Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:To provide the pediatrician with a comprehensive overview of the orthopedic considerations and potential issues in a child with Charcot-Marie-Tooth (CMT) disease. CMT is not one disease but rather a myriad of genetic and biochemical processes that manifest in a final common pathway of physical impairment with cardinal orthopedic elements. RECENT FINDINGS/RESULTS:This review incorporates the most current research on CMT, including its orthopedic elements, and the opinion of specialists in pediatric orthopedics specifically in the areas of foot and ankle, hip dysplasia and spinal deformity. SUMMARY/CONCLUSIONS:This article provides a framework for pediatricians to understand the complex and variable natural history of CMT with regard to neurologically produced musculoskeletal changes.

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair.

PURPOSE OF REVIEW/OBJECTIVE:To provide the pediatrician with a comprehensive synopsis of pediatric pes planus, also known as flatfoot. The term pes planus is a physical finding that generates some confusion in the medical community because it describes a spectrum of conditions that are diagnosed and managed differently. RECENT FINDINGS/RESULTS:Some of the recent data incorporated in this review come from pediatric, orthopaedic, and podiatric literature. These sources describe the clinical features and the latest treatment options for pes planus. SUMMARY/CONCLUSIONS:This article will provide some guidance to evaluate and treat the many causes of pediatric pes planus. Nonsurgical and operative management will be discussed.

Lead toxicity is a significant problem in the U.S. with elevated blood lead levels being highest among very young children and older adults >50 years old. Bone is the major reservoir of body lead, accounting for 75% in children and 90% in adults. Very little is known about the effect of lead on bone mineral properties in adults. We investigated the effect of lead on the femora from adult, 6 month old female C57/BL6 mice who were administered lead in the drinking water (250 ppm, blood lead 33 μg/dL) for 4 months. Bone mineral properties were examined using Fourier Transform Infrared Microscopy (FTIRM), quantitative microcomputed tomography (microCT) and whole bone mechanical testing. Lead significantly decreased the bone mineral density in the cortical and proximal cancellous bone and increased the marrow area in the cortical bone with microCT. Whole bone three-point bending showed a trend of decreased maximum and failure moments in the lead treated bones compared to controls. Lead significantly decreased the mineral/matrix ratio, collagen maturity and crystallinity in the trabecular bone as measured by FTIRM. In the cortical bone lead significantly decreased collagen maturity and bone crystal size by FTIRM. In contrast to cell culture studies, lead significantly increased serum osteocalcin levels. Lead also significantly increased the bone formation and resorption markers suggesting increased bone turnover. These data show that lead increases bone turnover resulting in weaker cortical bone in adult female mice and suggest that lead may exacerbate bone loss and osteoporosis in the elderly.