Associations of childhood overweight and obesity with upper-extremity fracture characteristics.

ABSTRACT: Childhood obesity is a growing epidemic in the United States, and is associated with an increased risk of lower-extremity physeal fractures, and fractures requiring operative intervention. However, no study has assessed the risk upper extremity physeal fractures among overweight children. Our purpose was to compare the following upper-extremity fracture characteristics in overweight and obese children with those of normal-weight/underweight children (herein, "normal weight"): mechanism of injury, anatomical location, fracture pattern, physeal involvement, and treatment types. We hypothesized that overweight and obese children would be higher risk for physeal and complete fractures with low-energy mechanisms and would therefore more frequently require operative intervention compared with normal-weight children.We performed a cross-sectional review of our database of 608 patients aged 2 to 16 years, and included patients who sustained isolated upper-extremity fractures at our level-1 pediatric tertiary care center from January 2014 to August 2017. Excluded were patients who sustained pathologic fractures and those without basic demographic or radiologic information. Using body mass index percentile for age and sex, we categorized patients as obese (≥95th percentile), overweight (85th to <95th percentile), normal weight (5th to <85th percentile), or underweight (<5th percentile). The obese and overweight groups were analyzed both separately and as a combined overweight/obese group. Demographic data included age, sex, height, and weight. Fractures were classified based on fracture location, fracture pattern (transverse, comminuted, buckle, greenstick, avulsion, or oblique), physeal involvement, and treatment type. Of the 608 patients, 58% were normal weight, 23% were overweight, and 19% were obese. There were no differences in the mean ages or sex distributions among the 3 groups.Among patients with low-energy mechanisms of injury, overweight/obese patients had significantly greater proportions of complete fractures compared with normal-weight children (complete: 65% vs 55%, P = .001; transverse: 43% vs 27%, P = .006). In addition, the overweight/obese group sustained significantly more upper-extremity physeal fractures (37%) than did the normal-weight group (23%) (P = .007).Compared with those in normal-weight children, upper-extremity fracture patterns differ in overweight and obese children, who have higher risk of physeal injuries and complete fractures caused by low-energy mechanisms.Level of Evidence: Level III, retrospective comparative study.

Bone-Grafting in Polyostotic Fibrous Dysplasia.

BACKGROUND: Polyostotic fibrous dysplasia is a skeletal disease that results from somatic activating mutations in the gene GNAS in skeletal stem cells, leading to proliferation of immature osteogenic cells with replacement of normal marrow and bone with fibro-osseous tissue. Lesions may cause bone deformity or fracture. In the surgical care of polyostotic fibrous dysplasia, the role of grafting and the optimal grafting material are not clear. The purpose of this study was to evaluate the long-term survival of bone-grafting procedures in subjects with polyostotic fibrous dysplasia over time. METHODS: The operative reports and radiographs of a cohort of subjects with polyostotic fibrous dysplasia followed in a natural history study were reviewed. Twenty-three subjects (mean age at the time of enrollment, thirteen years [range, two to forty years]) with fifty-two bone-grafting procedures had a mean follow-up time of 19.6 years (range, twenty-nine months to forty-seven years). Kaplan-Meier life table estimates, Cox proportional hazard models, and t tests comparing means were performed to assess various aspects of graft survival. RESULTS: Kaplan-Meier curves showed a 50% estimate of survival of 14.5 years. Cox proportional hazards models showed no advantage comparing allograft with autograft or structural with nonstructural graft materials. The mean age of the patients was significantly greater (p < 0.001) in the subgroup of subjects in whom grafts were maintained over time (20.9 years) compared with the subgroup of patients whose grafts were resorbed over time (9.8 years). CONCLUSIONS: Bone-grafting, including both allograft and autograft, is of limited value in ablating the lesions of fibrous dysplasia. The expectations of patients and surgeons should include the high probability of graft resorption over time with return of bone characteristics of fibrous dysplasia, particularly in younger patients. This suggests the maintenance of normal bone mechanics with implant support should be the priority of any surgical intervention.

Bent Telescopic Rods in Patients With Osteogenesis Imperfecta.

