A patent review of bisphosphonates in treating bone disease

References

• Wright NC, Looker AC, Saag KG, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. 2014;29:2520–2526.
   PubMed Web of Science ®Google Scholar
• Altman RD, Bloch DA, Hochberg MC, et al. Prevalence of pelvic Paget‘s disease of bone in the United States. J Bone Miner Res. 2000;15:461–465.
   PubMed Web of Science ®Google Scholar
• Bubendorf L, Schopfer A, Wagner U, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31:578–583.
   PubMed Web of Science ®Google Scholar
• Lee YT. Breast carcinoma: pattern of metastasis at autopsy. J Surg Oncol. 1983;23:175–180.
   PubMed Web of Science ®Google Scholar
• Hameed A, Brady JJ, Dowling P, et al. Bone disease in multiple myeloma: pathophysiology and management. Cancer Growth Metastasis. 2014;7:33–42.
   PubMedGoogle Scholar
• Fleisch H, Russell RG, Francis MD. Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science. 1969;165:1262–1264.
   PubMed Web of Science ®Google Scholar
• Masarachia P, Weinreb M, Balena R, et al. Comparison of the distribution of 3H-alendronate and 3H-etidronate in rat and mouse bones. Bone. 1996;19:281–290.
   PubMed Web of Science ®Google Scholar
• Azuma Y, Sato H, Oue Y, et al. Alendronate distributed on bone surfaces inhibits osteoclastic bone resorption in vitro and in experimental hypercalcemia models. Bone. 1995;16:235–245.
   PubMed Web of Science ®Google Scholar
• Coxon FP, Thompson K, Roelofs AJ, et al. Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells. Bone. 2008;42:848–860.
   PubMed Web of Science ®Google Scholar
• Khan SA, Kanis JA, Vasikaran S, et al. Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis. J Bone Miner Res. 1997;12:1700–1707.
   PubMed Web of Science ®Google Scholar
• Papapoulos SE, Cremers SC. Prolonged bisphosphonate release after treatment in children. N Engl J Med. 2007;356:1075–1076.
   PubMed Web of Science ®Google Scholar
• Von Baeyer H, Hofmann KA. Acetodiphosphorige Saure. Berichte Dtsch Chem Ges. 1897;20:1973–1978.
   Google Scholar
• Frith JC, Monkkonen J, Blackburn GM, et al. Clodronate and liposome-encapsulated clodronate are metabolized to a toxic ATP analog, adenosine 5‘-(beta, gamma-dichloromethylene) triphosphate, by mammalian cells in vitro. J Bone Miner Res. 1997;12:1358–1367.
   PubMed Web of Science ®Google Scholar
• Monkkonen H, Rogers MJ, Makkonen N, et al. The cellular uptake and metabolism of clodronate in RAW 264 macrophages. Pharm Res. 2001;18:1550–1555.
   PubMed Web of Science ®Google Scholar
• Frith JC, Monkkonen J, Auriola S, et al. The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis. Arthritis Rheum. 2001;44:2201–2210.
   PubMed Web of Science ®Google Scholar
• Lehenkari PP, Kellinsalmi M, Napankangas JP, et al. Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol Pharmacol. 2002;61:1255–1262.
   PubMed Web of Science ®Google Scholar
• Skorey K, Ly HD, Kelly J, et al. How does alendronate inhibit protein-tyrosine phosphatases? J Biol Chem. 1997;272:22472–22480.
   PubMed Web of Science ®Google Scholar
• Endo N, Rutledge SJ, Opas EE, et al. Human protein tyrosine phosphatase-sigma: alternative splicing and inhibition by bisphosphonates. J Bone Miner Res. 1996;11:535–543.
   PubMed Web of Science ®Google Scholar
• Heikkila P, Teronen O, Moilanen M, et al. Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines. Anticancer Drugs. 2002;13:245–254.
