Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST): Development and Validation of a Prognostic Model in Untreated Adolescent Idiopathic Scoliosis Using the Simplified Skeletal Maturity System.

STUDY DESIGN: Prognostic study and validation using prospective clinical trial data. OBJECTIVE: To derive and validate a model predicting curve progression to ≥45° before skeletal maturity in untreated patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Studies have linked the natural history of AIS with characteristics such as sex, skeletal maturity, curve magnitude, and pattern. The Simplified Skeletal Maturity Scoring System may be of particular prognostic utility for the study of curve progression. The reliability of the system has been addressed; however, its value as a prognostic marker for the outcomes of AIS has not. The BrAIST trial followed a sample of untreated AIS patients from enrollment to skeletal maturity, providing a rare source of prospective data for prognostic modeling. METHODS: The development sample included 115 untreated BrAIST participants. Logistic regression was used to predict curve progression to ≥45° (or surgery) before skeletal maturity. Predictors included the Cobb angle, age, sex, curve type, triradiate cartilage, and skeletal maturity stage (SMS). Internal and external validity was evaluated using jackknifed samples of the BrAIST data set and an independent cohort (n = 152). Indices of discrimination and calibration were estimated. A risk classification was created and the accuracy evaluated via the positive (PPV) and negative predictive values (NPV). RESULTS: The final model included the SMS, Cobb angle, and curve type. The model demonstrated strong discrimination (c-statistics 0.89-0.91) and calibration in all data sets. The classification system resulted in PPVs of 0.71-0.72 and NPVs of 0.85-0.93. CONCLUSIONS: This study provides the first rigorously validated model predicting a short-term outcome of untreated AIS. The resultant estimates can serve two important functions: 1) setting benchmarks for comparative effectiveness studies and 2) most importantly, providing clinicians and families with individual risk estimates to guide treatment decisions. LEVEL OF EVIDENCE: Level 1, prognostic.

Ultrasound in juvenile idiopathic arthritis.

BACKGROUND: In the recent years, musculoskeletal ultrasound (MSUS) has been regarded as especially promising in the assessment of juvenile idiopathic arthritis (JIA), as a reliable method to precisely document and monitor the synovial inflammation process. MAIN CONTENT: MSUS is particularly suited for examination of joints in children due to several advantages over other imaging modalities. Some challenges should be considered for correct interpretation of MSUS findings in children, due to the peculiar features of the growing skeleton. MSUS in JIA is considered particularly useful for its ability to detect subclinical synovitis, to improve the classification of patients in JIA subtypes, for the definition of remission, as guidance to intraarticular corticosteroid injections and for capturing early articular damage. Current evidence and applications of MSUS in JIA are documented by several authors. Recent advances and insights into further investigations on MSUS in healthy children and in JIA patients are presented and discussed in the present review. CONCLUSIONS: MSUS shows great promise in the assessment and management of children with JIA. Nonetheless, anatomical knowledge of sonographic changes over time, underlying immunopathophysiology, standardization and validation of MSUS in healthy children and in patients with JIA are still under investigation. Further research and educational efforts are required for expanding this imaging modality to more clinicians in their daily practice.

Effects of exclusive enteral nutrition on bone mass, linear growth and body composition in children with Crohn's disease.

Inflammatory bowel disease, especially Crohn's disease, is linked to significant growth stunting, sarcopenia (loss of skeletal muscle mass), deterioration of bone architecture and reduction in bone mass. Exclusive enteral nutrition (EEN) has been shown to correct nutritional deficiencies, provide adequate calories for growth, and alleviate intestinal inflammation in Crohn's disease with a favorable adverse effect profile. In this chapter, we report a summary of the effects of EEN on linear growth, skeletal health and lean body mass in children with Crohn's disease.

The short- and long- term effects of estrogen deficiency on apoptosis in musculoskeletal tissues: an experimental animal model study.

