Treatment of paget's disease with intermittent low-dose infusions of disodium pamidronate (APD)

Stone, Michael D.; Hawthorne, A. B.; Kerr, David; Webster, G. M.; Hosking, David J.

doi:10.1002/jbmr.5650051207

Cited by 30 publications

(11 citation statements)

References 17 publications

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“…In our study, 33 of 60 patients (55%) showed lack of therapeutic response to pamidronate after 6 mo. In keeping with previous observations, biochemical relapse in these patients was dependent on initial disease severity as assessed by total ALP and on previous bisphosphonate treatment (26–29) . The efficacy of pamidronate treatment in our study was lower than reported in several previous studies (19,28,30,31) .…”

Section: Discussionsupporting

confidence: 87%

“…An interesting study comparing a same total dose of intravenous pamidronate (180 mg for 1 yr, given as 30 mg weekly for the first 6 wk or 45 mg every 3 mo) with a higher dose (360 mg for 1 yr, given as 30 mg weekly for the first 6 wk and a further 60 mg weekly for other 3 wk) showed a dose–response effect, with the more severely affected patients requiring a higher total dose for disease suppression (32) . Other studies confirmed this observation (26,27,33) . It is possible that higher dose or more frequent administration of pamidronate might have increased response rates in our study.…”

Section: Discussionmentioning

confidence: 96%

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Comparison of Different Intravenous Bisphosphonate Regimens for Paget's Disease of Bone

Merlotti

Gennari

Martini

et al. 2007

Journal of Bone and Mineral Research

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This randomized study compared different intravenous bisphosphonates in PDB. Zoledronate was superior with respect to pamidronate in achieving biochemical remission, with therapeutic response maintained in most patients at 15 mo. Single neridronate and zoledronate infusion showed a similar efficacy in up to 90% of patients nonresponders to pamidronate.Introduction: Intravenous bisphosphonates represent a common therapy for Paget's disease of bone (PDB). However, there have been few head to head randomized trials comparing intravenous bisphosphonates. Materials and Methods: We performed a 15-mo, randomized study comparing different intravenous bisphosphonates in 90 subjects with active PDB. At baseline, patients were randomly assigned to receive pamidronate (30 mg, IV, for 2 consecutive days every 3 mo; n ‫ס‬ 60) or zoledronate (4 mg, IV; n ‫ס‬ 30). After 6 mo, nonresponders to pamidronate were crossed over to zoledronate or neridronate (100 mg, IV, for 2 consecutive days). The primary efficacy endpoint was therapeutic response at 6 mo, defined as normalization of alkaline phosphatase (ALP) or a reduction of at least 75% in total ALP excess. Results: At 6 mo, 97% of patients receiving zoledronate had a therapeutic response compared with 45% of patients receiving pamidronate. Normalization of ALP was achieved in 93% of patients in the zoledronate group and in 35% of patients in the pamidronate group. ALP normalization was maintained in 79% and 65% of zoledronate-treated patients after 12 and 15 mo, respectively; loss of therapeutic response was observed in 2 of 30 (6%) at 12 and 15 mo. At 6 mo, 27 patients showing therapeutic response to pamidronate continued the treatment, whereas nonresponders were crossed-over to neridronate (n ‫ס‬ 15) or zoledronate (n ‫ס‬ 18). Among these subjects, 14 of 15 (93%) in the neridronate group and 17 of 18 (94%) in the zoledronate group achieved a therapeutic response. Similar normalization rates were observed between neridronate-(80%) and zoledronate-(83%) treated subjects. Normalization and therapeutic response were maintained at 9 mo from treatment (corresponding to 15 mo from the baseline visit) in either neridronate or zoledronate groups. Conclusions: Single neridronate and zoledronate infusion showed a similar efficacy in achieving biochemical remission in up to 90% of patients nonresponders to pamidronate. Therapeutic response to zoledronate seems to be maintained in most patients at 15 mo.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 96%

Comparison of Different Intravenous Bisphosphonate Regimens for Paget's Disease of Bone

Merlotti

Gennari

Martini

et al. 2007

Journal of Bone and Mineral Research

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“…The drug's availability in the intravenous form for the treatment of malignant bone complications has led to a variety of regimens (60)(61)(62)(63)(64)(65)(66)(67)(68). The most-utilized protocol (off label in most countries) (82).…”

Section: Pamidronatementioning

confidence: 99%

Paget’s disease

et al. 2014

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Paget’s disease of bone is the most common metabolic bone disease after osteoporosis and affects 2-4% of adults over 55 years of age. Its etiology is only partly understood and includes both genetic and environmental factors. The disease may be asymptomatic and can be uncovered incidentally on x-ray or in biochemical tests performed for another condition. It can also manifest itself with bone pain, deformity, fracture or other complications. Paget’s disease is diagnosed by x-rays and in general has very typical radiological features, but occasionally the clinical picture may be unusual and a differential diagnosis of sclerotic or lytic metastases needs to be considered. Plasma total alkaline phosphatase activity is the most clinically useful indicator of disease activity. It is elevated in most untreated patients, but may be within the normal range in patients with monostotic or limited disease. Bisphosphonate therapy is indicated for patients with symptoms and should also be considered in patients with disease sites that suggest a risk of complications, such as long bones, vertebrae or base of the skull. Orthopedic surgery in Paget’s disease patients includes almost exclusively the correction of fractures and arthroplasty.

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“…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. 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.…”

Section: Treatment Options For Pdbmentioning

confidence: 78%

Current options for the treatment of Paget’s disease of the bone

Merlotti¹,

Gennari²,

Martini³

et al. 2009

OARRR

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Paget’s disease of bone (PDB) is a chronic bone remodelling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an incidence of less than 1%, but has a grave prognosis. Specific therapy for PDB is aimed at decreasing the abnormal bone turnover and bisphosphonates are currently considered the treatment of choice. These treatments are associated with a reduction in plasma alkaline phosphatase (ALP) activity and an improvement in radiological and scintigraphic appearance and with a reduction in bone pain and bone deformity, Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes, allowing a more effective and convenient management of this debilitating disorder.

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Treatment of paget's disease with intermittent low-dose infusions of disodium pamidronate (APD)

Cited by 30 publications

References 17 publications

Comparison of Different Intravenous Bisphosphonate Regimens for Paget's Disease of Bone

Comparison of Different Intravenous Bisphosphonate Regimens for Paget's Disease of Bone

Paget’s disease

Current options for the treatment of Paget’s disease of the bone

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Treatment of paget's disease with intermittent low-dose infusions of disodium pamidronate (APD)

Cited by 30 publications

References 17 publications

Comparison of Different Intravenous Bisphosphonate Regimens for Paget's Disease of Bone

Comparison of Different Intravenous Bisphosphonate Regimens for Paget's Disease of Bone

Paget’s disease

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

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Current options for the treatment of Paget’s disease of the bone