The scoliosis observed in chickens after pinealectomy resembles that seen in humans with an adolescent idiopathic scoliosis, suggesting that melatonin deficiency may be responsible. However, to date there have been no studies of pineal gland glucose metabolism in patients with adolescent idiopathic scoliosis that might support this hypothesis. We examined the excretion of urinary 6-sulfatoxyl-melatonin as well as the glucose metabolism of the pineal gland in 14 patients with an adolescent idiopathic scoliosis and compared them with those of 13 gender-matched healthy controls using F-18 fluorodeoxyglucose brain positron emission tomography. There was no significant difference in the level of urinary 6-sulfatoxyl-melatonin or pineal gland metabolism between the study and the control group. We conclude that permanent melatonin deficiency is not a causative factor in the aetiology of adolescent idiopathic scoliosis

We have undertaken an in vivo assessment of the tissue metabolism and cellular activity in torn tendons of the rotator cuff. Cellular oxygen consumption was measured in 13 patients undergoing mini-open repair of small, medium, large and massive full-thickness tears. Measurements were also taken from three control patients who were undergoing open stabilisation of the shoulder with grossly normal tendons. The level of oxygen and nitrous oxide was measured amperometrically using silver needle microelectrodes at the apex of the tear and 1.5 cm from its edge. With nitrous oxide indicating the degree of perfusion, oxygen consumption was calculated at each location to reflect cellular activity. All of the torn tendons had lower levels of cellular activity than the control group. This activity was lower still in the tissue nearest to the edge of the tear with the larger tears showing the lowest activity. This indicated reduced levels of tissue metabolism and infers a reduction in tendon viability. Our findings suggest that surgical repair of torn tendons of the rotator-cuff should include the more proximal, viable tissue, and may help to explain the high rate of re-rupture seen in larger tears

We describe a model which can be used for in vitro biocompatibility assays of biomaterials. We studied the in vitro response of human osteoarthritis or rheumatoid arthritis fibroblast-like synoviocytes to Al. 2. O. 3. or ZrO. 2. particles by analyzing the production of interleukin-1 (IL-1) and interleukin-6 (IL-6) and the metabolism of arachidonic acid via lipoxygenase and cyclo-oxygenase pathways. Our results show that, in these cells and under our experimental conditions, Al. 2. O. 3. and ZrO. 2. did not significantly modify the synthesis of IL-1 and IL-6 or the metabolism of arachidonic acid

After the simultaneous administration of radiocalcium and radiophosphorus to young rats the rate of deposition of calcium and of phosphorus in various skeletal parts was computed. Agreement was found between the two sets of data. No difference was thus found in the metabolism of the calcium and of the phosphorus of the bone salt

We measured the adenosine triphosphate (ATP) content of callus at various intervals during healing in 78 fractured tibiae in 10- to 12-week-old rabbits. The results, compared with the level in normal tissues, showed a high rate of energy metabolism in the early phase of fracture healing, which persisted until the callus was corticalised and remodelling had started. The ATP content could provide a more sensitive index to monitor fracture healing in animal studies. Our findings lend support to the need for nutritional supplements for patients with multiple fractures

1. The uptake of S³⁵ labelled sodium sulphate has been studied autoradiographically in the intervertebral disc of the young rabbit.

2. The sojourn of the isotope in the tissues includes an intracellular phase of approximately twenty-four hours, followed by an extracellular phase.

3. The cells exhibiting by far the greatest affinity for the sulphate ion are the peripheral groups of cells of the nucleus pulposus, while the chondrocyte-like cells of the cartilaginous segment of the annulus fibrosus are also fairly active. The central cells of the nucleus and the fibroblasts of the outer one-third of the annulus have a much lower uptake.

4. By analogy with similar studies on hyaline cartilage, and on the basis of correlation between the alcinophilia of the tissues and the concentration of the label, both before and after hyalase digestion of the tissue, it is considered that in the young rabbit disc, as in articular cartilage, the sulphate is incorporated primarily into chondroitin sulphate.

5. The elimination of the isotope from the nucleus at twenty-four days and the persistence of the label in the annulus fibrosus at thirty-two days tends to suggest that the metabolic turnover of acid mucopolysaccharide is considerably slower in the annulus than in the nucleus.

1. Methods for culturing cells isolated from slices of arthritic human or normal mammalian cancellous bone are described.

2. The capacity of the cultured cells to take up and hydroxylate labelled proline has been investigated.

3. Sections of the partially decalcified bone and of the isolated cells have been examined by transmission electron microscopy.

4. The possible significance of the results and observations are discussed. We are deeply grateful to Dame Janet Vaughan, who very kindly read this manuscript and made several valuable suggestions and criticisms. We are much obliged to Dr Sylvia Fitton-Jackson for her advice on the techniques of tissue culture and for giving us the composition of her chemically defined medium. Dr Palfrey kindly allowed one of us, M. J. Dickens, to learn transmission electron microscopy in his department at St Thomas's Hospital Medical School under the expert tuition of Mr G. Maxwell. Mr R. Hockhan and Mr M. Hepburn of the University of Surrey Structural Studies Unit helpfully instructed in the operation of the transmission electron microscope. Our special thanks are due to Mr E. P. Morris for his competent and enthusiastic technical assistance.

Aims. Tobacco, in addition to being one of the greatest public health threats facing our world, is believed to have deleterious effects on bone metabolism and especially on bone healing. It has been described in the literature that patients who smoke are approximately twice as likely to develop a nonunion following a non-specific bone fracture. For clavicle fractures, this risk is unclear, as is the impact that such a complication might have on the initial management of these fractures. Methods. A systematic review and meta-analysis were performed for conservatively treated displaced midshaft clavicle fractures. Embase, PubMed, and Cochrane Central Register of Controlled Trials (via Cochrane Library) were searched from inception to 12 May 2022, with supplementary searches in Open Grey, ClinicalTrials.gov, ProQuest Dissertations & Theses, and Google Scholar. The searches were performed without limits for publication date or languages. Results. The meta-analysis included eight studies, 2,285 observations, and 304 events (nonunion). The random effects model predicted a pooled risk ratio (RR) of 3.68 (95% confidence interval 1.87 to 7.23), which can be considered significant (p = 0.003). It indicates that smoking more than triples the risk of nonunion when a fracture is treated conservatively. Conclusion. Smoking confers a RR of 3.68 for developing a nonunion in patients with a displaced middle third clavicle fracture treated conservatively. We know that most patients with pseudarthrosis will have pain and a poor functional outcome. Therefore, patients should be informed of the significantly higher risks of nonunion and offered smoking cessation efforts and counselling. Moreover, surgery should be considered for any patient who smokes with this type of fracture. Cite this article: Bone Joint J 2023;105-B(7):801–807

