Arabella I. Leet

Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.

The repair of injured tendons remains a great challenge, largely owing to a lack of in-depth characterization of tendon cells and their precursors. We show that human and mouse tendons harbor a unique cell population, termed tendon stem/progenitor cells (TSPCs), that has universal stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity. The isolated TSPCs could regenerate tendon-like tissues after extended expansion in vitro and transplantation in vivo. Moreover, we show that TSPCs reside within a unique niche predominantly comprised of an extracellular matrix, and we identify biglycan (Bgn) and fibromodulin (Fmod) as two critical components that organize this niche. Depletion of Bgn and Fmod affects the differentiation of TSPCs by modulating bone morphogenetic protein signaling and impairs tendon formation in vivo. Our results, while offering new insights into the biology of tendon cells, may assist in future strategies to treat tendon diseases.

Secondary fractures associated with external fixation in pediatric femur fractures.

Sixty-six femur fractures sustained by children ages 4-14 years and treated with external fixation were reviewed retrospectively to assess factors influencing the incidence of refracture. The total rate of secondary fracture was 12% (eight patients) including five recurrent fractures at the original fracture site and three fractures through the pin sites. After removal of the external fixator, five patients refractured at the original fracture site and one patient fractured through a pin tract. Two patients fractured at pin sites while the fixator was still in place. Multivariate linear-regression analysis showed no correlation between the incidence of refracture and fracture pattern, percentage of bone fragment contact after fixator application, type of external fixator, or dynamization. A statistically significant association (p < 0.05) was found between the number of cortices demonstrating bridging callus [on both anteroposterior (AP) and lateral views] at the time of fixator removal and the rate of refracture. Fractures showing fewer than three cortices of bridging callus had a three (33%) in nine rate of refracture, whereas fractures with three or four cortices of bridging callus had a two (4%) of 57 rate of refracture.

Fracture Incidence in Polyostotic Fibrous Dysplasia and the McCune‐Albright Syndrome

In patients with polyostotic fibrous dysplasia of bone, the peak incidence of fractures is during the first decade of life, followed by a decrease thereafter. Phosphaturia is associated with an earlier incidence and increased frequency of fractures.

Delayed treatment of type 3 supracondylar humerus fractures in children

A retrospective review of 158 type 3 supracondylar humerus fractures was undertaken to determine whether any correlation exists between an increased time from injury to surgery and four unfavorable results: a longer operative time, an increase in hospital stay, an increase in the need to open the fracture, or an increase in unsatisfactory outcomes. The average age of the patients was 5.0 years. Five children had nerve injury on initial examination, and no arm was poorly perfused. The average time from injury to evaluation in the emergency department was 9.8 hours and the average time from the emergency department to surgery was 11.5 hours. The average total time from injury to surgical treatment was 21.3 hours. The patients were in the hospital between 1 to 6 days. The average operative time was 53 minutes. Thirty patients had unsatisfactory results, defined as a pin infection, more than 15° loss of motion in any plane, loss of normal carrying angle, neuropraxia, or retained hardware. There was no correlation between an increase in time to surgical intervention and longer operative time or need to open the fracture site, nor was there an indication that the delay to surgical treatment resulted in a longer hospital stay or an increase in unsatisfactory results.

Pediatric spinal cord injury without radiographic abnormality: A meta-analysis

Using a meta-analysis, we identified 392 published cases of patients recently diagnosed with spinal cord injuries without radiographic abnormalities (SCIWORA) and studied the epidemiologic, pathophysiologic, clinical, and radiologic data. To describe those at risk for this uncommon syndrome, mainly pediatric patients (90% of the cases) who sustain serious trauma in car accidents, serious falls, sports injuries, or child abuse, we analyzed the reported information in the literature. Magnetic resonance imaging scans may indicate neural (hemorrhages, edema, or both) or extraneural (disc protusions, extradural hematomas) injuries, and the location and type of the injury. Every patient having magnetic resonance imaging scans had either intraneural or extraneural injury. However, followup magnetic resonance imaging scans are necessary because evidence of the injury might not appear immediately. Late and recurrent spinal cord injuries without radiographic abnormalities are reported. External immobilization for 12 weeks helps patients who are moderately injured and helps prevent recurrence of these types of injuries. Approximately 44% of the patients in our study did not recover whereas complete recovery occurred in 39% of the population. The prognosis can be improved if the syndrome is diagnosed early, so we recommend considering spinal cord injuries without radiographic abnormalities as a possible diagnosis for any child who has a mechanism of injury that suggests trauma to the spine. Level of Evidence: Therapeutic study, Level III-3 (case-control study). See the Guidelines for Authors for a complete description of levels of evidence.

Surgical treatment of femoral fractures in obese children: does excessive body weight increase the rate of complications?

