Between 1980 and 1988, displacement bone-marrow transplantation was performed on 25 children with Hurler's syndrome (type-1 mucopolysaccharidosis). We describe the musculoskeletal development of 11 of the 12 surviving children and the orthopaedic procedures undertaken to treat progressive thoracolumbar kyphosis, hip subluxation and carpal tunnel syndrome. We found abnormal bone modelling, focal failures of ossification and an avascular disorder of the femoral head in every patient and offer an explanation for these phenomena. Increasing valgus deformity of the knees and progressive generalised myopathy caused loss of mobility as the children entered adolescence. The benefit of bone-marrow transplantation as a treatment for the skeletal disorders of Hurler's syndrome is limited by the poor penetration of the musculoskeletal tissues by the enzyme derived from the leucocytes.

This paper reports a high incidence of minor congenital anomalies in boys and girls with Perthes' disease compared with that in a control population. There is a similarity of the incidence of minor anomalies in the children with Perthes' disease to that in babies with a single major congenital defect. Multiple major defects were more numerous and more severe than in the control children. It is speculated that there may be a congenital abnormality affecting skeletal development which in some way makes the hip susceptible to Perthes' disease at a later date

1. Analyses are presented of comparable groups of the two commonest bone-forming tumours—osteochondroma and osteogenic sarcoma—derived from the following sources: Bristol Bone Tumour Register; British Empire Cancer Campaign Annual Report (1949); Stocks and Barrington (1925); Meyerding (1927); and Geschickter and Copeland (1949). 2. From this study, the following features emerge as characteristic and common to both tumours. 1) Both tumours are commoner in the male during the age periods 0-34 years, and over fifty years, with the possible exceptions of tumours of the humerus during early life and tumours of the pelvis. 2) The male preponderance is most marked for the appendicular long bones. 3) The male preponderance is greatest during the age period 15-34 years. 4) In the separate bones, these tumours tend to arise at a somewhat earlier age in the female. 5) In both sexes both tumours tend to arise at an earlier age in the bones of the upper arm and shoulder girdle than in those of the lower limb and pelvis. 6) Both tumours are related to an aberration of endochondral growth in length of bone. 3. The greater growth of the male, and differences in skeletal development in the two sexes, offer a simple and reasonably consistent explanation of these peculiarities and make it possible to discern the interplay of the three factors of age, sex and site of origin of the tumour. 4. From this concept it is possible to make a crude estimate of the factors of time and bulk of tissue which when combined may well account for the observed male preponderance of these tumours, and their anatomical distribution

Bone morphogenetic protein (BMP) has a crucial role in osteochondrogenesis of bone formation as well as in the repair of fractures. The interaction between hedgehog protein and BMPs is inferred from recent molecular studies. Hedgehog genes encode secreted proteins which mediate patterning and growth during skeletal development. We have shown that Indian hedgehog gene (Ihh) is expressed in cartilage anlage and later in mature and hypertrophic chondrocytes. This finding suggests that Ihh may regulate the development of chondrocytes. Our results in this study have shown that Ihh transcripts were expressed in hypertrophic chondrocytes in mice at three days but not at three weeks, although a similar expression pattern of α1 (X) collagen could be observed in both types of cartilage. To investigate the possibility that there are direct and age-dependent functions of Ihh in chondrocytes, cultured chondrocytes were treated with the amino-terminal fragment of Sonic hedgehog protein (Shh-N) which can functionally substitute for Ihh protein. Shh-N did not affect the proliferation and differentiation of chondrocytes from three-week-old mice but had a significant effect on three-day-old mice. It enhanced proliferation up to 128% of the control culture in a dose-dependent manner. Although there was no effect in Shh-N-treated cultures, Shh-N enhanced the stimulatory effect of parathyroid hormone (PTH) on the synthesis of proteoglycans. Because the effects of Shh-N on chondrocyte differentiation in this culture system differed from those of bone morphogenetic protein-2 (BMP2) and PTH, in terms of proteoglycan synthesis and ALPase activity, it is unlikely that BMP2 or PTH/PTH-related protein mediates the direct effects of Ihh in chondrocytes. Our study shows that Ihh can function in chondrocytes in a direct and age-dependent fashion

Aims

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

Aims

The purpose of this study was to explore the correlation between femoral torsion and morphology of the distal femoral condyle in patients with trochlear dysplasia and lateral patellar instability.