Relating the results of our investigations to the knowledge hitherto acquired about the etiology of osteoporosis (which I have already referred to), I am inclined to interpret the pathogenesis of osteoporosis in the following way: 1) Primary osteoblastic deficiency: congenital (Lobstein); involutive (senile osteoporosis?); 2) Reduced osteoblastic activity from absence of trophic stimuli: (inactivity, ovarian agenesia, eunuchoidism, menopause); 3) Reduced osteoblastic activity from inhibitory stimuli: (cortisone, adrenocorticotrophic hormone (A.C.T.H.), stress, Cushing's disease, thyrotoxicosis); 4) Normal osteoblastic activity but insufficiency of constructive material: (malnutrition, disturbances of the digestive system, insufficiency of vitamin C, diabetes, thyrotoxicosis, cortisone, A.C.T.H., stress, Cushing's disease). Osteoporosis may therefore be the consequence either of a congenital osteoblastic deficiency, such as that found in cases of osteogenesis imperfecta, or of reduced osteoblastic activity due to absence of trophic stimuli such as mechanical stress and the sex hormones, or of reduced activity of the bone cells due to anti-anabolic substances which inhibit them, such as cortisone and its derivatives and the thyroid hormone in strong doses, or lastly of reduced availability of construction material due to its introduction in reduced quantities (starvation, dysfunction of the digestive system) or due to hindering of synthesis (deficiency of vitamin C, diabetes, cortisone and its derivatives) or due to an excessive degree of destruction (thyrotoxicosis). In the case of anti-anabolic hormones from the adrenal cortex, the mechanism may thus be twofold: inhibition of the osteoblasts and deprivation of the osteoblasts of glucoprotein material due to a general anomaly of metabolism. This may perhaps explain the most serious forms of bone atrophy which are usually observable in cases of hyperfunction of the adrenal cortex. Senile osteoporosis should, in my opinion, be included in the first of our groups because it cannot be said to be brought about by any of the causes usually cited for osteoporosis– such as deficiency of sex hormones, excess of hormones from the adrenal cortex, deficiency of calcium, etc.–and in all probability it will depend on a progressive involution of the osteoblasts brought about by old age. Senile involution is an expression of the descending phase of life's parabola and it involves all the organs and all the parenchymatous tissues in the human body, but it does not cause a parallel reduction of functions and activities on all of them equally. The skeletal system is one of the first to feel these reductions, because in old age life necessarily becomes less intense. Consequently in the economy of the ageing subject the generally reduced level of metabolism brings about a sort of selection in the nourishment of the different organs and systems, and sometimes almost a dismantling of some of these in an attempt to fall in with the new and reduced level of activities of some of the parenchymatous tissues, activities which may be incomplete or even transferred elsewhere. We believe that the moment which originally determines the beginning of senile osteoporosis coincides with the involutional process of cellular metabolism that strikes at all parenchymatous tissue during old age–striking, in the case of osteoporosis, hardest of all at the bony tissues. There is, indeed, no doubt that certain essential processes of cellular metabolism do alter with age, and that the reduction in the activity of the gonads does have considerable importance. In any case, just as adolescence and old age cannot be explained only in terms of gonadal activity, so the involution of the skeleton cannot be due merely to the involution of the gonads. How should one then interpret the well known benefit afforded by administration of sex hormones in cases of osteoporosis? Probably the action of oestrogens and androgens is, in this case, of a pharmacological nature, and comparable, for instance, to the action of digitalis on the cardiac muscle. It will be remembered how digitalis acts almost exclusively on myofibrils which have become inadequate, and has little or no effect on a normal myocardium. Similarly, the sex hormones would seem to exert a stimulating action on osteoblasts that are on the way to involution, while they exert little or no action on normal osteoblasts. In support of this we have the findings of Urist and other workers, who demonstrated that the administration of sex hormones produces calcium and nitrogen retention only in osteoporotics, while in non-osteoporotic subjects of the same age it produces no effect. On the other hand, the action of the sex hormones might act in cases of senile osteoporosis by returning the changed level of protein metabolism to normal. From the data in the literature and from the results of our own investigations, I conclude that osteoporosis in general, and senile osteoporosis in particular, are first and foremost the result of a disturbance in the metabolism of bone, and that the metabolic disturbance is closely and exclusively related to the degree of activity and the state of activity of the cells in the bone. Lastly, I believe that senile osteoporosis should not be considered an actual disease but rather as one limited aspect of the normal descending parabola which affects to a greater or less degree all the tissues of the body

The discrepancy between successful experimental studies of cartilage repair and the clinical results is unexplained. We have evaluated the effect of metabolic alterations in joint homeostasis owing to an articular defect on the outcome of cartilage repair using tissue engineering methods. We used 21 adolescent Dutch goats divided into three groups. The control knees were left untreated while the contralateral knee was randomised to receive either no treatment (N), early treatment (E) or late treatment (L). The metabolism of proteoglycans in the surrounding joint surface was determined and correlated with the O’Driscoll score used to quantify the histological aspect of the repair of the defect. Synthesis of proteoglycan (PG) was increased in all groups. The release of glucosaminoglycan (GAG) was significantly higher in the untreated but not after early transplantation (1.3 v 1.8 NS). The cartilage repair scores in the early treatment group were not as good as those of the normal control group, but were significantly better when compared with both the untreated defects and the late treated defects. Defects which had been treated late showed a significantly decreased score when compared with those which had had early treatment or the normal control group and did not differ (p = 0.12) from those with no treatment. The histological and biochemical scores closely resembled the macroscopic and functional parameters which showed a significant deterioration for the late treated group and those without treatment compared with animals treated early. Thus, tissue-engineered cartilage repair is negatively influenced by altered matrix metabolism. Early treatment showed significantly better results for repair of cartilage than late or no treatment, with a concurrent decrease in the detrimental disturbance of cartilage metabolism which constituted a protective effect on the articulation

There is a disparity in sport-related injuries between sexes, with females sustaining non-contact musculoskeletal injuries at a higher rate. Anterior cruciate ligament ruptures are between two and eight times more common than in males, and females also have a higher incidence of ankle sprains, patellofemoral pain, and bone stress injuries. The sequelae of such injuries can be devastating to an athlete, resulting in time out of sport, surgery, and the early onset of osteoarthritis. It is important to identify the causes of this disparity and introduce prevention programmes to reduce the incidence of these injuries. A natural difference reflects the effect of reproductive hormones in females, which have receptors in certain musculoskeletal tissues. Relaxin increases ligamentous laxity. Oestrogen decreases the synthesis of collagen and progesterone does the opposite. Insufficient diet and intensive training can lead to menstrual irregularities, which are common in female athletes and result in injury, whereas oral contraception may have a protective effect against certain injuries. It is important for coaches, physiotherapists, nutritionists, doctors, and athletes to be aware of these issues and to implement preventive measures. This annotation explores the relationship between the menstrual cycle and orthopaedic sports injuries in pre-menopausal females, and proposes recommendations to mitigate the risk of sustaining these injuries.

Cite this article: Bone Joint J 2023;105-B(7):723–728.

Benefits of early stabilization of femoral shaft fractures, in mitigation of pulmonary and other complications, have been recognized over the past decades. Investigation into the appropriate level of resuscitation, and other measures of readiness for definitive fixation, versus a damage control strategy have been ongoing. These principles are now being applied to fractures of the thoracolumbar spine, pelvis, and acetabulum. Systems of trauma care are evolving to encompass attention to expeditious and safe management of not only multiply injured patients with these major fractures, but also definitive care for hip and periprosthetic fractures, which pose a similar burden of patient recumbency until stabilized. Future directions regarding refinement of patient resuscitation, assessment, and treatment are anticipated, as is the potential for data sharing and registries in enhancing trauma system functionality.

Cite this article: Bone Joint J 2023;105-B(4):361–364.

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI.

Cite this article: Bone Joint J 2022;104-B(5):575–580.

The weight-bearing status of articular cartilage has been shown to affect its biochemical composition. We have investigated the topographical variation of sulphated glycosaminoglycan (GAG) relative to the DNA content of the chondrocyte in human distal femoral articular cartilage. Paired specimens of distal femoral articular cartilage, from weight-bearing and non-weight-bearing regions, were obtained from 13 patients undergoing above-knee amputation. After papain enzyme digestion, spectrophotometric GAG and fluorometric DNA assays assessed the biochemical composition of the samples. The results were analysed using a paired t-test. Although there were no significant differences in cell density between the regions, the weight-bearing areas showed a significantly higher concentration of GAG relative to DNA when compared with non-weight-bearing areas (p = 0.02). We conclude that chondrocytes are sensitive to their mechanical environment, and that local loading conditions influence the metabolism of the cells and hence the biochemical structure of the tissue

The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors. Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes. There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism

Aims

The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study.

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

Conventional non-steroidal anti-inflammatory drugs (NSAIDs) and newer specific cyclo-oxygenase-2 (cox-2) inhibitors are commonly used in musculoskeletal trauma and orthopaedic surgery to reduce the inflammatory response and pain. These drugs have been reported to impair bone metabolism. In reconstruction of the anterior cruciate ligament the hamstring tendons are mainly used as the graft of choice, and a prerequisite for good results is healing of the tendons in the bone tunnel. Many of these patients are routinely given NSAIDs or cox-2 inhibitors, although no studies have elucidated the effects of these drugs on tendon healing in the bone tunnel. In our study 60 female Wistar rats were randomly allocated into three groups of 20. One received parecoxib, one indometacin and one acted as a control. In all the rats the tendo-Achillis was released proximally from the calf muscles. It was then pulled through a drill hole in the distal tibia and sutured anteriorly. The rats were given parecoxib, indometacin or saline intraperitoneally twice daily for seven days. After 14 days the tendon/bone-tunnel interface was subjected to mechanical testing. Significantly lower maximum pull-out strength (p < 0.001), energy absorption (p < 0.001) and stiffness (p = 0.035) were found in rats given parecoxib and indometacin compared with the control group, most pronounced with parecoxib

Aims

The aim of this study was to develop and internally validate a prognostic nomogram to predict the probability of gaining a functional range of motion (ROM ≥ 120°) after open arthrolysis of the elbow in patients with post-traumatic stiffness of the elbow.

Aims

BoneMaster is a thin electrochemically applied hydroxyapatite (HA) coating for orthopaedic implants that is quickly resorbed during osseointegration. Early stabilization is a surrogacy marker of good survival of femoral stems. The hypothesis of this study was that a BoneMaster coating yields a fast early and lasting fixation of stems.

Aims

Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4^-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue.