BACKGROUND: Telescopic rods require alignment of 2 rods to enable lengthening. A telescopic rod converts functionally into a solid rod if either rod bends, preventing proper engagement. Our goal was to characterize implant bending as a mode of failure of telescopic rods used in the treatment of osteogenesis imperfecta in children. METHODS: We conducted a retrospective review of our osteogenesis imperfecta database for patients treated with intramedullary telescopic rods at our institution from 1992 through 2010 and identified 12 patients with bent rods. The 6 boys and 6 girls had an average age at the time of initial surgery of 3.1 years (range, 1.8 to 8.3 y) and a total of 51 telescoping rods. Clinic notes, operative reports, and radiographs were reviewed. The rods were analyzed for amount of lengthening, characteristics of bending, presence of cut out, or disengagement from an anchor point. Bends in the rods were characterized by their location on the implant component. The bent and straight rods were compared. Data were analyzed with the Mann-Whitney test (statistical significance set at P≤0.05). RESULTS: Of the 51 telescoping rods, 17 constructs (33%) bent. The average interval between surgery and rod bending was 4.0 years (range, 0.9 to 8.2 y). Before bending, 11 of 17 telescoping rods had routine follow-up radiographs for review. In 10 of the rods, bending was present when early signs of rod failure were first detected. Rod bending did not seem to be related to rod size. There was no area on the rod itself that seemed more susceptible to bending. CONCLUSIONS: Rod bending can be an early sign of impending rod failure. When rod bending is first noted, it may predispose the rod to other subsequent failures such as loss of proximal and distal fixation and cut out. Rod bending should be viewed as an indicator for closer monitoring of the patient and discussions regarding future need for rod exchange. LEVEL OF EVIDENCE: Level III-retrospective review.

Does obesity affect fracture healing in children?

BACKGROUND: Obesity is a risk factor for various orthopaedic diseases, including fractures. Obesity's influence on circulating hormones and cytokines and bone mineralization ultimately influences the body's osteogenic response and bone mineralization, potentially increasing the risk of fracture and impacting fracture healing. QUESTIONS/PURPOSES: Does obesity delay fracture recovery in overweight or obese children as measured by the time to release to normal activity? Is this average time for return to activity influenced by the mechanism of the injury? Does obesity's effect on mineralization and loading in overweight or obese children lead to a greater proportion of upper extremity fracture versus lower extremity fracture? METHODS: We prospectively followed 273 patients with nonpathologic long bone fractures treated from January 2010 to October 2011. Patients were stratified into obese/overweight, normal weight, and underweight groups. All patients were followed until release to regular activities (mean, 41 days; range, 13-100 days). RESULTS: Release to regular activities occurred sooner in obese/overweight than in normal weight patients: 39 and 42 days, respectively. A greater proportion of obese/overweight patients had low to moderate energy mechanisms of injury than did normal weight patients, but we found no difference between the groups in terms of return to activity when stratified by mechanism. There was also no difference in the proportion of upper extremity injuries between the two groups. CONCLUSIONS: Obese/overweight children did not have a delay in release to activities compared with children of normal weight. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Spinal muscular atrophy: manifestations and management.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a homozygous deletion in the SMN1 gene and is manifested by loss of the anterior horn cells of the spinal cord. Classifications of the disorder are based on age of onset and the patient's level of function. Scoliosis and hip subluxation or dislocation are two musculoskeletal manifestations associated with SMA. Severity of scoliosis correlates with age at presentation. Bracing has been unsuccessful in halting curve progression and may interfere with respiratory effort. Early onset scoliosis associated with SMA has been successfully treated with growing rod constructs, and posterior spinal fusion can be used in older children. Hip subluxations and dislocations are best treated nonsurgically if the patient reports no pain because a high rate of recurrent dislocation has been reported with surgical intervention.

Spica casting for pediatric femoral fractures: a prospective, randomized controlled study of single-leg versus double-leg spica casts.

