Cicero Arrigo F G, Laghi Luca
D. Campanacci Clinical Medicine & Applied Biotechnology Department, Sant'Orsola-Malpighi Hospital, University of Bologna Via Massarenti, Bologna, Italy.
Clin Interv Aging. 2007;2(1):73-9. doi: 10.2147/ciia.2007.2.1.73.
Osteoarthritis is the most common form of arthritis. It is a progressive joint disease associated with aging. It may be found in the knees, hips, or other joints. It is estimated that costs associated with osteoarthritis exceed 2% of the gross national product in developed countries. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a mainstay in the treatment of inflammatory disease and are among the most widely used drugs worldwide. The main limitation in using NSAIDs consists in their side-effects, including gastrointestinal ulcerogenic activity and bronchospasm. The mechanism of action of these drugs is attributed to the inhibition of cyclooxygenase (COX), and, consequently, the conversion of arachidonic acid into prostaglandins. It is hypothesized that the undesirable side-effects of NSAIDs are due to the inhibition of COX-1 (constitutive isoform), whereas the beneficial effects are related to the inhibition of COX-2 (inducible isoform). Arachidonic acid can also be converted to leukotrienes (LTs) by the action of 5-lipoxygenase (5-LOX). Licofelone, a LOX/COX competitive inhibitor, decreases the production ofproinflammatory leukotrienes and prostaglandins (which are involved in the pathophysiology of osteoarthritis and in gastrointestinal (GI) damage induced by NSAIDs) and has the potential to combine good analgesic and anti-inflammatory effects with excellent GI tolerability. Preliminary data with this drug seem promising, but further well-designed clinical trials of this agent in the elderly will be necessary before a final evaluation is possible.
骨关节炎是最常见的关节炎形式。它是一种与衰老相关的进行性关节疾病。可出现在膝盖、臀部或其他关节。据估计，在发达国家，与骨关节炎相关的费用超过国民生产总值的2%。非甾体抗炎药（NSAIDs）是治疗炎症性疾病的主要药物，也是全球使用最广泛的药物之一。使用NSAIDs的主要限制在于其副作用，包括胃肠道致溃疡活性和支气管痉挛。这些药物的作用机制归因于对环氧化酶（COX）的抑制，从而使花生四烯酸转化为前列腺素。据推测，NSAIDs的不良副作用是由于对COX-1（组成型同工型）的抑制，而其有益作用与对COX-2（诱导型同工型）的抑制有关。花生四烯酸也可通过5-脂氧合酶（5-LOX）的作用转化为白三烯（LTs）。利考昔酮是一种脂氧合酶/环氧化酶竞争性抑制剂，可减少促炎白三烯和前列腺素的产生（这些物质参与骨关节炎的病理生理学以及NSAIDs诱导的胃肠道（GI）损伤），并有可能将良好的镇痛和抗炎作用与出色的胃肠道耐受性结合起来。该药物的初步数据似乎很有前景，但在进行最终评估之前，还需要对该药物在老年人中进行进一步精心设计的临床试验。
