MODULATION OF BONE-RESORPTION BY TETRACYCLINES
MODULATION OF BONE-RESORPTION BY TETRACYCLINES
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DOI：
10.1111/j.1749-6632.1994.tb24733.x
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发表时间：
1994-01-01
期刊：
影响因子：
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通讯作者：
RAMAMURTHY, NS
中科院分区：
文献类型：
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作者：
RIFKIN, BR;VERNILLO, AT;RAMAMURTHY, NS
四环素类抗生素（TC）于1948年首次作为广谱抗生素引入，自那时以来获得了广泛的治疗用途。TC已被用于牙科，特别是作为牙周治疗的辅助手段，这种方法基于三个公认的优点：（1）它们能有效抑制龈下菌斑中的革兰氏阴性厌氧牙周致病微生物;（2）它们能在龈沟液（GCF）中以远高于血清中的水平浓缩;（3）它们能在龈沟液（GCF）中以远高于血清中的水平浓缩。和（3）它们结合到牙齿表面然后以活性形式缓慢释放的能力，这是一种提高治疗效果的性质。[6]在20世纪80年代早期至中期，Golub及其同事首次发现TC也可以抑制哺乳动物胶原酶的活性，并且这种抑制与这些药物的抗菌功效无关。后一个发现得到了以下事实的支持：TC效应在无菌动物和常规动物、未感染的组织和无菌的体外系统中均可见。TC的一些类似物（即化学修饰的TC，CMT）被化学修饰以失去其抗微生物活性，但仍保留其抑制胶原酶的能力。Golub等人在早期的临床研究中发现，对非糖尿病患者和糖尿病成人牙周炎患者给予常规剂量的米诺环素、多西环素或四环素可降低GCF中过度的胶原酶活性。7，9 J 0在同一时期，Gomes et a/.“表明TC也抑制器官培养中甲状旁腺素诱导的骨吸收;几年后，Rifkin等证明了非抗菌化学修饰的四环素抑制骨吸收。因此，TC可能在以病理性胶原分解为特征的疾病的治疗中是有用的。13 J 4过度的胶原酶活性也可能与牙周病中的骨吸收相关，这导致了研究以确定TC是否对骨细胞代谢具有影响。a这项工作得到了国家牙科研究所的赠款R 01 DE-09576
Tetracyclines (TCs) were first introduced in 1948 as broad spectrum antibiotics and have gained wide therapeutic use since that time.'TCs have been used in dentistry, particularly as adjuncts to periodontal therapy, an approach based on three perceived advantages:(1) their effectiveness in suppressing Gram-negative anaerobic periodontopathogenic organisms in the subgingival plaq~ e;~,~(2) their ability to concentrate in the gingival crevicular fluid (GCF) at levels substantially greater than in ser~ m;~.~ and (3) their ability to bind to the tooth surface and then be slowly released in an active form, a property which prolongs therapeutic effectiveness. 6 In the early to mid-l980s, Golub and co-workers first made the key observation that TCs can also inhibit the activity of mammalian collagenase and that this inhibition was unrelated to the antimicrobial efficacy of these drugs. This latter finding was supported by the fact that the TC effect was seen in germ-free as well as conventional animals,'in uninfected tissues and in sterile in vitro~ ystems.~-lO Some analogs of TC (ie, chemically modified TC, CMT) were chemically modified to lose their antimicrobial activity, but still retained their ability to inhibit collagenase. s In their earlier clinical studies, Golub et al. found that regular doses of minocycline, doxycycline, or tetracycline administered to both nondiabetics and diabetics with adult periodontitis reduced the excessive collagenase activity in the GCF. 7, 9J0 During the same time period, Gomes et a/." showed that TCs also inhibited parathyroid hormone-induced bone resorption in organ culture; several years later, Rifkin et al. l2 demonstrated inhibition of bone resorption with nonantimicrobial chemically modified tetracycline. Therefore, TCs might be therapeutically useful in the management of diseases characterized by pathologic collagen breakdown. 13J4 That excessive collagenase activity might also be associated with bone resorption in periodontal disease led to investigations to determine whether TCs had an effect on bone cell metabolism. aThis work was supported by the National Institute of Dental Research grants R01DE-09576