osteoblasts in bone remodeling: - (1) stimulate osteoblasts - osteoblasts will then have (2) effects on other cells

1: - osteocytes - blood borne factors: PTH, Ca, PO4-, ect 2: - stimulates osteoclast development (differentiation) - activates osteoclasts

L17- Metabolic Bone Disorders Flashcards by Connor Patrick

describe the modeling and remodeling of bones of normal skeleton in different stages of life

1) childhood / adolescence: skeletal growth, osteoblastic activity&raquo_space; osteoclastic activity
2) 20s-30s: *Peak Bone Mass, 5-10% skeletal turnover per year; bone deposition = bone resorption
3) >late 30s: progressive bone loss (slow); bone loss > bone deposition

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(1) is the tightly regulated unit that regulates bone remodeling. (2) is the key regulatory part of (1).

1- basic multicellular unit = coordinated activity of osteoblasts and osteoclasts

2- osteoblasts

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osteoblasts in bone remodeling:

(1) stimulate osteoblasts
osteoblasts will then have (2) effects on other cells

osteocytes
blood borne factors: PTH, Ca, PO4-, ect

stimulates osteoclast development (differentiation)
activates osteoclasts

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(1) will upregulate (2) expression in osteoblasts. (2) binds to (3) on osteoclasts in order to produce (4) effect. (5) is able to inhibit (2) via (6).

1- PTH, vitD, some malignancies
2- RANKL (receptor activator of NF-κB ligand)
3- RANK (TNF family)
4- activate osteoclasts and its precursors
5- OPG (osteoprotegrin- TNF family)
6- binds RANKL to prevent RANKL-RANK interaction

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Regulation of Osteoclasts:

(1) from blood will activate (2) in bone
(2) has paracrine mechanisms to have (3) effect on osteoclasts
(4) in general will inc osteoclasts
(5) blocks or checks stimulation of osteoclasts

1- PTH, vitD3, IL-11
2- osteoblasts
3- inc activation, proliferation, fusion, differentiation, survival

4- M-CSF (macrophage colony stimulating factor)
5- OPG (osteoprotegrin)- binds RANKL

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Osteoporosis:

(1) definition leading to inc risk of (2) mainly in (3) people
(localized/diffuse)
(primary/secondary) disease

1- diminished bone mass
2- fractures
3- elderly
4- both (one bone –> few bones –> bones on one side –> all bones)
5- both (primary- aging, secondary requires additional factors)

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describe the effects aging has on bones and how it may lead to osteoporosis

dec activity of matrix-bound growth factors
dec replication from osteoprogenitor cells
dec synthetic activity of osteoblasts

-reduced physical activity

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______ osteoporosis results from aging

senile

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Post-menopausal Osteoporosis:

(1) years of progression
decreased levels of (2) in serum
(3) are the three effects from decreased (2)

1- ~10yrs post-menopause
2- estrogen

i) inc CSF, IL-6 via osteoblasts–> inc osteoclast differentiation
ii) inc local CKs via osteoblasts –> inc osteoclast activation
iii) inc IL-1, TNF via peripheral blood monocyte –> inc (i) and (ii)

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decreased estrogen levels will increase ______ levels which will stimulate osteoclast differentiation

CSF, IL-6

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decreased estrogen levels will increase ______ levels which will stimulate osteoclast activation

local CKs

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decreased estrogen levels will increase ______ levels from peripheral blood monocytes (include effects)

IL-1, TNF –> activates osteoblasts –> osteoclast proliferation/differentiation + activation

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describe the effect of osteoporosis on vertebral bodies

inc risk of compression fractures –> scoliosis

- characterized by loss of horizontal trabeculae and thickened vertical trabeculae

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list the general causes of secondary osteoporosis (hint- 5)

endocrine
neoplasia
GI
drugs

-immobilization (lack of physical activity)

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what endocrine changes can cause OP

**hyperparathyroidism

hyperthyroidism
DM
Addison’s disease (no adrenals)
pituitary tumors (via hormone secretion)

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what neoplasia can cause OP

carcinomatosis
multiple myeloma
paraneoplastic disease

what GI changes can cause OP

malnutrition
malabsorption
**vitD, vitC deficiencies
hepatic insufficiency

what drugs can cause OP

chemotherapy
corticosteroids
alcohol

describe all the effects on bone from increased osteoclastic activity via hyperparathyroidism

osteoporosis
osteoclastic tunneling
cystic spaces
Giant cell tumor-like mass
neovascularization, hemorrhage

Brown tumor b/c of dried blood

Paget’s Disease:

