High bone mass phenotype in a cohort of patients with Osteogenesis Imperfecta caused due to BMP1 and C-propeptide cleavage variants in COL1A1.

OBJECTIVES: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; extra-skeletal features in OI include blue sclerae, dentinogenesis imperfecta, skin laxity and joint hyper-extensibility. Most patients with OI are thought to have a low bone mass but contrary to expectations there are certain forms of OI with high bone mass which this study explores in further detail. METHOD: A cohort of n = 6 individuals with pathogenic variants in BMP1 and the C-propeptide cleavage variants in COL1A1 were included in this study. Detailed clinical and radiological phenotyping was done and correlated with genotype to identify patterns of clinical presentation and fracture history in this cohort of patients. This data was compared to previously reported literature in this group. RESULTS: 2 patients with BMP1 and 4 patients with pathogenic variants in C-propeptide region in COL1A1 were deep-phenotyped as part of this study and 1 patient with C-propeptide variant in COL1A1, showed low bone mineral density. In those with an elevated bone mineral density, this became even more apparent on bisphosphonate therapy. Patients in this cohort had variable clinical presentation ranging from antenatal presentation to more of an insidious course resulting in later confirmation of genetic diagnosis up to 19 years of age. CONCLUSIONS: Patients with pathogenic variants in the C-propeptide region of COL1A1/A2 and BMP1 appear to have a high bone mass phenotype with increased sensitivity to bisphosphonate therapy. It is important to closely monitor patients with these genotypes to assess their response to therapy and tailor their treatment regime accordingly.

Late presentation of spinal cord compression in hereditary multiple exostosis: case reports and review of the literature.

INTRODUCTION: Osteochondromas are usually found in the long bones of patients with hereditary multiple exostoses (HME). The spine is reported to be involved in over 50% of cases, but few of these patients are symptomatic as the result of an existing spinal exostosis. METHODS: We reviewed the current literature in order to find the right approach to patients with HME-complicated spinal exostosis and describe three paediatric patients that were diagnosed late with spinal cord compression due to cervical exostosis. RESULTS: Our three cases were all late presentations with neurology and unfortunately had minimal improvement of neurology after the lesion was surgically removed. There is general agreement that late presentation of spinal cord injury due to osteochondromas involving the cervical spine may cause severe and irreversible neurological sequelae. Our literature review revealed that there are no clear-cut guidelines to develop more comprehensive screening measures for these patients. CONCLUSIONS: A high index of suspicion is the most important factor for correct diagnosis and appropriate management. Physicians who treat HME should bear in mind that thorough history taking and a neurological examination at follow up are essential for these patients. Clearer guidelines for the development of more comprehensive screening programmes are essential. LEVEL OF EVIDENCE: IV.

Femoral neck fractures in osteogenesis imperfecta treated with bisphosphonates.

PURPOSE: Osteogenesis imperfecta (OI) is a condition characterised by bone fragility and multiple fractures, which cause considerable morbidity in the affected patients. Most cases are associated with mutations in one of the type I collagen genes. Recently, bisphosponates have been used widely to reduce pain and the incidence of fragility fractures in OI in children, even though there have been concerns raised regarding the long-term complications of it due to their effect on the bone. The fragility fractures involving the neck of the femur in children with intramedullary rods in the femoral shaft are very difficult to treat. Although these fractures are frequently un-displaced, they require optimal internal fixation to achieve fracture union. The aim of this study was to assess the clinical and radiological outcomes of OI patients with intracapsular femoral neck fracture treated with headless compression screws. METHOD AND RESULTS: At our institute, we identified seven patients (11 hips) with OI who underwent internal fixation with headless compression screws for a neck of femur fracture between June 2010 and Dec 2012. The time to fractures healing was on average 14 weeks (12 to 16). All patients gained their pre-injury ambulatory status. CONCLUSION: It is very challenging and technically demanding for orthopaedic surgeons when treating the fragility fracture of the neck of femur in patients with intramedullary rod in the femoral shaft. The published data regarding the management of these complex conditions are very limited. We describe our experience with the technique of percutaneous headless compression screw fixation for treating the femoral neck fractures in OI patients.

Fertilization and connectivity in the Garrucha Canyon (SE-Spain) implications for Marine Spatial Planning.

Marine Spatial Planning is usually based on benthic georeferenced information or GPS tracked human activities, whereas the pelagic ecosystem is often ignored because of scarce and limited surface information. However, the 3-D pelagic ecosystem plays a key role connecting all the other ecosystems by physical (currents) and biological (migration) processes. According to remote sensing the Garrucha Canyon is oligotrophic, but 3-D sampling reveals subsurface upwelling, and converts it into the richest area around the Cape of Gata. Vertical connectivity by means of zooplankton migration, measured at two sampling stations, is 40 and 220 times faster than microphytoplankton settling and vertical water velocities respectively. Thus coupled physical-biological connectivity models are necessary to estimate the ecosystem connection and the fate of carbon, but also other substances (e.g. radioactivity), that might accumulate throughout the food-web. This is especially important in the Garrucha Canyon and the Coastal Areas Management Programme Levante de Almería where natural heritage and extractive fishery are important for the local economy.

