Bone and Joint Diseases Flashcards
List the components of bone
- Organic - osteoid - 35% (type I collagen, GAG, proteins)
- Inorganic - mineral - 65% (hydroxyapatite)
List the histologic forms of bone
- Woven
-Made rapidly during development or fracture repair
-Less structural strength
-When present in adults it is always abnormal - Lamellar
-Slowly produced parallel collagen fibers
-More structural strength - Other bone structural forms
-Cortical (compact) bone - dense, thick layer on the outside of bone
-Trabecular bone (cancellous, spongy) - thin, lattice-like network inside of bone. Makes bones light and may contain red marrow
List the bone cells
Osteoblasts
Osteocytes
Osteoclasts
Describe Osteoblasts
-Derived from stem cells under the periosteum and in the medullary space
-Live on the matrix surface
-Synthesize, transport and assemble bone matrix
-Regulate mineralization
Describe Osteocytes
-Osteoblasts that become encased in lacunar spaces in bone, interconnected by cytoplasmic processes through canaliculi
-Control calcium, phosphate levels
-Detect mechanical forces and translate into biologic activity
Describe Osteoclasts
-On the bone surface
-Specialized multinucleated macrophages (from circulating monocytes) causing bone resorption
-Bind to bone matrix through integrins forming a resorption pit
-Secrete acid and neutral proteases (mostly MMPs) that resorb bone
Describe bone remodeling
-Adult skeleton is constantly turning over in a tightly regulated process (i.e. remodeling) on the bone surface
-Changes signaled through 3 factors:
1. Activator of NF-kB (RANK) - made by osteoclast precursors
2. RANK ligand (RANKL) - made by osteoblasts and marrow stromal cells
3. Osteoprotegerin (OPG) - made by osteoblasts
-Peak bone mass occurs in early adulthood. In 4th decade, resorption exceeds formation resulting in decline in skeletal mass
Describe the signaling effects in bone remodeling
-RANK and RANKL binding stimulates differentiation into osteoclast –> bone resorption
-If osteoblast makes OPG this blocks RANK/RANKL binding –> prevents osteoclast differentiation
Describe the systemic factors that affect the balance of bone remodeling
-Increased bone turnover/breakdown favored by PTH, IL-1, glucocorticoids
-Decreased bone turnover/breakdown - growth factors, sex hormones favors OPG expression
List the congenital bone disorders
-Osteogenesis imperfecta
-Osteopetrosis
List the metabolic bone disorders
-Osteopenia and osteoporosis
-Rickets and Osteomalacia
-Hyperparathyroidism - covered in endocrine
List bone tumors
-Bone-forming tumors
-Cartilage-forming tumors
-Metastatic tumors
List the joint diseases
-Arthritis
-Osteoarthritis
-Rheumatoid arthritis
-Gout
Describe Osteogenesis Imperfecta
-Also known as “brittle bone disease”
-Group of disorders of Type I collagen maturation (insufficient or abnormal) –> inadequate bone formation with think cortices and trabeculae –> weak bones that break easily
-Most (>90%) case are autosomal dominant collagen mutation - causing fractures and deformity
-Mistaken for child abuse
-Most show blue sclera due to choroid showing through thin sclera
-Most types have “opalescent teeth” which is clinically and radiographically identical to dentinogenesis imperfecta (no pulp chamber, bulbous crown) but different mutation)
Describe Osteopetrosis
-Hereditary bone disorders where osteoclasts can’t remodel bone. They are hard but brittle
What is the pathogenesis of Osteopetrosis
Bone deposition without resorption –> thickening of cortical bone and sclerosis of cancellous bone, obliterating the marrow space
Describe outcomes of Osteopetrosis
-Myelophthisic anemia and extramedullary hematopoeisis with hepatosplenomegaly
-Deafness and blindness due to constriction of nerve ostea
-Dense, opaque, solid tubular bones on radiographs become easily infected causing osteomyelitis
-Autosomal dominant type (most common) - pt survives, less severe effects
-Autosomal recessive types - death due to marrow failure
What is Osteopenia
Decreased bone mass (1-2.5 SD below mean peak bone mass)
What is Osteoporosis
Severe osteopenia with significantly increased risk of fracture (>2.5 SD below mean peak bone mass)
Describe the pathogenesis of Osteopenia and Osteoporosis
Imbalance between osteoblastic and osteoclastic activity leading to progressive loss of trabeculae and trabecular thickness (net loss of bone). (Note: collagen and mineralization are normal)
Describe the pathophysiology and associations of Osteopenia and Osteoporosis
-Peak bone mass at young adulthood; bone turnover continues with net deficit over time. Reduced peak bone mass in adolescent girls - tend to have low Ca2+ intake
-Osteoblasts less effective with age
-Aging and disuse (muscular loading stimulates bones)
-Dietary: low Ca2+, Vit D, increased PTH
-Estrogen is protective: prevents resorption caused by pro-inflammatory cytokines (IL-1, IL-6, TNF) and increases OPG
-Steroids, anticoagulants, alcohol, tobacco, proton pump inhibitors
What is the risk associated with Osteopenia and Osteoporosis?
bone compression and fractures (hip, vertebral, wrist) –> immobility which can lead to life-threatening complications (ex: embolism, pneumonia)
How do you diagnose Osteopenia and Osteoporosis
-Not seen on plain films until 30% bone loss
-DEXA scan (more sensitive method to show bone density)
What is the prevention and tx for Osteopenia and Osteoporosis?
-Increased calcium in diet and exercise
-Estrogen replacement after menopause
-Bisphosphonates - Fosamax and Actonel - kills and inactivates osteoclasts
Rickets and Osteomalacia are what type of defect?
Vit. D deficiency causing impairment of mineralization and a resultant accumulation of unmineralized bone matrix