MSK: 18.1: Skeletal System Flashcards
What is teriparatide?
- an osteoporosis tx drug
- Causes increased bone growth compared to antiresorptive therapies (eg bisphosphonates)
How is osteomyelitis diagnosed?
- blood culture
- elevated CRP and ESR
- x-ray and MRI
Why are the sclera blue in osteogenesis imperfecta?
- sclera usually contain lots of Type I collagen
- in O.I., the sclera are thin –> exposure of the choroidal veins
How do SERMs work to treat osteoporosis?
estrogen receptor agonist in bone
Dx?
- imbalance btw osteoclast and osteoblast function (clasts get out of control and blasts try to compensate)
- a localized process not involving the entire skeleton
Paget Disease of the Bone
Why do osteopetrosis pts get hydrocephalus?
narrowing of the foramen magnum
What causes Paget Disease of the Bone?
unknown- maybe viral
Why do pts with Paget Disease of the Bone get high output cardiac failure?
bone remodling = formation of AV shunts –> heart has to work harder to push against them
Dx?
- defective mineralization of osteoid due to low levels of Vitamin D
osteomalacia/Rickets
Which SERM is a good tx for osteoporosis?
Raloxifene
Where does osteomyelitis seed in adults? Children?
- adults = epiphysis
- children = metaphysis
When is alkaline phosphatase (ALP) high?
when osteoblasts are activated
What is endochondral bone production and what bones does it make?
- cartilage matrix is calcified and mineralized into bone
- long bones
An ______ environment is necessary in order to lay down Ca++ and therefore calcify and build bone.
alkaline
What are the clinical features of osteoporosis?
- bone pain and fractures in weight-bearing areas
What is osteoarthritis?
a wear and tear disease in which the joints are damaged
What is osteogenesis imperfecta?
congenital defect of bone formation, resulting in weak bones
Which drug gives these SEs?
- Esophagitis (if taken orally, patients are advised to take with water and remain upright for 30 minutes)
- osteonecrosis of jaw
- atypical stress fractures
- bisphosphonates
- all end in -dronate
- ex: Alendronate, ibandronate, risedronate, zoledronate
What are the SEs of bisphosphonates?
- Esophagitis (if taken orally, patients are advised to take with water and remain upright for 30 minutes)
- osteonecrosis of jaw
- atypical stress fractures
What is Caisson disease?
- nitrogen bubbles precipitate in ascending divers, causing air emboli
- aka “the bends” or decompression sickness
Give the serum levels for osteomalacia/Rickets:
- Ca++?
- PO4?
- Alk Phos (ALP)?
- PTH?
- Ca++ = decreased
- PO4 = decreased
- ALP = increased
- PTH = increased
Bone formation is a balance btw the ______, which lay down bone, and the _____, which resorb bone.
- osteoblasts = build
- osteoclasts = crack
What is achondroplasia?
impaired cartilage prolif. in the growth plates
Dx?
- carbonic anhydrase II mutation
osteopetrosis
Give the serum levels for osteoporosis:
- Ca++?
- PO4?
- Alk Phos (ALP)?
- PTH?
- Ca++ = normal
- PO4 = normal
- ALP = normal
- PTH = normal
Dx?
AD defect in collagen type I synthesis
osteogenesis imperfecta
Name the 2 most common forms of osteoporosis.
- senile (age-related)
- post-menopausal (estrogen loss)
What cells make cartilage?
chondrocytes
What are the complications of Paget Disease of the Bone?
- high output cardiac failure
- osteosarcoma
What does PTH bind to when released? What does this do?
osteoblasts –> tells osteoclasts to resorb bone (osteoblasts control osteoclasts)
Osteosarcoma is a malignant tumor of _______.
osteoblasts
What organism causes osteomyelitis most often in pts with prosthetic joints?
- Staph aureus
- S epidermidis
What diagnoses osteoporosis?
- DEXA scan T-score of less than 2.5
- fragility fracture of hip or vertebra
What is intramembranous bone production and what bones does it make?
- produce bone from a CT matrix
- makes skull, chest, wrist- **flat bones
Name a hormone that is protective for maintaining bone mass.
estrogen
What are the clinical features of achondroplasia?
- short extremities
- normal-sized head and chest
- normal cognition, life span, and fertility
What causes avascular (aseptic) necrosis?
- lack of blood flow to the bone from:
- Corticosteroids
- Alcoholism
- Sickle cell (dactylitis of bones of hands and feet)
- Trauma/fracture
- “the Bends” aka caisson disease (gas emboli in the bone)
- LEgg-Calvé-Perthe disease
- Gaucher disease
- Slipped capital femoral epiphysis
- ***“CAST Bent LEGS”
What causes osteomyelitis?
bacterial infection –> hematogenous spread
What is denosumab? How does it work?
