Bisphosphonate action: alendronate localization in rat bone and effects on osteoclast ultrastructure.

Sato, M; Grasser, W; Endo, N; Akins, R; Simmons, H; Thompson, D D; Golub, E; Rodan, G A

doi:10.1172/jci115539

Cited by 1,004Bone health and treatmentsBone Metabolism and DiseasesBone health and osteoporosis research

Bisphosphonate action: alendronate localization in rat bone and effects on osteoclast ultrastructure.

Open access

Sato, M, Grasser, W, Endo, N, Akins, R, Simmons, H, Thompson, D D, Golub, E, Rodan, G A·1991·Journal of Clinical Investigation

DOI 10.1172/jci115539

Open this paper in CoChat — free account Open PDF

Abstract

Studies of the mode of action of the bisphosphonate alendronate showed that 1 d after the injection of 0.4 mg/kg [3H]alendronate to newborn rats, 72% of the osteoclastic surface, 2% of the bone forming, and 13% of all other surfaces were densely labeled. Silver grains were seen above the osteoclasts and no other cells. 6 d later the label was 600-1,000 microns away from the epiphyseal plate and buried inside the bone, indicating normal growth and matrix deposition on top of alendronate-containing bone. Osteoclasts from adult animals, infused with parathyroid hormone-related peptide (1-34) and treated with 0.4 mg/kg alendronate subcutaneously for 2 d, all lacked ruffled border but not clear zone. In vitro alendronate bound to bone particles with a Kd of approximately 1 mM and a capacity of 100 nmol/mg at pH 7. At pH 3.5 binding was reduced by 50%. Alendronate inhibited bone resorption by isolated chicken or rat osteoclasts when the amount on the bone surface was around 1.3 x 10(-3) fmol/microns 2, which would produce a concentration of 0.1-1 mM in the resorption space if 50% were released. At these concentrations membrane leakiness to calcium was observed. These findings suggest that alendronate binds to resorption surfaces, is locally released during acidification, the rise in concentration stops resorption and membrane ruffling, without destroying the osteoclasts.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1172/jci115539