BACKGROUND: Estrogen is the major sex steroid affecting the growth, remodeling, and homeostasis of the female skeleton. Estrogen loss in postmenopausal women leads to osteoporosis. The aim of this study was to evaluate the early and long- term effects of estrogen loss on bones, tendons, muscles, and menisci in ovariectomized rats.  METHODS: Fifteen rats were randomized into three groups of five animals each. The first group was the control group with no additional surgical procedure, but the rest (groups 2 and 3) were bilaterally ovariectomized . All animals in the group 2 were sacrificed at 14th week to evaluate the short- term effect, and all of other animals in the groups 1 and 3 were sacrificed at 28th week to analyze the long- term effect of estrogen loss in the ovariectomized group and to control with the group 1. Quadriceps muscles, Achilles tendons, menisci, and femur cortical bones from both lower extremities were taken. The amount of apoptosis was measured. RESULTS: There was a significant increase in cell apoptosis in bones, muscles, and tendons with insignificant increase in cell apoptosis in menisci at early and late periods in rats with ovariectomies than the control.  CONCLUSION: The results indicated that estrogen loss after ovariectomy does not only affect bones; it may also increase cell apoptosis in different tissues such as muscles, tendons, and menisci.

Update on embryology of the upper limb.

Current concepts in the steps of upper limb development and the way the limb is patterned along its 3 spatial axes are reviewed. Finally, the embryogenesis of various congenital hand anomalies is delineated with an emphasis on the pathogenetic basis for each anomaly.

Orthopaedic management of Hurler's disease after hematopoietic stem cell transplantation: a systematic review.

OBJECTIVE: The introduction of hematopoietic stem cell transplantation (HSCT) has significantly improved the life-span of Hurler patients (mucopolysaccharidosis type I-H, MPS I-H). Yet, the musculoskeletal manifestations seem largely unresponsive to HSCT. In order to facilitate evidence based management, the aim of the current study was to give a systematic overview of the orthopaedic complications and motor functioning of Hurler's patients after HSCT. METHODS: A systematic review was conducted of the medical literature published from January 1981 to June 2010. Two reviewers independently assessed all eligible citations, as identified from the Pubmed and Embase databases. A pre-developed data extraction form was used to systematically collect information on the prevalence of radiological and clinical signs, and on the orthopaedic treatments and outcomes. RESULTS: A total of 32 studies, including 399 patient reports were identified. The most frequent musculoskeletal abnormalities were odontoid hypoplasia (72%), thoracolumbar kyphosis (81%), genu valgum (70%), hip dysplasia (90%) and carpal tunnel syndrome (63%), which were often treated surgically during the first decade of life. The overall complication rate of surgical interventions was 13.5%. Motor functioning was further hampered due to reduced joint mobility, hand dexterity, motor development and longitudinal growth. CONCLUSION: Stem cell transplantation does not halt the progression of a large range of disabling musculoskeletal abnormalities in Hurler's disease. Although prospective data on the quantification, progression and treatment of these deformities were very limited, early surgical intervention is often advocated. Prospective data collection will be mandatory to achieve better evidence on the effect of treatment strategies.

Juvenile osteochondritis dissecans.

Juvenile osteochondritis dissecans (JOCD) has been a recognized entity for more than 100 years. Despite our long recognition of OCD, the natural history and most effective therapies are poorly understood. Although conclusive evidence of an exact cause is lacking, there is widespread agreement that JOCD is related to repetitive trauma. Patients with JOCD present with vague pain and occasionally, mechanical symptoms. The diagnosis of JOCD can be confirmed on plain radiographs. Magnetic resonance imaging has emerged as the study of choice to evaluate the stability of the lesion and integrity of the overlying articular cartilage. Treatment decisions are based on the stability of the lesion. Stable JOCD lesions should be treated initially with activity modification and possibly, immobilization. Unstable lesions and stable lesions not responding to an initial course of nonoperative therapy should be surgically treated. Surgical treatment is based on the radiographic and arthroscopic characteristics of the lesion. Multiple techniques from simple arthroscopic drilling and fixation to salvage techniques for cartilage restoration are discussed.

