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Local communication on and within bone controls bone remodeling.

June 1, 2009

Bone

Abstract Bone remodeling is required for healthy calcium homeostasis and for repair of damage occurring with stress and age. Osteoclasts resorb bone and osteoblasts form bone. These processes normally occur in a tightly regulated sequence of events, where the amount of formed bone equals the amount of resorbed bone, thereby restoring the removed bone completely. […]

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Cartilage formation measured by a novel PIINP assay suggests that IGF-I does not stimulate but maintains cartilage formation ex vivo.

June 1, 2009

Scand J Rheumatol

Abstract OBJECTIVES The aim of this study was to investigate the time-dependent effect of insulin-like growth factor-I (IGF)-I on cartilage, evaluated by a novel procollagen type II N-terminal propeptide (PIINP) formation assay. This was performed in a cartilage model. METHODS Bovine articular cartilage explants were cultured in Dulbecco’s modified Eagle’s medium (DMEM):F12 in the presence […]

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Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development.

May 1, 2009

Biomarkers

Abstract The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples of protein degradation fragments–neoepitopes–that have proven useful for […]

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Influence of food intake on the bioavailability and efficacy of oral calcitonin.

April 1, 2009

Br J Clin Pharmacol

Abstract AIMS To investigate the influence of food intake on the bioavailability and pharmacodynamic effects of salmon calcitonin (sCT). METHODS A single-blind, randomized, partly placebo-controlled study was conducted in 36 healthy postmenopausal female volunteers aged 62-74 years. The influence of food intake on oral dosing with 0.8 mg of sCT at 22.00 h was evaluated […]

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Increased urinary excretion of C-telopeptides of type II collagen (CTX-II) predicts cartilage loss over 21 months by MRI.

March 1, 2009

Osteoarthritis Cartilage

Abstract OBJECTIVE Osteoarthritis (OA) is characterized by increased bone and cartilage metabolism leading to joint damage. The urinary excretion of C-telopeptides of type II collagen (CTX-II) has earlier predicted progression in radiographic OA (ROA)–useful for participant selection in clinical studies of potential disease modifying OA drugs (DMOADs). We investigated the longitudinal interrelationship between CTX-II and […]

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A pharmacokinetic and pharmacodynamic comparison of synthetic and recombinant oral salmon calcitonin.

February 1, 2009

J Clin Pharmacol

Abstract The aim of this study was to assess the bioavailability and pharmacodynamic efficacy of synthetic salmon calcitonin (ssCT) and recombinant salmon calcitonin (rsCT) in healthy postmenopausal women. The study was a single-blind, randomized study. Participants were 36 postmenopausal women 62 to 74 years old, randomly assigned to a comparison of dosing with ssCT (n […]

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Characterization of acid flux in osteoclasts from patients harboring a G215R mutation in ClC-7.

January 23, 2009

Biochem Biophys Res Commun

Abstract The chloride-proton antiporter ClC-7 has been speculated to be involved in acidification of the lysosomes and the resorption lacunae in osteoclasts; however, neither direct measurements of chloride transport nor acidification have been performed. Human osteoclasts harboring a dominant negative mutation in ClC-7 (G215R) were isolated, and used these to investigate bone resorption measured by […]

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Advances in osteoclast biology resulting from the study of osteopetrotic mutations.

January 1, 2009

Hum Genet

Abstract Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast phenotypes, we discuss how osteopetrosis models have clarified the function of the coupling […]

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Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers.

January 1, 2009

Arthritis Res Ther

Abstract INTRODUCTION At present, no disease-modifying osteoarthritis drugs (DMOADS) are approved by the FDA (US Food and Drug Administration); possibly partly due to inadequate trial design since efficacy demonstration requires disease progression in the placebo group. We investigated whether combinations of biochemical and magnetic resonance imaging (MRI)-based markers provided effective diagnostic and prognostic tools for […]

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Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteoporosis with oral calcitonin.

December 4, 2008

BMC Clin Pharmacol

Abstract BACKGROUND Bone resorption displays marked diurnal variation. Reversible inhibition of bone resorption may result in best possible efficacy when bone resorption peaks. The aim of the study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of 0.8 mg of oral salmon calcitonin (sCT) and the effect of timing of drug intake. METHODS […]

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