A heavy infiltrate of foreign-body macrophages is commonly seen in the fibrous membrane which surrounds an aseptically loose cemented implant. This is in response to particles of polymethylmethacrylate (PMMA) bone cement and other biomaterials. We have previously shown that monocytes and macrophages responding to particles of bone cement are capable of differentiating into osteoclastic cells which resorb bone. To determine whether the radio-opaque additives barium sulphate (BaSO. 4. ) and zirconium dioxide (ZrO. 2. ) influence this process, particles of PMMA with and without these agents were added to mouse monocytes and cocultured with osteoblast-like cells on bone slices. Osteoclast differentiation, as shown by the presence of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and lacunar bone resorption, was observed in all cocultures. The addition of PMMA alone to these cocultures caused no increase in TRAP expression or bone resorption relative to control cocultures. Adding PMMA particles containing BaSO. 4. or ZrO. 2. , however, caused an increase in TRAP expression and a highly significant increase in bone resorption. Particles containing BaSO. 4. were associated with 50% more bone resorption than those containing ZrO. 2. . Our results suggest that radio-opaque agents in bone cement may contribute to the bone resorption of aseptic loosening by enhancing macrophage-osteoclast differentiation, and that PMMA containing is BaSO. 4. likely to be associated with more osteolysis than that containing ZrO. 2.

We investigated the possibility that the macrophages which are seen around implants may stimulate bone resorption and cause loosening. We found that macrophages release mediators that stimulate bone resorption, and that the amount of resorption increased by between 2.5 and 10 times when the macrophages adhered to a foreign surface. This bone resorption depended on the surface energy and roughness of the foreign surface, varying with these physical properties rather than with the chemical nature of the material. It is concluded that loosening of orthopaedic implants is likely to be influenced by the surface energy and roughness of the implant

We investigated in vitro a mechanism by which particulate debris may induce bone resorption and cause implant loosening. We first studied two standard particles: latex, which is considered to be inert, and zymosan, which is inflammatory. Macrophages that phagocytosed either particle became activated, and stimulated 15 times as much bone resorption as did control macrophages. For activation to occur, 100 times more latex than zymosan had to be phagocytosed. We also found that bone cement and polyethylene particles activated macrophages in a similar manner, and that the necessary amounts of these were intermediate between those of latex and zymosan. None of the particles were toxic. It was concluded that implant loosening may result from bone resorption stimulated by mediators released by macrophages that have phagocytosed particles of bone cement or polyethylene

Calvaria from six-day-old infant mice were grown on a grid culture in a chemically defined medium under varying oxygen tensions. Quantitative isotope studies demonstrated a linear association between bone resorption and oxygen tension in the physiological range. This result was supported by histological, histochemical and vital staining experiments. The clinical finding of osteoporosis in areas of hyperaemia could therefore be attributed to a rise in oxygen tension causing increased bone resorption

Using a rat model, we created a bone-to-titanium interface and applied phagocytosable high-density polyethylene pArticles between the bone and implant, either initially or when the interface had matured. No fibrous membrane developed and no bone resorption was found. If sliding movements were initiated at the interface after two weeks, there was formation of a fibrous membrane. The additional application of pArticles did not change the thickness of the membrane, and there were only minor qualitative changes. Creation of a membrane by movement followed by cessation of movement and the application of pArticles caused the membrane to persist, whereas in a pArticle-free control group bone-to-metal contact was re-established. Our findings suggest that mechanical stimuli are of primary importance for prosthetic loosening, and that pArticles may modulate the later stages of the loosening process

We reviewed at a minimum elapsed time of five years a consecutive series of 143 primary Exeter hip replacements in which matt-surfaced femoral stems had been used. Twenty-five patients had died and six stems and two sockets had been revised before follow-up. The remaining 110 hips were all examined clinically and radiographically. In 15 hips there were radiographic signs of definite loosening of the stem and in eight suspected loosening. The acetabulum was loose in four hips. In another eight hips localised bone resorption was present without signs of loosening. Half the patients with loosening or localised bone resorption had mild pain or no pain at all. The late complication rate with the matt-surfaced Exeter femoral stem is unacceptably high

Wear particles commonly used for experiments may carry adherent endotoxin on their surfaces, which may be responsible for the observed effects. In this study, we attached titanium plates to the tibiae of 20 rats. After osseointegration, endotoxin-contaminated or uncontaminated high-density-polyethylene (HDPE) particles were applied. Contaminated specimens showed a dramatic resorption of bone after seven days but new bone filled the site again at 21 days. Uncontaminated specimens showed no resorption. In 18 rats we implanted intramuscularly discs of ultra-high-molecular-weight polyethylene (UHMWPE) with baseline or excess contamination of endotoxin. Excess endotoxin disappeared within 24 hours and the amount of endotoxin remained at baseline level (contamination from production). Uncontaminated titanium discs did not adsorb endotoxin in vivo. The endotoxin was measured by analytical chemistry. Locally-applied endotoxin stimulated bone resorption similarly to that in experiments with wear particles. Endotoxin on the surface of implants and particles appeared to be inactivated in situ. A clean implant surface did not adsorb endotoxin. Our results suggest that endotoxin adhering to orthopaedic implants is not a major cause for concern

Inadequate bone stock is often found in revision surgery of femoral components of total knee replacements. Our aim was to test the hypothesis that these remodelling patterns can be explained by stress shielding, and that prosthetic bonding characteristics affect maintenance of bone mass. We made a three-dimensional finite-element model of an average male femur with a cemented femoral knee component. This model was integrated with iterative remodelling procedures. Two extreme prosthetic bonding conditions were analysed and gradual changes in bone density were calculated. The long-term bone loss under the femoral knee component resembled clinical findings which confirms the hypothesis that stress shielding can cause distal femoral bone loss. Our study predicts, contrary to clinical findings, that an equilibrium situation is not reached after two years, but that bone resorption may continue. This hidden bone loss may be so drastic that large reconstructions are needed at the time of revision

Matrix metalloproteinases (MMPs) may have a role in the process of aseptic loosening. Doxycycline has been shown to inhibit MMPs. Our aim was to investigate the potential pharmacological effect of doxycycline on aseptic loosening. We used radiolabelled mouse calvariae cultured with human interface membrane cells from aseptically loosened hips. Bone resorption was confirmed in this model. The effect of doxycycline was assessed by culturing dead radiolabelled bone discs with cells from the interface membrane with doxycycline. The control group consisted of the same culture system without doxycycline. Supernatant . 45. calcium and the total . 45. calcium remaining in the bone discs at the completion of the culture were used to measure osteolysis. We found that doxycycline can inhibit osteolysis at the interface membrane of aseptically loosened hips. This may have therapeutic implications for the treatment of patients with aseptic loosening of total joint replacements

Aims

It has been hypothesized that proximal radial neck resorption (PRNR) following press-fit radial head arthroplasty (RHA) is due to stress-shielding. We compared two different press-fit stems by means of radiographs to investigate whether the shape and size of the stems are correlated with the degree of PRNR.

Peri-prosthetic osteolysis and subsequent aseptic loosening is the most common reason for revising total hip replacements. Wear particles originating from the prosthetic components interact with multiple cell types in the peri-prosthetic region resulting in an inflammatory process that ultimately leads to peri-prosthetic bone loss. These cells include macrophages, osteoclasts, osteoblasts and fibroblasts. The majority of research in peri-prosthetic osteolysis has concentrated on the role played by osteoclasts and macrophages. The purpose of this review is to assess the role of the osteoblast in peri-prosthetic osteolysis.

In peri-prosthetic osteolysis, wear particles may affect osteoblasts and contribute to the osteolytic process by two mechanisms. First, particles and metallic ions have been shown to inhibit the osteoblast in terms of its ability to secrete mineralised bone matrix, by reducing calcium deposition, alkaline phosphatase activity and its ability to proliferate. Secondly, particles and metallic ions have been shown to stimulate osteoblasts to produce pro inflammatory mediators in vitro. In vivo, these mediators have the potential to attract pro-inflammatory cells to the peri-prosthetic area and stimulate osteoclasts to absorb bone. Further research is needed to fully define the role of the osteoblast in peri-prosthetic osteolysis and to explore its potential role as a therapeutic target in this condition.

Cite this article: Bone Joint J 2013;95-B:1021–5.

Aims

The primary aim of this study was to compare the wear properties of vitamin E-diffused, highly crosslinked polyethylene (VEPE) and one formulation of moderately crosslinked and mechanically annealed ultra-high molecular weight polyethylene (ModXLPE) in patients five years after primary total hip arthroplasty (THA). The secondary aim was to assess the clinical results of patients treated with VEPE by evaluating patient-reported outcome measures (PROMs), radiological evidence of fixation, and the incidence of mechanical failure.

