Abstract
Background
Bisphosphonates are powerful inhibitors of osteoclast-mediated bone resorption. They are effective in the treatment of Paget's disease of the bone, tumor-associated hypercalcemia, and osteoporosis. They are also used to treat metastatic bone disease. YM-175 is a new highly potent bisphosphonate. Bisphosphonates are also used as radiopharmaceuticals in bone scintigraphy. The data remain unclear as to whether or not the administration of large amounts of bisphosphonate interferes with the bone scintigraphy process.
Methods
We have treated 8 patients with bone metastases from breast cancer with 10 mg IV, once a week for 5 weeks. The monitoring of bone pain, laboratory analysis with bone metabolic markers, and bone imaging including x-ray and bone scintigraphy, was performed for 8 weeks. A quantitative method was employed to evaluate serial bone scintigraphy.
Results
Bone pain improved in 5 out of 8 cases at 2 and 4 weeks post-treatment without serious adverse effects, but the duration of pain relief was short. Markers of osteoclast activity were decreased significantly to a minimum at 2 weeks. No significant changes were shown in markers of osteoblast activity or in serum calcium levels. Intact parathyroid hormone (PTH) was elevated at 2 and 4 weeks. It appears that YM-175 suppressed osteoclast activity, however, its effect was negated by a PTH elevation response. No changes were detected in either x-ray findings or serial bone scintigraphy by use of visual images and quantitative methods.
Conclusion
YM-175, a new bisphosphonate, was a safe and promising drug for the treatment of metastatic bone pain from breast cancer. Osteoclast activity was suppressed by bisphosphonate treatment, but, the PTH response negated the osteoclast suppression. Furthermore, YM-175 treatment did not alter bone scintigraphic images.
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References
Harinck HI, Papapoulos SE, Blanksma HJ, Moolenaar AJ, Vermeji P, Bijvoets OL. Paget's disease of bone: early and late response to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD). BMJ 1987;295:1301–1305.
Ralston SH, Gallacher SJ, Patel U, Dryburgh FJ, Fraser WD, Cowan RA. Comparison of three intravenous bisphosphonates in cancer-associated hypercalcemia. Lancet 1989;2:1180–1182.
Singer FR. Role of bisphosphonate etidronate in the therapy of cancer-related hypercalcemia. Semin Oncol 1990;17:34–39.
Fukumoto S, Matsumoto T, Takebe K, Onaya T, Eto S, Ogata E. Treatment of malignant-associated hypercalcemia with YM175, a new bisphosphonate: Elevated threshold for parathyroid hormone secretion in hypercalcemic patients. J Clin Endcrinol Metab 1994;79:165–170.
Watts NB, Harris ST, Genant HK, Wasnich RD, Miller PD, Jackson RD. Intermittent cyclical etidronate treatment of post menopausal osteoporosis. N Engl J Med 1990;323:73–79.
Van Holten-Verzantvoort AT, Bijvoet OL, Cleton FJ, Hermans J, Kroon HM, Harinick HI. Reduced morbidity from skeletal metastases in breast cancer patients during long-term bisphosphonate (APD) treatment. Lancet 1987;2:983–985.
Parerson AH, Powles TJ, Kanis JA, McCloskey E, Hanson J, Ashley S. Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer. J Clin Oncol 1993;11:59–65.
Coleman RE, Woll PJ, Miles M, Scrivener W, Rubens RD. Treatment of bone metastases from breast cancer with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD). Br J Cancer 1988;58:621–625.
Glover D, Lipton A, Keller A. Intravenous pamidronate disodium treatment of bone metastases in patients with breast cancer. Cancer 1994;74:2949–2955.
Pecherstorfer M, Schilling T, Janisch S, Woloszczuk W, Baumgartner G, Ziegler R, Ogris E. Effect of clodronate treatment on bone scintigraphy in metastatic breast cancer. J Nucl Med 1993;34:1039–1044.
Vellenga CJ, Pauwels EK, Bijvoet OL, Harick HI, Frijlink WB. Quantitative bone scintigraphy in Paget's disease treated with APD. Br J Radiol 1985;58:1165–1172.
Sandler ED, Parisi MT, Hattner RS. Duration of etidronate effect demonstrated by serial bone scintigraphy. J Nucl Med 1991;32:1633–1634.
Krasnow AZ, Collier BD, Isitman AT, Hellmann RS, Ewey D. False negative bone imaging due to etidronate disodium therapy. Clin Nucl Med 1988;13:264–267.
Nagao Y, Ishitobi Y, Kinoshita H, Fukushima S, Kawashima H. YM175, a new bisphosphonate, increase serum 1,25-dihydroxyvitamin D in rats via stimulating renal 1-hydroxylase activity. Biochem Biophys Res Commun 1991;180:1172–1178.
Tong D, Gillick L, Hendrickson F.R. The palliation of symptomatic osseous metastases: final results of the study by the Radiation Therapy Oncology Group. Cancer 1982;50:893–899.
Jung A, Bomand J, Mermillod B, Edonuard C, Meunier PI. Inhibition by disphosphonates of bone resorption induced by the Walker tumor of the rat. Cancer Res 1984;44:3007–3011.
Nemoto R, Nishijima Y, Uchida K, Koiso K. Inhibition by a new bisphosphonate (YM175) of bone resorption induced by the MTB-2 tumor of mice. Br J Cancer 1993;67:893–897.
Netelenbos JC, van Ginkel FC, Lips P, Leeuwenkamp OR, Barto R, van der Vijgh WJ. Effect of a single infusion of aminohydroxypropylidene on calcium and bone metabolism in healthy volunteers monitored during 2 months. J Clin Endoclinol Metab 1991;72:223–228.
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Koizumi, M., Sekine, H., Aoki, M. et al. Efficacy of YM-175, a new bisphosphonate, in the treatment of metastatic bone tumor from breast cancer and its effect on scintigraphy. Int J Clin Oncol 1, 18–22 (1996). https://doi.org/10.1007/BF02347263
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DOI: https://doi.org/10.1007/BF02347263