====== Paget's disease medical treatment ======

Although there is no cure for [[Paget's disease]], medications ([[bisphosphonate]]s and [[calcitonin]]) can help control the disorder and lessen pain and other symptoms. 

[[Medication]]s are often successful in controlling the disorder, especially when started before complications begin.

Medical treatment is indicated for cases that are not rapidly progressive where the diagnosis is certain, for patients who are poor surgical candidates, and pre-op if

Medical therapy reverses some neurologic deficit in 50% of cases,
((Chen J-R, Rhee RSC, Wallach S, et al. Neurologic Dis- turbances in Paget Disease of Bone: Response to Calcitonin. Neurology. 1979; 29:448–457))
but generally requires prolonged treatment (≈ 6–8 months) before improvement occurs, and may need to be continued indefinitely due to propensity for relapses. Medications used include the following.

=== Calcitonin derivatives ===

[[Parenteral]] salmon [[calcitonin]] (Calcimar®): reduces [[osteoclast]]ic activity directly, [[osteoblast]]ic hyperactivity subsides secondarily. [[Relapse]] may occur even while on calcitonin. Side effects include [[nausea]], facial flushing, and the development of antibodies to salmon calcitonin (these patients may benefit from a more expensive synthetic human preparation (Cibacalcin®) starting at 0.5 mg SQ q d).

50–100 IU (medical research council units) SQ q d × 1 month, then 3 injections per week for several months.

If used pre-op to help decrease bony vascularity, ≈ 6 months of treatment is ideal. Doses as low as ≈ 50 IU units 3 ×per week may be used indefinitely post-op or as a sole treatment ([[alkaline phosphatase]] and urinary hydroxyproline decline by 30–50% in > half of patients in 3–6 months, but they rarely normalize).

=== Bisphosphonates ===

[[Bisphosphonate]]s are pyrophosphate analogues that bind to [[hydroxyapatite]] crystals and inhibit [[bone resorption]]. They also alter [[osteoclast]]ic metabolism, inhibit their activity, and reduce their numbers. They are retained in [[bone]] until it is resorbed. [[Oral absorption]] of all is poor (especially in the presence of food). Bone formed during treatment is lamellar rather than woven.

Etidronate (Didronel®) (AKAEHDP): reduces normal bone [[mineralization]] (especially at doses ≥ 20 mg/kg/d) producing mineralization defects ([[osteomalacia]]) which may increase the risk of fracture but which tend to heal between courses
((Tiludronate for Paget's Disease of Bone. Med Letter. 1997; 39:65–66)).

Contraindicated in patients with [[kidney failure]], [[osteomalacia]], or severe lytic lesions of a LE. 5–10 mg/kg PO daily (average dose: 400 mg/d, or 200–300 mg/d in frail elderly patients) for 6 months, may be repeated after a 3–6 month hiatus if biochemical markers indicate relapse.

Tiludronate (Skelid®): unlike etidronate, does not appear to interfere with bone mineralization at
recommended doses. Side e ects: abdominal pain, diarrhea, N/V.  400 mg PO qd with 6–8 ounces 

Pamidronate (Aredia®): much more potent than etidronate. May cause a transient acute flu-like syndrome. Oral dosing is hindered by GI intolerance, and IV forms may be required. Mineralization defects do not occur in doses <180 mg/course.  90 mg/d IV×3 days, or as weekly or monthly infusions.

Alendronate (Fosamax®): does not produce mineralization defects.

Clodronate (Ostac®, Bonefos®): 400–1600 mg/d PO×3–6 months. 300 mg/d IV×5 days (may be available outside the U.S.).

Risedronate (Actonel®): does not interfere with bone mineralization in recommended doses
((Risedronate for Paget's Disease of Bone. Med Letter. 1998; 40:87–88)). 
30 mg PO q d with 6–8 oz. of water at least 30 minutes before the first meal of the day.