Adipose tissue as a stem cell source for musculoskeletal regeneration.

Adipose tissue is an abundant, easily accessible, and reproducible cell source for musculo-skeletal regenerative medicine applications. Initial derivation steps yield a heterogeneous population of cells of stromal vascular fraction (SVF) cells. Subsequent adherent selection of the SVF results in a relatively homogeneous population of adipose-derived stromal/stem cells (ASCs) capable of adipogenic, chondrogenic, myogenic, and osteogenic differentiation in vitro on scaffolds in bioreactors and in vivo in pre-clinical animal models. Unlike hematopoietic cells, ASCs do not elicit a robust lymphocyte reaction and instead release immunosuppressive factors, such as prostaglandin E2. These immunomodulatory features suggest that allogeneic and autologous ASCs will engraft successfully for tissue regeneration purposes. The differentiation and expansion potential of ASCs can be modified by growth factors, bio-inductive scaffolds, and bioreactors providing environmental control and biophysical stimulation. Gene therapy approaches using lentiviral transduction can be used to direct differentiation of ASCs to particular lineages. We discuss the utility of ASCs for musculo-skeletal tissue repair and some of the technologies that can be implemented to unlock the full regenerative potential of these highly valuable cells.

The effect of muscle dysfunction on bone mass and morphology.

There is little doubt that skeletal development and subsequent maintenance of bone mass and morphology during adulthood is greatly influenced by viable muscle function. In this review, we will summarize human observations that support this concept, then focus on models that have enabled (or may enable in the future) insight into the co-dependency of muscle and bone. Specifically, we will summarize data generated with three types of models: 1) spinal cord injury models, 2) transgenic mice with altered muscle function, and 3) experimental models affecting one hindlimb or a single muscle group. In sum, these data clearly support the concept that muscle function is critical for the successful development of the skeleton and is likely to play an important role in mediating bone health through life. The specific signaling pathways by which this interdependency is achieved, however, remain to be clarified.

Myostatin (GDF-8) as a key factor linking muscle mass and bone structure.

Myostatin (GDF-8) is a member of the transforming growth factor-beta (TGF-beta) superfamily that is highly expressed in skeletal muscle, and myostatin loss-of-function leads to doubling of skeletal muscle mass. Myostatin-deficient mice have been used as a model for studying muscle-bone interactions, and here we review the skeletal phenotype associated with altered myostatin signaling. It is now known that myostatin is a key regulator of mesenchymal stem cell proliferation and differentiation, and mice lacking the myostatin gene show decreased body fat and a generalized increase in bone density and strength. The increase in bone density is observed in most anatomical regions, including the limbs, spine, and jaw, and myostatin inhibitors have been observed to significantly increase bone formation. Myostatin is also expressed in the early phases of fracture healing, and myostatin deficiency leads to increased fracture callus size and strength. Together, these data suggest that myostatin has direct effects on the proliferation and differentiation of osteoprogenitor cells, and that myostatin antagonists and inhibitors are likely to enhance both muscle mass and bone strength.

The impact of chronic inflammation on the growing skeleton: lessons from interleukin-6 transgenic mice.

BACKGROUND: Chronic inflammatory diseases in children are associated with impairment of linear growth and bone mineral accrual. In addition to poor nutrition, reduced mobility and glucocorticoid treatment, several observations in patients suggest that inflammation itself may have a direct detrimental effect on the growing skeletal system. Among the various inflammatory cytokines produced during the inflammatory response, data in animals suggest that interleukin-6 (IL-6) may mediate the effects of inflammation on the developing skeleton. Mice overexpressing IL-6 during the prepubertal stage show stunted growth, abnormalities of the insulin-like growth factor I system, defective growth plates, delayed development of ossification centres, uncoupling of osteoblast and osteoclast activity and defective ossification. These changes appear to mirror the features observed in children with chronic inflammatory diseases. CONCLUSIONS: The tissue, cellular and molecular abnormalities reviewed provide a rationale for therapeutic approaches aimed at correcting the detrimental effects of inflammation on the developing skeletal system.

Embryology of the upper limb.

An increased understanding of embryogenesis has advanced our fundamental knowledge of limb anomalies. Animal models with similar limb patterning have been used to dissect and manipulate crucial signaling centers that affect limb development and orientation. Experimental embryologists can produce limb anomalies that are similar to the human phenotype encountered in clinical practice. The evaluating physician must possess a basic comprehension of embryogenesis and limb formation to comprehend congenital limb anomalies and to communicate relevant knowledge to the family. This Current Concepts article is intended to provide an update of limb development that is germane to the clinical scenario.

Ulnar and humeral heads forming separate bellies: a rare case of digastric flexor carpi ulnaris muscle / Cabezas ulnar y humeral formando vientres separados: un caso raro del músculo flexor ulnar del carpo digástri

Proper knowledge of muscular variations is essential for both anatomists and surgeons. Variations of the flexor carpi ulnaris (FCU) are not very common. We are reporting an unusual case of FCU muscle with two bellies. The two heads (ulnar and humeral) of the muscle continued as two separate bellies and the tendons of which joined each other slightly proximal to the wrist before getting inserted to pisiform bone. Further, detailed literature review of variations of FCU muscle is done and the developmental basis for the variation and its surgical importance are discussed.

El correcto conocimiento de las variaciones musculares es esencial para anatomistas y cirujanos. Variaciones del músculo flexor ulnar del carpo (MFUC) no son muy comunes. Se reporta un caso inusual del MFUC con dos vientres. Las dos cabezas (ulnar y humeral) del músculo continuaron como dos vientres separados. Los tendones se unieron entre sí, ligeramente proximal a la muñeca, antes de llegar a su inserción en el hueso pisiforme. Se hace una detallada revisión de la literatura de las variaciones del MFUC y son discutidas las bases del desarrollo de las variaciones, destacándose además su importancia quirúrgica.

Maturity assessment and curve progression in girls with idiopathic scoliosis.

BACKGROUND: Scoliosis progression during adolescence is closely related to patient maturity. Maturity has various indicators, including chronological age, height and weight changes, and skeletal and sexual maturation. It is not certain which of these indicators correlates most strongly with scoliosis progression. The purpose of the present study was to evaluate various maturity measurements and how they relate to scoliosis progression. METHODS: Physically immature girls with idiopathic scoliosis were evaluated every six months through their growth spurt with serial spinal radiographs; hand skeletal ages; Oxford pelvic scores; Risser sign determinations; height; weight; sexual staging; and serologic studies of the levels of selected growth factors, estradiol, bone-specific alkaline phosphatase, and osteocalcin. These measurements were then correlated with the curve-acceleration phase. RESULTS: The period and pattern of curve acceleration began during Risser stage 0 for all patients. Skeletal maturation scores derived with the use of the Tanner-Whitehouse-III RUS method, particularly those for the metacarpals and phalanges, were superior to all other indicators of maturity. Regression of the scores provided good estimates of maturity relative to the period of curve progression (Pearson r = 0.93). The initiation of this period occurred simultaneously with digital changes from Tanner-Whitehouse-III stage F to G. At this stage, curves also separated into rapid, moderate, and low-acceleration patterns, with specific curve types in the rapid and moderate-acceleration groups. The low-acceleration group was not confined to a specific curve type. CONCLUSIONS: The curve-acceleration phase separates curves into various types of curve progression. The Tanner-Whitehouse-III RUS scores are highly correlated with timing relative to the curve-acceleration phase and provide better maturity determination and prognosis determination during adolescence than the other parameters tested. Accurate skeletal maturity determination should be used as the primary maturity measurement in girls with idiopathic scoliosis.