The association between vitamin-D-resistant rickets and linear sebaceous naevus syndrome is extremely rare. Only eight cases have been described in the English literature and in none were the skeletal aspects addressed. We present three new cases and describe the musculoskeletal features. The details and outcome of surgery for correction of the deformities are discussed. The disturbances of metabolism of vitamin D and the effects of pharmacological treatment are also described

Aims

Periprosthetic joint infections (PJIs) are among the most devastating complications after joint arthroplasty. There is limited evidence on the efficacy of different antiseptic solutions on reducing biofilm burden. The purpose of the present study was to test the efficacy of different antiseptic solutions against clinically relevant microorganisms in biofilm.

1. Four cases of ochronotic arthropathy have been studied and the related literature has been reviewed. 2. Ochronotic arthropathy is a rare condition resulting from an inborn error of metabolism occurring as a Mendelian recessive characteristic. Its incidence, however, may have been underestimated. 3. Problems of differential diagnosis are discussed and it is suggested that more widespread screening should be undertaken in order to assess the true incidence of the condition

Aims

The aim of this study was to determine whether there is an increased prevalence of scoliosis in patients who have suffered from a haematopoietic malignancy in childhood.

We measured levels of calcitonin and other markers of calcium and phosphorus metabolism in both unconscious and conscious patients after multiple trauma. We found dramatic increases in calcitonin levels in unconscious patients, and smaller increases in conscious patients. In two cases, very high levels, more than 100 x normal, appeared to be related to more rapid healing of bone. Calcitonin levels were highest immediately after admission and decreased over the ensuing two weeks. The possible relationship between unconsciousness and the increased rate of healing of fractures is discussed

1. A case of hypophosphatasia in a boy who sustained a fractured left femur is described. 2. The literature is reviewed, and the reported cases are found to fall into severe, moderately severe and mild forms. 3. The diagnostic features of the disease are the radiological picture, which resembles that of rickets, very low serum alkaline phosphatase, and excessive phosphoethanolamine excretion in the urine. 4. Other clinical features may be a failure to thrive in early infancy, premature loss of deciduous teeth, hypercalcaemia and renal damage. 5. The function of alkaline phosphatase in bone metabolism in relation to this disease has been discussed

Rat patellae were preincubated with culture medium M199 for one hour and then with either fresh culture medium or Ringer's solution, Ringer lactate, Ringer glucose, normal saline or Betadine for another hour. The rate of proteoglycan synthesis in the articular cartilage was then measured by uptake of 35SO4 for the next 16 hours. Cartilage metabolism was inhibited by all of the solutions even after a recovery time of 16 hours. The inhibition was by 5% for Ringer's solution, 10% for Ringer glucose (p < 0.01), 20% for saline and Ringer lactate (p < 0.001) and 55% for Betadine (p < 0.001). Ringer's solution is therefore the best choice for joint irrigation during arthroscopy or other procedures

Aims

Although there is increasing legalization of the use of cannabis in the USA, few well-powered studies have evaluated the association between cannabis use disorder and outcomes following primary total hip arthroplasty (THA). Thus, the aim of this study was to determine whether patients who use cannabis and undergo primary THA have higher rates of in-hospital length of stay (LOS), medical complications, implant-related complications, and costs.

Thirteen patients suffering from rheumatoid arthritis had 19 stress fractures of the tibia or fibula. These patients characteristically presented with sudden, severe, unexplained pain with localised tenderness just below the knee or above the ankle. In seven patients examination of the adjacent joint indicated a flare-up of disease activity or a pyogenic arthritis. In six patients the diagnosis was delayed by the late appearance of callus in minute fractures. All patients had rheumatoid deformities of the ipsilateral lower limb: valgus deformities of the knee and subtalar joints occurred most frequently. All patients had osteoporosis; all except two had received steroid treatment and five had abnormalities of calcium metabolism. We suggest that deformities of the knee and ankle predispose patients with rheumatoid arthritis and osteoporosis to stress fractures of the tibia and fibula

Aims

To find out if there is an inverse association between estimated glomerular filtration rate (eGFR) and whole blood cobalt (Co) and chromium (Cr) levels in patients with metal-on-metal (MoM) hip arthroplasties and renal insufficiency, suggesting that renal insufficiency could cause accumulation of Co and Cr in blood.

Aims

The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time.

We studied the effect of a lipid clearing agent (clinofibrate) on the osteocytes of rabbits treated with corticosteroids. Thirty-one rabbits were divided into four groups: (A) steroid-treated with a normal diet, (B) steroid-treated and one a diet with added clinofibrate, (C) non-steroid-treated, on a diet with clinofibrate; and (D) non-steroid-treated on a normal diet. All the steroid-treated animals demonstrated hyperlipidaemia and fatty degeneration of the liver. Lipid-containing osteocytes were seen in the femoral heads of these animals. However, those which received clinofibrate (group B) had less severe lipidaemia, and less severe degeneration of the liver. In them, only the osteocytes around the haversian canals exhibited lipid inclusions. Clinofibrate appears to modify lipid metabolism, diminishing the steroid induced accumulation of lipids within osteocytes. This effect may protect against steroid-mediated osteonecrosis

The present study was undertaken to investigate the effect of fluorocarbon on the preservation of an amputated limb. The hind limbs of dogs were completely amputated through the mid-thigh; some were perfused with fluorocarbon, others with lactated Ringer's solution and some were not perfused at all. After six hours of ischaemia, all the limbs were replanted. Perfusion with fluorocarbon had an inhibitory effect on the anaerobic metabolism of an amputated limb, thus increasing the survival rate. Leakage of creatine phosphokinase from the replanted limb also was inhibited by perfusion with fluorocarbon. These effects were more striking when the amputated limb was perfused continuously rather than intermittently and when it was preserved in iced water rather than at room temperature; these measures helped to prevent replantation toxaemia and to preserve muscle function

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

1. Twenty-one cases of congenital dislocation of the hip were found on examination of 1,881 consecutive neonates on the first day of life, giving an incidence of eleven per 1,000 live births. 2. Insignificant high-pitched "clicks" were noted in 10 per cent of newborn children. 3. Conversion of half of the patients with hip dislocation to normal occurred during the first post-natal week. 4. Joint laxity was not a feature of the newborn with congenital dislocation of the hip. 5. Oestradiol, oestrone and oestriol were estimated in twenty-fourhour urine samples collected from sixteen patients with congenital dislocation of the hip and nineteen matched controls during the first six days of life. No significant differences in oestrogen output between the two groups were found. 6. The hypothesis that congenital dislocation of the hip is a result of an inborn error of oestrogen metabolism in the newborn is not supported

The protective effect of local hypothermia was studied in pig's limbs made ischaemic by long, repeated application of a pneumatic tourniquet. Twenty-one Landrace pigs were anaesthetised on two separate occasions six days apart and a pneumatic tourniquet at 500 mmHg pressure was applied to the same forelimb for three and two hours respectively. Ten of the pigs had local hypothermia from cold gel packs placed around the limb during the first tourniquet application; the other 11 had the ischaemic limb exposed to room temperature. In comparison with the normothermic limbs, the hypothermic ischaemic limbs had significant slowing of metabolism. The hypothermic limbs also showed less inflammatory response and a faster rate of recovery, both immediately after removal of the tourniquet, and by the end of the experiment, 10 days after the first tourniquet. Local hypothermia produced by this technique was shown to be safe and effective, while appearing to protect muscles exposed to prolonged tourniquet-induced ischaemia

Bone loss around replacement prostheses may be related to the activation of mononuclear phagocytes (MNP) by prosthetic wear particles. We investigated how osteoblast-like cells were regulated by human MNP stimulated by particles of prosthetic material. Particles of titanium-6-aluminium-4-vanadium (TiAlV) stimulated MNP to release interleukin (IL)-1β, tumour necrosis factor (TNF)α, IL-6 and prostaglandin E. 2. (PGE. 2. ). All these mediators are implicated in regulating bone metabolism. Particle-activated MNP inhibited bone cell proliferation and stimulated release of IL-6 and PGE. 2. The number of cells expressing alkaline phosphatase, a marker associated with mature osteo-blastic cells, was reduced. Experiments with blocking antibodies showed that TNFα was responsible for the reduction in proliferation and the numbers of cells expressing alkaline phosphatase. By contrast, IL-1β stimulated cell proliferation and differentiation. Both IL-1β and TNFα stimulated IL-6 and PGE. 2. release from the osteoblast-like cells. Our results suggest that particle-activated mono-nuclear phagocytes can induce a change in the balance between bone formation and resorption by a number of mechanisms

