Bones: Development and Ossification

Overview of Bone Development

Definitions

The formation of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types is called ossification or osteogenesis.

Types of ossification

The 2 primary types of ossification are:

• Endochondral ossification Endochondral ossification A hyaline cartilage model is created from mesenchyme, then replaced with bone. Development of the Limbs: a hyaline cartilage Hyaline cartilage A type of cartilage characterized by a homogeneous amorphous matrix containing predominantly type II collagen and ground substance. Hyaline cartilage is found in articular cartilage; costal cartilage; laryngeal cartilages; and the nasal septum. Cartilage: Histology model is created from mesenchyme, then replaced with bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types 
• Intramembranous ossification: bones develop directly from mesenchyme

Review of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types structure

The 2 primary types of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types are compact bone Compact bone A smooth, solid outer layer of osseous tissue. Bones: Structure and Types and spongy bone Spongy bone A type of osseous tissue which makes up the inner part of bone. It has a spongy, honeycomb-like structure with struts or trabecula and contains the bone marrow. It has higher rate of bone remodeling turnover than cortical bone. Bones: Structure and Types.

• Compact bone Compact bone A smooth, solid outer layer of osseous tissue. Bones: Structure and Types: 
  • Hard, dense outer layer of bones
  • Arranged in functional units known as osteons: a central canal containing nerves and vessels surrounded by concentric rings of calcified bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types matrix and osteocytes
• Spongy bone Spongy bone A type of osseous tissue which makes up the inner part of bone. It has a spongy, honeycomb-like structure with struts or trabecula and contains the bone marrow. It has higher rate of bone remodeling turnover than cortical bone. Bones: Structure and Types: 
  • Inner layer consisting of a lattice of thin pieces of osseous tissue Osseous tissue Bones: Structure and Types called trabeculae
  • Found at the ends of long bones Long bones Length greater than width. Bones: Structure and Types and in the middle of flat, short, and irregular bones Irregular bones Bones: Structure and Types

Endochondral Ossification

Overview of endochondral ossification Endochondral ossification A hyaline cartilage model is created from mesenchyme, then replaced with bone. Development of the Limbs

• Bones formed via endochondral ossification Endochondral ossification A hyaline cartilage model is created from mesenchyme, then replaced with bone. Development of the Limbs: all bones below the skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull: Anatomy except for the clavicles
• Hyaline cartilage Hyaline cartilage A type of cartilage characterized by a homogeneous amorphous matrix containing predominantly type II collagen and ground substance. Hyaline cartilage is found in articular cartilage; costal cartilage; laryngeal cartilages; and the nasal septum. Cartilage: Histology is used as a template for bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types formation. 
• Process overview:
  • Chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology create a hyaline cartilage Hyaline cartilage A type of cartilage characterized by a homogeneous amorphous matrix containing predominantly type II collagen and ground substance. Hyaline cartilage is found in articular cartilage; costal cartilage; laryngeal cartilages; and the nasal septum. Cartilage: Histology model of the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types.
  • Chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology within the model mature and hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation → allows mineralization
  • Mineralization → ↓ chondrocyte nutrition → chondrocye death
  • Chondrocyte death creates space within the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types called lacunae.
  • Lacunae are invaded by vessels carrying osteoblasts, which lay down new bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types.
  • New bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types is remodeled into mature bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types.

Detailed process of endochondral ossification Endochondral ossification A hyaline cartilage model is created from mesenchyme, then replaced with bone. Development of the Limbs

