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Intravenous aminobisphosphonate in Paget's disease: clinical, biochemical, histomorphometric and radiological responses
Author(s) -
Fenton Anna J.,
Gutteridge Donald H.,
Kent G. Nell,
Price Roger I.,
Retallack Robert W.,
Bhagat Chotoo I.,
Worth Graeme K.,
Thompson Richard I.,
Watson Ian G.,
BarryWalsh Caltriona,
Matz Leonard R.
Publication year - 1991
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1991.tb00294.x
Subject(s) - medicine , hypocalcaemia , adverse effect , excretion , gastroenterology , endocrinology , calcium
Summary Intravenous 3‐amino‐l‐hydroxypropylidene‐1, 1‐blsphosphonic 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 hydroxyprollne excretion (Hyp e ) 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 Hyp e . The Initial rate of decline of Hyp e 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‐hydroxyethylldene‐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 > 0·005 febrile group, n =19; P > 0·02 non‐febrile group, n =7) and a fever‐dependent rise in the neutrophil count ( P > 0·005 febrile group only). The occurrence of fever was associated with a more rapid decline in Hyp e , compared to the non‐febrile group, so that Hyp e was significantly lower in the febrile group by day 5 ( P > 0·025). Seventy‐two per cent of patients with bone and/or joint pain reported a reduction in pain. APD therapy resulted in repair or arrest of progression of Pagetic lytlc bone lesions in those seven patients with measurable lesions. Quantitative histomorphometry was performed in eight patients. Significant Improvement was seen in all Indices. In the six patients for whom a post‐treatment calcification rate could be deter‐mined, there was no evidence of a mineralization defect. All patients with mild‐moderate disease (Hyp e > 10 μmol/IGF) achieved normal Hyp e and alkaline phosphatase values following a single course of APD. Provided that pretreatment Hyp e was · 10 μmol/IGF, an upper limit for the total dose of APD required to achieve normalization of Hyp e could be estimated. For those patients with ‘severe’ disease (defined as Hyp e > 10 μmot/1 GF), a reduction of > 50% In Hyp e could be achieved readily, but biochemical normalization was not possible with a single course of up to 315 mg of APD .