Can Adding BMP2 Improve Outcomes in Patients Undergoing the SUPERhip Procedure?

Congenital femoral deficiency (CFD) Paley type 1b is characterized by severe bony deformity of the upper femur, extra-articular contractures of the hip, and, delayed ossification of the femoral neck and/or subtrochanteric region. The Systematic Utilitarian Procedure for Extremity Reconstruction of the hip (SUPERhip) procedure for the correction of CFD deformities was developed in 1997. Initially, a non-fixed angle device (rush rod) was used for fixation. Late complications of persistent delayed ossification and recurrent varus deformity occurred. In order to reduce and treat such complications, fixation with a fixed angle device and the off-label use of BMP2 to induce ossification of the un-ossified femoral neck were employed. The purpose of this study is to determine if the use of a fixed angle device, and, BMP2 inserted into a drill hole in the cartilage of the femoral neck, decreases the incidence of these late complications. We retrospectively reviewed 72 SUPERhip procedures performed for Paley type 1b CFD between 1997 and 2012. Due to recurrent varus or persistent delayed ossification of the femoral neck, 34 revision SUPERhip procedures were performed. In total, 106 SUPERhip procedures were studied. Sixty-eight SUPERhips were performed using internal fixation without BMP2, while 38 SUPERhips were performed with both internal fixation and the addition of BMP2. Forty-one were performed using non-fixed angle internal fixation while 65 had fixed angle internal fixation. Fixed angle devices significantly reduced the incidence of recurrent varus compared with non-fixed angle devices. Inserting BMP2 in the femoral neck significantly reduced the incidence of persistent delayed ossification. Using only a fixed angle device but no BMP2 did not reduce the incidence of delayed ossification. The combination of both a fixed angle device and BMP2 reduced the incidence of recurrent coxa vara and persistent delayed ossification of the femoral neck. The SUPERhip procedure corrects the pathoanatomy of the proximal femur in CFD Paley type 1b but is associated with a very high risk of recurrence of coxa vara and persistence of femoral neck delayed ossification, unless, a fixed angle internal fixation device is used to prevent recurrent coxa vara and BMP2 is used to induce ossification of the femoral neck.

Progression of Epiphyseal Cartilage and Bone Pathology in Surgically Treated Cases of Osteochondritis Dissecans of the Elbow

Background: Although a variety of pathologic conditions associated with osteochondritis dissecans (OCD) have been reported, the pathological progression has remained unclear. Hypothesis: Separation of the immature epiphyseal cartilage is an early event in OCD, and osteonecrosis in the articular fragment is a late event. Study Design: Case Series; Level of evidence, 4. Methods: The participants were 26 boys (mean age, 13.8 years; mean skeletal age score for the elbow, 24.6 points) with capitellar OCD who underwent osteochondral autograft transplantation. A total of 28 cylindrical osteochondral plugs, including the articular fragment, an intermediate layer, and proximal epiphyseal bone, were harvested from the central area of the capitellum and were examined histologically. The articular fragments of OCD were independently assessed by 5 observers and divided into 4 pathological variations: IA, nearly normal-cartilaginous; IB, deteriorated-cartilaginous; IIA, cartilage-ossifying; and IIB, cartilage-osteonecrotic. The reliability of assessment and the correlation of the pathological variations with the clinical data were examined. Results: The reliability of the assessment among 5 observers was almost perfect (Cohen kappa value = 0.91). OCD variations of IA, IB, IIA, and IIB were evident in 5, 10, 5, and 6 patients, respectively. OCD-I (cartilaginous) and OCD-II (osteochondral) corresponded significantly to radiographic stage I (radiolucency or slight calcification with open physis) and stage II (delayed ossification or bony fragment), respectively (Cohen kappa value = 0.79; percentage agreement = 81%). The pathological OCD variations were significantly correlated with the clinical data, including the period from symptom onset to surgery, patient age, and the skeletal age score ( P < .01, in each). Conclusion: The present study has revealed that the pathological variations correspond to the progression of OCD, thus proving our hypothesis. OCD-IA was shown to be an early lesion caused by separation of the immature epiphyseal cartilage. OCD-IB appeared to result from ossification arrest over a prolonged period from the onset of OCD-IA, whereas OCD-IIA showed delayed ossification in the epiphyseal cartilage where vascularization from the surrounding bone had been established. Osteonecrosis in OCD-IIB was shown to be a late pathological event caused by disruption of the vascular supply to OCD-IIA.