   PubMed Web of Science ®Google Scholar
• Plotkin LI, Lezcano V, Thostenson J, et al. Connexin 43 is required for the anti-apoptotic effect of bisphosphonates on osteocytes and osteoblasts in vivo. J Bone Miner Res. 2008;23:1712–1721.
   PubMed Web of Science ®Google Scholar
• van Beek E, Pieterman E, Cohen L, et al. Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo. Biochem Biophys Res Commun. 1999;255:491–494.
   PubMed Web of Science ®Google Scholar
• Luckman SP, Hughes DE, Coxon FP, et al. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 1998;13:581–589.
   PubMed Web of Science ®Google Scholar
• Benford HL, Frith JC, Auriola S, et al. Farnesol and geranylgeraniol prevent activation of caspases by aminobisphosphonates: biochemical evidence for two distinct pharmacological classes of bisphosphonate drugs. Mol Pharmacol. 1999;56:131–140.
   PubMed Web of Science ®Google Scholar
• Coxon FP, Helfrich MH, Van‘T Hof R, et al. Protein geranylgeranylation is required for osteoclast formation, function, and survival: inhibition by bisphosphonates and GGTI-298. J Bone Miner Res. 2000;15:1467–1476.
   PubMed Web of Science ®Google Scholar
• Luckman SP, Coxon FP, Ebetino FH, et al. Heterocycle-containing bisphosphonates cause apoptosis and inhibit bone resorption by preventing protein prenylation: evidence from structure-activity relationships in J774 macrophages. J Bone Miner Res. 1998;13:1668–1678.
   PubMed Web of Science ®Google Scholar
• Bergstrom JD, Bostedor RG, Masarachia PJ, et al. Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys. 2000;373:231–241.
   PubMed Web of Science ®Google Scholar
• van Beek E, Pieterman E, Cohen L, et al. Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Biochem Biophys Res Commun. 1999;264:108–111.
   PubMed Web of Science ®Google Scholar
• Dunford JE, Thompson K, Coxon FP, et al. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001;296:235–242.
   PubMed Web of Science ®Google Scholar
• Jauhiainen M, Monkkonen H, Raikkonen J, et al. Analysis of endogenous ATP analogs and mevalonate pathway metabolites in cancer cell cultures using liquid chromatography-electrospray ionization mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877:2967–2975.
   PubMedGoogle Scholar
• Tanaka Y, Morita CT, Tanaka Y, et al. Natural and synthetic non-peptide antigens recognized by human gamma delta T cells. Nature. 1995;375:155–158.
   PubMed Web of Science ®Google Scholar
• Kunzmann V, Bauer E, Wilhelm M. Gamma/delta T-cell stimulation by pamidronate. N Engl J Med. 1999;340:737–738.
   PubMed Web of Science ®Google Scholar
• Ory S, Brazier H, Pawlak G, et al. Rho GTPases in osteoclasts: orchestrators of podosome arrangement. Eur J Cell Biol. 2008;87:469–477.
   PubMed Web of Science ®Google Scholar
• Roy M, Roux S. Rab GTPases in osteoclastic endomembrane systems. Biomed Res Int. 2018;2018:4541538.
   PubMedGoogle Scholar
• Cremers SC, Pillai G, Papapoulos SE. Pharmacokinetics/pharmacodynamics of bisphosphonates: use for optimisation of intermittent therapy for osteoporosis. Clin Pharmacokinet. 2005;44:551–570.
   PubMed Web of Science ®Google Scholar
• Lin JH. Bisphosphonates: a review of their pharmacokinetic properties. Bone. 1996;18:75–85.
   PubMed Web of Science ®Google Scholar
• Cremers S, Drake MT, Ebetino FH, et al. Pharmacology of bisphosphonates. Br J Clin Pharmacol. 2019.
   Google Scholar
• Fogelman I, Bessent RG, Turner JG, et al. The use of whole-body retention of Tc-99m diphosphonate in the diagnosis of metabolic bone disease. J Nucl Med. 1978;19:270–275.
