Bone Abstracts

Screening gene function in vivo is a powerful approach to discover novel drug targets in the human genome (Nat Rev Drug Discov 2 38–51, 2003). We present data for 3776 distinct gene knockout (KO) mouse lines with viable adult homozygous mice generated using both gene-trapping and homologous recombination technologies. Bone mass was determined from PIXImus DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from ...

Cadmium (Cd) is regarded as a risk factor for various bone diseases in humans and experimental animals. To compare effects of different routes of Cd administration on femoral bone structure, ten 4-month-old male Wistar rats (group A) were injected intraperitoneally with a single dose of 2 mg CdCl2/kg body weight and killed 36 h after Cd had been injected. Ten 1-month-old male rats (group B) were dosed with a daily Cd intake of 30 mg CdCl2/l in drinking wa...

Objectives: Examine changes in volumetric BMD and cortical structure following Crohn Disease (CD) diagnosis, and identify associations with growth, glucocorticoid exposure and disease activity.Methods: Prospective cohort study in 76 CD participants, ages 5–21 years. Tibia pQCT scans were obtained at diagnosis, 6, 12 and a median of 42 months later. Sex, race and age-specific Z-scores were generated based on >650 controls. Cortical dimen...

Background: Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) and Hyperphosphatemic Hyperostosis Syndrome (HHS) are two phenotypes of a disease associated with autosomal recessive mutations in FGF23, GALNT3 and KL, leading to reduced levels and clinical effects of fibroblast growth factor 23 (FGF23). We describe a consanguineous family with two affected individuals with HFTC and HHS caused by a novel homozygous mutation in GALNT3. We also...

Menopause is accompanied by a decrease in bone mineral density which can be caused by a reduction in bone volume and/or degree of bone matrix mineralization. Both of them are suggested to contribute to the increased fracture risk in postmenopausal individuals. In the present work, we aimed for information whether a drop in bone matrix mineralization is occurring in the perimenopausal stage of women. For this purpose, we measured the bone mineralization density distribution (BM...

Introduction: Prostaglandin E2 has bone-anabolic effects through EP4 receptor but its clinical utility is hindered by gastrointestinal side effects. To avoid these side effects, EP4 agonists (EP4a) were covalently linked to the bisphosphonate alendronate (ALN) to create two ALN-EP4a conjugate drugs, C1 and C2. When administered systemically, C1 and C2 will be target delivered to bone through ALN, where local hydrolytic enzymes liberate EP4a from ALN to exert bone an...

Background: Breast cancer clinical trials have shown an enhanced anti-tumour activity of bone-targeted agents in postmenopausal patients. We have reported that zoledronic acid (ZOL) decreases serum levels of the tumour promoter follistatin in postmenopausal women and also inhibits expression of follistatin by breast tumour cells both in vitro and in vivo. We hypothesised that inhibin-A (InA) and ZOL may be altering bone levels of follistatin and its bound tum...

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: Respiratory insufficiency is the leading cause of mortality for individuals diagnosed with Osteogenesis Imperfecta (OI), a skeletal dysplasia clinically characterized by fractures, bone fragility, and scoliosis. The objective of this study is to explore respiratory function and its relation to quality of life, type of OI, presence of scoliosis, stature, and other factors such as age or co-existing co-morbidities.Methods: Adults with OI comple...

Objectives: Osteogenesis imperfecta (OI) is a group of rare genetic disorders characterized by osteoporosis, predisposition to fracture, and scoliosis. Recently, however, there has been increased focus on pulmonary insufficiency, as it is the leading cause of mortality in individuals with OI. The primary objective of this study is to determine if reduced pulmonary function in individuals with OI is intrinsic to the underlying connective tissue disorder. Another goal of this st...