Cites

72 of 72 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Bisphosphonates suppress bone resorption via injury to osteoclasts when they solubilize bisphosphonate-contaminated bone.
“This phenomenon is consistent with previous observations that bisphosphonates suppress bone resorption via injury to osteoclasts when they solubilize bisphosphonate-contaminated bone (139, 140).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [140]
Bisphosphonates do not appear to suppress osteoclastogenesis.
“Bisphosphonates do not appear to suppress osteoclastogenesis (129, 140, 141)”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [140]
Bisphosphonates act by binding directly to mineralized bone matrix and directly inhibiting activity of osteoclasts that attempt to degrade bisphosphonate-laden bone.
“These agents act by binding directly to mineralized bone matrix and directly inhibiting the activity of osteoclasts that attempt to degrade bisphosphonate-laden bone (140).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [140]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A SIMPLIFIED LEAD CITRATE STAIN FOR USE IN ELECTRON MICROSCOPY
Venable, J. H., & Coggeshall, R. E. (1965) · The Journal of Cell Biology · doi:10.1083/jcb.25.2.407 · Cited by 4,555 · see citing works
A highly sensitive adenylate cyclase assay
Salomon, Y., Londos, C., & Rodbell, M. (1974) · Analytical Biochemistry · doi:10.1016/0003-2697(74)90222-x · Cited by 4,188 · see citing works
Intermittent Cyclical Etidronate Treatment of Postmenopausal Osteoporosis
Watts, N. B., Harris, S. T., Genant, H. K., Wasnich, R. D., Miller, P. D., Jackson, R. D., Licata, A. A., Ross, P. D., Woodson, G. C., Yanover, M., et al. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007123230201 · Cited by 947 · see citing works
Effect of Intermittent Cyclical Etidronate Therapy on Bone Mass and Fracture Rate in Women with Postmenopausal Osteoporosis
Storm, T., Thamsborg, G., Steiniche, T., Genant, H. K., & Sørensen, O. H. (1990) · New England Journal of Medicine · doi:10.1056/nejm199005033221803 · Cited by 932 · see citing works
Osteoclastic Bone Resorption by a Polarized Vacuolar Proton Pump
Blair, H. C., Teitelbaum, S. L., Ghiselli, R. W., & Gluck, S. L. (1989) · Science · doi:10.1126/science.2528207 · Cited by 862 · see citing works
Diphosphonates Inhibit Hydroxyapatite Dissolution in vitro and Bone Resorption in Tissue Culture and in vivo
Fleisch, H. A., Graham, R., Russell, R. G. G., & Francis, M. D. (1969) · Science · doi:10.1126/science.165.3899.1262 · Cited by 755 · see citing works
Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border.
Baron, R., Neff, L., Louvard, D., & Courtoy, P. J. (1985) · The Journal of Cell Biology · doi:10.1083/jcb.101.6.2210 · Cited by 740 · see citing works
Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization.
Nicholson, G. C., Moseley, J. M., Sexton, P. M., Mendelsohn, F. A. O., & Martin, T. J. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112584 · Cited by 454 · see citing works
The bisphosphonate alendronate (MK-217) inhibits bone loss due to ovariectomy in rats
Seedor, J. G., Quartuccio, H. A., & Thompson, D. D. (1991) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650060405 · Cited by 410 · see citing works
Self-citation
Evidence for the presence of a proton pump of the vacuolar H(+)-ATPase type in the ruffled borders of osteoclasts.
Väänänen, H. K., Karhukorpi, E.-K., Sundquist, K. T., Wallmark, B., Roininen, I., Hentunen, T. A., Tuukkanen, J., & Lakkakorpi, P. T. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.111.3.1305 · Cited by 391 · see citing works
Inhibition of osteoclast-like cell formation by bisphosphonates in long-term cultures of human bone marrow.
Hughes, D. E., MacDonald, B. R., Russell, R. G. G., & Gowen, M. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114100 · Cited by 357 · see citing works
Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix.
Boonekamp, P. M., van der Wee-Pals, L. J. A., LENNEP, M. V., Cw, T., & Bijvoet, O. L. (1986) · PubMed · Cited by 345 · see citing works
PREVENTION OF STEROID-INDUCED OSTEOPOROSIS WITH (3-AMINO-1-HYDROXYPROPYLIDENE)-1, 1-BISPHOSPHONATE (APD)
Reid, I. R., Alexander, C. J., King, A. R., & Ibbertson, H. K. (1988) · The Lancet · doi:10.1016/s0140-6736(88)92721-3 · Cited by 340 · see citing works
Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat
Schenk, R., Eggli, P., Fleisch, H. A., et al. (1986) · Calcified Tissue International · doi:10.1007/bf02555748 · Cited by 316 · see citing works
Bisphosphonates directly inhibit the bone resorption activity of isolated avian osteoclasts in vitro.
Carano, A., Teitelbaum, S. L., Konsek, J. D., Schlesinger, P. H., & Blair, H. C. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114459 · Cited by 314 · see citing works
Isolated osteoclasts resorb the organic and inorganic components of bone.
Blair, H. C., Kahn, A. J., Crouch, E. C., Jeffrey, J. J., & Teitelbaum, S. L. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.102.4.1164 · Cited by 281 · see citing works
Effects of bisphosphonates on isolated Rat osteoclasts as examined by reflected light microscopy
Sato, M., & Grasser, W. (1990) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650050107 · Cited by 264 · see citing works
Self-citation
TREATMENT OF PAGET'S DISEASE WITH (3-AMINO-1-HYDROXYPROPYLIDENE)-1, 1-BISPHOSPHONATE (A.P.D.)
Frijlink, W. B., Bijvoet, O. L. M., Velde, J. T., & Heynen, G. (1979) · The Lancet · doi:10.1016/s0140-6736(79)91318-7 · Cited by 257 · see citing works
Osteoclast cytosolic calcium, regulated by voltage-gated calcium channels and extracellular calcium, controls podosome assembly and bone resorption.
Miyauchi, A., Hruska, K. A., Greenfield, E. M., et al. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.111.6.2543 · Cited by 234 · see citing works
Control of Cytosolic Free Calcium in Rat and Chicken Osteoclasts
Malgaroli, A., Meldolesi, J., Zallone, A. Z., & Teti, A. M. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)71683-9 · Cited by 228 · see citing works
‘Calcium-activated’ intracellular calcium elevation: A novel mechanism of osteoclast regulation
Zaidi, M., Datta, H. K., Patchell, A., Moonga, B. S., & MacIntyre, I. M. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)91143-1 · Cited by 214 · see citing works
DIPHOSPHONATES AND PAGET'S DISEASE OF BONE
Smith (1971) · The Lancet · doi:10.1016/s0140-6736(71)91447-4 · Cited by 205 · see citing works
Mammalian collagenase predisposes bone surfaces to osteoclastic resorption
Chambers, T. J., Darby, J. A., & Fuller, K. (1985) · Cell and Tissue Research · doi:10.1007/bf00214590 · Cited by 203 · see citing works
REDUCED MORBIDITY FROM SKELETAL METASTASES IN BREAST CANCER PATIENTS DURING LONG-TERM BISPHOSPHONATE (APD) TREATMENT
van Holten-Verzantvoort, A. T., Bijvoet, O. L. M., Hermans, J., Harinck, H. I. J., Elte, J. W. F., Beex, L. V. A. M., Cleton, F. J., Kroon, H. M., Vermey, P., Neijt, J. P., et al. (1987) · The Lancet · doi:10.1016/s0140-6736(87)92555-4 · Cited by 200 · see citing works
Echistatin is a potent inhibitor of bone resorption in culture.
Sato, M., Sardana, M. K., GRASSER, W. A., Garsky, V. M., Murray, J. M., & Gould, R. J. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.111.4.1713 · Cited by 197 · see citing works
Self-citation
Dichloromethylenebisphosphonate (Cl2MBP) inhibits bone resorption through injury to osteoclasts that resorb Cl2MBP-coated bone
Flanagan, A. M., & Chambers, T. J. (1989) · Bone and Mineral · doi:10.1016/0169-6009(89)90021-4 · Cited by 197 · see citing works
COMPARISON OF AMINOHYDROXYPROPYLIDENE DIPHOSPHONATE, MITHRAMYCIN, AND CORTICOSTEROIDSICALCITONIN IN TREATMENT OF CANCER-ASSOCIATED HYPERCALCAEMIA
