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Barbara D Boyan - One of the best experts on this subject based on the ideXlab platform.
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osteoinductivity of demineralized bone matrix is independent of donor bisphosphonate use
Journal of Bone and Joint Surgery American Volume, 2011Co-Authors: Zvi Schwartz, Shawn A Hunter, Chad J. Ronholdt, Sharon L Hyzy, Moon Hae Sunwoo, Mark Moore, Barbara D BoyanAbstract:Background: Demineralized bone matrix is commonly used as a bone graft substitute, either alone or to supplement an osteoconductive material, because of its osteoinductive properties. The aging of the population has led to an increase in the number of prospective donors of demineralized bone matrix who have taken Bisphosphonates to prevent osteoclastmediated bone resorption. The aim of this study was to determine whether oral bisphosphonate usage affects the osteoinductivity of demineralized bone matrix from donors. Methods: Sex-matched and age-matched pairs of samples were provided by four tissue banks (three or four pairs per bank). Demineralized bone matrix donors without bisphosphonate treatment had a mean age (and standard deviation) of 69.1 ± 2.5 years, and donors with bisphosphonate treatment had a mean age of 68.9 ± 2.0 years. Each pair included one donor known to have taken Bisphosphonates and one who had not taken Bisphosphonates. Demineralized bone matrix previously confirmed as osteoinductive was the positive control, and heat-inactivated demineralized bone matrix was the negative control. Demineralized bone matrix incubated with 1 mL of phosphate-buffered saline solution containing 0, 0.002, 2.0, or 2000 ng/mL of alendronate was also tested. Gelatin capsules containing 15 mg of demineralized bone matrix were implanted bilaterally in the gastrocnemius muscle of male nude mice (eight implants per group). The mice were killed thirty-five days after implantation, and hind limbs were recovered and processed for histological analysis. Osteoinductivity was measured with use of a qualitative score and by histomorphometry. Results: Nine of fifteen samples from donors who had had bisphosphonate treatment and ten of fifteen samples from patients who had not had bisphosphonate treatment were osteoinductive. Qualitative mean scores were comparable (1.7 ± 0.4 for those without Bisphosphonates and 1.9 ± 0.7 for those with Bisphosphonates). Osteoinductive demineralized bone matrix samples produced ossicles of comparable size, regardless of bisphosphonate usage. Histomorphometric measurements of the area of new bone formation and residual demineralized bone matrix were also comparable. The addition of alendronate to control demineralized bone matrix did not affect its osteoinductivity. Conclusions: Demineralized bone matrix samples from donors treated with Bisphosphonates and donors not treated with Bisphosphonates have the same ability to induce bone formation. However, it is not known if the quality of the new bone is affected, with subsequent consequences affecting bone remodeling. Clinical Relevance: These results show that demineralized bone matrix can be safe and effective as an osteoinductive material, even when the original bone graft is obtained from donors who have used Bisphosphonates.
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osteoinductivity of demineralized bone matrix is independent of donor bisphosphonate use
Journal of Bone and Joint Surgery American Volume, 2011Co-Authors: Zvi Schwartz, Shawn A Hunter, Chad J. Ronholdt, Sharon L Hyzy, Moon Hae Sunwoo, Mark Moore, Barbara D BoyanAbstract:Background: Demineralized bone matrix is commonly used as a bone graft substitute, either alone or to supplement an osteoconductive material, because of its osteoinductive properties. The aging of the population has led to an increase in the number of prospective donors of demineralized bone matrix who have taken Bisphosphonates to prevent osteoclastmediated bone resorption. The aim of this study was to determine whether oral bisphosphonate usage affects the osteoinductivity of demineralized bone matrix from donors. Methods: Sex-matched and age-matched pairs of samples were provided by four tissue banks (three or four pairs per bank). Demineralized bone matrix donors without bisphosphonate treatment had a mean age (and standard deviation) of 69.1 ± 2.5 years, and donors with bisphosphonate treatment had a mean age of 68.9 ± 2.0 years. Each pair included one donor known to have taken Bisphosphonates and one who had not taken Bisphosphonates. Demineralized bone matrix previously confirmed as osteoinductive was the positive control, and heat-inactivated demineralized bone matrix was the negative control. Demineralized bone matrix incubated with 1 mL of phosphate-buffered saline solution containing 0, 0.002, 2.0, or 2000 ng/mL of alendronate was also tested. Gelatin capsules containing 15 mg of demineralized bone matrix