BACKGROUND: At many centers, double-leg spica casting is the treatment of choice for diaphyseal femoral fractures in children two to six years old. We hypothesized that such patients can be effectively treated with single-leg spica casting and that such treatment would result in easier care and better patient function during treatment. METHODS: In a prospective, randomized controlled study, fifty-two patients two to six years old with a diaphyseal femoral fracture were randomly assigned to be treated immediately (after consent was obtained) with a single-leg (twenty-four patients) or double-leg (twenty-eight patients) spica cast. Serial radiographs were evaluated for maintenance of fracture reduction with respect to limb length, varus/valgus angulation, and procurvatum/recurvatum angulation. After cast removal, the performance version of the Activities Scale for Kids questionnaire and a custom-written survey were administered to the parents so that they could evaluate the ease of care and function of the children during treatment. Means were compared between treatment groups with use of Student t tests. P values of <0.05 were considered significant. RESULTS: All limbs healed in satisfactory alignment. The children treated with a single-leg spica cast were more likely to fit into car seats (p < 0.05) and fit more comfortably into chairs (p < 0.05). Caregivers of patients treated with a single-leg cast took less time off work (p < 0.05). There were no major complications. CONCLUSIONS: Treatment of pediatric femoral fractures with a single-leg spica cast is effective and safe, and postfracture patient care is facilitated. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Implant-related fractures in children: a 15-year review.

BACKGROUND: To our knowledge, there are no comprehensive clinical studies of implant-related fractures in children. Our goal was to identify the incidence, skeletal location, and associated diagnoses of implant-related fractures. METHODS: We reviewed our institutional database to identify cases of implant insertion (7584 cases) in patients less than 18 years old from January 1, 1995 through December 31, 2009. We calculated the overall incidence of these fractures and stratified the incidence by skeletal location and preoperative diagnoses. Fisher exact test was used to ascertain differences in fracture incidence. Risk ratios were calculated when appropriate. Significance was set at P<0.05. RESULTS: There were 25 cases of implant-related fractures: 22 in the femur, 2 in the tibia, and 1 in the radius. The overall incidence of implant-related fracture was 0.33%; the incidence by skeletal location was: femur, 0.89%; tibia, 0.1%; and radius, 0.14%. Associated diagnoses were cerebral palsy (9 cases), hip dysplasia (3 cases), spina bifida (2 cases), and avascular necrosis (1 case); 10 cases were associated with "other diagnoses," which included various skeletal syndromes (5 cases) and traumatic fractures (5 cases). The incidences of implant-related fractures by diagnoses were: cerebral palsy, 1.1%; hip dysplasia, 1.1%; spina bifida, 1.3%; and avascular necrosis, 0.35%. The incidence of implant-related fracture in the "other diagnoses" group was 0.16%, and the incidence of fracture in otherwise healthy patients was 0.084%. The femur was 15.2 times more likely to fracture than other bones (P<0.001). Diagnoses of cerebral palsy, hip dysplasia, spina bifida, and avascular necrosis were 6.1 times more likely to be associated with implant-related fractures than the "other diagnoses" (P<0.001). The mean time to fracture in the study was 2.8 years. The overall implant removal rate at our institution was 24.3%, and it varied significantly by patient diagnosis (P<0.01). CONCLUSIONS: Skeletal location and preoperative diagnosis should be factors of consideration in a surgeon's decision about removing implants to prevent implant-related fractures. LEVEL OF EVIDENCE: Prognostic Level III.

Effects of obesity on pediatric fracture care and management.

Obese children have a theoretically increased risk of sustaining an extremity fracture because of potential variations in their bone mineral density, serum leptin levels, and altered balance and gait. Trauma databases suggest an increased rate of extremity fractures in obese children and adolescents involved in polytrauma compared with nonobese children and adolescents. Anesthetic and other perioperative concerns for obese pediatric trauma patients undergoing surgery include higher baseline blood pressures, increased rates of asthma, and obstructive sleep apnea. A child's weight must be considered when choosing the type of implant for fixation of pediatric femoral fractures. Fracture prevention strategies in obese pediatric patients consist of ensuring properly sized safety gear for both motor vehicles and sporting activities and implementing structured weight-loss programs.

Enhanced biomechanical stiffness with large pins in the operative treatment of pediatric supracondylar humerus fractures.