Aims

The aim of this study was to evaluate the clinical and radiological outcome of using an anatomical short-stem shoulder prosthesis to treat primary osteoarthritis of the glenohumeral joint.

Aims. The aim of this study was to analyze how proximal radial neck resorption (PRNR) starts and progresses radiologically in two types of press-fit radial head arthroplasties (RHAs), and to investigate its clinical relevance. Methods. A total of 97 patients with RHA were analyzed: 56 received a bipolar RHA (Group 1) while 41 received an anatomical implant (Group 2). Radiographs were performed postoperatively and after three, six, nine, and 12 weeks, six, nine, 12, 18, and 24 months, and annually thereafter. PRNR was measured in all radiographs in the four radial neck quadrants. The Mayo Elbow Performance Score (MEPS), the abbreviated version of the Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH), and the patient-assessed American Shoulder and Elbow Surgeons score - Elbow (pASES-E) were used for the clinical assessment. Radiological signs of implant loosening were investigated. Results. The mean follow-up was six years (2 to 14). PRNR started after a mean of 7.5 weeks (SD 2.1) and progressed significantly during the first two years, by the end of which the bone resorption stabilized. PRNR was detected in 81% (n = 45) of patients in Group 1 and 88% (n = 36) in Group 2. The final mean PRNR was 3.0 mm (SD 2.3) in Group 1 and 3.7 mm (SD 2.5) in Group 2. The mean MEPS, QuickDASH, and pASES-E were 95.9 (SD 11.5), 4.4 (SD 9.2), and 94.8 (SD 10.9) in Group 1 and 92.2 (SD 16.2), 9.9 (SD 21.5), and 90.8 (SD 15) in Group 2, respectively. No significant differences were observed between groups in the clinical and radiological outcomes. No correlations were found between PRNR and the clinical results. Conclusion. PRNR after press-fit RHA is a common radiological finding that develops in the first 24 months before stabilizing definitively. PRNR does not affect the clinical results or implant survival in the mid term. Cite this article: Bone Joint J 2023;105-B(8):905–911

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. Results. The mean follow-up period was 92.5 months (25 to 140). Bony union was observed in all of our patients. Osteomyelitis developed in two patients with femoral shaft fractures, and two patients had peri-implant stress fractures. Conclusion. Treatment of fractures in OP patients is difficult, healing is protracted, and the risk of postoperative infection is high. In children and young adults with OP who have open medullary canal and the epiphyses are not closed, fractures can be treated with surgical techniques such as intramedullary titanium elastic nail (TENS) technique or fixation with Kirschner (K)-wire. Cite this article: Bone Joint J 2020;102-B(8):1082–1087

1. In growing rats oestrogen, cortisone and thyroxine in high doses suppress bone formation, and this effect is probably part of a general suppression of body growth. 2. Growth hormone and thyroxine in small doses stimulate both body growth and bone formation. 3. Testosterone has no effect on bone formation. 4. Oestrogen and cortisone suppress bone resorption. The effect of cortisone may be modified in conditions of calcium depletion. 5. Thyroxine appears on the other hand to increase bone resorption. 6. Testosterone has no effect on bone resorption

Ununited fractures of the scaphoid with extensive bone resorption are usually treated by bone grafting and internal fixation, using either an open or a minimally invasive technique. We studied the feasibility of percutaneous fixation without bone grafting in a consecutive series of 27 patients with established nonunion of an undisplaced fracture of the scaphoid and extensive local resorption of bone. They were treated by a single surgeon with rigid fixation alone, using a headless cannulated screw inserted through a volar percutaneous technique. Clinical examination, standard radiographs and CT confirmed that the fracture had united in all patients at a mean of 11.6 weeks (8 to 16), and that their functional scores had improved. We concluded that extensive resorption at the fracture site is not an absolute indication for bone grafting, and that percutaneous fixation alone will eventually produce healing of ununited undisplaced fractures of the scaphoid regardless of the size of the gap

Aims

Loosening of components after total knee arthroplasty (TKA) can be associated with the development of radiolucent lines (RLLs). The aim of this study was to assess the rate of formation of RLLs in the cemented original design of the ATTUNE TKA and their relationship to loosening.

Aims

Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI.

The effects of the method of fixation and interface conditions on the biomechanics of the femoral component of the Birmingham hip resurfacing arthroplasty were examined using a highly detailed three-dimensional computer model of the hip. Stresses and strains in the proximal femur were compared for the natural femur and for the femur resurfaced with the Birmingham hip resurfacing. A comparison of cemented versus uncemented fixation showed no advantage of either with regard to bone loading. When the Birmingham hip resurfacing femoral component was fixed to bone, proximal femoral stresses and strains were non-physiological. Bone resorption was predicted in the inferomedial and superolateral bone within the Birmingham hip resurfacing shell. Resorption was limited to the superolateral region when the stem was not fixed. The increased bone strain observed adjacent to the distal stem should stimulate an increase in bone density at that location. The remodelling of bone seen during revision of failed Birmingham hip resurfacing implants appears to be consistent with the predictions of our finite element analysis

We examined the cellular responses to various particles injected into the knees and the intramedullary femoral cavities of rats in the presence of polymethyl-methacrylate (PMMA) plugs. The intra-articular particles were mainly ingested by synovial fibroblasts. Increased numbers of macrophages were not detected and there was only a slight increase in synovial thickness. Cellular responses in the intramedullary space were similarly mild and bone resorption around the PMMA plug did not occur. Bone formation was inhibited only by polyethylene particles. In contrast to current views, our study shows that wear particles per se do not initiate bone resorption

The purpose of this study was to determine the biological effects of the elastic modulus of the femoral stem in canine hip arthroplasty. Cementless total hip arthroplasty was performed in 12 dogs, six had a low elastic modulus polyacetal resin stem and six had a high modulus stainless steel stem. The components were otherwise similar. At six and 12 months after operation, radiographic and histomorphometric analysis showed that those with steel implants had more cortical porosity than did the other group (p less than 0.01). We suggest that the elastic modulus of the implant is an important factor in controlling cortical bone resorption. A low modulus femoral prosthesis can significantly decrease bone resorption which might otherwise eventually lead to implant failure

Our aim was to investigate the relationship between urinary excretion of deoxypyridinoline (DPD) as a marker of bone resorption, and Perthes’ disease. There were 39 children with Perthes’ disease in the florid stage who collected first-morning urine samples at regular intervals of at least three months. The level of urinary DPD was analysed by chemiluminescence immunoassay and was correlated with the radiological stage of the disease as classified by Waldenström, and the severity of epiphyseal involvement according to the classification systems of Catterall and Herring. The urinary DPD levels of a group of 44 healthy children were used as a control. The median urinary DPD/creatinine (CREA) ratio was significantly reduced (p < 0.0001) in the condensation stage and increased to slightly elevated values at the final stage (p = 0.05) when compared with that of the control group. Herring-C patients showed significantly lower median DPD/CREA ratios than Herring-B patients (p = 0.03). The significantly decreased median DPD/CREA ratio in early Perthes’ disease indicated a reduced bone turnover and supports the theory of a systemic aetiology. Urinary levels of DPD may therefore be used to monitor the course of Perthes’ disease

Cancer-induced bone diseases are often associated with increased bone resorption and pathological fractures. In recent years, osteoprotective agents such as bisphosphonates have been studied extensively and have been shown to inhibit cancer-related bone resorption in experimental and clinical studies. The third-generation bisphosphonate, ibandronate (BM 21.0955), is a potent compound for controlling tumour osteolysis and hypercalcaemia in rats bearing Walker 256 carcinosarcoma. We have studied the effect of ibandronate given as an interventional treatment on bone strength and bone loss after the onset of tumour growth in bone. Our results suggest that it is capable of preserving bone quality in rats bearing Walker 256 carcinosarcoma cells. Since other bisphosphonates have produced comparable results in man after their success in the Walker 256 animal models our findings suggest that ibandronate may be a powerful treatment for maintaining skeletal integrity in patients with metastatic bone disease

The release of prostaglandins E and F from the tibiae of rabbits and the surrounding muscle in vitro after fracture and pinning, or pinning alone, has been compared to the release from unoperated tissues. The fractured tibiae released significantly more prostaglandins E and F than the control tibiae three to 14 days after operation. The pinned tibiae also released more of the two prostaglandins, although this was significant only after 14 days. Consequently it was only around the third day that the fractured tibiae released significantly more prostaglandin E than the tibiae which had been pinned, but not fractured. Similar results were obtained for the release from the muscles surrounding the tibiae. Prostaglandins are important mediators of inflammation as well as potent stimulators of bone resorption. Their increased formation in response to fracture and pinning may stimulate the vascular changes, bone resorption and the proliferation of osteogenic cells observed after trauma to bone

