Chapter 26: Bones and Joints Flashcards
Type of Bone formation:
Bones of axial and appendicular skeleton, base of skull
Cartilaginous model of bone is first made by chondrocytes (CT matrix). Osteoclasts and osteoblasts later replace (calification and mineralization) w/woven bone and then remodel to lamellar bone. Growth plates expand with proliferation of chondrocytes
In adults, woven bone occurs after fractures and in Paget disease
Endochondral ossification
Type of Bone formation:
Bones of calvarium and facial bones.
Woven bone formed directly w/o cartilage
Later remodelled to lamellar bone
Membranous ossification
Intramembranous
How do osteoblasts build bone?
Secrete collagen and catalyzing mineralization
Differentiate from mesenchymal stem cells in periosteum
How do osteoclasts resorb bone? Ie. bone break down
Multinucleated cells that dissolve bone by secreting acid and collagenase. Differentiate from monocytes/macrophages.
How does estrogen protect bone?
Inhibits apoptosis in bone-forming osteoblasts and induced apoptosis in bone-resorbing osteoclasts. If estrogen deficient (postmenopause), excess remodeling cycles and bone resorption lead to osteoporosis.
Failure of longitudinal bone growth at growth plate (endochondral ossification) => short limbs
Membranous ossification no affected => large head relative to limbs
Dwarfism, normal lifespan and fertility
Due to what mutation?
Achondroplasia
ACTIVATING MUTATION/constitutive activation in fibroblast growth receptor 3 (FGFR3) related to increased paternal age
Overexpression inhibits growth/chondrocyte proliferation
trivia: which famous Game of Thrones character has a condition due to impaired cartilage proliferation in the growth plate
Peter dinklage! Tyrion Lannister. DUHH bitches. Too easy.
Trabecular (spongy) bone loses mass and interconnections despite normal bone mineralization and lab values (Ca and phosphate).
How do you diagnose?
Can be caused by long term exogenous steroid use
Bone pain and Increased risk for fractures, vertebral crush fractures (acute back pain, loss of height, kyphosis)
Osteoporosis
DEXA scan T-score
Postmenopausal: increased bone resorption due to decreased estrogen levels
Femoral neck fractures, distal radius (Colles) fracture
Type 1 osteoporosis
Senile: affects men and women > 70 yo
Prophylaxis: regular weight bearing exercise and adequate calcium and vit D intake throughout adulthood
Treatment?
Type 2 osteoporosis
Treat: bisphosphonates, PTH, SERMS, rarely calcitonin, denosumab (monoclonal antibody against RANK-L), weight bearing exercise, vit D, calcium
Congenital defect of bone, weak bone AD defect in Type I collagen synthesis Multiple fractures of bone Blue sclera Hearing loss (middle ear bones easily fracture)
Osteogenesis imperfecta
“brittle bone disease”
Inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily
Due to poor osteoclast function
Due to what enzyme defect?
Bone fractures
Anemia, thrombocytopenia, leukopenia with extramedullary hematopoiesis (due to bony replacement of the marrow)
Vision and hearing impairment (impingement of CN)
Hydrocephalus (narrowing of foramen magnum)
Renal tubular acidosis (metabolic acidosis from CA2 mutation)
Treatment?
Osteopetrosis
“stone bone disease” “marble bone disease”
carbonic anhydrase II mutation leads to loss of the acidic environment required for bone resorption (need acidic env to remove calcium from bone)
Treat: bone marrow transplant, osteoclasts are derived from monocytes
Defective mineralization/calcification of osteoid => soft bones that bow out.
Due to Decreased Vit D => decreased serum calcium => increased PTH secretion => decreased serum phosphate
Hyperactivity of osteoblasts => increased Alk Phos (osteoblasts require alkaline env to build bone)
Rickets in children
Osteomalacia in adults
Abnormal bone mineralization Low Vit D Pigeon-breast deformity Frontal bossing (enlarged forehead) Rachitic rosary (osteoid deposition at the costochondral jxn) Bowing of the legs
Rickets
Common, localized disorder of bone remodeling caused by increase in both osteoblastic and osteoclastic activity. Doesn’t involve entire skeleton.
