01-31 Metabolic Bone Dz

Question 1

Define osteopenia

Answer 1

radiologic dx
—”low bone mass”
—two subcategories: osteo-malacia & -porosis

confusingly, also used to denote mild osteoporosis more particularly on Dexa scan read-out, so pay attn to context

Question 2

Define osteomalacia
—histo apperance
—clinical complaints/presentation

Answer 2

a pathological dx
—decrease in bone (osteopenia) due only to decreased mineralization; matrix is NOT decreased
—In kids: “rickets” = above + epiphyseal collagen troubles

HISTO
—see lots of osteoid (unmineralized bone; stains orange) that is thicker than usual
—same # of trabeculae as nl bone

PRESENTATION
—skeletal pain/tenderness/fxs diffusely w/o loss of skeletal mass
—prox muscle weak
—”Looser’s zones” = pseudofractures on x-ray

Question 3

Define osteoporosis

Answer 3

a pathological dx
—both a decr in matrix and mineralization that puts pt at increased r/o fx (esp hip, spine and distal wrist)
—both cortical and medullary bone become thinner w/ loss of trabeculae in the medulla
—dx of exclusion (i.e. you’ve ruled out osteomalacia)

Question 4

what lineage do osteoclasts come from?

—how are they activated?

Answer 4

osteoclasts come from the monocyte/M0 line
—activated by:
1. cytokines (IL-1, TNF, PTH, 1,25-D3) signal osteoBLastic precursor cells
2. osteoBLastic precursor cells use cytokines (IL-6 & IL-11) to signal osteoCLasts to differentiate from their precursors

Question 5

describe the histo appearance of osteoclasts vs. blasts

Answer 5

large mulitnucleated cells will resorption lacunae right up against bone
—vs. osteoblasts are smaller and applied closely to osteoid

Question 6

Mineralization is an ____ process.

Answer 6

passive

—only need to have Ca++ and PO4- around at the correct pH to make it happen

Question 7

Differentiating between osteoporosis and osteomalacia. Order some labs

Answer 7

—serum [Ca], [PO4], [25OH-VitD] and [PTH]
—BUN/Cr
—LFTs
—CBC (marrow issue?)
—SPEP (MM?)
—Alk phosphatase (signal of osteoBLast activity)

Question 8

Interpreting Dexa Scans
—"Dexa" means?
—Z-score?
—T-score?
—Cut-off for osteopenia?
—For osteoporosis?

Answer 8

—Dexa = dual xray absorptiometry
—Z-score = # of S.D.'s pt is away from mean for their age and sex
—T-score = # of S.D.'s pt is away from mean for a 30y/o of their sex (everyone eventually fits dx)
—osteopenia = T -1.0 to -2.5
—osteoporosis = T < -2.5

Question 9

Who should get a Dexa?

Answer 9

—post-menopausal ♀ or anyone else w/ estrogen def or other clinical r/o osteoporosis
—vertebral anomalies on xray
—pts w/ high-dose, long-term glucocorticoids Rx
—1°hyperparathyroidism
—metab dz that affects skeleton (e.g. chronic renal, GI, or liver dz)
—pts being tx’d for osteoporosis who need monitoring

Question 10

How does the risk of fracture increase w/ T-score?

Answer 10

—pretty much incrementally

—no “fracture threshold” per se

Question 11

review slides 23 & 25 which says

Answer 11

most women w/ fxs are actually osteopenic (probably b/c there are more women alive who are osteopenic > osteoporotic)
—point is that BMD is not the only factor at play

SLIDE 25
—Age has a huge risk, people with same BMD but increased age have much higher r/o fx

Question 12

What factors (besides low T-score) influence the fracture rate?
—Why is this?

Answer 12

—age
—previous h/o fx
—self-rated poor health
—poor mobility

This is because…
—bone density decr w/ age
—older bone is weaker even at same BMD (i.e. strength depends on more than BMD)
—elderly are more susceptible to falls due to decr muscle tone, peripheral neuropathy, poor vision, etc.

Question 13

Review slide 32

—Working backwards from osteomalacia’s final path, what are the possible etiologies of osteomalacia?

Answer 13

FINAL PATH
—inadequate Ca2+ or PO4 or abnl pH

RENAL
—abnl pH reg → hypophosphatemia
—renal dz → incr urinary Ca and/or PO4 loss

GI
—decreased GI Ca and/or PO4 absorption (usu 2°Vit D abnl’ty caused renal, GI, or liver dz; nutritional def, drugs)

Question 14

What are the ways in which glucocorticoids mess w/ bone and mineral homeostasis?

Answer 14

1. reduce GI Ca absorption
2. suppress bone formation
3. impair renal Ca reabsorption
4. 2° incr in PTH
5. suppress gonads

Question 15

What are biomarkers for:
—osteoclast activity?
—osteoblast activity?

Answer 15

OSTEOCLAST
—urinary N-telopeptide (type I collagen break down product)

OSTEOBLAST
—serum alkaline phosphatase
—serum osteocalcin

Question 16

What dzs fall under the umbrella of “metabolic bone dz”?

Answer 16

—osteoporosis
—osteomalacias
—osteosclerosis
—osteitis fibrosa (bone dz of hyperparathyroidism)

Question 17

Define osteosclerosis

Answer 17

increased bone mass
—caused when formation&raquo_space; resorption
—much rarer than osteopenia
—many causes

Question 18

Define osteitis fibrosa cystica

Answer 18

—subperiosteal bone resorption
—lytic bone lesions
—incr bone turnover
—fibrotic marrow cavity

CAUSE
—long-standing hyperparathyroidism

Question 19

What do osteoblasts deposits? (basic ansewr)

Answer 19

Type I collagen

—extracellular matrix

Question 20

M-CSF

Answer 20

Macrophage-colony stimulating factor
—from osteoBLasts
—promotes fusion of proto-osteoCLasts to form multinucleated giant cells

Question 21

OPG

Answer 21

osteoprotegerin
—blocks RANKL that sticks and from the surface of osteoBLasts thus preventing it from binding RANK on osteoCLast (so no activation)

Question 22

RANK

Answer 22

—osteoCLast surface receptor essential for development and proliferation of osteoCLasts
—binds RANKL which is embedded in the osteoBLast membrane

Question 23

TGF-β

Answer 23

inhibits osteoCLasts 2 ways:
—1. inhibits them and
—2. promotes their apoptosis

Question 24

Effect of estrogen deficiency on bone remodeling?

Answer 24

enhanced osteoCLast activity & decreased osteoBLast activity by:
—decreased M-CSF
—decreased RANKL on osteoblasts
—increased OPG secretion
—increased local TGF-β secretion

Question 25

Type I vs. Type II Osteoporosis

Answer 25

TYPE I
—rapid bone loss during first 5-7 years of menopause 2°to decr estrogen which causes resorption&raquo_space; formation
—can also occur s/p oophrectomy or in hypogonadal men

TYPE II
age related loss centered around:
—decr Ca uptake, incr Ca wsting and thus incr PTH
—decr Vit D (diet, sunshine, ability to absorb)

Question 26

Major categories of problems that lead to osteomalacia

Answer 26

1. Vit D def
2. Defective Vit D metab
3. Hypophosphatemia
4. Misc causes
5. Tumor

Question 27

Draw table of:
POROSIS–MALACIA–1° HYPER-PTH
—Say whether following lab values would be incr, decr, or normal

Serum Ca
Serum PO4
Serum Alk Phos
Urine Ca
Serum 25OH-D
Serum PTH
Bone Biopsy

Answer 27

See page 8 of notes