We present the clinical and radiological results of percutaneous vertebroplasty in the treatment of 58 vertebral compression fractures in 51 patients at a minimum follow-up of two years. Group 1 consisted of 39 patients, in whom there was no associated intravertebral cleft, whilst group 2 comprised 12 patients with an intravertebral cleft. The Oswestry disability index (ODI) and visual analogue scale (VAS) scores were recorded prospectively. The radiological evidence of kyphotic deformity, vertebral height, leakage of cement and bone resorption around the cement were studied restrospectively, both before and after operation and at the final follow-up. The ODI and VAS scores in both groups decreased after treatment, but the mean score in group 2 was higher than that in group 1 (p = 0.02 (ODI), p = 0.02 (VAS)). There was a greater initial correction of the kyphosis in group 2 than in group 1, although the difference was not statistically significant. However, loss of correction was greater in group 2. Leakage of cement was seen in 24 (41.4%) of 58 vertebrae (group 1, 32.6% (15 of 46); group 2, 75% (9 of 12)), mainly of type B through the basal vertebral vein in group 1 and of type C through the cortical defect in group 2. Resorption of bone around the cement was seen in three vertebrae in group 2 and in one in group 1. There were seven adjacent vertebral fractures in group 1 and one in group 2. Percutaneous vertebroplasty is an effective treatment for osteoporotic compression fractures with or without an intravertebral cleft. Nonetheless, higher rates of complications related to the cement must be recognised in patients in the presence of an intravertebral cleft

We evaluated the effect of low-intensity pulsed ultrasound stimulation (LIPUS) on the remodelling of callus in a rabbit gap-healing model by bone morphometric analyses using three-dimensional quantitative micro-CT. A tibial osteotomy with a 2 mm gap was immobilised by rigid external fixation and LIPUS was applied using active translucent devices. A control group had sham inactive transducers applied. A region of interest of micro-CT was set at the centre of the osteotomy gap with a width of 1 mm. The morphometric parameters used for evaluation were the volume of mineralised callus (BV) and the volumetric bone mineral density of mineralised tissue (mBMD). The whole region of interest was measured and subdivided into three zones as follows: the periosteal callus zone (external), the medullary callus zone (endosteal) and the cortical gap zone (intercortical). The BV and mBMD were measured for each zone. In the endosteal area, there was a significant increase in the density of newly formed callus which was subsequently diminished by bone resorption that overwhelmed bone formation in this area as the intramedullary canal was restored. In the intercortical area, LIPUS was considered to enhance bone formation throughout the period of observation. These findings indicate that LIPUS could shorten the time required for remodelling and enhance the mineralisation of callus

We investigated the circulating levels of the main cytokines involved in bone resorption (IL-1β, IL-6, TNF-α), prostaglandins (PGE. 2. ) and metalloproteases (MMP-1), as possible early markers of osteolysis, in the serum of eight patients with periprosthetic osteolysis and ten patients without osteolysis. All had received a cementless hip prosthesis (ABG-1). We also assessed the serum levels of IL-11 and TGF-β anti-inflammatory cytokines exerting protective effect on bone resorption. The mean serum levels of IL-1β, IL-6, TNF-α, TGF-β, MMP-1, and PGE. 2. in patients with periprosthetic osteolysis did not differ significantly from those of patients without osteolysis or from those of normal controls. IL-11 serum levels were not detectable at all in any of the patients, while they were detected within normal reference values in the control subjects (significant inverse correlation). We believe that circulating cytokines cannot be regarded as markers of osteolysis, a condition characterised by a local inflammation without systemic signs of inflammation. On the contrary, the undetectable levels of IL-11 in implanted patients could provide evidence for a lack of balance between pro- and anti-inflammatory cytokines in these patients

Aims

The aim of this study was to compare the mid-term patient-reported outcome, bone remodelling, and migration of a short stem (Collum Femoris Preserving; CFP) with a conventional uncemented stem (Corail).

Mononuclear osteoclast precursors are present in the wear-particle-associated macrophage infiltrate found in the membrane surrounding loose implants. These cells are capable of differentiating into osteoclastic bone-resorbing cells when co-cultured with the rat osteoblast-like cell line, UMR 106, in the presence of 1,25(OH). 2. vitamin D. 3. In order to develop an in vitro model of osteoclast differentiation which more closely parallels the cellular microenvironment at the bone-implant interface in situ, we determined whether osteoblast-like human bone-derived cells were capable of supporting the differentiation of osteoclasts from arthroplasty-derived cells and analysed the humoral conditions required for this to occur. Long-term co-culture of arthroplasty-derived cells and human trabecular-bone-derived cells (HBDCs) resulted in the formation of numerous tartrate-resistant-acid-phosphatase (TRAP) and vitronectin-receptor (VNR)-positive multinucleated cells capable of extensive resorption of lacunar bone. The addition of 1,25(OH). 2. vitamin D. 3. was not required for the formation of osteoclasts and bone resorption. During the formation there was release of substantial levels of M-CSF and PGE. 2. Exogenous PGE. 2. (10. −8. to 10. −6. M) was found to stimulate strongly the resorption of osteoclastic bone. Our study has shown that HBDCs are capable of supporting the formation of osteoclasts from mononuclear phagocyte precursors present in the periprosthetic tissues surrounding a loose implant. The release of M-CSF and PGE. 2. by activated cells at the bone-implant interface may be important for the formation of osteoclasts at sites of pathological bone resorption associated with aseptic loosening

Aims

The purpose of this study was to compare clinical results, long-term survival, and complication rates of stemless shoulder prosthesis with stemmed anatomical shoulder prostheses for treatment of osteoarthritis and to analyze radiological bone changes around the implants during follow-up.

Aims

This study compared the cobalt and chromium serum ion concentration of patients treated with two different metal-on-metal (MoM) hinged total knee arthroplasty (TKA) systems, as well as a titanium nitride (TiN)-coated variant.

The ageing population and an increase in both the incidence and prevalence of cancer pose a healthcare challenge, some of which is borne by the orthopaedic community in the form of osteoporotic fractures and metastatic bone disease. In recent years there has been an increasing understanding of the pathways involved in bone metabolism relevant to osteoporosis and metastases in bone. Newer therapies may aid the management of these problems. One group of drugs, the antibody mediated anti-resorptive therapies (AMARTs) use antibodies to block bone resorption pathways. This review seeks to present a synopsis of the guidelines, pharmacology and potential pathophysiology of AMARTs and other new anti-resorptive drugs. . We evaluate the literature relating to AMARTs and new anti-resorptives with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for Nuclear Factor Kappa-B Ligand. It is the first AMART approved by the National Institute for Health and Clinical Excellence and the US Food and Drug Administration. Other novel anti-resorptives awaiting approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and prevention of the complications of bone metastases. Recent evidence suggests, however, that denosumab may have an adverse event profile similar to bisphosphonates, including atypical femoral fractures. It is, therefore, essential that orthopaedic surgeons are conversant with these medications and their safe usage. . Take home message: Denosumab has important orthopaedic indications and has been shown to significantly reduce patient morbidity in osteoporosis and metastatic bone disease. Cite this article: Bone Joint J 2016;98-B:160–5

Aims

We aimed to evaluate the long-term outcome of highly cross-linked polyethylene (HXLPE) cemented acetabular components and assess whether any radiolucent lines (RLLs) which arose were progressive.

Aims

Highly cross-linked polyethylene (HXLPE) has greatly improved the durability of total hip arthroplasty (THA) in young patients because of its improved wear characteristics. Few studies have followed this population into the second decade, and therefore the purpose of this investigation was to evaluate the clinical outcome for THA patients 50 years of age and younger at a minimum of 15 years postoperatively. The second purpose was to evaluate the radiological findings secondary to wear or mechanical failure of the implant.

Aims

Cement-in-cement revision of the femoral component represents a widely practised technique for a variety of indications in revision total hip arthroplasty. In this study, we compare the clinical and radiological outcomes of two polished tapered femoral components.

Aims

Adverse local tissue reactions associated with abnormal wear considerably slowed down the general use of metal-on-metal (MoM) hip resurfacing arthroplasty (HRA), now limited to a few specialized centres. In this study, we provide the clinical results of 400 consecutive MoM HRAs implanted more than 20 years ago in one such centre.

Aims

Stemmed tibial components are frequently used in revision total knee arthroplasty (TKA). The purpose of this study was to evaluate patient satisfaction, overall pain, and diaphyseal tibial pain in patients who underwent revision TKA with cemented or uncemented stemmed tibial components.

