Bone Abstracts

The oim/oim mouse resembles type III OI. Our study mimics clinical questions: is RANK-Fc as efficacious as ALN in reducing fracture number? Is RANK-Fc safe to administer to children? Is there any advantage to receiving RANK-Fc treatment post adolescence, following no treatment or ALN treatment from infancy through adolescence?All animal work was done under an IACUC-approval. Mice – n=200, WT or oim/oim. Treatment spanned a...

Radiographs of the second metacarpal are used to assess bone strength development in paediatric populations. Children with achondroplasia and osteogenesis imperfecta (OI) have known differences in bone strength. Details of how bone strength develops and compares within these populations to unaffected children are lacking. A data set for patients with achondroplasia and OI was established.A retrospective IRB-approved review of bone-age films (n=6...

Objective: The purpose of this study was to determine whether osteogenesis imperfecta (OI) patients entering adulthood should continue with bisphosphonate therapy or would benefit from switching to a RANKL blockade therapy. To address this question, we used a mouse model of type III OI.Methods: Animal studies were performed under IACUC approval. OI (oim/oim) and wild-type (WT) mice were treated from 2–26 weeks with i) saline; ii) alendronat...

Objective: The purpose of this ongoing study was to determine whether osteogenesis imperfecta (OI) patients entering adulthood should continue with bisphosphonate therapy or would benefit from switching to a RANKL blockade therapy. To address this question, we used a mouse model of type-III OI.Methods: Under IACUC-approval, +/+ and oim/oim mice were treated from 2–26 weeks (n=20/treatment/genotype) with either 1) saline 24 weeks; 2...

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...

Objective: Osteocalcin, an osteoblast-derived hormone, is among the most abundant proteins in bone and is involved in the regulation of whole-body metabolism, muscle adaptation, and reproduction. High bone turnover and low bone mass are clinical hallmarks of Osteogenesis Imperfecta (OI), a bone disease mainly caused by mutations in the collagen-I gene. Recently, we have shown that growing mice with a severe dominant form of OI, Col1a1Jrt/+ mice, displayed significantly elevate...

Tumour necrosis factor receptor associated factors (TRAFs) play a key role in signal transduction in mammalian cells. Several members of the TRAF family have been identified but only TRAF2 and TRAF6 are implicated in the regulation of osteoclastogenesis. Here we studied the role of TRAF2 and TRAF6 in breast cancer induced bone cell activity and osteolysis. We observed that TRAF2, but not TRAF6, is highly expressed in the human MDA-MB-231 (MDA-231) bone-seeking breast cancer ce...

Background: The tyrosine kinase inhibitor (TKI) imatinib is applied as front-line treatment in adult and pediatric patients with chronic myeloid leukemia (CML) in order to selectively inhibit the causative oncogenic BCR-ABL1 tyrosine kinase. However, TKIs exhibit off-target effects on further kinases involved in the regulation of bone metabolism. As consequence, pediatric patients display longitudinal growth retardation while on imatinib treatment. As CML is a rare disease in ...

Osteolytic bone disease (OBD) is a frequent complication of multiple cancers, such as multiple myeloma. OBD is due to the disruption of balanced bone remodelling, with higher bone resorption due to increased osteoclast activation and osteoblast inhibition. Lectin–glycoprotein interactions have been implicated in osteoclast formation. In the current study, we set out to identify lectins that are involved in osteoclastogenesis and to study their role in this process. We ant...

Tumour necrosis factor receptor-associated factor 6 (TRAF6) plays a key role in osteoclastogenesis through the regulation of RANK/CD40 TRAF6-mediated signaling. Mice deficient in TRAF6 exhibit high bone mass and were protected against inflammation-induced bone loss. Here we describe the effects of a small-molecule 6877002 that has been shown to prevent the binding of TRAF6 to its domain on RANK/CD40 receptor on osteoclast formation in vitro and in vivo and on...