BACKGROUND: Various pin configurations have been recommended for the treatment of supracondylar humerus fractures on the basis of the choice between stability versus the risk of iatrogenic nerve injury. However, little attention has been paid to pin size. The purpose of this study was to evaluate the stability of large (2.8 mm or 0.110 inch) and small (1.6 mm or 0.062 inch) pin constructs in 6 configurations. METHODS: A transverse fracture pattern was created by sectioning synthetic humeri in the midolecranon fossa. The specimens were then reduced and pinned in one of 6 configurations: 2 small pins (Kirschner wires) placed crossed or lateral divergent, 2 large pins (Steinmann pins) placed crossed or lateral divergent, or 3 small pins placed crossed or lateral divergent. All specimens were then tested in sagittal extension bending. We investigated the effect of pin configuration and cycle on the sagittal stiffness using multiple linear regression. RESULTS: The 2 small lateral divergent pin configuration was significantly less stable than small crossed pins and large pins in a crossed or a lateral configuration. The addition of a third (lateral) pin to the small crossed pin construct made it significantly less stable than 2 large crossed pins. Although the stability between the remaining configurations was not significantly different, the 2 large crossed pins required the greatest torque to rotate the fragment 20 degrees. There was a significant reduction in torque as a function of cycle, suggesting a loss of fixation during cycling (P<0.05). CONCLUSIONS: Large pins (2.8 mm) in any configuration and the placement of small pins (1.6 mm) in a crossed configuration provided more stable reduction in sagittal extension bending than did the conventional 2 small pins in a lateral divergent pin configuration. The most stable configurations involve crossing the medial and lateral pins. CLINICAL RELEVANCE: There are more stable options than the traditional 2 small lateral pin configuration for fixation of unstable supracondylar fractures. The addition of a third pin is not always advantageous.

Pin size influences sagittal alignment in percutaneously pinned pediatric supracondylar humerus fractures.

BACKGROUND: No study examining pin constructs has adequately addressed pin size and its role in fracture fixation. Our goal was to review our experience with Wilkins-modified Gartland type-III pediatric supracondylar humerus fractures treated with closed reduction and percutaneous pinning to evaluate the effects of pin size within 2 different pin constructs on maintenance of reduction and on the risk of surgical complications. METHODS: We retrospectively reviewed the medical records of pediatric patients with Wilkins-modified Gartland type-III supracondylar humerus fractures that were closed reduced and percutaneously pinned at our institution from March 1999 through December 2008. We grouped those 159 patients by fracture stabilization method (lateral-entry-pin or crossed-pin constructs), by pin size ratio (ie, ratio of pin diameter to the humeral midshaft cortical thickness: small ≤0.9; large >0.9), and then by 4 combinations of pin construct and pin size ratio. For each group, we evaluated radiographs for immediate postoperative reduction (coronal and sagittal alignment), maintenance of reduction at last follow-up, and the number of surgical complications. We used the Student t test, χ² test, Mann-Whitney U test, and Wilcoxon Signed Rank test to examine for significance, which was set at P<0.05. RESULTS: Although we found no significant differences between the groups immediately after surgery, final follow-up sagittal alignment was significantly more likely to be maintained in the large pin size ratio group than in the small pin size ratio group. For 2 types of surgical complications, infection and nerve palsy, we found no statistically significant differences in these complications between the pin construct or pin size ratio groups. CONCLUSIONS: Large pin sizes improved radiographic sagittal alignment at final follow-up without an increased rate of infection or ulnar nerve palsy. LEVEL OF EVIDENCE: Level III Therapeutic Study.

Treatment of femur fractures in children with cerebral palsy.