Ralston, S. H., Dryburgh, F. J., Cowan, R. A., Gardner, M. D., Jenkins, A., & Boyle, I. T. (1985) · The Lancet · doi:10.1016/s0140-6736(85)90848-7 · Cited by 192 · see citing works
COMPARISON OF THREE INTRAVENOUS BISPHOSPHONATES IN CANCER-ASSOCIATED HYPERCALCAEMIA
Ralston, S. H., Patel, U., Fraser, W., Gallacher, S., Dryburgh, F. J., Cowan, R., & Boyle, I. (1989) · The Lancet · doi:10.1016/s0140-6736(89)91791-1 · Cited by 192 · see citing works
Migration and phenotypic transformation of osteoclast precursors into mature osteoclasts: The effect of a bisphosphonate
Löwik, C. W. G. M., van der Pluijm, G., van der Wee-Pals, L. J. A., Groot, H. B. V. T.-D., & Bijvoet, O. L. M. (1988) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650030210 · Cited by 191 · see citing works
Paget's disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD).
Harinck, H. I. J., Papapoulos, S. E., Blanksma, H. J., et al. (1987) · BMJ · doi:10.1136/bmj.295.6609.1301 · Cited by 185 · see citing works
Effects of Dichloromethylene Diphosphonate on Skeletal Mobilization of Calcium in Multiple Myeloma
Siris, E. S., Sherman, W. H., Baquiran, D. C., Schlatterer, J. P., Osserman, E. F., & Canfield, R. E. (1980) · New England Journal of Medicine · doi:10.1056/nejm198002073020602 · Cited by 185 · see citing works
A Comparative Study of Disaggregated Chick and Rat Osteoclasts in Vitro: Effects of Calcitonin and Prostaglandins*
Arnett, T. R., & Dempster, D. W. (1987) · Endocrinology · doi:10.1210/endo-120-2-602 · Cited by 181 · see citing works
PREVENTION OF POSTMENOPAUSAL BONE LOSS BY TILUDRONATE
Reginster, J. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92927-9 · Cited by 180 · see citing works
DIPHOSPHONATES IN PAGET'S DISEASE
Russell, R. G. G., Preston, C., Smith, R. F., et al. (1974) · The Lancet · doi:10.1016/s0140-6736(74)90347-x · Cited by 178 · see citing works
EFFECT OF DICHLOROMETHYLENE DIPHOSPHONATE IN PAGET'S DISEASE OF BONE AND IN HYPERCALCÆMIA DUE TO PRIMARY HYPERPARATHYROIDISM OR MALIGNANT DISEASE
Douglas, D. L., G, R. G., Preston, C., Prenton, M. A., Duckworth, T., Kanis, J., Preston, F. E., & Woodhead, J. S. (1980) · The Lancet · doi:10.1016/s0140-6736(80)91496-8 · Cited by 177 · see citing works
Physiological disposition of alendronate, a potent anti-osteolytic bisphosphonate, in laboratory animals.
Lin, J. H., Duggan, D. E., Chen, I. W., et al. (1991) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08972-x · Cited by 164 · see citing works
Diphosphonate Therapy of Paget's Disease of Bone
Canfield, R. E., Rosner, W., Skinner, J. B., McWHORTER, J., Resnick, L. M., Feldman, F., Kammerman, S., RYAN, K., KUNIGONIS, M., & Bohne, W. H. O. (1977) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-44-1-96 · Cited by 162 · see citing works
Bisphosphonates--history and experimental basis.
Fleisch, H. (1987) · PubMed · Cited by 154 · see citing works
EFFECTS OF DISODIUM DICHLOROMETHYLENE DIPHOSPHONATE ON PAGET'S DISEASE OF BONE
Meunier, P., Alexandre, C., Edouard, C. M., et al. (1979) · The Lancet · doi:10.1016/s0140-6736(79)91551-4 · Cited by 153 · see citing works
The effects of diphosphonates on the growth and glycolysis of connective-tissue cells in culture
Fast, D. K., Felix, R., Dowse, C. M., Neuman, W. F., & Fleisch, H. A. (1978) · Biochemical Journal · doi:10.1042/bj1720097 · Cited by 151 · see citing works
Maintained improvement in calcium balance and bone mineral content in patients with osteoporosis treated with the bisphosphonate APD
Valkema, R., Vismans, F. J. F. E., Papapoulos, S. E., Pauwels, E. K. J., & Bijvoet, O. L. M. (1989) · Bone and Mineral · doi:10.1016/0169-6009(89)90095-0 · Cited by 145 · see citing works
Effect of bisphosphonates on proliferation and viability of mouse bone marrow-derived macrophages
