The total plasma alkaline phosphatase level has long been recognised as an indicator of osteoblastic activity, but lack of specificity makes it an insensitive index of the progress of disease and the response to treatment. Selective precipitation by wheatgerm lectin allows measurement of the plasma bone-specific alkaline phosphatase. We measured the plasma levels of this isoenzyme in 170 normal Chinese adolescents and adults, in 49 adults with fractures of a long bone, in 15 patients with osteosarcoma and in 38 patients with osteolytic metastases. The enzyme activity was also determined in 39 patients with liver disease. Of the patients with fractures, 94% had increased plasma activity during the healing process. The level was also increased in those with osteosarcoma but not in those with osteolytic bone metastases. There was no significant increase in activity in the patients with liver disease. We conclude that the plasma bone-specific alkaline phosphatase activity is a sensitive and reliable measure of osteoblastic activity

Experimentally produced fractures in long bones studied by light and electron microscopic histochemistry were found to heal by a process of enchondral calcification. There was intense proliferation in the cells of the cambium layer of the periosteum, with differentiation to chondroblasts and osteoblasts, suggesting that this layer was the primary tissue responsible for development of the callus. Cytoplasmic processes of the hypertrophic chondrocytes appeared to bud and produce matrix vesicles. Alkaline phosphatase activity was detected along the plasma membrane of the hypertrophic chondrocytes and around the matrix vesicles, before any signs of mineral deposition. Calcification took place by deposition of hydroxyapatite crystals in and around these matrix vesicles which frequently showed alkaline phosphatase activity. It is suggested that there is a close functional association between alkaline phosphatase activity and calcification in the process of fracture healing, which is another type of enchondral calcification mediated by matrix vesicles

Osteomalacia may be a contributory factor in some patients in the development of fractures of the femoral neck and complicate the subsequent management. The level of serum alkaline phosphatase is often valuable in the diagnosis of metabolic bone disease but rises after any uncomplicated fracture, and since such a rise may limit the diagnostic usefulness of this measurement in detecting osteomalacia its extent was assessed in 106 patients. In the majority serum levels were normal on admission, rising after seven to nine days to reach a maximum within a month after fracture. Elevated levels on admission were found in patients with osteomalacia, liver damage or where there had been a delay of several weeks between injury and admission. In a small number of patients normal levels on admission subsequently reached very high values, usually in association with comminution or instability of the fracture. Elevated levels persisted for six to twelve weeks after fracture, the major influence upon the level at this time being the maximum value achieved rather than the presence of osteomalacia. If patients are to be screened for osteomalacia, the alkaline phosphatase must be measured within the first week after a fracture to avoid the distorting influences of the fracture itself

Estimations of serum alkaline phosphatase were carried out prospectively on a series of patients having a total hip replacement. The levels of serum alkaline phosphatase before operation indicated a group of patients who subsequently developed heterotopic ossification. Levels of this enzyme after operation did not indicate those patients who were developing heterotopic ossification

The acid and alkaline phosphatase activity in fluid aspirated from solitary bone cysts in six patients was measured, and large increases in the concentration of acid phosphatase were found. In some cases this increase was reflected in venous blood concentrations. The significance of these findings for the pathogenesis and the management of solitary bone cyst is discussed

Aims. The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS). Methods. We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS. Results. Patients with multiple LCH involving the spine accounted for 15.4% (28/182 cases) of all cases of spinal LCH: their lesions primarily involved the thoracic and lumbar spines. The most common symptom was pain, followed by neurological dysfunction. All patients presented with osteolytic bone destruction, and 23 cases were accompanied by a paravertebral soft-tissue mass. The incidence of vertebra plana was low, whereas the oversleeve-like sign was a more common finding. The alkaline phosphatase was significantly higher in patients with single-system multifocal bone LCH than in patients with multisystem LCH. At final follow-up, one patient had been lost to follow-up, two patients had died, three patients had local recurrence, six patients had distant involvement, and 17 patients were alive with disease. The median PFS and OS were 50.5 months (interquartile range (IQR) 23.5 to 63.1) and 60.5 months (IQR 38.0 to 73.3), respectively. Stage (hazard ratio (HR) 4.324; p < 0.001) and chemotherapy (HR 0.203; p < 0.001) were prognostic factors for PFS. Conclusion. Pain is primarily due to segmental instability of the spine from its destruction by LCH. Chemotherapy can significantly improve PFS, and radiotherapy has achieved good results in local control. The LCH lesions in some patients will continue to progress. It may initially appear as an isolated or single-system LCH, but will gradually involve multiple sites or systems. Therefore, long-term follow-up and timely intervention are important for patients with spinal LCH. Cite this article: Bone Joint J 2023;105-B(6):679–687

We examined cultured osteoblasts derived from paired samples from the greater tuberosity and acromion from eight patients with large chronic tears of the rotator cuff. We found that osteoblasts from the tuberosity had no apparent response to mechanical stimulation, whereas those derived from the acromion showed an increase in alkaline phosphatase activity and nitric oxide release which is normally a response of bone cells to mechanical strain. By contrast, we found that cells from both regions were able to respond to dexamethasone, a well-established promoter of osteoblastic differentiation, with the expected increase in alkaline phosphatase activity. Our findings indicate that the failure of repair of the rotator cuff may be due, at least in part, to a compromised capacity for mechanoadaptation within the greater tuberosity. It remains to be seen whether this apparent decrease in the sensitivity of bone cells to mechanical stimulation is the specific consequence of the reduced load-bearing history of the greater tuberosity in these patients

1. A quantitative study of phosphatase distribution in the limb bones of growing rabbits is reported. 2. Alkaline phosphatase is present in high concentrations in areas of deposition of new bone. Both local concentrations and the total alkaline phosphatase content of a bone are found to decrease with age. There is good correlation between total alkaline phosphatase activity and monthly increment of weight. 3. Acid phosphatase is present in these bones in greatly less concentrations than alkaline phosphatase. 4. The acid phosphatase of bone shows nearly full activity in the presence of 0·5 per cent formaldehyde. It can be subdivided into two enzymes with characteristically different distributions by the effect of M/100 tartrate on activity. 5. The formaldehyde-stable and tartrate-stable acid phosphatase of rabbit bone (FTS) has a distribution very similar to that of alkaline phosphatase, though very much less in amount, and, like the latter, declines in activity as the bone matures. 6. Tartrate-inhibited, formaldehyde-stable acid phosphatase (FSTI) is found mainly in red marrow and cancellous bone, and full activity persists in mature bone. This enzyme may be associated with resorption and remodelling of bone, or it may represent residual activity under these conditions of the acid phosphatase of developing erythrocytes in the marrow

1. Alkaline and acid phosphatase, non-specific esterase and beta-glucuronidase have been estimated and demonstrated histochemically in a series of bone tumours and allied lesions, of which ten were osteogenic sarcomata, ten were giant-cell lesions, eleven were fibroblastic lesions and seven were tumours of cartilage. 2. Osteogenic sarcoma was found to be characterised by high levels of alkaline phosphatase, with rich staining for this enzyme in the tumour cells. Similar high levels of alkaline phosphatase were found in other bone-forming lesions, such as fibrous dysplasia, a giant-cell sarcoma with osteogenic matrix, and fracture callus. 3. Giant-cell lesions were characterised by high levels of acid phosphatase, and intense staining for this enzyme in the osteoclasts. These cells were also found to be rich in non-specific esterase (as shown by the alpha-naphthyl acetate method) and in beta-glucuronidase, but almost or entirely lacking in alkaline phosphatase. High levels of alkaline phosphatase were not found in giant-cell lesions except in relation to osteogenic matrix. 4. Fibroblastic tumours were characterised by moderate levels of all four enzymes, with little or no staining for phosphatases in the tumour cells; non-specific esterase was generally present in a proportion of the cells. 5. In certain lesions intermediate stages in the differentiation of fibroblasts to osteoblasts were found, notably in fibrous dysplasia, in which the biochemical change preceded the histological. In such lesions high total levels of alkaline phosphatase were found. 6. Cartilaginous tumours were characterised by low levels of all four enzymes, and little histochemical staining except in hypertrophied cells in areas of ossification. 7. It was found in general that the enzyme distributions in these neoplasms and other lesions reflected the findings in comparable reactive and growing normal tissues