1 . Young Wistar rats fed on a diet containing 0·3 per cent semicarbazide hydrochloride developed the characteristic lesions of osteolathyrism. This consisted of kyphoscoliosis, displacement of epiphyses and dislocations of joints. A pathological study of the skeletal lesions showed widening, disorganisation and tears of the epiphysial plate with the zone of maturing cartilage showing the greatest increase in width. The severe kyphoscoliosis was due to a derangement and displacement at and through the epiphysial plates of the twelfth thoracic or first lumbar vertebra. 2. Some of the compounds that are known to produce osteolathyrism in laboratory animals are beta aminopropionitrile, amino acetonitrile, mercaptoethylamine and semicarbazide. The mode of action of the lathyrogenic compounds was analysed in the light of a number of experiments done in this laboratory. 3. lt is possible that they interfere with the metabolism of the epiphysial plate. There appears to be a decreased polymerisation of the ground substance of the epiphysial cartilage, but the exact metabolic reaction involved is not known. Other chemicals of similar structure, with the same reactive groups, did not show lathyrogenic properties. It is concluded that it is not a particular chemical structure, configuration or specific reactive group that is responsible for the production of osteolathyrism. The chemistry of the lesions still remains to be solved

We performed positron emission tomography (PET) with . 18. fluorine-fluoro-2-deoxy-D-glucose (FDG) on 55 patients with tumours involving the musculoskeletal system in order to evaluate its role in operative planning. The standardised uptake value (SUV) of FDG was calculated and, to distinguish malignancies from benign lesions, the cases were divided into high (≥ 1.9) and low (< 1.9) SUV groups. The sensitivity of PET for correctly diagnosing malignancy was 100% with a specificity of 76.9% and an overall accuracy of 83.0%. The mean SUV for metastatic lesions was twice that for primary sarcomas (p < 0.0015). Our results suggest that the SUV may be useful in differentiating malignant tumours from benign lesions. However, some of the latter, such as schwannomas, had high SUVs so that biopsy or wide resection was selected as the first operation. Thus, some other quantitative analysis may be required for preoperative planning in cases of high-SUV neurogenic benign tumours. The reverse transcription-polymerase chain reaction revealed that the RNA message of a key enzyme in glucose metabolism, phosphohexose isomerase (PHI)/autocrine motility factor, was augmented in only high FDG-uptake lesions, suggesting that a high expression of the PHI message may be associated with accumulation of FDG in musculoskeletal tumours

Two groups of intervertebral discs, one normal, as obtained from the post-mortem room, the other prolapsed, as removed at operation, have been compared by chemical analysis of their principal constituents. There is a progression of chemical changes associated with the ageing of the normal disc. This shows not only the expected slight increase in collagen as age advances, but also, surprisingly, that the polysaccharide content rises to a maximum in the fourth decade, in the same way as does polysaccharide in costal cartilage. In prolapsed discs the ageing process is superseded by a different and distinctive progression, which advances, not according to age, but according to the duration of the prolapse. There is a critical level to which the polysaccharide content must apparently fall, irrespective of the normal level for the patient's age, before a prolapse occurs. Normal ageing probably consists in the breakdown of a particular polysaccharide/protein linkage, with coincident "maturation" of collagen. In the prolapsing disc multiple, and possibly different, linkages are rapidly broken down. This depolymerisation of a gel structure must be presumed to be the basis of the decreased imbibition capacity of the nucleus pulposus, and to be the source of the hydrostatic abnormalities which result in disc prolapse. In both normal and prolapsing discs the products of mucopolysaccharide breakdown appear to participate in the metabolism of collagen

Sarcoma complicating Paget's disease is uncommon; ninety-five cases have been collected and seven further cases are now reported. Sarcoma probably complicates less than 2 per cent of all cases of Paget's disease. There is a relatively high incidence in males, especially in the sixth decade, whereas bone sarcoma over the age of fifty years without osteitis deformans is rare. Injury is prominent in the history of many cases. Comparison of Paget's sarcoma, "ordinary" bone sarcoma and the bones affected by uncomplicated osteitis deformans reveals some important differences. As to the type of tumour, osteogenic sarcoma is the commonest, but fibrosarcoma and round-cell sarcoma are also frequent. The serum phosphatase is a most useful prognostic guide in a disease with a generally poor prognosis. Magnesium metabolism in relation to bone sarcoma requires further study. Prophvlaxis is based on a clinical suspicion of this complication in Paget's disease, and measures are outlined which may be of assistance. Sarcoma in Paget's bone is highly lethal, but Nature in striking down these old people may have provided us with facts which will ultimately solve problems common to all sarcomas of bone

There is little information about the effects of extracorporeal shock-wave about application the effects (ESWA) of on normal bone physiology. We have therefore investigated the effects of ESWA on intact distal rabbit femora in vivo. The animals received 1500 shock-wave pulses each of different energy flux densities (EFD) on either the left or right femur or remained untreated. The effects were studied by bone scintigraphy, MRI and histopathological examination. Ten days after ESWA (0.5 mJ/mm. 2. and 0.9 mJ/mm. 2. EFD), local blood flow and bone metabolism were decreased, but were increased 28 days after ESWA (0.9 mJ/mm. 2. ). One day after ESWA with 0.9 mJ/mm. 2. EFD but not with 0.5 mJ/mm. 2. , there were signs of soft-tissue oedema, epiperiosteal fluid and bone-marrow oedema on MRI. In addition, deposits of haemosiderin were found epiperiosteally and within the marrow cavity ten days after ESWA. We conclude that ESWA with both 0.5 mJ/mm. 2. and 0.9 mJ/mm. 2. EFD affected the normal bone physiology in the distal rabbit femur. Considerable damaging side-effects were observed with 0.9 mJ/mm. 2. EFD on periosteal soft tissue and tissue within the bone-marrow cavity

Aims

The purpose of this study was to use pharmacogenetics to determine the frequency of genetic variants in our total knee arthroplasty (TKA) patients that could affect postoperative pain medications. Pharmacogenetic testing evaluates patient DNA to determine if a drug is expected to have a normal clinical effect, heightened effect, or no effect at all on the patient. It also predicts whether patients are likely to experience side effects from medicine. We further sought to determine if changing the multimodal programme based on these results would improve pain control or reduce side effects.

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.

1. In two dogs, approximately one to two years and three to four months of age, an experimental comparison was made between the calcium accretion rate as defined by the Bauer-Carlsson-Lindquist equation, and the bone formation rate determined by double tetracycline labelling. 2. The overall calcium accretion rate was determined from the specific activity of the blood plasma, and the urinary and faecal excretion of isotope, following an intravenous tracer dose of Ca. 45. A time of five days after injection was used for the calculation of accretion rates, but data for shorter times of calculation are included. 3. Local accretion rates were obtained for different parts of the skeleton by determining the specific activities of bone samples at the end of the experiment. 4. The amount of isotope the uptake of which was not related to new bone formation (the diffuse component) was determined autoradiographically. 5. Local values for appositional growth rate and bone formation rate were obtained, using sections of undecalcified bone specimens, by measuring the linear separation between two tetracycline bone markers and the area of new bone enclosed by them. 6. In the older dog, the measurements for cortical bone showed that the accretion rate was two to three times as great as the bone formation rate: the observed diffuse component was sufficient to account for the greater part of this difference. Measurement of the bone formation rate for cancellous bone presented difficulties, but the approximate values obtained suggested that the accretion rate and the bone formation rate were of about the same order for this tissue. 7. In the younger dog, the bone formation rate could be determined only in cortical bone: at the sites studied, the values for the accretion rate and the bone formation rate did not differ by more than 20 per cent. It is suggested that this is due partly to the low specific activity of the diffuse component in this young animal, and partly to the relatively large amounts of new bone formed during the period of the experiment. 8. Despite the important differences between the rates of calcium accretion and bone formation that were found to exist in regions where there was only a small amount of new bone formation, there was a strong correlation between the two rates. The value of the accretion rate as a parameter of bone metabolism is clear

Aims

As the population ages and the surgical complexity of lumbar spinal surgery increases, the preoperative stratification of risk becomes increasingly important. Understanding the risks is an important factor in decision-making and optimizing the preoperative condition of the patient. Our aim was to determine whether the modified five-item frailty index (mFI-5) and nutritional parameters could be used to predict postoperative complications in patients undergoing simple or complex lumbar spinal fusion.