Aims

The purpose of this study was to report bone adaptive changes after anatomical total shoulder arthroplasty (TSA) using a standard-length hydroxyapatite (HA)-coated humeral component, and to report on a computer-based analysis of radiographs to determine changes in peri-implant bone density objectively.

An operation is described in which a microvascular technique was used to transfer a living fibula, with its vascular pedicle intact, to replace the lower end of the radius after massive resection for giant-cell tumour. Angiography carried out six weeks later showed that the grafted bone was viable. Six months after operation the transplanted fibula showed no osteoporosis or bone resorption and bony union at the junction of host and graft

Chronic recurrent multifocal osteomyelitis (CRMO) is characterised by an insidious onset of fever, local swelling and pain in affected bones, and radiological abnormalities suggestive of osteomyelitis. The histopathological features in 14 patients are described. Morphologically CRMO begins as an acute inflammatory process with a predominance of polymorphonuclear leucocytes, which occasionally form an abscess and osteoclastic bone resorption. At a later stage the predominant features are lymphocytes in the inflammatory infiltrates and occasional granulomatous foci and sigans of bone formation. The clinical course may be prolonged for many years

Three madreporic prostheses in two patients were examined to evaluate resorption and formation of the surrounding bone tissue. All three prostheses were firmly fixed and had no clinical or radiographic signs of loosening. Transverse sections were examined by scanning electron microscopy at 40 days, 11 months and 2.5 years after implantation. The findings suggest that adaptive bone remodelling varies along the length of the stem; that bone resorption and formation are related to the time after implant; and that new bone formation (woven bone) can be found very close to the madreporic surface

1. The phosphonates are simple chemical compounds containing P-C-P bonds which are resistant to the action of naturally occurring phosphatases and pyrophosphatases. They inhibit the formation and dissolution of apatite crystals in vitro and prevent ectopic mineralisation and bone resorption in animals. 2. In man one diphosphonate (EHDP) has been shown to reduce the excessive turnover of bone in Paget's disease and also appears to slow the mineralisation of ectopic bone matrix in myositis ossificans progressiva. 3. The possible uses of the diphosphonates in bone disorders with excessive resorption and in ectopic mineralisation are being further investigated

1. Tetracycline labelling methods have been used to measure the rate of growth in length and the rate of growth in width of the tibia of the normal rat. 2. The main limitations of the tetracycline methods are that in very young animals the bands of labelled bone are indistinct and remodelling occurs quickly; in animals nearing maturity, the growth in width is very slow and periods of at least fourteen days are required to give reliable results. 3. The tetracycline labelling methods can be used also to determine changes in the basic processes of bone formation and bone resorption

1. Twenty-three patients were treated by cross screwing for diastasis of the tibia and fibula in fractures at the ankle. 2. It is suggested that limitation of ankle dorsiflexion after this treatment was caused by the presence of a mechanical block to dorsiflexion by spur formation at the margins of tibia and talus. 3. An ordinary bone screw controlled the diastasis satisfactorily in twenty patients. 4. The screw did not interfere with movement at the inferior tibio-fibular joint because bone resorption about that part of the screw in the fibula allowed a small range of movement. 5. Discomfort from the screw was relieved by its removal

1. The bone changes in four autopsied cases of Cushing's syndrome are described. The changes take the form of osteoporosis, which is most marked in the spine and the ribs. 2. The osteoporosis results from impaired osteoblastic bone formation in the presence of a normal degree of osteoclastic bone resorption. 3. Histological abnormalities of fracture callus in Cushing's syndrome indicate interference with the proliferation of osteoblasts and cartilage cells and with the formation of new tissue by these cells. 4. The bone changes in Cushing's syndrome are comparable with those produced in experimental animals by the administration of A.C.T.H. or cortisone

Aims

Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up.

We treated 50 patients with bony malignancy by en-bloc resection, extracorporeal irradiation with 50 Gy and re-implantation of the bone segment. The mean survivor follow-up was 38 months (12 to 92) when 42 patients were alive and without disease. There were four recurrences. The functional results were good according to the Mankin score (17 excellent, 13 good, nine fair, three failures), the Musculoskeletal Tumour Society score (mean 77) and the Toronto Extremity Salvage score (mean 81). There was solid union, but bone resorption was seen in some cases. The dose of radiation was lethal to all cells and produced a dead autograft of perfect fit. Extracorporeal irradiation is a useful technique for limb salvage when there is reasonable residual bone stock. It allows effective re-attachment of tendons and produces a lasting biological reconstruction. There should be no risk of local recurrence or of radiotherapy-induced malignancy in the replanted bone

We have investigated whether the particle-stimulated release of inflammatory cytokines from human primary macrophages in vitro was dependent upon the type of bone cement used. Particles of clinically relevant size were produced from Palacos R without radio-opacifier, Palacos R with BaSO. 4. , Palacos R with ZrO. 2. and from CMW3 which contains BaSO. 4. All four preparations produced significantly greater release of tumour necrosis factor alpha, interleukin-6 and interleukin-1 beta than a negative control but there were no significant differences between them. The differences in the ability to stimulate bone resorption and in clinical performance between proprietary bone cements previously recorded are not explained by the release of the cytokines most commonly implicated in osteolysis

In 44 consecutive patients, 60 porous-coated anatomic total knee (PCA) prostheses with a porous-coated central tibial stem were implanted without using cement. The clinical results and bony remodelling have been assessed after five years' follow-up. The average Hospital for Special Surgery knee score was 33.1 before operation and 95.7 at the latest follow-up, while the average range of movement improved from 63 degrees to 123 degrees. No subsidence or migration of the components was seen. A radiodense line appeared around the components at six months to one year after the operation and became more dense with time. There was no evidence of bone resorption related to stress-shielding in the tibial plateau

The role of inflammatory cells in aseptic loosening and failure of cemented joint replacements is unclear. Inflammatory cells from the revision joint capsule of four failed hip arthroplasties were examined to determine their nature and resorptive capacity. The capsules contained numerous macrophages and abundant foreign-body macrophage polykaryons, distinguished from osteoclasts by their antigenic phenotype and lack of response to calcitonin. When cultured on cortical bone slices in vitro, both macrophages and macrophage polykaryons produced small resorption pits and were associated with areas of superficial resorption of the bone surface. These results indicate that foreign-body induced macrophages and macrophage polykaryons are capable of a type of low-grade bone resorption which may be of pathogenic significance in the loosening of cemented joint prosthetic components

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 significance of cobalt as a cause of symptoms after McKee hip arthroplasty is discussed. Seven patients are described in whom such arthroplasties became unsatisfactory after periods varying from nine months to four years. Six of these patients were cobalt-positive but nickel-and chrome-negative on patch testing. Macroscopic and histological necrosis of bone, muscle and joint capsule around the prostheses was found in five patients whose hips were explored. The symptoms were progressive pain, a feeling of instability, and in two cases spontaneous dislocation. Radiological features included acetabular fracture, bone resorption, loosening and dislocation of the prosthesis. Increased cobalt concentrations (determined by atomic absorption spectrophotometry) in the urine of four patients and in a variety of tissues in one patient are presented. Patch testing is recommended in the investigation of patients with troublesome McKee hip arthroplasties

Four different experiments were performed to study the healing of a large, non-vascularised, diaphyseal, bone segment in adult cats. In the first experiment, a 4 cm segment of tibia with its periosteum was excised and replaced in its bed. The other experiments were similar, except that in the second, the periosteum of the segment was removed, in the third its medullary canal was blocked with a Silastic rod, and in the last group the segment was isolated from its muscle bed by a Silastic sheet. The reparative processes were quantified by estimating the resorption index, the cortical new bone formation index, the callus encasement index, and the osteocyte count. Bone resorption and apposition occurred in the segment even when the periosteum was absent or the medullary canal was blocked, with osseous union at both ends by eight to 12 weeks, provided the segment was not isolated from its muscle bed. Thus, the muscle bed played a significant role in these reparative processes

The cellular mechanisms which account for the formation of osteoclasts and bone resorption associated with enlarging benign and malignant mesenchymal tumours of bone are uncertain. Osteoclasts are marrow-derived, multinucleated, bone-resorbing cells which express a macrophage phenotype. We have determined whether tumour-associated macrophages (TAMs) isolated from benign and malignant mesenchymal tumours are capable of differentiating into osteoclasts. Macrophages were cultured on both coverslips and dentine slices for up to 21 days with UMR 106 osteoblastic cells in the presence of 1,25 dihydroxyvitamin D. 3. (1,25(OH). 2. D. 3. ) and human macrophage colony-stimulating factor (M-CSF) or, in the absence of UMR 106 cells, with M-CSF and RANK ligand. In all tumours, the formation of osteoclasts from CD14-positive macrophages was shown by the formation of tartrate-resistant-acid-phosphatase and vitronectin-receptor-positive multinucleated cells which were capable of carrying out lacunar resorption. These results indicate that the tumour osteolysis associated with the growth of mesenchymal tumours in bone is likely to be due in part to the differentiation of mononuclear phagocyte osteoclast precursors which are present in the TAM population of these lesions

