Paget Disease Medication

Updated: Sep 12, 2022
  • Author: Mujahed M Alikhan, MD; Chief Editor: Herbert S Diamond, MD  more...
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Medication Summary

The goals of pharmacotherapy are to reduce disease activity and morbidity and to prevent complications. Treatment with bisphosphonates should be considered first-line therapy in patients with Paget disease. Note that osteonecrosis of the jaw has recently been described in patients taking bisphosphonates and this should be discussed with patients before initiating treatment, when possible. [58]


Metabolic & Endocrine, Other

Class Summary

Bisphosphonates are analogues of inorganic pyrophosphate and act by binding to hydroxyapatite in bone matrix, thereby inhibiting the dissolution of crystals. They prevent osteoclast attachment to the bone matrix and osteoclast recruitment and viability.

For maximum gut absorption, all oral bisphosphonates should be taken at least 2 hours before or after meals. The newer bisphosphonates are not completely free of the risk of causing a mineralization defect, but their safe therapeutic window is much wider. They clearly are more potent than etidronate in reducing disease activity and normalizing alkaline phosphatase levels. [30, 35, 36]

Calcitonin analogues directly inhibit osteoclastic bone resorption and have a significant analgesic effect on bone. Human calcitonin is no longer available. Salmon calcitonin is more likely than human calcitonin to cause resistant antibodies. As many as 26% of patients treated with salmon calcitonin demonstrated loss of biochemical responsiveness after initial improvement. High titers of salmon calcitonin antibodies produce resistance. All patients resistant to salmon calcitonin responded to human calcitonin.

Alendronate (Fosamax)

Alendronate is a potent third-generation bisphosphonate that principally acts by inhibiting osteoclastic bone resorption. It is recommended for treatment of Paget disease. Retreatment may be considered after 6-month posttreatment evaluation in patients whose serum alkaline phosphatase level did not normalize.

Pamidronate (Aredia)

Pamidronate is a potent second-generation bisphosphonate that acts principally by inhibiting osteoclastic bone resorption. Intravenous (IV) pamidronate has been shown to be effective in the treatment of Paget disease and in patients unresponsive to treatment with etidronate or calcitonin.

Optimal dosing regimen has not yet been determined. Successful treatment consists of normalization of alkaline phosphatase level (biochemical remission) and stabilization of symptoms.

Risedronate (Actonel, Atelvia)

Risedronate is a potent aminobisphosphonate that principally acts by inhibiting osteoclastic bone resorption. It is recommended for the treatment of Paget disease.

Etidronate (Didronel)

Etidronate was the first bisphosphonate to be studied in humans and approved in the United States (1978) for the treatment of Paget disease. It is the least potent of currently available bisphosphonate drugs.

Tiludronate (Skelid)

Tiludronate is a sulfur-containing bisphosphonate of intermediate potency between etidronate and newer nitrogen-containing bisphosphonates. No food, indomethacin, or calcium should be ingested within 2 hours before and 2 hours after. A 3-month posttreatment evaluation follows.

Zoledronate (Reclast, Zometa)

Zoledronate inhibits bone resorption. It inhibits osteoclastic activity and induces osteoclastic apoptosis

Salmon calcitonin (Miacalcin, Calcimar injection)

Salmon calcitonin is recommended for treatment of Paget disease if bisphosphonates are contraindicated. This agent is a peptide hormone that binds to calcitonin receptors on osteoclasts and rapidly inhibits bone resorption. Osteoclasts do not induce cytotoxic effects in bone cells.

Salmon calcitonin induces reductions in urinary hydroxyproline and serum alkaline phosphatase levels. Serum alkaline phosphatase begins to decline 4 weeks after initiation of treatment. Levels of urinary hydroxyproline may decrease quickly, indicating inhibition of bone resorption. These laboratory markers slowly increase back to pretreatment levels if treatment is stopped. If no response is noted by 3 months, treatment should be discontinued.

Restoration of more normal bone can be seen radiographically, especially after chronic calcitonin treatment. Bone biopsy samples also reflect reduced disease activity because decreased bone cells, marrow fibrosis, and woven bone are present. Reduction in bone pain, cardiac output, and skin temperature over lower limb bones can be observed. Improvement of neurologic deficits and stabilization of hearing have been noted.

Reduction of hemorrhage from orthopedic procedures has been demonstrated with preoperative calcitonin treatment. However, salmon calcitonin only partially suppresses disease while treatment continues.