Bone Physiology and Fracture Healing Quiz

Skeletal-Soft Tissue Module

•  This module covers bone and soft tissue pathophysiology, including normal bone physiology and various pathologies.
•  Bone pathologies include infectious diseases (osteomyelitis), fractures, and bone and soft tissue tumors.
•  Musculoskeletal system function is not isolated. Primary diseases of the musculoskeletal system can significantly impact other body systems, and vice versa.
• Common musculoskeletal disorders include fracture, dislocation, subluxation, contusion, hematoma, repetitive overuse/microtrauma, strain, sprain, and degenerative diseases.

Overview of Bone and Soft Tissue Pathophysiology

• Decisions about treating bone and soft tissue pathology are based on cellular adaptations and reversible cell injury responses to stress, and the stages of healing.
•  Healing phases, such as Hemostasis, Inflammation, Proliferation/Migration, and Remodeling/Maturation, are crucial for tissue repair.

Phases of Tissue Healing

•  Hemostasis involves blood clot formation to stop bleeding
•  Inflammation stage involves immune response and cell recruitment to damaged tissues.
•  Proliferation and migration of new cells such as fibroblasts and endothelial cells support tissue regeneration
•  Remodeling and maturation of the tissue complete the healing process

Overview of Bone and Soft Tissue Pathophysiology (continued)

• Immobilization is initial to remove longitudinal stress, allowing for removal of necrotic bone tissue, followed by fibrocartilaginous callous deposition, and gradual stress application for proper bone healing.
• Various pathologies can affect bone and require reparative processes, including fractures, infections (e.g., tuberculosis or sarcoidosis), metabolic disturbances (e.g., Paget disease, osteoporosis, or osteogenesis imperfecta), tumors, response to implanted prostheses, bone infarction, and systemic diseases (e.g., sickle cell disease, amyloidosis, or hemochromatosis).

Bone Remodeling

• Bone remodeling involves two distinct phases: bone resorption followed by bone formation.
• Approximately 5-20% of the skeleton undergoes remodeling at any given time.
• Bone remodeling processes include: Activation, Resorption, Reversal, and Formation.

Bone Cells and Function

• Osteoblasts form new bone (osteoid), primarily Type-1 collagen, and reside on bone surfaces.
• Osteoclasts break down existing bone, located on bone surfaces.
• Osteocytes are embedded within bone matrix having branches for sensing damage and guiding repair.

Osteocyte Network

• Mechanical loading applied to the whole bone transmits through tissue to cellular level, causing interstitial fluid movement surrounding the osteocytes within the mineralized matrix.

Regulation of Calcium

• Three compartments store calcium in the body: extracellular matrix (~99%), extracellular fluid (~0.1%), and intracellular (~0.9%).
• Net intestinal calcium uptake is approximately 175 mg/day.
• The kidney reabsorbs 99% of calcium.
• Calcitonin (from the thyroid gland) decreases calcium level to maintain normal blood calcium levels.
• PTH (from the parathyroid gland) increases bone resorption and calcium reabsorption.
• Vitamin D aids in calcium and phosphate absorption in the small intestine, reabsorption in the kidneys, and bone mineralization.
• The parathyroid glands control calcium levels through PTH production, regulated through a Ca²⁺-sensing receptor.
•  PTH increases bone resorption, kidney calcium reabsorption, and intestinal calcium absorption.

Thyroid Gland

• Largest pure endocrine gland, located inferior to the larynx, and is highly vascular.
• Thyroid hormones T3 and T4 are produced, along with calcitonin.

Calcitonin

• Released from C cells (parafollicular cells) in the thyroid gland when blood calcium levels increase.
• Regulates calcium levels by decreasing blood calcium levels, primarily by inhibiting osteoclast activity.
• Deficiency or excess does not significantly affect calcium balance.
• Useful in treating bone disorders with accelerated bone turnover, such as hyperparathyroidism and Paget disease.

Vitamin D

• A fat-soluble vitamin crucial for calcium absorption and bone mineralization.
• Is produced in the skin upon exposure to UV light, is absorbed with dietary fats, stored in the liver, and converted to 1,25-dihydroxyvitamin D₃ before being utilized.
• 1,25 dihydroxyvitamin D₃ aids in the small intestine with calcium and phosphate absorption, in kidneys with calcium reabsorption, and in bone with mineralization.

Fracture

• Fracture healing is a process of regeneration and remodeling.
• Fracture healing has three main phases, including an inflammatory phase, a reparative phase, and a remodeling phase.
• The inflammatory phase involves vascular response, cell proliferation, and pain.
• The reparative phase involves granulation tissue formation, fibrocartilage and soft callus formation, and the replacement of soft callus with hard callus.
• The remodeling phase involves bone remodeling to replace the hard callus with mature organized lamellar bone to add stability back to the fracture site.

Bone Pathologies: Infectious Diseases (Osteomyelitis)

• Osteomyelitis is a bone infection, commonly affecting spine, pelvis and arms/legs.
• It frequently results from bacterial pathogens entering through open wounds or the gastrointestinal tract.
• In adults, it is often secondary to open injuries to bone and soft tissues.
• Acute osteomyelitis is rare in adults, but common in children.
• Bacterial seeding usually occurs in the vascular loop in growing bones.
• Signs and symptoms include initial lack of pain, pain and swelling with progression into the periosteum, fever and malaise, and deep constant lower extremity pain that worsens with weight-bearing.
• Immediate treatment is required, including antibiotics and surgical intervention (if infection spreads to joints) to drain exudates and debridement of bone and surrounding tissues.

Overview of Tumors (AKA Neoplasms)

• Bone and soft tissue tumors can be primary or metastatic.

• Benign tumors are typically not invasive, slow-growing, and do not metastasize.

• Malignant tumors can spread locally and distantly, are less common but more dangerous.

• Examples of benign bone tumors include bone islands, osteoid osteoma, and osteoblastomas.

• Examples of malignant bone tumors include osteosarcoma and Ewing's sarcoma.

• Osteolytic tumors cause bone destruction, while osteoblastic tumors cause bone formation.

• Tumor types include cartilage, bone, and bone marrow; and include primary benign and malignant tumors, and metastatic tumors resulting from elsewhere in the body.

• The most common presenting symptom is pain and swelling.

• Diagnostic approaches and treatment strategies exist for both benign and malignant bone tumor types, primarily surgical removal or chemo/radiation combinations.