PURPOSE: Children with cerebral palsy may have low bone density stemming from various etiologies and are, thereby, at risk for fractures. The treatment of femur fractures in children with cerebral palsy may need to be tailored to address the management of spastic muscle tone and multiple medical co-morbidities. METHODS: Our study is a retrospective review that evaluates the treatment of 47 femur fractures in children with cerebral palsy in both ambulatory and non-ambulatory patients. RESULTS: Thirty-two fractures in non-ambulators were treated non-operatively, 11 of which resulted in malunions and five developed pressure sores. Six fractures in non-ambulators were treated operatively, one of which resulted in a malunion. In ambulators, five fractures were treated non-operatively; one of these fractures lost reduction after 2 weeks and required surgical intervention. One of four fractures in ambulators treated operatively developed a malunion. CONCLUSION: Our study results suggest that femur fractures in children with cerebral palsy can be treated non-operatively; however, because of the high risk of malunion in this patient population, fracture alignment needs to be followed closely during healing. Careful attention during casting is necessary to prevent pressure sores. Strong consideration should be given to initial operative treatment in ambulatory patients in order to preserve function.

Surgical blood loss during femoral rodding in children with osteogenesis imperfecta.

BACKGROUND: Historically, patients with osteogenesis imperfecta (OI) have been reported to be at risk for significant surgical bleeding secondary to abnormalities in platelet function. By reviewing the operative blood loss in OI patients undergoing femoral osteotomies and rodding, we hoped to identify risk factors for excessive bleeding. METHODS: A retrospective review of 22 patients with 52 inserted femoral rods was conducted under Institutional Review Board approval. Information concerning patients and procedures was collected. Associations with mean blood loss were made for categorical variables using the unpaired t-test and for continuous variables using correlation. Multivariate linear regression was used to test the influence of potential risk factors for excessive bleeding. RESULTS: The mean blood loss was 197 cc (standard deviation [SD] 129 cc, range 10-500 cc). The adjusted mean blood loss (ratio of actual blood loss divided by the total predicted blood volume [Custer and Rau in "The Harriet Lane Handbook," 18th edn. Mosby-Elsevier, Philadelphia, p 382, 2009]) was 0.16 (SD 0.13, range 0.01-0.44). Six blood transfusions were required out of 42 cases for a transfusion rate of 14%. The mean blood loss in those patients who were transfused was 279 cc compared with 182 cc for those not transfused. There were no differences in the adjusted mean blood loss between acute fracture treatment versus elective reconstruction (P = 0.08), nor between primary rodding versus revision rodding (P = 0.66). Older patients tended to have lower adjusted mean blood loss, though this was not significant (P = 0.07). Increasing number of osteotomies tended to lead to increased adjusted mean blood loss (P = 0.05). There was no association between operative time and adjusted mean blood loss (P = 0.36). When adjusting for procedure characteristics, increasing age was associated with decreasing adjusted mean blood loss (P = 0.008). CONCLUSION: Predicting blood loss for femoral rodding in patients with OI is difficult, with no differences between revision and primary procedures or elective versus trauma cases. The blood loss in our patients undergoing femoral rodding was manageable, and the transfusion rate was reasonably low. Although massive blood loss has been described in patients with OI in the literature, we found that femoral rodding did not pose excessive risk of transfusion in our OI population.

Patterns of pediatric supracondylar humerus fractures.

PURPOSE: The Wilkins-modified Gartland classification of pediatric supracondylar humerus fractures does not consider coronal or sagittal obliquity. The purposes of our study were (1) to identify and describe fracture characteristics with unique properties and (2) to propose a fracture classification system that can be reproduced reliably. METHODS: We retrospectively studied 203 consecutive displaced pediatric extension-type supracondylar humerus fractures treated operatively from January 1998 to January 2003. Fracture characteristics (eg, coronal and sagittal obliquity, postoperative alignment), type of surgical treatment, outcome, and complications were assessed and analyzed statistically with Student t test and a receiver operating characteristic curve. Significance was defined as P < 0.05. We incorporated significant cutoff values for fracture obliquity into our classification scheme and tested the classification's interobserver and intraobserver reliability. RESULTS: We identified 4 coronal (typical transverse, medial oblique, lateral oblique, and high fractures) and 2 sagittal (low sagittal and high sagittal) subtypes with significantly different characteristics and outcome. Compared with fractures with coronal obliquity of less than 10 degrees, fractures with coronal obliquity of 10 degrees or greater were associated with significantly more comminution and rotational malunion. Compared with fractures with sagittal obliquity of less than 20 degrees, fractures with sagittal obliquity of 20 degrees or greater were associated with a significantly higher incidence of additional injuries and were more likely to result in extension malunion. Analysis of the interobserver and intraobserver reliability for our system identified correlation coefficients ranging from 0.772 to 0.907 and 0.860 to 0.899, respectively. CONCLUSIONS: Because pediatric extension-type supracondylar humerus fractures vary significantly in terms of characteristics, identification of sagittal oblique and coronal oblique angles may have an important role in surgical decision making and may impact outcomes.

