Effects of Oxytetracycline on Mineralization of Bone in Young Rats

Engesæter, Lars B.; Underdal, Trine; Langeland, Norvald

doi:10.3109/17453678008990823

Cited by 12 publications

(6 citation statements)

References 20 publications

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“…The reduced calcium/collagen and phosphondcollagen ratios observed in bones of rats receiving doxycycline indicate impairment of the mineral metabolism. These findings correspond well with those obtained in a study of another tetracycline antibiotic, oxytetracycline, which was found to reduce the incorporation of strontium-85 and to reduce the content of calcium and phosphorus in bones (Engesaeter et al 1980a).…”

Section: Discussionsupporting

confidence: 80%

“…This may indicate impairment of albumin synthesis since doxycycline inhibits the growth of microorganisms by interfering with the protein synthesis (Goodman & Gilman 1975). Several studies (Yeh & Shils 1966, Morgan & Ribush 1972, Vazquez 1974 have shown that tetracyclines may also affect the animal protein synthesis, although oxytetracycline has not been found to affect the albumin or collagen synthesis (Engesaeter et al 1980b) or the concentration of albumin in serum (Engesaeter et al 1980a) in our previous experiments. If these albumin findings in the doxycycline treated rats indicate a general inhibition in synthesis of proteins, including collagen, the effect of doxycycline on the crosslinking of collagen might then have been masked, since a reduced rate of collagen synthesis also reduces the solubility (Gross 1958, Dawson & Milne 1978.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Cloxacillin, Doxycycline, Fusidic Acid and Lincomycin on Mineralization and Solubility of Collagen in Young Rats

Engesæter¹,

Underdal²,

Lyngaas³

1980

Acta Orthopaedica Scandinavica

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The antibiotics doxycycline, fusidic acid and lincomycin have recently been shown to reduce growth of bones and tensile strength of skin in young rats. Such adverse effects were not found in rats receiving cloxacillin. The present investigation deals with the influences of these four antibiotics on the mineralization of bones and on the solubility of collagen in skin. In rats receiving doxycycline the content of calcium and phosphorus in bones and the concentration of albumin in serum were reduced. None of the antibiotics had a detectable effect on the solubility of collagen. In a previous study (Engesaeter & Skar 1979) the antibiotics doxycycline, fusidic acid and lincomycin were found to cause reduced growth of bones and reduced tensile strength of intact skin in young rats. Such unwanted effects were, however, not detected in a group of rats receiving cloxacillin.T h e purpose of the present investigation was t o examine the effects of these four antibiotics on the solubility (cross-linking) of collagen and on t h e mineralization of bones. These t w o parameters are of particular i n t e r e s t since a n o t h e r a n t i b i o t i c , o x ytetracyline, has been found to impair both collagen solubility and bone mineralization (Engesaeter e t al. 1980 a, b). M A T E R I A L S AND METHODSFifty male Wistar rats, initially weighing 39-44 g, were used. The animals were divided into five groups of 10 rats. The fist group received cloxacillin, the second doxycycline, the third fusidic acid, and the fourth lincomycin. The fifth group of animals served as control, receiving only isotonic sodium chloride solution. The antibiotics were administered as intraperitoneal injections every 12th hour for 14 days. Fusidic acid, however, was given by a stomach tube, as intraperitoneal injections in a pilot study caused massive abdominal adhesions. The doses of the drugs in mg/kg/day were 2-12 times higher than the recommended human doses. Plasma concentrations of the antibiotics were, however, comparable with the therapeutic levels in humans. Further information about the animals and the medication was reported in a previous paper dealing with the mechanical properties of bone and skin of these rats (Engesaeter & Skar 1979).At the end of the l 4 d a y medication period the rats were anaesthetized with ether and blood was collected by puncture of the aorta, death followed by exsanguination. Bones and skin were immediately removed and after mechanical testing stored at -2OoC until biochemical examination. Bone analyses were performed on the left femur after the soft tissues, the cartilages and the epiphyses had been removed. The bones were hydrolyzed in 6M HCl at 125OC for 18 hours, and the content of calcium, phosphorus and collagen was measured, as described below.Skin analyses were performed on skin from the back of the animals, i.e. the most cranial of the three intact skin specimens used in the mechanical testing. The fraction of collagen soluble in saline solution was determined by modifications of the methods of Kivirikko...