1. Idiopathic necrosis of the femoral head is generally considered to be a rare disease but it appears to be rather frequent in France in view of the fact that 139 cases were recorded in the orthopaedic clinic of Hôpital Cochin between 1959 and 1963. Ninety cases treated by operation have been analysed in this paper. Men are nearly exclusively affected between the ages of eighteen and seventy, with the highest incidence between thirty and fifty years of age. Both hips are affected in 52 per cent of cases. 2. The etiology is unknown, but steroid therapy was noted in 36 per cent of the cases and some history of slight injury in 30 per cent. The sudden onset of pain in half the cases suggests the obliteration of one of the blood vessels supplying the femoral head. 3. Radiographs are often normal at the time of onset of the symptoms but later they show increased density of the head localised to the antero-superior aspect, and later still collapse of this weight-bearing region. The extent of the lesion appears to be determined from the very beginning rather than to be progressive. The superior joint space is never reduced and may in fact be widened. 4. Pathological examination of the head and neck confirms necrosis of the cancellous bone and the integrity of the overlying cartilage, but shows deep to the necrotic region a highly reactive zone characterised by hypervascularity and raised metabolism. These features have been demonstrated by injection of the blood vessels and also by the uptake of phosphorus 32 and by the succino-deshydrogenase test. 5. In six cases microscopic vascular lesions were found in the antero-lateral pedicle of the femoral head. 6. The high degree of activity of the tissue deep to the necrotic zone gives some hope for revascularisation of the necrotic segment. For this reason protection from pressure may be the way to prevent dramatic collapse of the head. Rest, medical treatment and freedom from weight bearing, however, do not achieve adequate protection. Varus or rotation osteotomy of the femoral neck not only gives relief from pain but appears to prevent collapse of the femoral head. 7. When destruction of the head has already taken place good results may be expected from the insertion of a metallic prosthesis, provided the acetabulum is sound. The results are less favourable when the acetabulum has been altered by secondary arthritic change, and arthrodesis may have to be considered if the disease is unilateral or when a prosthesis has been successfully inserted on the other side

1. Individuals who are normal and not osteoporotic seem to show retention of cortical bone at successive decades of life in proportion to the total lean body-mass. In patients with osteoporosis the weight of the skeleton decreases at a rate exceeding the physiological rate of atrophy of muscle, tendon and bone tissue that occurs with the time-dependent process of ageing. 2. Six patients representing the typical forms of osteoporosis commonly found in orthopaedic practice were investigated intensively over a period of three years and compared with individuals in whom there was no osteoporosis by studies of metabolic balance, Sr85 osteograms, and tetracycline deposition. 3. Studies of metabolic balance in patients with osteoporosis showed normal or negative calcium balances, but an equilibrium for the metabolism of nitrogen and phosphorus. Increased intake of calcium in the diet produced retention of calcium but not sufficient phosphorus, nitrogen or gain in weight to prove that the patient had made new bone and healed the osteoporosis. 4. Radio-isotope osteograms showed high, normal or low rates of change of uptake of Sr85 and the accretion rate was calculated to be normal or low in individuals with osteoporosis. High uptake of tetracycline by a small mass of bone tissue and by a relatively small percentage of the total number of osteons suggested that in an adult human being the calcium reserve in the skeleton is enormous. Thirty to 50 per cent of the total bone mass was sufficient to turn over 0·5 to 1·0 gramme, the amount of calcium utilised in twenty-four hours by the human adult. This was accomplished by structural or old bone throughout the entire skeleton, and by labile or newer bone located in approximately 10 per cent of the total number of Haversian cylinders or osteons. 5. Some of the unclosed or half-closed osteons were hyperactive in osteoporotic bones. In the process of remodelling of cortical bone a significant quantity of bone tissue was incompletely restored and there were, presumably as a result, intermittently large or small negative calcium balances. Osteoporosis may have been the cause, rather than the result, of the negative calcium balance. 6. The experimental and clinical literature of the past ten years, and studies on patients described in this critical review, were interpreted to indicate that prolonged calcium deficiency, castration, hyperadrenal corticoidism or a sedentary life may precipitate, accentuate and accelerate osteoporosis in individuals who are genetically predisposed to develop it. Sometimes high calcium intake or sex hormones, or both, may have slowed the rate of resorption but did not replace the deficit in cortical bone. 7. Further research is necessary to find the chief etiological factor and to produce the cure for this increasingly common disorder of the skeleton

Aims

The aim of this study was to assess the effectiveness of perioperative essential amino acid (EAA) supplementation to prevent rectus femoris muscle atrophy and facilitate early recovery of function after total knee arthroplasty (TKA).

1 . The magnitude of the problem of congenital anomalies becomes evident when one takes into consideration the fact that they cause the death of approximately one quarter of the human race either before or shortly after birth, and handicap an appreciable proportion of the survivors throughout their lives. Further, a significant percentage of infants judged to be normal at birth are found in later life to suffer from "disguised" anomalies of the skeleton and soft tissues. Though the study of genetic factors leading to congenital defects has attracted a great deal of attention during the last few decades, the importance of environmental causes of human malformations has received relatively less emphasis. The association of congenital anomalies such as cataract and cardiac septal defects with maternal intercurrent infection of rubella during the early months of pregnancy demonstrates clearly that changes in the germplasm cannot always be invoked as the cause of developmental abnormalities. Congenital malformations that are sometimes genetically determined, such as microphthalmos, cleft palate, and certain skeletal abnormalities, can be caused in the offspring not only by maternal nutritional deficiencies and x-radiation but also, at least in some animals, such as chickens, rats and rabbits, by the introduction of certain substances like insulin into the environment of the embryo during its development. 2. Since very little is known of the detailed histology of the early human embryo, the histological examination of cases of perverted growth is mainly limited to aborted foetuses which, unfortunately, tend to present varying degrees of post-mortem degeneration before accurate histological methods can be applied. It is exactly in this field that animal experiments can offer valuable help. According to Mall and other embryologists the pathological changes that take place in human foetuses and those obtained experimentally in animals are not merely "analogous or similar but identical.". 3. An attempt has been made to review, in some detail, the more important work which has been carried out on experimental teratogenesis, on the epidemiological implications of developmental arrests in humans, and on foetal abnormalities associated with maternal metabolic and hormonal disorders during pregnancy. 4. The technique employed for injection of insulin into the egg yolk has been described. Methods used for the estimation of blood sugar in chick embryos at various stages after injection of insulin and special histochemical techniques for localising polysaccharides in cartilage have been outlined. 5. A few salient experimental results have been tabulated, and some of the insulin-induced abnormalities have been illustrated. 6. The possible mechanism of action of insulin in the causation of the various developmental anomalies has been discussed. Broadly speaking, insulin seems to affect primarily the part or tissue which is in the most active stage of growth or differentiation at the time of the injection. Within the range of 0·05 to 6 units of insulin employed, the incidence, severity and distribution of the deformities appear to increase with the dose of the hormone. It has been observed that the hypoglycaemia caused by insulin injection is not counteracted till about the twelfth day of incubation, presumably because of excessive accumulation of glycogen in the yolk-sac membrane immediately after the injection, and because of lack of glycogen storage in the embryonic liver and the absence of active secretion in the endocrine glands concerned with the carbohydrate metabolism of the embryo. It has been suggested that this unchecked hypoglycaemia may deprive the mesenchyme, pre-cartilage and cartilage of glycogen and mucopolysaccharides (chondroiten-sulphuric acid complexes), depending on the time of injection and the dose of insulin, and thus not only give rise to a variety of single and multiple deformities in the cartilaginous skeleton but also interfere with the normal endochondral ossification, resulting in a generalised developmental disturbance of bone resembling osteogenesis imperfecta in the human. 7. Insulin-induced abnormalities can be prevented to a remarkable extent by injecting nicotinamide and riboflavin into eggs along with insulin. 8. The question of the practical application of the knowledge gained from experimental observations on insulin-induced developmental abnormalities in explaining the possible causation of congenital anomalies in humans by genetic and environmental teratogenic factors, has been discussed. It is suggested that the orderly progression from the mesenchymatous condensation to cartilage, and then through calcified cartilage to bone, may be disturbed by these teratogenic factors at critical phases during the development of the embryo, and a variety of single and multiple skeletal deformities may thus be induced. 9. A plea is made for routine pathological and radiological examination of aborted foetuses and stillborn infants more or less on the lines followed for experimentally induced deformities with a view to applying the knowledge gained from animal experiments to a better understanding of the etiology and pathology of human congenital anomalies. 10. As regards the possible prevention of these deformities, it is not always easy to offer sound eugenic advice in the cases of congenital malformations determined partly or completely by genetic factors, for two important reasons. First, it is often difficult to distinguish between genetically determined congenital anomalies and their phenocopies. Secondly, genetically determined developmental defects sometimes show surprisingly variable expressivity and penetrance. For the conditions in which both genetic and environmental factors are involved, the most profitable immediate line of attack would be on the environmental factors. A relatively simpler problem is presented by the malformations which are, for all practical purposes, entirely caused by environmental factors. Measures to prevent congenital anomalies caused by prenatal rubella, such as exposure of girls to the disease during childhood and protection of pregnant women during the early stages of pregnancy by immune serum, are under active consideration. 11 . Further energetic investigation of the causes of permaturity, stillbirths, monstrosities and congenital malformations is urgently needed, before embarking on a successful programme for prevention. "The day of successful prophylaxis is not yet, but it is much nearer than seemed possible a few years ago."

Aims

The aim of this study was to determine the general postoperative opioid consumption and rate of appropriate disposal of excess opioid prescriptions in patients undergoing primary unilateral total knee arthroplasty (TKA).

