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  • 1
    ISSN: 1432-0827
    Keywords: Dichloromethylene diphosphonate ; Hypercalcemia ; Rat tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary There is a high frequency of Leydig cell tumors associated with hypercalcemia in the aged Fischer 344 rat. We studied a transplantable tumor cell line (Rice D-6) which is associated with hypercalcemia, hypercalciuria, hypophosphatemia, renal phosphate wasting, increased urinary cyclic adenosine monophosphate (AMP) excretion, absence of bone metastases, increased osteoclastic bone resorption, and suppressed immunoreactive parathyroid hormone (iPTH) concentrations. We examined the ability of dichloromethylene diphosphonate (Cl2MDP) to lower serum calcium and decrease the parameters of increased bone resorption. We used this drug also as a pharmacologic tool to determine the relationship of hypercalcemia and increased bone resorption to the abnormalities in renal tubular function associated with the humoral hypercalcemia of malignancy. Daily administration of Cl2MDP before development of hypercalcemia, in doses from 2.5–40 mg/kg body weight subcutaneously, delayed and suppressed both the hypercalcemia and hypercalciuria. There was an increase in bone mass and decrease in both osteoclast number and activity compared with bones from untreated tumor-bearing animals. The urinary hydroxyproline excretion in treated animals declined towards the normal range. There were no significant effects on serum phosphorus, urine phosphorus, or urine cyclic AMP excretion. These data suggest that Cl2MDP reverses the increased bone resorption that occurs in the humoral hypercalcemia of malignancy, and confirms that diphosphonates are effective agents in the prevention and treatment of increased bone resorption associated with malignant disease. They also suggest that renal phosphate wasting and increased urinary cyclic AMP excretion are not directly related to the hypercalcemia.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 9 (1972), S. 109-121 
    ISSN: 1432-0827
    Keywords: Arthritis ; Phosphonates ; Bone ; Resorption ; Pathology ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé De l'adjuvant de Freund, constitué deMycobacterium butyricum tués, en suspension dans de l'huile minérale, provoque une arthrite chez les rats qui rappelle certaines formes d'arthrites chez l'Homme. L'arthrite comporte une inflammation de tissu mou, une formation de pannus et deux ostéopathies distinctes, une résorption ossuse accélérée et une formation anormale d'os périarticulaire. L'étidronate disodique, administré à raison de 4 mg/kg/jour par voie cutanée, à partir de l'injection de l'adjuvant, inhibe nettement la résorption osseuse, la formation de pannus, l'érosion inflammatoire de cartilage et la formation d'os pathologique, en rapport avec l'adjuvant. Après arrêt du traitement à l'étidronate disodique, la formationd'os pathologique devient visible radiographiquement deux semaines après l'arrêt du traitement. Le rôle de l'étidronate disodique sur la régulation de la résorption osseuse et sur la concentration du calcium et du phosphate, dans les tissus environnants, ainsi que les rapports des phénomènes arthritiques avec ce type d'expérience sont envisagés. Les résultats suggèrent la possibilité de l'emploi de l'étidronate disodique dans certaines formes d'arthrites humaines.
    Abstract: Zusammenfassung Freund's Adjuvans, das aus abgetötetem und in Mineralöl suspendiertem Mycobacterium butyricum besteht, verursacht bei Ratten eine arthritische Reaktion, welche gewissen Arthritisformen beim Menschen ähnlich ist. Die arthritische Reaktion besteht in einer Entzündung der Weichteile, einer Pannusbildung und zwei verschiedenen Osteopathien, ferner in einer beschleunigten Knochenresorption und einer abnormen periartikulären Knochenbildung. Wird gleichzeitig mit der Verabreichung des Adjuvans Dinatriumetidronat in einer Dosis von 4 mg/kg/Tag subcutan gegeben, so werden sowohl die Knochenresorption, als auch die Pannusbildung, die entzündliche Knorpelerosion und die mit der Adjuvansgabe verbundene pathologische Knochenbildung merklich gehemmt. Wurde die Dinatriumetidronat-Behandlung abgebrochen, so wurde die pathologische Knochenbildung innerhalb 2 Wochen nach Behandlungsabbruch röntgenologisch sichtbar. Die Kontrollfunktion des Dinatriumetidronates bei der Knochenresorption und bei der Calcium- und Phosphatkonzentration in den umliegenden Geweben, sowie die Beziehung dieser Substanz zu den arthritischen Prozessen, wie sie bei diesem Rattenversuch vorliegen, werden besprochen. Auf Grund dieser Resultate ist eine potentielle Anwendung des Dinatriumetidronates bei gewissen Formen der menschlichen Arthritis denkbar.
    Notes: Abstract Freund's Adjuvant, consisting of deadMycobacterium butyricum suspended in mineral oil, produces an arthritic response in rats which resembles certain forms of arthritis in man. The arthritic response consists of soft tissue inflammation, pannus formation and two separate osteopathies; accelerated bone resorption and abnormal periarticular bone formation. Disodium etidronate administered at 4 mg/kg/day subcutaneously from the time of adjuvant injection markedly inhibited bone resorption, pannus formation, inflammatory erosion of cartilage, and the pathologic bone formation associated with the adjuvant model. When the disodium etidronate treatments were discontinued, the pathologic bone formation became radiologically visible within two weeks after cessation of treatment. The role of disodium etidronate in controlling bone resorption and surrounding tissue concentration of calcium and phosphate and the relation to arthritic processes in this rat model are discussed. The data suggest a potential use of disodium etidronate in some forms of human arthritis.
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