Benjamin Alman

Fibrous dysplasia is a benign condition caused by a known genetic mutation leading to dysplastic bone formation, which may be accompanied by extra-osseous manifestations including cafe-au-lait spots, precocious puberty, and hyperthyroidism. Clinically, these symptoms may present with pain and deformity, and recognition of these lesions is important to prevent pathologic fracture. The diagnosis of FD is made by plain radiograph, and bone scan remains an effective tool for measuring the extent of disease. The managed of FD of the proximal femur aims at preventing pathologic fracture, deformity correction, and pain control. Asymptomatic and small lesions may be managed by observation. Lesions of the proximal femur associated with pain and deformity require surgical intervention. Intramedullary, load sharing, devices are the preferred treatment for prophylactic fixation, and valgus osteotomy procedures are required for the coxa vara (shepherd’s crook) deformity that classically may present. FD is a disease of the growing patient, and once skeletal maturity is reached the disease process tends to stabilize or may normalize in select patients.

Osteosarcoma (OS) is a lethal disease with few known targeted therapies. Here, we show that decreased ATRX expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypic changes correspond with activation of NF-κB signaling, extracellular matrix remodeling, increased integrin αvβ3 expression, and ETS family transcription factor binding. Here, we characterize these changes in vitro, in vivo, and in a data set of human OS patients. This increased aggression substantially sensitizes ATRX-deficient OS cells to integrin signaling inhibition. Thus, ATRX plays an important tumor-suppression role in OS, and loss of function of this gene may underlie new therapeutic vulnerabilities. The relationship between ATRX expression and integrin binding, NF-κB activation, and ETS family transcription factor binding has not been described in previous studies and may impact the pathophysiology of other diseases with ATRX loss, including other cancers and the ATR-X α thalassemia intellectual disability syndrome.

Desmoid tumor (DT; other synonymously used terms: Desmoid-type fibromatosis, aggressive fibromatosis) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. Previously surgery was the standard primary treatment modality; however, in recent years a paradigm shift towards a more conservative management has been introduced and an effort to harmonise the strategy amongst clinicians has been made. We present herein an evidence-based, joint global consensus guideline approach to the management of this disease focussing on: molecular genetics, indications for an active treatment, and available systemic therapeutic options. This paper follows a one-day consensus meeting held in Milan, Italy, in June 2018 under the auspices of the European Reference Network for rare solid adult cancers, EURACAN, the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) as well as Sarcoma Patients EuroNet (SPAEN) and The Desmoid tumour Research Foundation (DTRF). The meeting brought together over 50 adult and pediatric sarcoma experts from different disciplines, patients and patient advocates from Europe, North America and Japan.

Pediatric proximal femur fractures are high-energy injuries with predictable and morbid complications. Osteonecrosis of the femoral head is the most common complication with identified risk factors including fracture type, patient's age, degree of displacement, timing to reduction, and stability of fixation. Additional complications include nonunion, coxa vara, and premature physeal arrest. The mainstay of treatment for traumatic pediatric osteonecrosis is hip preservation with total hip arthroplasty being reserved as a salvage procedure. An anatomic fracture reduction and a biomechanically stable construct are critical to prevent both nonunion and osteonecrosis. This review will look at the individual surgical interventions for the management of the associated complications of pediatric proximal femur fractures.

The mechanisms underlying bone development, repair and regeneration are reliant on the interplay and communication between osteoclasts and other surrounding cells. Osteoclasts are multinucleated monocyte lineage cells with resorptive abilities, forming the bone marrow cavity during development. This marrow cavity, essential to hematopoiesis and osteoclast-osteoblast interactions, provides a setting to investigate the origin of osteoclasts and their multi-faceted roles. This Review examines recent developments in the embryonic understanding of osteoclast origin, as well as interactions within the immune environment to regulate normal and pathological bone development, homeostasis and repair.