Clinical, biochemical, hematologic, and radiographic responses in Paget's disease following intravenous pamidronate disodium: A 2-year study

Gutteridge, D.H., Retallack, R.W., Ward, L.C., Stuckey, B.G.A., Stewart, G.O., Kent, G.N., Bhagat, C.I., Price, R.I. and Nicholson, G.C. (1996) Clinical, biochemical, hematologic, and radiographic responses in Paget's disease following intravenous pamidronate disodium: A 2-year study. Bone, 19 4: 387-394. doi:10.1016/S8756-3282(96)00224-4

Author Gutteridge, D.H.
Retallack, R.W.
Ward, L.C.
Stuckey, B.G.A.
Stewart, G.O.
Kent, G.N.
Bhagat, C.I.
Price, R.I.
Nicholson, G.C.
Title Clinical, biochemical, hematologic, and radiographic responses in Paget's disease following intravenous pamidronate disodium: A 2-year study
Journal name Bone   Check publisher's open access policy
ISSN 8756-3282
Publication date 1996-10
Sub-type Article (original research)
DOI 10.1016/S8756-3282(96)00224-4
Volume 19
Issue 4
Start page 387
End page 394
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Abstract An intravenous dosage schedule using pamidronate disodium, based on biochemical severity, was used to treat 71 patients with Paget's disease who had had no previous bisphosphonate treatment. Disease severity was stratified by fasting hydroxyproline excretion (Hyp(E)): Group (Gp) I (mild disease; Hyp(E) < 5.0 μmol/LGF) received a total dose of 120 mg; Gp II (moderate; Hyp(E), 5.00-9.99) received 180 mg; and Gp III (severe; Hyp(E) ≤ 10) received 240 mg. Within each group patients were randomly allocated to receive daily 30 mg or 60 mg infusions. Observations for 2 years included pain scores, indices of bone turnover, and radiology of lytic lesions. There was no difference in biochemical responses, or in the percentage of patients with early fever, between the 30 mg and 60 mg daily subgroups; for convenience, 60 mg infusions are recommended. Neutrophils and total white cell counts were both significantly below baseline 4 days after the first infusion; lymphocytes were significantly reduced by day 2; and all three measures had returned to within the reference range by day 6. Remission was assessed at 6 months, when both plasma alkaline phosphatase (ALP) and Hyp(E), had reached stable nadirs. Increasing severity was associated with increasing resistance to suppression of Hyp(E) at 6 months to within the reference range: Gp I, 87%; Gp II, 44%; and Gp III, O% (p < 0.0001 by chi-square test). Biochemical relapse at 2 years (defined as ALP 50% above the 6 month level) was also dependent on initial disease severity (Gp I, 6%; GpII, 39%; Gp III, 62%;p < 0.0005 by chi-square test). There was no association between time to relapse and either initial dose or log dose. Radiologic lytic lesions (in 22 patients) were all in remission at 3 months; however, relapse rates at 2 years appeared to be severity-dependent: Gp I, 13%; Gp II, 43%; and Gp III, 57% (n.s. by chi-square test). Remission rates based on a fall to < 50% of pretreatment of either Hyp(E) or ALP were more in accord with lytic lesion remission rates than were rates based on Hyp(E) falling to within the reference range. Pamidronate produced a significant reduction from baseline in Pagetic bone, Pagetic joint, and unrelated musculoskeletal pain in the first 6 months (p < 0.0001). From 0 months to 2 years the maintenance of improvement in bone pain (p < 0.005) and joint pain (p < 0.05) was significantly better than in unrelated pain. Pamidronate is a safe, well-tolerated, and effective treatment for Paget's disease. In spite of larger dosage in severe disease, increasing severity was associated with resistance to normalization of biochemistry and a higher incidence of biochemical and radiological relapse at 2 years. Our current dosage recommendation would be for two 60 mg infusions for mild disease (Gp I); and four 60 mg infusions for moderate disease (Gp II). Severe disease (Gp III) remains a challenge; regardless of dosage, the majority of patients will be in relapse 2 years after a single course of treatment.
Keyword Paget's disease
IV Pamidronate
Lytic XR lesions
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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