Bone Abstracts

Glucocorticoid (GC)-induced osteoporosis (GIO) occurs in patients undergoing therapeutic intervention for inflammatory disorders such as rheumatoid arthritis and lupus. The effect of long-term GC administration on bone turnover was investigated in two frequently used mouse strains; C57BL/6 and CD1 in order to assess the influence of genetic background.GIO was induced in 12 weeks old female C57BL/6 and CD1 mice by s.c. insertion of long-term (60 days) rel...

Background: Parathyroid hormone-like hormone (PTHLH) is an important regulator of endochondral bone development. Mutations of the PTHLH gene can cause a variety of different skeletal dysplasias, with duplications of the PTHLH gene resulting in a phenotype characterized by endochrondomatosis, metaphyseal dysplasia and osteolysis.Presenting problem: Our patient presented at the age of 4 months, given concerns regarding lower limb deformit...

Background: Families of children with Osteogenesis Imperfecta (OI) make costly modifications to their home, lifestyle and employment and incur costs of rehabilitative, preventative and adaptive care for their child. While parents have readily identified that these costs are financially burdensome, the degree of financial burden has not yet been described in families of children with OI.Objectives: To evaluate the out of pocket, OI related expenses (ExpOI...

Fibroblast growth factor-23 (FGF23) is a bone derived phosphate-regulating hormone which is elevated in hypophosphataemic rickets. Recent findings demonstrate iron deficiency as a potential mediator of FGF23 expression and murine studies have shown in utero effects of maternal iron deficiency leading to increased FGF23 concentration and disordered bone development (Clinkenbeard. JBMR 2013). Children with rickets in rural Gambia, West Africa, have high prevalences of i...

Multiple myeloma is usually incurable, the bone marrow niche providing a protective microenvironment for quiescent tumour cells. We hypothesised that manipulation of BMP activity, a regulator of cell differentiation in the bone marrow, might affect control of tumour growth by its niche and in addition alter the lytic bone disease of myeloma. Moreover BMP signalling contributes to the hepcidin upregulation and resultant inflammatory anaemia that is characteristic of myeloma. Re...

Cancer-associated muscle weakness is an important paraneoplastic syndrome for which there is currently no treatment. Human breast cancer bone metastases (MDA-MB-231 cells in immune deficient mice) induce extensive bone destruction, leading to the release of TGF-β from the bone matrix. We have previously shown that bone-derived TGF-β is responsible for muscle weakness in this model. Mechanistically, TGF-β signaling increases the expression of NADPH oxidase 4 (Nox...

Up to half of women treated with an aromatase inhibitor (AI) for breast cancer develop muscle weakness, bone loss, and joint pain. Moreover, an elevated state of osteoclastic bone resorption has been shown to prime the bone microenvironment in ways that accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases. Four-week female athymic nude mice underwe...

Breast cancer is the most frequent malignancy in women and frequently results in osteolytic bone metastases. Amino-bisphosphonates are a standard bone protective therapy and, similarly to statins, inhibit the mevalonate pathway that is crucial for posttranslational protein modifications (farnesylation and geranylation). Direct anti-tumor effects of amino-bisphosphonates and statins have been suggested but high concentrations are necessary to achieve meaningful effects. Our stu...

Effects of whole bone scaling on isolated osteoblast behaviours are unknown. Exhibiting a huge range in size, inbred canines are an ideal species to determine such relationships. We have therefore undertaken initial studies in both male and female red foxes (Vulpes vulpes), the most abundant and accessible wild canid member in the United Kingdom.Femoral heads were removed from five fresh red fox cadavers (see details on table) and bone fragments...

Hip osteoarthritis is a cause of significant morbidity to people and their canine companions. Medical management is frequently insufficient, leading to surgery to relieve pain and regain mobility. Hip replacements are not without potential complications, including loosening and infection. Currently, there is a focus on uncemented implants to decrease these problems, however these rely on the biology of the femur for osseointegration and long-term stability. It has been previou...