Bone Abstracts

Brittle bones have been reported in children, adolescents and adults with cystic fibrosis (CF), independently of sex; this has been termed CF-related bone disease. In CF patients with the F508del mutation in the (Cftr) gene, vertebral fractures and the subsequent dorsal kyphosis decrease pulmonary function, thus accelerating the course of the disease. Mice with the homozygous F508del mutation in CFTR develop a severe osteopenic phenotype early on, in both sexes (Le He...

Skeletogenesis is an intricate process controlled by numerous transcriptional factors, hormones and signalling pathways. Recently, microRNAs emerged as important players in skeletogenesis but, only few were identified and most of their targets remain unknown. Previous works showed that miR-199a-2/214 cluster is essential for skeletal development and that miR-214 inhibits bone formation in mammals. However, data regarding its skeletal role in other vertebrates is scarce and its...

Objective: Children with hypophosphatasia (HPP) treated with asfotase alfa in a Phase 2 study (NCT00952484) and its open-label extension (NCT01203826) experienced significant improvements in skeletal mineralization and physical function that were sustained through 5 years of treatment (1). Herein, we report data from these studies with a maximum of 7 years of treatment.Methods: Children with HPP aged 6–12 years at baseline received asfotase alfa (3 ...

Background: Severe vitamin D deficiency (VDD), is a common disorder, which has complications including rickets, hypocalcaemia, hypotonia, delayed development and cardiomyopathy. Although nutritional rickets associated craniosynostosis has been reported, there is little awareness of this or knowledge about its clinical course or severity. We present five cases of late onset craniosynostosis in association with nutritional rickets.Clinical presentation: Th...

Background: Mutations in the PLS3 gene, encoding plastin 3, cause X-linked osteoporosis. Osteoporosis is characterized by low bone mineral density (BMD) and increased susceptibility to fractures. Here we describe a 7-year-old boy with osteoporosis due to a novel PLS3 deletion.Presenting problem: The patient, born to non-consanguineous parents, had a history of one low-energy long-bone fracture, three vertebral fractures (T5, T6 T8) and kyphosis. DXA scan...

see PP205....

Communication between osteoblasts and osteoclasts is crucial for bone remodeling. Thrombin and its thrombin receptor (TR; PAR-1) are expressed in osteoclasts and osteoblasts, respectively. To date, the physiological roles of thrombin and TR in bone metabolism have not been elucidated. Therefore, we fully characterized the bone phenotype of mice lacking the thrombin receptor.We performed bone microarchitectural analyses of the femurs of 10–12 week ol...

Introduction: Lymphoblastic leukemia is the predominant form of childhood malignancies with survival rates of >80%. Late effects of cancer and treatment can affect endocrine function and may account for acute and chronic impairment of bone health.Aim and design: To assess bone health in pediatric patients after therapy for lymphoblastic leukemia we initiated a clinical trial investigating clinical and biochemical parameters of growth, puberty, bone t...

Juvenile Paget’s disease (JPD) is an extremely rare, yet painful and debilitating bone disease with onset occurring during early childhood. JPD can be caused by loss of function of osteoprotegerin, resulting in subsequent osteoclast stimulation via the activated receptor activator of nuclear factor-kappa B (RANK) pathway. Increased bone turnover and a lack of bone modelling lead to severe deformities, frequent fractures, short stature and loss of hearing.<p class="abs...

see PP92....