were implanted bilaterally in the gastrocnemius muscle of male nude mice (eight implants per group). The mice were killed thirty-five days after implantation, and hind limbs were recovered and processed for histological analysis. Osteoinductivity was measured with use of a qualitative score and by histomorphometry. Results: Nine of fifteen samples from donors who had had bisphosphonate treatment and ten of fifteen samples from patients who had not had bisphosphonate treatment were osteoinductive. Qualitative mean scores were comparable (1.7 ± 0.4 for those without Bisphosphonates and 1.9 ± 0.7 for those with Bisphosphonates). Osteoinductive demineralized bone matrix samples produced ossicles of comparable size, regardless of bisphosphonate usage. Histomorphometric measurements of the area of new bone formation and residual demineralized bone matrix were also comparable. The addition of alendronate to control demineralized bone matrix did not affect its osteoinductivity. Conclusions: Demineralized bone matrix samples from donors treated with Bisphosphonates and donors not treated with Bisphosphonates have the same ability to induce bone formation. However, it is not known if the quality of the new bone is affected, with subsequent consequences affecting bone remodeling. Clinical Relevance: These results show that demineralized bone matrix can be safe and effective as an osteoinductive material, even when the original bone graft is obtained from donors who have used Bisphosphonates.
Joseph M Lane - One of the best experts on this subject based on the ideXlab platform.
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atypical fracture with long term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance
Proceedings of the National Academy of Sciences of the United States of America, 2017Co-Authors: Ashley A Lloyd, Bernd Gludovatz, Christoph Riedel, Emma A Luengo, Rehan Saiyed, Eric Marty, Dean G Lorich, Joseph M LaneAbstract:Bisphosphonates are the most widely prescribed pharmacologic treatment for osteoporosis and reduce fracture risk in postmenopausal women by up to 50%. However, in the past decade these drugs have been associated with atypical femoral fractures (AFFs), rare fractures with a transverse, brittle morphology. The unusual fracture morphology suggests that bisphosphonate treatment may impair toughening mechanisms in cortical bone. The objective of this study was to compare the compositional and mechanical properties of bone biopsies from bisphosphonate-treated patients with AFFs to those from patients with typical osteoporotic fractures with and without bisphosphonate treatment. Biopsies of proximal femoral cortical bone adjacent to the fracture site were obtained from postmenopausal women during fracture repair surgery (fracture groups, n = 33) or total hip arthroplasty (nonfracture groups, n = 17). Patients were allocated to five groups based on fracture morphology and history of bisphosphonate treatment [+BIS Atypical: n = 12, BIS duration: 8.2 (3.0) y; +BIS Typical: n = 10, 7.7 (5.0) y; +BIS Nonfx: n = 5, 6.4 (3.5) y; -BIS Typical: n = 11; -BIS Nonfx: n = 12]. Vibrational spectroscopy and nanoindentation showed that tissue from bisphosphonate-treated women with atypical fractures was harder and more mineralized than that from bisphosphonate-treated women with typical osteoporotic fractures. In addition, fracture mechanics measurements showed that tissue from patients treated with Bisphosphonates had deficits in fracture toughness, with lower crack-initiation toughness and less crack deflection at osteonal boundaries than that of bisphosphonate-naive patients. Together, these results suggest a deficit in intrinsic and extrinsic toughening mechanisms, which contribute to AFFs in patients treated with long-term Bisphosphonates.
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case report of spontaneous nonspinal fractures in a multiple myeloma patient on long term pamidronate and zoledronic acid
HSS Journal, 2008Co-Authors: Greg Wernecke, Surena Namdari, Edward F Dicarlo, Robert Schneider, Joseph M LaneAbstract:Pamidronate and zoledronic acid are two potent intravenous Bisphosphonates used in the treatment of multiple myeloma as well as osteoporosis. While the concern for heightened fracture risk in a patient on long-term bisphosphonate treatment for malignancy has been previously noted, we present the first case of spontaneous, nonspinal fractures in a patient undergoing treatment for multiple myeloma. The patient had a positive 9-year history of bisphosphonate treatment and presented with sequential subtrochanteric stress fractures of the left and right femurs. Pathological reports of fracture site biopsies demonstrate signs consistent with ametabolic bone and no malignancy. These findings point to extreme inhibition of bone turnover by Bisphosphonates as the cause of this patient’s morbidity. This is a single retrospective case study (level IV evidence).
Zvi Schwartz - One of the best experts on this subject based on the ideXlab platform.
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osteoinductivity of demineralized bone matrix is independent of donor bisphosphonate use
Journal of Bone and Joint Surgery American Volume, 2011Co-Authors: Zvi Schwartz, Shawn A Hunter, Chad J. Ronholdt, Sharon L Hyzy, Moon Hae Sunwoo, Mark Moore, Barbara D BoyanAbstract:Background: Demineralized bone matrix is commonly used as a bone graft substitute, either alone or to supplement an osteoconductive material, because of its osteoinductive properties. The aging of the population has led to an increase in the number of prospective donors of demineralized bone matrix who have taken Bisphosphonates to prevent osteoclastmediated bone resorption. The aim of this study was to determine whether oral bisphosphonate usage affects the osteoinductivity of demineralized bone matrix from donors. Methods: Sex-matched and age-matched pairs of samples were provided by four tissue banks (three or four pairs per bank). Demineralized bone matrix donors without bisphosphonate treatment had a mean age (and standard deviation) of 69.1 ± 2.5 years, and donors with bisphosphonate treatment had a mean age of 68.9 ± 2.0 years. Each pair included one donor known to have taken Bisphosphonates and one who had not taken Bisphosphonates. Demineralized bone matrix previously confirmed as osteoinductive was the positive control, and heat-inactivated demineralized bone matrix was the negative control. Demineralized bone matrix incubated with 1 mL of phosphate-buffered saline solution containing 0, 0.002, 2.0, or 2000 ng/mL of alendronate was also tested. Gelatin capsules containing 15 mg of demineralized bone matrix were implanted bilaterally in the gastrocnemius muscle of male nude mice (eight implants per group). The mice were killed thirty-five days after implantation, and hind limbs were recovered and processed for histological analysis. Osteoinductivity was measured with use of a qualitative score and by histomorphometry. Results: Nine of fifteen samples from donors who had had bisphosphonate treatment and ten of fifteen samples from patients who had not had bisphosphonate treatment were osteoinductive. Qualitative mean scores were comparable (1.7 ± 0.4 for those without Bisphosphonates and 1.9 ± 0.7 for those with Bisphosphonates). Osteoinductive demineralized bone matrix samples produced ossicles of comparable size, regardless of bisphosphonate usage. Histomorphometric measurements of the area of new bone formation and residual demineralized bone matrix were also comparable. The addition of alendronate to control demineralized bone matrix did not affect its osteoinductivity. Conclusions: Demineralized bone matrix samples from donors treated with Bisphosphonates and donors not treated with Bisphosphonates have the same ability to induce bone formation. However, it is not known if the quality of the new bone is affected, with subsequent consequences affecting bone remodeling. Clinical Relevance: These results show that demineralized bone matrix can be safe and effective as an osteoinductive material, even when the original bone graft is obtained from donors who have used Bisphosphonates.