Aims

The aim of this study was to investigate the influence of age on the cost-effectiveness of arthroscopic rotator cuff repair.

Aims

The aim of this study was to evaluate the outcomes of a salvage procedure using a 95° angled blade plate for failed osteosynthesis of atypical subtrochanteric femoral fractures associated with the long-term use of bisphosphonates. These were compared with those for failed osteosynthesis of subtrochanteric fractures not associated with bisphosphonate treatment.

Aims

The aim of this study was to evaluate antegrade autologous bone grafting with the preservation of articular cartilage in the treatment of symptomatic osteochondral lesions of the talus with subchondral cysts.

Tuberculosis (TB) remains endemic in many parts of the developing world and is increasingly seen in the developed world due to migration. A total of 1.3 million people die annually from the disease. Spinal TB is the most common musculoskeletal manifestation, affecting about 1 to 2% of all cases of TB. The coexistence of HIV, which is endemic in some regions, adds to the burden and the complexity of management.

This review discusses the epidemiology, clinical presentation, diagnosis, impact of HIV and both the medical and surgical options in the management of spinal TB.

Cite this article: Bone Joint J 2018;100-B:425–31.

Aims

The intra-articular administration of tranexamic acid (TXA) has been shown to be effective in reducing blood loss in unicompartmental knee arthroplasty and anterior cruciate reconstruction. The effects on human articular cartilage, however, remains unknown. Our aim, in this study, was to investigate any detrimental effect of TXA on chondrocytes, and to establish if there was a safe dose for its use in clinical practice. The hypothesis was that TXA would cause a dose-dependent damage to human articular cartilage.

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

To evaluate the effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D and a long bone fracture.

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.

The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders with clinical manifestations relevant to the orthopaedic surgeon. Our aim was to review the recent advances in their management and the implications for surgical practice.

The current literature about MPSs is summarised, emphasising orthopaedic complications and their management.

Recent advances in the diagnosis and management of MPSs include the recognition of slowly progressive, late presenting subtypes, developments in life-prolonging systemic treatment and potentially new indications for surgical treatment. The outcomes of surgery in these patients are not yet validated and some procedures have a high rate of complications which differ from those in patients who do not have a MPS.

The diagnosis of a MPS should be considered in adolescents or young adults with a previously unrecognised dysplasia of the hip. Surgeons treating patients with a MPS should report their experience and studies should include the assessment of function and quality of life to guide treatment.

Cite this article: Bone Joint J 2017;99-B:1132–9

Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging.

The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation.

The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity.

This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties.

Take home message: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications.

Cite this article: Bone Joint J 2016;98-B:6–13.

Aims

The purpose of this study was to investigate the prevalence of sarcopenia and to examine its impact on patients with degenerative lumbar spinal stenosis (DLSS).

Hypovitaminosis D has been identified as a common risk factor for fragility fractures and poor fracture healing. Epidemiological data on vitamin D deficiency have been gathered in various populations, but the association between vertebral fragility fractures and hypovitaminosis D, especially in males, remains unclear. The purpose of this study was to evaluate serum levels of 25-hydroxyvitamin D (25-OH D) in patients presenting with vertebral fragility fractures and to determine whether patients with a vertebral fracture were at greater risk of hypovitaminosis D than a control population. Furthermore, we studied the seasonal variations in the serum vitamin D levels of tested patients in order to clarify the relationship between other known risk factors for osteoporosis and vitamin D levels. We measured the serum 25-OH D levels of 246 patients admitted with vertebral fractures (105 men, 141 female, mean age 69 years, sd 8.5), and in 392 orthopaedic patients with back pain and no fractures (219 men, 173 female, mean age 63 years, sd 11) to evaluate the prevalence of vitamin D insufficiency. Statistical analysis found a significant difference in vitamin D levels between patients with vertebral fragility fracture and the control group (p = 0.036). In addition, there was a significant main effect of the tested variables: obesity (p < 0.001), nicotine abuse (p = 0.002) and diabetes mellitus (p < 0.001). No statistical difference was found between vitamin D levels and gender (p = 0.34). Vitamin D insufficiency was shown to be a risk factor for vertebral fragility fractures in both men and women.

Cite this article: Bone Joint J 2015;97-B:89–93.

Corticosteroid use has been implicated in the development of osteonecrosis of the femoral head (ONFH). The exact mechanism and predisposing factors such as age, gender, dosage, type and combination of steroid treatment remain controversial. Between March and July 2003, a total of 539 patients with severe acute respiratory syndrome (SARS) were treated with five different types of steroid. There were 129 men (24%) and 410 women (76%) with a mean age of 33.7 years (21 to 59). Routine screening was undertaken with radiographs, MRI and/or CT to determine the incidence of ONFH.

Of the 129 male patients with SARS, 51 (39.5%) were diagnosed as suffering from ONFH, compared with only 79 of 410 female patients (19.3%). The incidence of ONFH in the patients aged between 20 and 49 years was much higher than that of the group aged between 50 and 59 years (25.9% (127 of 491) versus 6.3% (3 of 48); p = 0.018). The incidence of ONFH in patients receiving one type of steroid was 12.5% (21 of 168), which was much lower than patients receiving two different types (28.6%; 96 of 336) or three different types of steroid (37.1%; 13 of 35).

Cite this article: Bone Joint J 2014;96-B:259–62.

Periprosthetic joint infection (PJI) is a devastating complication for patients and results in greatly increased costs of care for both healthcare providers and patients. More than 15 500 revision hip and knee procedures were recorded in England, Wales and Northern Ireland in 2013, with infection accounting for 13% of revision hip and 23% of revision knee procedures.

We report our experience of using antibiotic eluting absorbable calcium sulphate beads in 15 patients (eight men and seven women with a mean age of 64.8 years; 41 to 83) as part of a treatment protocol for PJI in revision arthroplasty.

The mean follow-up was 16 months (12 to 22). We report the outcomes and complications, highlighting the risk of hypercalcaemia which occurred in three patients.

We recommend that serum levels of calcium be routinely sought following the implantation of absorbable calcium sulphate beads in orthopaedic surgery.

Cite this article: Bone Joint J 2015;97-B:1237–41.

This study evaluated whether obese patients who lost weight before their total joint replacement and kept it off post-operatively were at lower risk of surgical site infection (SSI) and re-admission compared with those who remained the same weight.

We reviewed 444 patients who underwent a total hip replacement and 937 with a total knee replacement who lost weight pre-operatively and sustained their weight loss after surgery. After adjustments, patients who lost weight before a total hip replacement and kept it off post-operatively had a 3.77 (95% confidence interval (CI) 1.59 to 8.95) greater likelihood of deep SSIs and those who lost weight before a total knee replacement had a 1.63 (95% CI 1.16 to 2.28) greater likelihood of re-admission compared with the reference group.

These findings raise questions about the safety of weight management before total replacement of the hip and knee joints.

Cite this article: Bone Joint J 2014;96-B:629–35.

Wrist block has been used to provide pain relief for many procedures on the hand and wrist but its role in arthroscopy of the wrist remains unexplored. Chondrotoxicity has been a concern with the intra-articular infiltration of local anaesthetic. We aimed to evaluate and compare the analgesic effect of portal and wrist joint infiltration with a wrist block on the pain experienced by patients after arthroscopy of the wrist.

A prospective, randomised, double-blind trial was designed and patients undergoing arthroscopy of the wrist under general anaesthesia as a day case were recruited for the study. Levo-bupivacaine was used for both techniques. The effects were evaluated using a ten-point visual analogue scale, and the use of analgesic agents was also compared. The primary outcomes for statistical analyses were the mean pain scores and the use of analgesia post-operatively.

A total of 34 patients (63% females) were recruited to the portal and joint infiltration group and 32 patients (59% males) to the wrist block group. Mean age was 40.8 years in the first group and 39.7 years in the second group (p > 0.05). Both techniques provided effective pain relief in the first hour and 24 hours post-operatively but wrist block gave better pain scores at bedtime on the day of surgery (p = 0.007) and at 24 hours post-operatively (p = 0.006).

Wrist block provides better and more reliable analgesia in patients undergoing arthroscopy of the wrist without exposing patients to the risk of chondrotoxicity.

Cite this article: Bone Joint J 2015;97-B:1250–6.

The purpose of this study was to evaluate the expression of acid-sensing ion channels (ASICs) in the capsule and synovial fluid of patients with frozen shoulder. Capsular tissue and synovial fluid were obtained from 18 patients with idiopathic frozen shoulder (FS group) and 18 patients with instability of the shoulder (control group). The expressions of ASIC1, ASIC2, and ASIC3 in the capsule were determined using the reverse transcriptase-polymerase chain reaction, immunoblot analysis, and immunohistochemistry (IHC). The concentrations in synovial fluid were evaluated using an enzyme-linked immunosorbent assay.

