Paget disease of bone + osteoporosis

Question 1

Complications of Paget disease (2)

Answer 1

1) High output cardiac failure - due to formation of AV shunts in bone (increased vasculaity in Paget bone)
2) High risk of osteosarcoma

Question 2

Lab findings of Paget

Answer 2

Increased ALP (rest of labs normal including liver enzymes)

Question 3

Histology of Paget

Answer 3

1) Increased number of osteoclasts w/ many more nuceli
2) Mosaic pattern of woven bone (jigsaw)

Question 4

Average age of presentation of Paget disease

Answer 4

Late adulthood (>60 years)

Question 5

Etiology of Paget

Answer 5

Possible viral (paramyxovirus, which infects osteoclasts, increasing its activity)

Mutation in SQSTM1 gene- constitutive activation of NfKB (RANKL pathway) –> increased osteoclast activity

Question 6

Presentation of paget

Answer 6

Typically asymptomatic and picked up incidentally on x-ray

1) Bone pain
2) Bone deformities- weak bone can result in bowing of limbs
3) Increasing hat size - skull commonly affected
4) “Chalk stick-like fractures”- due to weak bone
5) Hearing loss- impingement of cranial nerve
6) Lion like facies- involvement of craniofacial bones (e.g. frontal bossing, protuberant jaw)

Question 7

Stages of Paget

Answer 7

1) Lytic- osteoclastic activity predominants with tremendous bone resorption
2) Mixed stage- both osteoclast/ blast activity high
3) Sclerotic stage- osteoblast activity predominates to try to make up for los of bone in lytic stage; however, they rapidly deposit new bone of poor quality (woven rather than lamellar)
4) Quiescent- both osteoclast + osteoblasts burnt out –> ultimately results in sclerotic and very dense bone that is very fragile

Question 8

Main similarities + differences between Paget disease of bone and Osteopetrosis

Answer 8

Main differences:

1) Age of onset- Paget occurs in older adults, while osteopetrosis occurs in kids (congenital)
2) Etiology- Paget is unknown (possibly paramyxovirus infection), while osteopetrosis is due to CA II mutation/ RANKL or RANK mutation

Main similarity:

Both results in dense bone that is fragile, due to defective osteoclasts

Question 9

Lab findings for osteoporosis and why this is important

Answer 9

Serum Ca2+, phosphate, PTH, ALP are normal. Important bc this excludes osteomalacia, which presents similarly. Osteomalacia has low vitamin D, low phosphate and Ca2+, and high PTH (secondary parathyroidism)

Question 10

Primary problem in Paget

Answer 10

Osteoclastic bone resorption; osteoblast function is typically normal

Question 11

Presnetation of osteoporosis

Answer 11

Bone pain and fractures in weight bearing areas (e.g. vertebrae, hip, distal radius)

Vertebral involvement may lead to vertebral compression fractures (acute back pain, loss of height, kyphosis)

Question 12

Pattern of skeletal involvement in Paget

Answer 12

Localized process that involves one or more bones; does not involve entire skeleton