Cleidocranial Dysostosis – An Enigma Developmental Bones Anomaly

Cleidocranial Dysostosis, known also as Cleidocranial dysplasia, Mutational Dysostosis, Scheuthauer Marie-Sainton syndrome, is a rare condition which is characterized by delayed ossification of midline structures. Case study of the phenomenon has been reported here. Reports revealed that the classical association of a spectacular dental anarchy, with non-closure of cranial sutures, retention of deciduous teeth and delayed eruption of permanent denture and typical facies of underdevelopment raise strong suspicion of autosomal syndrome. The reviewed patient as a classic demonstration of cleidocranial dysostosis, succinctly represented the condition.

Delayed ossification and abnormal development of tarsal bones in idiopathic clubfoot: should it affect bracing protocol when using the Ponseti method?

Purpose To point out the need to take into account the dysplastic nature of tarsal bones when treating idiopathic clubfoot (CF). Methods Review the published evidence on the developmental abnormalities of tarsal bones in idiopathic CF. Results The literature review provides abundant proof of the existence of delayed appearance and slower development of ossification centres of tarsal bones in idiopathic clubfoot. Conclusion Gentle manipulations and casting are the cornerstone of the Ponseti method. The biological response of all foot elements is critical for a successful outcome. Delayed ossification and abnormal development of tarsal bones in idiopathic CF may affect the results. Development of a personalized tailored bracing protocol based on severity assessment and response to casting treatment will improve results and quality of care in CF management. Level of Evidence V

Osteochondrosis in the Distal Femoral Physis of Pigs Starts With Vascular Failure

Articular osteochondrosis (OC) arises due to vascular failure and ischemic chondronecrosis. The aim of the study was to describe the histological and computed tomographic (CT) characteristics of changes in the distal femoral physis of pigs, to determine if they represented OC lesions and if the pathogenesis was the same as for articular OC. The material included 19 male Landrace pigs bred for predisposition to OC. One or 2 pigs were euthanized and CT-scanned at 2-week intervals from 82 to 180 days of age. Material from 10 pigs was available for histological validation. The CT scans revealed 31 lesions confirmed in 3 planes and 1 additional macroscopically visible lesion confirmed in 2 CT planes. Twelve of the lesions were histologically validated. All lesions were compatible with OC. Cartilage canal and eosinophilic streak morphological changes corresponded to failure of end arteries coursing from the epiphysis, toward the metaphysis. The location of lesions was compatible with failure at the point of vessel incorporation into bone. Vascular failure was associated with retention of viable hypertrophic chondrocytes and delayed ossification but not cartilage necrosis. Lesion width ranged from 1.1% to 45.6% of the physis. Several lesions were expected to resolve due to small size and evidence of CT-identifiable, reparative ossification. Angular limb deformity was not detected in any pig. The pathogenesis of physeal OC started with vascular failure that was morphologically identical to articular OC. The heritable predisposition may therefore be the same. The association between lesions and limb deformity should be studied further in older pigs in future.

Prenatal hypocalvaria after prolonged intrauterine exposure to angiotensin II receptor antagonists

We report a case of prenatal exposure to angiotensin II receptor antagonists (ARA II) from the beginning of pregnancy in a patient with a hypokinetic dilated cardiomyopathy. This case report emphasizes the fetal renal impact of prolonged intrauterine exposure to renin-angiotensin system (RAS) blockers, and highlights that this exposure can cause severe prenatal hypocalvaria. This delayed ossification can be reversible after birth, but the presence of anhydramnios indicates an early and irreversible block of RAS blockers in the fetus that is responsible for fetal kidney development abnormalities. This association carries a high risk of neonatal death. Prolonged exposure to ARA II or other RAS blockers remains prohibited throughout pregnancy.