Aims. The purpose of this study was to identify prognostic indicators of outcome at presentation to the orthopaedic surgeon, in patients with metastatic prostate cancer. Our aim was to use this information in a pragmatic, clinic-based approach so that surgical decision making could be optimized to benefit the patient in their remaining lifetime. Patients and Methods. A cohort analysis was undertaken of all patients with metastatic disease of the prostate who presented to a regional orthopaedic centre in the United Kingdom between 2003 and 2016. Biochemical data were collected in addition to disease and demographic data. These included: prostate-specific antigen (PSA) at orthopaedic presentation; haemoglobin (Hb); platelets (plt); alkaline phosphatase (ALP); albumin (Alb); and corrected calcium (CaC). Statistical analysis included Kaplan–Meier survival analysis, and a Cox proportional hazards model was fitted to the data. Results. From the departmental database, 137 episodes were identified in 136 patients with a median age at presentation of 72 years (interquartile range (IQR) 66 to 78). Most patients had stage IV disease (n = 98, 72%), and most did not undergo surgical intervention. At one-year follow-up, 50% of patients had died. Biomarkers found to be independently associated with poor survival were: low Hb, low Alb, relatively low PSA (< 30 mmol/l), and a raised ALP. Patients who needed surgical intervention had a poorer survival rate than patients who were managed nonoperatively. Conclusion. The study findings are important for orthopaedic clinical practice in the management of patients with metastatic prostate cancer. The interpretation of routine blood tests can help to predict survival in patients who present with orthopaedic manifestations of prostate cancer. A lower PSA is not necessarily a good prognostic sign. We believe that simple blood testing should be carried out routinely when assessing a patient, guiding potential surgical management and palliative care in the future

1. Histochemical studies have been made of the distribution of alkaline phosphatase, glycogen and acid mucopolysaccharides in normal growing bones (mice, rats and men) and also in forty cases of pathological bone processes (neoplastic and dystrophic). 2. The study of normal material confirmed that alkaline phosphatase is plentiful in calcification of cartilage and even more plentiful in bone formation (whether enchondral or direct). 3. It was observed that glycogen increased in the cartilage areas about to be calcified, and that it disappeared in those calcified. It seemed that osteoblasts did not always contain glycogen. 4. In the pathological material (tumours and dystrophic processes) there was great phosphatase activity in the osteogenic areas and also in the cartilage about to be calcified. Whereas glycogen was plentiful in some cases of neoplastic or reactive osteogenesis, it was absent from others. 5. In every area of normal or pathological ossification, the presence of phosphatase seems to be a rule; glycogen is often but not always present. 6. It appears that alkaline phosphatase plays an important role in the formation of the protein matrix of bone, but is not associated with the elaboration of the mucoprotein cartilage matrix. We believe it is premature to draw any definite conclusion on the behaviour and role of the metachromatic substances in the processes of calcification and ossification. The histochemical study of alkaline phosphatase has shown that this is a valuable method in the detection of reactionary or pathological osteogenic processes which in some cases are difficult to demonstrate with the usual histological methods

1. Histochemical staining and correlated biochemical estimations of five hydrolytic enzymes were done on eighteen benign and twenty malignant fibroblastic lesions of bone and soft tissue. 2. Alkaline phosphatase activity was moderate in a fibroma and very high in fibrous dysplasia. In a typical fibrosarcoma the fibroblasts showed no enzyme activity and estimations were low. Exceptions indicated an osteogenic potential in the tumour. 3. ß-glucuronidase, leucine aminopeptidase, and to a less extent non-specific esterase, were more active in malignant than in benign lesions, and the highest activities were found in sarcomata arising in Paget's disease of bone. 4. Acid phosphatase showed no correlation with malignancy and was generally unremarkable except for high activity in osteoclasts, but was raised in two sarcomata that occurred after irradiation of giant-cell tumours. 5. A non-osteogenic fibroma and a fibrous cortical defect, though poorly represented in this series, are not uncommon; they sometimes lead to pathological fracture, but sarcoma is very rare in such lesions. They tend to show more alkaline phosphatase than fibrosarcoma but not the very high activity of fibrous dysplasia, which is related to its osteogenic potential. 6. Fibrous dysplasia most often presents in the five to fifteen age group but seldom leads to malignancy, though this may occur, usually as osteosarcoma, which has a similar high content of alkaline phosphatase. Fibrosarcoma is typically negative or very weak in this enzyme: the exceptional cases with high activity were tumours which were in part osteosarcoma. Generally the demonstration of high alkaline phosphatase activity in a fibroblastic lesion of bone, in the absence of trauma or inflammation, suggests the diagnosis of fibrous dysplasia

In an attempt to increase the life of cementless prostheses, an hydroxyapatite-coated implant which releases a bisphosphonate has been suggested as a drug-delivery system. Our in vitro study was designed to determine the maximum dose to which osteoblasts could be safely exposed. Our findings demonstrated that zoledronate did not impair the proliferation of human osteoblasts when used at concentrations below 1 μ. m. Murine cells can be exposed to concentrations as high as 10 μ. m. . A concentration of 0.01% of titanium particles did not impair the proliferation of either cell line. Zoledronate affected the alkaline phosphatase activity of murine osteoblasts through a chelation phenomenon. The presence of titanium particles strongly decreased the alkaline phosphatase activity of murine osteoblasts. We did not detect any synergic effect of zoledronate and titanium particles on the behaviour of both human and murine osteoblasts

The alkaline phosphatase activity of pre-osseous tibial cartilage of rachitic bone stored in the deep freeze for two weeks at -25 degrees centigrade was only slightly less than that of fresh controls from the same animals. The deep frozen pre-osseous tissue did not calcify in in vitro calcifying media containing either inorganic phosphorus or organic phosphate ester. The fresh controls calcified equally well in both media. In addition, after deep-freeze storage the tissue hydrolysed the organic phosphate to the same degree as did the fresh tissue. Bones heated at 65 degrees centigrade will calcify in vitro after calcium chloride treatment despite the destruction of phosphatase activity. It appears unlikely that a relationship exists between alkaline phosphatase and the minimal system required for calcification of pre-osseous cartilage in vitro. These findings do not exclude the possibility that alkaline phosphatase plays some critical role in vivo

We have investigated whether cells derived from haemarthrosis caused by injury to the anterior cruciate ligament could differentiate into the osteoblast lineage in vitro. Haemarthroses associated with anterior cruciate ligament injuries were aspirated and cultured. After treatment with β-glycerophosphate, ascorbic acid and dexamethasone or 1,25 (OH). 2. D. 3. , a significant increase in the activity of alkaline phosphatase was observed. Matrix mineralisation was demonstrated after 28 days and mRNA levels in osteoblast-related genes were enhanced. Our results suggest that the haemarthrosis induced by injury to the anterior cruciate ligament contains osteoprogenitor cells and is a potential alternative source for cell-based treatment in such injury

The aim of our study was to investigate the effect of platelet-rich plasma on the proliferation and differentiation of rat bone-marrow cells and to determine an optimal platelet concentration in plasma for osseous tissue engineering. Rat bone-marrow cells embedded in different concentrations of platelet-rich plasma gel were cultured for six days. Their potential for proliferation and osteogenic differentiation was analysed. Using a rat limb-lengthening model, the cultured rat bone-marrow cells with platelet-rich plasma of variable concentrations were transplanted into the distraction gap and the quality of the regenerate bone was evaluated radiologically. Cellular proliferation was enhanced in all the platelet-rich plasma groups in a dose-dependent manner. Although no significant differences in the production and mRNA expression of alkaline phosphatase were detected among these groups, mature bone regenerates were more prevalent in the group with the highest concentration of platelets. Our results indicate that a high platelet concentration in the platelet-rich plasma in combination with osteoblastic cells could accelerate the formation of new bone during limb-lengthening procedures

Systemic factors are believed to be pivotal for the development of heterotopic ossification in severely-injured patients. In this study, cell cultures of putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum from 12 healthy control subjects. The serum from the polytraumatised patients significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM cells. The activity of alkaline phosphatase in MG-63 and hBM cells was significantly decreased when exposed to the serum of the severely-injured patient. After three weeks in 3D cell cultures, matrix production and osteogenic gene expression of hBM cells were equal in the patient and control groups. However, the serum from the polytraumatised patients significantly decreased apoptosis of hBM cells compared with the control serum (4.3% vs 19.1%, p = 0.031). Increased proliferation of osteoblastic cells and reduced apoptosis of osteoprogenitors may be responsible for increased osteogenesis in severely-injured patients

