Side effects of disodium aminohydroxypropylidenediphosphonate (APD) during treatment of bone diseases.

Mautalén, C.; Casco, C.; Gonzalez, Diana; Ghiringhelli, G; Massironi, C; Fromm, Günther A.; Plantalech, L.

doi:10.1136/bmj.288.6420.828-a

Cited by 39 publications

(6 citation statements)

References 3 publications

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“…The observed fall in total white cell count after treatment was slight and not significant when those patients who had received concomitant cytotoxic chemotherapy were excluded. This compares favourably with the toxicity profile observed with the other amino bisphosphonates pamidronate and alendronate, both of which are normally associated with an acute-phase response (Mautalen et al, 1984;Adami et al, 1987).…”

Section: Discussionsupporting

confidence: 56%

Treatment of malignant hypercalcaemia with aminohexane bisphosphonate (neridronate)

O'Rourke

McCloskey²,

Rosini³

et al. 1994

Br J Cancer

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Summary Twenty patients with hypercalcaemia due to malignancy, which persisted following rehydration, were treated with the bisphosphonate, aminohexane bisphosphonate (AHBP), which is structurally similar to pamidronate. The treatment given was a single infusion of 125 mg of AHBP in 500 ml of normal saline infused over 4 h. Serum and urine biochemistry were measured before and after treatment. Acute toxicity was evaluated with particular attention to gastrointestinal symptoms, acute-phase reaction and change in renal function, as judged by serum creatinine. The infusion of AHBP induced a rapid fall apparent by day 3 (P<0.001), with a nadir at day 7. The serum calcium remained lower at days 14 and 28 than at day 0, but the numbers followed up were low (n = 5 and n = 4). In all 20 patients there was a fall in serum calcium after treatment, and in 13 (65%) normocalcaemia was achieved. Failure to respond completely to AHBP appeared to be associated with a renal mechanism of hypercalcaemia. Treatment was associated with a significant decrease in fasting urinary calcium excretion (P<0.05). There was no change in white cell count or renal function following AHBP and only two cases of mild pyrexia after infusion. We conclude that aminohexane bisphosphonate is an effective agent in the treatment of tumour-induced hypercalcaemia, with rapid onset of effect and low toxicity.Hypercalcaemia is a common complication of malignancy, occurring both in patients with solid tumours, particularly carcinoma of the breast and bronchus, and in patients with haematological malignancy. The pathophysiology of the condition varies according to the primary tumour and the presence or absence of focal bone metastases, but in the majority of cases the predominant mechanism is one of increased bone resorption (Bonjour & Rizzoli, 1989). Treatment strategies have therefore focused on the inhibition of bone resorption, and over the past decade the bisphosphonates, specific and potent inhibitors of osteoclastmediated bone resorption, have become the treatment of choice (Coleman & Rubens, 1987;Kanis et al., 1991).The bisphosphonates have in common the central P-C-P structure, but modifications of the side chains alter their biological characteristics, particularly their potency. There are currently three bisphosphonates available for the treatment of tumour-induced hypercalcaemia: 1-hydroxyethylidene-1,1-bisphosphonic acid (HEBP or etidronate), dichloromethylenebisphosphonic acid (Cl2MBP or clodronate) and 3-amino-ihydroxypropylidene-l ,1-bisphosphonic acid (AHPrBP or pamidronate). Pamidronate is the most potent, and research on other experimental compounds suggests that the amino derivatives are particularly active (Shinoda et al., 1983;Rizzoli et al., 1992).However, clinical studies have shown that pamidronate may be associated with a transient acute-phase response which can be manifested as pyrexia or leucopenia Morton et al., 1989). In addition, there are reports of muscle rigors, general malaise, thrombophlebitis and hypocalcaemia, and with the...

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Section: Discussionsupporting

confidence: 56%

Treatment of malignant hypercalcaemia with aminohexane bisphosphonate (neridronate)

O'Rourke

McCloskey²,

Rosini³

et al. 1994

Br J Cancer

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“…It has been successfully and extensively used in Paget's disease of bone,28 , 29 malignant hypercalcemia,30 lytic bone metastases,31 , 32 multiple myeloma,33 and osteoporosis 34 , 35. Intravenous administration is preferred to oral intake because of the poor digestive tolerance (gastralgia, esophagitis) of the compound when it is given orally36 and of the low intestinal absorption of bisphosphonates in general 37. The intravenous administration allows a rapid and prolonged intake of pamidronate in bone matrix.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Intravenous Pamidronate in Fibrous Dysplasia of Bone

