MSK Lecture 20 - Histology of Bone Formation, Maintenance, and Repair PDF

Basic Principles of Medicine 1 Module: Musculoskeletal System | Lecture 20 Histology of Bone Formation, Maintenance, and Repair Dr. Ali Drigo [email protected] Department of Anatomical Sciences School of Medicine, St. George’s Univers...

Basic Principles of Medicine 1 Module: Musculoskeletal System | Lecture 20 Histology of Bone Formation, Maintenance, and Repair Dr. Ali Drigo [email protected] Department of Anatomical Sciences School of Medicine, St. George’s University  Copyright All year-1 course materials, whether in print or online, are protected by copyright. The work, or parts of it, may not be copied, distributed, or published in any form, printed, electronic, or otherwise. As an exception, students enrolled in year 1 of St. George’s University School of Medicine and their faculty are permitted to make electronic or print copies of all downloadable files for personal and classroom use only, provided that no alterations to the documents are made and that the copyright statement is maintained in all copies. ‘View only’ files, such as lecture recordings, are explicitly excluded from download, and creating copies of these recordings by students and other users is strictly illegal. BMP1 | MSK | Lecture 20 | Bone II The author of this document has made the best effort to observe current copyright law and the copyright policy of St. George's University. Users of this document identifying potential violations of these regulations are asked to bring their concerns to the attention of the author.  Recommended Reading Histology – A Text and Atlas Pawlina 9th Edition Chapter 8: Bone Bone | Histology: A Text and Atlas: With Correlated Cell and Molecular Biology, 9e | Premium Basic Sciences | Health Library (lwwhealthlibrary.com) BMP1 | MSK | Lecture 20 | Bone II  Your Objectives will show here! Objectives SOM.MK.I.BPM1.1.FTM.3.HCB.0226 List the two types of bone formation. SOM.MK.I.BPM1.1.FTM.3.HCB.0227 Describe the process of intramembranous ossification. SOM.MK.I.BPM1.1.FTM.3.HCB.0228 Describe the process of endochondral ossification. SOM.MK.I.BPM1.1.FTM.3.HCB.0229 Identify trabeculae & bony spicules. SOM.MK.I.BPM1.1.FTM.3.HCB.0230 State the function of the epiphyseal plate. SOM.MK.I.BPM1.1.FTM.3.HCB.0231 Describe the zones of the epiphyseal plate. SOM.MK.I.BPM1.1.FTM.3.HCB.0232 Describe the process of bone repair and bone remodeling. Describe the hormonal regulation of the bone growth and relate it with the SOM.MK.I.BPM1.1.FTM.3.HCB.0233 development of gigantism, acromegaly and dwarfism. BMP1 | MSK | Lecture 20 | Bone II Describe the influence of calcitonin, parathyroid and growth hormones on bone SOM.MK.I.BPM1.1.FTM.3.HCB.0234 development and maintenance of blood calcium levels. SOM.MK.I.BPM1.1.FTM.3.HCB.0235 Describe the main histological and clinical features of rickets and osteomalacia. SOM.MK.I.BPM1.1.FTM.3.HCB.0236 Describe the main histological and clinical features of osteoporosis  SOM.MK.I.BPM1.1.FTM.3.HCB.0226 Histogenesis Bone develops in one of two ways: A. Intramembranous (“membrane”) bone formation - involves development within layer of mesenchyme B. Endochondral bone formation - occurs via a cartilage model that is replaced by bone Immature bone forms first in either bone formation process and is later replaced by mature bone Remodeling continues throughout life, although it is slower in BMP1 | MSK | Lecture 20 | Bone II mature bone 5  SOM.MK.I.BPM1.1.FTM.3.HCB.0227 A. Intramembranous Bone Formation Begins when mesenchymal cells condense to form primary ossification centers, from which osteoblasts differentiate and begin secreting osteoid Osteoblasts become trapped in their own matrix ossification osteoblast center mesenchymal osteoid connective tissue osteocyte mesenchymal osteoprogenitor cells newly calcified osteoid bone matrix a osteoblast I b Development of ossification center: Calcification: calcium and other mineral salts BMP1 | MSK | Lecture 20 | Bone II osteoblasts secrete organic extracellular are deposited and extracellular matrix calcifies matrix (hardens)  SOM.MK.I.BPM1.1.FTM.3.HCB.0227 A. Intramembranous bone formation Ossification centers expand into spicules as more osteoblasts aggregate Bone trabeculae (fused spicules) is the name given to the bone developing at these sites BMP1 | MSK | Lecture 20 | Bone II Bone spicule (blue) stained with Developing trabeculae stained with H&E Mallory-Azan stain  SOM.MK.I.BPM1.1.FTM.3.HCB.0227 A. Intramembranous Bone Formation Spongy bone develops as bony trabeculae join together Blood vessels invade the area at the same time that undifferentiated mesenchymal cells give rise to bone marrow cells Periosteum forms from surrounding