In this study 201 elderly patients with femoral neck fractures were compared with 30 osteomalacic patients with the same injury. Hypocalcaemia and a raised alkaline phosphatase level are common biochemical abnormalities in elderly patients with femoral neck fractures. In only a minority of patients, however, were they associated with histologically proven osteomalacia. By using the combination of hypocalcaemia and a raised alkaline phosphatase it is possible to identify a subgroup (approximately 10% of all admissions) in whom osteomalacia is relatively likely

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

A study of two siblings with a severe infantile form of familial idiopathic hyperphosphatasia is reported. A girl aged one year was followed for two years while receiving intermittent treatment with porcine calcitonin. This induced a clinical remission, a reduction of both the high serum level of alkaline phosphatase and the raised urinary excretion of hydroxyproline, and a remarkable improvement in bone structure as seen radiologically. Her sister aged two months received porcine calcitonin for three weeks, during which clinical improvement, no change in the serum level of alkaline phosphatase and a marked decrease of the excretion of hydroxyproline were recorded

The haematoma occurring at the site of a fracture is known to play an important role in bone healing. We have recently shown the presence of progenitor cells in human fracture haematoma and demonstrated that they have the capacity for multilineage mesenchymal differentiation. There have been many studies which have shown that low-intensity pulsed ultrasound (LIPUS) stimulates the differentiation of a variety of cells, but none has investigated the effects of LIPUS on cells derived from human fracture tissue including human fracture haematoma-derived progenitor cells (HCs). In this in vitro study, we investigated the effects of LIPUS on the osteogenic activity of HCs. Alkaline phosphatase activity, osteocalcin secretion, the expression of osteoblast-related genes and the mineralisation of HCs were shown to be significantly higher when LIPUS had been applied but without a change in the proliferation of the HCs. These findings provide evidence in favour of the use of LIPUS in the treatment of fractures

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

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

We investigated the effect of calcitonin in the prevention of acute bone loss after a pertrochanteric fracture and its ability to reduce the incidence of further fractures in the same patient. Fifty women aged between 70 and 80 years who had a pertrochanteric fracture of the hip were randomly allocated to group A (200 IU of nasal salmon calcitonin daily for three months) or group B (placebo). Patients in group A showed a significantly higher level of total alkaline phosphatase and osteocalcin on the 15th day after injury and a significantly higher level of bone alkaline phosphatase on the 90th day after surgery. These patients also had significantly lower levels of urinary C-telopeptide (CrossLaps) on the 15th, 45th and 90th days after injury and lower levels of urinary hydroxyproline on the 15th and 45th days after injury. Patients in group A had significantly higher bone mineral density at all recorded sites except the greater trochanter at three months and one year after operation. After a four-year period of clinical observation, five patients (24%) in group B sustained a new fracture, in four of whom (20%) it was of the contralateral hip. Our findings show that calcitonin reduces acute bone loss in patients with pertrochanteric fractures and may prevent the occurrence of new fractures of the contralateral hip in the elderly

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 have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised β-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised β-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches

Hypophosphatasia in adults is rare. Two elderly sisters presenting with pathological fractures of the femur are reported to illustrate the difficulties in orthopaedic management of this disease. All patients with a history of repeated fractures, especially from minor trauma and with generalised radiological bony abnormality, should be screened for this rare disease. A consistently low level of serum alkaline phosphatase with the presence of phosphoethanolamine in the urine is diagnostic

We report four patients with unilateral postpartum sacroiliitis presenting with agonising unilateral pain, an elevated ESR, elevated alkaline phosphatase levels, leucocytosis and positive bone scans. The diagnosis of a non-infectious inflammatory cause was supported by the postpartum onset, the response to non-steroidal anti-inflammatory drugs, negative aspiration cultures in two cases and the lack of changes in the sacroiliac joints on long-term follow-up radiographs

1. A metabolic study in a case of myositis ossificans progressiva is reported. 2. The serum showed an increased power of calcification of rachitic rat cartilage. 3. Estimations of alkaline phosphatase showed slightly raised values. 4. Surgical removal of a bony bar was followed by prolonged administration of ACTH and cortisone, but no effect on the calcium-phosphorus balance or on the re-ossification within the area of operation was observed

1. A report is given of a family suffering from dystrophia myotonica and familial Paget’s disease of bone. 2. Radiological changes in the skull occur in both disorders, which are quite dissimilar. Thickening of the calvarium, however, may be common to both. 3. The serum alkaline phosphatase is high in Paget's disease and normal in dystrophia myotonica. 4. In one patient the Paget's disease was complicated by the development of multiple sarcomata. Sarcomatous involvement of the vertebral column, observed in one of the cases, has not been recorded before

A study of cadaveric vertebral biopsy and a review of 100 clinical biopsies has shown that needles and trephines producing tissue specimens of two millimetres or more in diameter can be expected to give a high degree of diagnostic accuracy. The erythrocyte sedimentation rate was a more useful screening investigation than were estimations of serum alkaline phosphatase. The complications are described. It is suggested that patients with painful thoracic metastases and evidence of progressive cord compression should have early decompression after open biopsy if further neurological compromise is to be prevented

The main findings in this experimental work on rats fed on lathyrus odoratus (sweet-pea) meal are as follows:. 1. Growth is retarded. 2. The growth plate is disorganised and normal ossification at the metaphysis is interfered with. 3. The small blood vessels are seriously affected and probably contribute quite largely to the disorganisation and lack of calcification. 4. Alkaline phosphatase activity is increased. 5. Raising of the periosteum and laying down of new bone result in exostoses. The possible underlying etiology and the role of cement substance, endocrine factors and the blood vessels are discussed

We cultured human osteoblasts from trabecular bone explants and confirmed their phenotype by alkaline phosphatase assay, increased cyclic adenosine monophosphate production in response to prostaglandin E2 and radiographic micro-analysis of nodules of calcification. The osteoblasts were seeded on to demineralised human bone fragments and examined at ten-day intervals over a 50-day period by scanning electron microscopy. During this time the bank bone became progressively repopulated by the cultured osteoblasts. This system may offer a means of graft enhancement in elective orthopaedic and maxillofacial surgery by delivery of cultured autologous human osteoblasts to bone defects

We studied 55 patients with stage-IIB osteosarcoma around the knee with respect to the expression of matrix metalloproteinase (MMP)-9 in the surviving tumour cells in surgical resection specimens. They were followed up for a minimum of 2.5 years. Factors significantly associated with poor overall survival were a high serum level of alkaline phosphatase at diagnosis and tumour cells expressing MMP-9 in the resection specimens. The only factor strongly associated with disease-free survival was the immunohistochemical status of tumour cells for MMP-9 in the resection specimens. The percentage of necrosis after chemotherapy failed marginally to reach statistical significance. On Cox regression analysis only MMP-9 remained significant for overall and disease-free survival

Seven patients with stress fractures of the femoral neck were treated at the Military Hospital of Thessaloniki, Greece between 1972 and 1976. Their average age was 22 years. Stress fractures of the femoral neck are not as common as stress fractures of the metatarsals or tibia and other bones. Intense muscular activity was the main cause of these stress fractures which were only classed as such in the absence of any injury. Pain and stiffness around the hip were reported by all seven patients before admission. Results of laboratory investigations of the patients' alkaline phosphatase and serum calcium levels were normal. One patient received surgical treatment and the other patients were treated conservatively. Healing was uneventful in all

1. A method is described of demonstrating in vivo the utilisation of radioactive sulphur. 35. and of radioactive phosphorus. 32. during bone growth and repair. 2. The relationship between labelled chondroitin sulphuric acid and labelled phosphate complexes has been studied, the importance and significance of vascularity and the localisation of the enzyme alkaline phosphatase being noted. 3. It was found that bone growth by external accretion, both epiphysial and periosteal, was accompanied by an increased utilisation of radioactive chondroitin sulphuric acid and calcium phosphate complexes. 4. During repair in a fracture site, although there was deposition of radioactive phosphate, no preferential localisation of radioactive sulphur was observed and the possible explanations of this are discussed

