Chapter 11: Skeletal Healing Michael Zuscik and Regis J. O’Keefe

From the Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 7th Edition. www.asbmrprimer.org Figure 1 Figure 1 Tissue morphogenesis during bone repair. (A) Periosteum is a well-microvascularized tissue (vessels in black) consisting of an outer fibrous layer and an inner cambium layer. The cambium layer contains abundant stem/progenitor cells that can differentiate into bone and cartilage. (B) After fracture or osteotomy, blood supply is disrupted at the defect, and a blood clot (hematoma) forms near the disjunction. (C) Progenitor cells residing in the periosteum are recruited to differentiate into osteoblasts to facilitate intramembraneous bone formation where intact blood supply is preserved and chondrocytes to facilitate endochondral bone formation adjacent to the fracture where the tissue is hypoxic. In this panel, osteogenic tissue is labeled (1) with newly mineralized tissue labeled (2). Tissues supporting chondrogenesis are labeled (3). (D) Intramembraneous bone formation proceeds with robust matrix mineralization (1) where blood supply is present distal to the fracture site. Endochondral bone formation proceeds simultaneously with chondrogenic tissue supporting a growing population of chondrocytes that comprise the hypertrophic cartilage which is labeled (4). (E) Cartilage tissue continues to mature, ultimately encompassing the callus nearest the fracture site. Revascularization of the callus also ensues. (F) Chondrocytes in the hypertrophic cartilage undergo terminal differentiation and the matrix is progressively mineralized expanding the portion of the callus that is comprised of woven bone. (G) The remodeling process proceeds with osteoclasts and osteoblasts facilitating the conversion of woven bone into lamellar bone, culminating in the re-creation of the appropriate anatomic shape. Figure 1 Tissue morphogenesis during bone repair. (A) Periosteum is a well-microvascularized tissue (vessels in black) consisting of an outer fibrous layer and an inner cambium layer. The cambium layer contains abundant stem/progenitor cells that can differentiate into bone and cartilage. (B) After fracture or osteotomy, blood supply is disrupted at the defect, and a blood clot (hematoma) forms near the disjunction. (C) Progenitor cells residing in the periosteum are recruited to differentiate into osteoblasts to facilitate intramembraneous bone formation where intact blood supply is preserved and chondrocytes to facilitate endochondral bone formation adjacent to the fracture where the tissue is hypoxic. In this panel, osteogenic tissue is labeled (1) with newly mineralized tissue labeled (2). Tissues supporting chondrogenesis are labeled (3). (D) Intramembraneous bone formation proceeds with robust matrix mineralization (1) where blood supply is present distal to the fracture site. Endochondral bone formation proceeds simultaneously with chondrogenic tissue supporting a growing population of chondrocytes that comprise the hypertrophic cartilage which is labeled (4). (E) Cartilage tissue continues to mature, ultimately encompassing the callus nearest the fracture site. Revascularization of the callus also ensues. (F) Chondrocytes in the hypertrophic cartilage undergo terminal differentiation and the matrix is progressively mineralized expanding the portion of the callus that is comprised of woven bone. (G) The remodeling process proceeds with osteoclasts and osteoblasts facilitating the conversion of woven bone into lamellar bone, culminating in the re-creation of the appropriate anatomic shape. © 2008 American Society for Bone and Mineral Research