3 stages:
1) osteoclastic (lytic)
2) mixed
3) osteoblastic (sclerotic)
Unknown cause: maybe viral
Thick, sclerotic bone that fractures easily
Long bone chalk-stick fractures
Mosaic pattern of lamellar and woven bone
Paget Disease of Bone
Bone pain
Increasing hat size
Hearing loss
Lion-like facies
Isolated elevated alk phos (normal Ca, phosphate, PTH)
What are two complications to worry about?
Paget Disease of Bone
1) High-Output cardiac failure due to formation of AV shunts in bone (increased blood flow)
2) Osteosarcoma b/c osteoblasts at stage 3 could become mutated
Infarction of bone and marrow, usually very painful.
Caused by trauma, high-dose corticosteroids, alcoholism, sickle cell, caisson disease (gas emboli lodge in bone).
Most common site is femoral head (due to insufficiency of medial circumflex artery).
Osteoarthritis and fracture are major complications.
Avascular (asceptic) necrosis
“Brown tumors” due to fibrous replacement of bone, subperiosteal thinning
Osteitis fibrosa cystica
Brown tumors due to fibrous replacement of bone, subperiosteal thinning
Causes: Idiopathic or parathyroid hyperplasia, adenoma, carcinoma (Name type)
Labs: increased Ca, decreased phosphate, increased alk phos, increased PTH
Osteitis fibrosa cystica
Primary hyperparathyroidism
Brown tumors due to fibrous replacement of bone, subperiosteal thinning
Causes: Compensation for end stage renal disease (decreased phosphate excretion and production of activated vit D)
Labs: decreased Ca, increased phosphate, increased alk phos, increased PTH
Osteitis fibrosa cystica Renal osteodystrophy (result from chronic renal failure) result of 2ndary hyperparathyroidism
Increase serum Ca, increased phosphate, decreased PTH, alk phos no change
Caused by over supplementation or granulomatous disease (sarcoidosis)
Hypervitaminosis D
Benign tumor of bone
Commonly arises on surface of facial bones
Associated with Gardner syndrome
Osteoma
Gardner = FAP + fibromatosis of peritoneum + osteomas
Benign tumor of osteoblasts (that produce osteoid) surrounded by a rim of reactive bone
Arises in cortex of long bones
Occurs in young adults
Osteoid osteoma
Imaging: bony mass > 2cm, arises in vertebrae, bone pain does not resolve w/aspirin
Osteoblastoma
Most common benign tumor of bone
tumor of mature bone with an overlying cartilage cap
Males
Osteochondroma
2nd most common primary malignant bone tumor (after multiple myeloma)
Malignant proliferation of osteoblasts
Pathologic fracture or bone pain w/swelling
Imaging: lucent sunburst pattern on x-ray, MRI heterogenous mass w/periosteal elevation (Codman triangle)
Arises: metaphysis of long bones, distal femur or proximal tibia (around knee)
Osteosarcoma
Who does osteosarcoma affect commonly? Risk factors?
Bimodal distribution:
10-20 yo
>65 yo
[RF: familal retinoblastoma, Paget disease, radiation, Li-Fraumeni syndrome (germline p53 mutation)]
Locally aggressive benign tumor often around knee
Arises in epiphysis of long bones
20-40 yo adults
Soap bubble appearance on X-ray
Giant cell tumor
comprised of multinucleated giant cells and stromal cells
Malignant proliferation of poorly differentiated (anaplastic) cells derived from neuroectoderm
Arises in diaphysis of long bones
Male children
Ewing sarcoma
Confused with lymphoma or chronic osteomyelitis
t(11;22)
11 + 22 = 33 (Patrick ewing’s jersey number)
Benign tumor of cartilage
Usually arises in medulla of small bones of hands and feet
Chondroma
Rare, malignant, cartilaginous tumor
Arises in medulla of pelvis or central skeleton, spine, scapula, humerus, tibia or femur
Men 30-60 yo
Expansile glistening mass w/i the medullary cavity
Chondrosarcoma
