lec 5- skeletal physiology and pathology

osteoblasts

produce new bone matrix, mainly collagen; help mineralize it w calcium and phosphate

osteoclasts

dissolve mineral, degrade matrix, release calcium and phosphate into bloodstream

central canals

lymphatic drainage, blood vessels, nerves

what is hydroxyapatite

bones are made of several organic/inorganic tissue- primarily made of collagen and hydroxyapatite

hydroxyapatite is made up of

two salts, calcium phosphate, calcium hydroxide

where is hydroxyapatite located

extracullular matrix (ECM); HA crystals are deposited in/around collagen fibers of the bone matrix; form along collagen fibrils, filling gaps between them

HA makes the bone ___ while collagen gives it ___

HA- rigid

collagen- tensile strengths

HA can also be found in the ___

macroscale; throughout both cortical and trabecular bone

two major phases of bone remodeling cycle

resorption, formation

resorption

old bone broken down by osteoclasts; secrete digestive enzymes and H ions to destroy bone matrix

formation

new bone built by osteoblasts; synthesize/secrete collagen fibers, initiate calcification

bone response to injury

hematoma formation, capillaries form, macrophages clean debris, fibroblasts prod. collagen fibers, chondroblasts secrete cartilage matrix, osteoblasts start forming spongy bone

parathyroid hormone (PTH)

raises serum calcium levels by stimulating osteoclast-mediated bone breakdown; causes calcium release into bloodstream

subperiosteal bone resorption

loss of cortical bone along outer surface

brown tumors

benign focal lytic lesions filled w fibrous tissue and blood products

PTH negative feedback loop

decreased blood (plasma) Ca2+, release of PTH, increased osteoclast activity, increased blood Ca2+

PTH negative feedback loop- bone resorption increasing causes

increased serum calcium

Calcitonin negative feedback loop

increased blood Ca2+, release of calcitonin, decreased osteoclast activity, increased osteoblast activity, decreased blood Ca2+

calcitonin is released by

C cells of the thyroid in response to high calcium plasma levels

primary role of calcitonin

lower serum calcium levels (PTH antagonist)

calcitonin inhibiting osteoclast activity does what?

decreases plasma calcium, promotes calcium deposition in bone

NM and PET bone scans are ___, not ___; they detect what?

sensitive, not specific; detect activity, not the cause

Tc-99m labeled phosphate drugs (MDP, HDP) : mechanism

binds to calcium in HA at sites of osteoblastic activity

Tc-99m labeled phosphate drugs (MDP, HDP) : result

sensitive for detecting abnormal bone turnover; sites of new crystal deposition show up bc it’s where HA is laid down (arthritis, lesions)

Tc-99m labeled phosphate drugs (MDP, HDP) : limitation

not specific- uptake occurs in trauma, infections, mets, etc

F-18 NaF : mechanism

fluoride ion exchanges w hydroxyl groups in HA- forms fluorapatite

F-18 NaF : result

sensitive for detecting abnormal bone turnover; better localization than phosphate

F-18 NaF : limitation

not specific

what are common physiological/pathological bone conditions

normal uptake, growth plates, injury, infection, paget’s disease, hyperparathyroidism, mets disease

normal bone scan features

symmetric upatke, high uptake in joints/growth plates, kidney/bladder visible, mild background soft tissue uptake

growth plates in children

active bone formation sites- very high osteoblastic activity; symmetry is key

most obvious growth plate sites

knees, ankles, wrists, shoulders

fracture eval

uptake seen within 24 hrs, uptake usually resolves in 24 months

shin splints

stress induced posteromedial tibia pain; increased uptake in middle to distal tibia

for injury/fracture, what is the imaging protocol

3-phase protocol to assess blood flow into area

vascularity with injury/fracture

increased or decreased perfusion at site of interest

osteomyelitis

infection in bone, increased bone turnover; increased blood flow/soft tissue activity (hyperemia)

cellulitis

soft tissue infection; increased flow/pool, no focal delayed bone uptake

infection of prosthetic joints

uptake at prosthesis interface and diffuse, extending into adjacent bone; increase activity in flow, pool, delays

aseptic loosening of prosthetic joints

linear/rim-like uptake where bone remodeling occurring around prosthesis; no marked flow/pool activity, only on delays

paget’s disease (metabolic bone disease)

chronic condition of disorganized bone remodeling leading to enlarged, weak, deformed bones

pathophysiology of paget’s disease

osteoclastic overactivity (excessive resorption), compensatory osteoblastic activity (chaotic new bone formation)

paget’s disease shows what on a bone scan

intense uptake involving 1+ bones; usually diffuse through entire affected bone. common sites: pelvis, spine, skull, long bones

hyperparathyroidism

chronically elevated PTH; leads to increased bone turnover (both resorption and reactive osteoblastic repair)

hyperparathyroidism on bone scan

whole skeleton looks uniformly “hot”; relative decreased renal visualization; “super scan” pattern (skeleton dominates, kidneys faint/absent)

paranasal sinus uptake suggests

sinusitis (sinus infection)

maxilla/right mandible uptake is typical for

odontogenic disease vs recent procedures/hardware

metastatic disease location: benign

common in long bones, joints, areas of known trauma

metastatic disease uptake: malignancy

frequently spine, pelvis, ribs, skull

mets disease correlative imaging

xray, ct, mri help clarify if uptake is benign/malignant lesion

history of trauma, surgery, growth supports…

benign bone-building

history of known malignancy, unexplained pain, systemic symptoms supports…

suspicion for cancer

mets to bone primarily occurs from what primary cancers?

prostate, breast, lung cancers

cold lesions

osteolytic, i.e. multiple myeloma, renal cell cancers, sarcoma

flare phenomenon

lesion may appear to worsen initially after chemotherapy

most cancers that mets to the bone stimulate…

osteoblastic repair activity around lesion

which cancers do not stimulate osteoblastic processes?

renal cell carinoma, multiple myeloma, sarcoma; these are purely lytic lesions

multiple focal lesions are common in patients with

history of prostate cancer

mult focal lesions on bone scan look like

asymmetrical uptake pattern; focal spots include right scapula, sternum, left 5th rib, several vertebral bodies, femurs