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osteoinductivity of demineralized bone matrix is independent of donor bisphosphonate use
Journal of Bone and Joint Surgery American Volume, 2011Co-Authors: Zvi Schwartz, Shawn A Hunter, Chad J. Ronholdt, Sharon L Hyzy, Moon Hae Sunwoo, Mark Moore, Barbara D BoyanAbstract:Background: Demineralized bone matrix is commonly used as a bone graft substitute, either alone or to supplement an osteoconductive material, because of its osteoinductive properties. The aging of the population has led to an increase in the number of prospective donors of demineralized bone matrix who have taken Bisphosphonates to prevent osteoclastmediated bone resorption. The aim of this study was to determine whether oral bisphosphonate usage affects the osteoinductivity of demineralized bone matrix from donors. Methods: Sex-matched and age-matched pairs of samples were provided by four tissue banks (three or four pairs per bank). Demineralized bone matrix donors without bisphosphonate treatment had a mean age (and standard deviation) of 69.1 ± 2.5 years, and donors with bisphosphonate treatment had a mean age of 68.9 ± 2.0 years. Each pair included one donor known to have taken Bisphosphonates and one who had not taken Bisphosphonates. Demineralized bone matrix previously confirmed as osteoinductive was the positive control, and heat-inactivated demineralized bone matrix was the negative control. Demineralized bone matrix incubated with 1 mL of phosphate-buffered saline solution containing 0, 0.002, 2.0, or 2000 ng/mL of alendronate was also tested. Gelatin capsules containing 15 mg of demineralized bone matrix were implanted bilaterally in the gastrocnemius muscle of male nude mice (eight implants per group). The mice were killed thirty-five days after implantation, and hind limbs were recovered and processed for histological analysis. Osteoinductivity was measured with use of a qualitative score and by histomorphometry. Results: Nine of fifteen samples from donors who had had bisphosphonate treatment and ten of fifteen samples from patients who had not had bisphosphonate treatment were osteoinductive. Qualitative mean scores were comparable (1.7 ± 0.4 for those without Bisphosphonates and 1.9 ± 0.7 for those with Bisphosphonates). Osteoinductive demineralized bone matrix samples produced ossicles of comparable size, regardless of bisphosphonate usage. Histomorphometric measurements of the area of new bone formation and residual demineralized bone matrix were also comparable. The addition of alendronate to control demineralized bone matrix did not affect its osteoinductivity. Conclusions: Demineralized bone matrix samples from donors treated with Bisphosphonates and donors not treated with Bisphosphonates have the same ability to induce bone formation. However, it is not known if the quality of the new bone is affected, with subsequent consequences affecting bone remodeling. Clinical Relevance: These results show that demineralized bone matrix can be safe and effective as an osteoinductive material, even when the original bone graft is obtained from donors who have used Bisphosphonates.
Michael J. Rogers - One of the best experts on this subject based on the ideXlab platform.
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biochemical and molecular mechanisms of action of Bisphosphonates
Bone, 2011Co-Authors: Michael J. Rogers, Julie C Crockett, Fraser P Coxon, Jukka MonkkonenAbstract:Abstract This review describes the key discoveries over the last 15 years that have led to a clearer understanding of the molecular mechanisms by which bisphosphonate drugs inhibit bone resorption. Once released from bone mineral surfaces during bone resorption, these agents accumulate intracellularly in osteoclasts. Simple Bisphosphonates such as clodronate are incorporated into non-hydrolysable analogues of adenosine triphosphate, which induce osteoclast apoptosis. The considerably more potent nitrogen-containing Bisphosphonates are not metabolised but potently inhibit farnesyl pyrophosphate (FPP) synthase, a key enzyme of the mevalonate pathway. This prevents the synthesis of isoprenoid lipids necessary for the post-translational prenylation of small GTPases, thereby disrupting the subcellular localisation and normal function of these essential signalling proteins. Inhibition of FPP synthase also results in the accumulation of the upstream metabolite isopentenyl diphosphate, which is incorporated into the toxic nucleotide metabolite ApppI. Together, these properties explain the ability of bisphosphonate drugs to inhibit bone resorption by disrupting osteoclast function and survival. These discoveries are also giving insights into some of the adverse effects of Bisphosphonates, such as the acute phase reaction that is triggered by inhibition of FPP synthase in peripheral blood monocytes. This article is part of a Special Issue entitled Bisphosphonates.
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identification of adenine nucleotide containing metabolites of bisphosphonate drugs using ion pair liquid chromatography electrospray mass spectrometry
Journal of Chromatography B: Biomedical Sciences and Applications, 1997Co-Authors: Seppo Auriola, Michael J. Rogers, Julie C Frith, Antti Koivuniemi, Jukka MonkkonenAbstract:Bisphosphonates are synthetic pyrophosphate analogues, which are used as therapeutic drugs for the treatment of metabolic bone disorders. Some of these Bisphosphonates can be metabolised in cells into non-hydrolysable nucleotide analogues. In this paper, we describe an ion-pairing high-performance liquid chromatography method that is compatible with negative ion electrospray mass spectrometry for the separation of these metabolites. Tandem mass spectrometry and collision-induced dissociation (CID) were used for identification of the metabolites. The CID mass spectra of bisphosphonate-adenine nucleotide adducts are very informative, because major fragment ions are formed by cleavage of the bisphosphonate moiety from the conjugate. The method was used for detection of the nucleotide metabolites of clodronate, tiludronate and etidronate in extracts from mammalian cells after treatment with Bisphosphonates.
