Basic Science



Basic Science


Adam S. Levin



MUSCULOSKELETAL GROWTH DEVELOPMENT



  • Embryology



    • Initial three layers of embryologic development:



      • Endoderm


      • Mesoderm


      • Ectoderm


    • Musculoskeletal system and connective tissues derive from the mesoderm.


    • Limb bud development



      • 4 to 8 weeks’ gestation


      • Central core becomes skeleton.


      • Three cardinal axes (Figure 1.1):



        • Proximal-distal



          • Largely governed by apical ectodermal ridge (overlying ectoderm)


          • Fibroblast growth factors, homeobox (HOX)


        • Anterior-posterior



          • Governed by zone of polarizing activity



            • Preaxial—radial, tibial


            • Postaxial—ulnar, fibular


          • Sonic hedgehog (SHH)


        • Dorsal-ventral



          • Bone morphogenetic proteins, Wnt signaling


    • Axial skeleton



      • Paired consolidations of mesoderm (somites) develop.


      • Somites consist of skeletal and dermatomal elements.






        Figure 1.1 Limb bud. Apical ectodermal ridge extends from anterior to posterior along dorsal/ventral boundary of growing limb bud. Proximal to apical ectodermal ridge is the progress zone (an area of proliferating mesodermal cells). In posterior mesoderm is the zone of polarizing activity, an important signaling center. These centers are interconnected, so limb patterning and growth are partly dependent on coordinated function. From Donohue CM. Congenital digital deformities: ectrodactyly. In: Southerland JT, ed. McGlamry’s Comprehensive Textbook of Foot and Ankle Surgery. Vol 2. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013:1109-1116. Redrawn after Jorde LB, Carey JC, Bamshad M, White RW. Medical Genetics. London, England: Mosby; 1999.



  • Cartilage growth and development



    • Appendicular skeleton derives from endochondral ossification.


    • Cartilage differentiation at approximately 6 weeks’ gestation


    • Vascular invasion into the cartilage by 8 weeks—primary ossification center


  • Bone growth and development (Figure 1.2)



    • Bone is formed from remodeling of collagenous scaffold (intramembranous ossification), calcified cartilage (endochondral ossification), or other bone (lamellar bone formation).






      Figure 1.2 Photomicrographs demonstrating the development of a long bone. A, Essential dumbbell shape of the long bone organizes from the primitive mesenchymal tissue. B, Initially, the structure comprises cartilage. C, A calcified coliform in the mid-diaphysis, which is associated with vascular channels. D, Later, secondary ossification centers develop in the epiphysis. E, As skeletal maturation approaches, the physis attenuates and disappears. From Vigorita VJ. Basic science of bone. In: Orthopaedic Pathology. 3rd ed. Philadelphia, PA: Wolters Kluwer; 2016:1-54.







      Figure 1.2 (continued)


    • Endochondral development



      • Periosteal sleeve allows capillary invasion into the cartilage anlage.


      • Capillaries deliver osseous precursors to produce calcified cartilage.



        • Primary ossification center


        • As bone replaces cartilage, perichondrium is replaced by periosteum.


      • Development of physis (Figure 1.3)



        • Secondary ossification center at epiphysis



          • Secondary ossification center has largely spherical growth pattern, rather than longitudinal pattern.


    • Intramembranous development



      • Osteoblasts form bone directly onto a collagen scaffold.


      • Typically flat bones (clavicle, pelvis)


    • Physeal growth (see Figure 1.3)



      • Growth plate structure (Figure 1.4)



        • Reserve zone



          • Adjacent to epiphysis/secondary ossification center



            • Vascularity through epiphysis (epiphyseal artery branches)


            • Vessels pass through, but give little blood supply


            • Low partial pressure of oxygen (PO2), anaerobic metabolism


          • Minimal longitudinal growth


          • Relatively fewer cells in abundant matrix



            • High type-II collagen


        • Proliferative zone



          • Columns of flat, ovoid cells


          • Responsible for longitudinal growth



            • Based on rate of cell division


          • Nutrient supply from epiphysis, with diffusion through the matrix


          • High PO2, aerobic


        • Hypertrophic zone



          • Plump, rounded cells


          • Responsible for matrix production and calcification







            Figure 1.3 Sites of bone growth. The metaphysis grows in length from the physis (bottom) but the epiphysis itself grows radially in three dimensions from the deep zone of the articular cartilage (top). Both articular cartilage and physeal cartilage maintain a consistent architecture, which is critical for function. From Salter RB. Disorders of epiphyses and epiphyseal growth. In: Textbook of Disorders and Injuries of the Musculoskeletal System. 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins; 1999:340.


