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
Describe Rickets
- Vitamin D deficiency in children
-Dietary deficiency (formular-fed infants)
-Inadequate sunlight - Soft, deformable bones
-Bowed legs
-Pigeon breast (protruding sternum) - Enamel hypoplasia
Describe Osteomalacia
- Vit D deficiency in adults
-Pancreatic, intestinal or biliary diseases causes fat malabsorption
-Reduced sunlight and dietary intake - Poor remodeling of existing bones
-New matrix is poorly mineralized resulting in weak bones of normal contour
Describe Vit D-resistant Rickets
-X-linked dominant inheritance
-Kidney cannot resorb phosphate (causes hypophosphatemia)
-Same clinical appearance as rickets (short stature) but does not respond to Vit D
-Dental: elongated pulp horns causes pulp exposures at DEJ
What is Hypophosphatasia
-Inherited condition (dominant and recessive forms)
-Deficiency of tissue alkaline phosphatase
-Bony findings resembling rickets (short stature, bowed legs, fractures)
What are the dental findings with Hypophosphatasia?
-Wide pulp canals
-Early deciduous tooth loss because of poorly formed cementum (ex: Md incisors)
What diagnostic tests are performed with Hypophosphatasia?
-Urinary phosphoethanolamine
-Low serum alk phosphatase
Describe Paget Disease of Bone
- Increased/uncontrolled generalized bone remodeling resulting in distortion and weakening of bone; unknown etiology
-Older pts (rare <40yrs), Anglo-saxon ancestory; decreasing incidence
-Asymptomatic or Bone pain +/-, usually >1 bone (polyostotic) enlarges
-Elevated serum alkaline phosphatase; Ca+2 and PO4 normal
What do you see in the H&N with Paget Disease? In Radiographs?
H&N:
-Skulls, jaws - Mx/Md - hat/denture won’t fit, spaces between teeth (due to jaw expansion)
Radiographs:
-thick cortices, “cotton wool” appearance at late stage, generalized hypercementosis
What is the tx for Paget Disease?
Bisphosphonates
Describe the Histologic Phases of Paget Disease of Bone
- Osteolytic phase: initial resorption with numerous enlarged osteoclasts
- Osteoblastic phase: increased osteoblastic activity (“cotton wool” appearance)
- Osteosclerotic (Burned out) phase: dense “mosaic” bone with prominent reversal lines
Describe Fibrous Dysplasia
- A developmental condition: continual production of immature bone matrix
- Bone expands but is soft and immature
- Disease severity increases the earlier the mutation occurs during development
-Albright syndrome: severe polyostotic fibrous dysplasia + precocious puberty in females + cafe-au-lait spots on skin
-Polyostotic - many bones affected
-Monostotic disease - only one bone affected
What is the pathogenesis of Fibrous Dysplasia?
Spontaneous G protein mutation –> continual adenylyl cyclase production of cAMP –> bone matrix formation
What are the clinical findings of Fibrous Dysplasia?
-Slow growing, firm, painless, fusiform bone expansion starts in childhood and stops after growth is complete
-Bone is weak and deformable
-Most common in ribs, long bones, jaws, skull
What is the histology of Fibrous Dysplasia
Cellular fibrous stroma with haphazard, woven bone trabeculae (“Chinese character letters”) without osteoblastic rimming
What is the tx for Fibrous Dysplasia
Surgical reduction after growth stops. Don’t radiate, b/c can cause sarcoma
Describe Osteomyelitis
-Inflammation of bone and marrow, virtually always secondary to infection
-Primary focus of disease or complication of systemic infection
-All types of organisms but most often pyogenic bacteria
-Spread to bone: hematogenous, direct extension or implantation (ex: fracture)
Describe Acute Osteomyelitis
-Bacterial growth and neutrophilic rxn in first 48 hours –>
-Bone necrosis and spread along the periosteum. If periosteum ruptures –>
-ST abscess which can exit the skin as a draining sinus tract
-After 1 week, fibrous tissue ingrowth and reactive vital bone forms at periphery (involucrum) around the dead infected bone (sequestrum)
Describe Chronic Osteomyelitis
-Up to 25% of acute cases don’t resolve and persist as a chronic infection. Can have spontaneous acute flareups or occur after years of dormancy
-Marrow fibrosis, sequestrum and chronic inflammation (lymphocytes, plasma cells)
Describe Osteoma
-Benign bone tumor often growing on bone surface (periosteal)
-Painless, slow growing
-Multiple osteomas of facial/jaw bones could represent Gardner Syndrome (precancerous colon polyps leading to colon cancer)
Describe Osteoblastoma
- 2-4cm up to 10cm
-Pain common, not well relieved by salicylates
-Expansile, well/ill-defined RL with patchy to diffuse mineralization
-Reactive sclerosis not always present
Describe Osteoid Osteoma (OO)
