Acquired Resistance to Bisphosphonates in Paget's Disease of Bone

Papapoulos, Socrates E.; Eekhoff, Elisabeth M. W.; Zwinderman, Aeilko H.

doi:10.1359/jbmr.06s216

Cited by 32 publications

(19 citation statements)

References 26 publications

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“…Previous observations in other PDB samples suggested that the development of secondary hyperparathyroidism is associated with reduced response to bisphosphonate treatment. (9) These data are also consistent with similar observations derived from studies of amino-bisphosphonates for osteoporosis, generally showing increased bone mineral density (BMD) gain and higher antifracture efficacy in vitamin D-depleted compared with vitamin D-deficient subjects. (29)(30)(31)(32) Taken together, these observations further underline the necessity to recommend adequate vitamin D intake in PDB patients undergoing bisphosphonate treatment.…”

Section: Discussionsupporting

confidence: 87%

“…As a counterpart, acquired resistance to the intravenous infusion of some amino-bisphosphonates such as pamidronate has been reported in different studies. (9,15,18,19) In one of these studies, we demonstrated that intravenous infusions with either zoledronate or neridronate are effective in achieving therapeutic response at 6 months in up to 90% of patient nonresponders to multiple courses of pamidronate. (15) Results from this study confirm and extend these observations and indicate that a single course with neridronate 200 mg is effective and normalizes bone turnover in up to 85% of patients with PDB within the first year of treatment and in up to 55% after the second year.…”

Section: Discussionmentioning

confidence: 99%

“…(9) Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes. These compounds have a high binding affinity to hydroxyapatite as well as increased potency in terms of inhibition of bone resorption.…”

mentioning

confidence: 99%

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Comparison of intravenous and intramuscular neridronate regimens for the treatment of paget disease of bone

Merlotti

Rendina

Gennari

et al. 2010

Journal of Bone and Mineral Research

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Aminobisphosphonates actually represent the most common treatment for Paget disease of bone (PDB). In a previous study we demonstrated that either zoledronic acid (4 mg) or neridronate (200 mg) given as a single intravenous infusion showed a similar shortterm efficacy in achieving biochemical remission in up to 90% of patient nonresponders to pamidronate. In this study we compared the long-term (36 months) effects of a same neridronate dose (200 mg) given as an intravenous (100-mg infusion for 2 consecutive days) or intramuscular (25-mg injection weekly for 2 months) regimen in 56 patients with active PDB. All patients were advised to receive calcium plus vitamin D supplementation throughout the study period. At 6 months, 92.6% and 96.5% of patients receiving intravenous and intramuscular neridronate, respectively, achieved a therapeutic response [defined as normalization of alkaline phosphatase (ALP) levels or a reduction of at least 75% in total ALP excess]. The response to treatment was significantly correlated with baseline ALP and 25-hydroxyvitamin D [25(OH)D] levels at 6 months. The decrease in ALP levels was highest in patients with higher baseline total or bonespecific ALP levels and with higher 25(OH)D levels at 6 months. Response rates were maintained at 12 months but decreased progressively at 24 and 36 months without significant differences between the two neridronate regimens. Both regimens were well tolerated. The only relevant side effect was an acute-phase response occurring in 14% of the patients. In conclusion, these results indicate that a 200-mg intramuscular neridronate course has a similar efficacy as an intravenous infusion of the same dose for the treatment of PDB and might be of particular value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusions. ß

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Comparison of intravenous and intramuscular neridronate regimens for the treatment of paget disease of bone

Merlotti

Rendina

Gennari

et al. 2010

Journal of Bone and Mineral Research

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“…In studies on patients who had not previously received bisphosphonates, the response could be higher, with biochemical normalization in up to 85% of patients with moderate disease [84]. However, in patients with severe disease, multiple visits and treatment courses are generally required and resistance has been described in a proportion of cases [84,91]. Higher cumulative dosages of pamidronate have been also used in patients with severe PDB, with contrasting Table 2.…”

Section: Treatment Regimens For Pdbmentioning

confidence: 99%

Paget’s disease of bone: epidemiology, pathogenesis and pharmacotherapy

Gennari

Merlotti

Rendina

et al. 2014

Expert Opinion on Orphan Drugs

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“…The physicochemical effects of many of the bisphosphonates are very similar to those of pyrophosphate 26,27. Thus, they inhibit the formation, delay the aggregation, and also slow down the dissolution of calcium phosphate crystals.…”

Section: Treatment Options For Pdbmentioning

confidence: 99%

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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Acquired Resistance to Bisphosphonates in Paget's Disease of Bone

Cited by 32 publications

References 26 publications

Comparison of intravenous and intramuscular neridronate regimens for the treatment of paget disease of bone

Comparison of intravenous and intramuscular neridronate regimens for the treatment of paget disease of bone

Paget’s disease of bone: epidemiology, pathogenesis and pharmacotherapy

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

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Acquired Resistance to Bisphosphonates in Paget's Disease of Bone

Cited by 32 publications

References 26 publications

Comparison of intravenous and intramuscular neridronate regimens for the treatment of paget disease of bone

Comparison of intravenous and intramuscular neridronate regimens for the treatment of paget disease of bone

Paget’s disease of bone: epidemiology, pathogenesis and pharmacotherapy

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

Contact Info

Product

Resources

About

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