The present invention relates to compositions for the modulation of inflammation in connective tissues in humans and animals and the modulation of markers of such inflammation, including COX-2, TNF-.alpha., IL-1.beta., iNOS, p38, and chemokines, comprising any or all of anabolic, anti-catabolic, anti-oxidant and analgesic agents, including aminosugars, S-adenosylmethionine, arachadonic acid, GAGs, including pentosan, collagen type II, tetracyclines or tetracycline-like compounds, diacerin, super oxide dismutase, L-ergothioneine, methylsulfanylmethane, one or more avocado/soybean unsaponifiables, and an analgesic, e.g., acetaminophen, and to methods of treating humans and animals by administration of these novel compositions to humans and animals in need thereof.