Chapurlat

Delmas

Liens

et al. 1997

Journal of Bone and Mineral Research

215

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Fibrous dysplasia of bone (FD) is a rare disorder characterized by proliferation of fibrous tissue in bone marrow leading to osteolytic lesions. It causes bone pain and fractures. To date the only treatment is orthopedic. Histological and biochemical similarities between FD and Paget's bone disease related to increased osteoclastic resorption led us to propose treatment with the bisphosphonate pamidronate. The aim of the study was to assess the long-term effects of intravenous pamidronate in FD. In this open label phase III study, 20 patients with FD (11 males and 9 females; mean age 31 years) received courses of 180 mg of intravenous pamidronate every 6 months (60 mg/day during 3 days by infusion). The mean duration of follow-up was 39 months (range 18 -64). Severity of bone pain, number of painful skeletal sites per patient, X-rays of all involved areas, serum alkaline phosphatase, fasting urinary hydroxyproline, and urinary type I collagen C-telopeptide were assessed every 6 months. The severity of bone pain and the number of painful sites appeared to be significantly reduced. All biochemical markers of bone remodeling were substantially lowered. We observed a radiographic response in nine patients with refilling of osteolytic lesions. A mineralization defect proven by bone biopsy was observed in one case. Four patients sustained bone stress lines, but no fracture occurred. We suggest that intravenous pamidronate alleviates bone pain, reduces the rate of bone turnover assessed by biochemical markers, and improves radiological lesions of FD. Few side effects were

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“…A few sporadic cases of toxiderma have been reported with clodronic acid, [102] pamidronic acid [103,104] and tiludronic acid.£I05] The skin reactions were moderate and short lasting in these reports, but in the patients described by Roux et al,u05] the erythematous lesions were generalised, severe and lasted several months, despite the low doses of tiludronic acid administered (200 mg/day orally for 20 days). The cause of these lesions is unclear.…”

Section: 4 Other Drug-related Adverse Effectsmentioning

confidence: 99%

Adverse Effects of Bisphosphonates

1996

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The bisphosphonates comprise a new class of drugs, and are increasingly being used to treat bone diseases characterised by increased osteoclastic bone resorption. These compounds are generally well tolerated, but toxicity may vary considerably from one compound to another. Dosages of etidronic acid above 800 mg/day impair the normal skeletal mineralisation and this may be associated with the appearance of fractures, but at the doses used for the treatment of osteoporosis, none of the bisphosphonates induce clinical or histological signs of impaired mineralisation. The skeletal half-life of bisphosphonates is of the order of several years, but this appears to be of little clinical consequence since the pharmacological effect is of relatively short duration. The mechanical properties of the skeleton of animals treated over long periods with high doses of various bisphosphonates have been shown to be perfectly preserved. However, in growing individuals, excess inhibition of bone remodelling might induce osteopetrotic-like alterations. When high doses of amino-bisphosphonates are given to patients who have never received bisphosphonate therapy, the patients may experience fevers up to 39 degrees C for 1 to 3 days, associated with transient haematological changes resembling a typical acute-phase response. Rapid intravenous injection of bisphosphonates at doses greater than 200 to 300 mg may cause severe renal failure; this can be prevented by slowing the rate of infusion (< 200 mg/h). Administration of high doses of bisphosphonates to patients with high bone turnover may induce a rapid and transient drop in serum calcium which is seldom symptomatic. The gastrointestinal absorption of bisphosphonates is low, and they must be taken without food. Oral amino derivatives may induce dose-related serious gastrointestinal lesions, with the sporadic appearance of erosive oesophagitis. Amino-bisphosphonate administration has been also associated with the sporadic occurrence of uveitis, scleritis and phlebitis and, in single cases, with irritative reactions at the skin, peritoneum and pericardium.

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Side effects of disodium aminohydroxypropylidenediphosphonate (APD) during treatment of bone diseases.

Abstract: 1-hydroxypropylidene-1,1-bisphosphonate (APD) in the treatment of patients with Paget's bone disease. Medicina (B Aires) (in press). Van Breukelen FJM, Bijvoet OL, Van Oosterom AT. Inhibition of osteolytic bone lesions by (3-amino-i-hydroxypropylidene)-1,1-bis

Cited by 39 publications

References 3 publications

Treatment of malignant hypercalcaemia with aminohexane bisphosphonate (neridronate)

Treatment of malignant hypercalcaemia with aminohexane bisphosphonate (neridronate)

Long-Term Effects of Intravenous Pamidronate in Fibrous Dysplasia of Bone

Adverse Effects of Bisphosphonates

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