Pagets disease of the bone Flashcards
what is Paget’s disease of the bone?
degenerative bone disease
disorder of bone metabolism
increased rate of bone remodelling at localised sites
how common is it?
second most common degenerative bone disorder after osteoporosis
how many people does it affect?
> 5% of over 55s in UK
prevalence varies between countries and races
unusual geographic distribution
where is there high incidence ?
australia
new zealand
north america
risk factors
male>female
increased incidence in pet owners
genetic susceptibility - increased risk in family history of disease
disease occurs in local geographical clusters
causes
environmental factors in a predisposed individual
viral infection
incidence increases with age
clinical features
chronic progressive
often asymptomatic
discovered incidentally with raised ALP of on x-ray
15-20% have symptoms
symptoms
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
bone pain
late feature
deep constant aching pain
worse with weight bearing
persists through night
common sites affected
pelvis lumbar spine femur thoracic spine sacrum skull tibia humerus
what causes deafness/headaches?
compression of vestibulocochlear nerve when skull is affected
what is an osteosarcoma?
primary bone cancer
what is bowing deformity?
altered gait
joint pain - hips and lower back
when long bones are affected
pathology
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
what happens to bones?
increased size
more brittle
more prone to fracture
investigations required
bloods x-rays radionuclide bone scan bone biopsy CT/MRI to better define unusual bone lesions
blood tests
ALP - bone-sepcific GGT serum calcium serum phoshate vitamin D
ALP/Alk P
indicator of osteoblastic activity
raised
GGT
to rule out liver cause if ALP is raised and bone-specific ALP cannot be tested
severity of disease
correlated with ALP
serum calcium and phosphates
normal
abnormal may indicate parathyroid disease rather than other pagets disease
vitamin D
can be used to rule out another cause of raised ALP
to ensure levels are sufficient to undertake bisphosphonate therapy
x-ray findings
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
widening of cortical region
hollow cortex at centre of bone is wider
mixed areas of sclerosis and lysis
lots of opaque dark splodges in bone
seen in early disease
bone thickening and enlargement
seen in later disease
easier to differentiate
bone deformities
bone bends anteriorly in tibia and bone bends laterally in femur
bone scan
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
urine
may contain collagen due to very high bone resorption
differentials
bone malignancy
osteoarthritis
osteoporosis
treatment aims
reduce pain
slow down rate of bone remodelling
deciding who to treat
based on symptom severity
asymptomatic disease not often treated
who to treat?
severe pain
nerve compression from expanding bone or neurological complications
fractures
asymptomatic disease with significant biochemical abnormalities
abnormal biochemistry that requires treatment
ALP >2 x normal
raised ALP and paget disease at a site that commonly results in fracture
what is the treatment?
bisphosphonates
how do bisphosphonates work?
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
pre-treatment checks
serum calcium and vitamin D
start patients on supplemental vitamin S and calcium
length of treatment
often able to induce remission
typically treated for 2 months
what type of bisphosphonates are used?
newer/ nitrogen containing bisphosphonates
what bisphosphonates can be used?
zolendronic acid
pamidronate
risedronate/alendronate - oral
what can be used for those that cannot tolerate bisphosphonates?
calcitonin
zolendronic acid
IV infusion - 5mg over 15 mins
resistance can develop
side effects of zolendronic acid
can cause flu-like symptoms after first dose
what to use when there is resistance developed to zolendronic acid?
pamidronate
pamidronate
IV older bisphosphonate
oral bisphosphonate therapies
risedronate
alendronate
when to use oral bisphosphonates?
younger patients
less severe disease
risedronate dose
30mg for 2 months daily
alendronate dose
40mg daily for 3-6 months
cautions when taking oral bisphosphonates
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
calcitonin
doesn’t induce remission but can reduce disease progression
adverse effects of bisphosphonates
osteonecrosis of jaw
bone pain
flu-like symptoms
other management options
simple analgesia orthoses orthotics education treat complications
orthoses
braces for support and protection
orthotics
shoe inserts
help correct deformity and altered gait
treating complications
joint replacement
hearing aids
physio
ongoing management
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
complications
increased risk of bone tumours - osteosarcoma
osteosarcoma
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