In vitamin D-fed chicks 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were implanted into experimentally-produced fractures of the mid-tibia. The mechanical and biochemical properties of the tibia were evaluated for two weeks, including torsion tests, measurement of alkaline phosphatase activity, 45Ca incorporation, and Ca2+ content. Both dihydroxylated metabolites of vitamin D3 had a direct effect on endochondral bone formation. 24,25(OH)2D3 strengthened the callus, and raised alkaline phosphate activity in the first seven days after fracture. 1,25(OH)2D3 decreased the strength of the callus concomitant with a reduction in 45Ca incorporation. It is suggested that local application of 24,25(OH)2D3 into fractures may accelerate healing and prevent non-union

1. A type of bony sclerosis is described, occurring in nine members of a Jamaican family and resembling the more benign form of Albers-Schönberg's disease. The parents were consanguineous. Three of the patients developed facial palsy at the same age, and one had bilateral optic atrophy and proptosis. 2. Although radiological changes occurred of all grades of severity, certain features often described in this condition were lacking. In one child the onset of radiological changes was observed at the age of eleven years. 3. Serum studies showed increased alkaline phosphatase activity. 4. These features are discussed in the light of present-day knowledge and theory of the pathology of Albers-Schönberg's disease

We report 40 cases in one family of an autosomal dominant bone dysplasia, which, though similar in some aspects to Paget's disease, seems unique in some features and in its natural history. The disease shows both general and focal skeletal changes, the latter being mainly in the limbs with an onset from the second decade. Progressive osteoclastic resorption is accompanied by medullary expansion which leads to pain, severe deformity and a tendency to pathological fracture. The serum alkaline phosphatase and urinary hydroxyproline are variably elevated, while other biochemical indices are normal. Most patients had an associated deafness of early onset and loss of dentition. No previous description of this disease has been found in the literature

Hyperphosphatasia, or hereditary bone dysplasia with hyperphosphatasaemia, is a rare genetic disorder which is characterised by failure to transform woven into lamellar bone. Clinical, radiological and histological features establish the diagnosis, fractures, deformities, diffuse sclerosis on radiographs and high serum alkaline phosphatase being characteristic. We report the case of a 27-year-old man with follow-up at the same hospital for 20 years. Attempts at treatment with calcitonin and disocium etidronate (EHDP) failed, but stapling of the growth plates at the knee was successfully performed. Transverse "brittle" fractures of the humerus, lower leg and ribs healed normally, but internal fixation and late bone grafting were required for a subtrochanteric stress fracture of the femur at the age of 24 years. At present the patient has no clinical problems and leads a normal life

There is increasing evidence that non-steroidal anti-inflammatory drugs (NSAIDs) can adversely affect bone repair. We have, therefore, studied the in vitro effects of NSAIDs, which differentially inhibit cyclooxygenases (COX), the prostaglandin/thromboxane synthesising enzymes, on human osteoblasts. Indomethacin and the new nitric oxide (NO)-donating NSAIDs block the activity of both COX-1 and COX-2. Indomethacin and 5,5-dimethyl-3-(3 fluorophenyl)-4-(4 methylsulphonal) phenyl-2 (5H)-furanone (DFU) reduced osteoblast numbers in a dose-dependant manner and increased collagen synthesis and alkaline phosphatase activity. The reduction in osteoblast numbers was not caused by loss of adhesion and was reversible. Neither NSAID influenced DNA synthesis. There was no difference between the effects of indomethacin and DFU. NO-NSAIDs did not affect cell numbers. These results suggest that care should be taken when administering NSAIDs to patients with existing skeletal problems and that NO-NSAIDs may be safer

Periprosthetic bone loss after total joint arthroplasty is a major clinical problem resulting in aseptic loosening of the implant. Among many cell types, osteoblasts play a crucial role in the development of peri-implant osteolysis. In this study, we tested the effects of calcitriol (1α,25-dihydroxy-vitamin-D. 3. ) and the bisphosphonate pamidronate on titanium-particle- and TNF-α-induced release of interleukin-6 and suppression of osteoblast-specific gene expressions in bone-marrow-derived stromal cells with an osteoblastic phenotype. We monitored the expression of procollagen α1[1], osteocalcin, osteonectin and alkaline phosphatase mRNAs by Northern blots and real-time reverse transcription and polymerase chain reaction analyses. The release of various cytokines was also analysed by ELISA. We found that calcitriol or pamidronate could only partially recover the altered functions of osteoblasts when added alone. Only a combination of these compounds restored all the tested functions of osteoblasts. The local delivery of these drugs may have therapeutic potential to prevent or to treat periprosthetic osteolysis and aseptic loosening of implants

From 1981 to 1986 we treated 413 patients for acute spinal-cord injuries. We reviewed 356 patients followed for a minimum of two years of whom 71 (20%) developed heterotopic ossification around one or more joints. Heterotopic ossification occurred more often in male patients (23%) than in female (10%), and was most frequent in the 20- to 30-year age group. It was also more common after injuries of the lower cervical or thoracic spine than after those of the lumbar spine. Patients with severe neurological deficits (Frankel grades A and B) showed significantly more heterotopic ossification but there was no correlation with the number or severity of associated head and limb injuries. Serum calcium levels did not change significantly in either group for 30 weeks after injury, but the erythrocyte sedimentation rate and the alkaline phosphatase level were significantly increased at six weeks in patients with heterotopic ossification

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

1. A clinical, radiological and histological description of a patient with fibrogenesis imperfecta ossium is given. We think that this is the first case in which diagnosis has been made during the life of the patient. 2. The disease is characterised by a defect in the formation of the collagen fibres of the bone matrix. There is also a failure of normal calcification of the matrix, giving rise to the appearance of wide "osteoid" seams. When examined with the polarising microscope and when stained with Gomori's reticulin stain the collagen fibres can be seen to be grossly deficient and abnormal. 3. The patient presented at the age of fifty-four years with bone pain and multiple fractures. The only biochemical abnormality detected in the plasma was an elevated alkaline phosphatase. He was also in negative calcium balance. 4. Treatment with vitamin D. 2. , later changed to dihydrotachysterol, appears to have produced clinical, biochemical and radiological improvement. It appears that a direct action of the vitamin on the abnormal bone collagen must be postulated, in addition to its known actions on the calcifying mechanisms. 5. An unusual feature of the case was the slow development of a total unresponsiveness to large doses of vitamin D. 2. , in spite of a markedly elevated level of vitamin D in the plasma. There was later a response to a much smaller dose of dihydrotachysterol, which is being maintained to date

1. It has been shown that in experimental rickets the well known changes in the epiphysial cartilage which so seriously affect growth are accompanied by severe interference with the progress of the metaphysial vessels into the growth cartilage. 2. Further evidence has been found that, by the repeated increase in their number, the cartilage cells occupying the more distal part of the proliferative segment become more and more affected by their remoteness from the epiphysial vessels, which supply the transudates to these cells. At a given distance these cells are affected and change, becoming hypertrophic, with increasingly large vacuolae, and are rich in glycogen and alkaline phosphatase. 3. The hypertrophic cells alter the nature of the intercellular substance they deposit and this becomes calcifiable. Provided that the metaphysial vessels are situated at an appropriate distance–about three cell capsules away–and that the blood has its necessary components, calcification occurs. 4. Calcification produces the advancing, rigid multitubular structure within which the progressing metaphysial vessels are protected. 5. The interruption of calcification by the withdrawal of fat-soluble vitamins breaks down the whole mechanism of growth and stops the vessels growing into their proper position. The administration of the required vitamins re-establishes the normal sequence of events and allows the vessels to play their decisive role in osteogenesis. 6. Any mechanism which causes the interruption of the vascular progression, whether from metaphysial ischaemia (Trueta and Amato 1960), from severe pressure (Trueta and Trias 1961) or from lack of calcification by withdrawing the fat-soluble vitamins, equally interrupts growth

