Bone Composition and Structure

• Bone is studied by the School of Pharmacy

Specific Learning Objectives

• Understand the roles of osteoclasts, osteoblasts, and osteocytes and their involvement in osteogenesis.
• Learn the structure and composition of bone and bone marrow.
• Identify types of bone marrow and understand ongoing cellular processes, including haematopoiesis.

Bone Composition and Structure

• Bone shape can be long, irregular, or flat.
• The summary focuses on the structure and composition of bone.
• Cells within the bone and their function.
• Osteoblasts, osteoclasts, and osteocytes.
• Ossification is the process of bone formation.
• Marrow function.
• Haematopoiesis.

Bone as a Biomaterial

• Bone is strong like iron but light like wood.
• It can adapt to functional requirements and repair itself.
• Bone functions include structural support for the heart, lungs, and marrow, protection for the brain and internal organs.
• Bone functions include attachment sites for muscles allowing limb movement.
• Bone assists in mineral reservoir for calcium and phosphorus.
• Aids in defense against acidosis, and traps dangerous minerals like lead.

Bone Architecture

• Cortical bone (compact bone) forms the outermost layer, having layers.
• Cortical bone is strong, dense, and has a regular structure.
• Trabecular bone (cancellous, spongy bone) is lightweight with irregular lattice.
• Trabecular is porous.
• The marrow cavity exists within bones.

Bone Anatomy: Gross Level

• Initially, woven bone is deposited and then replaced by lamellar bone
• Cortical and trabecular bone.
• Lamellar bone forms from systems called Haversian systems.

Bone Anatomy: Microscopic Level

• Lamellar bone consists of concentric lamellae and osteons.
• Structure contains Haversian canals, Volkmann's canals, blood vessels, and collagen fibers.
• Hydroxyapatite crystals are present.

Bone Composition Breakdown

• Bone composition constitutes 30% organic (cells, matrix) and 70% mineral.
• 2% of bone is cells.
• 98% matrix.
• Osteoblasts, osteocytes, and osteoclasts are cell types.
• Collagen is a key matrix component
• Hydroxyapatite is (Ca10(PO4)6(OH)2).
• Bone contains calcium-rich and phosphorus-rich components.
• Unlike concrete, bone is not static or fixed.
• Bone comprises both mineral and organic components.

Osteoblasts

• Form bone and are derived from mesenchymal stem cell lines.
• They are similar to fibroblasts and chondroblasts.
• All "Builders".
• Osteoblasts are found on the surface of bone and marrow cavities.
• Secrete proteinous/organic matrix
• High mitochondrial and Golgi content.
• Responsible for the mineralization of the matrix.

Osteoblast Detail

• Osteoblasts have hormone receptors for vitamin D, estrogen, and parathyroid hormone (PTH).
• They secrete factors to activate osteoclasts (RANK-ligand) and other cells.
• Osteoblasts become osteocytes when new bone traps them.
• Osteoblasts remaining on the surface of new bone differentiate into lining cells.
• Remaining osteoblasts undergo apoptosis.

Osteoclasts

• Osteoclasts function in bone breakdown (clearance).
• They derive from the blood cell line as macrophages or monocytes.
• Formed by the fusion of precursor cells into a large, multinucleated syncytium.
• Stimulated by RANK receptors.
• Osteoclasts resorb bone.

Bone Resorption

• Osteoclast-mediated process, also called bone resorption.
• Required for radial growth, bone remodeling, maintaining vascularity, and liberating ions.
• Osteoclasts feature red propellers, black arrows indicate resorption pits.
• Resorption pits enable surface to expose collagen bundles.
• Yellow stars indicate non-resorbed bone surfaces and blue triangles indicate mononuclear cells.

Osteogenesis

• Process where calcium phosphate crystals precipitate and attach to a collagenous lattice support.
• Bone always arises by replacement of pre-existing tissue.
• Pre-existing tissue can be cartilage (in long bones) or embryonic mesenchyme (in flat bones).
• Endochondral and intramembranous ossification.
• Requires matrix formation and mineralization.

Ossification

• Red color indicates hardened bone.
• Blue indicates cartilage model.
• Ossification starts at the primary ossification zone.
• Occurs in the middle of long bones and extends as a wave of ossification.

