LONG-TERM ELEVATION OF 1,25-DIHYDROXYVITAMIN-D AFTER SHORT-TERM INTRAVENOUS ADMINISTRATION OF PAMIDRONATE (AMINOHYDROXYPROPYLIDENE BISPHOSPHONATE, APD) IN PAGETS-DISEASE OF BONE

We report the prolonged biochemical changes that occurred in patients with Paget's disease when treated for 2-10 days with pamidronate disod ium (3-amino-1-hydroxypropylidine-1,1-bisphosphonate, APD), by IV admi nistration and observed for 6 months following therapy. In all 24 pati ents studied, bone resorption (measured by urinary hydroxyproline/crea tinine ratio, OHP/Cr) fell sharply on treatment, from 0.12 +/- 0.02 (m ean +/- SEM; above reference limits) to 0.04 +/- 0.008 (reference rang e 0.006-0.027 for females, 0.005-0.020 for males), remaining at this l evel for 6 months after therapy. A fall in serum ionized calcium (Ca2) to just below the reference limits with treatment (1.11 +/- 0.02 mM; reference range 1.14-1.18 mM), followed by a rapid return to normal l evels (1.14 +/- 0.02 mM, mean +/- SEM) within 8 days of treatment, was presumably due to the cessation of release of calcium from bone. This was followed by secondary hyperparathyroidism and a rise in serum 1,2 5-dihydroxyvitamin D [1,25-(OH)(2)D]. The hormonal responses, however, were profound. Serum immunoreactive PTH (iPTH) rose to twice pretreat ment values (86 +/- 11 pM, mean +/- SEM; reference range for iPTH, >50 years, <50 pM; <50 years, <40 pM), returning to normal 4-8 weeks afte r therapy. Serum 1,25-(OH)(2)D levels rose to three times pretreatment values (300 +/- 20 pM, mean +/- SEM; reference range 50-150 pM), rema ining above reference limits 4-8 weeks after therapy (188 +/- 15 pM, m ean +/- SEM) and returning to normal values only after 12 weeks. The m agnitude of the hormonal responses leads to speculation that factors o ther than serum calcium are involved in affecting these levels. Serum 24,25-dihydroxyvitamin D [24,25-(OH)(2)D] levels were below the mean o f the reference range before treatment(3.93 +/- 0.5 nM, mean +/- SEM) and fell significantly with APD therapy (2.44 +/- 0.25 nM, mean +/- SE M), returning to pretreatment values only 12 weeks later(4.14 +/- 0.35 nM). Serum 25-hydroxyvitamin D (25-OHD) did not change with treatment . We previously reported an increase in serum 1,25-(OH)(2)D levels in patients with Paget's disease treated with calcitonin (CT) or etidrona te (EHDP). We now find a more pronounced and prolonged change in serum 1,25-(OH)(2)D with short-term IV APD treatment, which could indicate that with this bisphosphonate there is a long-term increase in gut cal cium absorption. Also, 1,25-(OH)(2)D may play a role in the healing of pagetic lesions whether the treatment is CT, EHDP, or APD.