Pedicle and spinal canal parameters of the lower thoracic and lumbar vertebrae in the achondroplast population.

STUDY DESIGN: Retrospective morphometric population study. OBJECTIVE: To characterize pedicle and spinal canal morphology of the achondroplastic lower thoracic and lumbar vertebrae and to suggest dimensions for improving pedicle screw selection and placement. SUMMARY OF BACKGROUND DATA: Although morphometric population studies exist for various races, to our knowledge, no such analysis has been made in achondroplastic patients. METHODS: With computer software, we measured pedicle parameters on the computed tomography images of 19 adult achondroplastic patients. RESULTS: Pedicle and chord lengths ranged from 9.5-12.5 mm and 29.5-36.4 mm, respectively. Transverse pedicle diameter increased from T9 (5.5 mm) to L5 (14.2 mm). Sagittal pedicle diameter declined from L1 (11.6 mm) to L5 (7.8 mm). Transverse angulation was greatest at L5 (15.7 degrees ) and smallest at T12 (1.1 degrees ). Pedicles were directed cranially at all levels, ranging from 3.8 degrees -15.6 degrees . Interpedicular distance and cross-sectional area were smallest at L4 (14.9 mm and 119 mm, respectively). Pedicle starting points diverged from T9 (13.6 mm) to L5 (19.2 mm2). CONCLUSION: Achondroplastic pedicle morphology differs markedly from those of the normal spine: chord lengths are substantially shorter, pedicles are inclined cranially, pedicle starting points diverge progressively in the lumbar spine, and pedicle shape transitions from vertically to horizontally oriented ellipsoids along the lumbar spine. Consideration of this variation could maximize the effectiveness and safety of pedicle instrumentation.

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.

Onset, progression, and plateau of skeletal lesions in fibrous dysplasia and the relationship to functional outcome.

UNLABELLED: 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. INTRODUCTION: Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder in which normal bone is replaced by abnormal fibro-osseous tissue. Variable amounts of skeletal involvement and disability occur. The age at which lesions are established, the pace at which the disease progresses, if (or when) the disease plateaus, and how these parameters relate to the onset of disability are unknown. To answer these questions, we performed a retrospective analysis of a group of subjects with FD. MATERIALS AND METHODS: One hundred nine subjects with a spectrum of FD were studied for up to 32 years. Disease progression was assessed in serial (99)Tc-MDP bone scans by determining the location and extent of FD lesions using a validated bone scan scoring tool. Physical function and the need for ambulatory aids were assessed. RESULTS: Ninety percent of the total body disease skeletal burden was established by age 15. Disease was established in a region-specific pattern; in the craniofacial region, 90% of the lesions were present by 3.4 yr, in the extremities, 90% were present by 13.7 yr, and in the axial skeleton, 90% were present by 15.5 yr. Twenty-five of 103 subjects eventually needed ambulatory aids. The median age at which assistance was needed was 7 yr (range, 1-43 yr). The median bone scan score for subjects needing assistance was 64.3 (range, 18.6-75) compared with 23.1 (range, 0.5-63.5) in the unassisted subjects (p < 0.0001). Among subjects needing assistance with ambulation, 92% showed this need by 17 yr. CONCLUSIONS: The majority of skeletal lesions and the associated functional disability occur within the first decade of life. The implication is that the window of time for preventative therapies is narrow. Likewise, therapeutic interventions must be tailored to where the patient is in the natural history of the disease (i.e., progressive disease [young] versus established disease [older subjects]). These findings have implications for prognosis, the timing and type of therapy, and the development of trials of new therapies and their interpretation.