- a monoclonal Ab against RANKL
- tx for osteoporosis
- inhibits osteoclast maturation
What is avascular (aseptic) necrosis?
painful focal, ischemic necrosis of the bone and marrow
What organism causes osteomyelitis most often overall?
Staph. aureus
What is the function of vitamin D? Where does it do this?
- allows absorption of Ca++ and PO4- (maintain their levels in the blood)
- in the kidney, intestine, and bones
What causes osteomalacia/Rickets?
defective mineralization of osteoid due to low levels of Vitamin D
What drug is contraindicated in osteoporosis? Why?
- glucocorticoids
- increase the risk of osteoporosis
An acidic environment is necessary in order to ______ and therefore _____ bone.
remove Ca++ –> resorb bone
What are the SEs of teriparatide?
Transient hypercalcemia
How do bisphosphonates work?
- they are pyrophosphate analogs
- bind hydroxyapatite in bone –> inhibit osteoclast activity
What is the most common site of avascular (aseptic) necrosis? Why?
- the femoral head
- insufficiency of medial circumflex artery
______ is a malignant tumor of osteoblasts.
Osteosarcoma
How is osteogenesis imperfecta inherited?
AD
What organism causes osteomyelitis after a dog or cat bite or scratch?
Pasteurella multocida
Dx?
- x-ray showing a lytic focus (liquefactive necrosis) surrounded by sclerosis
osteomyelitis
Why do osteogenesis imperfecta pts have hearing loss?
bc the ossicles fracture, too
What are SERMs? Name 2 of them.
- Selective Estrogen Receptor Modulators
- tx for osteoporosis, breast CA
- ex: Tamoxifen and Raloxifene
How is achondroplasia inherited?
it’s auto dominant, but most mutations are sporadic
What genetic defect causes osteopetrosis?
- there are multiple variants
- ex: carbonic anhydrase II mutation –> lack of acidic environment req’d for absorption of bone
Where is Type I collagen found?
- bone
- “bONE has ONE in it”
What determines the risk of osteoporosis?
- peak bone mass
- the rate of bone loss thereafter
Why do pts with Paget Disease of the Bone get osteosarcoma?
- osteoblasts = lots of bone production
- If they get mutated –> osteosarcoma
What are the x-ray findings for Rickets?
- osteopenia
- “Looser zones”- pseudofractures
- epiphyseal widening
- metaphyseal cupping/fraying
What are the clinical features of osteomyelitis?
- bone pain
- fever (infection)
- leukocytosis (infection)
What organism causes osteomyelitis most often in sexually active pts?
Neisseria gonorrhoea (this is rare)
What are the clinical features of osteopetrosis?
- bone fractures
- anemia/thrombocytopenia/leukopenia (pancytopenia) with extramedullary hematopoesis
- vision and hearing impairment
- hydrocephalus
- renal tubular acidosis
Name and describe the 2 ways by which bone can be formed.
- intramembranous (produce bone from a CT matrix- makes skull, chest, wrist- flat bones)
- endochondral (cartilage matrix is calcified and mineralized into bone- long bones)
An alkaline environment is necessary in order to _____ and therefore _______.
lay down Ca++ –> calcify and build bone
Dx?
- a wear and tear disease in which the joints are damaged
osteoarthritis
What are the clinical features of Paget Disease of the Bone?
- bone pain (microfractures of the bone)
- increasing hat size (thick skull bones)
- hearing loss (cranial nerve impingement)
- lion-like faces (thickened facial bones)
- isolated elevated Alk phosphatase (bc of blast activity)
What is the end result of Paget Disease of the Bone?
thick, sclerotic bone that fractures easily
What is osteoid? Where does it come from?
- the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone
- from osteoblasts
What is Paget Disease of the Bone?
- imbalance btw osteoclast and osteoblast function (clasts get out of control and blasts try to compensate)
- a localized process not involving the entire skeleton
What is the tx for osteopetrosis?
bone marrow transplant
What do bisphosphonates end in?
- -dronate
- ex: Alendronate, ibandronate, risedronate, zoledronate
Dx?
- activating mutation in FGFR3
achondroplasia
What is osteopetrosis?
an inherited defect of bone resorption (osteoclasts) –> abnormally thick, heavy bone that fractures easily
What do osteoblasts produce?
osteoid
Osteoclasts are derived from ______ cells.
monocytes
What organism causes osteomyelitis most often in sickle cell pts?
Salmonella
Dx?
- painful, focal, ischemic necrosis of the bone and marrow
avascular (aseptic) necrosis
What cell controls osteoclasts?
osteoblasts
What is a fracture of the distal radius called?
