{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:49:51Z","timestamp":1777614591126,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2010,6,10]],"date-time":"2010-06-10T00:00:00Z","timestamp":1276128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Substance P (SP) has been shown in vitro to stimulate both formation and resorption of bone. This seemingly contradictory observation could be explained by in vivo variations in skeletal loading and rate of bone turnover, features which may be explored during different phases of fracture healing. In 50 SD rats, the right tibia was fractured and fixed with an intramedullary pin in straight alignment and in anterior angulation resulting in a convex and concave side under different load. Fracture repair was assessed by radiography, histology, and semi\u2010quantitative immunohistochemistry of SP nerve fiber occurrence at days 7, 21, 35, 56, and 84 post\u2010fracture. During regeneration, days 7\u201335, abundant SP\u2010nerve ingrowth was observed in the fracture callus reaching a side\u2010symmetrical peak at day 21 in straight fractures. In angulated fractures, the SP peak was also observed at day 21 on the concave loaded side, but not until day 35 on the convex unloaded side. Each SP\u2010peak coincided with cortical bridging. During remodeling, days 35\u201384, a side\u2010symmetrical disappearance of SP\u2010positive fibers was seen in straight fractures. The same pattern was seen on the concave loaded side of angulated fractures. However, on the convex unloaded side, where resorption now took place, SP\u2010fibers remained until the end of the experiment. Our study suggests that neuronal SP during bone regeneration has a stimulatory role on bone formation, while during remodeling increased SP fiber density in unloaded areas may be related to bone resorption. \u00a9 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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