and the male:female ratio was 3.3:1.

We compared 402 patients with a matched control group of non-affected children (n = 1 025 952) from the Norwegian Medical Birth Registry and analysed maternal data (age at delivery, parity, duration of pregnancy), birth length and weight, birth presentation, head circumference, ponderal index and the presence of congenital anomalies. Children with Perthes’ disease were significantly shorter at birth and had an increased frequency of congenital anomalies.

Applying Sartwell’s log-normal model of incubation periods to the distribution of age at onset of Perthes’ disease showed a good fit to the log-normal curve. Our findings point toward a single cause, either genetic or environmental, acting prenatally in the aetiology of Perthes’ disease.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1292 - 1297
1 Sep 2005
Lietman SA Inoue N Rafiee B Deitz LW Chao EYS

We used a canine intercalary bone defect model to determine the effects of recombinant human osteogenic protein 1 (rhOP-1) on allograft incorporation. The allograft was treated with an implant made up of rhOP-1 and type I collagen or with type I collagen alone.

Radiographic analysis showed an increased volume of periosteal callus in both test groups compared with the control group at weeks 4, 6, 8 and 10. Mechanical testing after 12 weeks revealed increased maximal torque and stiffness in the rhOP-1 treated groups compared with the control group.

These results indicate a benefit from the use of an rhOP-1 implant in the healing of bone allografts. The effect was independent of the position of the implant. There may be a beneficial clinical application for this treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 2 | Pages 261 - 266
1 Feb 2005
Földhazy Z Arndt A Milgrom C Finestone A Ekenman I

Strains applied to bone can stimulate its development and adaptation. High strains and rates of strain are thought to be osteogenic, but the specific dose response relationship is not known. In vivo human strain measurements have been performed in the tibia to try to identify optimal bone strengthening exercises for this bone, but no measurements have been performed in the distal radial metaphysis, the most frequent site of osteoporotic fractures. Using a strain gauged bone staple, in vivo dorsal metaphyseal radial strains and rates of strain were measured in ten female patients during activities of daily living, standard exercises and falls on extended hands. Push-ups and falling resulted in the largest compression strains (median 1345 to 3146 με, equivalent to a 0.1345% to 0.3146% length change) and falling exercises in the largest strain rates (18 582 to 45 954 με/s). On the basis of their high strain and/or strain rates these or variations of these exercises may be appropriate for distal radial metaphyseal bone strengthening.


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 1 | Pages 2 - 9
1 Jan 2005
Giannoudis PV Grotz MRW Papakostidis C Dinopoulos H

Over the past 40 years, the management of displaced fractures of the acetabulum has changed from conservative to operative. We have undertaken a meta-analysis to evaluate the classification, the incidence of complications and the functional outcome of patients who had undergone operative treatment of such injuries.

We analysed a total of 3670 fractures. The most common long-term complication was osteoarthritis which occurred in approximately 20% of the patients. Other late complications, including heterotopic ossification and avascular necrosis of the femoral head, were present in less than 10%. However, only 8% of patients who were treated surgically needed a further operation, usually a hip arthroplasty, and between 75% and 80% of patients gained an excellent or good result at a mean of five years after injury. Factors influencing the functional outcome included the type of fracture and/or dislocation, damage to the femoral head, associated injuries and co-morbidity which can be considered to be non-controllable, and the timing of the operation, the surgical approach, the quality of reduction and local complications which are all controllable. The treatment of these injuries is challenging. Tertiary referrals need to be undertaken as early as possible, since the timing of surgery is of the utmost importance. It is important, at operation, to obtain the most accurate reduction of the fracture which is possible, with a minimal surgical approach, as both are related to improved outcome.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 646 - 655
1 May 2005
Victor J Banks S Bellemans J

We performed a prospective, randomised trial of 44 patients to compare the functional outcomes of a posterior-cruciate-ligament-retaining and posterior-cruciate-ligament-substituting total knee arthroplasty, and to gain a better understanding of the in vivo kinematic behaviour of both devices.

At follow-up at five years, no statistically significant differences were found in the clinical outcome measurements for either design. The prevalence of radiolucent lines and the survivorship were the same. In a subgroup of 15 knees, additional image-intensifier analysis in the horizontal and sagittal planes was performed during step-up and lunge activity. Our analysis revealed striking differences. Lunge activity showed a mean posterior displacement of both medial and lateral tibiofemoral contact areas (roll-back) which was greater and more consistent in the cruciate-substituting than in the cruciate-retaining group (medial p < 0.0001, lateral p = 0.011). The amount of posterior displacement could predict the maximum flexion which could be achieved (p = 0.018). Forward displacement of the tibiofemoral contact area in flexion during stair activity was seen more in the cruciate-retaining than in the cruciate-substituting group. This was attributed mainly to insufficiency of the posterior cruciate ligament and partially to that of the anterior cruciate ligament. We concluded that, despite similar clinical outcomes, there are significant kinematic differences between cruciate-retaining and cruciate-substituting arthroplasties.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 593 - 603
1 May 2005
Harvey A Thomas NP Amis AA