Cecchini, M. G., Felix, R., Fleisch, H. A., & Cooper, P. H. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020209 · Cited by 144 · see citing works
Antiresorptive dose-response relationships across three generations of bisphosphonates.
Sietsema, W. K., Ebetino, F. H., Salvagno, A. M., et al. (1989) · PubMed · Cited by 141 · see citing works
COMPARISON OF INTRAVENOUS (3-AMINO-1-HYDROXYPROPYLIDENE)-1, 1-BISPHOSPHONATE AND VOLUME REPLETION IN TUMOUR-INDUCED HYPERCALCAEMIA
Sleeboom, H., van Oosterom, A. T., Bijvoet, O. L. M., GLEED, J. H., & O'Riordan, J. H. (1983) · The Lancet · doi:10.1016/s0140-6736(83)90231-3 · Cited by 138 · see citing works
A comparsion of various procedures for fine grain development in electron microscopic radioautography
Kopriwa, B. M. (1975) · Histochemistry and Cell Biology · doi:10.1007/bf00491492 · Cited by 129 · see citing works
Isolated osteoclasts in primary culture: first observations on structure and survival in culture media
Zallone, A. Z., Teti, A. M., & Primavera, M. V. (1982) · Anatomy and Embryology · doi:10.1007/bf00305576 · Cited by 122 · see citing works
Comparison of two parenteral diphosphonates in hypercalcemia of malignancy
Jung, A. (1982) · The American Journal of Medicine · doi:10.1016/0002-9343(82)90813-0 · Cited by 122 · see citing works
Differential Action of the Bisphosphonates (3-Amino-1-Hydroxypropylidene)-1,1-Bisphosphonate (APD) and Disodium Dichloromethylidene Bisphosphonate (Cl2MDP) on Rat Macrophage-mediated Bone Resorption In Vitro
Reitsma, P. H., Teitelbaum, S. L., Bijvoet, O. L. M., & Kahn, A. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110704 · Cited by 120 · see citing works
The effect of dichloromethylene diphosphonate, a pyrophosphate analog, on bone and bone cell structure in the growing rat
Miller, S. C., & Jee, W. S. S. (1979) · The Anatomical Record · doi:10.1002/ar.1091930309 · Cited by 113 · see citing works
Parathyroid Hormone Bindingin Vivoto Renal, Hepatic, and Skeletal Tissues of the Rat Using a Radioautographic Approach*
Rouleau, M. F., Warshawsky, H., & Goltzman, D. (1986) · Endocrinology · doi:10.1210/endo-118-3-919 · Cited by 111 · see citing works
Inhibition of osteoclastic acid phosphatase abolishes bone resorption
Zaidi, M., Moonga, B. S., Moss, D., & MacIntyre, I. M. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)92405-4 · Cited by 98 · see citing works
Bisphosphonates in vitro specifically inhibit, among the hematopoietic series, the development of the mouse mononuclear phagocyte lineage
Cecchini, M. G., & Fleisch, H. A. (1990) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650051005 · Cited by 95 · see citing works
Sclerosis of lytic bone metastases after disodium aminohydroxypropylidene bisphosphonate (APD) in patients with breast carcinoma.
Morton, A. R., Cantrill, J. A., Pillai, G. V., et al. (1988) · BMJ · doi:10.1136/bmj.297.6651.772 · Cited by 88 · see citing works
Aminohydroxybutane bisphosphonate inhibits bone loss due to immobilization in rats
Thompson, D. D., Seedor, J. G., Weinreb, M., et al. (1990) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650050312 · Cited by 83 · see citing works
Self-citation
Direct action of the parathyroid hormone-like human hypercalcemic factor on bone.
Thompson, D. D., Seedor, J. G., Fisher, J., et al. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.15.5673 · Cited by 79 · see citing works
Self-citation
Treatment of Paget's disease of bone with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate
Adámi, S., Salvagno, G. L., Guarrera, G. M., et al. (1986) · Calcified Tissue International · doi:10.1007/bf02555208 · Cited by 75 · see citing works
Cytotoxic and migration inhibitory effects of bisphosphonates on macrophages
Stevenson, P. H., & Stevenson, J. R. (1986) · Calcified Tissue International · doi:10.1007/bf02556715 · Cited by 74 · see citing works
