Long-term elevation of 1,25-dihydroxyvitamin D after short-term intravenous administration of pamidronate (aminohydroxypropylidene bisphosphonate, APD) in paget's disease of bone

Open Access
Publisher Website
Google Scholar
Abstract
We report the prolonged biochemical changes that occurred in patients with Paget's disease when treated for 2–10 days with pamidronate disodium (3-amino-1-hydroxypropylidine-1,1-bisphosphonate, APD), by IV administration and observed for 6 months following therapy. In all 24 patients studied, bone resorption (measured by urinary hydroxyproline/creatinine ratio, OHP/Cr) fell sharply on treatment, from 0.12 ± 0.02 (mean ± SEM; above reference limits) to 0.04 ± 0.008 (reference range 0.006–0.027 for females, 0.005–0.020 for males), remaining at this level 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 levels (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 1,25-dihydroxyvitamin D [1,25-(OH)2D]. The hormonal responses, however, were profound. Serum immunoreactive PTH (iPTH) rose to twice pretreatment values (86 ± 11 pM, mean ± SEM; reference range for iPTH, >50 years, 2D levels rose to three times pretreatment values (300 ± 20 pM, mean ± SEM; reference range 50–150 pM), remaining above reference limits 4–8 weeks after therapy (188 ± 15 pM, mean ± SEM) and returning to normal values only after 12 weeks. The magnitude of the hormonal responses leads to speculation that factors other than serum calcium are involved in affecting these levels. Serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] levels were below the mean of the reference range before treatment (3.93 ± 0.5 nM, mean ± SEM) and fell significantly with APD therapy (2.44 ± 0.25 nM, mean ± SEM), 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)2D levels in patients with Paget's disease treated with calcitonin (CT) or etidronate (EHDP). We now find a more pronounced and prolonged change in serum 1,25-(OH)2D with short-term IV APD treatment, which could indicate that with this bisphosphonate there is a long-term increase in gut calcium absorption. Also, 1,25-(OH)2D may play a role in the healing of pagetic lesions whether the treatment is CT, EHDP, or APD.