defining characteristics
Misshaped legs/head, gait problems, progression over time,warm to touch; moth-eaten deteriorated bone, pitting of pagetic bone; usually involves spine/ skull, most painful in pelvis/long bones
hearing loss, platybasia (softening at skull base–> headache w/ valsalva), Pagetic steal syndrome (shunt blood to ext carotid, stroke-like sx), osteoporosis circumscripta (bone loss around skull), leontiasis ossea (rare, enlarged facial/jaw bones), high output heart failure
disease development
3 stage of localized, chaotic(mosaic) bone remodeling:
1. osteoclastic activity
2. mixed osteoclastic-osteoblastic activity, where osteoblasts try to compensate with deposition of disorganized, hypervascularized lamellar bone
3. exhaustive (burnout) stage (dense pagetic bone as hypercellularity of bone diminishes)
All results in deformity, fracture, metabolic derangement
DIsorganized communication btwn osteoclasts and osteoblasts (coupled chaotic activity)
potential causes
Genetic predisposition (chrom 18, overlap w/ familial expansile osteolysis, p62 mutation- nl degrades RANKL signaling; Juvenile Paget’s – mutated OPG)
Problem with osteclasts (inc #, size, nuclei, fx, sensitivity to vitD); nl osteoblasts
possible involvement of slow viral inf
epidemiology
More common in people from British Isles,
Caucasians
adult disease (~60y.o.)
200,000 cases in U.S. (~3% prev)
5-20% w/ symptoms M>F
risk factors
Age
labimaging
Elevated bone-specific alkaline phosphatase (overactive osteoblasts, >2x inc)
Histology? Woven mosaic bone
XR? Pagetic flame lytic lesions, cotton wool skull, sclerotic + resorbed areas, inc Calvarian thickness), picture frame vertebral bodies (thick cortex frames lesion), fissure/chalk stick fractures (straight across)
Bone scan? show sclerotic dz
conventional treatment
Most people are asymptomatic sx? NSAIDs, COX2 inh, PT,
surgery for fx
Advanced disease? Use osteoporosis drugs (bisphosphonates, since they too kill osteoclasts)
hypercalcemia tx if know pt will be immobilized
complications
Pagetic bone is hemorrhagic so activity needs to reduced before surgery
Spinal cord/nerve root compressions
Fractures
Osteosarcoma!! (10% of older pts) – but no inc in non-skeletal malignancy!
hypercalcemia (immobilization)
gout (23% of pts w/ gout have paget’s)
prevention
Prophylactic bisphosphonate treatment prior to surgery!!!