Macrophages and their fused products are commonly found at the polymethylmethacrylate cement-bone interface, but it is not known if they contribute directly to the osteolysis associated with loosening of the cemented prosthesis. We isolated mononuclear phagocytes from granulomas formed by subcutaneous implantation of polymethylmethacrylate into mice and incubated them on bone slices in which they formed resorption lacunae after co-culture for seven to 14 days with both marrow stromal cells and osteoblast-like cells (in the presence of 1 alpha,25-dihydroxyvitamin D3 and dexamethasone). Increased numbers of tartrate-resistant acid phosphatase-positive mononuclear and multinucleated cells formed in these cultures. Both in the presence and absence of stromal cells, macrophages produced extensive superficial roughening of the bone surface. Polymethylmethacrylate-induced macrophages are thus capable of low-grade surface and high-grade lacunar osteolysis, the latter requiring the presence of specific hormonal and stromal cell elements. These two forms of bone resorption could account for the pathogenesis and clinical patterns associated with loosening of the cemented prosthesis

Fifty-three of 55 consecutive elbow replacements for post-traumatic arthritis were followed for a minimum of two years (mean 6.3, range 2 to 14.4). The patients presented difficult management problems, having undergone an average of two previous operations per joint; 22 joints had suffered prior complications; 18 had less than 50 degrees of flexion and six were flail. One of three versions of the Coonrad prosthesis was employed in all. During the follow-up period, 10 patients underwent 14 revision procedures for aseptic loosening; 38 elbows are currently without progressive radiolucent lines. In two patients an elbow had to be resected, one for deep infection and the other for bone resorption following a foreign-body reaction to titanium. The current design of the Coonrad prosthesis offers a reliable option for the treatment of post-traumatic arthritis but should be used only in carefully selected patients over the age of 60 years

1. Prosthetic acetabular cups of the Charnley and McKee-Farrar designs were cemented into cadaveric pelves using different procedures for preparing the acetabulum. 2. The torsional moments needed to loosen these cups were measured. 3. The torsional moments so measured were found to be from about four to more than twenty times higher than the frictional moments measured in independent tests on the two designs of prosthesis. 4. It is argued that late looseness of the acetabular component after total hip replacement, in the absence of infection, seems most likely to be due to thermal damage to the bone occurring at the time of polymerisation of the cement, and to subsequent bone resorption. 5. Surgical preparation of the acetabulum should include removal of all the articular cartilage and cleaning of the acetabular fossa, but the drilling of additional holes in the floor of the acetabulum seems unimportant. 6. The possibility of fatigue fracture in bone as a factor contributing to late loosening is an argument in favour of metal-on-polyethylene prostheses with their lower frictional moments, although the importance of this factor cannot be estimated

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

Aims

The use of frozen tumour-bearing autograft combined with a vascularized fibular graft (VFG) represents a new technique for biological reconstruction of massive bone defect. We have compared the clinical outcomes between this technique and Capanna reconstruction.

We implanted 51 Metal-Cancellous Cementless Lübeck (MCCL) prostheses into 45 patients with dysplastic hips and followed 49 hips (96.1%) for five to nine years. One had needed revision for stem fracture and one for infection; the clinical outcome of the other 47 hips was assessed using the Merle d’Aubigné and Postel hip score. All hips were either excellent (63%) or good (37%). Three patients (6%) had mild thigh pain at six months, but this had settled within two years. Serial radiographs showed stable fixation with bone ingrowth in all hips, with increased density of the cancellous bone in contact with the implant and some trabecular ingrowth. There was early varus shift of the stem in one hip, but this stabilised in three months. Osteolysis of the femoral cortex was seen in one hip at seven years after surgery, and mild bone resorption due to stress shielding in 31 (63%). Acetabular bone grafting with autogenous bone from the femoral head gave successful support to the socket in 13 hips. The MCCL prosthesis gave satisfactory mid-term results in patients with osteoarthritis secondary to hip dysplasia

We used a rat model in vivo to study the effects of particulate bone cements at the bone-implant interface. A ceramic pin was implanted into the tibiae of 48 rats. Three types of particle of clinically relevant size were produced from one bone-cement base without radio-opacifier, with zirconium dioxide (ZrO. 2. ) and with barium sulphate (BaSO. 4. ). The rats were randomly assigned to four groups to receive one of the three bone cements or normal saline with 2% v/v Sprague-Dawley serum as the control. A total of 10. 9. particles was injected into the knee at 8, 10 and 12 weeks after the original surgery. The animals were killed at 14 weeks and the tibiae processed for histomorphometry. The area of fibrous tissue and the gap between the implant and bone were measured using image analysis. All three types of particle were associated with a larger area of bone resorption than the control. Only in the case of the BaSO. 4. -containing cement did this reach statistical significance (p = 0.01). Particles of bone cement appear to promote osteolysis at the bone-implant interface and this effect is most marked when BaSO. 4. is used as the radiopaque agent

1. A detailed study of density variations with age in cortical bone samples from different areas of the femoral diaphysis has been carried out. 2. Bone of relatively high density and, conversely, of low density was found to have a spiral pattern along the bone shaft. 3. Moving distally along the femoral shaft there was a transposition of the greatest density from the anterior to the posterior aspect. 4. In the erect body posture the femoral inclination is such that areas of denser bone might be expected to be aligned vertically because of the weight-bearing characteristics of the femur. 5. Most areas of the cortex tended to decrease in density after the age of fifty, the less dense areas changing more than those with an initial high density. Thus, osteoporosis tended not only to maintain but to accentuate the spiral pattern of density distribution by increasing the difference between dense and less dense bone. 6. In the distal region of the diaphysis bone resorption was greatest anteriorly but hardly affected the posterior aspect. A densitometric comparison between these two sites provided a clear indication of the effect of osteoporosis

Particulate wear debris can induce the release of bone-resorbing cytokines from cultured macrophages and fibroblasts in vitro, and these mediators are believed to be the cause of the periprosthetic bone resorption which leads to aseptic loosening in vivo. Much less is known about the effects of particulate debris on the growth and metabolism of osteoblastic cells. We exposed two human osteoblast-like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt-chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic to both cell lines and inhibited the production of type-I collagen, osteocalcin and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by both cell lines, producing no cytotoxicity and no inhibition of type-I collagen synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium alloy inhibited osteocalcin expression. Our results clearly show that particulate metal debris can modulate the growth and metabolism of osteoblastic cells in vitro. Reduced osteoblastic activity at the bone-implant interface may be an important mechanism by which particulate wear debris influences the pathogenesis of aseptic loosening in vivo

1. Bones consist essentially of bundles of collagenous fibres united by a cementing substance in which the inorganic material lies in the form of minute plate-like crystals. 2. During weight bearing and muscle action bones as a whole are deformed to a variable extent. Periods of deformation are followed by periods of relaxed pressure during which the bones tend to return to their normal form. 3. These variations in deformation and elastic recoil set up alternating pressures and tensions within the bones along the bone cyrstal encrusted fibres which make up the trabeculae, lamellae and Haversian systems, and these alternating phases of compression and tension stimulate the activity of osteoblasts so that bone formation predominates over bone resorption. 4. These alterations of pressure and tension are intermittent and reciprocal in nature and do not, as postulated by the trajectorial theory, involve different trabeculae, nor is it necessary to consider whether tension or pressure is the more important phase in determining bone deposition. 5. The pressure exerted by cysts, tumours, erupting teeth, etc., is of a quite different nature, as is the response to trauma or callus formation in the healing of fractures. These processes are essentially vascular phenomena involving localised areas of bony tissue and not bones as mechanical units

Six pairs of human cadaver femora were divided equally into two groups one of which received a non-cemented reference implant and the other a very short non-dependent experimental implant. Thirteen strain-gauge rosettes were attached to the external surface of each specimen and, during application of combined axial and torsional loads to the femoral head, the strains in both groups were measured. After the insertion of a non-cemented femoral component, the normal pattern of a progressive proximal-to-distal increase in strains was similar to that in the intact femur and the strain was maximum near the tip of the prosthesis. On the medial and lateral aspects of the proximal femur, the strains were greatly reduced after implantation of both types of implant. The pattern and magnitude of the strains, however, were closer to those in the intact femur after insertion of the experimental stem than in the reference stem. On the anterior and posterior aspects of the femur, implantation of both types of stem led to increased principal strains E1, E2 and E3. This was most pronounced for the experimental stem. Our findings suggest that the experimental stem, which has a more anatomical proximal fit without having a distal stem and cortex contact, can provide immediate postoperative stability. Pure proximal loading by the experimental stem in the metaphysis, reduction of excessive bending stiffness of the stem by tapering and the absence of contact between the stem and the distal cortex may reduce stress shielding, bone resorption and thigh pain