The mRNA expression of ASIC1, ASIC2 and ASIC3 in the capsule were significantly increased in the FS group compared with the control group. The protein levels of these three ASICs were also increased. The increased expressions were confirmed by IHC. Of the ASICs, ASIC3 showed the greatest increase in both mRNA and levels of expression compared with the control group. The levels of ASIC1 and ASIC3 in synovial fluid were significantly increased in the FS group.

This study suggests that ASICs may play a role as mediators of inflammatory pain and be involved in the pathogenesis of frozen shoulder.

Cite this article: Bone Joint J 2015;97-B:824–9.

MicroRNAs (miRNAs ) are small non-coding RNAs that regulate gene expression. We hypothesised that the functions of certain miRNAs and changes to their patterns of expression may be crucial in the pathogenesis of nonunion. Healing fractures and atrophic nonunions produced by periosteal cauterisation were created in the femora of 94 rats, with 1:1 group allocation. At post-fracture days three, seven, ten, 14, 21 and 28, miRNAs were extracted from the newly generated tissue at the fracture site. Microarray and real-time polymerase chain reaction (PCR) analyses of day 14 samples revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p, were highly upregulated in nonunion. Real-time PCR analysis further revealed that, in nonunion, the expression levels of all five of these miRNAs peaked on day 14 and declined thereafter.

Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p may play an important role in the development of nonunion. These findings add to the understanding of the molecular mechanism for nonunion formation and may lead to the development of novel therapeutic strategies for its treatment.

Cite this article: Bone Joint J 2015; 97-B:1144–51.

This in vivo controlled laboratory study was performed to evaluate various intra-articular clinical injection regimes that might be less toxic than some in vitro studies suggest. We hypothesised that low-concentration, preservative-free, pH-balanced agents would be less toxic than high-concentration non-pH-balanced agents with preservatives, and that injections of individual agents are less toxic than combined injections. The left knees of 12- to 13-week-old Sprague–Dawley rats were injected once with eight different single agents, including low and high concentrations of ropivacaine and triamcinolone, alone and in combination, as well as negative and positive controls. The rats were killed at one week or five months, and live–dead staining was performed to quantify the death of chondrocytes. All injections except pH-balanced 0.2% ropivacaine combined with preservative-free 1 mg/ml triamcinolone acetonide resulted in statistically significant decreases in chondrocyte viability, compared with control knees, after one week and five months (p < 0.001). After one week there was no significant difference in viability between 0.2% and 0.5% ropivacaine; however, 4 mg/ml triamcinolone resulted in a lower viability than 1 mg/ml triamcinolone.

Although many agents commonly injected into joints are chondrotoxic, in this in vivo study diluting preservative-free 10 mg/ml triamcinolone 1:9 in 0.2% pH-balanced ropivacaine resulted in low toxicity.

Cite this article: Bone Joint J 2015; 97-B:933–8.

We measured the plasma 25-hydroxyvitamin D₃ (25(OH)D₃) levels in 62 consecutive Caucasian patients undergoing total hip replacement for osteoarthritis. The patients were divided into two groups based on whether they were vitamin D sufficient or deficient. The groups were matched for age, gender and the American Society of Anaesthesiologists (ASA) grade. The prevalence of vitamin D deficiency in our patients was comparable with recent population-based studies performed in the United Kingdom. Patients with vitamin D deficiency had lower pre-operative Harris hip scores (Mann-Whitney test, p = 0.018) and were significantly less likely to attain an excellent outcome from total hip replacement (chi-squared test, p = 0.038). Vitamin D levels were found to positively correlate with both pre- and post-operative Harris hip scores.

These results warrant further study of vitamin D deficiency in patients undergoing joint replacement as it is a risk factor for a suboptimal outcome which is relatively simple and cheap to correct.

Drug therapy forms an integral part of the management of many orthopaedic conditions. However, many medicines can produce serious adverse reactions if prescribed inappropriately, either alone or in combination with other drugs. Often these hazards are not appreciated. In response to this, the European Union recently issued legislation regarding safety measures which member states must adopt to minimise the risk of errors of medication.

In March 2014 the Medicines and Healthcare products Regulatory Agency and NHS England released a Patient Safety Alert initiative focussed on errors of medication. There have been similar initiatives in the United States under the auspices of The National Coordinating Council for Medication Error and The Joint Commission on the Accreditation of Healthcare Organizations. These initiatives have highlighted the importance of informing and educating clinicians.

Here, we discuss common drug interactions and contra-indications in orthopaedic practice. This is germane to safe and effective clinical care.

Cite this article: Bone Joint J 2015;97-B:434–41.

Treatment strategies for osteoarthritis most commonly involve the removal or replacement of damaged joint tissue. Relatively few treatments attempt to arrest, slow down or reverse the disease process. Such options include peri-articular osteotomy around the hip or knee, and treatment of femoro-acetabular impingement, where early intervention may potentially alter the natural history of the disease. A relatively small proportion of patients with osteoarthritis have a clear predisposing factor that is both suitable for modification and who present early enough for intervention to be deemed worthwhile. This paper reviews recent advances in our understanding of the pathology, imaging and progression of early osteoarthritis.

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.

Total knee replacement (TKR) is an effective method of treating end-stage arthritis of the knee. It is not, however, a procedure without risk due to a number of factors, one of which is diabetes mellitus. The purpose of this study was to estimate the general prevalence of diabetes in patients about to undergo primary TKR and to determine whether diabetes mellitus adversely affects the outcome. We conducted a systematic review and meta-analysis according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The Odds Ratio (OR) and mean difference (MD) were used to represent the estimate of risk of a specific outcome. Our results showed the prevalence of diabetes mellitus among patients undergoing TKR was 12.2%. Patients with diabetes mellitus had an increased risk of deep infection (OR = 1.61, 95% confidence interval (CI), 1.38 to 1.88), deep vein thrombosis (in Asia, OR = 2.57, 95% CI, 1.58 to 4.20), periprosthetic fracture (OR = 1.89, 95% CI, 1.04 to 3.45), aseptic loosening (OR = 9.36, 95% CI, 4.63 to 18.90), and a poorer Knee Society function subscore (MD = -5.86, 95% CI, -10.27 to -1.46). Surgeons should advise patients specifically about these increased risks when obtaining informed consent and be meticulous about their peri-operative care.

Cite this article: Bone Joint J 2014;96-B:1637–43.

Total knee arthroplasty (TKA) is known to lead to a reduction in periprosthetic bone mineral density (BMD). In theory, this may lead to migration, instability and aseptic loosening of the prosthetic components. Bisphosphonates inhibit bone resorption and may reduce this loss in BMD. We hypothesised that treatment with bisphosphonates and calcium would lead to improved BMD and clinical outcomes compared with treatment with calcium supplementation alone following TKA. A total of 26 patients, (nine male and 17 female, mean age 67 years) were prospectively randomised into two study groups: alendronate and calcium (bisphosphonate group, n = 14) or calcium only (control group, n = 12). Dual energy X-ray absorptiometry (DEXA) measurements were performed post-operatively, and at three months, six months, one, two, four, and seven years post-operatively.

Mean femoral metaphyseal BMD was significantly higher in the bisphosphonate group compared with controls, up to four years following surgery in some areas of the femur (p = 0.045). BMD was observed to increase in the lateral tibial metaphysis in the bisphosphonate group until seven years (p = 0.002), and was significantly higher than that observed in the control group throughout (p = 0.024). There were no significant differences between the groups in the central femoral metaphyseal, tibial medial metaphyseal or diaphyseal regions of interest (ROI) of either the femur or tibia.

Bisphosphonate treatment after TKA may be of benefit for patients with poor bone quality. However, further studies with a larger number of patients are necessary to assess whether this is clinically beneficial.

Cite this article: Bone Joint J 2015;97-B:337–45.

We compared the clinical and radiographic results of total ankle replacement (TAR) performed in non-diabetic and diabetic patients. We identified 173 patients who underwent unilateral TAR between 2004 and 2011 with a minimum of two years’ follow-up. There were 88 male (50.9%) and 85 female (49.1%) patients with a mean age of 66 years (sd 7.9, 43 to 84). There were 43 diabetic patients, including 25 with controlled diabetes and 18 with uncontrolled diabetes, and 130 non-diabetic patients. The clinical data which were analysed included the Ankle Osteoarthritis Scale (AOS) and the American Orthopaedic Foot and Ankle Society (AOFAS) scores, as well the incidence of peri-operative complications.

