Bone disorders I

Question 1

bone structure: cortical vs. trabecular

Answer 1

cortical and trabecular bone
cortical bone is dense and non-porous. it provides most of the structural strength of the skeleton
trabecular boneis continuous with the inner surface of cortex. it has a plate and bar structure arranged along lines of stress and strain
more metabolically active portion of bone
bone marrow fills the spaces

Question 2

diaphysis, metaphysis, and epiphysis ratios of trabecular: cortical bone

Answer 2

diaphysis: mostly cortical
metaphysis: large portion of trabecular bone
epiphysis: growth, articular structure, and subchondral bone

Question 3

What is in the extracellular matrix of bone

Answer 3

collagen, and calcium hydroxyapatite

Question 4

From where are osteoblasts dervied?

Answer 4

mesenchymal stem cells

Question 5

what do osteoblasts do? What receptors do they have? What do they produce?

Answer 5

synthesize organic bone matrix
have estrogen, PTH, and vitamin D receptors
produce OPG (a decoy receptor), RANK ligand, and alkaline phosphatase

Question 6

What are osteocytes? What do they do? where do they come from? What do they respond to?

Answer 6

they come from osteoblasts encased in matrix

they no longer form bone, though they remain connected to cells on the bone surface
they respond to mechanical signals and influence remodeling. they also stimulate a systemic response

Question 7

Where to osteoclasts come from? What do they do? What stimulates them? What do they secrete?

Answer 7

come from monocyte precursors
They are stimulated by RANK ligand and M-CSF
the resorb bone at ruffled membrane and secrete protons, lysosomal enzymes, and MMPs (matrix metalloproteins)

Question 8

What is the RANK/RANK ligand system?

Answer 8

RANK is a receptor on the osteoclast
RANK ligand is a signal on the surface of osteoblasts. Osteoblasts secrete RANK-ligand
OPG is a decoy receptor and an inhibitor of RANK ligand, also secreted by osteoblasts.
This is part of what drives the process of bone remodeling

Question 9

How does age contribute to osteoporosis?

Answer 9

after age 30, bone turnover usually does not replace the full bone unit

Question 10

What hormones/minerals are also important in the process of osteoporosis, besides the cells themselves?

Answer 10

calcium, vitamin D, parathyroid hormone, and calcitonin

Question 11

Calcitonin: who makes it, what does it do

Answer 11

made by thyroid C cells (parafollicular cells)
causes osteoclasts to shrink, inhibits resorption of bone, and causes lose of the ruffled border
also decreases calcium and phosphate resorption in the kidney

Question 12

What are the two categories of osteoporotic diseases (based on pathogenesis)

Answer 12

osteoclast-mediated bone loss: too much resorption
aka high turnover osteoporosis. primary form that occurs at menopause. High n-telopeptide

osteoblast-mediated bone loss: normal resorption with not enough subsequent bone building
aka low turnover osteoporosis. occurs in elderly and in ppl with underlying genetic collagen disease.

Question 13

Common fracture sites for a pt with osteoporosis

Answer 13

spine, wrist, and hip

Question 14

bone mass vs. bone quality in osteoporosis

Answer 14

mass plus distribution = strength
the architecture of the bone matters- distrubtion and balance
structural integrity matters: remodeling rate, and collagen structure

Question 15

How do you assess for osteoporosis?

Answer 15

Patients who have fragility fractures (fractures from standing height or less)
Or DEXA scans: low dose radiation to look at bone density
may be diagnostic if the pt hasn’t had a fracture
may help assess severity if the pt has had a fracture
DEXA loos at hip, spine, and forearm. more negative scores mean more osteoporotic.

Question 16

Risk factors for osteoporosis independent of bone mass

Answer 16

age, low body weight, personal or parental hx of fragility fracture, smoking, steroids, inflammatory autoimmune disorder (esp. rheumatoid arthritis), high alcohol intake, drugs that cause bone loss
assess risk with the FRAX calculator.
consider treatment in pts with 3% 10 yr risk of hip fracture or 20% risk of major osteoporotic fracture

Question 17

What lab tests should you do for osteoporosis? What do you look for? In which patients is this particularly important?

Answer 17

always look for secondary causes of osteoporosis- esp. in premenopausal women and men with osteoporosis
look for low vitamin D levels
consider calcium and vitamin D levels, look for 1,25 vitamin D (activated vitamin D) if the pt has kidney failure
look at peak testosterone levels in men
consider evaluation for multiple myeloma

Question 18

What drugs are bad for bones?

Answer 18

steroids

heparin, seizure meds, tetracycline, furosemide, lupron (GNRH agonist), aromatase inhibitors