Ellen M. Raney

Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen

Although biallelic mutations in non-collagen genes account for <10% of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes. We identified mutations in FKBP10, which encodes the 65 kDa prolyl cis-trans isomerase, FKBP65, in 38 members of 21 families with OI. These include 10 families from the Samoan Islands who share a founder mutation. Of the mutations, three are missense; the remainder either introduce premature termination codons or create frameshifts both of which result in mRNA instability. In four families missense mutations result in loss of most of the protein. The clinical effects of these mutations are short stature, a high incidence of joint contractures at birth and progressive scoliosis and fractures, but there is remarkable variability in phenotype even within families. The loss of the activity of FKBP65 has several effects: type I procollagen secretion is slightly delayed, the stabilization of the intact trimer is incomplete and there is diminished hydroxylation of the telopeptide lysyl residues involved in intermolecular cross-link formation in bone. The phenotype overlaps with that seen with mutations in PLOD2 (Bruck syndrome II), which encodes LH2, the enzyme that hydroxylates the telopeptide lysyl residues. These findings define a set of genes, FKBP10, PLOD2 and SERPINH1, that act during procollagen maturation to contribute to molecular stability and post-translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result.

Evidence-Based Analysis of Removal of Orthopaedic Implants in the Pediatric Population

Background: Requested project of the Pediatric Orthopaedic Society of North America Evidenced-Based Medicine Committee. Methods: The English literature was systematically reviewed for scientific evidence supporting or disputing the common practice of elective removal of implants in children. Results: Several case series reported implant removal, but none contained a control group with retained implants. No articles reported long-term outcomes of retained implants in large numbers. Several small series describe complications associated with retained implants without evidence of causation. The existing literature was not amenable to a meta-analysis. By compiling data from the literature, it is possible to calculate a complication rate of 10% for implant removal surgery. The complication rate for removal of implants placed for slipped capital femoral epiphysis is 34%. Articles regarding postmarket implant surveillance and basic science were also reviewed. Conclusions: There is no evidence in the current literature to support or refute the practice of routine implant removal in children.

Bone lengthening in children: how to predict the complications rate and complexity?

Purpose: Complications arising from limb-lengthening procedures are often severe leading to long-term residuals. The aim of this study was to determine whether the complication rate and complexity could be predicted using a distraction index for bone lengthening in children. Study Design: This study retrospectively reviewed a series of 116 lower limbs lengthening in 88 consecutive patients (mean age 13.5). Mean follow-up 3.8 years. Lengthening percentage, lengthening index, distraction regenerate length, additional surgeries, and complications rate were used to evaluate the results of limb lengthening. The correlation between lengthening percentage and complication rate was particularly analyzed and its practicability illustrated. Scatter plots of complication rate (%) against lengthening percentage were constructed, and linear regression was used to investigate mathematical relationship between the variables. Results: The lengthening index was 33 ± 12.1 days/cm. The length of distraction regenerate was 6 ± 3.2 cm. The lengthening percentage was 21 ± 16.5. The scatter plots of neurological complication rate, residual deformities rate, broken pins rate, joint contractures rate, and hypertension rate against lengthening percentage showed a positive linear relationship with r = 0.8. Conclusions: The number of complications increased considerably with the increase in lengthening percentage. The lengthening percentage correlates very well with the complication rate and can be used to predict the complication rate. Clinical Relevance: During planning a lengthening procedure, the lengthening percentage should be a useful tool to predict the complications rate and to discuss the risks and benefits with patients and their families. The knowledge about predictable complications should help prevent and early detect expected complications.

Complications of supracondylar osteotomies for cubitus varus.