New insights into the biomechanics of Legg-Calvé-Perthes’ disease

Objectives Legg–Calvé–Perthes’ disease (LCP) is an idiopathic osteonecrosis of the femoral head that is most common in children between four and eight years old. The factors that lead to the onset of LCP are still unclear; however, it is believed that interruption of the blood supply to the developing epiphysis is an important factor in the development of the condition. Methods Finite element analysis modelling of the blood supply to the juvenile epiphysis was investigated to understand under which circumstances the blood vessels supplying the femoral epiphysis could become obstructed. The identification of these conditions is likely to be important in understanding the biomechanics of LCP. Results The results support the hypothesis that vascular obstruction to the epiphysis may arise when there is delayed ossification and when articular cartilage has reduced stiffness under compression. Conclusion The findings support the theory of vascular occlusion as being important in the pathophysiology of Perthes disease. Cite this article: M. Pinheiro, C. A. Dobson, D. Perry, M. J. Fagan. New insights into the biomechanics of Legg-Calvé-Perthes’ disease: The Role of Epiphyseal Skeletal Immaturity in Vascular Obstruction. Bone Joint Res 2018;7:148–156. DOI: 10.1302/2046-3758.72.BJR-2017-0191.R1.

An evolutionary and developmental perspective on the loss of regionalization in the limbs of derived ichthyosaurs

Ichthyosaurs, a lineage of extinct Mesozoic marine reptiles, have garnered attention in both the palaeontological and developmental literature for the unique limb morphology seen in derived genera. These morphologies include an increase in the number of phalanges per digit (hyperphalangy) and in the number of digits (hyperdactyly), but most interestingly also a shift in element identity. Elements distal to the stylopodium acquire characteristics of mesopodial elements, such as a rounded, nodular shape and a loss of perichondral bone on the anterior and posterior surfaces. Here, we examine numerous aspects of the loss of proximodistal identity in ichthyosaur limbs including phylogenetic progression of the loss of perichondral bone, histology and microstructure of the elements retaining perichondral bone in derived taxa, and correlates of intraspecific variation in degree of perichondral bone reduction in a derived ichthyosaur, Stenopterygius quadriscissus. Results show that loss of limb element identity occurred progressively over ichthyosaurian evolution, and the notches seen on the anterior surface of limb elements in derived ichthyosaurs are homologous to the long bone shafts in terrestrial tetrapods. Variation in the number of notches in S. quadriscissus can best be explained through delayed ossification of the anterior perichondrium, indicating a heterochronic component to the loss of identity. We propose a developmental mechanism – gradual expansion of the polyalanine region of HoxD13 over ichthyosaurian evolution – to explain the progressive loss of limb regionalization as well as the heterochronic delay in perichondral ossification.

Ontogenetic sequence reconstruction and sequence polymorphism in extinct taxa: an example using early tetrapods (Tetrapoda: Lepospondyli)

Ontogenetic sequence reconstruction is challenging particularly for extinct taxa because of when, where, and how fossils preserve. Different methods of reconstruction exist, but the effects of preservational bias, the applicability of size-independent methods, and the prevalence of sequence polymorphism (intraspecific variation) remain unexplored for paleontological data. Here I compare five different methods of ontogenetic sequence reconstruction and their effects on the detection of sequence polymorphism, using a large collection of the extinct vertebrates Microbrachis pelikani and Hyloplesion longicostatum. The postcranial ossification sequences presented here for those taxa are the first examples known for extinct lepospondyls. Sequences were reconstructed according to skull length, trunk length, increasing number of ontogenetic events, majority-rule consensus, and Ontogenetic Sequence Analysis (OSA). Results generally were in agreement, demonstrating that paleontological data may be used to robustly reconstruct developmental patterns. When reconstructing sequences based on fossils, size-based methods and OSA are more objective and less dependent on preservational bias than other techniques. Apart from the other methods, OSA also allows for statistical analysis of observed and predicted polymorphism. However, OSA requires a large sample size to yield meaningful results, and size-based methods are justified in paleontological studies when sample size is limited by poor preservation. Different methods of reconstruction detected different patterns of sequence polymorphism, although across all methods the magnitude of sequence variation for M. pelikani and H. longicostatum (1.3−3.4%) was within the lower range of values reported for extant vertebrates. Compared with other extinct and extant tetrapods, all sequence reconstruction methods consistently showed that M. pelikani and H. longicostatum exhibit advanced ossification of the pubis and delayed ossification of the scapula. However, the postcranial ossification sequences of these two taxa largely are congruent with those of other tetrapods, suggesting an underlying conservative ancestral pattern that evolved early in tetrapod history.