Effect of diphosphonates on the synthesis of prostaglandins in cultured calvaria cells
Felix, R., Bettex, J.-D., & Fleisch, H. A. (1981) · Calcified Tissue International · doi:10.1007/bf02409488 · Cited by 74 · see citing works
Treatment of paget's disease of bone with aminohydroxybutylidene bisphosphonate
O’Doherty, D. P., Bickerstaff, D. R., McCloskey, E. V., et al. (1990) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650050510 · Cited by 72 · see citing works
Influence of a diphosphonate on the cellular aspect of young bone tissue
Plasmans, C. M. T., Jap, P. H. K., Kuijpers, W., Slooff, T. J. J. H., & Wijers, M. (1980) · Calcified Tissue International · doi:10.1007/bf02408548 · Cited by 72 · see citing works
Prevention of glucocorticoid-induced osteoporosis
Reid, I. R., SCHOOLER, B. A., & Stewart, A. W. (1990) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650050611 · Cited by 69 · see citing works
LONG‐TERM EFFECTS OF PARENTERAL DICHLOROMETHYLENE BISPHOSPHONATE (CL2MBP) ON BONE DISEASE OF MYELOMA PATIENTS TREATED WITH CHEMOTHERAPY
Merlini, G., Parrinello, G. A., Piccinini, L., et al. (1990) · Hematological Oncology · doi:10.1002/hon.2900080104 · Cited by 68 · see citing works
The subcellular distribution of [14C]dichloromethylenebisphosphonate and [14C]1-hydroxyethylidene-1,1-bisphosphonate in cultured calvaria cells
Felix, R., Guenther, H. L., & Fleisch, H. A. (1984) · Calcified Tissue International · doi:10.1007/bf02405302 · Cited by 66 · see citing works
Application of an in vitro model and a clinical protocol in the assessment of the potency of a new bisphosphonate
Papapoulos, S. E., Hoekman, K., Löwik, C. W. G. M., Vermeij, P., & Bijvoet, O. L. M. (1989) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650040518 · Cited by 65 · see citing works
Effects of a bisphosphonate (1-hydroxy ethylidene-1,1 bisphosphonic acid) on osteoclast number during prolonged bed rest in healthy humans
Chappard, D., Alexandre, C., Palle, S., Vico, L., Morukov, B. V., Rodionova, S. S., MINAIRE, P. M., & Riffat, G. (1989) · Metabolism · doi:10.1016/0026-0495(89)90226-6 · Cited by 52 · see citing works
Prevention of steroid-induced osteoporosis with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD)
Reid, I., Alexander, C., King, A., & Ibbertson, H. K. (1988) · Maturitas · doi:10.1016/0378-5122(88)90035-7 · Cited by 49 · see citing works
Clodronate for osteolytic metastases due to breast cancer.
Elomaa, I., BLOMQVIST, C. P., Porkka, L., et al. (1988) · PubMed · Cited by 48 · see citing works
Treatment of malignant hypercalcaemia with clodronate
Percival, R. C., Paterson, A. D., Yates, A. J. P., et al. (1985) · British Journal of Cancer · doi:10.1038/bjc.1985.100 · Cited by 47 · see citing works
Effects of a New Aminodiphosphonate (Aminohydroxybutylidene Diphosphonate) in Patients With Osteolytic Lesions From Metastases and Myelomatosis
Attardo-Parrinello, G. (1987) · Archives of Internal Medicine · doi:10.1001/archinte.1987.00370090105018 · Cited by 44 · see citing works
Treatment of paget's disease with intermittent low-dose infusions of disodium pamidronate (APD)
Stone, M. D., Hawthorne, A. B., Kerr, D., et al. (1990) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650051207 · Cited by 33 · see citing works
Comparison of different dose regimes of aminohydroxypropylidene‐1,1‐ bisphosphonate (APD) in hypercalcaemia of malignancy.
Davis, J. R., & Heath, D. (1989) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1989.tb05426.x · Cited by 27 · see citing works
Short-term effects on bone and mineral metabolism of 4-amino-1-hydroxybutylidene-1,1-diphosphonate (ABDP) in Paget's disease of bone
Pedrazzoni, M., Palummeri, E., Ciotti, G., et al. (1989) · Bone and Mineral · doi:10.1016/0169-6009(89)90086-x · Cited by 20 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

