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The Bone & Joint Journal
Vol. 98-B, Issue 1 | Pages 14 - 20
1 Jan 2016
Zywiel MG Cherian JJ Banerjee S Cheung AC Wong F Butany J Gilbert C Overgaard C Syed K Jacobs JJ Mont MA

As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 μg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity.

Take home message: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately.

Cite this article: Bone Joint J 2016;98-B:14–20.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 5 | Pages 684 - 689
1 May 2012
Tsirikos AI Smith G

We reviewed 31 consecutive patients with Friedreich’s ataxia and scoliosis. There were 24 males and seven females with a mean age at presentation of 15.5 years (8.6 to 30.8) and a mean curve of 51° (13° to 140°). A total of 12 patients had thoracic curvatures, 11 had thoracolumbar and eight had double thoracic/lumbar. Two patients had long thoracolumbar collapsing scoliosis with pelvic obliquity and four had hyperkyphosis. Left-sided thoracic curves in nine patients (45%) and increased thoracic kyphosis differentiated these deformities from adolescent idiopathic scoliosis. There were 17 patients who underwent a posterior instrumented spinal fusion at mean age of 13.35 years, which achieved and maintained good correction of the deformity. Post-operative complications included one death due to cardiorespiratory failure, one revision to address nonunion and four patients with proximal junctional kyphosis who did not need extension of the fusion. There were no neurological complications and no wound infections. The rate of progression of the scoliosis in children kept under simple observation and those treated with bracing was less for lumbar curves during bracing and similar for thoracic curves. The scoliosis progressed in seven of nine children initially treated with a brace who later required surgery. Two patients presented after skeletal maturity with balanced curves not requiring correction. Three patients with severe deformities who would benefit from corrective surgery had significant cardiac co-morbidities.


Bone & Joint Research
Vol. 5, Issue 10 | Pages 461 - 469
1 Oct 2016
Liu YK Deng XX Yang H

Objectives

The cytotoxicity induced by cobalt ions (Co2+) and cobalt nanoparticles (Co-NPs) which released following the insertion of a total hip prosthesis, has been reported. However, little is known about the underlying mechanisms. In this study, we investigate the toxic effect of Co2+ and Co-NPs on liver cells, and explain further the potential mechanisms.

Methods

Co-NPs were characterised for size, shape, elemental analysis, and hydrodynamic diameter, and were assessed by Transmission Electron Microscope, Scanning Electron Microscope, Energy Dispersive X-ray Spectroscopy and Dynamic Light Scattering. BRL-3A cells were used in this study. Cytotoxicity was evaluated by MTT and lactate dehydrogenase release assay. In order to clarify the potential mechanisms, reactive oxygen species, Bax/Bcl-2 mRNA expression, IL-8 mRNA expression and DNA damage were assessed on BRL-3A cells after Co2+ or Co-NPs treatment.


Bone & Joint Research
Vol. 5, Issue 6 | Pages 218 - 224
1 Jun 2016
Cheng N Guo A Cui Y

Objectives

Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA.

Methods

Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting.


The Bone & Joint Journal
Vol. 97-B, Issue 10 | Pages 1405 - 1410
1 Oct 2015
Fu J Song K Zhang YG Zheng GQ Zhang GY Liu C Wang Y

Cardiac disease in patients with ankylosing spondylitis (AS) has previously been studied but not in patients with a kyphosis or in those who have undergone an operation to correct it.

The aim of this study was to measure the post-operative changes in cardiac function of patients with an AS kyphosis after pedicle subtraction osteotomy (PSO).

The original cohort consisted of 39 patients (33 men, six women). Of these, four patients (two men, two women) were lost to follow-up leaving 35 patients (31 men, four women) to study. The mean age of the remaining patients was 37.4 years (22.3 to 47.8) and their mean duration of AS was 17.0 years (4.6 to 26.4). Echocardiographic measurements, resting heart rate (RHR), physical function score (PFS), and full-length standing spinal radiographs were obtained before surgery and at the two-year follow-up.

The mean pre-operative RHR was 80.2 bpm (60.6 to 112.3) which dropped to a mean of 73.7 bpm (60.7 to 90.6) at the two-year follow-up (p = 0.0000). Of 15 patients with normal ventricular function pre-operatively, two developed mild left ventricular diastolic dysfunction (LVDD) at the two-year follow-up. Of 20 patients with mild LVDD pre-operatively only five had this post-operatively. Overall, 15 patients had normal LV diastolic function before their operation and 28 patients had normal LV function at the two-year follow-up.

The clinical improvement was 15 out of 20 (75.0%): cardiac function in patients with AS whose kyphosis was treated by PSO was significantly improved.

Cite this article: Bone Joint J 2015;97-B:1405–10.


The Bone & Joint Journal
Vol. 95-B, Issue 11_Supple_A | Pages 70 - 73
1 Nov 2013
Lanting BA MacDonald SJ

Total hip replacement (THR) is a very common procedure undertaken in up to 285 000 Americans each year. Patient satisfaction with THR is very high, with improvements in general health, quality of life, and function while at the same time very cost effective. Although the majority of patients have a high degree of satisfaction with their THR, 27% experience some discomfort, and up to 6% experience severe chronic pain. Although it can be difficult to diagnose the cause of the pain in these patients, this clinical issue should be approached systematically and thoroughly. A detailed history and clinical examination can often provide the correct diagnosis and guide the appropriate selection of investigations, which will then serve to confirm the clinical diagnosis made.

Cite this article: Bone Joint J 2013;95-B, Supple A:70–3.


The Bone & Joint Journal
Vol. 96-B, Issue 1 | Pages 43 - 47
1 Jan 2014
Craig P Bancroft G Burton A Collier S Shaylor P Sinha A

The issues surrounding raised levels of metal ions in the blood following large head metal-on-metal total hip replacement (THR), such as cobalt and chromium, have been well documented. Despite the national popularity of uncemented metal-on-polyethylene (MoP) THR using a large-diameter femoral head, few papers have reported the levels of metal ions in the blood following this combination. Following an isolated failure of a 44 mm Trident–Accolade uncemented THR associated with severe wear between the femoral head and the trunnion in the presence of markedly elevated levels of cobalt ions in the blood, we investigated the relationship between modular femoral head diameter and the levels of cobalt and chromium ions in the blood following this THR.

A total of 69 patients received an uncemented Trident–Accolade MoP THR in 2009. Of these, 43 patients (23 men and 20 women, mean age 67.0 years) were recruited and had levels of cobalt and chromium ions in the blood measured between May and June 2012. The patients were then divided into three groups according to the diameter of the femoral head used: 12 patients in the 28 mm group (controls), 18 patients in the 36 mm group and 13 patients in the 40 mm group. A total of four patients had identical bilateral prostheses in situ at phlebotomy: one each in the 28 mm and 36 mm groups and two in the 40 mm group.

There was a significant increase in the mean levels of cobalt ions in the blood in those with a 36 mm diameter femoral head compared with those with a 28 mm diameter head (p = 0.013). The levels of cobalt ions in the blood were raised in those with a 40 mm diameter head but there was no statistically significant difference between this group and the control group (p = 0.152). The levels of chromium ions in the blood were normal in all patients.

The clinical significance of this finding is unclear, but we have stopped using femoral heads with a diameter of ≤ 36 mm, and await further larger studies to clarify whether, for instance, this issue particularly affects this combination of components.

Cite this article: Bone Joint J 2014;96-B:43–7.


The Bone & Joint Journal
Vol. 96-B, Issue 1 | Pages 100 - 105
1 Jan 2014
Shapiro F Zurakowski D Bui T Darras BT

We determined the frequency, rate and extent of development of scoliosis (coronal plane deformity) in wheelchair-dependent patients with Duchenne muscular dystrophy (DMD) who were not receiving steroid treatment. We also assessed kyphosis and lordosis (sagittal plane deformity). The extent of scoliosis was assessed on sitting anteroposterior (AP) spinal radiographs in 88 consecutive non-ambulatory patients with DMD. Radiographs were studied from the time the patients became wheelchair-dependent until the time of spinal fusion, or the latest assessment if surgery was not undertaken. Progression was estimated using a longitudinal mixed-model regression analysis to handle repeated measurements.

Scoliosis ≥ 10° occurred in 85 of 88 patients (97%), ≥ 20° in 78 of 88 (89%) and ≥ 30° in 66 of 88 patients (75%). The fitted longitudinal model revealed that time in a wheelchair was a highly significant predictor of the magnitude of the curve, independent of the age of the patient (p <  0.001). Scoliosis developed in virtually all DMD patients not receiving steroids once they became wheelchair-dependent, and the degree of deformity deteriorated over time.

In general, scoliosis increased at a constant rate, beginning at the time of wheelchair-dependency (p < 0.001). In some there was no scoliosis for as long as three years after dependency, but scoliosis then developed and increased at a constant rate. Some patients showed a rapid increase in the rate of progression of the curve after a few years – the clinical phenomenon of a rapidly collapsing curve over a few months.

A sagittal plane kyphotic deformity was seen in 37 of 60 patients (62%) with appropriate radiographs, with 23 (38%) showing lumbar lordosis (16 (27%) abnormal and seven (11%) normal).

This study provides a baseline to assess the effects of steroids and other forms of treatment on the natural history of scoliosis in patients with DMD, and an approach to assessing spinal deformity in the coronal and sagittal planes in wheelchair-dependent patients with other neuromuscular disorders.

Cite this article: Bone Joint J 2014;96-B:100–5.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 567 - 573
1 May 2007
Keegan GM Learmonth ID Case CP

The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis.


The Bone & Joint Journal
Vol. 95-B, Issue 8 | Pages 1045 - 1051
1 Aug 2013
Arthroplasty Society C

The purpose of this study was twofold: first, to determine whether the five-year results of hip resurfacing arthroplasty (HRA) in Canada justified the continued use of HRA; and second, to identify whether greater refinement of patient selection was warranted.

This was a retrospective cohort study that involved a review of 2773 HRAs performed between January 2001 and December 2008 at 11 Canadian centres. Cox’s proportional hazards models were used to analyse the predictors of failure of HRA. Kaplan–Meier survival analysis was performed to predict the cumulative survival rate at five years. The factors analysed included age, gender, body mass index, pre-operative hip pathology, surgeon’s experience, surgical approach, implant sizes and implant types. The most common modes of failure were also analysed.

The 2773 HRAs were undertaken in 2450 patients: 2127 in men and 646 in women. The mean age at operation was 50.5 years (sd 8.72; 18 to 82) and mean follow-up was 3.4 years (sd 2.1; 2.0 to 10.1). At the last follow-up a total of 101 HRAs (3.6%) required revision. Using revision for all causes of failure as the endpoint, Kaplan–Meier survival analysis showed a cumulative survival of 96.4% (95% confidence interval (CI) 96.1 to 96.9) at five years. With regard to gender, the five-year overall survival was 97.4% in men (95% CI 97.1 to 97.7) and 93.6% in women (95% CI 92.6 to 94.6). Female gender, smaller femoral components, specific implant types and a diagnosis of childhood hip problems were associated with higher rates of failure. The most common cause of failure was fracture of the femoral neck, followed by loosening of the femoral component.

The failure rates of HRA at five years justify the ongoing use of this technique in men. Female gender is an independent predictor of failure, and a higher failure rate at five years in women leads the authors to recommend this technique only in exceptional circumstances for women.

Cite this article: Bone Joint J 2013;95-B:1044–50.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 2 | Pages 289 - 292
1 Feb 2010
Lewis JRP Gibson PH

The management of joint replacement in lysosomal storage diseases has not been well reported. We present three patients with progressive degenerative changes of the hips who required bilateral total hip replacement in early childhood. The stature of the patients make it essential to have access to appropriately scaled prostheses. Consideration has to be given to associated disorders of the skeleton which must be carefully screened to ensure safety in providing appropriate anaesthesia as well as ensuring that there is no cardiac abnormality. In one patient, a periprosthetic fracture was sustained in one hip in the early post-operative course requiring internal fixation.

The patient made a full recovery and all six hips were clinically and radiologically satisfactory at mid-term review.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 9 | Pages 1201 - 1209
1 Sep 2011
Peng K Hsu W Shih H Hsieh C Huang T Hsu RW Chang P

In this study of 41 patients, we used proteomic, Western blot and immunohistochemical analyses to show that several reactive oxygen species scavenging enzymes are expressed differentially in patients with primary osteoarthritis and those with non-loosening and aseptic loosening after total hip replacement (THR). The patients were grouped as A (n = 16, primary THR), B (n = 10, fixed THR but requiring revision for polyethylene wear) and C (n = 15, requiring revision due to aseptic loosening) to verify the involvement of the identified targets in aseptic loosening. When compared with Groups A and B, Group C patients exhibited significant up-regulation of transthyretin and superoxide dismutase 3, but down-regulation of glutathione peroxidase 2 in their hip synovial fluids. Also, higher levels of superoxide dismutase 2 and peroxiredoxin 2, but not superoxide dismutase 1, catalase and glutathione perioxidase 1, were consistently detected in the hip capsules of Group C patients.