1. When cortisone is administered to rabbits there is early rapid resorption of bone and a partial inhibition of new bone formation. After a few days the effect becomes less obvious, so that, if observations are made at later stages, the results may be ascribed then to simple inhibition of bone growth. 2. The effect of mechanical stress has been studied in the jaw. When tooth movement is induced mechanically there is, in ordinary circumstances, a resorption of bone on the side to which the tooth is moving (the "pressure" side) and bone formation on the opposite side (the "tension" side). After administration of cortisone there is increased resorption on the "pressure" side and there is greater resorption of connective tissues here. On the "tension" side there is resorption and inhibition of bone formation. 3. In the areas of stress, when cortisone is administered, collagen fibres are no longer in apposition, being separated by spaces presumably filled with altered ground substance; this kind of change may be responsible for many of the observed phenomena. 4. A.C.T.H. does not produce a demonstrable resorptive effect on bone or connective tissue until it has been administered for periods longer than is required for cortisone (three weeks); even then the change is not pronounced. 5. In the guinea pig there is slight delay in bone formation with large doses of both cortisone and A.C.T.H., but no significant bone resorption occurs

Proponents of the biological theory of aseptic loosening have in recent years tended to concentrate on the production and distribution of particulate ultra-high-molecular-weight polyethylene (UHMWPE) debris around the potential joint space. However, mechanical loading of cemented implants with the differing elastic moduli of metal stems, polymethylmethacrylate (PMMA) cement and bone can result in relative micromotion, implying the potential for production of metal and PMMA particles from the stem-cement interface by fretting wear. In order to investigate the production and biological reactivity of debris from this interface, PMMA and metal particulate debris was produced by sliding wear of PMMA pins containing barium sulphate and zirconium dioxide against a Vaquasheened stainless steel counterface. This debris was characterised by SEM, energy-dispersive analysis by X-ray (EDAX) and image analysis, then added to cell cultures of a human monocytic cell line, U937, and stimulation of pro-osteolytic cytokines measured by ELISA. Large quantities of PMMA cement debris were generated by the sliding wear of PMMA pins against Vaquasheened stainless steel plates in the method developed for this study. Both cements stimulated the release of pro-osteolytic TNFα from the U937 monocytic cell line, in a dose-dependent fashion. There was a trend towards greater TNFα release with Palacos cement than CMW cement at the same dose. Palacos particles also caused significant release of IL-6, another pro-osteolytic cytokine, while CMW did not. The particulate cement debris produced did not stimulate the release of GM-CSF or IL1β from the U937 cells. These results may explain the cytokine pathway responsible for bone resorption caused by particulate PMMA debris. Radio-opaque additives are of value in surgical practice and clinical studies to quantify the relevance of these in vitro findings are required before the use of cement containing radio-opacifier is constrained

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.

Aims

We propose a state-of-the-art temporary spacer, consisting of a cobalt-chrome (CoCr) femoral component and a gentamicin-eluting ultra-high molecular weight polyethylene (UHMWPE) tibial insert, which can provide therapeutic delivery of gentamicin, while retaining excellent mechanical properties. The proposed implant is designed to replace conventional spacers made from bone cement.

Aseptic loosening is a major cause of failure of total hip arthroplasty. The adverse tissue response to prosthetic wear particles, with activation of cytokine and prostanoid production, contributes to bone loss around the implants. We have investigated the possibility that inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) are expressed in macrophages in the pseudomembrane at the bone-implant interface, thereby contributing to the periprosthetic bone resorption. We also assessed whether peroxynitrite, a nitric oxide (NO)-derived oxidant associated with cellular injury, is generated in the membrane. Enzymatic activity of iNOS was measured using the arginine-citrulline assay technique and prostaglandin E. 2. (PGE. 2. ), as an indicator of COX-2 activity, was measured using an enzyme immunoassay. Cellular immunoreactivity for iNOS, nitrotyrosine (a marker of peroxynitrite-induced cellular injury) and COX-2 was assessed by quantitative peroxidase immunocytochemistry while immunofluorescence methods were used for subsequent co-localisation studies with CD68. +. macrophages. The presence of calcium-independent iNOS activity and PGE. 2. production was confirmed in the homogenized interface membrane. Immunocytochemistry showed that periprosthetic CD68. +. wear-debris-laden macrophages were the most prominent cell type immunoreactive for iNOS, nitrotyrosine and COX-2. Other periprosthetic inflammatory and resident cell types were also found to immunolocalise nitrotyrosine thereby suggesting peroxynitrite-induced protein nitrosylation and cellular damage not only in NO-producing CD68. +. macrophages, but also in their neighbouring cells. These data indicate that both iNOS and COX-2 are expressed by CD68. +. macrophages in the interface membrane and peroxynitrite-induced cellular damage is evident in such tissue. If high-output NO and peroxynitrite generation were to cause macrophage cell death, this would result in the release of phagocytosed wear debris into the extracellular matrix. A detrimental cycle of events would then be established with further phagocytosis by newly-recruited inflammatory cells and subsequent NO, peroxynitrite and prostanoid synthesis. Since both NO and have been implicated in the induction and PGE. 2. maintenance of chronic inflammation with resulting loss of bone, and peroxynitrite in the pathogenesis of disease states, they may be central to the pathogenesis of aseptic loosening

Aims

The aim of this study was to conduct the largest low contact stress (LCS) retrieval study to elucidate the failure mechanisms of the Porocoat and Duofix femoral component. The latter design was voluntarily recalled by the manufacturer.

When large daily doses of vitamin D were administered to rats endochondral growth was inhibited and bone resorption occurred; later in the process uncalcified matrix (osteoid) like that seen in rickets formed on trabecular margins. When vitamin D was given only for a short period and then discontinued, little resorption of bone was seen during the withdrawal period and wide seams of osteoid material appeared which eventually calcified in an irregular manner. When normal endochondral growth was resumed a wide transverse band of dense bone with enclosed cartilaginous cores was left in the marrow cavity. If, after a few days, a second large dose of the vitamin was given resorption again occurred and calcification of osteoid material was accelerated, the first microscopic sign being a dense, wide, granular, deeply staining line at the junction of the bone and new osteoid. After a second withdrawal period a second layer of osteoid formed; eventually another transverse band appeared in the metaphysis. If this hypervitaminosis D cycle (+4 -12) was continued rats continued to form new bone with relatively little remodelling, so that after three such cycles bones became dense and hard. Histological study showed that little marrow cavity remained in either skull, vertebrae or epiphyses and a dense mass of bone enclosing cartilage cores filled the metaphysial part of the long bones. In addition, ankylosis ofteeth, calcification of spinal ligaments and widespread metastatic calcification were present. When hypervitaminosis D cycles (+1 -12, +1 -21) were adjusted to produce minimal resorptive changes a wide range of bone change was observed. This varied from uniform dense metaphysial bone containing abnormal cartilage matrix arranged in longitudinal striations, dense transverse bands parallel to the epiphysial cartilage, to remnants of dense trabeculae extending into the marrow cavity. Bone changes in osteopetrosis structurally closely resembled the induced bone changes in the rat. It is concluded that an important mechanism in the production of osteopetrosis is an accentuated rhythm of bone change like that shown experimentally to be produced in these animals. It is emphasised that these changes are but part of a range of bone disorders associated with abnormalities of cycles of resorption and deposition of bone, the type of change differing with the nature of the cycles

Aims

The aim of this study was to compare the osseous reactions elicited by all-suture, polyetheretherketone (PEEK), and two different biodegradable anchors used during rotator cuff repair.

Aims

Currently, periprosthetic fractures are excluded from the American Society for Bone and Mineral Research (ASBMR) definition of atypical femoral fracture (AFFs). This study aims to report on a series of periprosthetic femoral fractures (PFFs) that otherwise meet the criteria for AFFs. Secondary aims were to identify predictors of periprosthetic atypical femoral fractures (PAFFs) and quantify the complications of treatment.

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.

