Intravenous aminobisphosphonate in Paget's disease: clinical, biochemical, histomorphometric and radiological responses.
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)
Fenton
A J
AJ
Department of Endocrinology, Sir Charles Gairdner Hospital, Nedlands, Australia.
Gutteridge
D H
DH
Kent
G N
GN
Price
R I
RI
Retallack
R W
RW
Bhagat
C I
CI
Worth
G K
GK
Thompson
R I
RI
Watson
I G
IG
Barry-Walsh
C
C
D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D007262:Infusions, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077268:Pamidronate; D011859:Radiography
D004164:Diphosphonates; D000077268:Pamidronate; D006909:Hydroxyproline