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Effects of Cloxacillin, Doxycycline, Fusidic Acid and Lincomycin on Mineralization and Solubility of Collagen in Young Rats

Engesæter¹,

Underdal²,

Lyngaas³

1980

Acta Orthopaedica Scandinavica

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“…The affinity of the TETs for bone is mediated by their calcium chelating capacity [25]. High doses of TETs can impede bone growth and/or mineralization under natural growth or culture conditions [26][27][28], but this effect is probably quite distinct from their MMP-inhibitory capacity. The finding that pretreatment of bone slices with Dox maintains the inhibitory effect reinforces the notion that the action of Dox is probably not due to toxicity on the OCs; binding of a TET to bone collagen could interfere with formation of the collagen-collagenase complex and thereby reduce the apparent enzymatic activity.…”

Section: Discussionmentioning

confidence: 99%

Effect of tetracyclines which have metalloproteinase inhibitory capacity on basal and heparin-stimulated bone resorption by chick osteoclasts

et al. 1993

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Several tetracyclines (TETs) are potent inhibitors of collagenase (CGase) and can inhibit connective tissue degradation in a variety of inflammatory and degenerative disorders. The role of CGase in bone resorption by osteoclasts (OC) remains unclear. Disaggregated OCs from chick embryos were cultured for 24 h on devitalized bovine cortical bone +/- heparin in the presence of various TETs. Doxycycline (Dox) inhibited pit formation in a dose-dependent manner. CMT, a TET derivative which inhibits matrix metalloproteinases (MMPs) but is not antimicrobial, also inhibited chick OC bone resorption. Heparin markedly stimulated bone resorption at 5 micrograms/ml, which was reversed by Dox, 5 micrograms/ml. TETs can reversibly inhibit both basal and heparin-stimulated bone resorption by chick OCs. These findings suggest that MMPs may play a role in osteoclastic bone resorption, and that safe and effective inhibitors of MMPs, including certain TETs, might have a potential therapeutic role.

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“…Multiple labels combined with short intervals additionally have the risk of inhibiting bone mineralization. 74 The latter reference also provides an indication for optimal intervals in mice, rats, mini pigs, sheep, dogs, monkeys, and man. We found a label interval of 2 or 3 weeks to be most appropriate to investigate directed bone formation.…”

mentioning

confidence: 98%

Use of Fluorochrome Labels inIn VivoBone Tissue Engineering Research

Gaalen

Kruyt²,

Geuze³

et al. 2010

Tissue Engineering Part B: Reviews

158

120

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The use of fluorochromes in bone research is a widely accepted technique that dates back to the 1950s. Several pioneers, such as Harold Frost, have thoroughly investigated the potential of fluorochrome use for the study on bone formation and bone remodeling dynamics. Since the development of bone tissue engineering, a renewed interest in the benefits of fluorochrome use was perceived. Fluorochrome use in animal models makes it possible to determine the onset time and location of osteogenesis, which are the fundamental parameters in bone tissue engineering studies. There is, however, a lack of standardized procedures for using this technique. In addition, many types of fluorochromes exist and one could be confused upon selecting the appropriate type, the appropriate concentration, the route of administration, and methods of visualization. All these variables can potentially affect the outcome during fluorescence microscopy. This work aims at providing the bone tissue engineering researcher with an overview of the history, working mechanism, and the potential pitfalls in the use of fluorochromes in animal studies. Experiments using some of the more frequently used fluorochromes are explained and illustrated.

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Effects of Oxytetracycline on Mineralization of Bone in Young Rats

Cited by 12 publications

References 20 publications

Effects of Cloxacillin, Doxycycline, Fusidic Acid and Lincomycin on Mineralization and Solubility of Collagen in Young Rats

Effects of Cloxacillin, Doxycycline, Fusidic Acid and Lincomycin on Mineralization and Solubility of Collagen in Young Rats

Effect of tetracyclines which have metalloproteinase inhibitory capacity on basal and heparin-stimulated bone resorption by chick osteoclasts

Use of Fluorochrome Labels inIn VivoBone Tissue Engineering Research

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