• Mesenchyme differentiates into chondroblasts Chondroblasts Perichondrial cells that are located at the periphery of the cartilage and develop into chondrocytes. Cartilage: Histology.
• Chondroblasts Chondroblasts Perichondrial cells that are located at the periphery of the cartilage and develop into chondrocytes. Cartilage: Histology secrete a hyaline cartilage Hyaline cartilage A type of cartilage characterized by a homogeneous amorphous matrix containing predominantly type II collagen and ground substance. Hyaline cartilage is found in articular cartilage; costal cartilage; laryngeal cartilages; and the nasal septum. Cartilage: Histology matrix:
  • Forms a model of the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types
  • Model surrounded by membrane called perichondrium
  • Chondroblasts Chondroblasts Perichondrial cells that are located at the periphery of the cartilage and develop into chondrocytes. Cartilage: Histology trapped within the matrix become chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology.
• Formation of the primary ossification center Primary ossification center Development of the Limbs:
  • Occurs in the diaphysis Diaphysis The shaft of long bones. Bones: Structure and Types (shaft) of long bones Long bones Length greater than width. Bones: Structure and Types
  • Chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology near the center of the model mature and hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation.
  • Hypertrophied chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology alter matrix contents (add collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology X and fibronectin Fibronectin Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. Connective Tissue: Histology) → allows mineralization to begin
• Matrix mineralization:
  • Leads to ↓ nutrient delivery to chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology → chondrocyte apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage 
  • Holes (called lacunae) develop in the matrix where chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology used to exist 
• Invasion of blood vessels:
  • Vascular buds (called periosteal buds) arise from the perichondrium
  • Grow toward the lacunae in the primary ossification center Primary ossification center Development of the Limbs (center of diaphysis Diaphysis The shaft of long bones. Bones: Structure and Types) 
  • Carry osteogenic cells with them into the lacunae:
    • Osteoblasts form new bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types.
    • Osteoclasts break down bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types and matrix.
  • Invading periosteal buds break down walls between lacunae, creating the primary marrow space (which will eventually become the medullary cavity Medullary Cavity Ewing Sarcoma).
• Seeding Seeding The local implantation of tumor cells by contamination of instruments and surgical equipment during and after surgical resection, resulting in local growth of the cells and tumor formation. Grading, Staging, and Metastasis of osteogenic cells:
  • Periosteal buds deposit osteoblasts into the marrow space.
  • At the same time, perichondrium ossifies into a bony collar surrounding the forming bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types → now known as periosteum Periosteum Thin outer membrane that surrounds a bone. It contains connective tissue, capillaries, nerves, and a number of cell types. Bones: Structure and Types
• Osteoblasts create woven bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types:
  • Osteoblasts now lining the marrow spaces lay down osteoid tissue (organic components of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types matrix) and calcify it → called woven bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types
  • Bone remodeling Bone remodeling The continuous turnover of bone matrix and mineral that involves first an increase in bone resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling’s two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. Bones: Remodeling and Healing (via osteoclasts and osteoblasts) replaces woven bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types with mature trabecular (spongy) bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types
• Growth in bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types length:
  • Cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology continues dividing at the epiphyses → ↑ bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types length
  • Area is known as the epiphyseal plates (i.e., growth plates Growth Plates The area between the epiphysis and the diaphysis within which bone growth occurs. Osteosarcoma).
  • Continues providing longitudinal growth into early adulthood
• Secondary ossification centers:
  • Located within the epiphyses
  • Appear around the time of birth
  • Follow the same pattern as the primary ossification center Primary ossification center Development of the Limbs:
    • Matrix mineralization
    • Chondrocyte death → creation of lacunae
    • Invasion of blood vessels
    • Seeding Seeding The local implantation of tumor cells by contamination of instruments and surgical equipment during and after surgical resection, resulting in local growth of the cells and tumor formation. Grading, Staging, and Metastasis of the lacunae with osteoblasts, which create bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types
• After birth, cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology remains at:
  • Articular surfaces
  • Epiphyseal plates: 
    • Also known as growth plates Growth Plates The area between the epiphysis and the diaphysis within which bone growth occurs. Osteosarcoma
    • Ossify after puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty (resulting in no further longitudinal growth)

Intramembranous Ossification

Intramembranous ossification is a direct conversion of mesenchymal cells into osseous tissue Osseous tissue Bones: Structure and Types.