Aims

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

Aims

Modular dual mobility (DM) prostheses in which a cobalt-chromium liner is inserted into a titanium acetabular shell (vs a monoblock acetabular component) have the advantage of allowing supplementary screw fixation, but the potential for corrosion between the liner and acetabulum has raised concerns. While DM prostheses have shown improved stability in patients deemed ‘high-risk’ for dislocation undergoing total hip arthroplasty (THA), their performance in young, active patients has not been reported. This study’s purpose was to assess clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) in young, active patients receiving a modular DM acetabulum and recently introduced titanium, proximally coated, tapered femoral stem design.

Aims

Scapular notching is a frequently observed radiographic phenomenon in reverse shoulder arthroplasty (RSA), signifying impingement of components. The purposes of this study were to evaluate the effect of glenoid component size and glenosphere type on impingement-free range of movement (ROM) for extension and internal and external rotation in a virtual RSA model, and to determine the optimal configuration to reduce the incidence of friction-type scapular notching.

Aims

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

Aims

Post-operative migration of cemented acetabular components as measured by radiostereometric analysis (RSA) has a strong predictive power for late, aseptic loosening. Also, radiolucent lines predict late loosening. Migration has been reduced by systemic bisphosphonate treatment in randomised trials of hip and knee arthroplasty. Used as a local treatment, a higher local dose of bisphosphonate can be achieved without systemic exposure. We wished to see if this principle could be applied usefully in total hip arthroplasty (THA).

Aims

We present a retrospective review of patients treated with extracorporeally irradiated allografts for primary and secondary bone tumours with the mid- and long-term survivorship and the functional and radiographic outcomes.

Aims

To assess the extent of osteointegration in two designs of shoulder resurfacing implants. Bony integration to the Copeland cylindrical central stem design and the Epoca RH conical-crown design were compared.

Aims

The aims of this retrospective study were to report the feasibility of using 3D-printing technology for patients with a pelvic tumour who underwent reconstruction.

The aim of this study was to evaluate the functional and oncological outcome of extracorporeally irradiated autografts used to reconstruct the pelvis after a P1/2 internal hemipelvectomy.

The study included 18 patients with a primary malignant bone tumour of the pelvis. There were 13 males and five females with a mean age of 24.8 years (8 to 62). Of these, seven had an osteogenic sarcoma, six a Ewing’s sarcoma, and five a chondrosarcoma. At a mean follow-up of 51.6 months (4 to 185), nine patients had died with metastatic disease while nine were free from disease. Local recurrence occurred in three patients all of whom eventually died of their disease. Deep infection occurred in three patients and required removal of their graft in two while the third underwent a hindquarter amputation for extensive flap necrosis.

The mean Musculoskeletal Tumor Society functional score of the 16 patients who could be followed-up for at least 12 months was 77% (50 to 90). Those 15 patients who completed the Toronto Extremity Salvage Score questionnaire had a mean score of 71% (53 to 85).

Extracorporeal irradiation and re-implantation of bone is a valid method of reconstruction after an internal hemipelvectomy. It has an acceptable morbidity and a functional outcome that compares favourably with other available reconstructive techniques.

Cite this article: Bone Joint J 2014;96-B:1404–10

Neuropathic changes in the foot are common with a prevalence of approximately 1%. The diagnosis of neuropathic arthropathy is often delayed in diabetic patients with harmful consequences including amputation. The appropriate diagnosis and treatment can avoid an extensive programme of treatment with significant morbidity for the patient, high costs and delayed surgery. The pathogenesis of a Charcot foot involves repetitive micro-trauma in a foot with impaired sensation and neurovascular changes caused by pathological innervation of the blood vessels. In most cases, changes are due to a combination of both pathophysiological factors. The Charcot foot is triggered by a combination of mechanical, vascular and biological factors which can lead to late diagnosis and incorrect treatment and eventually to destruction of the foot.

This review aims to raise awareness of the diagnosis of the Charcot foot (diabetic neuropathic osteoarthropathy and the differential diagnosis, erysipelas, peripheral arterial occlusive disease) and describe the ways in which the diagnosis may be made. The clinical diagnostic pathways based on different classifications are presented.

Cite this article: Bone Joint J 2016;98-B:1155–9.

Aims

Patients with multiple myeloma (MM) develop deposits in the spine which may lead to vertebral compression fractures (VCFs). Our aim was to establish which spinopelvic parameters are associated with the greatest disability in patients with spinal myeloma and VCFs.

We assessed the short- to mid-term survival of metallic press-fit radial head prostheses in patients with radial head fractures and acute traumatic instability of the elbow.

The medical records of 42 patients (16 males, 26 females) with a mean age of 56 years (23 to 85) with acute unstable elbow injuries, including a fracture of the radial head requiring metallic replacement of the radial head, were reviewed retrospectively. Survival of the prosthesis was assessed from the radiographs of 37 patients after a mean follow-up of 50 months (12 to 107). The functional results of 31 patients were assessed using range-of-movement, Mayo elbow performance score (MEPS), Disabilities of the Arm, Shoulder and Hand (DASH) score and the RAND 36-item health survey.

At the most recent follow-up 25 prostheses were still well fixed, nine had been removed because of loosening, and three remained implanted but were loose. The mean time from implantation to loosening was 11 months (2 to 24). Radiolucent lines that developed around the prosthesis before removal were mild in three patients, moderate in one and severe in five. Range of movement parameters and mass grip strength were significantly lower in the affected elbow than in the unaffected side. The mean MEPS score was 86 (40 to 100) and the mean DASH score was 23 (0 to 81). According to RAND-36 scores, patients had more pain and lower physical function scores than normal population values.

Loosening of press-fit radial head prostheses is common, occurs early, often leads to severe osteolysis of the proximal radius, and commonly requires removal of the prosthesis.

If a modular convertible total shoulder system is used as a primary implant for an anatomical total shoulder arthroplasty, failure of the prosthesis or the rotator cuff can be addressed by converting it to a reverse shoulder arthroplasty (RSA), with retention of the humeral stem and glenoid baseplate. This has the potential to reduce morbidity and improve the results.

In a retrospective study of 14 patients (15 shoulders) with a mean age of 70 years (47 to 83) we reviewed the clinical and radiological outcome of converting an anatomical shoulder arthroplasty (ASA) to a RSA using a convertible prosthetic system (SMR system, Lima, San Daniele, Italy).

The mean operating time was 64 minutes (45 to 75). All humeral stems and glenoid baseplates were found to be well-fixed and could be retained. There were no intra-operative or early post-operative complications and no post-operative infection.

The mean follow-up was 43 months (21 to 83), by which time the mean visual analogue scale for pain had decreased from 8 pre-operatively to 1, the mean American Shoulder and Elbow Surgeons Score from 12 to 76, the mean Oxford shoulder score from 3 to 39, the mean Western Ontario Osteoarthritis of the Shoulder Score from 1618 to 418 and the mean Subjective shoulder value from 15 to 61.

On radiological review, one patient had a lucency around the humeral stem, two had stress shielding. There were no fatigue fractures of the acromion but four cases of grade 1 scapular notching.

The use of a convertible prosthetic system to revise a failed ASA reduces morbidity and minimises the rate of complications. The mid-term clinical and radiological results of this technique are promising.

Cite this article: Bone Joint J 2015;97-B:1662–7.

In 2012 we reviewed a consecutive series of 92 uncemented THRs performed between 1986 and 1991 at our institution using the CLS Spotorno stem, in order to assess clinical outcome and radiographic data at a minimum of 21 years. The series comprised 92 patients with a mean age at surgery of 59.6 years (39 to 77) (M:F 43;49).

At the time of this review, seven (7.6%) patients had died and two (2.2%) were lost to follow-up. The 23-year Kaplan–Meier survival rates were 91.5% (95% confidence intervals (CI) 85.4% to 97.6%; 55 hips at risk) and 80.3% (95% CI, 71.8% to 88.7%; 48 hips at risk) respectively, with revision of the femoral stem or of any component as endpoints. At the time of this review, 76 patients without stem revision were assessed clinically and radiologically (mean follow-up 24.0 years (21.5 to 26.5)). For the 76 unrevised hips the mean Harris hip score was 87.1 (65 to 97). Femoral osteolysis was detected in five hips (6.6%) only in Gruen zone 7. Undersized stems were at higher risk of revision owing to aseptic loosening (p = 0.0003). Patients implanted with the stem in a varus position were at higher risk of femoral cortical hypertrophy and thigh pain (p = 0.0006 and p = 0.0007, respectively).

In our study, survival, clinical outcome and radiographic data remained excellent in the third decade after implantation. Nonetheless, undersized stems were at higher risk of revision owing to aseptic loosening.

Cite this article: Bone Joint J 2014;96-B:455–61.