Limb reconstruction in Ollier's disease.

We present our experience of lengthening and correction of complex deformities in the management of patients with Ollier's dysplasia (multiple enchondromatosis) from 1985 and 2002. All patients were under 18 years with a minimum follow-up time of 2 years (mean 9.6 years, range 2-15 years). There were a total of ten patients of which seven were male and three female. The mean age at presentation was 10.7 years (range 5-17 years; SD 3.7 years). The total length gain was 42.3 mm (range 30-110 mm; SD 28.9 mm). The number of days in external fixation was 164.8 days (range 76-244 days; SD 42.9 days). The bone healing index was 32.5 days/cm (18-50 days/cm; SD 10.3 days/cm). Patients with Ollier's disease have limb length inequality and angular deformities and require multiple reconstructive procedures owing to a high incidence of recurrence. We identified a tendency for the osteotomy to prematurely consolidate and advise the latency period after surgery to be 4-5 days and for distraction to proceed at a faster rate.

Physical mapping of 18S rDNA and heterochromatin in species of family Lygaeidae (Hemiptera: Heteroptera).

Analyses conducted using repetitive DNAs have contributed to better understanding the chromosome structure and evolution of several species of insects. There are few data on the organization, localization, and evolutionary behavior of repetitive DNA in the family Lygaeidae, especially in Brazilian species. To elucidate the physical mapping and evolutionary events that involve these sequences, we cytogenetically analyzed three species of Lygaeidae and found 2n (♂) = 18 (16 + XY) for Oncopeltus femoralis; 2n (♂) = 14 (12 + XY) for Ochrimnus sagax; and 2n (♂) = 12 (10 + XY) for Lygaeus peruvianus. Each species showed different quantities of heterochromatin, which also showed variation in their molecular composition by fluorochrome staining. Amplification of the 18S rDNA generated a fragment of approximately 787 bp. The alignment of the consensus sequence with sequences from other species of Heteroptera deposited in the GenBank revealed a similarity of 98% with small differences. Fluorescent in situ hybridization with the 18S rDNA fragment revealed that this ribosomal gene was located in 1 autosomal pair at different positions in the three species. No cytogenetic data are available for these Brazilian species. The basal number and the possible chromosomal changes that occurred among the different species, as well as the evolution of these DNA sequences, are discussed.

High diversity in CMA3/DAPI-banding patterns in Heteropterans.

Heteroptera is the most numerous and diverse suborder of Hemiptera, with about 38,000 species. This diversity also involves cytogenetic features, including chromosome number and a sex determining system. Information about heterochromatin occurrence and distribution is scarce in heteropterans, but still, there is some evidence of variability. We determined the chromosome number and CMA3/DAPI-banding pattern of 179 individuals of 25 heteropteran species from Brazil. Eight species of Pentatomidae exhibited a constant chromosome number (2n = 12 + XY), but in Coreidae (12 species), Largidae (1 species), Rhopalidae (1 species), and Pyrrhocoridae (3 species), the numbers ranged from 2n = 10 + 2m + X0 to 2n = 24 + 2m + X0. Although there were no large differences in the chromosome size between species, the CMA3/DAPI-banding patterns differed markedly. Among the genera, species of Edessa, Spartocera, Hypselonotus, Phtia,Holhymenia and Euryophthalmus showed a large accumulation of heterochromatin, while the other species exhibited few or no heterochromatic bands. In general, when heterochromatin was more accumulated, this occurred preferentially at terminal positions, except in Holhymenia histrio, which exhibited intercalary bands. This study made it possible to identify some chromosome rearrangements and to enhance our knowledge of the evolutionary mechanisms that determine karyotype differentiation in Heteroptera.

Epiphysiodesis for limb length discrepancy: a comparison of two methods.

A retrospective review of 42 patients from 1999 to 2008 with at least 1-year follow-up was performed. The type and location of epiphysiodesis, average operative time and hospital stay, complications, timing and the final limb length discrepancy (LLD) were recorded. Computer tomography scanograms and mechanical axis view with grids were done to assess LLD. Twenty-six patients underwent Canale type epiphysiodesis compared with 14 receiving Metaizeau screw epiphysiodesis. The average operation time for Canale type was 42 and 45 min for screw epiphysiodesis. In the Canale group, there was a mean reduction in 2.5 cm in LLD from 3.7 to 1.2 cm over an average follow-up of 2.1 years. There were 4 minor and 2 major complications with a 92 % success rate defined as achieving the desired discrepancy correction. In the screw epiphysiodesis group, the mean change was 1.8 cm from 3.2 to 1.4 cm, over 2.2 years with 2 minor and 2 major complications and a success rate of 85 %. Percutaneous epiphysiodesis by any method is a reliable, minimally invasive method with minimal morbidity and an acceptable complication rate when compared to a corrective osteotomy or an open Phemister-type epiphysiodesis. This study has led to our preference for the Canale method, which in our hands has fewer complications and is more successful at reaching the desired discrepancy correction.

