Bone Abstracts

Duchenne muscular dystrophy (DMD) causes progressive muscle weakness and loss of ambulation. While glucocorticoid (GC) therapy improves motor function, many boys sustain fractures due to osteoporosis. Recently, i.v. bisphosphonate (i.v.BP) therapy has shown promise in the treatment of DMD-related osteoporosis. At the same time, bone histomorphometry revealed lowered bone volume and significant reductions in bone formation pre-i.v.BP treatment, and a further drop after 2 years&...

Introduction: Acromegaly is a rare disease caused by excess growth hormone (GH) production by an adenoma of the anterior pituitary gland. The skeletal complications of GH and IGF-1 excess include increased bone turnover, increased cortical bone mass and deteriorated microarchitecture of trabecular bone, associated with a high risk of vertebral fractures in the presence of a relatively normal Bone Mineral Density (BMD). There are no data on bone material properties in patients ...

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 SATB2 have been described in association with a unique phenotype known as SATB2-associated syndrome (SAS). This condition is characterised by severe intellectual disability affecting speech development, behaviour, facial features and dental anomalies. Skeletal features and osteoporosis have been reported in older individuals (aged 15–36), in association with point mutations. We report a 24-year-old man with a SATB2 misse...

Interleukin-34 (IL-34) is a newly discovered cytokine which regulates, like macrophage-colony stimulating factor (M-CSF), the differentiation/activation of the myeloid lineage. IL-34 and M-CSF are homodimers known to bind to the M-CSF receptor (M-CSFR) in a competitive manner. In this system, IL-34 can substitute for the M-CSF to induce osteoclastic differentiation. The aim of the present work was to study the functional relationships of these cytokines on cells expressing the...

Objectives: Young male jockeys undertake calorie restriction and high volumes of physical activity during periods of musculoskeletal growth and development. Previous research shows that jockeys have compromised bone health1–4 and display disordered eating5–7. Restricted intakes of calcium and vitamin D, together with excessive amounts of exercise, increase the risk of osteoporosis in males8. The aim of this study was to establish whet...

Objective: Mobility is an important endpoint in patient care with implications for activities of daily living, community participation, and quality of life. We adapted the performance-oriented mobility assessment (POMA-G),1 a widely used and validated clinical gait assessment tool for adults, to use in children with hypophosphatasia (HPP). HPP is the rare metabolic disease caused by loss-of-function mutation(s) in the gene encoding tissue non-specific alkaline phosp...

In advanced ER+ve breast cancer, the propensity of bone involvement is 85%. Similarly in advanced lung cancer, 30–40% of patients develop bone metastases, and as recent advances in lung cancer therapies improve survival, the number of patients living with bone metastases is expected to increase. At the same time there is a paucity of especially ER+ and osteoblastic animal models available. We present herein the development of four mouse models of breast and lung cancer su...

Mutations in the C-propeptide cleavage site of both COL1A1 and COL1A2 cause dominant high bone mass (HBM) osteogenesis imperfecta (OI), characterized by bone hypermineralization. To elucidate the role of C-propeptide processing in bone formation, we generated heterozygous HBM mice in which both residues of the COL1A1 cleavage site were mutated to prevent cleavage by BMP1. HBM mice are smaller than WT in both weight and length and have extremely brittle bones....

It is well-established that in vitro differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can recapitulate embryonic development through germ layer induction, enrichment and expansion of specific lineages. We have used PSC technology and developed a novel, mESC differentiation system for investigating the mechanisms of chondrocyte and osteoblast lineage commitment and differentiation. This step-wise, serum-free protocol uses specif...