Paget's Disease

Question 1

second most common disease of bones after osteoporosis in older persons

Answer 1

Paget’s disease

Question 2

when are people typically diagnosed with paget’s disease

Answer 2

diagnosed after bone lesions

discovered on imagine or high levels of serum alkaline phosphatase

discovered incidentally

Question 3

which bones does paget’s MC affect

Answer 3

bones of axial skeleton

vertebrae, pelvis, demur, sacrum, skull

Question 4

paget’s disease etiology

Answer 4

unknown

believed to be genetic or viral factors

Question 5

paget’s epidemiology

Answer 5

affects men more frequently than women

increasing incidence with age

caucasians, northern latitudes

high anglo-waxen populations

Question 6

phases of paget’s

Answer 6

1. lytic (rapid bone reabsorption)
2. mixed lytic and plastic phase (bone reabsorption + bad bone creation)
3. sclerotic (abnormal bone formation)

Question 7

lytic phase

Answer 7

first phase

increased number and activity of osteoclasts

9x reabsorptive rate of normal bone

Question 8

osteoclasts in paget’s

Answer 8

much larger than normal osteoclasts

7 times more resorptive capacity or normal

Question 9

lytic/blastic phase of paget’s

Answer 9

second phase

large numbers of normal osteoblasts act to rebuild bone as it is breaking down

produces bone matrix rapidly and haphazardly

“mosaic pattern”

bone marrow is replaced by fibrous tissue and increased number of blood vessels in the bone

Question 10

sclerotic phase

Answer 10

bone reabsorption ceases but abnormal formation continues leading to hard, dense vascular mosaic bone

bone is weaker than normal adult bone

Question 11

pathophysiology of paget’s

Answer 11

bone breakdown and bone rebuilding (shotty rebuild)

development of new sites of disease occurs uncommonly

predilection for axial skeleton and long bones

Question 12

bony manifestations of paget’s

Answer 12

increased risk of fracture

bony enlargement of the skull and face

bowing go long bones and periarticular osteoarthritis

vertebral enlargement and kyphosis

nerve entrapment

bone pain

Question 13

less common manifestations of paget

Answer 13

increased bleeding w/bone fractures

vascular steal (less blood)

CV

RARE but possible progression to osteosarcoma

Question 14

clinical manifestations of paget’s

Answer 14

asymptomatic and disease is found incidentally

most frequent symptom is bone pain (dull, constant, boring, deep)

prone to fracture

Question 15

lab abnormalities of paget’s

Answer 15

serum calcium levels are normal in untreated pt

elevated serum alkaline phosphatase and uric acid

secondary hyperparathyroidism (bc cant take in enough Ca)

Question 16

radiologic diagnosis of Paget’s

Answer 16

characteristics seen on X-rays

bone scan is study of choice (extent of disease)

CT/MRI (diagnosis of malignant transformation)

Question 17

pharmacologic treatment is indicated in

Answer 17

patients with symptomatic disease and in asymptomatic patients with high risk of complications

Question 18

pharmacologic treatment of choice

Answer 18

cyclic doses of oral bisphosphonates in fairly high doses

Question 19

bisphosphates used

Answer 19

alendronate/Fosamax

zoledronic acid (zometa) IV- most effective

etidronate - least effective

Question 20

bisphosphates MOA

Answer 20

analogues of inorganic pyrophosphate and bind to hydroxyapatite in bone matrix

inhibits dissolution of crystals by osteoclasts

MAKE BONE

Question 21

administration of bisphosphates

patient direction

Answer 21

poorly absorbed from GI tract

should be taken 2 hours before or after meals WITH NO calcium

taken with full 8oz of water

pt must sit or stand upright for 30 min

Question 22

ADRs to bisphosphate

Answer 22

hypocalcemia (should take vitamin D and calcium)

urticaria/angioedema

esophageal ulceration

osteonecrosis of jaw

Question 23

goals of bisphosphate therapy

Answer 23

success of treatment is measured by normalization of alkaline phosphatase levels

check for alkaline phosphatase remission every 2-3 months and when it falls start them again

Question 24

prognosis of paget

Answer 24

generally favorable

younger age of diagnosis is poorest prognosis

rapid institution of effective tx reduces likelihood of complications