Thompson, D. D., J. G. Seedor, J. E. Fisher, M. Rosenblatt, and G. A. Rodan. 1988. Direct action ofthe parathyroid hormone-like human hypercalce- mic factor on bone. Proc. Natd. Acad. Sci. USA. 85:5673-5677.

Sorted by citations

Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease
Kearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824 · see citing works
The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates.
Balena, R., Toolan, B. C., Shea, M., Markatos, A., Myers, E. R., Lee, S. C., Opas, E. E., Seedor, J. G., Klein, H., & Frankenfield, D. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116872 · Cited by 396 · see citing works
Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D.
Price, P. A., June, H. H., Buckley, J. R., & Williamson, M. K. (2001) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/hq1001.097102 · Cited by 376 · see citing works
Myeloma interacts with the bone marrow microenvironment  to induce osteoclastogenesis and is dependent on osteoclast activity
Yaccoby, S., Pearse, R. N., Johnson, C. L., Barlogie, B., Choi, Y., & Epstein, J. (2002) · British Journal of Haematology · doi:10.1046/j.1365-2141.2002.03257.x · Cited by 305 · see citing works
Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption.
Price, P. A., Faus, S. A., & Williamson, M. K. (2001) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.21.5.817 · Cited by 301 · see citing works
Matrix metalloproteinases are obligatory for the migration of preosteoclasts to the developing marrow cavity of primitive long bones
Blavier, L., & Delaissé, J. M. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.12.3649 · Cited by 221 · see citing works
Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis.
Halasy-Nagy, J. M., Rodan, G. A., & Reszka, A. A. (2001) · Bone · doi:10.1016/s8756-3282(01)00615-9 · Cited by 190 · see citing works
Self-citation
Osteoclasts are important for bone angiogenesis
Cackowski, F. C., Anderson, J. L., Patrene, K. D., Choksi, R. J., Shapiro, S. D., Windle, J. J., Blair, H. C., & Roodman, G. D. (2010) · Blood · doi:10.1182/blood-2009-08-237628 · Cited by 188 · see citing works
Zoledronic acid suppresses lung metastases and prolongs overall survival of osteosarcoma‐bearing mice
Ory, B., Heymann, M., Kamijo, A., Gouin, F., Heymann, D., & Redini, F. (2005) · Cancer · doi:10.1002/cncr.21530 · Cited by 169 · see citing works
Intracellular membrane trafficking in bone resorbing osteoclasts
Mulari, M., Vääräniemi, J., & Väänänen, H. K. (2003) · Microscopy Research and Technique · doi:10.1002/jemt.10371 · Cited by 104 · see citing works
The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared with bisphosphonates in two models of humoral hypercalcemia of malignancy.
Morony, S., Warmington, K., Adamu, S., Asuncion, F., Geng, Z., Grisanti, M., Tan, H. L., Capparelli, C., Starnes, C., Weimann, B., et al. (2005) · Endocrinology · doi:10.1210/en.2004-1583 · Cited by 97 · see citing works
Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis
Zheng, Y., Zhou, H., Brennan, K., Blair, J. M., Modzelewski, J. R. K., Seibel, M. J., & Dunstan, C. R. (2007) · Bone · doi:10.1016/j.bone.2006.09.016 · Cited by 82 · see citing works
Inhibition of bone resorption by pamidronate cannot restore normal gain in cortical bone mass and strength in tail-suspended rapidly growing rats.
Kodama, Y., Nakayama, K., Fuse, H., Fukumoto, S., Kawahara, H., Takahashi, H., Kurokawa, T., Sekiguchi, C., Nakamura, T., & Matsumoto, T. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.7.1058 · Cited by 76 · see citing works
Use of bisphosphonates for the treatment of bone metastasis in experimental animal models.
Yoneda, T., Michigami, T., Yi, B., Williams, P. J., Niewolna, M., & Hiraga, T. (1999) · Cancer Treatment Reviews · doi:10.1053/ctrv.1999.0133 · Cited by 52 · see citing works
Comparison of Fc-osteoprotegerin and zoledronic acid activities suggests that zoledronic acid inhibits prostate cancer in bone by indirect mechanisms
Quinn, J. E., Brown, L. G., Zhang, J., Keller, E. T., Vessella, R. L., & Corey, E. (2005) · Prostate Cancer and Prostatic Diseases · doi:10.1038/sj.pcan.4500815 · Cited by 29 · see citing works
Drug disposition of incadronate, a new bisphosphonate, in rats with bone metastases.
USUI*, T., TANAKA, S., SONODA, T., OZAWA, Y., TERAMURA, K., NAKAMURA, E., WATANABE, T., & HIGUCHI, S. (1997) · Xenobiotica · doi:10.1080/004982597240442 · Cited by 13 · see citing works
Histochemical evidence of zoledronate inhibiting c-src expression and interfering with CD44/OPN-mediated osteoclast adhesion in the tibiae of mice
Liu, H., Cui, J., Sun, J., Du, J., Feng, W., Sun, B., Li, J., Han, X., Liu, B., Yimin, et al. (2015) · Journal of Molecular Histology · doi:10.1007/s10735-015-9620-9 · Cited by 11 · see citing works