Bones formed via intramembranous ossification

These bones have a middle layer of spongy bone Spongy bone A type of osseous tissue which makes up the inner part of bone. It has a spongy, honeycomb-like structure with struts or trabecula and contains the bone marrow. It has higher rate of bone remodeling turnover than cortical bone. Bones: Structure and Types sandwiched between layers of compact bone Compact bone A smooth, solid outer layer of osseous tissue. Bones: Structure and Types:

• Flat bones Flat bones Bones: Structure and Types of the skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull: Anatomy
• Facial bones
• Mandible Mandible The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. Jaw and Temporomandibular Joint: Anatomy
• Clavicle Clavicle A bone on the ventral side of the shoulder girdle, which in humans is commonly called the collar bone. Clavicle Fracture

Process

• Mesenchymal cells condense into sheets and differentiate into:
  • Osteogenic cells → further differentiate into osteoblasts
  • Capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology
• Between mesenchymal sheets:
  • Osteogenic cells/osteoblasts condense into ossification centers 
  • Osteoblasts begin secreting osteoid: soft collagenous bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types matrix (soft trabeculae)
  • Trabeculae grow → osteoblasts deposit calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes onto the matrix
• Osteoblasts trapped within the mineralizing matrix transform into osteocytes
• Mineralized trabeculae:
  • Middle portion: becomes permanent spongy bone Spongy bone A type of osseous tissue which makes up the inner part of bone. It has a spongy, honeycomb-like structure with struts or trabecula and contains the bone marrow. It has higher rate of bone remodeling turnover than cortical bone. Bones: Structure and Types (middle layer of flat bones Flat bones Bones: Structure and Types)
  • Surface portions: 
    • Continue calcifying until all the spaces are filled in → compact bone Compact bone A smooth, solid outer layer of osseous tissue. Bones: Structure and Types
    • Remodeling occurs via osteoclasts and osteoblasts to form lamellar bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types.
• Surface mesenchyme:
  • Remains uncalcified
  • Becomes more and more fibrous Fibrous Fibrocystic Change
  • Eventually differentiates into periosteum Periosteum Thin outer membrane that surrounds a bone. It contains connective tissue, capillaries, nerves, and a number of cell types. Bones: Structure and Types

Bone Growth and Mineralization

Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types growth

The epiphyseal plates are found in the metaphysis Metaphysis Bones: Structure and Types of long bones Long bones Length greater than width. Bones: Structure and Types, the transitional region between the diaphysis Diaphysis The shaft of long bones. Bones: Structure and Types (shaft) and epiphysis Epiphysis The head of a long bone that is separated from the shaft by the epiphyseal plate until bone growth stops. At that time, the plate disappears and the head and shaft are united. Bones: Structure and Types (ends). There are 5 distinct histologic zones:

1. Zone of reserve cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology: 
   • Located farthest from the marrow
   • Consists of resting cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology
   • The chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology disappear after puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty → “closing” the growth plates Growth Plates The area between the epiphysis and the diaphysis within which bone growth occurs. Osteosarcoma
2. Zone of proliferation: 
   • Chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology arrange themselves in columns and divide.
   • Leads to longitudinal growth
3. Zone of hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation: 
   • Chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation, mature, and transform (just as in endochondral ossification Endochondral ossification A hyaline cartilage model is created from mesenchyme, then replaced with bone. Development of the Limbs).
   • Allows for mineralization and additional longitudinal growth
4. Zone of calcification: Matrix is mineralized. 
5. Zone of resorption and bone deposition Bone deposition Bones: Remodeling and Healing: 
   • Chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology die, creating longitudinal channels Channels The Cell: Cell Membrane that are invaded by vessels carrying osteogenic cells.
   • Osteoclasts dissolve the calcified cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology.
   • Osteoblasts line the channel walls and lay down concentric lamellae of matrix until only a narrow channel remains → the central channel of a mature osteon

Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types mineralization

• Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes ( Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺) and phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes (PO₄^3–) combine to form hydroxyapatite crystals Hydroxyapatite crystals A group of compounds with the general formula m10(PO4)6(OH)2, where m is barium, strontium, or calcium. The compounds are the principal mineral in phosphorite deposits, biological tissue, human bones, and teeth. They are also used as an anticaking agent and polymer catalysts. Calcium Hemostasis and Bone Metabolism on the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types matrix.
• Crystals can form only when certain threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction levels for Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ and PO₄^3– are exceeded:
  • Most tissues have inhibitors preventing this from happening.
  • Bone-forming cells secrete osteocalcin, which binds extracellular Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ → allows Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ to accumulate
• Osteoblasts respond to ↑ Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ by secreting alkaline phosphatase Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma, which ↑ PO₄^3– ions.
• At ↑ levels, calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes crystallize into hydroxyapatite crystals Hydroxyapatite crystals A group of compounds with the general formula m10(PO4)6(OH)2, where m is barium, strontium, or calcium. The compounds are the principal mineral in phosphorite deposits, biological tissue, human bones, and teeth. They are also used as an anticaking agent and polymer catalysts. Calcium Hemostasis and Bone Metabolism ( Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)₁₀(PO₄)₆OH₂) on the organic matrix.