          • Essentially lacks vascularity


          • Increasingly anaerobic toward metaphysis


          • Three parts:



            • Maturation zone


            • Degeneration zone


            • Zone of provisional calcification



              • Attaches to the primary spongiosa of the metaphysis


          • Vascularity from metaphyseal branches of the nutrient artery and metaphyseal arteries







            Figure 1.4 At the growth plate, resting cartilage at the subchondral plate begins to proliferate in columns. Following this incipient growth, cartilage cells begin to hypertroph, and following vascular penetration, undergo calcification forming a primary spongiosa or calcified cartilage zone (inset). This primary tissue remodels into bone or secondary spongiosa. From Vigorita VJ. Basic science of bone. In: Orthopaedic Pathology. 3rd ed. Philadelphia, PA: Wolters Kluwer; 2016:1-54.


      • Perichondrial ring of La Croix



        • Ring of woven bone around the physis for structural support


      • Ossification groove of Ranvier



        • Responsible for appositional growth of the physis/epiphysis


  • Nerve growth and development



    • Nervous system originates from ectoderm.



      • Neural crest—sensory neurons


      • Neural tube—brain, spinal cord, motor neurons


    • Axonal growth guided by growth factors and matrix glycoproteins


  • Abnormalities of musculoskeletal growth and development



    • Skeletal dysplasias



      • Many skeletal dysplasias and disorders of growth are related to the specific function within defined areas of the growth plate (Table 1.1).


    • Connective tissue disorders (Table 1.2)


BONE STRUCTURE AND FUNCTION



  • Bone has multiple functions:



    • Structural support


    • Attachments for muscle activity


    • Mineral homeostasis


    • Hematopoiesis (bone marrow)


  • Long bones



    • Epiphysis



      • Trabecular bone surrounded by thin cortical rim


      • Bordered by subchondral plate and physis/physeal scar


      • Apophysis—secondary ossification centers that are nonarticular (eg, greater trochanter, humeral epicondyles)









        Table 1.1 Skeletal Dysplasias and Growth Disorders Related to Areas of the Growth Plate












































































































































        Condition by Growth Plate Location


        Genetic Mutation


        Inheritance


        Epiphysis



        Multiple epiphyseal dysplasia


        COMP or type-IX collagen


        AD


        Reserve zone



        Pseudoachondroplasia


        COMP


        AD



        Diastrophic dysplasia


        Diastrophic dysplasia sulfate transporter


        AR



        Kniest dysplasia


        COL2A1


        AD


        Proliferative zone



        Achondroplasia


        FGFR3


        AD



        Hypochondroplasia


        FGFR3


        AD



        Spondyloepiphyseal dysplasia


        Type-II collagen


        AD (congenital)





        Type-II collagen


        AR (tarda)





        Unknown


        XLD


        Hypertrophic zone



        Mucopolysaccharidosis




        Hurler syndrome


        Alpha-L-iduronidase


        AR




        Morquio syndrome


        Beta-galactosidase


        AR




        Hunter syndrome


        Iduronate sulfatase


        XLR



        Rickets (provisional calcification)


        1,25(OH)2D3


        Primary spongiosa



        Metaphyseal chondrodysplasia




        Schmid type



        AD




        Jansen type


        PTH receptor


        AD


        Secondary spongiosa



        Osteogenesis imperfecta




        Type I


        COL1A1


        AD




        Type II


        COL1A1


        AR




        Type III


        COL1A1


        AR




        Type IV


        COL1A1


        AD



        Osteopetrosis


        M-CSF


        AR


        AD, autosomal dominant; AR, autosomal recessive; COL1A1, collagen type-I alpha-1 chain; COL2A1, collagen type-II alpha-1 chain; COMP, cartilage oligomeric matrix protein; FGFR3, fibroblast growth factor receptor-3; M-CSF, macrophage colony-stimulating factor; PTH, parathyroid hormone; XLD, X-linked dominant; XLR, X-linked recessive.



    • Metaphysis



      • Trabecular bone surrounded by thin cortical rim


      • Typically a flare of the bone to connect the diaphysis to the epiphysis


      • Often a site of ligamentous and tendinous attachments, and site of anastomosing vessels


    • Diaphysis

Dec 19, 2019 | Posted by in ORTHOPEDIC | Comments Off on Basic Science
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