Bone Abstracts

STRUCTURE was a phase 3, open-label study evaluating the effect of romosozumab or TPTD for 12 months in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy (NCT01796301). This study enrolled women with postmenopausal osteoporosis who had taken an oral bisphosphonate for ≥3 years prior to screening and alendronate in the year prior to screening; had a BMD T-score ≤−2.5 at the total hip (TH), lumbar spine (LS), or femoral neck (FN);...

Vertebral fractures (VF) defined by morphometric analysis of spine radiographs are the most common complication of osteoporosis. Those that come to medical attention, with symptoms such as back pain and kyphosis are termed clinical vertebral fractures (CVF) and account for significant morbidity and mortality. Although much progress was made in identifying loci for bone mineral density, the genetic determinants of CVF remain unclear. Here we present the initial results from a g...

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Denosumab (DMAb) has a unique profile of bone resorption inhibition: CTX decreases rapidly by 3 days and inhibition is released at the end of the 6-month dosing interval, when DMAb serum levels decrease (McClung NEJM 2006). The dynamic CTX inhibition profile is not curtailed by continued treatment. In the 3-year FREEDOM study, CTX values at 6 months were influenced by baseline CTX values and days since the 1st injection (Eastell JBMR 2011). With 3 additional ...

Mutations in the PHEX gene cause X-linked familial hypophosphatemic rickets (XLH) with severe bone (osteomalacia) and tooth abnormalities being the distinguishing features of this disease. The PHEX mutations lead to an increase in ASARM peptides (acidic serine- and aspartate-rich motif) and osteopontin fragments which inhibit bone extracellular matrix mineralization. MEPE-derived ASARM has been shown to accumulate in tooth dentin of patients with XLH where it may impair dentin...

Autosomal dominant osteopetrosis type II (ADO2) is a rare osteosclerotic disease due heterozygous missense mutations of the CLC7 gene encoding the type seven chloride channel. Our two labs independently generated the first C57 black 6 (B6) mouse model of ADO2 by inserting the pG213R-clc7 mutation. Homozygous mice showed lack of tooth eruption and died within 30 days of age with severe osteopetrosis and central nervous system degenera...

Autosomal dominant type II osteopetrosis (ADO2) is a rare osteosclerotic disorder due to heterozygous missense mutations of CLC7 gene encoding the type 7 chloride channel. Our two labs (L’Aquila and Indianapolis) independently generated the first C57 black 6 (B6) mouse model of ADO2 by inserting the pG213R-clc7 mutation. We created pG213R-clc7 KI mice using a gene targeting approach. Homozygous mice showed lack of tooth eruption and died within ...

Objectives: Creation of reference curves for areal bone mineral density (aBMD) and bone mineral content (BMC) with consideration of relevant anthropometric variables.Methods: Analysis of the dual-energy X-ray absorptiometry (DXA) data collected as part of the Bone Mineral Density in Childhood Study1, including 2012 boys and girls, 5–22 years old, with a total of 10 525 visits, resulting in aBMD and BMC observations at the lumbar spine, hi...

Background: Low vitamin D concentrations among children and adolescents at northern latitudes are frequently observed. Also, inverse associations between 25-hydroxyvitamin D (25(OH)D) and PTH concentrations have been found in children of different ages. More studies on the link between vitamin D status and childhood bone health are needed.Objective: To evaluate the status of serum 25(OH)D in autumn and the association between 25(OH)D concentrations and b...

Objective: Evidence for further reduction of nonvertebral fracture (NVFX) beyond 3 years of antiresorptive therapy is limited. Since long-term denosumab (DMAb) treatment is associated with continuous increases in BMD and sustained fracture reduction, we analyzed the influence of femoral neck (FN) BMD after 3 years on NVFX rates.Methods: Long-term subjects received 7 continuous years of DMAb; cross-over subjects received 3 years of placebo (FREEDOM) and 4...