Clinical Relevance

• Achondroplasia: autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance condition caused by mutations in the FGFR3 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics, which inhibits chondrocyte proliferation, impairing endochondral bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types formation. Clinically, achondroplasia presents in infants with short stature, shortening of the limbs, characteristic facies, abnormalities in the spinal curvature, and slow motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology development. Intellectual development is normal. Management is aimed at optimizing functional capacity and treating complications, such as recurrent ear infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea, leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy bowing, and spinal stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS).
• Osteogenesis imperfecta Osteogenesis imperfecta Osteogenesis imperfecta (OI), or “brittle bone disease,” is a rare genetic connective tissue disorder characterized by severe bone fragility. Although OI is considered a single disease, OI includes over 16 genotypes and clinical phenotypes with differing symptom severity. Osteogenesis Imperfecta: also known as “ brittle bone disease Brittle bone disease Osteogenesis imperfecta (oi), or “brittle bone disease,” is a rare genetic connective tissue disorder characterized by severe bone fragility. Although oi is considered a single disease, oi includes over 16 genotypes and clinical phenotypes with differing symptom severity. Osteogenesis Imperfecta.” Osteogenesis imperfecta Osteogenesis imperfecta Osteogenesis imperfecta (OI), or “brittle bone disease,” is a rare genetic connective tissue disorder characterized by severe bone fragility. Although OI is considered a single disease, OI includes over 16 genotypes and clinical phenotypes with differing symptom severity. Osteogenesis Imperfecta is a rare genetic connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology disorder characterized by severe bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types fragility. Although it is considered a single disease, it includes over 16 genotypes, with the most common types causing mutations in type 1 Type 1 Spinal Muscular Atrophy collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology. Some forms are lethal in utero. There is no definitive cure; treatment is supportive, usually involving bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix “-dronate” or “-dronic acid” (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates, and is focused on reducing pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures frequency, and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types deformity Deformity Examination of the Upper Limbs and increasing ambulation. 
• Rickets Rickets Disorders caused by interruption of bone mineralization manifesting as osteomalacia in adults and characteristic deformities in infancy and childhood due to disturbances in normal bone formation. The mineralization process may be interrupted by disruption of vitamin d; phosphorus; or calcium homeostasis, resulting from dietary deficiencies, or acquired, or inherited metabolic, or hormonal disturbances. Osteomalacia and Rickets: disorder of decreased bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types mineralization in children. In rickets Rickets Disorders caused by interruption of bone mineralization manifesting as osteomalacia in adults and characteristic deformities in infancy and childhood due to disturbances in normal bone formation. The mineralization process may be interrupted by disruption of vitamin d; phosphorus; or calcium homeostasis, resulting from dietary deficiencies, or acquired, or inherited metabolic, or hormonal disturbances. Osteomalacia and Rickets, the hypertrophic chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology in the epiphyseal growth plates Growth Plates The area between the epiphysis and the diaphysis within which bone growth occurs. Osteosarcoma fail to undergo apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage. This failure results in insufficient mineralization of the cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology and is most commonly due to a deficiency in vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies, the vitamin that promotes bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types mineralization. Rickets Rickets Disorders caused by interruption of bone mineralization manifesting as osteomalacia in adults and characteristic deformities in infancy and childhood due to disturbances in normal bone formation. The mineralization process may be interrupted by disruption of vitamin d; phosphorus; or calcium homeostasis, resulting from dietary deficiencies, or acquired, or inherited metabolic, or hormonal disturbances. Osteomalacia and Rickets presents with skeletal deformities, including bowed legs, and growth abnormalities.  Treatment includes vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies, calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes, and phosphorus supplementation.