Paget's disease profoma Flashcards
What is Paget’s disease?
Chronic focal disease of bone remodelling
Local area of bone deformed.
Characterised by increased bone resorption, bone formation & remodelling, which may lead to major long-bone & skull deformities.
Epidemiology of Paget’s disease
2ndmost common metabolic bone disease
More common in males
Unusual under 40
Often asymptomatic- unusual after presentation to involve other bone.
Incidence has declined rapidly in recent years.
Pathophysiology of Paget’s disease
- Increased bone cell activity. Osteoclastare bigger w/ multiple nuclei = ↑ reabsorbtion of bone
- Osteoblastslay down bone in a haphazard way because they are trying to catch up - poor bone architecture.
- Therefore,expansion ofpoor qualitybonethat is weak
- Marrow replaced w/ fibrous tissue & blood vessels
- Increased blood flow = bone feels warm.
- Increased risk ofsarcomaw/in bone
Risk factors for Paget’s disease
- Family history - related toadefect in SQSTM1 gene
- Older age
- Male sex
- Northern latitudes
Clinical features of Paget’s disease
Cause of symptoms = bone expansion
- Monostotic(1 bone) orpolystotic(2 or more bones).
- Bone deformity e.g. commonly bowing of the tibia.
- Bone pain-generalised, progressive & night pain. Poorly responsive to analgesia. Constant, dull pain.
- Abnormal biomechanics (joint alignment) e.g. pain in joint that is affected by malalignment, bowing of legs
- Fractures- particularly lower limb.
- Spinal stenosis- expansion of vertebrae = encroach nerve root / spinal nerve root entrapment
- Secondary OA - due to deformity of bones creating pressure.
- Acetabular protrusions
- if the skull is involved it can cause DEAFNESS
Bones commonly involved:
- Femur
- Tibia
- Spine
- Skull
- Sternum
- Pelvis
- Any bone in body
Upon examination:
- Warm - due to increased blood vessel supply that is required to keep up w/ ↑sed osteoclast/blast activity.
- Tender - due to periosteum being stretched
- Deformity
Clinical features of Paget’s disease: neurological presentation
Caused by boney overgrowth of the skull/spine & compression of neurological structures.
-DEAFNESS
- Tinnitus - ringing noise in ear that is not caused by the outside world.
- Basilar invaginations - occurs when the top of the second vertebrae moves upward. It can press on the lower brainstem. Causes headache, dizziness, parasthesia…
- Cerebellar dysfunction- if spine is involved. Can cause balance problems & ataxic “drunk” gait.
- Obstructive hydrocephalus - CFS unable to circulate due to squashed skull.
- Cranial nerve palsies - can cause double vision & eyesight issues.
- Spinal stenosis / cauda equina
- Para or quadripegia
Rare complications of Paget’s disease?
Cardiovascular
- Increased cardiac output to bone i.e. increased blood flow.
- Heart failure
- Aortic stenosis - valve becomes tighter = harder to get blood through.
- Endocardial calcification- the innermost layer of tissue that lines chambers of the heart.
- Atherosclerosis
Metabolic
- High uric acid
- High calcium - it is usually normal in Paget’s.
- Imbolisationhypercalciuria i.e. high Ca in urine.
- Kidney stones
Neoplasia
- Osteosarcoma
- Chondrosarcoma
- Fibrosarcoma
- Giant cell tumors
Investigations for Paget’s disease: blood test
High bone-specific alkaline phosphatase (ALP) - enzyme:
- Also seen in growing children (normal)
- Sometimes seen in people w/ fractures
Serum calcium & phosphate are normal - very rarely hypercalcaemia.
NOTE: hypercalcaemia is associated w/ primary hyperparathyroidism.
PTH is normal
25-hydroxyvitamin D= normal!
Other markers of bone turnover high:
- Serum P1NP - marker of bone formation
- Serum CTX - marker of bone resorption
Compare blood tests in osteomalacia vs Paget’s
Osteomalacia:
- Low serum Ca
- Low serum phosphate
- Raised ALP
- Raised PTH
- Low Vitamin D (25-hydroxyvitamin D)!
Pagets:
- Normal serum Ca
- Normal serum Phospahte
- Raised ALP
- PTH normal
- Normal Vitamin D !
Things to exclude in Paget’s
Hyperparathyroidism - high PTH & calcium.
Hyperthyroidism - can cause osteoporosis.
Renalosteodystrophy - characterised by bone mineralisation insufficiency due to electrolyte and endocrine abnormalities (due CKD). Present in osteomalacia, osteonecrosis & fractures.
Malignancy -e.g.osteosarcoma or chondrosarcoma.
Investigations for Paget’s disease: Radiological
Paget’s starts at one end & then usually progreses down or up the bone. Doesn’t start from the centre of the bone.
X-rays:
- Bones are expanded
- Cortical thickening
- Coarsened trabeculae
- May show deformity
- Mixture of lytic & scleroticareas - lytic changes are commonly seen in early stages & sclerotic predominates later.
NOTE: view notes for x-ray images !! important!
Isotope bone scans - looks for uptake by skeleton -showshowextensivedisease is
- Shows 1 or 2 focal areas of high metabolic activity.
CT or MRI - to evalutae neurological involvement & to check for malignancy.
Management for Paget’s disease
Bisphosphonates - IV Zoledronate 5 mg one off or Risedronate
- all reduce osteoclast function
NOTE: zolendronate is an injection whereas risendronate is oral. Injection better.
Calcium + vitamin D
Analgesia & treat OA
Ensure vitamin D levelsadequate - if not, don’t give IV bisphosphonate.
Physiotherapy
Surgery - fractures, joint replacements, spinal stenosis.
NOTE: Bisphosphonates can cause osteonecrosis of jaw, cause acid reflux & GI problems.
Prognosis for Paget’s disease
If treatment occurs before major changes in bone occur, the majority of patients w/ Paget’s areable to live a normal, active life
When complications do develop, surgical treatment is usually effective in relieving pain & improving function.