Periprosthetic osteolysis is a major cause of aseptic loosening in artificial joint replacement. It is assumed to occur in conjunction with the activation of macrophages. We have shown in vitro that human osteoblast-like cells, isolated from bone specimens obtained from patients undergoing hip replacement, phagocytose fine particles of titanium alloy (TiAlV). The human osteoblast-like cells were identified immunocytochemically by the presence of bone-specific alkaline phosphatase (BAP). With increasing duration of culture, a variable number of the osteoblastic cells became positive for the macrophage marker CD68, independent of the phagocytosis of particles, with a fine granular cytoplasmic staining which was coexpressed with BAP as revealed by immunodoublestaining. The metal particles were not toxic to the osteoblastic cells since even in culture for up to four weeks massively laden cells were vital and had a characteristic morphology. Cells of the human osteosarcoma cell line (HOS 58) were also able to phagocytose metal particles but had only a low expression of the CD68 antigen. Fluorescence-activated cell scanning confirmed our immunocytochemical results. Additionally, the cells were found to be negative for the major histocompatibility complex-II (MHC-II) which is a marker for macrophages and other antigen-presenting cells. Negative results of histochemical tests for tartrate-resistant acid phosphatase excluded the contamination by osteoclasts or macrophages in culture. Our observations suggest that the osteoblast can either change to a phagocytosing cell or that the phagocytosis is an underestimated property of the osteoblast. The detection of the CD68 antigen is insufficient to prove the monocytic lineage. In order to discriminate between macrophages and osteoblasts additional markers should be used. To our knowledge, this is the first demonstration of cells of an osteoblastic origin which have acquired a mixed phenotype of both osteoblasts and macrophages

Extracorporeal shock-wave (ESW) treatment hasbeen shown to be effective in promoting the healing of fractures. We aimed to determine whether ESW could enhance the growth of bone-marrow osteoprogenitor cells. We applied ESW to the left femur of rats 10 mm above the knee at 0.16 mJ/mm. 2. in a range of between 250 and 2000 impulses. Bone-marrow cells were harvested after ESW for one day and subjected to assessment of colony-forming unit (CFU) granulocytes, monocytes, erythocytes, megakaryocytes (CFU-Mix), CFU-stromal cells (CFU-S) and CFU-osteoprogenitors (CFU-O). We found that the mean value for the CFU-O colonies after treatment with 500 impulses of ESW was 168.2 CFU-O/well (. sem. 11.3) compared with 88.2 CFU-O/well (. sem. 7.2) in the control group. By contrast, ESW treatment did not affect haematopoiesis as shown by the CFU-Mix (p = 0.557). Treatment with 250 and 500 impulses promoted CFU-O, but not CFU-Mix formations whereas treatment with more than 750 impulses had an inhibiting effect. Treatment with 500 impulses also enhanced the activity of bone alkaline phosphatase in the subculture of CFU-O (p< 0.01), indicating a selective promotion of growth of osteoprogenitor cells. Similarly, formation of bone nodules in the long-term culture of bone-marrow osteoprogenitor cells was also significantly enhanced by ESW treatment with 500 impulses. The mean production of TGF-β1 was 610 pg/ml (. sem. 84.6) in culture supernatants from ESW-treated rats compared with 283 pg/ml (. sem. 36.8) in the control group. Our findings suggest that optimal treatment with ESW could enhance rat bone-marrow stromal growth and differentiation towards osteoprogenitors presumably by induction of TGF-β1

We have attempted to summarise in a short space investigations that have occupied several years, and we realise that whatever the merits of such an effort the results can only be modest. Many important aspects of the osteogenetic process still remain a mystery and thus are subjected to theory and controversy. Such is the case with this constant attendant at osteogenesis which is alkaline phosphatase. But of one thing we are certain, namely that bone is an organised "soft" tissue of which only part has been made rigid by the deposit of calcium salts. The organiser is the osteogenetic vessel from which springs the syncytial frame of cells and their connections on which the bone architecture is established. Endothelial cell, intermediate cell, osteoblast, osteocyte, osteoclast; these constitute the normal sequence of cellular phylogeny in the constant elaboration and removal of the bone substance. The initial cells on which the whole process rests are those of the capillary-sinusoid vessel which is responsible for providing the transudates on which the life and health of the whole syncytium depends. If our findings were confirmed, a better understanding of the nature and characteristics of primitive malignant bone tumours would be possible. Each type of tumour from endothelioma to malignant osteoclastoma, including reticulum-cell sarcoma and osteogenic sarcoma, would be initiated by a different cell of the syncytium, but in its monstrous deviation from the normal would still preserve most of the characteristics of its healthy ancestor. Thus the endothelioma causes bone expansion, bone reaction and even bone necrosis, but not proper bone formation, whereas the osteogenic sarcoma or osteoblastoma forms bone; and with the same fidelity to their origin osteoclasts are seen in the malignant osteolytic tumour. Over thirty years ago the late Sir Arthur Keith (1927) expressed his suspicion that the cells which assume a bone-forming role are derived from the endothelium of the capillary system. We hope we have contributed to show that his suspicion was right

Aims

This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival.

1. The clinical features, diagnosis and treatment of osteomalacia are discussed in relation to thirty-seven recently recognised cases. It is suggested that this disease is not uncommon in elderly women, among whom it is liable to be confused with senile osteoporosis. Osteomalacia may be distinguished by, firstly, the history, in which persistent skeletal pain of long duration and muscular weakness are typical of osteomalacia, but not of osteoporosis in which transient episodes of pain usually associated with a fracture are more characteristic. There is a high incidence of previous gastric surgery in the osteomalacia patients. Secondly, the physical examination shows skeletal tenderness in osteomalacia but this is not a particular feature of osteoporosis. A shuffling "penguin gait" suggests osteomalacia. Thirdly, the biochemistry shows a low plasma calcium and phosphate, and raised alkaline phosphatase levels commonly in osteomalacia but these are usually normal in osteoporosis. Reduced twenty-four-hour urinary calcium is characteristic of osteomalacia but not of osteoporosis. Fourthly, radiology will show diminished bone density which is common to both diseases, but if the changes are more marked in the peripheral bones than in the axial skeleton osteomalacia is suggested; the opposite is typical of osteoporosis. Skeletal deformity without fracture suggests osteomalacia, as do stress fractures and greenstick fractures in the elderly. Looser's zones are diagnostic of osteomalacia in which they are the most important radiological feature. Finally, histology will show the presence of excess osteoid tissue in undecalcified sections of bone in osteomalacia. This may be the earliest and most sensitive index of the disease and biopsy is indicated in all doubtful cases. 2. The etiology is discussed and it is suggested that a dietary deficiency of vitamin D, limited exposure to sunlight and mild degrees of malabsorption may all be important either alone or in combination. No satisfactory explanation is offered for the predominant female incidence. 3. A practical method of treatment is given and the dangers of uncontrolled administration of vitamin D indicated. 4. Treatment of osteomalacia is rapidly and consistently successful, and well justifies a thorough screening of all elderly patients presenting with weakness, skeletal pain, pathological fractures or with diminished radiographic density of bone

Adolescent idiopathic scoliosis (AIS), defined by an age at presentation of 11 to 18 years, has a prevalence of 0.47% and accounts for approximately 90% of all cases of idiopathic scoliosis. Despite decades of research, the exact aetiology of AIS remains unknown. It is becoming evident that it is the result of a complex interplay of genetic, internal, and environmental factors. It has been hypothesized that genetic variants act as the initial trigger that allow epigenetic factors to propagate AIS, which could also explain the wide phenotypic variation in the presentation of the disorder. A better understanding of the underlying aetiological mechanisms could help to establish the diagnosis earlier and allow a more accurate prediction of deformity progression. This, in turn, would prompt imaging and therapeutic intervention at the appropriate time, thereby achieving the best clinical outcome for this group of patients.

Cite this article: Bone Joint J 2022;104-B(8):915–921.

Aims

The incidence of bone metastases is between 20% to 75% depending on the type of cancer. As treatment improves, the number of patients who need surgical intervention is increasing. Identifying patients with a shorter life expectancy would allow surgical intervention with more durable reconstructions to be targeted to those most likely to benefit. While previous scoring systems have focused on surgical and oncological factors, there is a need to consider comorbidities and the physiological state of the patient, as these will also affect outcome. The primary aim of this study was to create a scoring system to estimate survival time in patients with bony metastases and to determine which factors may adversely affect this.

Aims

There is a lack of evidence about the risk factors for local recurrence of a giant cell tumour (GCT) of the sacrum treated with nerve-sparing surgery, probably because of the rarity of the disease. This study aimed to answer two questions: first, what is the rate of local recurrence of sacral GCT treated with nerve-sparing surgery and second, what are the risk factors for its local recurrence?

Aims

The primary aim of this study was to compare the postoperative systemic inflammatory response in conventional jig-based total knee arthroplasty (conventional TKA) versus robotic-arm assisted total knee arthroplasty (robotic TKA). Secondary aims were to compare the macroscopic soft tissue injury, femoral and tibial bone trauma, localized thermal response, and the accuracy of component positioning between the two treatment groups.

Aims

This study aimed to determine the minimal detectable change (MDC), minimal clinically important difference (MCID), and substantial clinical benefit (SCB) under distribution- and anchor-based methods for the Mayo Elbow Performance Index (MEPI) and range of movement (ROM) after open elbow arthrolysis (OEA). We also assessed the proportion of patients who achieved MCID and SCB; and identified the factors associated with achieving MCID.

Aims

The early mortality in patients with hip fractures from bony metastases is unknown. The objectives of this study were to quantify 30- and 90-day mortality in patients with proximal femoral metastases, and to create a mortality prediction tool based on biomarkers associated with early death.

Aims

The aims of this study were to characterize the frequency of missing data in the National Surgical Quality Improvement Program (NSQIP) database and to determine how missing data can influence the results of studies dealing with elderly patients with a fracture of the hip.

Aims

Surgical intervention in patients with bone metastases from breast cancer is dependent on the estimated survival of the patient. The purpose of this paper was to identify factors that would predict survival so that specific decisions could be made in terms of surgical (or non-surgical) management.

Aims

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

The development and pre-clinical evaluation of nano-texturised, biomimetic, surfaces of titanium (Ti) implants treated with titanium dioxide (TiO₂) nanotube arrays is reviewed. In vitro and in vivo evaluations show that TiO₂ nanotubes on Ti surfaces positively affect the osseointegration, cell differentiation, mineralisation, and anti-microbial properties. This surface treatment can be superimposed onto existing macro and micro porous Ti implants creating a surface texture that also interacts with cells at the nano level. Histology and mechanical pull-out testing of specimens in rabbits indicate that TiO₂ nanotubes improves bone bonding nine-fold (p = 0.008). The rate of mineralisation associated with TiO₂ nanotube surfaces is about three times that of non-treated Ti surfaces. In addition to improved osseointegration properties, TiO₂ nanotubes reduce the initial adhesion and colonisation of Staphylococcus epidermidis. Collectively, the properties of Ti implant surfaces enhanced with TiO₂ nanotubes show great promise.

Cite this article: Bone Joint J 2018;100-B(1 Supple A):9–16.

Aims

Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function.

Aims

Little is known about the effect of haemorrhagic shock and resuscitation on fracture healing. This study used a rabbit model with a femoral osteotomy and fixation to examine this relationship.

Aims

The aim of this study was to evaluate the outcome of spinal instrumentation in haemodialyzed patients with native pyogenic spondylodiscitis. Spinal instrumentation in these patients can be dangerous due to rates of complications and mortality, and biofilm formation on the instrumentation.

We evaluated the long-term outcome of patients with an osteosarcoma who had undergone prior manipulative therapy, a popular treatment in Asia, and investigated its effects on several prognostic factors. Of the 134 patients in this study, 70 (52%) patients had manipulative therapy and 64 (48%) did not. The age, location, and size of tumour were not significantly different between the groups. The five-year overall survival rate was 58% and 92% in the groups with and without manipulative therapy (p = 0.004). Both the primary and overall rates of lung metastasis were significantly higher in the manipulative group (primary: 32% vs 3%, p = 0.003; overall lung metastasis rate: 51.4% vs 18.8%, p < 0.001). Patients who had manipulative therapy had higher local recurrence rates in comparison to patients who did not (29% vs 6%, p = 0.011). The prognosis for patients with osteosarcoma who had manipulative therapy was significantly poorer than those who had not. Manipulative therapy was an independent factor for survival.

This form of therapy may serve as a mechanism to accelerate the spread of tumour cells, and therefore must be avoided in order to improve the outcome for patients with an osteosarcoma.

Aims

The aims of this study were to evaluate the long-term outcome of surgery for bone or soft-tissue metastases from renal cell carcinoma (RCC) and to determine factors that affect prognosis.

When transferring tissue regenerative strategies involving skeletal stem cells to human application, consideration needs to be given to factors that may affect the function of the cells that are transferred. Local anaesthetics are frequently used during surgical procedures, either administered directly into the operative site or infiltrated subcutaneously around the wound. The aim of this study was to investigate the effects of commonly used local anaesthetics on the morphology, function and survival of human adult skeletal stem cells.

Cells from three patients who were undergoing elective hip replacement were harvested and incubated for two hours with 1% lidocaine, 0.5% levobupivacaine or 0.5% bupivacaine hydrochloride solutions. Viability was quantified using WST-1 and DNA assays. Viability and morphology were further characterised using CellTracker Green/Ethidium Homodimer-1 immunocytochemistry and function was assessed by an alkaline phosphatase assay. An additional group was cultured for a further seven days to allow potential recovery of the cells after removal of the local anaesthetic.

A statistically significant and dose dependent reduction in cell viability and number was observed in the cell cultures exposed to all three local anaesthetics at concentrations of 25% and 50%, and this was maintained even following culture for a further seven days.

This study indicates that certain local anaesthetic agents in widespread clinical use are deleterious to skeletal progenitor cells when studied in vitro; this might have relevance in clinical applications.

We describe a case of oncogenic osteomalacia in an adult male who presented with low back pain and bilateral hip pain. Extensive investigations had failed to find a cause. A plain pelvic radiograph showed Looser’s zones in both femoral necks. MRI confirmed the presence of insufficiency fractures bilaterally in the femoral head and neck. Biochemical investigations confirmed osteomalacia which was unresponsive to treatment with vitamin D and calcium. A persistently low serum phosphate level suggested a diagnosis of hypophosphataemic osteomalacia. The level of fibroblast growth factor-23 was highly raised, indicating the cause as oncogenic osteomalacia. This was confirmed on positron-emission tomography, MRI and excision of a benign fibrous histiocytoma following a rapid recovery.

The diagnosis of oncogenic osteomalacia may be delayed due to the non-specific presenting symptoms. Subchondral insufficiency fractures of the femoral head may be missed unless specifically looked for.

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.

We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate in vitro into osteogenic, chondrogenic and adipogenic cells.

Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis.

Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure.

After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site.

The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour.

Slipped capital femoral epiphysis (SCFE) is uncommon in India and we routinely look for associated metabolic or endocrine abnormalities. In this study we investigated a possible association between vitamin D deficiency and SCFE. All children presenting with SCFE during the study period had their 25-hydroxyvitamin D levels measured as part of an overall metabolic, renal and endocrine status evaluation, which included measurement of body mass index (BMI). Vitamin D status was compared with age-, gender- and habitat-matched controls with acute trauma or sepsis presenting to our emergency department.

A total of 15 children (12 boys and three girls) with a mean age of 13 years (sd 1.81; 10 to 16) presented for treatment for SCFE during a two-year period beginning in January 2010. Renal and thyroid function was within the normal range in all cases. The mean BMI was 24.9 kg/m² (17.0 to 33.8), which was significantly higher than that of the controls (p = 0.006). There was a statistically significant difference between the mean values of 25-hydroxyvitamin D in the children with SCFE and the controls (11.78 ng/ml (sd 5.4) versus 27.06 ng/ml (sd 5.53), respectively; p < 0.001). We concluded that, along with high BMI, there is a significant association of vitamin D deficiency and SCFE in India.

Cite this article: Bone Joint J 2013;95-B:851–4.

Sacral insufficiency fractures are traditionally treated with bed rest and analgesia. The importance of early rehabilitation is generally appreciated; but pain frequently delays this, resulting in prolonged hospital stay and the risk of complications related to immobility. We describe three women with sacral insufficiency fractures who were treated with percutaneous sacroiliac screws and followed up for a mean of 18 months (12 to 24). They had immediate pain relief, uncomplicated rehabilitation and uneventful healing.

Aims

We aimed to assess the influence of ethnicity on the incidence of heterotopic ossification (HO) after total hip arthroplasty (THA).

We evaluated the incidence of heterotopic ossification following total ankle replacement to determine whether the degree of ossification was associated with the clinical outcome. We evaluated 90 ankles in 81 consecutive patients who underwent total ankle replacement, and heterotopic ossification was assessed according to proportional involvement of the ankle joint. Correlation analysis was used to investigate the association between heterotopic ossification and outcome.

No significant association was found between the formation of heterotopic ossification and the clinical outcome. The degree of heterotopic ossification in the posterior ankle joint was not significantly correlated with posterior ankle pain (p = 0.929), the American Orthopaedic Foot and Ankle Society score (p = 0.454) or range of movement (p = 0.283).

This study indicates that caution should be observed in attributing symptoms and functional limitation to the presence of heterotopic ossification in the posterior ankle joint when considering excision of heterotopic bone after total ankle replacement.

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.

The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a ‘waste’ bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA.

The solid fraction from the filtrate was digested for 60 minutes at 37°C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105).

MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 μl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114 983 (16 500 to 477 750), RIA-solid = 12 785 (7210 to 28 475).

The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion.

Nutritional osteomalacia is a metabolic bone disorder common among the Asian female immigrant population in the United Kingdom. We describe the case of a female of Asian origin, who was found to have a unilateral undisplaced pseudofracture of the neck of the femur during pregnancy. Although not operated on the fracture was treated successfully with calcium and vitamin D supplement therapy. Within one month of treatment, the bone pain subsided and she was able to bear full weight. Subsequent radiological follow-up showed the pseudofracture to have healed sufficiently with no evidence of avascular necrosis.

There should be a high index of suspicion of this disease, particularly among Asian patients presenting with persistent and non-specific musculoskeletal pain.

There have been recent reports linking alendronate and a specific pattern of subtrochanteric insufficiency fracture. We performed a retrospective review of all subtrochanteric fractures admitted to our institution between 2001 and 2007. There were 20 patients who met the inclusion criteria, 12 of whom were on long-term alendronate. Alendronate-associated fractures tend to be bilateral (Fisher’s exact test, p = 0.018), have unique radiological features (p < 0.0005), be associated radiologically with a pre-existing ellipsoid thickening of the lateral femoral cortex and are likely to be preceded by prodromal pain. Biomechanical investigations did not suggest overt metabolic bone disease. Only one patient on alendronate had osteoporosis prior to the start of therapy. We used these findings to develop a management protocol to optimise fracture healing. We also advocate careful surveillance in individuals at-risk, and present our experience with screening and prophylactic fixation in selected patients.

Metal-on-metal bearings for total hip replacement (THR) are becoming increasingly popular. Improved wear characteristics mean that these articulations are being inserted into younger patients in the form of THR and resurfacing procedures. This has led to concerns regarding potential carcinogenicity because of the increased exposure to metal ions that the procedure brings.

We have studied the serum cobalt and chromium concentrations in patients who had primary, well-fixed Ring metal-on-metal THRs for more than 30 years. The levels of cobalt and chromium were elevated by five and three times, respectively compared with those in our reference groups. Metal-on-metal articulations appear to be the source of metal ions throughout the life of the prosthesis. In three patients who had undergone revision of a previous metal-on-metal THR to a metal-on-polyethylene replacement the levels of metal ions were within the normal range. The elevations of cobalt and chromium ions seen in our study were comparable with those in patients with modern metal-on-metal THRs.

Conventional cemented acetabular components are reported to have a high rate of failure when implanted into previously irradiated bone. We recommend the use of a cemented reconstruction with the addition of an acetabular reinforcement cross to improve fixation.

We reviewed a cohort of 45 patients (49 hips) who had undergone irradiation of the pelvis and a cemented total hip arthroplasty (THA) with an acetabular reinforcement cross. All hips had received a minimum dose of 30 Gray (Gy) to treat a primary nearby tumour or metastasis. The median dose of radiation was 50 Gy (Q1 to Q3: 45 to 60; mean: 49.57, 32 to 72).

The mean follow-up after THA was 51 months (17 to 137). The cumulative probability of revision of the acetabular component for a mechanical reason was 0% (0 to 0%) at 24 months, 2.9% (0.2 to 13.3%) at 60 months and 2.9% (0.2% to 13.3%) at 120 months, respectively. One hip was revised for mechanical failure and three for infection.

Cemented acetabular components with a reinforcement cross provide good medium-term fixation after pelvic irradiation. These patients are at a higher risk of developing infection of their THA.

Cite this article: Bone Joint J 2015;97-B:177–84.

Opinion remains divided as to whether the development of pathological fracture affects the prognosis of patients with an osteosarcoma of the extremities.

We conducted a comprehensive systematic review and meta-analysis of papers which reported the outcomes of osteosarcoma patients with and without a pathological fracture. There were eight eligible papers for final analysis which reported on 1713 patients, of whom 303 (17.7%) had a pathological fracture. The mean age for 1464 patients in six studies was 23.2 years old (2 to 82). The mean follow-up for 1481 patients in seven studies was 90.1 months (6 to 240).

The pooled estimates of local recurrence rates in osteosarcoma patients with and without pathological fractures were 14.4% (8.7 to 20.0) versus 11.4% (8.0 to 14.8). The pooled estimate of relative risk was 1.39 (0.89 to 2.20). The pooled estimates of five-year event-free survival rates in osteosarcoma patients with and without a pathological fracture were 49.3% (95% CI 43.6 to 54.9) versus 66.8% (95% CI 60.7 to 72.8). The pooled estimate of relative risk was 1.33 (1.12 to 1.59). There was no significant difference in the rate of local recurrence between patients who were treated by amputation or limb salvage.

The development of a pathological fracture is a negative prognostic indicator in osteosarcoma and is associated with a reduced five-year event-free survival and a possibly higher rate of local recurrence. Our findings suggest that there is no absolute indication for amputation, as similar rates of local recurrence can be achieved in patients who are carefully selected for limb salvage.

Cite this article: Bone Joint J 2014; 96-B:1396–1403

We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft–bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL–bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft.

Cite this article: Bone Joint J 2013;95-B:923–8.

This multicentre prospective clinical trial aimed to determine whether early administration of alendronate (ALN) delays fracture healing after surgical treatment of fractures of the distal radius. The study population comprised 80 patients (four men and 76 women) with a mean age of 70 years (52 to 86) with acute fragility fractures of the distal radius requiring open reduction and internal fixation with a volar locking plate and screws. Two groups of 40 patients each were randomly allocated either to receive once weekly oral ALN administration (35 mg) within a few days after surgery and continued for six months, or oral ALN administration delayed until four months after surgery. Postero-anterior and lateral radiographs of the affected wrist were taken monthly for six months after surgery. No differences between groups was observed with regard to gender (p = 1.0), age (p = 0.916), fracture classification (p = 0.274) or bone mineral density measured at the spine (p = 0.714). The radiographs were assessed by three independent assessors. There were no significant differences in the mean time to complete cortical bridging observed between the ALN group (3.5 months (se 0.16)) and the no-ALN group (3.1 months (se 0.15)) (p = 0.068). All the fractures healed in the both groups by the last follow-up. Improvement of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, grip strength, wrist range of movement, and tenderness over the fracture site did not differ between the groups over the six-month period. Based on our results, early administration of ALN after surgery for distal radius fracture did not appear to delay fracture healing times either radiologically or clinically.

Cite this article: Bone Joint J 2013;95-B:1544–50.

Florid reactive periostitis is a pronounced periosteal reaction, usually affecting the hands and feet, for which there is no obvious cause. It is rare in children and in long bones. We report an unusual case of florid reactive periostitis in a ten-year-old girl that involved both bones of the forearm. The lesion resolved over a period of one year, leaving a residual exostosis. She developed a physeal bar in the distal ulna in the region of the lesion at one-year follow-up. This was thought to be a complication of the biopsy procedure and was treated by resection and proximal ulnar lengthening.

