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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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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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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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Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?

June 27, 2008

BMC Cancer

Abstract BACKGROUND Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover in breast and prostate cancer patients is associated with […]

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Should subchondral bone turnover be targeted when treating osteoarthritis?

June 1, 2008

Osteoarthritis Cartilage

Abstract OBJECTIVE Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, including bone and cartilage, thereby presenting alternative approaches for treatment. This review summarizes emerging observations from cell biology […]

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Calcitonin: a drug of the past or for the future? Physiologic inhibition of bone resorption while sustaining osteoclast numbers improves bone quality.

January 1, 2008

BioDrugs

Abstract Postmenopausal osteoporosis results from a continuous imbalance between bone resorption and bone formation, favoring bone resorption. An increasing number of treatments for osteoporosis are in development and on the market. A range of differences and similarities are found between these treatment options, and these need to be carefully evaluated before the initiation of treatment. […]

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Diphyllin, a novel and naturally potent V-ATPase inhibitor, abrogates acidification of the osteoclastic resorption lacunae and bone resorption.

October 1, 2007

J Bone Miner Res

Abstract UNLABELLED Dissolution of the inorganic phase of bone by the osteoclasts mediated by V-ATPase and ClC-7 is a prerequisite for bone resorption. Inhibitors of osteoclastic V-ATPase or ClC-7 are novel approaches for inhibition of osteoclastic bone resorption. By testing natural compounds in acidification assays, diphyllin was identified. We characterized diphyllin with respect to the […]

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