Pagets disease of the bone

Question 1

what is Paget’s disease of the bone?

Answer 1

degenerative bone disease
disorder of bone metabolism
increased rate of bone remodelling at localised sites

Question 2

how common is it?

Answer 2

second most common degenerative bone disorder after osteoporosis

Question 3

how many people does it affect?

Answer 3

> 5% of over 55s in UK
prevalence varies between countries and races
unusual geographic distribution

Question 4

where is there high incidence ?

Answer 4

australia
new zealand
north america

Question 5

risk factors

Answer 5

male>female
increased incidence in pet owners
genetic susceptibility - increased risk in family history of disease
disease occurs in local geographical clusters

Question 6

causes

Answer 6

environmental factors in a predisposed individual
viral infection
incidence increases with age

Question 7

clinical features

Answer 7

chronic progressive
often asymptomatic
discovered incidentally with raised ALP of on x-ray
15-20% have symptoms

Question 8

symptoms

Answer 8

bone pain
bony deformity - warm skin overlying the lesion due to increased blood flow 
osteoarthritis 
fractures - due to brittle bones 
deafness
headaches 
non-specific neurological features such as dizziness 
osteosarcoma 
bowing deformity

Question 9

bone pain

Answer 9

late feature
deep constant aching pain
worse with weight bearing
persists through night

Question 10

common sites affected

Answer 10

pelvis 
lumbar spine
femur
thoracic spine
sacrum 
skull 
tibia
humerus

Question 11

what causes deafness/headaches?

Answer 11

compression of vestibulocochlear nerve when skull is affected

Question 12

what is an osteosarcoma?

Answer 12

primary bone cancer

Question 13

what is bowing deformity?

Answer 13

altered gait
joint pain - hips and lower back
when long bones are affected

Question 14

pathology

Answer 14

increased number of osteoclasts which are larger
osteoblasts are normal and overactive due to increased factors released by osteoclasts
osteoclasts oversensitive to vitamin D
accelerated rate of bone turnover and subsequent rapid new bone formation with a disorganised matrix

Question 15

what happens to bones?

Answer 15

increased size
more brittle
more prone to fracture

Question 16

investigations required

Answer 16

bloods 
x-rays 
radionuclide bone scan 
bone biopsy 
CT/MRI to better define unusual bone lesions

Question 17

blood tests

Answer 17

ALP - bone-sepcific 
GGT 
serum calcium 
serum phoshate 
vitamin D

Question 18

ALP/Alk P

Answer 18

indicator of osteoblastic activity

raised

Question 19

GGT

Answer 19

to rule out liver cause if ALP is raised and bone-specific ALP cannot be tested

Question 20

severity of disease

Answer 20

correlated with ALP

Question 21

serum calcium and phosphates

Answer 21

normal

abnormal may indicate parathyroid disease rather than other pagets disease

Question 22

vitamin D

Answer 22

can be used to rule out another cause of raised ALP

to ensure levels are sufficient to undertake bisphosphonate therapy

Question 23

x-ray findings

Answer 23

widening of cortical region 
mixed areas of sclerosis and lysis 
bone thickening and enlargement 
bone deformities 
localised osteoporosis in areas of very high osteoclast activity - osteoporosis circumscripta

Question 24

widening of cortical region

Answer 24

hollow cortex at centre of bone is wider

Question 25

mixed areas of sclerosis and lysis

Answer 25

lots of opaque dark splodges in bone | seen in early disease

Question 26

bone thickening and enlargement

Answer 26

seen in later disease | easier to differentiate

Question 27

bone deformities

Answer 27

bone bends anteriorly in tibia and bone bends laterally in femur

Question 28

bone scan

Answer 28

increased isotope uptake in affected bones often performed after initial lesions have been diagnosed to assess the extent of disease any areas that show uptake on bone scan should be further investigated with x-ray to confirm paget's disease

Question 29

urine

Answer 29

may contain collagen due to very high bone resorption

Question 30

differentials

Answer 30

bone malignancy osteoarthritis osteoporosis

Question 31

treatment aims

Answer 31

reduce pain | slow down rate of bone remodelling

Question 32

deciding who to treat

Answer 32

based on symptom severity | asymptomatic disease not often treated

Question 33

who to treat?

Answer 33

severe pain nerve compression from expanding bone or neurological complications fractures asymptomatic disease with significant biochemical abnormalities

Question 34

abnormal biochemistry that requires treatment

Answer 34

ALP >2 x normal | raised ALP and paget disease at a site that commonly results in fracture

Question 35

what is the treatment?

Answer 35

bisphosphonates

Question 36

how do bisphosphonates work?

Answer 36

inhibit osteoclast activity and cause osteoclast apoptosis | damage cytoskeleton of osteoclast so the cells is unable to bind to bone and unable to do bone resorption

Question 37

pre-treatment checks

Answer 37

serum calcium and vitamin D | start patients on supplemental vitamin S and calcium

Question 38

length of treatment

Answer 38

often able to induce remission | typically treated for 2 months

Question 39

what type of bisphosphonates are used?

Answer 39

newer/ nitrogen containing bisphosphonates

Question 40

what bisphosphonates can be used?

Answer 40

zolendronic acid pamidronate risedronate/alendronate - oral

Question 41

what can be used for those that cannot tolerate bisphosphonates?

Answer 41

calcitonin

Question 42

zolendronic acid

Answer 42

IV infusion - 5mg over 15 mins | resistance can develop

Question 43

side effects of zolendronic acid

Answer 43

can cause flu-like symptoms after first dose

Question 44

what to use when there is resistance developed to zolendronic acid?

Answer 44

pamidronate

Question 45

pamidronate

Answer 45

IV older bisphosphonate

Question 46

oral bisphosphonate therapies

Answer 46

risedronate | alendronate

Question 47

when to use oral bisphosphonates?

Answer 47

younger patients | less severe disease

Question 48

risedronate dose

Answer 48

30mg for 2 months daily

Question 49

alendronate dose

Answer 49

40mg daily for 3-6 months

Question 50

cautions when taking oral bisphosphonates

Answer 50

take with water no food for 30 mins after don't lie down for 2 hours after to avoid oesophageal irritation and gastroesophageal reflux dental work needs to be done before initiating therapy as it increases risk of osteonecrosis of jaw

Question 51

calcitonin

Answer 51

doesn't induce remission but can reduce disease progression

Question 52

adverse effects of bisphosphonates

Answer 52

osteonecrosis of jaw bone pain flu-like symptoms

Question 53

other management options

Answer 53

``` simple analgesia orthoses orthotics education treat complications ```

Question 54

orthoses

Answer 54

braces for support and protection

Question 55

orthotics

Answer 55

shoe inserts | help correct deformity and altered gait

Question 56

treating complications

Answer 56

joint replacement hearing aids physio

Question 57

ongoing management

Answer 57

consider repeating ALP at 3-6 months to assess efficacy of treatment repeat ALP annually initiate treatment again when ALP starts to rise or patient becomes symptomatic again

Question 58

complications

Answer 58

increased risk of bone tumours - osteosarcoma

Question 59

osteosarcoma

Answer 59

1% incidence of paget's disease patients consider this in lesions that do not respond to medical therapy - especially pain often advanced and fatal more common in people with long standing disease