Bone Abstracts

Objective: Osteogenesis imperfecta (OI) is primarily characterized by bone fragility but is also associated with lower muscle mass and function. As muscle mass and bone mass are closely linked, an intervention that increases muscle mass should also increase bone mass. Here we investigated the effect of a novel activin receptor IIB ligand trap, ACE-2494 (Acceleron Pharma), on skeletal muscle mass and bone properties in a mouse model of severe dominant OI, the Col1a1<su...

Bone fractures can be a serious and frequent problem for patients suffering from osteoporosis, metastatic bone cancer and congenital bone disorders. The promotion of new bone formation and mineralization can facilitate healing and stronger union of fractured bones. Our laboratory has identified important developmental roles of sphingomyelin phosphodiesterase 3 (SMPD3), which include the promotion of apoptosis of hypertrophic chondrocytes and mineralization of cartilage and bon...

Objectives: This study analysed prospective associations between two distinct developmental trajectories of objectively-measured physical activity and late adolescent bone parameters (age 17 yr) by exploring the mediating effects of lean soft tissue (LST), a surrogate of muscle mass.Methods: In approximately 349 participants (191 girls) of the Iowa Bone Development Study, physical activity was measured by accelerometry starting at age 5 and continuing at...

Introduction: Giant cell tumour of the bone (GCTB) is a benign, locally aggressive tumour whose neoplastic stromal cells express receptor activator of nuclear factor kappa-B ligand (RANKL) and activate its receptor RANK on osteoclast-like giant cells. Denosumab (RANKL inhibitor) is an FDA/EMA approved treatment for GCTB in adults and ‘skeletally mature’ adolescents. Safety concerns include oversuppression of bone remodelling, with risk of osteonecrosis of the jaw [ON...

Objectives: As osteoblasts mature, they acquire the expression of multiple molecules involved in phosphate metabolism, including dentin matrix protein 1 (DMP1) and fibroblast growth factor 23 (FGF23). This suggests that osteoblasts and osteocytes may sense and respond to alterations in the phosphate availability in their microenvironment. We previously reported that increased extracellular inorganic phosphate (Pi) triggered signal transduction in various cell types to alter ge...

Fanconi anemia (FA) is a rare genetic disease associated with a progressive decline in hematopoietic stem cells leading to bone marrow failure. FA is also characterized by various developmental defects including short stature and skeletal malformations of the upper and lower limbs. Indeed, more than half of children affected with FA have radial-ray abnormalities with a tendency to early osteoporosis and osteopenia. However, the underlying mechanisms leading to bone defects in ...

Background: Sarcopenia and osteoporosis are among the late complications of type 1 diabetes (T1D) in adults. Whether and to what extent musculoskeletal impairment is present in childhood and adolescence has yet to be determined. The aim of this study was to assess volumetric bone mineral density (BMD) and dynamic muscle function in adolescents with T1D and to assess the clinical and biochemical predictors of their musculoskeletal system.Methods: Ninety-f...

Animal studies suggest that fetal movements are key to healthy skeletal development, but evidence in humans is limited. Breech presentation occurs in 3% of term births and is associated with reduced fetal movement and higher incidence of hip dysplasias, but more general effects on bone development have not been explored.Offspring whole body bone outcomes were measured using dual-energy X-ray absorptiometry (DXA) at mean(SD) 6(5) days after birth in 993 i...

Background: Children with inflammatory bowel disease (IBD) have reduced bone mineral density (BMD). The aim of this study was to investigate whether changes in patient’s cellular immune response correlate with reductions in BMD.Method: Children undergoing lower gastrointestinal endoscopy disease were approached with an aim of recruiting 15 patients newly diagnosed with Crohn’s Disease (CD) and 15 healthy controls. Lymphocytes were isolated from...

Introduction: Whilst it is well-established that sedentary behaviour may increase the risk of paediatric obesity, and potentially result in early onset cardio-metabolic diseases such as type 2 diabetes and cardiovascular disease, there is less consensus about the potential detrimental effects that long-term sedentary behaviour may have on bone health during childhood.Purpose: To determine if long-term sedentary behaviour affects accrual of bone mass, str...