Circulating connective tissue precursors: extreme rarity in humans and chondrogenic potential in guinea pigs.

Using a variety of cell separation techniques and cultivation conditions, circulating, adherent, connective tissue, clonogenic cells were found in just 3 donors out of 66, demonstrating that these precursors are extremely rare in postnatal human blood. Contrary to humans, guinea pig blood shows much more reproducible connective tissue colony formation; it was therefore chosen to study the differentiation potential of adherent blood-derived clonogenic cells. Out of 22 single colony-derived strains of various morphologies, only 5 spindle-shaped strains showed extensive proliferative capacity in vitro. None of these strains formed bone upon in vivo transplantation, whereas two strains formed cartilage in high-density pellet cultures in vitro. Both chondrogenic strains included cells expressing aggrecan, whereas nonchondrogenic strains did not. Out of four polyclonal strains studied, one formed both cartilage and abundant bone accompanied by hematopoiesis-supporting stroma. Evidently, there are cells in adult guinea pig blood capable of both extensive proliferation and differentiation toward cartilage: circulating chondrogenic precursors. Although some of these cells lack osteogenic potential and therefore represent committed chondrogenic precursors, others may be multipotential and consequently belong to the family of skeletal stem cells. This is the first demonstration of postnatal circulating chondrogenic precursors, as well as of precursor cells with chondrogenic but not osteogenic potential. Disclosure of potential conflicts of interest is found at the end of this article.

Current approach to fibrous dysplasia of bone and McCune-Albright syndrome.

Fibrous dysplasia (FD) of bone is an uncommon disease caused by sporadic, congenital mutations in the cAMP regulating protein, G(s)alpha. It is an example of somatic mosaicism in which a wide spectrum of disease is possible. Widespread skeletal involvement is often associated with varying combinations of café-au-lait skin spots, and/or endocrine dysfunction (precocious puberty, renal phosphate wasting, hyperthyroidism, and/or growth hormone excess). Unrecognized and untreated endocrine dysfunction can exacerbate the skeletal disease. The diagnosis is usually established on clinical grounds on the basis of physical examination and typical radiographic appearance. Occasionally, gene testing of affected tissue may be helpful. The skeletal sites involved with disease are established at an early age, and the complications of fracture deformity are most pronounced in childhood. Bone pain in the absence of a fracture is more common in adults, but can also be present in children. Treatment with bisphosphonates is usually effective at relieving pain, but probably has no effect on the natural history of the disease. Scoliosis, which was previously thought to be an uncommon occurrence, has been shown to be common and progressive, and as such, warrants investigation and, when necessary, surgical treatment. The surgical management of FD remains challenging. Timing and technique remain controversial, but some consensus exists in that grafting materials (of any type) usually fail and should not be a central aspect of the surgical approach. Intramedullary devices are in general superior to side plates and screws. In extremely widespread disease with very early fracture and deformity, no surgical approach will affect final functional outcome. Efforts should be made for the initiation of international collaborative studies to better define optimal surgical approaches to the treatment of this challenging disease.

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 (chi = 14.7, P < 0.01); chi 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 x 0.17) + (age x 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.

Cervical spinal stenosis in metatropic dysplasia.

Metatropic dysplasia is a rare skeletal dysplasia characterized by rapid collapse of the thoracolumbar spine into kyphoscoliosis. Other spinal anomalies associated with metatropic dysplasia include odontoid hypoplasia and atlantoaxial instability leading to cervical myelopathy. Children with metatropic dysplasia evaluated at our institution for spinal deformity showed evidence of cervical stenosis with or without associated cord compression. Magnetic resonance imaging was found to demonstrate these changes. The association of cervical spinal stenosis and metatropic dysplasia has not been previously described. This has significant treatment implications, because decompression over the stenotic segments should be considered in conjunction with spinal fusion for treatment of odontoid hypoplasia or atlantoaxial instability. A retrospective review of 13 cases of metatropic dysplasia was performed. Despite the challenges provided by this patient population, the chance to halt or reverse neurological dysfunction and improve deformity necessitates prompt surgical intervention.