Bone Abstracts

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 ...

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...

The relationship between BMD T-score and FX risk has not been established in patients receiving osteoporosis therapy. In the FREEDOM Extension study, continuous DMAb therapy for up to 10 years increased BMD levels with no therapeutic plateau at lumbar spine or TH [Bone et al, ASBMR 2015]. Such improvements would only be meaningful if associated with FX reductions. We investigated the relationship between TH BMD T-score and NVFX in women who received DMAb during FREEDOM and tho...

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);...

We have shown that genetic ablation of Cdh2 (N−cadherin gene) in osteolineage cells results in osteopenia and decreased osteoprogenitor number. Paradoxically, others have shown that mice overexpressing Cdh2 in osteoblasts are also osteopenic; an action linked to a negative effect of N−cadherin (Ncad) on Wnt signaling, via sequestration of low density lipoprotein receptor−related protein−...

DMAb increases BMD and reduces bone resorption and risk of vertebral, nonvertebral and hip fractures in women with PMO. Transiliac crest bone biopsies in 47 subjects treated with DMAb for 1–3 years showed reduced bone turnover vs 45 Pbo-treated subjects, which reversed on treatment cessation. Since bone turnover reduction is sustained and fracture incidence low over 6 years’ DMAb treatment, we evaluated DMAb’s effects on tissue-level remodelling in the FREEDOM E...

Senile osteoporosis and age-related osteopenia are associated with decreased osteoblastogenesis and increased bone marrow adipogenesis. The mechanisms controlling the fate determination of osteoblast to adipocyte differentiation of bone marrow stromal cells (BMSC) during aging are not known. We and others previously showed that the cell-cell adhesion molecule N-cadherin (N-Cadh) expressed in osteoblasts controls bone formation, but little is known about its role in BMSC fate d...

This study examined the anti-osteoclastogenic effect of n-butanol extracts of Panax notoginseng on the receptor activator of NF-kB ligand (RANKL) induced RAW264.7 cells. Panax notoginseng is commonly used to treat chronic liver disease. Notoginseng has many beneficial effects, such as the suppression of liver fibrosis and anti-cancer activities. Notoginseng contains several biologically active components, such as ginsenosides Rb1, Rg1...

Type 2 diabetes mellitus impairs bone quality and increases fracture risk. We showed that diabetic ZDF rats have low bone mass due to impaired osteoblastogenesis, which can be partially reversed with an intermittent parathyroid hormone 1–84 (PTH) therapy. It remains unclear, why PTH treatment does not fully restore osteoblast (OB) function in diabetic conditions. Here, we tested if high glucose (HG) conditions lead to a partial PTH resistance in osteoblasts. Pre-osteoblas...

Denosumab treatment is associated with low fracture incidence, sustained BMD increases, and reduced sCTX. The decrease in median sCTX is at the quantifiable limit (0.049 ng/ml) one month post-dose, remains low, and attenuates at the end of the 6-month dosing interval. Using 7 years of data from the FREEDOM study and its extension, we characterized changes in sCTX over time and the influencing factors. In the bone turnover marker and pharmacokinetic substudies, serum was collec...