Bone Abstracts

Aim: To determine the safety, tolerability, pharmacokinetics and pharmacodynamics of the cathepsin K inhibitor MIV-711.Methods: A double-blind, placebo-controlled, randomized study in 27 healthy subjects of both genders. Single ascending doses 20–600 mg were investigated for adverse events, clinical chemistry, vital signs, ECG parameters, pharmacokinetics, and serum levels of CTX-I.Results: MIV-711 was well tolerated with no a...

Osteogenesis imperfecta (OI) is a hereditary disease with a generalized involvement of the connective tissue caused by collagen type 1 mutations. The clinical appearance is broad with fractures as the key symptom. Only few genotype–phenotype correlations have been established. We aim to characterize the Danish OI population thoroughly including DXA and HRpQCT, anthropometry, patient history, and genetic background.This cross-sectional study includes...

High fat diet (HFD), obesity, and physical inactivity characterize the modern lifestyle. This can lead to coronary heart diseases and type 2 diabetes mellitus. Recent studies have shown that these conditions frequently are associated with poor bone quality. However, the molecular mechanisms are poorly understood. To analyze the effect of HFD and exercise (EX) on bone homeostasis, we fed 6-week-old C57BL/6 mice a high fat (60% fat) or standard chow diet for 10 weeks (10–20...

High fat diet (HFD), obesity, and physical inactivity characterize the modern lifestyle. This can lead to coronary heart diseases and type 2 diabetes mellitus. Recent studies have shown that these conditions frequently are associated with poor bone quality. However, the molecular mechanisms are poorly understood. To analyze the effect of HFD and exercise (EX) on bone homeostasis, we fed 6 week-old C57BL/6 mice a high fat (60% fat) or standard chow diet for 10 weeks (10-20 mice...

Objectives: XLH features renal phosphate (Pi) wasting, hypophosphatemia, rickets, and skeletal deformities from elevated circulating levels of fibroblast growth factor 23 (FGF23). KRN23, an investigational fully human monoclonal antibody, binds FGF23 and inhibits its action. Our Phase 2 study of KRN23 in XLH children (ages 5–12 years) is demonstrating improvements in serum Pi and rickets. Here we present our Phase 2 trial evaluating the efficacy and safety of KRN23 in you...

In this case report, we present a brother and sister with hereditary vitamin D resistant rickets (HVDRR). Both children presented at the age of 18 months with severe rickets and elevated serum levels of 1,25-(OH)2D3. They differ from each other in that the girl presented with hypophosphatemia instead of hypocalcemia. Besides, she developed alopecia earlier than the boy and needed more 1,25-(OH)2D3 supplementation. Interestingly, the ...

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Purpose: In X-linked hypophosphatemia (XLH), elevated serum FGF23 causes low serum phosphorus (Pi) and inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH)2D) levels. We report safety, tolerability and biochemistry markers following single ascending dose administration of KRN23 in adults with XLH.Methods: 38 XLH subjects with baseline FGF23≥30 pg/ml were randomized to receive single doses of KRN23 (K) or placebo (P) either (0.003&#15...

Purpose: In X-linked hypophosphatemia (XLH), elevated serum FGF23 causes low serum phosphorus (Pi) and inappropriately normal 125-dihydroxyvitamin D (125(OH)2D) levels. We report PK and PD of KRN23 following single ascending dose administration in adults with XLH.Methods: 38 XLH patients with baseline FGF23≥30 pg/ml were randomized to receive a single dose of KRN23 (K) or placebo (P) either i.v. (0.003–0.3 mg/kg) or s.c. (0.1–1...