Bone Abstracts

Background: Recently, we showed that treatment with COBRA-light therapy including prednisone with initially 30 mg/day was as effective as the original COBRA scheme, with initially 60 mg/day (Ter Wee, ARD 2015), in the treatment of rheumatoid arthritis (RA). Since high-dose glucocorticoids are associated with bone loss, we investigated the differences in bone mineral density (BMD) after 1 year of treatment in both arms.Objective: To determine whether ther...

Bruck syndrome, a disorder caused by bi-allelic mutations in either PLOD2 or FKBP10, is characterized by flexion contractures and bone fractures and shows strong clinical overlap with the brittle bone disease Osteogenesis Imperfecta. PLOD2 encodes the Lysyl hydroxylase 2 (LH2) enzyme, which is responsible for the hydroxylation of lysine residues in the type-I collagen telopeptides. This hydroxylation directs cross-linking of the collagen fibrils in t...

Introduction: Alcoholism can result in a compromised regenerative capacity of bone and delayed osteointegration of dental implants. One of the mechanisms is that the thereby overdosed all-trans retinoic acid (ATRA), a main metabolite of alcohol, can significantly inhibit osteoblastogenesis. Bone morphogenetic proteins, potent osteinductive growth factors, can be applied to promote osteogenesis. We previously showed that heterodimerized BMP2/7 could promote osteoblastogenesis i...

Hyperthyroidism in mice is associated with a low bone mass, an increased bone turnover and high serum levels of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either reducing bone turnover with bisphosphonates or increasing bone formation with neutralizing sclerostin antibodies (Scl-Ab) on bone mass and estimated strength in hyperthyroid mice.Twelve-week-old C57BL/6 male mice were rendered hyperthyroid by adding L-thy...

Bone is a tissue that continually adapts to changing external loading conditions (so-called modeling) and has the capacity for self-repair and renewal (remodeling). These processes construct and reconstruct the skeleton by the removal and formation of bone packets that mediate the size, architecture, mass, and consequently the bone’s strength, allow bones to perform their mechanical functions successfully over long periods of time. Both adaptation and self-repair are beli...

Objectives: The aim of this study was to evaluate the association between the age at onset of walking and bone mineral content (BMC) in healthy 2-year-old children participating in the Vitamin D in Infants Trial (VIDI).Methods: Altogether 253 children (120 girls, 133 boys) with a daily vitamin D3 intake of 10 μg and a sufficient serum 25-hydroxyvitamin D (25-OHD) concentration (>50 nmol/l) were included in the analysis. BMC was measur...

Background: Rett Syndrome (RS) is a disabling condition due to mutations in MECP2. Girls affected with RS are at risk of developing osteoporosis and fractures at a young age because of their lack of mobility and through a direct effect of MECP2 on bone mineralization. In these girls, bone fragility inflicts pain and may seriously impair the quality of life.Objective: To retrospectively assess the effect of IV bisphosphonates on fracture, bone mineral den...

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...

Achondroplasia is the most common form of short-limbed dwarfism with a frequency of 1 in 10,000 to 30,000 births. Although it can be inherited in a autosomal dominant manner, 80% of the cases are sporadic. Achondroplasia is classified as one of the FGFR3 chondrodysplasias and more than 97% occur from an activating mutation at residue 380 (p.R380G) of the FGFR3 gene. Current treatment of achondroplasia is mainly directed at prevention and treatment of its complications (obstruc...

Objectives: Achondroplasia, the most common form of short limb dwarfism, is a rare genetic disorder caused by a gain-of-function mutation of the FGFR3 receptor (FGFR3-G380R) and there are currently no effective treatments available. We have developed TA-46, a recombinant human soluble FGFR3(sFGFR3) form of the FGFR3 cell surface receptor containing an extra-cellular ligand-binding domain, including three IgG domains, which confer binding specificity. TA-46 is designed to block...