bone pathology Flashcards
bone forming cells
osteoprogenitor cells
osteoblasts
osteocytes (quiescent /mature osteblast)
bone composition
type of connective tissue
(35%) 1/3 organic - cells/collagen and osteoid (proteinaceous matrix)
(65%) 2/3 inorganic - calcium hydroxyapatite
calcium hydroxyapatite
bones inorganic matrix - gives the hardness properties
storehouse for 99% of bodies calcium
85% pf phosporus
65% of body’s sodium and magnesium
is osteoid unmineralized or mineralized
unmineralized - organic
microscopically two types of bones
woven bone -
lamellar bone
what activates /regulates osteoclasts?
PARACRINE MECHANISM REGULATING OSTEOCLASTS –> with RANK receptor and RANK ligand –> interaction causes activation of transcription factors that activate the precursor cell to differentiate into an osteoclasts
T/F osteoblasts have a receptor for RANK
this is true - so we see a balance in the paracrine signaling
osteoprotegrin
decreases the osteclasts formation by preventing Rank ligans from interacting with the receptor
receptors on osteoblasts
for hormones like PTH. vitamin D, estrogen, cytokines, growth factors, and ECM matrix proteins
epiphysis
ends of the long bones where we can see growth plate and have production of bone
metaphysis
flairing of the epiphysis
diaphysis
central core part of the bone - between the epiphysis
layers of bone
periosteum –> compact (hard and thick) –> medullary bone–> that has the trabecular network of bone with the bone marrow between the networks) this is SPONGY BONE
BONE MASS CONTINUUM
peaks at age 30
Achondroplasia
Most common form of dwarfism
developmental disorder in bone
due to a POINT mutation in the FGFR3 (fibroblast grwoth factor receptor 3)
effecting all bones that form from endochondrial ossification because the FGFR3 is inhibiting chondrocyte proliferation so we dont see growth in the epiphyseal plates really -stunting the growth of long bones
normal thorax/trunk but do have bowing of legs, lordotic posture, bulging forehead
inherited in autosommal dominant manner
Thanatrophic dwarfism
more severe than achondroplasia and also is due to a mutation in FGFR3 - but different one - also see reduce in thorax size which compromises the ability of the lungs to expand and this is lethal and will die from a respiratory failure
diseases of decreased bone
Osteogenesis imperfecta –> defective type 1 collagen so aka brittle bone disease - DENTIN IN TEETH ALSO COMPROMISED
Osteoporosis -decrease in bone mass with primary (age and onset of menopause) and secondary causes
types of osteoporosis
disuse - localized like having a cast
metabolic bone - generalized - more common and associatiated with post menopausal woman and elderly
maximize bone mass/ density
try and do this before age 30 to increase peak bone density
nutrition - sufficient amounts of calcium and vitamin d supplements
exercise
bisphosphonate
decreases bone resorption
diagnosis of osteoporosis
radiographic technique that screen the bone density
dual energy absorptiometry and quantatiative computed tomography
diseases associated with osteoclast dysfunction
osteopetrosis and paget’s disease
Paget Disease
prominent CEMENT LINES
diseases associated with abnormal mineral homeostasis
Rickets/osteomalacia
hyperparathyroidism
osteonecrosis and causes
aka avascular necrosis
- osteonecrosis is an ischemic event with resultant bone and marrow infarction (loss of blood supply)
caused by sickle cell disease, vascular compression or disruption following a fracture, thromboembolic event, treatment with steriods, and vasculitis
two types of osteomyelitis
bacteria (pyogenic)
Tuberculous
pyogenic osteomyelitis
inflammation of the bone marrow due to infectious etiology
starts out as an acute systemic illness
Staphylococcus aureus is the most frequent bacteria causing this
caused by three ways
- hematogenous dissemination - infection through blood stream
- extension from an infection in an adjacent joint or soft tissue
- traumatic implantation after compound fractures or orthopedic procedure
pyogenic osteomyelitis
inflammation of the bone marrow due to infectious etiology
starts out as an acute systemic illness
Staphylococcus aureus is the most frequent bacteria causing this
caused by three ways
- hematogenous dissemination - infection through blood stream
- extension from an infection in an adjacent joint or soft tissue
- traumatic implantation after compound fractures or orthopedic procedure
bacteria involved in osteomyelitis
STaph. aureus
E. coli and group B strep in neonates
salmonella (common in sickle cell disease)
mixed bacteria including anaerobes - likely in bone trauma
two types of osteomyelitis and main causes
bacteria (pyogenic)
Tuberculous
pyogenic Bacteria and mycobacterium tuberculosis are the most common causes
pyogenic osteomyelitis clinical findings
characteristic radiograph findings such as destructive lytic focus surrounded by a sclerotic rim
biopsy and bone culture usually rewuired to identify pathogen
Gardner’s syndrome
when there are multiple osteomas present (especially in mandible) this may be the cause
Osteoma
benign overgrowth of bone most commonly seen in the head and neck region.