   PubMed Web of Science ®Google Scholar
• Cremers SC, Eekhoff ME, Den Hartigh J, et al. Relationships between pharmacokinetics and rate of bone turnover after intravenous bisphosphonate (olpadronate) in patients with Paget‘s disease of bone. J Bone Miner Res. 2003;18:868–875.
   PubMed Web of Science ®Google Scholar
• Riggs MM, Cremers S. Pharmacometrics and systems pharmacology for metabolic bone diseases. Br J Clin Pharmacol. 2019.
   PubMedGoogle Scholar
• Wiemer AJ, Hohl RJ, Wiemer DF. The intermediate enzymes of isoprenoid metabolism as anticancer targets. Anticancer Agents Med Chem. 2009;9:526–542.
   PubMed Web of Science ®Google Scholar
• Gnant M, Mlineritsch B, Schippinger W, et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009;360:679–691.
   PubMed Web of Science ®Google Scholar
• Morgan GJ, Davies FE, Gregory WM, et al. Long-term follow-up of MRC Myeloma IX trial: survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res. 2013;19:6030–6038.
   PubMed Web of Science ®Google Scholar
• Marra M, Salzano G, Leonetti C, et al. Nanotechnologies to use bisphosphonates as potent anticancer agents: the effects of zoledronic acid encapsulated into liposomes. Nanomedicine. 2011.
   PubMed Web of Science ®Google Scholar
• Shmeeda H, Amitay Y, Tzemach D, et al. Liposome encapsulation of zoledronic acid results in major changes in tissue distribution and increase in toxicity. J Control Release. 2013;167:265–275.
   PubMed Web of Science ®Google Scholar
• Hodgins NO, Al-Jamal WT, Wang JT, et al. In vitro potency, in vitro and in vivo efficacy of liposomal alendronate in combination with gammadelta T cell immunotherapy in mice. J Control Release. 2016;241:229–241.
   PubMed Web of Science ®Google Scholar
• Schiraldi C, Zappavigna S, D‘ Agostino A, et al. Nanoparticles for the delivery of zoledronic acid to prostate cancer cells: a comparative analysis through time lapse video-microscopy technique. Cancer Biol Ther. 2014;15:1524–1532.
   PubMed Web of Science ®Google Scholar
• Ebetino FH, Mazur A, Lundy MW, et al. ISIS Inovation, LTD. Imidazo[1,2-a]pyridinyl bisphosphonates. WO2010033978. 2010.
   Google Scholar
• Tanaka Y, Field KP, Ueda H. Novel fluorine-containing bisphosphonic acid derivative and use thereof. WO2016125757A1. National University, Nagasaki University; 2016.
   Google Scholar
• Lawson MA, Ebetino FH, Mazur A, et al. The pharmacological profile of a novel highly potent bisphosphonate, OX14 (1-Fluoro-2-(Imidazo-[1,2-alpha]Pyridin-3-yl)-Ethyl-bisphosphonate). J Bone Miner Res. 2017;32:1860–1869.
   PubMed Web of Science ®Google Scholar
• Mingqi L, Junnan P, Han W, et al. Chengdu Yunke Pharmaceutical Co, Ltd. Bisphosphonate compounds as well as preparation method and application thereof. CN106083925A; 2016.
   Google Scholar
• Ling Q, Jianguo L, Gaochao L, et al. Jiangsu Institute of Atomic Medicine. 2-alkyl substituted imidazolyl diphosphonic acid compound as well as preparation method and application thereof. CN106749406A; 2016.
   Google Scholar
• Jianguo L, Ying P, Ling Q, et al. Jiangsu Institute of Atomic Medicine. Imidazole heterocyclic diphosphonic acid compound as well as preparation method and application thereof. CN106749405A; 2016.
   Google Scholar
• Ying P, Jianguo L, Ling Q, et al. Jiangsu Institute of Atomic Medicine. Application of zoledronic acid compound in preparation of drugs for treating cancers. CN107213153A; 2017.