The alteration of osteoclast morphology by diphosphonates in bone organ culture
Rowe, D. J., & Hausmann, E. (1976) · Calcified Tissue International · doi:10.1007/bf02546397 · Cited by 76 · see citing works
Inhibition of Osteoclast Recruitment at a Local Site by 1-Hydroxyethylidene-1,1-Bisphosphonate (HEBP)
Adachi, K., & Chole, R. A. (1990) · Annals of Otology Rhinology & Laryngology · doi:10.1177/000348949009900914 · Cited by 12 · see citing works
Use of bisphosphonates in cancer patients
Body, J., Coleman, R. E., & Piccart, M. J. (1996) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(96)90020-1 · Cited by 89 · see citing works
Structure-activity relationships of various bisphosphonates
Shinoda, H., Adamek, G., Felix, R., Fleisch, H. A., Schenk, R., & Hagan, P. (1983) · Calcified Tissue International · doi:10.1007/bf02405012 · Cited by 306 · see citing works
Updates on bisphosphonates and potential pathobiology of bisphosphonate‐induced jaw osteonecrosis
Sarin, J., DeRossi, S. S., & Akintoye, S. O. (2007) · Oral Diseases · doi:10.1111/j.1601-0825.2007.01381.x · Cited by 132 · see citing works

Authors: Sato, M., Grasser, W., Endo, N., Akins, R., Simmons, H., Thompson, D. D., Golub, E., & Rodan, G. A.
Affiliations: Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
ORCID: Sato, M
Endo, N
Akins, R
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1991-12-01
Volume: 88
Issue: 6
Pages: 2095-2105
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci115539
OpenAlex: W1994414479
Cited by: 1,004
References: 72
Citations by year: 2026: 5 · 2025: 5 · 2024: 10 · 2023: 17 · 2022: 24 · 2021: 16 · 2020: 20 · 2019: 24 · 2018: 20 · 2017: 18 · 2016: 15 · 2015: 28 · 2014: 37 · 2013: 31 · 2012: 28
FWCI: 7.87
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Bone health and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords: alendronate, bisphosphonates, osteoclasts, osteoclast ultrastructure, ruffled border, bone resorption inhibition, parathyroid hormone-related protein, acidification, growth plate
MeSH terms: Cyclic AMP, Animals, Bone and Bones, Bone Resorption, Calcium, Cells, Cultured, Chickens, Diphosphonates, Osteoclasts, Rats, Inbred Strains, Alendronate, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Bisphosphonate action: alendronate localization in rat bone and effects on osteoclast ultrastructure.

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks