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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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Characterization of the bone phenotype in ClC-7-deficient mice.

December 1, 2008

Calcif Tissue Int

Abstract Mice deficient in the chloride channel ClC-7, which is likely involved in acidification of the resorption lacuna, display severe osteopetrosis. To fully characterize the osteopetrotic phenotype, the phenotypes of osteoclasts and osteoblasts were evaluated. ClC-7(-/-) mice and their corresponding wild-type littermates were killed at 4-5 weeks of age. Biochemical markers of bone resorption (CTX-I), […]

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Tibolone inhibits bone resorption without secondary positive effects on cartilage degradation.

November 18, 2008

BMC Musculoskelet Disord

Abstract BACKGROUND Osteoarthritis is associated with increased bone resorption and increased cartilage degradation in the subchondral bone and joint. The objective of the present study was to determine whether Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties, would have similar dual actions on both bone and cartilage turnover, as reported previously with some […]

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Efficient segmentation by sparse pixel classification.

October 1, 2008

IEEE Trans Med Imaging

Abstract Segmentation methods based on pixel classification are powerful but often slow. We introduce two general algorithms, based on sparse classification, for optimizing the computation while still obtaining accurate segmentations. The computational costs of the algorithms are derived, and they are demonstrated on real 3-D magnetic resonance imaging and 2-D radiograph data. We show that […]

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Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: the effect of water and timing of meal intake on oral delivery of Salmon Calcitonin.

September 9, 2008

BMC Clin Pharmacol

Abstract BACKGROUND To investigate the influence of water intake and dose timing on the pharmacokinetic and pharmacodynamic parameters of an oral formulation of salmon calcitonin (sCT). METHODS The study was a randomized, partially-blind, placebo-controlled, single dose, exploratory crossover phase I study. 56 healthy postmenopausal women were randomly assigned to receive five treatments. The treatments comprised […]

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The effects of oral calcitonin on bone collagen maturation: implications for bone turnover and quality.

September 1, 2008

Osteoporos Int

Abstract UNLABELLED Anti-resorptive strategies may affect bone collagen maturation differently depending on the mode of action. Orally administrated calcitonin resulted in a dose dependent inhibition of bone resorption but did not change bone collagen maturation. This may reflect aspects of bone quality. INTRODUCTION The aim of the present study was to evaluate the effect of […]

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Ion transporters involved in acidification of the resorption lacuna in osteoclasts.

September 1, 2008

Calcif Tissue Int

Abstract Osteoclasts possess a large amount of ion transporters, which participate in bone resorption; of these, the vacuolar-adenosine trisphosphatase (V-ATPase) and the chloride-proton antiporter ClC-7 acidify the resorption lacuna. However, whether other ion transporters participate in this process is currently not well understood. We used a battery of ion channel inhibitors, human osteoclasts, and their […]

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The disease modifying osteoarthritis drug (DMOAD): Is it in the horizon?

July 1, 2008

Pharmacol Res

Abstract Till date, the pharmaceutical industry has failed to bring effective and safe disease modifying osteoarthritic drugs (DMOADs) to the millions of patients suffering from this serious and deliberating disease. We provide a review of recent data reported on the investigation of DMOADs in clinical trials, including compounds inhibiting matrix-metalloproteinases (MMPs), bisphosphonates, cytokine blockers, calcitonin, […]

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