(1) definition
(2) affected age group
(males/females) are more affected
(4) most affected race

1- acquired disorder of bone remodeling, unknown cause
2- >40 y/o, incidence inc after 55 y/o
3- equally affected
4- whites

Paget’s Disease:

(1) definition
(2) affected age group
(males/females) are more affected
(4) most affected race

1- acquired disorder of bone remodeling, unknown cause –> monoostotic (one bone) or polyostotic
2- >40 y/o, incidence inc after 55 y/o
3- equally affected
4- whites

list the risk factors for Paget’s disease

Genetics- 15% have FHx, more prevalent in whites

Environmental- most likely viral infection (RSV) => trigger unregulated osteoclastic activity

Paget’s Disease:

(1) brief pathogenesis
(2) list stages

1- unregulated osteoclastic activity –> inc resorption –> stimulated inc osteoblastic activity –> abnormal bone deposition

i) osteolytic stage
ii) mixed lytic and blastic stage
iii) osteosclerotic (burnt-out) stage / end stage (inc bone mass)

describe the osteolytic stage of Paget’s

unregulated osteoclastic activity
patchy, florid (red) bone
multinucleated osteoclasts, >100 nuclei
lytic lesions

describe the mixed lytic and blastic stage of Paget's

- patchy areas of alternating osteoclastic and osteoblastic activity => remodeling, fibrosis, osteoid formation - thick and thin bony trabeculae

describe the osteosclerotic stage of Paget's

Burnt-out osteoclasts = end stage - irregular bone deposition - inc vascularity --> warmth - Histology: mosaic pattern with irregular cement lines

describe the highlights of Paget's disease histology

mosaic pattern of bone with dense sclerosis and haphazard / wavy cement lines (irregular bone formation)

Paget's disease clinical features

i) commonly asymptomatic ii) generalized bone pain iii) bone pain, warmth, tenderness, arthritis iv) fractures with trivial trauma, localized bone deformities - inc skull/head size - CN-VIII compression via foramina --> deafness

describe the diagnosis of Paget's disease

X-Ray: results depend on stage (hypodense, mixed, hyperdense + thickening of layers) - inc ALP - inc urinary hydroxyproline

Paget's disease: - (1) sites in monoostotic form - (2) sites in polyostotic form

1- skull, tibia, femur, vertebra, humerus 2- pelvis, vertebra, skull Note- 80% involve axial bone or femur

Paget's disease: - (1) common complications, bone - (2) rare complications

1: - deformities --> pain via nerve compression - fractures/microfractures --> pain - degenerative joint disease --> pain 2: - high output CHF (osteoblastic phase) - Tumors- sarcoma (5-10%, lethal), giant cell tumor, extra-osseous hematopoiesis

(1) are the secondary changes to bone as a result of chronic renal insufficiency or (2).

1- renal osteodystrophy 2- secondary to changes from dialysis

list the many mechanisms of renal osteodystophy (hint- 5)

- CRF --> hyperphosphatemia --> hypocalcemia --> secondary inc PTH - renal tubular acidosis / low pH --> demineralization of matrix => osteomalacia (vitD deficiency) - dec production of secretory factors - Hypocalcemia: i) dec vitD metabolism via phosphate inhibition (kidney); ii) vitD malabsorption -Dialysis --> Fe, Al (in dialysate) accumulates in bone --> prevents further bone deposition

list the clinical features of renal osteodystrophy

-inc PTH --> inc osteoclastic activity --> inc resorption --> ***inc risk of fractures - dec matrix mineralization --> osteomalacia - osteoporosis --> inc risk of fractures - growth retardation

list the risk factors / etiology of Vitamin D Deficiency

- inadequate synthesis (lack of sun) - dec absorption (malnutrition, malabsorption) - end-organ resistance (inherited abnormal receptor) - phosphate depletion

Vitamin D deficiency in children = ______ + clinical presentation and appearance of growth plate

Rickett's- weak, misshapen long bones in growing skeleton Growth plate: irregular hypertrophy of chondrocytes + poorly calcified osteoid

Vitamin D deficiency in adults = ______ + clinical features

Osteomalacia- mature bone --> soft bones --> fractures, osteoporosis

how does vitamin D deficiency affect bone health

- dec calcium absorption, resorption, reabsorption - -> abnormal mineralization = undermineralized matrix - -> persistent hyaline cartilage - -> fractures, skeletal deformity

describe the pathogenesis of scurvy and its affects on bone

i) vitC deficency ii) failed cross-linking of collagen iii) fragile capillaries and venules --> subperiosteal hemorrhages iv) defective osteoid synthesis --> microfractures v) bony deformities