mesenchymal cells Numerous ossification centers fuse together forming bone Examples of bone formed in this fashion include most of the flat bones of the skull blood vessel osteoblast plate of compact bone trabeculae of spongy bone BMP1 | MSK | Lecture 20 | Bone II woven bone containing osteoclast marrow endosteal cells periosteum Formation of trabeculae Development of periosteum  SOM.MK.I.BPM1.1.FTM.3.HCB.0229 Intramembranous ossification SOM.MK.I.BPM1.1.FTM.3.HCB.0227 As the spicules continue to grow, they fuse with adjacent spicules to form trabeculae. As growth continues, trabeculae become interconnected and woven/primary bone is formed. It is later replaced by BMP1 | MSK | Lecture 20 | Bone II secondary/mature bone.  SOM.MK.I.BPM1.1.FTM.3.HCB.0227 A. Intramembranous Bone Formation - Mandible Tongue Tooth Tooth BMP1 | MSK | Lecture 20 | Bone II 9  SOM.MK.I.BPM1.1.FTM.3.HCB.0229 SOM.MK.I.BPM1.1.FTM.3.HCB.0227 A. Intramembranous Bone Formation - Mandible ymM V31 > ^ Bone spicules BMP1 | MSK | Lecture 20 | Bone II 10  SOM.MK.I.BPM1.1.FTM.3.HCB.0228 BMP1 | MSK | Lecture 20 | Bone II B. Endochondral bone formation Session ID: histobone  SOM.MK.I.BPM1.1.FTM.3.HCB.0228 BMP1 | MSK | Lecture 20 | Bone II B. Endochondral bone formation Session ID: histobone  SOM.MK.I.BPM1.1.FTM.3.HCB.0228 B. Endochondral Bone Formation A small portion of bone spicule showing endochondral ossification. Remnants of calcified cartilage matrix (light blue) appear covered by dark blue stained bone tissue. The newly formed bone is surrounded by osteoblasts. Some osteoblasts that were captured by the osseous BMP1 | MSK | Lecture 20 | Bone II matrix become osteocytes Bone spicule (blue) stained with Mallory Azan stain  SOM.MK.I.BPM1.1.FTM.3.HCB.0232 Development of Osteons Periosteal ridges Periosteum Endosteum Periosteal Perforating canal Tunnel Groove Q Ridges in periosteum create © Periosteal ridges fuse, forming an groove for periosteal blood vessel. endosteum-lined tunnel. — Circumferential lamellae Periosteum Endosteum — New osteon O Osteoblasts in endosteum build new O Bone grows outward as osteoblasts in periosteum concentric lamellae inward toward center of build new circumferential lamellae. Osteon tunnel, forming a new osteon. formation repeats as new periosteal ridges fold over blood vessels. (a) Microscopic details Longitudinal ridges form along the bone and osteogenic cells in the BMP1 | MSK | Lecture 20 | Bone II periosteum transform into osteoblasts. Osteoblast start producing bone matrix which form ridges that close off periosteal capillaries as they meet. Periosteum lining the newly formed canal becomes the endosteum and starts forming concentric lamellae to form the osteon  SOM.MK.I.BPM1.1.FTM.3.HCB.0230 2. Endochondral Bone Formation – Epiphyseal Plate Epiphyseal plate Remnant cartilage at the ends of the marrow cavity (metaphyseal region) Contributes to growth in bone length by adding new cartilage at the epiphyseal end while it is being replaced by bone at the diaphyseal end Contains five histologically distinctive zones BMP1 | MSK | Lecture 20 | Bone II Diaphyseal bone become continuous with epiphyseal bone (connecting the two marrow cavities) at age ~20  SOM.MK.I.BPM1.1.FTM.3.HCB.0231 Epiphyseal Plate EPIPHYSIS Zone of reserve cartilage: cartilage with small, randomly arranged inactive chondrocytes. Serves as stem cell line. Zone of Reserve Zone of cell proliferation: rapid mitotic divisions give rise to rows of cartilage cells. Zone of Zone of hypertrophy: the chondrocytes Proliferation. are greatly enlarged and the cartilage matrix between neighboring cells becomes thin. zone of hypertrophy Zone of calcified cartilage: lacunae zone of calcified coalesce and the interlacunar matrices cartilage become calcified, causing apoptosis of chondrocytes BMP1 | MSK | Lecture 20 | Bone II zone of resorption bone Zone of resorption: bone is beginning to be elaborated upon the calcified osteoclast cartilage, and osteolytic activity begins to resorb the calcified bone-cartilage blood vessel osteoblasts complex DIAPHYSIS  SOM.MK.I.BPM1.1.FTM.3.HCB.0232 BMP1 | MSK | Lecture 20 | Bone II Bone Repair  SOM.MK.I.BPM1.1.FTM.3.HCB.0232 Timeline for Bone Healing How long does it take for bone to heal under normal circumstances? In healthy individuals, bone healing (formation of at least new, immature/woven/bundle bone – hard callus) usually takes 6-12 weeks( 1 ½ to 3 months). Remodeling is required for to convert the hard callus to lamellar/mature bone and restore bone to its original shape (months to years). Bone healing sequence - Fracture hematoma (minutes to hours) - Inflammation (lasts ~1 week) - Granulation tissue (CT with fibroblasts and new blood vessels) replaces fracture hematoma (