The mean AOS and AOFAS scores were significantly better in the non-diabetic group (p = 0.018 and p = 0.038, respectively). In all, nine TARs (21%) in the diabetic group had clinical failure at a mean follow-up of five years (24 to 109), which was significantly higher than the rate of failure of 15 (11.6%) in the non-diabetic group (p = 0.004). The uncontrolled diabetic subgroup had a significantly poorer outcome than the non-diabetic group (p = 0.02), and a higher rate of delayed wound healing.

The incidence of early-onset osteolysis was higher in the diabetic group than in the non-diabetic group (p = 0.02). These results suggest that diabetes mellitus, especially with poor glycaemic control, negatively affects the short- to mid-term outcome after TAR.

Cite this article: Bone Joint J 2014;96-B:1674–80.

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.

Patients with osteoarthritis undergoing knee replacement have been reported to have an overall reduced mortality compared with that of the general population. This has been attributed to the selection of healthier patients for surgery. However, previous studies have had a maximum follow-up time of ten years. We have used information from the Swedish Knee Arthroplasty Register to study the mortality of a large national series of patients with total knee replacement for up to 28 years after surgery and compared their mortality with that of the normal population. In addition, for a subgroup of patients operated on between 1980 and 2002 we analysed their registered causes of death to determine if they differed from those expected.

We found a reduced overall mortality during the first 12 post-operative years after which it increased and became significantly higher than that of the general population. Age-specific analysis indicated an inverse correlation between age and mortality, where the younger the patients were, the higher their mortality. The shift at 12 years was caused by a relative over-representation of younger patients with a longer follow-up. Analysis of specific causes of death showed a higher mortality for cardiovascular, gastrointestinal and urogenital diseases. The observation that early onset of osteoarthritis of the knee which has been treated by total knee replacement is linked to an increased mortality should be a reason for increased general awareness of health problems in these patients.

We randomised 120 patients who were undergoing either primary total hip or knee arthroplasty to receive either ferrous sulphate or a placebo for three weeks after surgery. The level of haemoglobin and absolute reticulocyte count were measured at one and five days, and three and six weeks after operation. Ninety-nine patients (ferrous sulphate 50, placebo 49) completed the study. The two groups differed only in the treatment administered.

Recovery of level of haemoglobin was similar at five days and three weeks and returned to 85% of the pre-operative level, irrespective of the treatment group. A small, albeit greater recovery in the level of haemoglobin was identified at six weeks in the ferrous sulphate group in both men (ferrous sulphate 5%, placebo 1.5%) and women (ferrous sulphate 6%, placebo 3%). The clinical significance of this is questionable and may be outweighed by the high incidence of reported side effects of oral iron and the cost of the medication. Administration of iron supplements after elective total hip or total knee arthroplasty does not appear to be worthwhile.

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 pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries.

This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors.

We matched 78 patients with a loose cemented Charnley Elite Plus total hip replacement (THR) by age, gender, race, prosthesis and time from surgery with 49 patients with a well-fixed stable hip replacement, to determine if poor bone quality predisposes to loosening. Clinical, radiological, biomechanical and bone mineral density indicators of bone quality were assessed.

Patients with loose replacements had more pain, were more likely to have presented with atrophic arthritis and to have a history of fragility fracture, narrower femoral cortices and lower peri-prosthetic or lumbar spine bone mineral density (all t-test, p < 0.01). They also tended to be smokers (chi-squared test, p = 0.08). Vitamin-D deficiency was common, but not significantly different between the two groups (t-test, p = 0.31)

In this series of cemented hip replacements performed between 1994 and 1998, aseptic loosening was associated with poor bone quality. Patients with a THR should be screened for osteoporosis and have regular radiological surveillance.

Narrowing of the femoral neck after resurfacing arthroplasty of the hip has been described previously in both cemented and uncemented hip resurfacing. The natural history of narrowing of the femoral neck is unknown. We retrospectively measured the diameter of the femoral neck in a series of 163 Birmingham hip resurfacings in 163 patients up to a maximum of six years after operation to determine the extent and progression of narrowing.

There were 105 men and 58 women with a mean age of 52 years (18 to 82). At a mean follow-up of five years, the mean Harris hip score was 94.8 (47 to 100) and the mean flexion of the hip 112.5° (80° to 160°). There was some narrowing of the femoral neck in 77% (125) of the patients reviewed, and in 27.6% (45) the narrowing exceeded 10% of the diameter of the neck. A multiple logistic regression analysis showed a significant association (chi-squared test (derived from logistic regression) p = 0.01) of narrowing with female gender and a valgus femoral neck/shaft angle. There was no significant association between the range of movement, position or size of the component or radiological lucent lines and narrowing of the neck (chi-squared test; p = 0.10 (flexion), p = 0.08 (size of femoral component), p = 0.09 (size of acetabular component), p = 0.71 (femoral component angulation), p = 0.99 (lucent lines)). There was no significant difference between the diameter of the neck at a mean of three years (2.5 to 3.5) and that at five years (4.5 to 5.5), indicating that any change in the diameter of the neck had stabilised by three years (sign rank test, p = 0.60).

We conclude that narrowing of the femoral neck which is found with the Birmingham hip resurfacing arthroplasty is in most cases associated with no adverse clinical or radiological outcome up to a maximum of six years after the initial operation.

Low bone mass and osteopenia have been described in the axial and peripheral skeleton of patients with adolescent idiopathic scoliosis (AIS). Recently, many studies have shown that gene polymorphism is related to osteoporosis. However, no studies have linked the association between IL6 gene polymorphism and bone mass in AIS. This study examined the association between bone mass and IL6 gene polymorphism in 198 girls with AIS. The polymorphisms of IL6-597 G→A, IL6-572 G→C and IL6-174 G→A and the bone mineral density in the lumbar spine and femoral neck were analysed and compared with their levels in healthy controls. The mean bone mineral density at both sites in patients with AIS was decreased compared with controls (p = 0.0022 and p = 0.0013, respectively). Comparison of genotype frequencies between AIS and healthy controls revealed a statistically significant difference in IL6-572 G→C polymorphism (p = 0.0305). There was a significant association between the IL6-572 G→C polymorphism and bone mineral density in the lumbar spine, with the CC genotype significantly higher with the GC (p = 0.0124) or GG (p = 0.0066) genotypes.

These results suggest that the IL6-572 G→C polymorphism is associated with bone mineral density in the lumbar spine in Korean girls with AIS.

Avascular necrosis (AVN) is a serious complication of high-dose chemotherapy for haematological malignancy in childhood. In order to describe its incidence and main risk factors and to evaluate the current treatment options, we reviewed 105 children with a mean age of 8.25 years (1 to 17.8) who had acute lymphoblastic or acute myeloid leukaemia, or a non-Hodgkin’s lymphoma. Overall, eight children (7.6%) developed AVN after a mean of 16.8 months (8 to 49). There were four boys and four girls with a mean age of 14.4 years (9.8 to 16.8) and a total of 18 involved sites, 12 of which were in the femoral head. All these children were aged > nine years (p < 0.001). All had received steroid treatment with a mean cumulative dose of prednisone of 5967 mg (4425 to 9599) compared with a mean of 3943 mg (0 to 18 585) for patients without AVN (p = 0.005). No difference existed between genders and no thrombophilic disorders were identified. Their initial treatment included 11 core decompressions and two bipolar hip replacements. Later, two salvage osteotomies were done and three patients (four hips) eventually needed a total joint replacement. We conclude that AVN mostly affects the weight-bearing epiphyses. Its risk increases with age and higher steroid doses. These high-risk patients may benefit from early screening for AVN.

Cite this article: Bone Joint J 2013;95-B:1708–13.

Avascular necrosis of the femoral head creates considerable morbidity in successful renal transplant recipients who are generally young and expect active lifestyles. Total hip replacement is considered the treatment of choice in these patients, but surgeons may be wary because of a supposed increase in the risk of infection and other complications.

A review of the literature reveals that cemented hip arthroplasty provides good to excellent functional outcomes for renal transplant patients. Most authors have found that the risk of infection is not increased despite chronic immunosuppression, but the rates of general complications are and should be anticipated and treated. There is a high rate of early failure in these patients because of their young age and diffuse osteopenia as a result of secondary hyperparathyroidism related to the underlying renal disease and chronic steroid use. Recent studies have found that despite decreased bone stock in these patients, porous-coated prostheses are not contraindicated.

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.

We used interconnected porous calcium hydroxyapatite ceramic to bridge a rabbit ulnar defect. Two weeks after inducing the defect we percutaneously injected rabbit bone marrow-derived mesenchymal stromal cells labelled with ferumoxide. The contribution of an external magnetic targeting system to attract these cells into the ceramic and their effect on subsequent bone formation were evaluated.

This technique significantly facilitated the infiltration of ferumoxide-labelled cells into ceramic and significantly contributed to the enhancement of bone formation even in the chronic phase. As such, it is potentially of clinical use to treat fractures, bone defects, delayed union and nonunion.