Background: Humeral osteotomies for cubitus varus have a notoriously high complication rate. Pitfalls of this difficult procedure are highlighted. Methods: A 50-year experience of 68 consecutive surgeries was reviewed. Factors such as surgical approach and fixation technique were compared for complication incidence and type. Results: Seventeen patients (25%) had 23 (34%) clinically remarkable complications. Nine postoperative nerve palsies occurred in 8 patients. Loss of reduction requiring revision or manipulation was seen in 3 patients. The following complications were noted in 2 patients each: nonunion, loss of flexion, lateral prominence, and unsatisfactory scar. Growth arrest, osteomyelitis, and under-correction requiring revision each occurred once. A lateral, triceps-sparing approach was associated with an overall prevalence of complications of 24% (5 of 21) equivalent to the posterior, triceps splitting approach of 24% (10 of 42). An olecranon osteotomy was used in 2 patients both with complications. No nerve injuries occurred in patients who underwent a lateral approach, whereas nerve palsies occurred in 14% (6 of 42) of the patients where a posterior approach was used. An olecranon osteotomy was used in 2 patients with nerve injury occurring in both. A medial approach in 2 patients and a combined medial-lateral approach in 1 patient were used with no complications. Plate and screw fixation was implemented in 29 cases with complications occurring in 6 of them; pin fixation, in 30 cases, 7 of which had complications. There was a higher incidence of under-correction requiring additional surgery with plate fixation (1 of 29) compared with pin fixation which had no under correction but had loss of fixation in 2 of 30. The average correction obtained was similar in the group with complications (32 degrees) versus those without (27 degrees). Conclusions: Supracondylar humeral osteotomy is a technically demanding procedure fraught with complications. Plate fixation and pin fixation techniques resulted in similar complication rates, but the surgical approach used appeared to make a difference. The posterior, triceps splitting, approach resulted in a high incidence of nerve palsies versus none with the lateral, triceps-sparing approach. Level of Evidence: This is a retrospective case series, Level IV.

Trevorʼs disease: the clinical manifestations and treatment of dysplasia epiphysealis hemimelica

Trevors disease is a rare abnormality characterized by aberrant osteocartilaginous growth from an epiphysis. We describe six new cases from our institution. A patient with isolated tibial tuberosity involvement is described for the first time. Each patient was classified according to Azouz into localized (three), classical (two) and generalized (one) form. We recommend that parents be counseled regarding the progressive nature of this disorder owing to the chance of worsening deformity with surgical excision alone, and the need to be followed until skeletal maturity.

Reliability of radiographic assessment of distraction osteogenesis site

The presence of three of four continuous cortices on anteroposterior and lateral radiographs has been stated to be an indication of bony healing of distraction osteogenesis. In this study the authors assessed the level of agreement of radiographic assessment of bony union. Forty-two lower extremity radiographs of consolidating distraction gaps were reviewed by nine examiners on two occasions for number of cortices and whether fixator removal was indicated. For number of cortices, the kappa coefficients for interobserver and intraobserver variability were 0.127 and 0.290. For fixator removal, the interobserver and intraobserver coefficients were 0.352 and 0.461. Variation in assessment of number of cortices was slightly better than chance, indicating an inadequate measure of healing. The clinicians used radiographic criteria other than three of four cortices for fixator removal. The decision to remove an external fixation device based on radiographic assessment alone resulted in intraobserver and interobserver variability moderately above chance.

Transfixion wire positioning within the bone: an option to control proximal tibia external fixation stiffness.

Purpose: The greatest angle that can be formed by the crossing wires at the proximal tibia level without altering safe corridors approaches only 60 degrees. Consequently, the wires are positioned more in the coronal than the sagittal plane. Looking for an increase in sagittal bending stiffness, we evaluated different wire positioning within the proximal tibia and their effect on the stiffness of external fixation of proximal tibia. Study Design: A fiberglass composite tibia fixed into an idealized ring external frame was tested with a servohydraulic test frame. Load-deformation behavior was compared among the different wire positioning within the proximal tibia under identical conditions of central axial compression, medial compression-bending, posterior compression-bending, posteromedial compression-bending, and torsion. Stiffness values were calculated from the load-deformation and the torque-angle curves. Results: The sample with 3 wires positioned within the bone-2 wires crossed 1 cm posteriorly from the center of the tibia and the third wire placed in coronal plane 1 cm anteriorly from the center of the tibia-was significantly (P < 0.05) stiffer in posterior, posteromedial, and torsional loading configurations compared with all other wire positions within the bone. Conclusions: This new wire positioning within the proximal tibia-2 wires crossed 1 cm posteriorly from the center of the tibia and the third wire placed in coronal plane 1 cm anteriorly from the center of the tibia-increased overall stiffness of external fixation, predominantly in sagittal plane. Clinical Relevance: This work provides a rationale to control proximal tibia external fixation stiffness in sagittal plane.