usually solitary, however when multiple present (like in mandible may be gardners syndrome) and could cause compression - but not locally invasice or malignant
Gardner’s syndrome
when there are multiple osteomas present (especially in mandible) this may be the cause
Osteoid osteoma and osteoblastomas
benign bone-producing neoplasms with similar histological features
2nd and 3rd decade
involve the cortex
osteoid osteoma - smaller (less than 2 cm) and localized bone pain can be treated with aspirin
osteoblastomas - present with diffuse bone pain usually in the vertebral area and bigger than 2cm - aspirin does not relieve the pain
Osteoid osteoma and osteoblastomas
benign bone-producing neoplasms with similar histological features
2nd and 3rd decade
involve the cortex
osteoid osteoma - smaller (less than 2 cm) and localized to the proximal femur and tibia bone pain can be treated with aspirin
osteoblastomas - present with diffuse bone pain usually in the vertebral area and bigger than 2cm - aspirin does not relieve the pain
osteosarcoma
bone-producing malignant mesenchymal tumor
most common behind myeloma and lymphoma in primary tumor of the bone
bi-modal age distribution
75% occurring before age 20 and second peak in elderly
show specific anatomical involvement with 60% occuring at the knee region (proximal tibia with distal femur) 15 % in iliac bone
10% in proximal humerus
8% in the jaw (mandible)
most ostecarcomas occurring in the metaphysis
primary and seconday osteosarcomas
primary - young patients with no known specific underlying cause
secondary - more common in elderyl and could be from Paget disease or previous radiation exposure
genetic mutations seen in osteosarcomas
Retinoblastoma gene (RB) mutated in 60-70% of tumors
p53 mutations
cylcins, cyclin-dependent kinases, kinase inhibitors
primary and seconday osteosarcomas
primary - young patients with no known specific underlying cause (most common type)
secondary - more common in elderyl and could be from Paget disease or previous radiation exposure
genetic mutations / pathogenesis seen in osteo-sarcomas
Retinoblastoma gene (RB) mutated in 60-70% of tumors
p53 mutations
cylcins, cyclin-dependent kinases, kinase inhibitors
characteristics of primary osteosarcoma
solitary, intramedullary, poorly differentiated, and producing a predominately bony matrix
treatment yields 60-70% survival
first treat with chemo then limb-salvage - excising the bone completely
secondary with metastasis does not respond well to treatment
characteristics of primary osteosarcoma
solitary, intramedullary, poorly differentiated, and producing a predominately bony matrix - most in the metaphysis
treatment yields 60-70% survival
first treat with chemo then limb-salvage - excising the bone completely
secondary with metastasis does not respond well to treatment
most likely metastasis for bone cancer
lung - 10/20% of first time diagnosis will present with pulmonary metastases
cartilage forming tumors
osteochondroma
chondroma
chondrosarcoma
osteochondroma
benign cartilage capped outgrowth attached by a bony stalk to the underlying bone.
cap is composed of hyaline cartilage resembling a disorganized growth plate undergoing endochondral ossification
chondroma and two names depending on region
benign tumors of hyaline cartilage
arise within medulla = enchondromas
arise on the bone surface = juxtacorticol chondromas
chondrosarcoma location and defintion
malignant tumor of cartilage - made of malignant chondrocytes
common in the pelvis, shoulder, and ribs- presenting with painful, progressively enlarging masses
arise within the medullary cavity of the bone to form an expansile glistening mass that erodes the cortex
clinical aspects / manifestations/ details about chondrosarcoma
eroding the cortex
malignant chondrocytes show atypia in the form of hyperchromatic nuclei and multinucleation
matrix is composed of hyaline cartilage and myxoid cartilage
tumor grade determination of chondrosarcomas
grade 1,2,3 determined by cellularity, cytologic atypia, and mitotic activity
low grade - resembles normal cartialge
higher grade - contain pleomorphic chondrocytes with frequent mitotic figures
correlation between grade and biologic behavior of a chondrosarcoma tumor
DIRECT correlation
low grade - 80-90% chance survival and rarely metastasize
vs 43% chance in high grade -
bigger more aggressive (larger than 10 cm) and can metastasis to lungs and distant bone
Ewing Sarcoma
primary, malignant small round-cell tumor of bone.
PEDIATRIC TUMOR seen between ages 10-15 years old.
Caucasian population >
femur diaphysis or pelvic flat bones
approximately 95% of patients have TRANSLOCATIONS OF t(11;22) (q24;q12) or t(21;22)(q22;q12)
PNET
primitive neuroectodermal tumor - close relationship to Ewing’s sarcoma but involves soft tissue and more neural differentiation
metastatic disease
metastatic tumors involving bone is more common than a primary bone tumor.
in adults more than 75 % of skeletal metastasis originate from cancers in the prostate, breast, kidney, and lung
Common causes/sources of pediatric bony metastases
neuroblastoma, Wilm’s tumor, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma