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Bisphosphonates induce apoptosis in human myeloma cell lines a novel anti tumour activity
British Journal of Haematology, 1997Co-Authors: C M Shipman, Jane Apperley, R G G Russell, Michael J. Rogers, Peter I CroucherAbstract:Bisphosphonates are in widespread use to prevent bone resorption in a number of metabolic and tumour-induced bone diseases including multiple myeloma. Recent reports suggest that bisphosphonate treatment may be associated with an increase in patient survival, raising the possibility that these compounds may have a direct effect on the tumour cells. We have investigated whether the Bisphosphonates clodronate, pamidronate and YM175 can directly affect the human myeloma cell lines U266-B1, JJN-3 and HS-Sultan in vitro. The effect of bisphosphonate treatment on cell number and cell cycle progression was examined using flow cytometry. The ability of Bisphosphonates to induce apoptosis in human myeloma cell lines was determined on the basis of changes in nuclear morphology and of DNA fragmentation. Pamidronate and the more potent bisphosphonate, YM175, significantly decreased cell number (P < 0.001) in JJN-3 and HS-Sultan cells. YM175 also caused cells to arrest in the S-phase of the cell cycle in the JJN-3 cell line. Both pamidronate and YM175 also caused an increase in the proportion of cells with altered nuclear morphology (P < 0.05) and fragmented DNA, characteristic of apoptosis, in both JJN-3 and HS-Sultan cells. In contrast, clodronate had little effect on cell number and did not cause apoptosis at the concentrations examined. These data raise the possibility that some Bisphosphonates could have direct anti-tumour effects on human myeloma cells in vivo.
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inhibition of growth of dictyostelium discoideum amoebae by bisphosphonate drugs is dependent on cellular uptake
Pharmaceutical Research, 1997Co-Authors: Michael J. Rogers, R G G Russell, Frank H Ebetino, X Xiong, Jukka Monkkonen, Michael P Williamson, D J WattsAbstract:Purpose. The aim of the study was to determine whether Bisphosphonates are internalised by Dictyosteliumamoebae and whether cellular uptake is required for their growth-inhibitory effects. Bisphosphonates inhibit growth of amoebae of the slime mould Dictyostelium discoideum, by mechanisms that appear to be similar to those that cause inhibition of osteoclastic bone resorption. Methods. Cell-free extracts prepared from amoebae that had been incubated with Bisphosphonates were analysed by 3lP-n.m.r. spectroscopy or ion-exchange f.p.l.c., to identify the presence of Bisphosphonates or bisphosphonate metabolites respectively. The growth-inhibitory effect of Bisphosphonates towards Dictyostelium amoebae was also examined under conditions in which pinocytosis was inhibited. Results. All of the Bisphosphonates studied were internalised by Dictyostelium amoebae, probably by fluid-phase pinocytosis, and could be detected in cell-free extracts. Amoebae that were prevented from internalising Bisphosphonates by pinocytosis were markedly resistant to the growth-inhibitory effects of these compounds. In addition, Bisphosphonates encapsulated within liposomes were more potent growth inhibitors of Dictyostelium owing to enhanced intracellular delivery of Bisphosphonates. Conclusions. All Bisphosphonates inhibit Dictyostelium growth by intracellular mechanisms following internalisation of Bisphosphonates by fluid-phase pinocytosis. It is therefore likely that Bisphosphonates also affect osteoclasts by interacting with intracellular, rather than extracellular, processes.
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structure activity relationships of new heterocycle containing Bisphosphonates as inhibitors of bone resorption and as inhibitors of growth of dictyostelium discoideum amoebae
Molecular Pharmacology, 1995Co-Authors: Michael J. Rogers, R G G Russell, X Xiong, D J Watts, Richard Brown, A V Bayless, F H EbetinoAbstract:The mechanisms by which bisphosphonate drugs inhibit osteoclast-mediated bone resorption are unclear. Effects of Bisphosphonates on cellular enzymes, metabolic pathways, and osteoclast morphology have previously been described and could culminate in a generalized cytotoxic effect or a decreased capacity of osteoclasts to resorb bone. Recent studies of the structure-activity relationship for the bisphosphonate side chain indicate, however, that at least the newer generations of nitrogen-containing Bisphosphonates probably act by binding to a specific target at a site that is complementary in structure to the bisphosphonate side chain. We have previously proposed that such a target for Bisphosphonates is also present in amoebae of the cellular slime mold Dictyostelium discoideum, because growth of this microorganism is inhibited by a wide range of Bisphosphonates in a manner that closely reflects the antiresorptive potencies of the Bisphosphonates in vivo. We have added support for this view by examining the potency towards Dictyostelium of Bisphosphonates in which slight changes in the structure of the side chain or conformational restrictions to the side chain have marked effects on antiresorptive potency. The changes in the side chain that affected the in vivo antiresorptive potency of the Bisphosphonates consistently affected in a similar manner the potency of the Bisphosphonates as inhibitors of the growth of Dictyostelium amoebae. These observations confirm that bisphosphonate drugs have a molecular target that is common to both Dictyostelium amoebae and osteoclasts.
D J Watts - One of the best experts on this subject based on the ideXlab platform.
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inhibition of growth of dictyostelium discoideum amoebae by bisphosphonate drugs is dependent on cellular uptake
Pharmaceutical Research, 1997Co-Authors: Michael J. Rogers, R G G Russell, Frank H Ebetino, X Xiong, Jukka Monkkonen, Michael P Williamson, D J WattsAbstract:Purpose. The aim of the study was to determine whether Bisphosphonates are internalised by Dictyosteliumamoebae and whether cellular uptake is required for their growth-inhibitory effects. Bisphosphonates inhibit growth of amoebae of the slime mould Dictyostelium discoideum, by mechanisms that appear to be similar to those that cause inhibition of osteoclastic bone resorption. Methods. Cell-free extracts prepared from amoebae that had been incubated with Bisphosphonates were analysed by 3lP-n.m.r. spectroscopy or ion-exchange f.p.l.c., to identify the presence of Bisphosphonates or bisphosphonate metabolites respectively. The growth-inhibitory effect of Bisphosphonates towards Dictyostelium amoebae was also examined under conditions in which pinocytosis was inhibited. Results. All of the Bisphosphonates studied were internalised by Dictyostelium amoebae, probably by fluid-phase pinocytosis, and could be detected in cell-free extracts. Amoebae that were prevented from internalising Bisphosphonates by pinocytosis were markedly resistant to the growth-inhibitory effects of these compounds. In addition, Bisphosphonates encapsulated within liposomes were more potent growth inhibitors of Dictyostelium owing to enhanced intracellular delivery of Bisphosphonates. Conclusions. All Bisphosphonates inhibit Dictyostelium growth by intracellular mechanisms following internalisation of Bisphosphonates by fluid-phase pinocytosis. It is therefore likely that Bisphosphonates also affect osteoclasts by interacting with intracellular, rather than extracellular, processes.
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structure activity relationships of new heterocycle containing Bisphosphonates as inhibitors of bone resorption and as inhibitors of growth of dictyostelium discoideum amoebae
Molecular Pharmacology, 1995Co-Authors: Michael J. Rogers, R G G Russell, X Xiong, D J Watts, Richard Brown, A V Bayless, F H EbetinoAbstract:The mechanisms by which bisphosphonate drugs inhibit osteoclast-mediated bone resorption are unclear. Effects of Bisphosphonates on cellular enzymes, metabolic pathways, and osteoclast morphology have previously been described and could culminate in a generalized cytotoxic effect or a decreased capacity of osteoclasts to resorb bone. Recent studies of the structure-activity relationship for the bisphosphonate side chain indicate, however, that at least the newer generations of nitrogen-containing Bisphosphonates probably act by binding to a specific target at a site that is complementary in structure to the bisphosphonate side chain. We have previously proposed that such a target for Bisphosphonates is also present in amoebae of the cellular slime mold Dictyostelium discoideum, because growth of this microorganism is inhibited by a wide range of Bisphosphonates in a manner that closely reflects the antiresorptive potencies of the Bisphosphonates in vivo. We have added support for this view by examining the potency towards Dictyostelium of Bisphosphonates in which slight changes in the structure of the side chain or conformational restrictions to the side chain have marked effects on antiresorptive potency. The changes in the side chain that affected the in vivo antiresorptive potency of the Bisphosphonates consistently affected in a similar manner the potency of the Bisphosphonates as inhibitors of the growth of Dictyostelium amoebae. These observations confirm that bisphosphonate drugs have a molecular target that is common to both Dictyostelium amoebae and osteoclasts.