C-reactive protein response following pediatric orthopaedic surgery.

The purpose of this study was to describe the pediatric C-reactive protein (CRP) response following orthopaedic surgery, specifically addressing whether CRP values in children return to normal within 3 weeks as they do in adults. Children undergoing elective orthopaedic procedures had serum CRP values measured before surgery and then on days 3, 7, and 21 after surgery. These intervals were chosen to assess the rise, fall, and return to normal of CRP levels. Twenty-two children were studied. CRP levels on day 3 varied from normal to 22.2 mg/dL (mean 7.3 mg/dL), on day 7 they averaged 2.2 mg/dL, and at 3 weeks all values were normal. None of the patients had postoperative infections. The authors concluded that the CRP rise in children may be more varied than in adults. In children, CRP levels return to normal within 3 weeks after surgery. This information can be useful in identifying postoperative infections in children.

Comparison of distraction osteogenesis for congenital and acquired limb-length discrepancy in children.

This study evaluated 116 lower limb lengthenings in 88 consecutive patients (mean age, 13.5 years) treated for congenital (31 patients [46 lengthened segments]) and acquired (57 patients [70 lengthened segments]) limb-length discrepancy. Mean follow-up was 3.8 years. Mean lengthening index was 34+/-16 days/cm in the congenital group and 32+/-9 days/cm in the acquired group; this difference was not statistically significant (P> .05). Mean length of distraction regenerate was 6.4+/-3.7 cm in the congenital group and 5.7+/-2.9 cm in the acquired group; this difference was not statistically significant (P> .05). Lengthening percentage was significantly higher in the congenital group (25+/-17.6) than in the acquired group (19+/-15.4). The increase in the complications rate in congenital limb-length discrepancy correlates with a significantly higher lengthening percentage. Bone regenerate is produced equally regardless of whether the etiology is acquired or congenital.

Pedicle rotation in scoliosis: a marker for occult intrathecal abnormalities.

Study Design. The Perdriolle method was used to assess retrospectively radiographic pedicle rotation for association with occult intrathecal abnormalities in patients with scoliosis. Objective. To determine if pedicle rotation can be predictive of underlying intrathecal abnormalities. Summary of Background Data. Scoliosis associated with intrathecal abnormalities is thought to produce less rotation than true idiopathic scoliosis. No supporting evidence was found in the literature. Methods. A consecutive series of patients with a presenting diagnosis of idiopathic scoliosis were reviewed for anteroposterior radiographs and spinal magnetic resonance imaging (MRI). A blinded single examiner evaluated radiographic curve parameters. MRI reports were reviewed for the presence or absence of intrathecal abnormalities. Results. A total of 78 MRIs included 15 intrathecal abnormalities and 63 normals. The abnormal MRI group had more males and apex left curves. Primary curve in the intrathecal abnormality group had a mean of 9.6° of apical vertebrae rotation compared to 17.7° in idiopathic curves (average 37° and 40° Cobb angles, respectively). Of angulation, 1° correlated with 0.21° and 0.34° of rotation in intrathecal abnormality versus no abnormality groups, respectively. Conclusions. Curves with occult intrathecal pathology had significantly less rotation than those without. Pedicle rotation assessment is a useful adjuvant for identifying scoliosis with intrathecal abnormalities.