Bone Physiology and Remodeling Quiz

Introduction to Skeletal Anatomy and Physiology

• Skeletal system is responsible for muscle attachment, locomotion, body shape, protection, mineral storage and is an adaptive biological system.
• It detects and processes multiple inputs to produce an appropriate response.

Learning Objectives

• Understand the basic structure, function, and organization of the human skeletal system.
• Detail the major stimuli impacting bone and the skeleton's response to these stimuli.
• Identify and describe the main cell types of bone (osteoblasts, osteocytes, and osteoclasts).

Types of Bone

• Long bones:
  • Composed of a diaphysis (shaft), metaphysis (between epiphysis and diaphysis), and epiphysis (ends).
  • Contain compact bone (strong outer layer), spongy bone (inner layer containing red marrow), medullary cavity (yellow marrow).
  • Have articular cartilage at the ends for joint movement.
  • Nutrient artery opening in the diaphysis.
• Flat bones: (skull, ribs, sternum)
• Sesamoid bones: small, round bones embedded in tendons (e.g., patella).
• Short bones: small, cube-shaped bones (e.g., carpals, tarsals).
• Irregular bones: complex shapes (e.g., vertebrae, facial bones).

Bone Types: Tissue

• Compact/Cortical bone: Main weight-bearing structure.
• Trabecular/Spongy/Cancellous bone: Principal site of calcium exchange, optimized for maximum support with minimum mass.

Bone Composition

• ~25% water
• ~25% organic components: Type I collagen fibers, chondroitin sulfate, proteins, cytokines, growth factors.
• ~50% inorganic components: Hydroxyapatite, minerals.

Bone Development

• Intramembranous: Bones form directly from mesenchymal cells (e.g., skull, some facial bones).
• Endochondral: Bones form from a cartilaginous template (e.g., long bones).

Bone Formation Stages

• Intramembranous development:
  • Mesenchymal condensations form early in embryogenesis.
  • These differentiate into osteoblasts, which form osteoid.
  • Osteoid is then mineralized.
  • Appositional growth occurs.
  • Genetically regulated by patterning genes (e.g., HOX, PAX).
• Endochondral ossification:
  • Bone forms from a cartilaginous template.
  • Morphogenetic and growth phases follow.

Growth Plate Organization

• Site of longitudinal bone growth.
• Chondrocytes are arranged in columns.
• Proliferation and differentiation are precisely regulated in distinct zones.

Bone Marrow

• Important for blood cell formation (erythrocytes, lymphocytes, etc.).

Bone Cell Lineages

• Osteoblasts: responsible for bone formation and mineralization.
• Bone lining cells: monitor and regulate bone resorption.
• Osteocytes: main mechanosensitive cells.
• Osteoclasts: responsible for bone resorption.

Physiological Factors Affecting Bone Homeostasis

• Serum calcium fluctuations: Influence bone resorption and formation.
• Mechanical loading changes: Affect bone remodeling.
• Microdamage repair: Essential for bone maintenance.
• Hormonal status: Impacts bone growth and homeostasis.

Osteoclasts and Calcium Homeostasis

• Low calcium levels trigger PTH release, leading to bone resorption, vitamin D activation, increased intestinal calcium absorption, and increased renal calcium reabsorption.

Bone as a Dynamic Structure

• Bone is a dynamic tissue that is constantly being remodeled.

Hormonal Status

• Hormonal influences on bone mass and density vary across different age groups (adolescence, adulthood, aging) due to estrogen levels, etc.

Remodeling Cycle

• Continuous process of bone resorption (osteoclasts) and deposition (osteoblasts) for maintenance.
• Stages include resorption, reversal, formation, and mineralization.

Osteoblastic Lineage

• Derived from stromal precursors.
• Synthesize organic bone matrix (osteoid).
• Control mineralisation.
• Differentiate into osteocytes or bone lining cells after mineralization.

Osteoid Formation and Mineralisation

• Osteoid is organic matrix composed of collagen fibers.
• Followed by mineralisation by calcium hydroxyapatite.

Osteoclasts

• Form from pluripotent CD34+ mononuclear phagocyte precursors.
• Precursor differentiation regulated by cytokines/growth factors.
• Responsible for bone resorption.
• Can be multinucleated.
• Express calcitonin receptors, cathepsin K, other proteases.

Pathological Regulators of Osteoclasts

• Disruption of hormone levels: (e.g., steroids).
• Inflammation: can affect osteoclast function.
• Cancer: can lead to abnormal bone turnover and remodeling.

Process of Bone Resorption

• Attaches to surface through integrins.
• Forms ruffled border, actin ring, and sealed zone.
• Acidifies sealed zone to dissolve bone matrix.
• Releases proteases to digest collagen.
• Creates resorption pits.

Pathological Consequences of Aberrant Turnover

• Paget's Disease: Increased bone turnover leading to weakened bone.
• Primary bone sarcomas: Malignant bone tumors.
• Osteoporosis: Reduced bone density and increased fracture risk.
• Osteolytic secondary cancers: Cancer affecting bone.