Prevention of appendicular bone loss in Paget's disease following treatment with intravenous pamidronate disodium

It has been shown previously that intravenous pamidronate treatment for sev ere Paget's disease is associated with appendicular bone loss. This 2 year study was designed to determine whether cotreatment with calcitriol and a c alcium supplement would prevent this, Intravenous pamidronate was used to t reat 49 patients with symptomatic Paget's disease. Patients were stratified into two groups of differing biochemical severity based on hydroxyproline excretion (Hyp(E)) expressed as micromoles per liter of glomerular filtrate (GF): (1) a severe group with Hyp(E) > 10 mu mol/L GF; and (2) a moderate group with Hyp(E) 5-10 mu mol/L GF, Within each group, patients were random ly allocated to receive supplements of calcium and calcitriol (supplemented ) or no supplements (unsupplemented) after initiation of pamidronate therap y. The severe group received 360 mg of pamidronate as six doses of 60 mg on ce weekly and the moderate group received 240 mg as four weekly doses of 60 mg, Patients were followed for 24 months following treatment and had seria l bone densitometry of the forearm measured as well as urine and plasma bio chemistry, When the groups were combined, the unsupplemented patients showe d a decrease in bone mineral density (BMD) at the ultradistal forearm site, which persisted to 24 months. Those supplemented with calcium and calcitri ol showed an increase in BMD and the difference between the two groups was significant at all times posttreatment (p < 0.03). When the groups were ana lyzed separately, those with moderate disease again showed significant diff erences in BMD between supplemented and unsupplemented patients at all time points. In the severe group, the differences did not reach statistical sign ificance due to smaller patient numbers. Similar changes in BMD were also o bserved at the forearm shaft site. When serial parathyroid hormone (PTH) le vels (with the moderate and severe groups combined) were plotted against ti me since treatment the rise in PTH in the supplemented patients was less th an the rise in the unsupplemented patients (p < 0.04), These results sugges t that forearm bone loss after intravenous pamidronate treatment for modera te-to-severe Paget's disease can largely be prevented by administration of calcium and calcitriol, The mechanism may be a blunting of the secondary hy perparathyroidism that occurs after intravenous pamidronate. These findings may have wider application in moderate-to-severe Paget's disease treated w ith other bisphosphonates, (Bone 24:139-144; 1999) (C) 1999 by Elsevier Sci ence Inc. All rights reserved.