Intravenous aminobisphosphonate in Paget's disease: clinical, biochemical, histomorphometric and radiological responses

Abstract

Intravenous 3-amino-1-hydroxypropylidene-1, 1-bisphosphonic acid (APD) was used to treat 26 patients with Paget's disease. Three daily dosages were studied; 20-30 mg/day in 20 patients, 45 mg/day in three patients and 60 mg/day in three patients, by daily 4-hour infusions for 2-10 days. The fasting urinary hydroxyproline excretion (HypE) declined exponentially, reaching 50% of pretreatment values at 1.92 +/- 0.16 (mean +/- SEM) days. This initial rapid decline was complete by 4 days following treatment to a mean of 28.0 +/- 3.4% of pretreatment values. Thereafter, there was no significant decline in HypE. The initial rate of decline of HypE was unchanged by increasing the daily dose of APD. Transient non-symptomatic hypocalcaemia with secondary hyperparathyroidism occurred in all patients. No adverse changes in the renal handling of calcium or phosphate, as seen with high-dose 1-hydroxyethylidene-1, 1-bisphosphonate (EHDP), were seen in any patient on any daily dose. Fever occurred in 73% of patients in the first 2 days of treatment. Overall, there was a significant fall in the lymphocyte count (P less than 0.005 febrile group, n = 19; P less than 0.02 non-febrile group, n = 7) and a fever-dependent rise in the neutrophil count (P less than 0.005 febrile group only). The occurrence of fever was associated with a more rapid decline in HypE, compared to the non-febrile group, so that HypE was significantly lower in the febrile group by day 5 (P less than 0.025). Seventy-two per cent of patients with bone and/or joint pain reported a reduction in pain.(ABSTRACT TRUNCATED AT 250 WORDS)

A six‐month randomized, controlled, double‐blind, dose‐response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug–refractory ankylosing spondylitis

“…A high frequency of arthralgia and myalgia after the first IV infusion of pamidronate, even in those who received only 10 mg, highlights the potential difficulties in ensuring effective patient blinding during the conduct of a placebo‐controlled trial with this agent. The observed frequency was higher than that reported in previous studies evaluating pamidronate in metabolic bone disease (26), and our results therefore could at least partly reflect some degree of expectation bias. On the other hand, the similar high frequency of adverse events in the 2 treatment arms does suggest that the strategy of using a 10‐mg dose of pamidronate as the comparator arm as opposed to placebo was successful in ensuring effective patient blinding.…”

An In Vitro and In Vivo Study of Cytokines in the Acute-Phase Response Associated with Bisphosphonates

“…The mode of bisphosphonates action is still not completely clear but it has been shown that pamidronate suppresses the accession of osteoclast precursors onto bone, and their transformation into mature osteoclasts [2,3]. Pamidronate is generally well tolerated [5][6][7][8][9], but some patients treated for the first time develop a transient, selflimiting, febrile reaction alone or associated with flu-like symptoms (e.g., malaise and myalgias) and hematological changes [2, 5-7, 9, 10]. This reaction closely resemble the acute phase response (APR) found only with bisphosphonates that, like pamidronate, contain nitrogen.…”

A 2-Year Phase II Study with 1-Year of Follow-up of Risedronate (NE-58095) in Postmenopausal Osteoporosis

“…Etidronate, pamidronate and clodronate are clinically useful in diseases with increased bone resorption, particularly Paget's disease and hypercalcemia of malignancy [7][8][9]41,42]. Risedronate, etidronate, and clodronate affect experimental bone model systems to different degrees.…”

“…The main biological effect is a decrement in bone resorption through inhibition of osteoclast activity. The bisphosphonates have been used to treat a variety of disorders characterized by increased bone resorption, including Paget's disease, hypercalcemia, metastatic bone disease, and recently osteoporosis [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Presently, only etidronate and alendronate are approved for osteoporosis treatment.…”