The twy (tiptoe-walking-Yoshimura) mouse is a mutant showing multiple osseous lesions accompanied by accelerated bone remodeling. In the calvarium, periosteal bone formation was activated until about 6 weeks of age, and high-turnover osteoporosis developed after maturation. To demonstrate the collagen metabolism in high-turnover osseous tissue, bone collagenase secreted by twy mouse calvariae was quantitatively analyzed in explant culture. During the first 3 days of culture, the amounts of collagenase secreted by twy bones (39.1±9.9mU/calvarium) were significantly greater than those secreted by normal bones (10.1±8.8mU/calvarium) (p<0.01). No significant difference was noted in the response to parathyroid hormone or heparin between twy and normal bones. These results indicated that the production of collagenase was increased in twy bones in vivo, and this enzyme seemed to play an important role during the pathological bone loss in high-turnover osseous tissue.