Many different lengths of stem are available for use in primary total hip replacement, and the morphology of the proximal femur varies greatly. The more recently developed shortened stems provide a distribution of stress which closely mimics that of the native femur. Shortening the femoral component potentially comes at the cost of decreased initial stability. Clinical studies on the performance of shortened cemented and cementless stems are promising, although long-term follow-up studies are lacking. We provide an overview of the current literature on the anatomical features of the proximal femur and the biomechanical aspects and clinical outcomes associated with the length of the femoral component in primary hip replacement, and suggest a classification system for the length of femoral stems.

Cite this article: Bone Joint J 2014;96-B:442-8.

Bone preservation and physiological distribution of forces on the proximal femur are key elements in introducing a successful uncemented total hip replacement. In order to achieve this, in the mid 1990s, we developed an ultra short proximal loading custom-made component with a lateral flare, a high femoral neck osteotomy and without a diaphyseal stem.

We report the outcome of 129 custom-made hydroxyapatite-coated uncemented short femoral components inserted into 109 patients between June 1995 and May 2004. The mean age of the patients was 51 years (21 to 71) and the mean follow-up was eight years (4.9 to 14.1). Bone behaviour around the implant was studied on the post-operative radiographs. The mean Harris hip score improved from 44 (8 to 66) pre-operatively to 95 (76 to 100) at final follow-up. The Western Ontario MacMaster University Osteoarthritis index was 93 of 100 at final review. None of the patients reported thigh pain. A total of five hips were revised, three for polyethylene liner exchange and two for complete revision of the acetabular component. No femoral components were revised. The radiological changes in the proximal femur were generally good, as evidenced by spot welds both on the medial and lateral aspects of the femur. No component migrated. The presence of a lateral flare and use of a high osteotomy of the femoral neck provided good clinical and radiological results. The absence of a diaphyseal portion of the stem did not impair stability.

We have investigated the effectiveness of the transplantation of bone-marrow-derived mononuclear cells (BMMNCs) with interconnected porous calcium hydroxyapatite (IP-CHA) on early bone repair for osteonecrosis of the femoral head. We studied 22 patients (30 hips) who had osteonecrosis with a minimum follow-up of one year after implantation of BMMNCs. The mean age at surgery was 41 years (18 to 64) and the mean period of follow-up was 29 months (19 to 48). In a control group, cell-free IP-CHA was implanted into a further eight patients (9 hips) with osteonecrosis of the femoral head and the outcomes were compared.

A reduction in the size of the osteonecrotic lesion was observed subsequent to hypertrophy of the bone in the transition zone in the BMMNC group. In three patients in the treatment group progression to extensive collapse was detected. In the control group subtle bone hypertrophy was observed, but severe collapse of the femoral head occurred in six of eight hips.

In this limited study the implantation of BMMNCs and IP-CHA appears to confer benefit in the repair of osteonecrosis and in the prevention of collapse.

The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the ‘biologically active area’ of all metal wear particles may predict the type of peri-prosthetic tissue response.

Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6).

The overall distribution of the size and area of the particles in both lymphocyte and non-lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles.

14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß), and growth factors (granulocyte macrophage colony stimulating factor (GM-CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group.

Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri-prosthetic response compared with those without this response.

These results suggest that the ‘biologically active area’ predicts the type of peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA.

Cite this article: Bone Joint J 2015;97-B:917–23.

Revision knee arthroplasty presents a number of challenges, not least of which is obtaining solid primary fixation of implants into host bone. Three anatomical zones exist within both femur and tibia which can be used to support revision implants. These consist of the joint surface or epiphysis, the metaphysis and the diaphysis. The methods by which fixation in each zone can be obtained are discussed. The authors suggest that solid fixation should be obtained in at least two of the three zones and emphasise the importance of pre-operative planning and implant selection.

Cite this article: Bone Joint J 2015;97-B:147–9.

Cemented femoral stems with force closed fixation designs have shown good clinical results despite high early subsidence. A new triple-tapered stem in this category (C-stem AMT) was introduced in 2005. This study compares this new stem with an established stem of similar design (Exeter) in terms of migration (as measured using radiostereometric analysis), peri-prosthetic bone remodelling (measured using dual energy x-ray densitometry, DXA), Oxford Hip Score, and plain radiographs.

A total of 70 patients (70 hips) with a mean age of 66 years (53 to 78) were followed for two years. Owing to missing data of miscellaneous reasons, the final analysis represents data from 51 (RSA) and 65 (DXA) patients. Both stems showed a typical pattern of migration: Subsidence and retroversion that primarily occurred during the first three months. C-stem AMT subsided less during the first three months (p = 0.01), before stabilising at a subsidence rate similar to the Exeter stem from years one to two. The rate of migration into retroversion was slightly higher for C-stem AMT during the second year (p = 0.03). Whilst there were slight differences in movement patterns between the stems, the C-stem AMT exhibits good early clinical outcomes and displays a pattern of migration and bone remodelling that predicts good clinical performance.

Cite this article: Bone Joint J 2015;97-B:755–61.

Biochemical markers of bone-turnover have long been used to complement the radiological assessment of patients with metabolic bone disease. Their implementation in daily clinical practice has been helpful in the understanding of the pathogenesis of osteoporosis, the selection of the optimal dose and the understanding of the progression of the onset and resolution of treatment. Since they are derived from both cortical and trabecular bone, they reflect the metabolic activity of the entire skeleton rather than that of individual cells or the process of mineralisation.

Quantitative changes in skeletal-turnover can be assessed easily and non-invasively by the measurement of bone-turnover markers. They are commonly subdivided into three categories; 1) bone-resorption markers, 2) osteoclast regulatory proteins and 3) bone-formation markers. Because of the rapidly accumulating new knowledge of bone matrix biochemistry, attempts have been made to use them in the interpretation and characterisation of various stages of the healing of fractures. Early knowledge of the individual progress of a fracture could help to avoid delayed or nonunion by enabling modification of the host’s biological response.

The levels of bone-turnover markers vary throughout the course of fracture repair with their rates of change being dependent on the size of the fracture and the time that it will take to heal. However, their short-term biological variability, the relatively low bone specificity exerted, given that the production and destruction of collagen is not limited to bone, as well as the influence of the host’s metabolism on their concentration, produce considerable intra- and inter-individual variability in their interpretation. Despite this, the possible role of bone-turnover markers in the assessment of progression to union, the risks of delayed or nonunion and the impact of innovations to accelerate fracture healing must not be ignored.

We present the extended follow-up (≥ 20 years) of a series of fully hydroxyapatite-coated femoral components used in 72 primary total hip replacements (THRs). Earlier results of this cohort have been previously published. All procedures were performed between 1986 and 1991. The series involved 45 women and 15 men with 12 bilateral procedures. Their mean age at the time of surgery was 60 years (46 to 80) and the mean duration of follow-up was 22.5 years (20 to 25). At final follow-up, the mean Merle d’Aubigné and Postel hip scores were 5.5 (4.5 to 6), 3.8 (3.5 to 5) and 3.3 (3.0 to 5.0) for pain, mobility and function, respectively. Of the patients 92% were very satisfied at the time of final follow-up.

There were seven revisions: six of the acetabular component for aseptic loosening and one of both the stem and the acetabular component for loosening due to deep infection. The survival of this prosthesis at 22.5 years with revision for any reason as the endpoint was 91.7% (95% confidence interval (CI) 84 to 99). Survival with aseptic loosening of the stem as the endpoint was 100% (95% CI 90 to 100).

This prosthesis provides pain relief in the long term. Survival of this component is comparable to the best results for primary THR with any means of fixation.

Cite this article: Bone Joint J 2013;95-B:467–71.

Stems may improve fixation and stability of components during revision total knee replacement. However, the choice between cemented and cementless stems is not a clear one. Cemented stems offer several advantages in terms of versatility, mechanical stability, surgical technique and clinical outcome over their cementless counterpart.

Cite this article: Bone Joint J 2014;96-B(11 Suppl A):115–7.

For over a decade, bisphosphonate administration has evolved and become the cornerstone of the prevention and treatment of fragility fractures. Millions of post-menopausal women have relied on, and continue to depend on, the long-acting, bone density-maintaining pharmaceutical drug to prevent low-energy fractures. In return, we have seen the number of fragility fractures decrease, along with associated costs and emotional benefits. However, with any drug, there are often concerns with side effects and complications, and this unique drug class is seeing one such complication in atypical subtrochanteric femoral fracture, counterproductive to that which it was designed to prevent. This has created concern over long-term bisphosphonate administration and its potential link to these atypical fractures. There is controversial evidence surrounding such a definitive link, and no protocol for managing these fractures.

This review offers the latest information regarding this rare but increasingly controversial adverse effect and its potential connection to one of the most successful forms of treatment that is available for the management of fragility fractures.