Aims

It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway.

Aims

Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection.

We investigated the development of CT-based bony radiological parameters associated with femoroacetabular impingement (FAI) in a paediatric and adolescent population with no known orthopaedic hip complaints. We retrospectively reformatted and reoriented 225 abdominal CTs into standardised CT pelvic images with neutral pelvic tilt and inclination (244 female and 206 male hips) in patients ranging from two to 19 years of age (mean 10.4 years). The Tönnis angle, acetabular depth ratio, lateral centre–edge angle, acetabular version and α-angle were assessed.

Acetabular measurements demonstrated increased acetabular coverage with age and/or progressive ossification of the acetabulum. The α-angle decreased with age and/or progressive cortical bone development and resultant narrowing of the femoral neck. Cam and pincer morphology occurred as early as ten and 12 years of age, respectively, and their prevalence in the adolescent patient population is similar to that reported in the adult literature. Future aetiological studies of FAI will need to focus on the early adolescent population.

Cite this article: Bone Joint J 2013;95-B:598–604.

A self-control ratio, the spine-pelvis index (SPI), was proposed for the assessment of patients with adolescent idiopathic scoliosis (AIS) in this study. The aim was to evaluate the disproportionate growth between the spine and pelvis in these patients using SPI. A total of 64 female patients with thoracic AIS were randomly enrolled between December 2010 and October 2012 (mean age 13 years, standard deviation (sd) 2.17; 9 to 18) and a further 73 healthy female patients with a mean age of 12.4 years (mean age 12.4 years, sd 2.24; 9 to 18), were randomly selected from a normal control database at our centre. The radiographic parameters measured included length of spine (LOS), height of spine (HOS), length of thoracic vertebrae (LOT), height of thoracic vertebrae (HOT), width of pelvis (WOP), height of pelvis (HOP) and width of thorax (WOT). SPI was defined as the ratio LOS/HOP. The SPI and LOT/HOP in patients with AIS showed a significant increase when compared with normal girls (p < 0.001 and p < 0.001 respectively), implying an abnormal pattern of growth of the spine relative to the pelvis in patients with AIS.

No significant difference in SPI was found in different age groups in the control group, making the SPI an age-independent parameter with a mean value of 2.219 (2.164 to 2.239). We also found that the SPI was not related to maturity in the control group.

This study, for the first time, used a self-control ratio to confirm the disproportionate patterns of growth of the spine and pelvis in patients with thoracic AIS, highlighting that the SPI is not affected by age or maturity.

Cite this article: Bone Joint J 2015;97-B:1668–74.

We compared the accuracy of the growth remaining method of assessing leg-length discrepancy (LLD) with the straight-line graph method, the multiplier method and their variants. We retrospectively reviewed the records of 44 patients treated by percutaneous epiphysiodesis for LLD. All were followed up until maturity. We used the modified Green–Anderson growth-remaining method (Method 1) to plan the timing of epiphysiodesis. Then we presumed that the other four methods described below were used pre-operatively for calculating the timing of epiphysiodesis. We then assumed that these four methods were used pre-operatively. Method 2 was the original Green–Anderson growth-remaining method; Method 3, Paley’s multiplier method using bone age; Method 4, Paley’s multiplier method using chronological age; and Method 5, Moseley’s straight-line graph method. We compared ‘Expected LLD at maturity with surgery’ with ‘Final LLD at maturity with surgery’ for each method. Statistical analysis revealed that ‘Expected LLD at maturity with surgery’ was significantly different from ‘Final LLD at maturity with surgery’. Method 2 was the most accurate. There was a significant correlation between ‘Expected LLD at maturity with surgery’ and ‘Final LLD at maturity with surgery’, the greatest correlation being with Method 2. Generally all the methods generated an overcorrected value. No method generates the precise ‘Expected LLD at maturity with surgery’. It is essential that an analysis of the pattern of growth is taken into account when predicting final LLD. As many additional data as possible are required.

Cite this article: Bone Joint J 2013;95-B:993–1000.