The treatment of severe slipped capital femoral epiphysis via the Ganz surgical dislocation and anatomical reduction: a prospective study.

We present our experience of the modified Dunn procedure in combination with a Ganz surgical dislocation of the hip to treat patients with severe slipped capital femoral epiphysis (SCFE). The aim was to prospectively investigate whether this technique is safe and reproducible. We assessed the degree of reduction, functional outcome, rate of complications, radiological changes and range of movement in the hip. There were 28 patients with a mean follow-up of 38.6 months (24 to 84). The lateral slip angle was corrected by a mean of 50.9° (95% confidence interval 44.3 to 57.5). The mean modified Harris hip score at the final follow-up was 89.1 (sd 9.0) and the mean Non-Arthritic Hip score was 91.3 (sd 9.0). Two patients had proven pre-existing avascular necrosis and two developed the condition post-operatively. There were no cases of nonunion, implant failure, infection, deep-vein thrombosis or heterotopic ossification. The range of movement at final follow-up was nearly normal. This study adds to the evidence that the technique of surgical dislocation and anatomical reduction is safe and reliable in patients with SCFE.

Limb lengthening in congenital posteromedial bow of the tibia.

Congenital posteromedial bowing of the tibia (PMBT) is a rare condition affecting one lower limb. The bowing of the tibia usually resolves; however, there is associated limb length discrepancy (LLD), which often persists and can cause functional deficits. Advances in limb lengthening techniques allow this issue to be addressed, often with concomitant angular deformity correction. This study examined eleven patients who have had limb lengthening procedures with mean pre-operative LLD of 3.7 cm (range 1.5-5 cm), mean increase in length was 3.9 cm (range 1.5-5.8 cm), and mean LLD at last follow-up was less than 0.6 cm (range 0-2.0 cm). The main complications were minor or moderate grades, such as pin site infection. Greater LLD was found than previously reported, and we believe that the tertiary referrals were those of a severe form of PMBT. The authors conclude that in view of deformity with discrepancy, in select cases, correction and lengthening would be an option rather than only contralateral epiphysiodesis.

Changing pattern of femoral fractures in osteogenesis imperfecta with prolonged use of bisphosphonates.

PURPOSE: Osteogenesis imperfecta (OI) has been treated with bisphosphonates for many years, with some clear clinical benefits. In adults, there are reports of a new pattern of atraumatic subtrochanteric fractures with bisphosphonate treatment. This study assesses if bisphosphonate treatment leads to an altered pattern of femoral fractures. METHODS: Retrospective review of imaging for a cohort of 176 bisphosphonate-treated OI patients to identify the locations of femoral fractures over a two-year period, as compared to a historical control group managed pre-bisphosphonates. RESULTS: Sixteen femoral fractures were identified in this time period in the bisphosphonate-treated group. All but two were within the subtrochanteric region. In comparison, the historical group-composed of 26 femoral fractures-had a more widespread fracture pattern, with the most frequent location being the mid-diaphysis. Many of the subtrochanteric fractures in the treatment group occurred with minimal trauma. CONCLUSIONS: It appears that concerns over the treatment of the adult osteoporotic population with bisphosphonates are amplified and mirrored in OI. It is possible that the high bending moments in the proximal femur together with altered mechanical properties of cortical bone secondary to the use of this group of drugs increase the risk of this type of injury, which warrants further modification of surgical management of the femur.

"Asymmetric scalloping of the regenerate": a radiological sign of pseudoaneurysm in distraction osteogenesis.

Pseudoaneurysm formation is an uncommon but well-recognised and important complication in limb reconstruction surgery. Postoperative diagnosis is usually clinical or an incidental finding. We present an 11-year-old girl, who underwent two-stage limb lengthening with a circular fixator, for a previously treated pseudoarthrosis of the tibia. During the lengthening plan, a concave defect was noted on one side of the regenerate, which was found to be due to extrinsic compression by a pseudoaneurysm. Normal regenerate formation was seen after selective embolisation of the pseudoaneurysm. This concave appearance on one side of the regenerate has previously been described secondary to a difference in stability on the two sides of the osteotomy, when a monolateral fixator is used, but not due to extrinsic compression by a pseudoaneurysm. The authors propose that this radiographic appearance of "asymmetrical scalloping" on one side of the regenerate may represent a radiological sign of a pseudoaneurysm formation and should provoke investigation for the same.

A novel method of applying a split cast.

Split plaster casts have been shown to be better than back slabs at accommodating increasing intracompartmental pressure due to swelling. Splitting a wet plaster cast can be time consuming and difficult both for the patient and the medical staff. We describe a novel method of applying a split plaster of Paris cast, which is safe, quick, convenient and inexpensive.