   Google Scholar
• Tabuteau H; Antecip Bioventures II, LLC. Dosage forms for oral administration of zoledronic acid or related compounds for treating disease. US10137139B2; 2017.
   Google Scholar
• Adami S, Fossaluzza V, Gatti D, et al. Bisphosphonate therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis. 1997;56:201–204.
   PubMed Web of Science ®Google Scholar
• Manicourt DH, Brasseur JP, Boutsen Y, et al. Role of alendronate in therapy for posttraumatic complex regional pain syndrome type I of the lower extremity. Arthritis Rheum. 2004;50:3690–3697.
   PubMed Web of Science ®Google Scholar
• Varenna M, Adami S, Rossini M, et al. Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study. Rheumatology (Oxford). 2013;52:534–542.
   PubMed Web of Science ®Google Scholar
• Robinson JN, Sandom J, Chapman PT. Efficacy of pamidronate in complex regional pain syndrome type I. Pain Med. 2004;5:276–280.
   PubMed Web of Science ®Google Scholar
• Varenna M, Zucchi F, Ghiringhelli D, et al. Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study. J Rheumatol. 2000;27:1477–1483.
   PubMed Web of Science ®Google Scholar
• Burn C, Quan L, Haixia L. Hangzhou Dancheng Pharmaceutical Technology Co., Ltd. Use of zoledronic acid, powder aerosol and preparation method. CN107550919A; 2017.
   Google Scholar
• Ueno M, Maeno T, Nishimura S, et al. Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages. Nat Commun. 2015;6:6332.
   PubMed Web of Science ®Google Scholar
• McKenna CE, Kashemirov BA, Nguyen K. University of Southern California. Bone active nitrogen-containing bisphosphonates with a near infrared fluorescent label. WO2017053486A1; 2016.
   Google Scholar
• McKenna CE, Kasemurovi BA, Shuting S, et al. University of Southern California. Fluorescent bisphosphonate analogs. CN107667110A; 2016.
   Google Scholar
• Danilenko ED, Zakabunin AI, Volosnikova E, et al. Federal Budgetary Institution of Science “State Research Center of Virology and Biotechnology” Vector. Method for preparing antineoplastic drug against bone metastases in form of conjugate of protein-cytokine and aminobisphosphonate. RU2631486C1; 2016.
   Google Scholar
• Soo BC, Kang TC, Wu BM; The Reagents of the University of California. Bone-targeting therapeutic conjugate and methods of making and using the same. WO2017160855A1 (2017)
   Google Scholar
• Ivanova EA, Karpeyskiy A, Zinnen SP, et al. Limited Liability Company “Osteros Biomedica”. Stabilized dosage form of etidronate-cytarabine conjugate and its application. RU2657833C2; 2015.
   Google Scholar
• Ebetino F, Boeckman R, Xing L, et al.; University of Rochester. Bortezomib conjugates and methods using same. WO2017079262A1 (2016)
   Google Scholar
• Ebetino FH, Sun S, Lundy MW, et al.. Biovinc, Llc. Bisphosphonate quinolone conjugates and uses thereof. WO2017210611A1; 2017.
   Google Scholar
• Boeckman R, Boyce B, Xiao L, et al.. University of Rochester. Phosphonate-Chloroquine Conjugates and Methods Using Same. US20180318282A1; 2016.
   Google Scholar
• Thevenin M, Young RN, Chen G. Simon Fraser University. Amide-linked ep4 agonist-bisphosphonate compounds and uses thereof. US2018170951A1; 2016.
   Google Scholar
• Peizhi Z, Jingcheng W, Lianqi Y, et al. Yangzhou University. Heparin bisphosphonate derivative and synthetic method and application thereof. CN105085717A; 2015.
   Google Scholar
• Baogang X, Wei W, Haipeng W, et al. Nanchang University. Alendronate sodium solid lipid nanoparticle and preparation method thereof. CN106821984A; 2017.
