Paget's disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD).

Harinck, H. I. J.; Papapoulos, Socrates E.; Blanksma, H. J.; Moolenaar, A. J.; Vermeij, P.; Bijvoet, O. L. M.

doi:10.1136/bmj.295.6609.1301

Cited by 180 publications

(70 citation statements)

References 19 publications

(9 reference statements)

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“…The relationship between post-treatment bone turnover and prolonged remission is well recognized, (6,7,(11)(12)(13)(14) but this study extends these observations. The plots of individual data points are important because they allow comparison between the two bisphosphonates at any given level of bone turnover.…”

Section: Discussionsupporting

confidence: 61%

“…Although the level of bone turnover 6 months after the initiation of treatment with ZOL was related to the pretreatment value, as is seen in some (14,17) but not all (11,18) previous studies, the propensity to relapse was independent of this influence. A similar lack of effect of baseline bone turnover on the duration of remission was also shown for olpadronate (14) but not for less potent bisphosphonates such as tiludronate.…”

Section: Discussionmentioning

confidence: 70%

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Long-Term Control of Bone Turnover in Paget's Disease With Zoledronic Acid and Risedronate

Hosking

Lyles

Brown

et al. 2007

Journal of Bone and Mineral Research

147

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A single 5-mg infusion of zoledronic acid restores biochemical markers of bone turnover into the reference range in the majority of patients with Paget's disease and maintains biochemical remission for at least 2 years. This effect is largely independent of pretreatment disease activity and prior bisphosphonate therapy.Introduction: Zoledronic acid (ZOL) is a potent bisphosphonate that produces a rapid and complete control of the increased bone turnover of Paget's disease. Long-term control of disease activity is an important aim of treatment in the hope that this will reduce the risk of complications such as deformity, fracture, and degenerative joint disease. Materials and Methods:This study compares the ability of ZOL 5 mg given as a 15-minute intravenous infusion with risedronate (RIS) 30 mg daily by mouth for 60 days to maintain long-term control of bone turnover. No bisphosphonate was given during the extension study. All patients (n ‫ס‬ 296) who achieved a therapeutic response, defined as normalization or a >75% reduction in the total alkaline phosphatase (total ALP) excess above the midpoint of the reference range, were eligible for inclusion. Results: ZOL maintained the mean level of total ALP at the middle of the reference range, whereas those treated with risedronate showed a linear increase in total ALP from the 6-month post-treatment time-point. Both treatments resulted in a linear relationship between the 6-month nadir and 24-month total ALP. The relationship for RIS was shifted upward, showing that for a given level of post-treatment biochemical activity, bone turnover increased with time. This was in contrast to the ZOL-treated patients where total ALP generally remained unchanged over this 18-month extension period. A similar pattern of response was seen with the other bone turnover markers. Conclusions: ZOL maintains bone turnover within the reference range over 24 months from the initiation of treatment. A reduction in the incidence and severity of long-term complications may require persistent normalization of bone turnover over many years, and this now seems a realistic possibility with ZOL.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 70%

Long-Term Control of Bone Turnover in Paget's Disease With Zoledronic Acid and Risedronate

Hosking

Lyles

Brown

et al. 2007

Journal of Bone and Mineral Research

147

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“…Intravenous pamidronate is well tolerated, although a transient leukopaenia and mild pyrexia (usually asymptomatic) may occur in some cases Harinck et al, 1987a).…”

Section: Pamidronatementioning

confidence: 99%

Medical management of hypercalcaemia.

Ralston¹

1992

Brit J Clinical Pharma

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1. Hypercalcaemia is a common disorder, which frequently requires specific treatment either to control symptoms, or to prevent the development of irreversible organ damage or death. Although the best and most effective way of controlling hypercalcaemia in the long‐term is to treat the underlying cause, medical antihypercalcaemic therapy is often required in clinical practice, either as a holding measure, or because the primary disease cannot itself be treated. 2. The mainstays of medical antihypercalcaemic therapy are firstly, to promote calcium excretion by the kidney by restoring extracellular volume with intravenous saline and secondly, to administer pharmacological agents which inhibit bone resorption. Measures which seek to reduce intestinal calcium absorption are seldom effective. 3. Intravenous bisphosphonates are the treatment of first choice for the initial management of hypercalcaemia, followed by continued oral, or repeated intravenous bisphosphonates to prevent relapse. These drugs have a relatively slow onset of action (1‐3 days) but have potent and sustained inhibitory effects on bone resorption, resulting in a long duration of action (12‐ 30 days). 4. Of the other agents available, calcitonin has an important place in the management of severe hypercalcaemia where a rapid effect is desirable; calcitonin is best used in conjunction with a bisphosphonate however, because of its short duration of action. Intravenous phosphate also has a place in the emergency management of severe hypercalcaemia, but is probably best reserved for patients in whom other less toxic therapies have failed. Corticosteroids are generally ineffective except in certain specific instances and are best avoided in the routine treatment of undiagnosed hypercalcaemia.

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“…(14)(15)(16) A commonly used approach is to give 60-90 mg as a single infusion in patients with mildly elevated SALP and multiple 90-mg infusions to patients with higher degrees of abnormal turnover. The number of doses will depend on patient response.…”

Section: Specific Anti-osteoclast Therapy For Paget's Disease Of Bonementioning

confidence: 99%

Medical Management of Paget's Disease of Bone: Indications for Treatment and Review of Current Therapies

Siris

Lyles

Singer

et al. 2006

Journal of Bone and Mineral Research

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Treatment with a potent bisphosphonate is indicated in patients with Paget's disease who have symptoms likely to respond to reduced bone turnover at pagetic sites. In asymptomatic patients with active disease at sites susceptible to local progression and late complications, treatment is also recommended. Biochemical remission is achievable in a majority of patients with pamidronate, alendronate, risedronate, or zoledronic acid. Indications for medical treatment of active Paget's disease of bone include symptoms referable to sites of the disease such as bone pain, joint pain, and neurological complications; elective surgery at an active pagetic site to reduce intraoperative blood loss from highly vascular bone; management of rare instances of immobilization hypercalcemia with polyostotic disease; and presence of disease activity in asymptomatic patients at sites at risk for future complications to limit progression and possibly lower that risk. The treatment of choice is a potent nitrogen-containing bisphosphonate, including oral alendronate or risedronate or intravenous pamidronate or zoledronic acid. Etidronate and tiludronate are less potent and are second-line choices. Recent data with zoledronic acid indicate that a single infusion of 5 mg is associated with normalization of serum alkaline phosphatase in 89% of patients and a prolonged biochemical remission, making it the most effective therapy available to date. Side effect profiles with alendronate and risedronate include esophageal irritation in a minority of patients. Intravenous pamidronate and zoledronic acid may induce an acute phase reaction with fever and flu-like symptoms with the first dose, primarily in patients who are treatment naïve to nitrogen-containing bisphosphonates. Calcium and vitamin D repletion are mandatory with these potent anti-osteoclast therapies to avoid hypocalcemia. Acquired resistance to etidronate and pamidronate has been reported in some patients, leading to lesser reductions in bone turnover and shorter periods of remission, but substitution with a different bisphosphonate provides a more robust response. It is not known whether resistance to other bisphosphonates in Paget's disease occurs.

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Paget's disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD).

Cited by 180 publications

References 19 publications

Long-Term Control of Bone Turnover in Paget's Disease With Zoledronic Acid and Risedronate

Long-Term Control of Bone Turnover in Paget's Disease With Zoledronic Acid and Risedronate

Medical management of hypercalcaemia.

Medical Management of Paget's Disease of Bone: Indications for Treatment and Review of Current Therapies

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