BACKGROUND In light of the increasing rate of obesity among children in the United States, this study examines whether obese children have an increased rate of complications following surgical treatment of femoral shaft fractures. METHODS A retrospective review of the charts of children between six and fourteen years of age who were treated operatively for a femoral shaft fracture was performed, and complications were identified. RESULTS One hundred and three children (104 fractures), with a mean age at the time of injury of 9.3 years, were identified. Fifty-nine fractures were treated with external fixation, and forty-five were treated with an intramedullary rod. Six children (6%) were considered obese, with a weight for age at the 95th percentile or higher. An additional four children were extremely heavy at the 90th to the 94th percentile of weight for age. Three complications occurred in the six obese children, and one complication occurred in the four extremely heavy children. Eleven (12%) of the remaining ninety-three children had a complication. When examined according to treatment groups, the complication rate for heavier children was higher for both the group managed with an intramedullary rod and the group that had external fixation (p = 0.004). CONCLUSIONS Obese children have an increased rate of postoperative complications compared with children who are not obese. Therefore, parents of obese children should be warned that such children may have a potentially increased risk of complications associated with surgical management of a femoral fracture.

An Instrument to Measure Skeletal Burden and Predict Functional Outcome in Fibrous Dysplasia of Bone

An instrument to measure skeletal burden in fibrous dysplasia was developed. Biological and clinical relevance was shown by correlating skeletal burden scores with bone markers, quality of life, and ambulatory status. Childhood scores predict adult ambulatory status, and scores were unaffected when bone markers decreased with bisphosphonate treatment or aging.

Fibrous Dysplasia in the Spine: Prevalence of Lesions and Association with Scoliosis

BACKGROUND Lesions of fibrous dysplasia involving the spine and scoliosis are thought to be uncommon entities in patients with polyostotic fibrous dysplasia and McCune-Albright syndrome. By examining bone scans of a relatively large cohort of patients with these disorders, we sought to determine the prevalence of spinal involvement and any association with scoliosis. METHODS Sixty-two patients with polyostotic fibrous dysplasia were studied. There were twenty-three male and thirty-nine female patients, and they had a mean age of twenty-five years (range, four to eighty years). Technetium-99m-methylene diphosphonate (MDP) bone scans of the patients were evaluated for evidence of increased uptake in the spine. The presence or absence of scoliosis or a level pelvis and the distribution of other lesions in the skeleton were noted. RESULTS Thirty-nine (63%) of sixty-two patients were found to have seventy-six lesions of fibrous dysplasia in the spine. Fifty-four lesions (71%) demonstrated increased uptake in the posterior aspects of the spine. Most lesions were located in the lumbar spine (thirty-two lesions) and the thoracic spine (twenty-seven), with less frequent involvement in the sacrum (ten) and cervical spine (six). Twenty-five (40%) of the sixty-two patients had scoliosis; seventeen had a thoracolumbar curve; six, a lumbar curve; and two, a thoracic curve. Seven patients had curves that could not be accurately measured by bone scanning and, therefore, could not be classified. Thirty patients (48%) had no evidence of scoliosis. Thus, the prevalence of scoliosis in patients with polyostotic fibrous dysplasia was between 40% and 52%. There was a strong correlation between spinal lesions and scoliosis (p < 0.001) and pelvic asymmetry (p < 0.05). Back pain was an uncommon symptom. Two patients had a neurologic abnormality; neither abnormality was related to the location of the lesions or the curve. CONCLUSIONS Spinal lesions and scoliosis may be more common in patients with polyostotic fibrous dysplasia than has been previously reported. Since there is a strong correlation between a spinal lesion and scoliosis, these patients should be screened clinically for scoliosis. LEVEL OF EVIDENCE Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence.

Onset, Progression, and Plateau of Skeletal Lesions in Fibrous Dysplasia and the Relationship to Functional Outcome†

Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy.

Fractures in children with cerebral palsy.

Introduction: We studied the fracture history in a large population of patients with cerebral palsy to determine which children were at the highest risk for fracture. Methods: The International Classification of Diseases (Ninth Revision) coding identified 763 children with cerebral palsy. Patients and caregivers were contacted for information about fracture history and risk factors for low bone density. Of the 763 children identified, 418 children (54.8%) were available for this study; 243 (58%) had quadriplegia, 120 (29%) diplegia, and 55 (13%) hemiplegia. Three hundred sixty-six children were spastic, 23 mixed tone, 13 athetoid, and 16 classified as others. We identified 50 children (12%) who fractured; 15 of these same children had, over time, multiple fractures. Results: The number of fractures showed a normal distribution by age, with a mean of 8.6 (SD, 4.0). Children with cerebral palsy with mixed tone had a higher rate of fracture (&khgr;2 = 14.7, P < 0.01); &khgr;2 analysis indicated that the children who fractured were, as a group, more likely to use a feeding tube, have a seizure disorder, take valproic acid (VPA), and use standing equipment in therapy. Multiple regression analysis demonstrated older age and VPA use as predictive of fracture and gave the following equation: fracture = −0.01 + (VPA × 0.17) + (age × 0.15). The subgroup that sustained multiple fractures were older at the time of first fracture than the children who had only one reported fracture (t = −2.3, P < 0.05). Conclusions: The main finding of our article is that older age at first fracture and use of VPA are predictive of fractures and define a group of children with cerebral palsy who may benefit from treatment interventions to increase bone density.