Pamidronate is effective for paget's disease of bone refractory to conventional therapy

Abstract

Paget's disease of bone is characterized by primary osteoclastic dysfunction and prolonged treatment with conventional medications including calcitonin and etidronate, results in a number of patients becoming refractory to treatment. We have evaluated the effectiveness of three dosage regimes of aminohydroxypropylidene bisphosphonate (pamidronate) in 15 patients with extensive Paget's disease who had become refractory to conventional therapy. Nine patients had pamidronate (intravenous infusion of 30 mg over 4-5 hours at monthly intervals) for 6 months. A further four patients received 30 mg of pamidronate infusion daily for 6 consecutive days and another two patients, 60 mg on 3 consecutive days (total dose of 180 mg/patient). In all three groups the bone-specific alkaline phosphatase and urinary hydroxyproline excretion both fell by 75% (P < 0.001). All but one patient showed a marked improvement in clinical symptomatology (pain and mobility) and biochemical parameters indicating decreased bone turnover. Remissions achieved (> 12 months) with all three regimens were comparable. The pagetic bone pain was reduced and the mobility was significantly improved after 3 months of therapy and was continued for up to 1 year. Currently, it may be difficult to justify the use of intravenous bisphosphonate as the first line of therapy for Paget's disease, but it does seem to have a definite place in patients with severe Paget's disease who do not respond to other therapeutic agents. Here we demonstrate that pamidronate is highly effective in patients with extensive Paget's disease who became refractory to conventional treatment. Further studies are necessary to optimize the dosage and frequency of administration of pamidronate.

Current options for the treatment of Paget&rsquo;s disease of the bone

“…Other studies confirmed this observation,57–60 and higher cumulative dosages of pamidronate have been used in patients with severe PDB, with contrasting results. Similar to etidronate and clodronate, reduced effectiveness with repeated treatments (tachyphylaxis or acquired resistance) has also been reported with pamidronate 26,53,61–63. In different studies, biochemical relapse was dependent on initial disease severity as assessed by total ALP and on previous bisphosphonate treatment.…”

“…In studies on patients who had not previously received bisphosphonates, the response could be higher, with biochemical normalization in up to 85% of PDB patients with moderate disease 50–52. Pamidronate therapy has also been reported to improve pagetic pain and overall mobility in symptomatic patients 53–55. A study comparing a same total dose of intravenous pamidronate (180 mg for 1 year, given as 30 mg weekly for the first 6 weeks or 45 mg every 3 months) with an higher dose (360 mg for 1 year, given as 30 mg weekly for the first 6 weeks and a further 60 mg weekly for other 3 weeks) demonstrated a dose response effect, with the more severely affected patients requiring a higher total dose for disease suppression 56.…”

Ribbing disease: radiographic and biochemical characterization, lack of response to pamidronate

“…Pamidronate is a second-generation bisphosphonate, which has been shown to be effective in decreasing bone pain in a number of diseases [9,10,11]. This report provides the most complete biochemical and radiographic analysis of a patient with Ribbing disease to date, and documents a lack of clinical and biochemical response to treatment with pamidronate.…”

Changes in calcium homoeostasis in patients undergoing liver transplantation: effects of a single infusion of pamidronate administered pre-operatively

“…The bisphosphonates are synthetic analogues of pyrophosphate which inhibit bone resorption and reduce bone turnover. They have been used in a wide variety of skeletal disorders including post-menopausal osteoporosis, Paget's disease, malignancy-associated hypercalcaemia and primary hyperparathyroidism [9][10][11][12]. In this randomized controlled study we have investigated the effects of intravenous pamidronate, given pre-operatively, on biochemical indices of skeletal metabolism during the first 30 days after liver transplantation.…”