Colles fracture
What is vitamin D deficiency in children called?
Rickets
What causes osteogenesis imperfecta?
defect in collagen type I synthesis
Name the drug class and give an example:
- they are pyrophosphate analogs
- bind hydroxyapatite in bone, inhibiting osteoclast activity
- bisphosphonates
- all end in -dronate
- ex: Alendronate, ibandronate, risedronate, zoledronate
What has to happen to osteoid in order to make true bone?
it has to be mineralized with Ca++ and PO4-
What are the x-ray findings of osteomyelitis?
lytic focus (liquefactive necrosis) surrounded by sclerosis
Why do osteopetrosis pts get renal tubular acidosis?
Lack of carbonic anhydrase –> decreased tubular reabsorption of bicarb and no elimination of acid –> metabolic acidosis
What are the clinical features of osteogenesis imperfecta?
- blue sclera
- multiple fractures of bone
- hearing loss
What are the SEs for SERMs?
- both = increased risk of thromboembolic events
- Tamoxifen = increased risk of endometrial CA, hot flashes
An ______ environment is necessary in order to remove Ca++ and therefore resorb bone.
acidic
Dx?
- an inherited defect of bone resorption (osteoclasts)resulting in abnormally thick, heavy bone that fractures easily
osteopetrosis
How old is a pt that gets Paget Disease of the Bone?
late adult (usu around 60yo)
What organism causes osteomyelitis most often in diabetic pts?
Pseudomonas
What drugs can cause osteoporosis?
- steroids
- alcohol
- anticonvulsants
- anticoagulants
- thyroid replacement therapy
H2O + CO2 –> H2CO3 via what enzyme?
carbonic anhydrase
What will Paget Disease of the Bone look like on histology?
thick bone with “cement lines” (looks like puzzle pieces- Mosaic pattern of woven and lamellar bone)
Name 2 complications of avascular (aseptic) necrosis.
- osteoarthritis
- fractures
Dx?
- loss of trabecular bone mass –> porous bones easily fracture
osteoporosis
What causes vitamin D deficiency?
- low sun exposure
- poor diet
- malabsorption
- liver/renal failure
What x-ray findings will be seen in osteopetrosis?
thickened, completely white bone (no dark space of the medulla)
Give the serum levels for Pagets Disease of the Bone:
- Ca++?
- PO4?
- Alk Phos (ALP)?
- PTH?
- Ca++ = normal
- PO4 = normal
- ALP = increased
- PTH = normal
What medical conditions can cause osteoporosis?
- hyperparathyroidism
- hyperthyroidism
- multiple myeloma
- malabsorption syndromes
Name some treatments for osteoporosis.
- bisphosphonates
- teriparatide
- SERMs
- rarely calcitonin
- denosumab
Who most often gets osteomyelitis?
children
What is vitamin D deficiency in adults called?
osteomalacia
What causes achondroplasia?
activating mutation in FGFR3
What does Calcitonin do?
inhibits osteoclasts from resorbing bone
Name the 4 phases of Paget Disease of the Bone and their features.
- Lytic = osteoclasts
- Mixed = clasts + blasts
- Sclerotic = blasts
- Quiescent = minimal clast/blast activity
What organism causes osteomyelitis in the vertebra?
- Staph aureus
- Mycobacterium tuberculosis (Pott disease)
What is a myelophthisic process?
- replacement of the bone medulla with bone
- “bone in bone” or “stone bone” appearance on x-ray
What is osteomyelitis?
infection of the bone marrow space and bones
How does Rickets present clinically?
- pigeon breast deformity (inward bending of the ribs with an anterior protrusion of the sternum)
- frontal bossing (deposition of osteoid in skull)
- rachitic rosary (desposition of osteoid at the costochondral junction- feels “bead-like”)
- bowing of legs
Give the serum levels for osteopetrosis:
- Ca++?
- PO4?
- Alk Phos (ALP)?
- PTH?
- Ca++ = normal/decreased
- PO4 = normal
- ALP = normal
- PTH = normal
What organism causes osteomyelitis most often in IV drug abusers?
- Pseudomonas
- Candida
- Staph. aureus
Why do osteopetrosis pts get hearing and vision loss?
impingement on cranial nerves as they exit the skull
How does teriparatide work?
- Recombinant PTH analog given subcutaneously daily
- Increases osteoblastic activity
- Causes increased bone growth compared to antiresorptive therapies (eg bisphosphonates).
What is osteoporosis?
loss of trabecular bone mass –> porous bones easily fracture
What is the tx for Paget Disease of the Bone?
- calcitonin
- bisphosphonates (all end in -dronate ex: Alendronate, ibandronate, risedronate, zoledronate)