#11: Paget's Disease Flashcards
Treatment of choice in Paget’s disease
Cyclic oral doses of bisphosphonates in fairly high doses
Alendronate
(Fosamax) PO 30mg/day x 2 months
Bisphosphonate
Risedronate
(Actonel) PO tx for Paget’s dz
Bisphosphonate
Tiludronate
(Skelid)- PO tx for Paget’s dz
Bisphosphonate
Etidronate
(Didronel)—> least effective bisphosphonate drug; try to pick a different one
Zoledronic acid
(Zometa, Reclast)- parenteral bisphosphonate; most effective tx for paget’s dz
Pamidronate
(Aredia)- parenteral bisphosphonate
MOA for bisphosphonates:
- analogues of organic pyrophosphates
- Bind at hydroxyapatite on bone surface in bone matrix, and inhibit osteoclastic activation and bone resorption
Instructions w/ taking a bisphosphonate:
- 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
AE’s of bisphosphonates:
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
Papillary thyroid carcinomas are staged using this system (& explain):
- MACIS scoring system
- metastasis
- age
- completeness of resection
- size
- invasion
Second MC disease of the bones
Paget’s dz
Most patients present w/ these s/s
70-90% asymptomatic
Bones typically involved in Paget’s dz: (5)
- MC affects bones of AXIAL skeleton
- sacrum
- femur
- vertebra
- skull
- pelvis
(Not extremities)
MC Incidental findings include:
- Osteolytic lesions on imaging
- elevated serum alkaline phosphatases
Etiology of Paget’s Dz:
- 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
Describe the 3 distinct phases of Paget’s dz:
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
Paget’s dz can occur at any given site, but development of new site dz is ______________
Uncommon
Paget’s dz prefers these areas:
- axial skeleton and long bones
Boney manifestations in Paget’s Dz: (6)
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
Less common manifestations:
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
MC presentation symptom (though MC asymptomatic)
Bone pain (especially at night; dull, constant, boring, and deep to SC tissues) - also prone to fx
Most feared complication of Paget’s dz:
Osteosarcoma- which is rapidly fatal
- very rare 4 this malignant transformation!!!!
- but seen w/ increased bone pain & Alk. Phos levels, pathological fx, mass growth
Labs:
- normal calcium
- elevated alkaline phosphatase and UA
- secondary hyperparathyroidism may develop (due to low calcium intake)