We propose that dysregulated reactive oxygen species-related enzymes may play an important role in the pathogenesis and progression of aseptic loosening after THR.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 4 | Pages 502 - 505
1 Apr 2008
Khan WS Agarwal M Malik AA Cox AG Denton J Holt EM

Metallosis after shoulder replacement has not previously been described in the literature. We report a patient who developed extensive metallosis after implantation of an uncemented Nottingham shoulder replacement. He underwent a revision procedure.

Examination of the retrieved prosthesis showed that the titanium porous coating was separating from the humeral stem and becoming embedded in the ultra-high-molecular-weight polyethylene glenoid component, resulting in abrasive wear of the humeral component. There was metallosis despite exchange of the modular humeral head. Both components had to be exchanged to resolve the problem.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 8 | Pages 988 - 994
1 Aug 2008
Richardson J Hill AM Johnston CJC McGregor A Norrish AR Eastwood D Lavy CBD

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing.

The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone.

Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 3 | Pages 301 - 305
1 Mar 2007
Ziaee H Daniel J Datta AK Blunt S McMinn DJW

Metal-on-metal bearings are being increasingly used in young patients. The potential adverse effects of systemic metal ion elevation are the subject of ongoing investigation. The purpose of this study was to investigate whether cobalt and chromium ions cross the placenta of pregnant women with a metal-on-metal hip resurfacing and reach the developing fetus. Whole blood levels were estimated using high-resolution inductively-coupled plasma mass spectrometry.

Our findings showed that cobalt and chromium are able to cross the placenta in the study patients with metal-on-metal hip resurfacings and in control subjects without any metal implants. In the study group the mean concentrations of cobalt and chromium in the maternal blood were 1.39 μg/l (0.55 to 2.55) and 1.28 μg/l (0.52 to 2.39), respectively. The mean umbilical cord blood concentrations of cobalt and chromium were comparatively lower, at 0.839 μg/l (0.42 to 1.75) and 0.378 μg/l (0.14 to 1.03), respectively, and this difference was significant with respect to chromium (p < 0.05).

In the control group, the mean concentrations of cobalt and chromium in the maternal blood were 0.341 μg/l (0.18 to 0.54) and 0.199 μg/l (0.12 to 0.33), and in the umbilical cord blood they were 0.336 μg/l (0.17 to 0.5) and 0.194 μg/l (0.11 to 0.56), respectively. The differences between the maternal and umbilical cord blood levels in the controls were marginal, and not statistically significant (p > 0.05). The mean cord blood level of cobalt in the study patients was significantly greater than that in the control group (p < 0.01). Although the mean umbilical cord blood chromium level was nearly twice as high in the study patients (0.378 μg/l) as in the controls (0.1934 μg/l), this difference was not statistically significant. (p > 0.05)

The transplacental transfer rate was in excess of 95% in the controls for both metals, but only 29% for chromium and 60% for cobalt in study patients, suggesting that the placenta exerts a modulatory effect on the rate of metal ion transfer.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 10 | Pages 1369 - 1374
1 Oct 2005
Athwal GS Chin PY Adams RA Morrey BF

We reviewed 20 patients who had undergone a Coonrad-Morrey total elbow arthroplasty after resection of a primary or metastatic tumour from the elbow or distal humerus between 1980 and 2002. Eighteen patients underwent reconstruction for palliative treatment with restoration of function after intralesional surgery and two after excision of a primary bone tumour. The mean follow-up was 30 months (1 to 192).

Five patients (25%) were alive at the final follow-up; 14 (70%) had died of their disease and one of unrelated causes. Local control was achieved in 15 patients (75%). The mean Mayo Elbow Performance Score improved from 22 (5 to 45) to 75 points (55 to 95). Four reconstructions (20%) failed and required revision. Seven patients (35%) had early complications, the most frequent being nerve injury (25%). There were no infections or wound complications although 18 patients (90%) had radiotherapy, chemotherapy or both.

The Coonrad-Morrey total elbow arthroplasty provides good relief from pain and a good functional outcome after resection of tumours of the elbow. The rates of complications involving local recurrence of tumour (25%) and nerve injury (25%) are of concern.