Bone Abstracts

see P221b....

It is well established that tumor expression of Gli2, a Hedgehog family transcription factor, contributes to tumor-induced bone disease. Our previous studies investigating genetic inhibition of Gli2 expression in tumor cells have shown promise for the development of therapeutics. While many groups have focused on developing upstream Hedgehog inhibitors for soft-tissue tumors that aberrantly express Gli proteins, we have previously demonstrated that the expression of Gli2 in tu...

Background, subjects and methods: Vitamin D insufficiency in older people in the UK is common and may cause secondary hyperparathyroidism and bone loss. In a randomised, double blind intervention trial to optimise “Vitamin D status in Older People’ (VDOP) three oral dosages of vitamin D3 (12 kIU, 24 kIU or 48 kIU/month) were given for 12 months to 375 participants aged over 70 years (ANOVA) adjustment for covariables with results below presented in ascendi...

Atypical femoral fractures (AFF) of the subtrochanteric region are rare. Bisphosphonates account to a large extent to their occurrence, however AFF also occur without exposure to bone medication. We here assessed the genetic factors associated with AFF among subtrochanteric fractures. Cases of subtrochanteric or femoral shaft fractures were identified through ICD-10 codes in three French academic centers from 2007 to 2010. Medical records were analyzed by two investigators tha...

Objective: We constructed height growth curves for children with XLH from birth to early adolescence, a majority of whom received conventional therapy consisting of multiple daily doses of oral phosphate and active vitamin D.Methods: Growth data from four clinical studies were pooled to construct the growth curves. UX023-CL002 was an observational, retrospective chart review of 103 children with XLH, 1–14 years of age. Pre-treatment data were collec...

Biallelic ENPP1 deficiency in humans induces hypophosphatemic rickets in children characterized by increased circulating FGF23 levels and renal phosphate wasting (‘Autosomal Recessive Hypophosphatemic Rickets Type 2’, or ARHR2), but osteopenia or osteoporosis has not been described in adults. Here, we describe three adult male patients (ages 43, 59, and 62) suffering from early-onset osteoporosis who presented to the Institute of Osteology and Biomechanics at the Uni...

see PP416....

Recent meta-analyses of vitamin D without co-administration of calcium have not demonstrated fracture prevention, possibly through lack of power, inappropriate choice of doses, or failure to target the intervention to deficient populations. Bone mineral density (BMD) is able to detect biologically significant effects in much smaller cohorts, so is a relevant surrogate measure with which to re-assess the skeletal efficacy of these supplements. We searched Web of Science, Embase...

Bone sialoprotein regulates osteoblast activity and bone formation. In knockout (BSP−/−) mouse bone marrow (BM) stromal cell cultures, the pool of osteoprogenitor (OP) cells (CFU-F number) is not different from wild-type (+/+), nor is their early differentiation (same numbers of alkaline phosphatase positive colonies=CFU-ALP, although these are smaller), while the number of osteoblast, mineralized colonies (CFU-OB) is dramatically reduced. Because ossifi...

Mutations in LRP5 cause a variety of phenotypes, including high bone mass and low bone mass disorders. In patients with high bone mass, different heterozygous mutations have been described, all of them clustering in a region including the binding pocket for DKK1 and sclerostin. The pathogenic mechanism is thought to be a gain-of-function mediated by an impaired inhibition of the canonical Wnt signalling pathway, thereby leading to increased bone modelling.<p class="abstext...