We describe two patients aged 16 and 25 years with osteogenesis imperfecta who sustained displaced fractures of the acetabulum following minor trauma. The femoral heads were deformed by impact against the acetabular margin and both cases underwent surgical reconstruction. The quality of the bone and soft tissues made the operations challenging. There were potential complications specific to osteogenesis imperfecta, including bleeding, the creation of secondary fracture lines and shredding of the soft-tissue. The cases provide useful guidelines for addressing these difficulties

Study of 16 patients with Type III osteogenesis imperfecta showed marked elongation of the pedicles of the vertebrae in all cases, a deformity which was not seen in other types of the disease. Posterior rib angulation was also noted in Type III disease. These features have proved useful in suggesting the diagnosis of osteogenesis imperfecta even before long bones have fractured and in categorizing patients with osteogenesis imperfecta into the correct type for prognostic purposes

Basilar impression is a well-recognised though rare complication of osteogenesis imperfecta. Three patients, all members of the same family, with advanced basilar impression complicating osteogenesis imperfecta tarda, are described. The clinical features in these cases illustrate the natural history of this condition: from asymptomatic ventricular dilatation, through the foramen magnum compression syndrome, to death from brain-stem compression. The radiological criteria on which the diagnosis is based, are defined. Review of the literature reveals only seven previously documented cases, all in patients with mild forms of osteogenesis imperfecta. The unusually low incidence of basilar impression in osteogenesis imperfecta and its apparent restriction to patients with mild forms of the disease is discussed. The examination of close relatives of patients with basilar impression and osteogenesis imperfecta is emphasised in order to anticipate the onset of severe neurological complications

Osteogenesis imperfecta is a rare inherited disorder of connective tissue which may present with recurrent fractures which are prone to nonunion and malunion resulting in deformity. Some patients develop osteoarthritis of the hip. Formation of hyperplastic callus after recurrent fractures may deform the shape of the femur and preclude the use of standard implants at joint replacement. Replacement can thus be technically demanding. We present a case of bilateral hip replacement in a patient with osteogenesis imperfecta and hyperplastic callus which was treated by the use of long femoral allografts and cemented femoral stems

We investigated the fracture-free survival of long bones stabilised by a telescopic intramedullary rod (TIMR) in patients with osteogenesis imperfecta with respect to the remodelling status of fracture or osteotomy sites and TIMR regions, in order to identify risk factors for fracture. A total of 44 femora and 28 tibiae in 25 patients with a mean age of 5.0 years (1.9 to 10.5) at presentation were studied. There were six patients with Sillence type I, five with type III, 13 with type IV and one with type V osteogenesis imperfecta. All received bisphosphonate treatment at the same stage during the mean follow-up of 7.3 years (0.5 to 18.1). The fracture-free survival was estimated at 6.2 years (95% confidence interval 5.1 to 7.3) by Kaplan-Meier analysis. More than half the fracture or osteotomy sites remained in a less-remodelled state at the latest follow-up or time of fracture. Of the 33 fractures, 29 (87.9%) occurred in long bones containing a less-remodelled site, and these fractures were located at this site. The relative fracture risk at the rod tip was significantly greater than in any other TIMR region (p < 0.001), and this was higher in bone segments having a less-remodelled site. This study shows a persistent fracture risk in TIMR-stabilised long bones, especially at less-remodelled fracture or osteotomy sites and at the rod tip

We report the results of using 83 expanding intramedullary rods in 24 children with osteogenesis imperfecta after a mean follow-up of five years three months. In all, 62% of the rods have expanded after one primary operation. Thirty-four additional operations were necessary; 11 for the correction of rotation or angulation deformities and 23 for revision of the rod or T-piece. All these revisions were successful. Complications were more frequent in children who required very small rods. Problems with Bailey-Dubow rods led to the development of the Sheffield rod system; 17 bones treated with these rods are included in the series. Before surgery only eight of the 24 children were able to walk but at review 20 children were walking, 15 without walking aids. Elongating intramedullary rods should be available to all children with osteogenesis imperfecta as they improve walking capability, reduce the number of fractures, prevent deformity and allow integration of the child into society

We used dual-energy X-ray absorptiometry (DEXA) to compare the bone mineral density (BMD) of nine children aged from 2 years 7 months to 13 years 5 months who had mild osteogenesis imperfecta with an age- and sex-matched control group. The patients had only mild clinical symptoms but DEXA detected highly significant differences in BMD between them and the controls. The mean BMD in the children with osteogenesis imperfecta was 76.7% of normal in the lumbar spine (p < 0.001) and 71.2% of normal in the femoral neck (p < 0.001). DEXA is an objective, reproducible and sensitive method of measurement of BMD in children. It may help to establish the diagnosis, to assess prognosis and possibly to monitor the response to different types of treatment

A survey was conducted to document the results of bracing and spinal fusion for scoliosis associated with osteogenesis imperfecta. Observations were made of 121 patients who underwent treatment by bracing or spinal fusion and who had been treated by 51 orthopaedic surgeons in 14 countries. The average curve before bracing measured 43 degrees. The braces were ineffective in stopping progression even in small curves. We were unable to determine whether braces slowed the rate of progression of curvature. The average age at fusion was 15 years 7 months, the average curve before operation measured 74 degrees, and the average correction was 36 per cent. The high incidence of complications was related to the size of the curve before spinal fusion, the use of Harrington instrumentation, and the presence of associated kyphosis. In the absence of pseudarthrosis or kyphosis, late bending of the fused spine did not seem to occur

Paraplegia occurred in an adolescent girl with osteogenesis imperfecta after chiropractic manipulation. The child had been able to walk freely out of doors. Complete motor paralysis with sensory sparing resulted due to anterior compression of the cord by spondyloptotic cervical vertebrae. Reconstructed computerised tomography was very helpful in demonstrating the abnormality. Anterior and then posterior decompression relieved the tethered spinal cord and were supplemented with bone grafting. Early diagnosis and surgical treatment will prevent similar neurological accidents

Three cases of severe osteogenesis imperfecta are reported. Each was treated by closed intramedullary rodding, combined with osteoclasis to correct deformity. Operation was performed within a few months of birth. Both tibiae and both femora were stabilised in one operation, using x-ray image intensification to monitor placement of the rods. The technique used to insert the rods is described. The procedure appeared to be entirely satisfactory in reducing the incidence of fractures and it allowed the affected infants to be handled much more easily

We describe two patients with osteogenesis imperfecta who developed transient osteoporosis in both hips sequentially

We obtained specimens of growth-plate cartilage from four patients with osteogenesis imperfecta. Light microscopy showed structural changes in the tissue and morphological changes in chondrocytes and matrix, particularly in the hypertrophic zone. There were changes in the process of calcification in the primary mineralisation zone of the cartilage. We also found histochemical changes in the matrix glycosaminoglycans (GAGs) in the zones where physiological mineralisation was disturbed and where the trabeculae were interrupted and poorly mineralised. In addition to the known molecular defects in collagen, changes in GAGs and non-collagenous proteins are important factors in the pathogenesis of the disease

This paper describes the design, development and early surgical experience with a stereotactic device to allow closed retrieval and interchange of intramedullary rods in children with osteogenesis imperfecta. This relatively atraumatic procedure may allow more frequent rod interchange than with other techniques, lessening the likelihood of deformity and fracture in the unsupported skeleton when the bone has outgrown the intramedullary rod. The procedure was developed by design studies in vitro followed by intramedullary rodding of tibiae of New Zealand white rabbits. It has been used in children 12 times, in six tibiae and six femora: 11 rods have been successfully retrieved, with rod interchange in eight of these cases

We performed limb lengthening and correction of deformity of nine long bones of the lower limb in six children (mean age, 14.7 years) with osteogenesis imperfecta (OI). All had femoral lengthening and three also had ipsilateral tibial lengthening. Angular deformities were corrected simultaneously. Five limb segments were treated using a monolateral external fixator and four with the Ilizarov frame. In three children, lengthening was done over previously inserted femoral intramedullary rods. The mean lengthening achieved was 6.26 cm (mean healing index, 33.25 days/cm). Significant complications included one deep infection, one fracture of the femur and one anterior angulation deformity of the tibia. The abnormal bone of OI tolerated the external fixators throughout the period of lengthening without any episodes of migration of wires or pins through the soft bone. The regenerate bone formed within the time which is normally expected in limb-lengthening procedures performed for other conditions. We conclude that despite the abnormal bone characteristics, distraction osteogenesis to correct limb-length discrepancy and angular deformity can be performed safely in children with OI

This paper examines the fate of decalcified allografts (homografts) of iliac cancellous bone impregnated with autologous red marrow and implanted intermuscularly into the anterior abdominal wall of rabbits. In contrast to the findings of Urist and other workers that cortical bone decalcified with hydrochloric acid (HCl) and then freeze-dried is inductive to new bone formation in various heterotopic sites, evidence is presented that iliac bone decalcified by HCl and grafted alone to a muscular site is itself very weakly inductive to bone formation. However, when combined with autologous bone marrow the HCl-decalcified bone provides a better substrate for bone formation by marrow cells than does either undecalcified iliac bone, or iliac bone decalcified with ethylene-diamine-tetra-acetic acid. The freezing or freeze-drying of decalcified bone does not affect new bone formation when implanted alone or with autologous marrow. The differences between the cortical and cancellous bone as inductive substrates for osteogenesis are discussed and the interrelationship of bone and marrow in combined bone grafts are re-evaluated

The Sheffield Expanding Intramedullary Rod System was developed after experiencing problems with existing rod systems in the management of osteogenesis imperfecta. Between 1986 and 1996 we treated 74 bones in the lower limb in 28 children at a median follow-up of 5.25 years. We have reviewed 24 children with a total of 60 rods. Before surgery, all children had had multiple fractures of the lower limb. At review eight patients had experienced no further fractures, but three had suffered five or more subsequently. Before initial stabilisation, 15 children had never walked, and only three (13%) used walking as their main means of mobility. After surgery, half of those who showed motor arrest were able to walk (p = 0.016). The number of patients able to walk, with or without aids, increased to 17 (p = 0.0001). We have experienced no evidence of epiphyseal damage after the procedure, and complication rates requiring rod exchange have been low (7%)

The results and complications of the use of Bailey-Dubow extensible rods in 28 lower limb bones of 10 patients suffering from osteogenesis imperfecta are reviewed. Twenty-eight operations were for the primary insertion of the rods into the femur or tibia; a further nine operations were needed for the treatment of complications. These complications included 10 instances of proximal migration of the distal end of the rod, one of incorrect placement in the proximal femur, four instances of loosening of a T-piece and three of infection about a rod, two of these being in one child. Most complications arose from technical faults at insertion. The details of technique which have evolved from experience are described. Only one fracture has occurred in a bone after correct placement of a rod. Of the 10 patients, seven of whom had never walked before, seven were able to walk and two others had achieved walking, but were under treatment for complications at the time of review. There was no evidence of damage to growth epiphyses. The greater technical complexity of insertion of Bailey-Dubow rods is well justified by the results obtained when they are correctly applied

We have reviewed the results of the Sofield-Millar operation on 58 long bones in ten patients. If more than three osteotomies were undertaken the time to union of the bone was significantly prolonged (p< 0.001) with significant thinning of the bone (p< 0.02).

We have used a modified technique in order to minimise surgical trauma and devascularisation of the bone. The rod is introduced under the control of an image-intensifier. Small surgical exposures are made only at the sites of corrective wedge osteotomies. The number of osteotomies is kept to the minimum.

Aims

Distraction osteogenesis with intramedullary lengthening devices has undergone rapid development in the past decade with implant enhancement. In this first single-centre matched-pair analysis we focus on the comparison of treatment with the PRECICE and STRYDE intramedullary lengthening devices and aim to clarify any clinical and radiological differences.

Aims. It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. Materials and Methods. An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium. RNA sequencing analysis was performed using sorted CD31. hi. EMCN. hi. endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. Results. Flow cytometry revealed that anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. Conclusion. VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31. hi. EMCN. hi. endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108–114

Most patients with dominantly inherited osteogenesis imperfecta have blue sclerae and relatively mild symptoms. However, in a small group of families the patients have normal sclerae and this disorder has been classified as Type 4 osteogenesis imperfecta. This paper reports the clinical and radiographical features of 48 patients from 16 families with Type 4 osteogenesis imperfecta and compares the findings with those of the classical disorder with blue sclerae (Type 1 osteogenesis imperfecta). The two types are similar in usually causing a mild disease but with a wide range of severity, and in both types the rate of fracture declines in adolescence. There are, however, some significant differences apart from the colour of the sclerae. In Type 4 the first fracture more commonly occurs at birth, dentinogenesis imperfecta is more frequent than in Type 1 and bruising and nose-bleeds are less common. As in Type 1, the radiographic appearances of the bones may be normal. It is important that Type 4 osteogenesis imperfecta should be recognised because of the need for competent genetic counselling, because the management may be different from that appropriate for Type 1 and because it may be mistaken for idiopathic juvenile osteoporosis or child abuse

Aims. The Fassier Duval (FD) rod is a third-generation telescopic implant for children with osteogenesis imperfecta (OI). Threaded fixation enables proximal insertion without opening the knee or ankle joint. We have reviewed our combined two-centre experience with this implant. Methods. In total, 34 children with a mean age of five years (1 to 14) with severe OI have undergone rodding of 72 lower limb long bones (27 tibial, 45 femoral) for recurrent fractures with progressive deformity despite optimized bone health and bisphosphonate therapy. Data were collected prospectively, with 1.5 to 11 years follow-up. Results. A total of 24 patients (33%) required exchange of implants (14 femora and ten tibiae) including 11 rods bending with refracture. Four (5%) required reoperation with implant retention. Loss of proximal fixation in the femur and distal fixation in the tibia were common. Four patients developed coxa vara requiring surgical correction. In total, 13 patients experienced further fractures without rod bending; eight required implant revision. There was one deep infection. The five-year survival rate, with rod revision as the endpoint, was 63% (95% confidence interval (CI) 44% to 77%) for femoral rods, with a mean age at implantation of 4.8 years (1.3 to 14.8), and 64% (95% CI 36% to 82%) for tibial rods, with a mean age at implantation of 5.2 years (2.0 to 13.8). Conclusion. FD rods are easier to implant but do not improve on the revision rates reported for second generation T-piece rods. Proximal femoral fixation is problematic in younger children with a partially ossified greater trochanter. Distal tibial fixation typically fails after two years. Future generation implants should address proximal femoral and distal tibial fixation to avoid the majority of complications in this series. Cite this article: Bone Joint J 2020;102-B(8):1048–1055

The continual cycle of bone formation and resorption is carried out by osteoblasts, osteocytes, and osteoclasts under the direction of the bone-signaling pathway. In certain situations the host cycle of bone repair is insufficient and requires the assistance of bone grafts and their substitutes. The fundamental properties of a bone graft are osteoconduction, osteoinduction, osteogenesis, and structural support. Options for bone grafting include autogenous and allograft bone and the various isolated or combined substitutes of calcium sulphate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. Not all bone grafts will have the same properties. As a result, understanding the requirements of the clinical situation and specific properties of the various types of bone grafts is necessary to identify the ideal graft. We present a review of the bone repair process and properties of bone grafts and their substitutes to help guide the clinician in the decision making process. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):6–9

Aims

The aim of this retrospective cohort study was to assess and investigate the safety and efficacy of using a distal tibial osteotomy compared to proximal osteotomy for limb lengthening in children.

It has been shown in experimental animals that the living cells in a bone autograft can make an important contribution to osteogenesis. However, some common clinical techniques, such as the topical use of antibiotic powders on grafts or on the graft bed, are likely to damage or kill the cells. In this experimental study in rats, bone isografts dusted with chloramphenicol or methicillin powder or with Polybactrin spray before subcutaneous implantation produced little or no new bone over a period of two weeks whereas untreated, control grafts showed abundant osteogenesis, as did grafts pretreated with solutions of antibiotics. The effect of short-term storage of the grafts for 3 to 24 hours in air, saline or culture medium before implantation was also examined. Grafts stored in culture medium generally did as well as, or better than, fresh control grafts whereas immersion in saline inhibited osteogenesis. The importance of these results for clinical bone grafting is discussed

Aims

Heterotopic ossification (HO) is a common complication after elbow trauma and can cause severe upper limb disability. Although multiple prognostic factors have been reported to be associated with the development of post-traumatic HO, no model has yet been able to combine these predictors more succinctly to convey prognostic information and medical measures to patients. Therefore, this study aimed to identify prognostic factors leading to the formation of HO after surgery for elbow trauma, and to establish and validate a nomogram to predict the probability of HO formation in such particular injuries.

Limited success in regenerating large bone defects has been achieved by bridging them with osteoconductive materials. These substitutes lack the osteogenic and osteoinductive properties of bone autograft. A direct approach would be to stimulate osteogenesis in these biomaterials by the addition of fresh bone-marrow cells (BMC). We therefore created osteoperiosteal gaps 2 cm wide in the ulna of adult rabbits and either bridged them with coral alone (CC), coral supplemented with BMC, or left them empty. Coral was chosen as a scaffold because of its good biocompatibility and resorbability. In osteoperiosteal gaps bridged with coral only, the coral was invaded chiefly by fibrous tissue. It was insufficient to produce union after two months. In defects filled with coral and BMC an increase in osteogenesis was observed and the bone surface area was significantly higher compared with defects filled with coral alone. Bony union occurred in six out of six defects filled with coral and BMC after two months. An increase in the resorption of coral was also observed, suggesting that resorbing cells or their progenitors were present in bone marrow and survived the grafting procedure. Our findings have shown that supplementation of coral with BMC increased both the resorption of material and osteogenesis in defects of a clinical significance

The advent of modular porous metal augments has ushered in a new form of treatment for acetabular bone loss. The function of an augment can be seen as reducing the size of a defect or reconstituting the anterosuperior/posteroinferior columns and/or allowing supplementary fixation. Depending on the function of the augment, the surgeon can decide on the sequence of introduction of the hemispherical shell, before or after the augment. Augments should always, however, be used with cement to form a unit with the acetabular component. Given their versatility, augments also allow the use of a hemispherical shell in a position that restores the centre of rotation and biomechanics of the hip. Progressive shedding or the appearance of metal debris is a particular finding with augments and, with other radiological signs of failure, should be recognized on serial radiographs. Mid- to long-term outcomes in studies reporting the use of augments with hemispherical shells in revision total hip arthroplasty have shown rates of survival of > 90%. However, a higher risk of failure has been reported when augments have been used for patients with chronic pelvic discontinuity.

Cite this article: Bone Joint J 2024;106-B(4):312–318.

Aims

Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury.

Aims

Arthroscopic microfracture is a conventional form of treatment for patients with osteochondritis of the talus, involving an area of < 1.5 cm². However, some patients have persistent pain and limitation of movement in the early postoperative period. No studies have investigated the combined treatment of microfracture and shortwave treatment in these patients. The aim of this prospective single-centre, randomized, double-blind, placebo-controlled trial was to compare the outcome in patients treated with arthroscopic microfracture combined with radial extracorporeal shockwave therapy (rESWT) and arthroscopic microfracture alone, in patients with ostechondritis of the talus.

Aims

The aim of this study was to report the patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia (TIO) to allow the early diagnosis of this rare condition.

Paediatric bone sarcomas are a dual challenge for orthopaedic surgeons in terms of tumour resection and reconstruction, as it is important to minimize functional and growth problems without compromising survival rates. Cañadell’s technique consists of a Type I epiphysiolysis performed using continuous distraction by an external fixator prior to resection. It was designed to achieve a safe margin due to the ability of the physeal cartilage to be a barrier to tumour spread in some situations, avoiding the need for articular reconstruction, and preserving the growth capacity most of the times. Despite initial doubts raised in the scientific community, this technique is now widely used in many countries for the treatment of metaphyseal paediatric bone sarcomas. This annotation highlights the importance of Cañadell’s work and reviews the experience of applying it to bone sarcoma patients over the last 40 years.

Cite this article: Bone Joint J 2023;105-B(1):11–16.

Aims

Endoprosthetic reconstruction following distal femur tumour resection has been widely advocated. In this paper, we present the design of an uncemented endoprosthesis system featuring a short, curved stem, with the goal of enhancing long-term survivorship and functional outcomes.

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis. In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment

Aims

As an alternative to external fixators, intramedullary lengthening nails (ILNs) can be employed for distraction osteogenesis. While previous studies have demonstrated that typical complications of external devices, such as soft-tissue tethering, and pin site infection can be avoided with ILNs, there is a lack of studies that exclusively investigated tibial distraction osteogenesis with motorized ILNs inserted via an antegrade approach.

1. Two girls with non-familial osteogenesis imperfecta who subsequently developed osteosarcoma of the femur are described. One is of special interest in that there were multiple bone metastases. 2. It is suggested that the tumours arose spontaneously and were not related to the underlying bone disorder. 3. Because of the relative frequency of hyperplastic callus formation in osteogenesis imperfecta it is most important that adequate biopsy material of any suspicious lesion is examined because the early clinical picture may be indistinguishable from a tumour

We report a postal survey of 59 families of children with osteogenesis imperfecta. From the 51 replies we collected data on developmental milestones and walking ability and related them to the Sillence and the Shapiro classifications of osteogenesis imperfecta. Twenty-four of the patients had been treated by intramedullary rodding. Both classifications helped to predict eventual walking ability. We found that independent sitting by the age of ten months was a predictor for the use of walking as the main means of mobility with 76% attaining this. Of the patients who did not achieve sitting by ten months, walking became the main means of mobility in only 18%. The developmental pattern of mobility was similar in the rodded and non-rodded patients

The beneficial effect upon osteogenesis of imprenating bone grafts with autologous red marrow is well documented. The experimental findings reported in a previous paper suggested that prepared xenograft bone might provide a good medium for osteogenesis by marrow cells. This paper is a preliminary report of the first clinical attempt to use xenografts of bone combined with autologous red marrow. Kiel bone, which was found the most suitable, was impregnated with marrow aspirated from the iliac crest and, apart from one case of infection, gave excellent results in twenty-eight patients under conditions covering a wide range of indications for bone grafting. Further trials should allow a more valid assessment

Six patients are described with idiopathic osteoporosis which began between the ages of 4 and 16 years. In four children the disorder was mild with pain in the back, vertebral collapse, qualitatively normal iliac bone biopsies, variable calcium balance and spontaneous recovery. The two remaining patients had progressive bone disease with deformity. One with a previously normal skeleton developed changes similar to those of osteogenesis imperfecta; in the other patient, who rapidly developed structural collapse associated with severe metaphysial osteoporosis, treatment was ineffective and the histological appearances of the bone suggested osteoblastic failure. Quantitative bone histology in four patients showed no evidence of excessive active resorption; and the ratio of Type III to Type I collagen in the skin was normal, in contrast to the findings in osteogenesis imperfecta. The significance of this study in relation to previous accounts is reviewed

1. The humoral immune response of rats against sheep iliac bone grafts has been examined. 2. Fresh, marrow-containing grafts elicited a brisk and sustained antibody response. Attempts to wash out the marrow were not uniformly successful in removing cellular antigens from the grafts. 3. Decalcifying and freezing bone grafts at —20 degrees Celsius do not impair immunogenicity to any significant extent. Immunogenicity was found to be reduced in grafts subjected to freeze-drying. 4. Deproteinised Oswestry bone grafts and Kiel grafts gave rise to antibody production in a few recipients, and in the case of the former this response did not occur until after six or seven weeks from grafting. 5. The highest degree of osteogenesis in composite bone xenograft-autografts was found by Salama and colleagues (1973) to occur in Oswestry bone grafts. It is suggested that osteogenesis in xenografts may be impaired by an immune response

1. Osteogenesis imperfecta is characterised by osseous fragility. Patients with the "congenita" form have multiple fractures before birth; those with the "tarda" form have osteoporosis, and develop multiple fractures and milder deformities of long bones at varying times after birth. 2. The frequency of blue sclera, dentinogenesis imperfecta, bruising, ligamentous laxity, and deafness are recorded in sixty patients seen at the Hospital for Sick Children, Toronto, from 1949 to 1969. The major orthopaedic deformities of long bones were antero-lateral bowing of femur and anterior bowing (sabre shin) of tibia. 3. The incidence of scoliosis (40 per cent) is high in osteogenesis imperfecta. Two patients, one in Toronto and one in Seattle, have had Harrington instrumentation and fusion for this. 4. Fractures were commonest in the femur and tibia and few in the cervical spine and femoral neck. There were four cases of disturbing hyperplastic callus formation. 5. Twenty-one patients were operated on for long bone deformities and recurrent fractures by the Sofield technique. Despite extensive subperiosteal dissection non-union is rare (four cases). Fourteen of twenty-one patients so treated are able to walk, with or without assistance. Surgical intervention to both correct and prevent deformities is justified. 6. Patients with osteogenesis imperfecta compensated for their disability by reasonable academic achievement and by choosing a sedentary occupation

1. In the experiments undertaken autogenous vesical mucosal transplants were made in guinea-pigs. The transplanted mucosa proliferates and forms a nodule. Central necrosis of the nodule and the secretion of the proliferating epithelium combine to form a cyst filled with a viscous fluid. 2. Before the cyst is well defined some of this fluid diffuses into the sub-epithelial connective tissue, producing areas of tissue oedema which later are transformed into translucent hyaloid islands. With further condensation of the collagen fibres, these areas are converted into primitive bone. The hyaloid islands act as a bone precursor. Bone always formed in the wall of the cyst within thirty days except in cases of sepsis or death of the transplant, when there was no osteogenesis. Homografts of vesical mucosa were found unreliable in their capacity to induce bone. 3. The results of the histochemical investigation and radiographic diffraction of the hyaloid areas suggest that the proliferating mucosa is the source of the inducing agent. 4. Bone can be induced only in sites where a primitive vascular connective tissue is growing and where there exists an adequate blood supply. 5. The rapid rate of osteogenesis can be seen in the radiographs of induced bone in radial defects. The electron-microscopic study of the induced bone at three weeks confirmed that osteoid had been formed so quickly that calcification had not yet taken place. 6. The relationship between the bone induced by transplanting vesical epithelium and the formation of urinary calculi is discussed and their common origin postulated

In osteogenesis imperfecta the formation of callus is usually plentiful and sometimes rather excessive but the excess is absorbed in the normal way as consolidation occurs. In hyperplastic callus formation the amount of callus formed is large, or even enormous; and, once its limits are defined and ossification has occurred, some part of the original swelling remains as a thickening of the bone. "Callus" may form with or without injury and with or without fracture. The interest of the present case lies partly in the fact that there is no history of multiple fractures to indicate classical osteogenesis imperfecta, and partly in the familial incidence which has also been noted in other records. It is important to recognise the true nature of the condition in order to avoid the tragedy of unnecessary amputation. In one of Brailsford's cases the lesion is said to have become malignant but there is no other evidence in the literature that the condition has any relationship to malignancy. The clinical appearance can easily give rise to the suspicion of malignancy, and on histological examination the highly cellular and rapidly growing callus can be confused with a malignant condition. In fact, for the short time in which the bone formation runs riot the behaviour of a malignant neoplasm is closely simulated. It is thought that the present account may be of interest because of the invariable relief of pain after x-ray treatment of each new lesion, the length of time over which the case has been followed and the resemblance between the radiographic appearances in the patient now and those of her aunt taken twenty years ago

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

We describe a series of 20 patients with ununited fractures of the femoral neck following neglected trauma or failed primary internal fixation who were seen at a mean of 7.5 months (2 to 18) following injury. Open reduction and internal fixation of the fracture was performed in all patients, together with a myoperiosteal flap on the quadratus femoris muscle pedicle. Union occurred at a mean of 4.9 months (2 to 10) in all patients. The mean follow-up was for 70 months (14 to 144). There was no further progression in six of seven patients with pre-operative radiological evidence of osteonecrosis of the femoral head. One patient had delayed collapse and flattening of the femoral head ten years after union of the fracture, but remained asymptomatic. This study demonstrates the orthopaedic application of myoperiosteal grafting for inducing osteogenesis in a difficult clinical situation

1. The present study is an attempt to analyse and apportion significance to the role of inductive mechanisms in bone transplantation. 2. The experimental model used in the present work is that of the composite homograftautograft of cancellous bone previously described (Burwell 1964a). 3. Iliac bone was removed from hooded rats and washed free from its marrow. The bone was then treated by various physical and chemical methods (some of which have been used by other workers to prepare bank bone), namely freezing (-20 degrees Centigrade, -79 degrees Centigrade, -196 degrees Centigrade); freeze-drying (without sterilisation, sterilisation with high energy radiation, sterilisation with ß-propiolactone); decalcification (with E.D.T.A.); irradiation (in the frozen state at a dose of 4 million rads); boiling in water; immersion in merthiolate solution; extraction of organic components with ethylenediamine: and calcining at 660 degrees Centigrade. The treated bone was then impregnated with fresh autologous marrow procured from the femoral shaft of the Wistar rat into which the treated composite graft was to be implanted. The grafts were inserted intramuscularly and removed for study after two, six and twelve weeks. 4. After fixation, serial sectioning and staining, each graft was examined microscopically, and the proportion of new bone/grafted bone scored using an arbitrary scale (0-4). The mean score (and the standard error of the mean score) was then plotted for each treated composite graft and also for several types of fresh cancellous bone grafts. 5. It was found (Fig. 2) that the various treated composite grafts formed a spectrum of bone-forming capacities–the maximum scores being attained by the frozen and freeze-dried composite grafts, the lowest scores by the "deproteinised" composite grafts. 6. The reasons for these differences are discussed. It is concluded that cancellous bone, after transplantation, has the property to induce and promote osteogenesis in marrow; moreover, that this property is contained in the organic components of bone. 7. From the standpoint of inductive mechanisms, cancellous bone treated by freezing or freeze-drying seems to be the most suitable devitalised bone for grafting purposes; bone which has been boiled or merthiolated less suitable; and "deproteinised" bone the least suitable. 8. Freeze-dried bone sterilised physically (by high energy radiation) or chemically (by ß-propiolactone) did not form significantly less new bone than did freeze-dried bone which had not been sterilised. 9. Remodelling mechanisms in bone transplantation are briefly discussed and attention drawn to the deficiencies of present knowledge. The quantitative studies of other workers have indicated that freeze-dried bone may be more rapidly remodelled than is frozen bone. 10. The importance of fresh red marrow in promoting osteogenesis in bone transplantation and in the healing of certain fractures, is emphasised. It seems likely that the interrelationship of bone and marrow revealed by experiment has wider significance not only in health and in response to injury but also in causation of certain idiopathic bone disorders

Aims

The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses.

Aims

To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (β-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes.

A case of osteogenesis imperfecta, presenting with bowed deformity of both forearm bones and dislocation of the radial head was treated by separate elongation of both bones using Ilizarov's external fixator

1. Fifty operations of fragmentation and rodding in the long bones of patients with osteogenesis imperfecta are reported. 2. The technique of the operation is described and a modification of Sofield's original method is suggested. 3. The results and complications of treatment are described

1. The effects of frozen irradiated homogenous bone grafts on the healing of circumscribed defects in the mandibles and femora of forty albino rats have been studied. 2. The grafts were well tolerated by the host animals and did not appear in any way either to stimulate or to inhibit osteogenesis. The rate of healing of the defects containing the homografts compared favourably with that of the control defects

A case of hyperplastic callus formation is reported in a girl of eleven; several bones were affected. There were no associated fractures. She is believed to be suffering from a mild non-familial type of osteogenesis imperfecta without blue sclerotics and presents multiple bony excrescences unassociated with injury. The relevant literature is reviewed. The effect of a trial of treatment with A.C.T.H. and with deep x-ray is reported

New methods of limb lengthening are being adopted in the hope of overcoming the poor osteogenic responses characteristic of distraction. Delay between the osteotomy and starting distraction is said to be important but there is little experimental evidence. We have compared immediate with delayed distraction in the rabbit tibia and shown that delay is an important factor in promoting osteogenesis. It seems that its effects are partly mediated by an improvement in the extra-osseous blood supply

1. The venographic findings in clinical primary osteoarthritis are described. 2. Experimental venous engorgement, of the knee joint and of healing fibular fractures, results in accelerated bone formation and disturbed cartilage formation. 3. Changes in pH, ppCO. 2. , and PPO. 2. are indicated as the chemical means by which chondrogenesis and osteogenesis can be altered. 4. It is suggested that chronic venous stress in joints is a causal factor in primary osteoarthritis

This paper describes a procedure of activating osteogenesis by the use of the "petal" technique. The osteogenetic effect of these "petals" has been established in experimentally produced fractures and pseudarthroses in rats by radiographical, biomechanical, mechanical and histological examinations. The conventional concept of the osteogenetic activity of bone transplants is discussed. The authors feel that this method will find its clinical application in the operative treatment of pseudarthroses and, in selected cases, of fractures that are known for their tendency to unite slowly

Results are given of a study of four cases of osteogenesis imperfecta using biophysical methods comprising microradiography, microscopy using polarised light, and x-ray diffraction. Rebuilding of bone tissue was infrequent in the material studied and has been shown to occur in an abnormal manner. The mineralisation of the bone is more uniform than is found in normal bone. The collagen has an abnormal organisation and is sparse. The ultrastructure of bone salts and their orientation are as in normal bone

1. Osteogenesis in the osteoarthritic femoral head has been examined with radioactive . 32. P and tetracycline bone markers. 2. In advanced osteoarthritis considerable osteogenic activity was observed, particularly in osteophytes, around cysts and in some areas of bone sclerosis. 3. Two forms of osteogenesis were seen: a form of enchondral ossification, and apposition of new bone to existing bone trabeculae. 4. The findings support previous studies suggesting that rapid turnover of bone tissues occurs in advanced osteoarthritis

1. A method is described for the in vivo and in vitro study of osteogenesis by implanting a modified transparent chamber in half lop-eared rabbits (as originated by Sandison 1928). This method allows the daily observation and photography of the developing bone and the study of its intimate connection with the vascularity of the area. 2. The osteogenetic potential of a variety of substances can also be investigated by this method. The tissue in the chamber can easily be prepared for its final examination by optical and electron microscopy and by other laboratory techniques

Miller-Galante II total knee arthroplasty (MG II TKA) was performed on 32 knees in 30 patients. On both the femoral and tibial components, the fibre-metal area was plasma-sprayed with hydroxyapatite-tricalcium phosphate (HA-TCP). The clinical and radiographic outcome was evaluated. A mean pre-operative knee score of 26.0 ± 18.6 (SD) increased to 97.5 ± 3.5 and a mean pre-operative functional score of 21.7 ± 15.0 (SD) increased to 83.4 ± 12.4 at follow-up of seven years. Clear zones were common around the components at one month post-operatively but had completely disappeared after six months. An autopsy of a patient who underwent MG II TKA with HA-TCP two years previously, showed osteogenesis in all parts of the fibre-metal, and bone tissue comprised 77.7% of the interface. This coated prosthesis has good early fixation which is maintained at seven years with good clinical and radiographic outcomes

1. In tuberculous disease of the hip, premature epiphysial fusion at the knee joint is due to rupture of the epiphysial cartilaginous plates consequent upon resorption of cancellous support and suppression of osteogenesis. 2. In the tibia, premature fusion is usually preceded by near-central "bulging" of the metaphysial and tibial marrow through the epiphysial plate. In the femur, epiphysial changes preceding fusion are of a fragmentary type. 3. Injury, in quiescent disease, plays little or no part in the causation of premature epiphysial fusion. 4. The factors which are responsible for these changes—local toxaemia and prolonged immobilisation—must exist for not less than two years. 5. In cases which are treated conservatively for long periods the incidence of premature fusion, with serious shortening of the limb, is so high that the wisdom of such treatment must be reconsidered

Using bone decalcilied with 0.6 N hydrochloric acid as an inducing agent, the inductive capacity of different soft tissue sites was investigated. Muscle and fascia regularly permitted the induction of bone, while spleen, liver and kidney suppressed bone induction. Bone formation could be induced in these organs if living autologous fascia was implanted together with the inducing agent; while bone formation was inhibited when living autologous spleen tissue was implanted with the inducing agent to normally favourable sites. The administration of systemic heparin and the diphosphonate ethane-1-hydroxyl, 1-diphosphonic acid (EHDP) suppressed bone induction. It is suggested that for bone induction to occur in soft tissues, three conditions must be present: 1) an inducing agent; 2) an osteogenic precursor cell; and 3) an environment which is permissive to osteogenesis. The presence of osteogenic inhibitors in spleen, liver and kidney is postulated

1. Experimental defects in the cranial vaults of young adult rabbits were implanted with decalcified, deproteinised and deep frozen homogenous whole bone. The experiments were similar to those of Ray and Holloway (1957) except that these workers used rats as the experimental animals. In addition, six control defects were made and not implanted. 2. All animals were killed six weeks after operation and thirty-four defects were studied by radiology and by histology. 3. All implants became surrounded by connective tissue and in all cases some new bone formed in apposition to implanted fragments. The degree of incorporation of the implants in new bone varied widely, not only between the three implanted groups, but also within each group. In general, new bone formation was greatest in defects implanted with deproteinised and whole bone, least in defects implanted with decalcified bone. 4. The fate of bone implants and the extent to which they can be said to induce osteogenesis are discussed

Three elderly sibling dwarfs are reported from a large and otherwise normal family. Their condition is an unusual and irregular form of cartilaginous defect, combined with club-feet, and bearing some resemblance to the Morquio type. A brief consideration of the literature of the generahised developmental bony syndromes shows confusion of thought and nomenclature. A plea is therefore made for simplification and a rational and simple grouping of these conditions is attempted. It seems particularly desirable that many confusing names for particular syndromes should be scrapped (for example, dyschondroplasia, chondro-osteodystrophy), although quite evidently the terms achondroplasia and osteogenesis imperfecta must remain because of their long-standing and general usage. Incidentally I have suggested elsewhere (Jackson 1951) that the name cleido-cranial dysostosis should be dropped, because it tends to lead the investigator away from the clinically more important lesions in the teeth and the cartilage bones of the pelvis and legs. It seems reasonable to confine the nomenclature of these various syndromes to the names used in the above classification, or something on those lines

We performed posterior fixation with a Hartshill-Ransford contoured loop in 43 patients with instability at the craniocervical junction. No external bracing was used. Fifteen patients had congenital malformations, ten had tumours, seven had 'bone-softening' conditions (such as osteogenesis imperfecta), five had suffered complicated fractures, three had occipito-C1-C2 hypermobility due to lax ligaments and three had severe degenerative spondylosis with pseudotumours of the transverse ligament. Twenty-nine patients had transoral decompression of the cord before fixation. In most cases, cancellous bone grafts taken from the iliac crest were used to induce fusion; in nine very ill patients, no bone graft was used. In the whole series there was no instance of construct failure, broken wire or laminar fracture. The best results were achieved in patients with tumours or bone-softening conditions. No patient with normal neurology deteriorated after surgery but seven had worse neurological deficits after operation than before. Neck stiffness caused half the patients to change their lifestyle

In a clinical, radiological and biochemical study of forty-two patients from Oxford with osteogenesis imperfecta, it was found that patients could be divided simply into mild, moderate and severe groups according to deformity of long bones. In the severe group (seventeen patients) a family history of affected members was uncommon and fractures began earlier and were more frequent than in the mild group (twenty-two patients); sixteen patients in the severe group had scoliosis and eleven had white sclerae; no patients in the mild group had white sclerae or scoliosis. Radiological examination of the femur showed only minor modelling defects in patients in the mild group, whereas in the severe group five distinct appearances of bone (thin, thick, cystic and buttressed bones, and those with hyperplastic callus) were seen. The polymeric (structural) collagen from skin was unstable to depolymerisation in patients in the severe group, but normal in amount, whereas the reverse was found in the mild group. This division according to long bone deformity may provide a basis for future research more useful than previous classifications

We used an experimental rabbit model of leg lengthening to study the morphology and function of muscle after different distraction rates. Lengthening was in twice-daily increments from 0.4 to 4 mm per day. New contractile tissue formed during lengthening, but some damage to the muscle fibres was seen even at rates of less than 1 mm per day; abnormalities increased with larger rates of lengthening. There was proliferation of fibrous tissue between the muscle fibres at distraction rates of over 1 mm per day. Active muscle function showed adaptation when the rate was 1.0 mm per day or less, but muscle compliance was normal only after rates of 0.4 mm per day. Muscle responded more favourably at rates of distraction slower than those shown to lead to the most prolific bone formation. At present the rate of distraction in clinical practice is determined mainly by factors which enhance osteogenesis. Our study suggests that it may be advisable to use a slower rate of elongation in patients with poor muscle compliance associated with the underlying pathology; this will allow better accommodation by the contractile and connective tissues of the muscles

We have examined the process of fusion of the intertransverse processes and bone graft in the rabbit by in situ hybridisation and evaluated the spatial and temporal expression of genes encoding pro-α1 (I) collagen (COL1A1), pro-α1 (II) collagen (COL2A1) and pro-α1 (X) collagen (COL10A1). Beginning at two weeks after operation, osteogenesis and chondrogenesis occurred around the transverse process and the grafted bone at the central portion of the area of the fusion mass. Osteoblasts and osteocytes at the newly-formed woven bone expressed COL1A1. At the cartilage, most chondrocytes expressed COL2A1 and some hypertrophic chondrocytes COL10A1. In some regions, co-expression of COL1A1 and COL2A1 was observed. At four weeks, such expressions for COL1A1, COL2A1 and COL10A1 became prominent at the area of the fusion mass. From four to six weeks, bone remodelling progressed from the area of the transverse processes towards the central zone. Osteoblasts lining the trabeculae expressed a strong signal for COL1A1. At the central portion of the area of the fusion mass, endochondral ossification progressed and chondrocytes expressed COL2A1 and COL10A1. Our findings show that the fusion process begins with the synthesis of collagens around the transverse processes and around the grafted bone independently. Various spatial and temporal osteogenic and chondrogenic responses, including intramembranous, endochondral and transchondroid bone formation, progress after bone grafting at the intertransverse processes. Bone formation through cartilage may play an important role in posterolateral spinal fusion

Experiments on white mice were undertaken to determine the reaction of bone to the intramedullary introduction of the virus of tick-borne encephalitis. The following conclusions were drawn. 1. The tick-borne encephalitis virus S47, when introduced intraosteally in white mice, provokes osteitis. 2. Inflammation may lead to acute necrosis of bone, preceded by marked medullary oedema and subsequent proliferation, or it may take a milder form with haemorrhagic effusion into the marrow tissue and subsequent hyperplasia of connective tissue. 3. Damage to the epiphysial and articular cartilage may ensue in the course of acute necrotic osteitis. 4. Skeletal and extra-skeletal osteogenesis is a characteristic feature of viral osteitis. 5. In radiographs in acute viral osteitis with extensive necrosis the expanded bone appears to be thickened. 6. Viruses of the S47 strain introduced intraosteally preserve their affinity for brain tissue after three passages through bone. 7. Viruses introduced into the bony tissue preserve their toxicity and are found in the bony tissue after ten days in quantities lethal for young mice when inoculated intracerebrally. 8. The tick-borne encephalitis virus S47 is pathogenic when inoculated into the marrow in white mice. 9. In osteitis of non-bacterial origin in man the possibility of viral infection should be considered

Aims

The aim of this study was to compare the surgical and quality-of-life outcomes of children with skeletal dysplasia to those in children with idiopathic early-onset scoliosis (EOS) undergoing growth-friendly management.

In this study the direct relationship between the type of bone implant used, the vascular reaction caused to the host and the revascularisation of the implant has been studied. It was found that the best graft was that which was the most rapidly and permanently vascularised. Not only was the biological affinity between the graft and the bed important, but the structural facilities offered by the implant for the "penetration" by the host vessels were also of paramount importance. Thus small, fresh, cancellous bone grafts offered the best chance of rapid incorporation provided they were not crushed to the point of making vascular progress difficult. The findings from this investigation so strongly suggest that the rapid revascularisation of the bone grafts was because of an end-to-end anastomosis of the vessels of the host with those in the implant that it seems justified to consider that the best bone graft is that which is richest in vessels. Apart from a recent short paper by Graf (1960), we have not found this assertion before. It is this which seems to make the fresh, autogenous, cancellous implant so superior to all others. We believe that any new material for bone grafts should be tested by the technique described here. The material which one day may replace fresh, autogenous, cancellous implants will have to show the same readiness to vascular penetration, vascular osteogenesis and vascular permanency that at present is exhibited only by the cancellous autograft

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. 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

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

A significant percentage of patients remain dissatisfied after total knee arthroplasty (TKA). The aim of this study was to determine whether the sequential addition of accelerometer-based navigation for femoral component preparation and sensor-guided ligament balancing improved complication rates, radiological alignment, or patient-reported outcomes (PROMs) compared with a historical control group using conventional instrumentation.

Aims

Heterotopic ossification (HO) is a potentially devastating complication of the surgical treatment of a proximal humeral fracture. The literature on the rate and risk factors for the development of HO under these circumstances is lacking. The aim of this study was to determine the incidence and risk factors for the development of HO in these patients.

1. Previous immunological studies have shown that homografts of fresh marrow-free iliac bone are only weakly, if at all, antigenic. 2. In view of this finding an attempt was made to produce a foreign bone graft capable of forming new bone as readily as an iliac autograft by the following method. Living cells of high osteogenic potential and of autologous type were introduced into the graft by combining homologous fresh marrow-free iliac bone with the animal's own red marrow to form a fresh composite homograft-autograft of cancellous bone. 3. Such fresh composite homograft-autografts were inserted into a muscular site in Wistar rats and removed for microscopical examination at intervals of one to seven days and at two, six and twelve weeks after transplantation. 4. It is found that bone and marrow together as a fresh composite homograft-autograft form considerably more new bone than do either of the components of the graft transplanted separately. Homografts of fresh marrow-free iliac bone form, in general, a small amount of early phase and late phase new bone. Autografts of red marrow transplanted alone to a muscular site formed new bone in thirteen to thirty experiments (43 per cent). 5. The stimulus to osteogenesis, and the cellular source of osteoblasts, in marrow autografts is discussed in the light of present knowledge. The concept is suggested that after its transplantation there develops in marrow an inductive system leading to osteoblastic differentiation and bone formation. It is proposed that the necrosis of a portion of a marrow graft liberates osteogenic substances which are taken up by primitive wandering cells derived from littoral cells lining the vascular sinusoids of the surviving portions of the marrow which are induced, thereby, to differentiate as osteoblasts. 6. The cellular source of osteoblasts in a fresh composite homograft-autograft of cancellous bone is discussed. It is deduced that the new bone is derived mainly from the contained marrow of the graft, by mechanisms similar to those leading to osteoblastic differentiation in transplanted autografts of marrow. 7. The stimulus to the greater formation of new bone by fresh composite autograft-homografts than by autografts of marrow transplanted alone is discussed. Two explanations are suggested: 1) a more extensive necrosis of marrow in a composite homograft-autograft than in marrow transplanted alone; and 2) an inductive effect of bone upon marrow. 8. The new bone formed by autografts of fresh marrow-containing iliac bone, it is concluded, is derived not only from osteoblasts on the surfaces of the grafted bone but also from primitive wandering cells derived from littoral cells lining the vascular sinusoids of the surviving portions of its marrow. 9. Mechanisms which may play a role in the histogenesis of woven bone are discussed. 10. The significance of the relation of bone and marrow is considered briefly in the light of knowledge concerning the venous patterns of bone and marrow

Aims

The primary aim of this study was to evaluate the performance and safety of magnetically controlled growth rods in the treatment of early onset scoliosis. Secondary aims were to evaluate the clinical outcome, the rate of further surgery, the rate of complications, and the durability of correction.

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

Aims

The aim of this study was to describe the technique of distraction osteogenesis followed by arthrodesis using internal fixation to manage complex conditions of the ankle, and to present the results of this technique.

Aims

The success of anterior cruciate ligament reconstruction (ACLR) depends on osseointegration at the graft-tunnel interface and intra-articular ligamentization. Our aim was to conduct a systematic review of clinical and preclinical studies that evaluated biological augmentation of graft healing in ACLR.

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

Aims

The aim of this double-blind prospective randomised controlled trial was to assess whether low intensity pulsed ultrasound (LIPUS) accelerated or enhanced the rate of bone healing in adult patients undergoing distraction osteogenesis.

Aims

The management of a significant bony defect following excision of a diaphyseal atrophic femoral nonunion remains a challenge. We present the outcomes using a combined technique of acute femoral shortening, stabilized with a long retrograde intramedullary nail, accompanied by bifocal osteotomy compression and distraction osteogenesis with a temporary monolateral fixator.

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

This study describes the use of the Masquelet technique to treat segmental tibial bone loss in 12 patients.

Aims

We reviewed 34 consecutive patients (18 female-16 male) with isthmic spondylolysis and grade I to II lumbosacral spondylolisthesis who underwent in situ posterolateral arthodesis between the L5 transverse processes and the sacral ala with the use of iliac crest autograft. Ten patients had an associated scoliosis which required surgical correction at a later stage only in two patients with idiopathic curves unrelated to the spondylolisthesis.

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses.

Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure.

In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future.

Cite this article: Bone Joint J 2014;96-B:291–8.

Aims

Heterotopic ossification (HO) occurs after arthroplasty, especially total hip arthroplasty. In this study we describe the incidence, evolution, morphology and clinical consequences of HO following reverse shoulder arthroplasty.

For the treatment of ununited fractures, we developed a system of delivering magnetic labelled mesenchymal stromal cells (MSCs) using an extracorporeal magnetic device. In this study, we transplanted ferucarbotran-labelled and luciferase-positive bone marrow-derived MSCs into a non-healing femoral fracture rat model in the presence of a magnetic field. The biological fate of the transplanted MSCs was observed using luciferase-based bioluminescence imaging and we found that the number of MSC derived photons increased from day one to day three and thereafter decreased over time. The magnetic cell delivery system induced the accumulation of photons at the fracture site, while also retaining higher photon intensity from day three to week four. Furthermore, radiological and histological findings suggested improved callus formation and endochondral ossification. We therefore believe that this delivery system may be a promising option for bone regeneration.

Aims

We evaluated clinical and radiographic outcomes of total shoulder arthroplasty (TSA) using the second-generation Trabecular Metal (TM) Glenoid component. The first generation component was withdrawn in 2005 after a series of failures were reported. Between 2009 and 2012, 40 consecutive patients with unilateral TSA using the second-generation component were enrolled in this clinical study. The mean age of the patients was 63.8 years (40 to 75) and the mean follow-up was 38 months (24 to 42).

Tibial nonunion represents a spectrum of conditions which are challenging to treat, and optimal management remains unclear despite its high rate of incidence. We present 44 consecutive patients with 46 stiff tibial nonunions, treated with hexapod external fixators and distraction to achieve union and gradual deformity correction. There were 31 men and 13 women with a mean age of 35 years (18 to 68) and a mean follow-up of 12 months (6 to 40). No tibial osteotomies or bone graft procedures were performed. Bony union was achieved after the initial surgery in 41 (89.1%) tibias. Four persistent nonunions united after repeat treatment with closed hexapod distraction, resulting in bony union in 45 (97.8%) patients. The mean time to union was 23 weeks (11 to 49). Leg-length was restored to within 1 cm of the contralateral side in all tibias. Mechanical alignment was restored to within 5° of normal in 42 (91.3%) tibias. Closed distraction of stiff tibial nonunions can predictably lead to union without further surgery or bone graft. In addition to generating the required distraction to achieve union, hexapod circular external fixators can accurately correct concurrent deformities and limb-length discrepancies.

Cite this article: Bone Joint J 2015;97-B:1417–22.

We report patient-reported outcomes and complications associated with contemporary periacetabular osteotomy (PAO) surgery in treating symptomatic acetabular dysplasia and compare these outcomes with total hip arthroplasty (THA) in patients with similar demographic details. Two consecutive cohorts included patients between aged 18 to 40 years who had undergone either PAO (100 hips; 24 male, 76 female) or THA (55 hips; 18 male, 37 female). At a mean follow-up of 5.9 years (2 to 13), there was significant improvement in the modified Harris hip pain (p < 0.001, PAO and p < 0.001, THA), function (p < 0.001, PAO and p = 0.001, THA), and total scores (p < 0.001, PAO and p < 0.001, THA) within each cohort. There were no significant differences in the clinical outcome scores between the groups. Complication rates were low and similar in each cohort (p = 0.68). Similar to THA, contemporary PAO surgery is a clinically effective procedure that improves function and activity levels, provides pain relief and is associated with an acceptable complication rate.

Cite this article: Bone Joint J 2015;97-B:1322–7.

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.

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

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

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

A common situation presenting to the orthopaedic surgeon today is a worn acetabular liner with substantial acetabular and pelvic osteolysis. The surgeon has many options for dealing with osteolytic defects. These include allograft, calcium based substitutes, demineralised bone matrix, or combinations of these options with or without addition of platelet rich plasma. To date there are no clinical studies to determine the efficacy of using bone-stimulating materials in osteolytic defects at the time of revision surgery and there are surprisingly few studies demonstrating the clinical efficacy of these treatment options. Even when radiographs appear to demonstrate incorporation of graft material CT studies have shown that incorporation is incomplete. The surgeon, in choosing a graft material for a surgical procedure must take into account the efficacy, safety, cost and convenience of that material.

Cite this article: Bone Joint J 2014;96-B (11 Suppl A):70–2.

The incidence of acute and chronic conditions of the tendo Achillis appear to be increasing. Causation is multifactorial but the role of inherited genetic elements and the influence of environmental factors altering gene expression are increasingly being recognised. Certain individuals’ tendons carry specific variations of genetic sequence that may make them more susceptible to injury. Alterations in the structure or relative amounts of the components of tendon and fine control of activity within the extracellular matrix affect the response of the tendon to loading with failure in certain cases.

This review summarises present knowledge of the influence of genetic patterns on the pathology of the tendo Achillis, with a focus on the possible biological mechanisms by which genetic factors are involved in the aetiology of tendon pathology. Finally, we assess potential future developments with both the opportunities and risks that they may carry.

Cite this article: Bone Joint J 2013;95-B:305–13.

Failure of bone repair is a challenging problem in the management of fractures. There is a limited supply of autologous bone grafts for treating nonunions, with associated morbidity after harvesting. There is need for a better source of cells for repair. Mesenchymal stem cells (MSCs) hold promise for healing of bone because of their capacity to differentiate into osteoblasts and their availability from a wide variety of sources. Our review aims to evaluate the available clinical evidence and recent progress in strategies which attempt to use autologous and heterologous MSCs in clinical practice, including genetically-modified MSCs and those grown on scaffolds. We have compared various procedures for isolating and expanding a sufficient number of MSCs for use in a clinical setting.

There are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone.

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.