Nejm 1997;336:558

Cause:Benign neoplasia of bone remodeling unit?

Pathophys:Excessive formation and destruction of bone constantly; normally sequence is increased osteoclast followed by increased osteoblast activities; but in Paget’s the rate of this progression is markedly increased (Nejm 1973;289:15). High blood flow due to idiopathic shunting at a capillary level, no true arteriovenous shunts (Nejm 1972;287:686). Increased vertebral size leads to neural compression syndromes

3% of population will develop it sometime in lifetime, although severe disease much less common

Sx:Fractures; knee, hip, and other joint arthritis; bone pain

Si:Angioid streaking of retina (r/o sickle cell disease and pseudoxanthoma elasticum) (Pseudoxanthoma Elasticum); deformed long bones; head enlargement

CNS compression syndromes including deafness from calvarial deformities (eg, Beethoven), pathologic fractures, high-output CHF, osteogenic sarcoma (2%), renal stones (esp with immobilization), heart block due to bundle calcifications

Lab:

Chem:Alkaline phosphatase increased markedly, highest values of any disease, r/o osteomalacia (Am J Med 2000;108;296)

Urine:Calcium and phosphate levels elevated

Xray:Sclerotic bone, expanded bone size (only Paget’s will do this); bone scan hot spots correlate with pain sx better than plain film changes (Ann IM 1973;79:348)

Rx:

1st: Bisphosphonates (Osteoporosis)

• Alendronate (Fosamax) 40 mg po qd; $120/mo
• Etidronate (Didronel) 5-20 mg/kg/d po × 6 mo (use in osteoporosis—Nejm 1990;323:73), can cause fractures at high doses (Ann IM 1982;96:619)
• Pamidronate (Aredia) 60 mg iv over 24 h q 1-3 yr (Med Let 1992;34:1)
• Risedronate (Actonel) (Med Let 1998;40:89) 30 mg po qd × 2 mo; $763
• Tiludronate (Skelid) (Med Let 1997;39:65) 400 mg po qd; $450/mo
• Zoledronic acid (Zometa/Aclasta) 5 mg iv q 6 mo (Nejm 2005;353:898)

2nd:

• Calcitonin, human 0.5 mg sc, $177/mo (Med Let 1987;29:47); or salmon calcitonin (Calcimar) (Jama 1972;221:1127), 50 U sc qd until asx, then tiw, $81/mo. Both inhibit osteocyte progenitor duplication and speed conversion of clasts to blasts (Ann IM 1981;95:192)

Others:

• Gallium nitrate? iv/sc × weeks (Ann IM 1991;114:846)