Objective: Expansion of bone marrow, accumulation of iron, growth failure and delayed puberty affect bone health in thalassemia; data on bone density and geometry are scarce. Our objective was to assess bone density (by Dual Energy X-ray Absorptiometry, DXA) and geometry (by peripheral quantitative computed tomography, pQCT) in children with thalassemia major.Methods: Children with thalassemia were recruited from a hematology clinic in Pune (India) (Mean...

Osteogenesis Imperfecta (OI) is a brittle bone disease, characterized with reduced bone mass and bone fragility of different severity due to collagen type I defects. Patients suffer from recurrent spontaneous fractures starting in the early childhood or before birth.The main aim of the study was to relate time of the first fracture with COL1A1/2 mutations causing OI.Total number of 167 unrelated OI patients from the Osteog...

Objectives: Quadriplegic children are more susceptible to osteoporosis because of various risk factors for the inhibition of bone metabolism. The importance of bone metabolism is being emphasized based on extending life span of the patients but research on this area is insufficient. Intravenous (IV) pamidronate is well known as an effective treatment for pediatric osteoporosis, but there are no treatment guidelines for accurate dose capacity and duration in quadriplegic childr...

Cole-Carpenter syndrome (CCS) is commonly classified as a rare Osteogenesis Imperfecta disorder. This was following the description of two unrelated patients with very similar phenotypes who were subsequently shown to have a heterozygous missense mutation in P4HB. Here, we report a 3-year old female patient who was diagnosed with a severe form of OI. Exome sequencing identified the same missense mutation in P4HB as reported in the original cohort, thus reinfo...

Physiotherapy is one of the most important therapeutic approaches in Osteogenesis imperfecta (OI) besides medical and surgical treatment. At the moment there are no guidelines and no consensus about appropriate physiotherapeutic concepts for children with OI. In each country different preferences regarding the therapeutic approaches (neuro developmental techniques, active and passive training, treadmill training, pool therapy etc) are used. There are hardly any scientific rese...

Objectives: To identify and determine the extent to which effective/ineffective steps in the implementation of the Kaiser Permanente Southern California Healthy Bones Model of Care were perceived by physician champions and Healthy Bones Care Managers.Methods: The subjects in the study included 20 Physician Champions and 35 Healthy Bones Care Managers employed in the Kaiser Permanente Southern California Healthy Bones Model of Care.25 have been employed i...

Objectives: Poor bone health in boys with Duchenne Muscular Dystrophy (DMD) due to muscle weakness and glucocorticoid treatment is a major concern. This study assesses the bone health status in DMD boys with glucocorticoid treatment in a single centre.Methods: A retrospective chart review from January 2009 to January 2017 was undertaken on all DMD cases with active follow-up in a single paediatric unit in a University-affiliated hospital. We assessed the...

Objective: Bone fractures are very common in children and their number is growing every year. Vitamin D has a proven role in the prevention of fractures. In the recent study, we have shown that children with low-energy fractures have significantly lower vitamin D blood levels compared to the children without fractures. Our data indicate that higher levels of vitamin D reduced the risk of fracture by 1.06 times (P<0.0005).Past decade has seen...

Bone fractures may depend on Vitamin D Receptor Gene (VDR), bone mineral density, bone turnover markers.Patients and methods: About 161 patients were recruited and underwent: skeletal densitometry (DXA) method and bone turnover studies (Osteocalcin and Ntx).The study group was evaluated using restriction enzyme digestion at BsmI (rs1544410), FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236), polymorphic sites of t...

Background: Skeletal dysplasias include many pathological conditions that involve bone metabolism and health and most of them are associated with short stature. 211 genes are associated with bone dysplasia and short stature. Presenting problem: To present a boy with severe short stature and skeletal abnormalities. He was born at term AGA. Growth failure was noted from the age of 8 months. IGF-I levels were low and he was tested for growth hormone deficie...

Background: Pseudohypoparathyroidism type 1A (PHP1A) is a rare genetic disorder caused by mutations in the gene GNAS. It is characterized by multi-hormone resistance, obesity, cognitive impairment and the Albright hereditary osteodystrophy phenotype. A recent study found a 4.4-fold increase risk of sleep apnea in children with PHP1A compared with similarly obese children.Objective: To describe a case of morbid obesity and respiratory failure in ...