Bone Physiology Flashcards
______ is dense and used for support
Compact bone
____ or ____ forms a calcified lattice
spongy bone or trabecular bone
What is the primary responsibility of bone?
to develop and maintain mass and architecture sufficient to carry functional loads without fracture.
______: occurs when resorption precedes formation
re-modeling (structure present, then taken down, then remodeled)
4 stages of bone re-modeling
1)quiescence
osteoclasts: recruitment, differentiation, activation
2)resorption
osteoblasts: recruitment, proliferation
osteoclasts: apoptosis, removal
3)reversal
matrix synthesis
4)formation
mineralization
_______ are unique bone resorbing cells of the monocyte-macrophage lineage
osteoclasts
characteristics of osteoclasts:
nucleus - _______
activated by - ______
multinucleated
receptor activator of nf kappa b ligand (RANKL)
Osteoclasts:
polarization facilitates _____, _______, and _____
clear zone, ruffled border formation, and bone resorption
disease in which osteoclasts are unable to resorb bone. What is the shape seen on X-ray?
Osteopetrosis
erlenmeyer flask appearance
bone remodeling is accelerated with _______
age
Name some other scenarios in which osteoclasts would be more active than osteoblasts
low testosterone
low estrogen
low systemic calcium levels
osteoblasts come from what progenitor cell?
mesenchymal cells
mesenchymal cells can differentiate into which cells?
what is the determining factor?
chondrocytes, myoblasts, adipocytes, and tendon cells
TRANSCRIPTION FACTORS
osteoblasts make ______, express the ______ receptor, also produce ____ and ____ (ECM proteins),
type I collagen, EXPRESS PARATHYROID HORMONE RECEPTOR, osteocalcin and bone sialoprotein
osteoblast transcription factor: ______
Runx2, (Runx2 -/-mice don’t make bone)
______ have osteoblast phenotype
osteocytes
Sclerostin is made in _____, blocks _____, and inhibits _____.
osteocytes, Wnt signaling, bone formation.
disease associated with sclerostin?
osteosclerosis (sclerostin always missing)
_________ molecules are a fundamental control of bone remodeling.
Wnt signaling molecules
Name two ways to increase bone formation.
- ab to RANKL would decrease the availability of RANKL to bind osteoblasts and activate osteoclasts, and would increase bone mass.
- Ab that inhibits sclerostin would unblock Wnt signaling and lead to increased bone formation.
______ are the most abundant cell type in bone
osteocytes
osteocytes are ______ in origin
mesenchymal
bone formation inhibitor associated with osteocytes?
sclerostin
sclerostin plays a role in both ____ and ____
bone modeling and bone remodeling
Name some diseases of altered calcium homeostasis and bone metabolism.
osteoporosis osteopetrosis osteosclerosis cancer diabetes, cardiovascular disease, treatment side-effects
decrease in _____ is associated with increased Fracture risk
bone mineral density (BMD)
mortality rate associated with hip fractures
24%
________ inhibit bone resorption by inhibiting farnesyl synthase and preventing formation of __________
bisphosphonates
ruffled border
bisphosphonates reverse _____ and decrease ____
bone loss
bone turnover
two treatments for osteoporosis?
bisphosphonates and blocking RANKL
Current treatment used to block RANKL?
Xgeva, used to block downstream differentiated products, blocking eventual formation of osteoclasts (WITHOUT INTERFERING WITH PROGENITOR CELL)
a bone disease that makes bones abnormally dense and prone to fracture. Associated with diminished OSTEOCLAST function. Characterized by skeletal fragility.
osteopetrosis
a bone disease of abnormal hardening of bone and an elevation in density. Associated with increased OSTEOBLAST function. Characterized by increased bone mass.
osteosclerosis
______ ______ is associated with hypercalcemia, nerve compression, bone pain, and fracture.
bone metastasis
bone metastasis is facilitated by the activity of ______
osteoclasts (intravasation, homing and survival, extravasation)
Therapeutic targets blocking steroid-dependent tumor cell proliferation
androgen and estrogens via aromatase inhibitors
treatments for cancer can cause ___ and ____
osteopenia and osteoporosis
how does type 2 diabetes increase risk of bone fracture?
- hyperglycemia and hypercalciuria lead to low bone turnover.
- hyperinsulinemia, hyperglycemia, treatment with TZD, low vitamins (D) leads to lone bone quality.
- concomitant meds, cataracts, peripheral neuropathy, retinopathy, ulcers, hypoglycemia, nocturia can all increase the risk of falls
correlation between cardiovascular disease and PTH?
increased risk of vascular disease over time with high levels of PTH
bone fractures are a major risk factor with significant morbidity and mortality with which age group?
ANY AGE GROUP!!!!
DISEASE: the skeleton plays a central role in _____, _____, and ____
disease development, response to treatment, and quality of life.