The purpose of this study was to evaluate the long-term functional and radiological outcomes of arthroscopic removal of unstable osteochondral lesions with subchondral drilling in the lateral femoral condyle. We reviewed the outcome of 23 patients (28 knees) with stage III or IV osteochondritis dissecans lesions of the lateral femoral condyle at a mean follow-up of 14 years (10 to 19). The functional clinical outcomes were assessed using the Lysholm score, which improved from a mean of 38.1 (sd 3.5) pre-operatively to a mean of 87.3 (sd 5.4) at the most recent review (p = 0.034), and the Tegner activity score, which improved from a pre-operative median of 2 (0 to 3) to a median of 5 (3 to 7) at final follow-up (p = 0.021). The radiological degenerative changes were evaluated according to Tapper and Hoover’s classification and when compared with the pre-operative findings, one knee had grade 1, 22 knees had grade 2 and five knees had grade 3 degenerative changes. The overall outcomes were assessed using Hughston’s rating scale, where 19 knees were rated as good, four as fair and five as poor.

We found radiological evidence of degenerative changes in the third or fourth decade of life at a mean of 14 years after arthroscopic excision of the loose body and subchondral drilling for an unstable osteochondral lesion of the lateral femoral condyle. Clinical and functional results were more satisfactory.

Interest in football continues to increase, with ever younger age groups participating at a competitive level. Football academies have sprung up under the umbrella of professional clubs in an attempt to nurture and develop such talent in a safe manner. However, increased participation predisposes the immature skeleton to injury. Over a five-year period we have prospectively collected data concerning all injuries presenting to the medical team at Newcastle United football academy. We identified 685 injuries in our cohort of 210 players with a mean age of 13.5 years (9 to 18). The majority of injuries (542;79%) were to the lower limb. A total of 20 surgical procedures were performed. Contact injuries accounted for 31% (210) of all injuries and non-contact for 69% (475).The peaks of injury occurred in early September and March. The 15- and 16-year-old age group appeared most at risk, independent of hours of participation. Strategies to minimise injury may be applicable in both the academy setting and the wider general community.

Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice.

Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1⁺) and stem cell factor receptor, CD117 (c-kit⁺) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1⁺ mononuclear cell (MNC^sca-1+) populations were then cultured and examined for functional vascular endothelial differentiation. Bone marrow MNC^{sca-1+,c-kit+} counts increased almost twofold within 48 hours of the event, compared with baseline levels, before decreasing by 72 hours.

Sca-1⁺ mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1′-dioctadecyl- 3,3,3,’3′-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium.

Our findings suggest that a systemic provascular response of bone marrow is initiated by musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of neovascularisation and the healing of fractures.

We attempted to repair full-thickness defects in the articular cartilage of the trochlear groove of the femur in 30 rabbit knee joints using allogenic cultured chondrocytes embedded in a collagen gel. The repaired tissues were examined at 2, 4, 8, 12 and 24 weeks after operation using histological and histochemical methods. The articular defect filling index measurement was derived from safranin-O stained sections. Apoptotic cellular fractions were derived from analysis of apoptosis in situ using TUNEL staining, and was confirmed using caspase-3 staining along with quantification of the total cellularity. The mean articular defect filling index decreased with time. After 24 weeks it was 0.7 (sd 0.10), which was significantly lower than the measurements obtained earlier (p < 0.01). The highest mean percentage of apoptotic cells were observed at 12 weeks, although the total cellularity decreased with time. Because apoptotic cell death may play a role in delamination after chondrocyte transplantation, anti-apoptotic gene therapy may protect transplanted chondrocytes from apoptosis.

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

We have investigated in vitro the release kinetics and bioactivity of fibroblast growth factor-2 (FGF-2) released from a carrier of fibrin sealant. In order to evaluate the effects of the FGF-2 delivery mechanism on the repair of articular cartilage, full-thickness cylindrical defects, 5 mm in diameter and 4 mm in depth, which were too large to undergo spontaneous repair, were created in the femoral trochlea of rabbit knees. These defects were then filled with the sealant.

Approximately 50% of the FGF-2 was released from the sealant within 24 hours while its original bioactivity was maintained. The implantation of the fibrin sealant incorporating FGF-2 successfully induced healing of the surface with hyaline cartilage and concomitant repair of the subchondral bone at eight weeks after the creation of the defect.

Our findings suggest that this delivery method for FGF-2 may be useful for promoting regenerative repair of full-thickness defects of articular cartilage in humans.