Endochondral Ossification Process

• Cartilage model is laid down by chondrocytes.
• Calcified cartilage provides a scaffold for osteoblasts.
• Osteoblasts form matrix (secreting osteoid), which is unmineralized pre-bone (type 1 collagen).
• Osteoblasts secrete alkaline phosphatase to calcify the matrix.
• Osteoclasts and blasts remove calcified cartilage and woven bone.
• Replaced with lacunar bone.
• Growth in length occurs by proliferation of chondrocytes, such as epiphyseal plates.
• Simultaneously, growth in diameter occurs by deposition of new bone under the periosteal collar.
• Osteoclastic resorption maintains bone shape.

Bone Marrow

• Large organ, approximately 3.5 kg.
• Fills hollow center of bones, responsible for haematopoiesis.
• Responsible for formation, and specialization of cellular elements.
• Immune cell production.
• Bone marrow contains different populations of stem cells.
• Bone marrow is either red or yellow.
• Yellow marrow can revert to red in times of blood loss or reduced haematopoietic activity.
• Bone marrow structure features extensive capillary network around a central vein.
• Haematopoiesis occurs in the extravascular spaces between sinuses.
• Sieve-like openings in epithelial cells allow passage of mature blood cells into circulation.

Metabolic Bone Disorders

• Role of bone in mineral the mineral homeostasis of calcium and phosphate.
• Symptoms of bone diseases affecting is bone composition.
• Pharmacological treatments are available for metabolic bone disorders.

Calcium and Phosphorus Roles

• Calcium (Ca) is required for muscle contraction, neurotransmitter release.
• Contributes to resting membrane potential, signal transduction, blood coagulation, and bone structure.
• Phosphorus (P) is required for signal transduction and energy transaction as phosphate.
• Bone structure.
• Levels of both calcium and phosphorus are regulated by parathyroid hormone (PTH) and vitamin D
• Primary regulation of phosphorus occurs in the kidneys.
• Parathyroid hormone (PTH) enhances urinary phosphate excretion.
• Vitamin D inhibits PTH production.
• However, control of phosphate is not as tight as calcium.
• Renal tubular disease is an exception
• Body contains.
• ECF only contains small amount.
• . Hypocalcemia prompts rapid mobilization of calcium from skeletal stores.
• Maintenance of the right EC levels.
• Plasma calcium regulation.
• PTH and vit D
• Each are both.

Summary Regulation by PTH

• Fast control.
• PTH has three mechanisms.
• Increases bone reabsorption
• Increases increases dital.
• Increases synthesis
• Regulation by Vit D.

Vitamin D Regulation

• The activity form.
• Each a role with
• Slows/prolonged control.
• Increases absorption. Increases bone
• Vit D inhibits transcription.

Calcium and Kidney Relation

• Calcium derives from kidneys.
• Pi is pushed into urine.
• There is a serum.

##PTH Method

• PTH binds and activates at PTH acceptor
• Not expressed
• Activation:
• .Prolonged
• The more reabsorption of the bone.
• *But if Intermittently is done, the formation of bone will be promoted

Vitamin D synthesis

• Enzyme with sun.
• Synthesis increase-Pth. 0- Activity stimulations
• The lack there of causes hypophosphate

Actions of Vitamin D

• Increases absorption
• There is a better absorption rate.
• Increases protein amounts
• Directly opens channels.
• Is indirectly involved

Osteomalacia/Rickets

• Defective mineralization
• Causes bones and remodelling
• Defective mineralization in growing.
• Types differ
• Subtypes can be present mostly due to defiencies.

Osteomalacia / Rickets

• Largerly eradicated
• Vitamin D persists.
• Most supplements are now recommended.

Metabolic Bone Disease

• Causes disorder.
• Distrophy of bone.

Kidney

• Primary has high.
• O- osteoalcia.

Hyperthroid

• Symptoms affect the Kidneys.
• Bones
• Glands
• All body elements

Disorder

• Increased PTH
• Renal :decreased filtration :hypocaciaema :no feedback.

Osteoporosis

• An estimation of the affect one in UK.
• Fractures in UK :common fractures .Spinefractures
• Can be genetic or familial

Detail Osteoporosis

• BMD = 1 below YAM
• • osteo
• BMD1to2 below YAM2
• • osteoporosis
• BMD2 SD below YAM5

Facts

• Age makes more likly.
• And sex
• Ething And
• smoking, alcohol

Osteoporosis detail

• Architecture
• Low power scanning bone
• eroded
• fragility