#11: Paget's Disease

Question 1

Treatment of choice in Paget’s disease

Answer 1

Cyclic oral doses of bisphosphonates in fairly high doses

Question 2

Alendronate

Answer 2

(Fosamax) PO 30mg/day x 2 months

Bisphosphonate

Question 3

Risedronate

Answer 3

(Actonel) PO tx for Paget’s dz

Bisphosphonate

Question 4

Tiludronate

Answer 4

(Skelid)- PO tx for Paget’s dz

Bisphosphonate

Question 5

Etidronate

Answer 5

(Didronel)—> least effective bisphosphonate drug; try to pick a different one

Question 6

Zoledronic acid

Answer 6

(Zometa, Reclast)- parenteral bisphosphonate; most effective tx for paget’s dz

Question 7

Pamidronate

Answer 7

(Aredia)- parenteral bisphosphonate

Question 8

MOA for bisphosphonates:

Answer 8

• analogues of organic pyrophosphates

- Bind at hydroxyapatite on bone surface in bone matrix, and inhibit osteoclastic activation and bone resorption

Question 9

Instructions w/ taking a bisphosphonate:

Answer 9

• Take w/ 8 oz water
• Stand for 30 minutes post-dosage
• cannot take w/ food or drinks (bc contain Ca)
• taken at least 2 hours before or after a meal (esophageal ulcers)
• general poor GI absorption

Question 10

AE’s of bisphosphonates:

Answer 10

1- hypocalcemia
2- urticaria/angiodema
3- esophageal ulceration: avoid w/ concurrent esophageal probs
4- osteonecrosis of the jaw: recommend edentulism prior to starting bisphosphonate tx; cyclic bone changes lead to loosening of tooth attachment structures; higher risk w/ invasive procedures; cancer of the mandible; chronic steroid use; CTX; poor oral hygiene

Question 11

Papillary thyroid carcinomas are staged using this system (& explain):

Answer 11

• MACIS scoring system
• metastasis
• age
• completeness of resection
• size
• invasion

Question 12

Second MC disease of the bones

Answer 12

Paget’s dz

Question 13

Most patients present w/ these s/s

Answer 13

70-90% asymptomatic

Question 14

Bones typically involved in Paget’s dz: (5)

Answer 14

• MC affects bones of AXIAL skeleton
• sacrum
• femur
• vertebra
• skull
• pelvis
  (Not extremities)

Question 15

MC Incidental findings include:

Answer 15

• Osteolytic lesions on imaging

- elevated serum alkaline phosphatases

Question 16

Etiology of Paget’s Dz:

Answer 16

• MC caucasians
• MC in men
• genetic predisposition and positive fam hx (40%)
• etiology w/ viral factors
• Northern latitudes
• MC in areas w/ high Anglo-Saxen populations

Question 17

Describe the 3 distinct phases of Paget’s dz:

Answer 17

1- Lytic: rapid bone resorption
—> increased in # and activity of osteoclasts
—> large, abnormal osteoclasts w/ tons of nuclei; up to 9x the rate of reabsorption
2- Mixed lytic and blastic: bone reabsorption and haphazard bone formation
—> Osteoblasts drawn into area of bone destruction & attempt to rapidly repair; “a mosaic pattern”
—> Bone marrow becomes fibrotic; elevated BV to bone tissue
3- Sclerotic: abnormal bone formation
—> Bone reabsorption stops; bone formation continues—> hard, dense, vascular “pagetic” bone
—> outcome: actually weaker bone

Question 18

Paget’s dz can occur at any given site, but development of new site dz is ______________

Answer 18

Uncommon

Question 19

Paget’s dz prefers these areas:

Answer 19

• axial skeleton and long bones

Question 20

Boney manifestations in Paget’s Dz: (6)

Answer 20

MC asymptomatic presentation w/:
1- Bone pain
2- Bowing of long bones and periarticular osteoarthritis
3- Boney enlargement of the skull and face (compression of auditory nerve—> deafness; tooth loss; HA; frontal bossing)
4- Increased risk for fx (stress fractures; recurrent fx)
5- Nerve entrapment: cauda equina, numbness, & radiculopathies
6- Vertebral enlargement and kyphosis

Question 21

Less common manifestations:

Answer 21

1- CV: calcific aortic valvular dz; high output HF & vascular calcification
2- bleeding: increased bleeding w/ bone surgeries
3- Vascular “steal”: Bones begin to steal blood supply from tissues leading to ischemia in some areas

Question 22

MC presentation symptom (though MC asymptomatic)

Answer 22

Bone pain (especially at night; dull, constant, boring, and deep to SC tissues)
- also prone to fx

Question 23

Most feared complication of Paget’s dz:

Answer 23

Osteosarcoma- which is rapidly fatal

• very rare 4 this malignant transformation!!!!
• but seen w/ increased bone pain & Alk. Phos levels, pathological fx, mass growth

Question 24

Labs:

Answer 24

• normal calcium
• elevated alkaline phosphatase and UA
• secondary hyperparathyroidism may develop (due to low calcium intake)

Question 25

Radiologic Diagnostics:

Answer 25

On x-ray: cotton wool/ivory vertebra
Study of choice: bone scan to assess extent of the dz
W/ malignancy: like prefer CT/MRI for dx or to look @ nerve entrapment

Question 26

Pharmacological tx is indicated in all cases of Paget’s Dz w/:

Answer 26

Symptomatic dz and in asymptomatic pts. W/ high risk of complications

Question 27

IV bisphosphonates are used in these pts:

Answer 27

Non-responders

Unable to take PO meds

Question 28

Patients taking bisphosphonates should also take:

Answer 28

calcium (1500mg/d) and vitamin D (400mg/d)- however not @ the same time as bisphosphonate medication- to tx hypocalcemia

Question 29

Goal of therapy:

Answer 29

• normalize serum alkaline phosphatase levels rapidly
• assess alk. Phos. Levels Q2-3 months to ensure continued remission
  (Most bisphosphonates induce a remission lasting 24 mos.)

Question 30

Prognosis:

Answer 30

• generally favorable
• dx @ younger age w/ poorest prognosis
• early effective tx reduces the likelihood of complications