- <2cm
-Pain, usually nocturnal, relieved by salicylates because tumor makes prostaglandins (usually extragnathic lesions)
-Non-expansile, usually well circumscribed RL with variably thick reactive sclerosis
-Small RO nidus may be present (target-like)
(RL = radiolucent)
(RO = radiopaque)
Describe Osteosarcoma
-Malignant appearing cells producing bone
-2nd decade peak occurrence; also occurs in older adults with Paget disease, bone infarcts or previous radiation
-Genetic mutation - often RB gene
-Painful enlarging mass
-Knee joint - most common site; 8% in the jaw
-Radiograph: expansile RL/RO mass that pushes out the periosteum
-Sunburst appearance due to reactive bone formation
-Hematogenous spread to lungs
-Tx: neoadjuvant chemotx (chemo before surgery), surgery, chemtx
Describe Chondroma
Benign cartilage producing tumor that often occur in the hands but never found in the jaws. Any cartilage tumor seen in the jaws is malignant
Describe Chondrosarcoma
-Malignant tumor producing cartilage not bone
-Painful, enlarging mass
-Seen in adults (>40 yrs)
-Pelvis, shoulder, ribs
-Radiograph: mixed RL/RO mass
-Variable grades - higher grades spread through blood to lungs
-Tx: surgery
Describe Ewing Sarcoma
-Small round cell tumor (resembles lymphocytes) of neuroectoderm
-Medullary bone in children and young adults
-Most in leg bones and pelvis; some in jaws
-Rapid growth with pain and expansion, can mimic acute infection
-Radiograph: ill-defined radiolucency and periosteal reaction produces “onion-skin” layers of reactive bone
-Tx: surgery and chemotx
Describe Metastatic tumors
-Mets to bone are much more common than primary bone cancer
-75% of skeletal metastases originate from cancers of the prostate, breast, kidney, and lung
-Typically axial skeleton (often vertebral) and can be multiple lesions
-Poor prognosis
Describe the clinical presentation of Metastatic tumors
-Pain, possible paresthesia
-Can cause hypercalcemia
-Can replace marrow –> myelophthisic anemia
Describe the radiographic presentation of Metastatic tumors
-Irregular, ill-define radiolucency most often
-Prostate or breast mets can cause mixed or radioopaque lesions
List the types of joints
- Solid (nonsynovial) joints or synarthroses
- Cavitated (synovial) joints
Describe Solid (nonsynovial) joints or syarthroses
-Provide structure and only minimal movement
-No joint space
-Fibrous tissue (i.e. cranial structures, periodontal ligaments) or cartilage bridge (sternum/ribs, pelvis) at ends of bones
Describe Cavitated (synovial) joints
- Have a joint space for range of motion
- Enclosed by a synovial membrane lined by synoviocytes that make synovial fluid (plasma filtrate) containing hyaluronic acid (liubrication) and nutrition for articular cartilage
- Hyaline cartilage: elastic shock absorber and wear-resistant- had no blood supply, lymphatic drainage or innervation
-Water (70%) and proteoglycans resist compression and limit friction
-Type II collagen - resists tensile stress and transmits vertical loads
-Chondrocytes - make and digest matrix
Describe Osteoarthritis
-“Degenerative joint disease” (DJD)
-Degeneration of cartilage without repair, leading to failure of the joint
-A disorder of cartilage not an inflammatory process
-Most common joint disease; increases exponentially >50yrs
What is the pathogenesis of Osteoarthritis?
Genetic and mechanical factors predispose to chondrocyte injury –> they release cytokines (TGF-beta, TNF) and factors (MMPs) that change the ECM (degradation exceeds synthesis) –> chondrocyte loss and degraded matrix
What is the clinical presentation of Osteoarthritis?
-Hips, knees, lower spine, phalanges (Heberden nodes-osteophytes in women); can affect the TMJ
-Pain that increases with use; morning stiffness for about 30 min; crepitus; limited range of motion
-Joint deformity but not joint fusion can occur; see bony outgrowths from the joint = osteophyte (bone spur)
What is the tx of Osteoarthritis?
Pain management and inflammation reduction with NSAIDs, intra-articular steroids, reduce use, joint replacement (arthroplasty)
-Unfortunately, can’t prevent or halt progression
Describe Gout
Acute inflammatory arthritis due to formation of urate crystals (tophus) in joints (big toe, ankle and wrists); can also affect kidney and ear lobes
What is the pathogenesis of Gout?
Excess uric acid (from purine metabolism) –> hyperuricemia and urate crystal precipitation
What is the pathophysiology of Gout?
Precipitated urate is extremely irritating and evokes an acute inflammatory response causing extreme pain, redness and swelling
What is the tx for Gout?
Colchicine; avoid red meat and alcohol