Periosteum is important for bone homoeostasis through the release of bone morphogenetic proteins (BMPs) and their effect on osteoprogenitor cells. Smoking has an adverse effect on fracture healing and bone regeneration. The aim of this study was to evaluate the effect of smoking on the expression of the BMPs of human periosteum. Real-time polymerase chain reaction was performed for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from 45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured bones (21 smokers, 39 non-smokers). A hierarchical model of BMP gene expression (BMP-2 > BMP-6 > BMP-4 > BMP-7) was demonstrated in all samples. When smokers and non-smokers were compared, a remarkable reduction in the gene expression of BMP-2, -4 and -6 was noticed in smokers. The comparison of fracture and non-fracture groups demonstrated a higher gene expression of BMP-2, -4 and -7 in the non-fracture samples. Within the subgroups (fracture and non-fracture), BMP gene expression in smokers was either lower but without statistical significance in the majority of BMPs, or similar to that in non-smokers with regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In smokers, BMP gene expression of human periosteum was reduced, demonstrating the effect of smoking at the molecular level by reduction of mRNA transcription of periosteal BMPs. Among the BMPs studied, BMP-2 gene expression was significantly higher, highlighting its role in bone homoeostasis.

We examined whether enamel matrix derivative (EMD) could improve healing of the tendon–bone interface following reconstruction of the anterior cruciate ligament (ACL) using a hamstring tendon in a rat model. ACL reconstruction was performed in both knees of 30 Sprague-Dawley rats using the flexor digitorum tendon. The effect of commercially available EMD (EMDOGAIN), a preparation of matrix proteins from developing porcine teeth, was evaluated. In the left knee joint the space around the tendon–bone interface was filled with 40 µl of EMD mixed with propylene glycol alginate (PGA). In the right knee joint PGA alone was used. The ligament reconstructions were evaluated histologically and biomechanically at four, eight and 12 weeks (n = 5 at each time point). At eight weeks, EMD had induced a significant increase in collagen fibres connecting to bone at the tendon–bone interface (p = 0.047), whereas the control group had few fibres and the tendon–bone interface was composed of cellular and vascular fibrous tissues. At both eight and 12 weeks, the mean load to failure in the treated specimens was higher than in the controls (p = 0.009). EMD improved histological tendon–bone healing at eight weeks and biomechanical healing at both eight and 12 weeks. EMD might therefore have a human application to enhance tendon–bone repair in ACL reconstruction.

A 64-year-old man presented with a severe deformity of the tibia caused by Paget’s disease and osteoarthritis of the ipsilateral knee. Total knee replacement required preliminary correction of the tibial deformity. This was successfully achieved by tibial osteotomy followed by distraction osteogenesis using the Taylor spatial frame. The subsequent knee replacement was successful, with no recurrence of deformity.

Various chemicals are commonly used as adjuvant treatment to surgery for giant-cell tumour (GCT) of bone. The comparative effect of these solutions on the cells of GCT is not known. In this study we evaluated the cytotoxic effect of sterile water, 95% ethanol, 5% phenol, 3% hydrogen peroxide (H₂O₂) and 50% zinc chloride (ZnCI₂) on GCT monolayer tumour cultures which were established from six patients. The DNA content, the metabolic activity and the viability of the cultured samples of tumour cells were assessed at various times up to 120 hours after their exposure to these solutions.

Equal cytotoxicity to the GCT monolayer culture was observed for 95% ethanol, 5% phenol, 3% H₂O₂ and 50% ZnCI₂. The treated samples showed significant reductions in DNA content and metabolic activity 24 hours after treatment and this was sustained for up to 120 hours. The samples treated with sterile water showed an initial decline in DNA content and viability 24 hours after treatment, but the surviving cells were viable and had proliferated. No multinucleated cell formation was seen in these cultures.

These results suggest that the use of chemical adjuvants other than water could help improve local control in the treatment of GCT of bone.

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.

Heterotopic ossification (HO) of the hip after injury to the central nervous system can lead to joint ankylosis. Surgery is usually delayed to avoid recurrence, even if the functional status is affected. We report a consecutive series of patients with HO of the hip after injury to the central nervous system who required surgery in a single, specialised tertiary referral unit. As was usual practice, they all underwent CT to determine the location of the HO and to evaluate the density of the femoral head and articular surface. The outcome of surgery was correlated with the pre-, peri- and post-operative findings.

In all, 183 hips (143 patients) were included of which 70 were ankylosed. A total of 25 peri-operative fractures of the femoral neck occurred, all of which arose in patients with ankylosed hips and were associated with intra-articular lesions in 18 and severe osteopenia of the femoral head in seven. All the intra-articular lesions were predicted by CT and strongly associated with post-operative complications.

The loss of the range of movement before ankylosis is a more important factor than the maturity of the HO in deciding the timing of surgery. Early surgical intervention minimises the development of intra-articular pathology, osteoporosis and the resultant complications without increasing the risk of recurrence of HO.

Non-accidental injury (NAI) in children includes orthopaedic trauma throughout the skeleton. Fractures with soft-tissue injuries constitute the majority of manifestations of physical abuse in children. Fracture and injury patterns vary with age and development, and NAI is intrinsically related to the mobility of the child. No fracture in isolation is pathognomonic of NAI, but specific abuse-related injuries include multiple fractures, particularly at various stages of healing, metaphyseal corner and bucket-handle fractures and fractures of ribs. Isolated or multiple rib fractures, irrespective of location, have the highest specificity for NAI. Other fractures with a high specificity for abuse include those of the scapula, lateral end of the clavicle, vertebrae and complex skull fractures.

Injuries caused by NAI constitute a relatively small proportion of childhood fractures. They may be associated with significant physical and psychological morbidity, with wide- ranging effects from deviations in normal developmental progression to death.

Orthopaedic surgeons must systematically assess, recognise and act on the indicators for NAI in conjunction with the paediatric multidisciplinary team.

This paper summarises the current knowledge on the effects of medullary reaming of long-bone fractures. Following a review of intramedullary vascular physiology, the consequences for vascularity, the autograft effects, the generation of heat, and fat embolism are outlined. Also, alternative reaming techniques are described.

Critical size defects in ovine tibiae, stabilised with intramedullary interlocking nails, were used to assess whether the addition of carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant would affect the implant’s efficacy for bone regeneration. The biomaterial carriers were a ‘putty’ carrier of carboxymethylcellulose and bovine-derived type-I collagen (OPP) or the standard with collagen alone (OPC). These two treatments were also compared to “ungrafted” negative controls. Efficacy of regeneration was determined using radiological, biomechanical and histological evaluations after four months of healing. The defects, filled with OPP and OPC, demonstrated radiodense material spanning the defect after one month of healing, with radiographic evidence of recorticalisation and remodelling by two months. The OPP and OPC treatment groups had equivalent structural and material properties that were significantly greater than those in the ungrafted controls. The structural properties of the OPP- and OPC-treated limbs were equivalent to those of the contralateral untreated limb (p > 0.05), yet material properties were inferior (p < 0.05). Histopathology revealed no residual inflammatory response to the biomaterial carriers or OP-1. The OPP- and OPC-treated animals had 60% to 85% lamellar bone within the defect, and less than 25% of the regenerate was composed of fibrous tissue. The defects in the untreated control animals contained less than 40% lamellar bone and more than 60% was fibrous tissue, creating full cortical thickness defects. In our studies carboxymethylcellulose did not adversely affect the capacity of the standard OP-1 implant for regenerating bone.

This paper reviews the current literature concerning the main clinical factors which can impair the healing of fractures and makes recommendations on avoiding or minimising these in order to optimise the outcome for patients. The clinical implications are described.

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group.

Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months.

The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm³ (sd 261) and 545 cells/mm³ (sd 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm³ (sd 343)) still remained lower than that of group I (1071 cells/mm³ (sd 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator.

Between 2000 and 2006 we performed salvage tibiotalar arthrodesis in 17 diabetic patients (17 ankles) with grossly unstable ankles caused by bimalleolar fractures complicated by Charcot neuro-arthropathy. There were ten women and seven men with a mean age of 61.6 years (57 to 69). A crossed-screw technique was used. Two screws were used in eight patients and three screws in nine. Additional graft from the malleoli was used in all patients. The mean follow-up was 26 months (12 to 48) and the mean time to union was 5.8 months (4 to 8). A stable ankle was achieved in 14 patients (82.4%), nine of whom had bony fusion and five had a stiff fibrous union. The results were significantly better in underweight patients, in those in whom surgery had been performed three to six months after the onset of acute Charcot arthropathy, in those who had received anti-resorptive medication during the acute stage, in those without extensive peripheral neuropathy, and in those with adequate peripheral oxygen saturation (> 95%). The arthrodesis failed because of avascular necrosis of the talus in only three patients (17.6%), who developed grossly unstable, ulcerated hindfeet, and required below-knee amputation.