   Google Scholar
• Haney SL, Wills VS, Wiemer DF, et al. Recent advances in the development of mammalian geranylgeranyl diphosphate synthase inhibitors. Molecules. 2017;22:886.
   Web of Science ®Google Scholar
• Szabo CM, Matsumura Y, Fukura S, et al. Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents. J Med Chem. 2002;45:2185–2196.
   PubMed Web of Science ®Google Scholar
• Shull LW, Wiemer AJ, Hohl RJ, et al. Synthesis and biological activity of isoprenoid bisphosphonates. Bioorg Med Chem. 2006;14:4130–4136.
   PubMed Web of Science ®Google Scholar
• Wiemer AJ, Tong H, Swanson KM, et al. Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase. Biochem Biophys Res Commun. 2007;353:921–925.
   PubMed Web of Science ®Google Scholar
• Wiemer AJ, Yu JS, Lamb KM, et al. Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors. Bioorg Med Chem. 2008;16:390–399.
   PubMed Web of Science ®Google Scholar
• Zhou X, Ferree SD, Wills VS, et al. Geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase. Bioorg Med Chem. 2014;22:2791–2798.
   PubMed Web of Science ®Google Scholar
• Wills VS, Allen C, Holstein SA, et al. Potent triazole bisphosphonate inhibitor of geranylgeranyl diphosphate synthase. ACS Med Chem Lett. 2015;6:1195–1198.
   PubMed Web of Science ®Google Scholar
• Allen C, Kortagere S, Tong H, et al. Olefin isomers of a triazole bisphosphonate synergistically inhibit geranylgeranyl diphosphate synthase. Mol Pharmacol. 2017;91:229–236.
   PubMed Web of Science ®Google Scholar
• Wills VS, Metzger JI, Allen C, et al. Bishomoisoprenoid triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase. Bioorg Med Chem. 2017;25:2437–2444.
   PubMed Web of Science ®Google Scholar
• Matthiesen RA, Varney ML, Xu PC, et al. alpha-Methylation enhances the potency of isoprenoid triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors. Bioorg Med Chem. 2018;26:376–385.
   PubMed Web of Science ®Google Scholar
• Matthiesen RA, Wills VS, Metzger JI, et al. Stereoselective synthesis of homoneryl and homogeranyl triazole bisphosphonates. J Org Chem. 2016;81:9438–9442.
   PubMed Web of Science ®Google Scholar
• Holstein S, Wiemer D. Board of Reagents of the University of Nebraska, University of Iowa Research Foundation. Triazole bisphosphonate geranylgeranyl diphosphate synthase inhibitors. WO2018200603A1; 2018.
   Google Scholar
• Haney SL, Chhonker YS, Varney ML, et al. Preclinical investigation of a potent geranylgeranyl diphosphate synthase inhibitor. Invest New Drugs. 2018;36:810–818.
   PubMed Web of Science ®Google Scholar
• Haney SL, Chhonker YS, Varney ML, et al. In vivo evaluation of novel geranylgeranyl diphosphate synthase inhibitors. Blood. 2018;132:215.
   Web of Science ®Google Scholar
• Haney SL, Varney ML, Chhonker YS, et al. Inhibition of geranylgeranyl diphosphate synthase is a novel therapeutic strategy for pancreatic ductal adenocarcinoma. Oncogene. 2019. epub ahead of print.
   PubMedGoogle Scholar
• Lacbay CM, Waller DD, Park J, et al. Unraveling the prenylation-cancer paradox in multiple myeloma with novel geranylgeranyl pyrophosphate synthase (GGPPS) inhibitors. J Med Chem. 2018;61:6904–6917.
   PubMed Web of Science ®Google Scholar
• Tsantrizos YS, Sebag M. Royal Institute for the Advancement of Learning, McGill University. Substituted bicyclic pyrimidine-based compounds and compositions and uses thereof. WO2018137036A1; 2018.
   Google Scholar
• Coxon FP, Helfrich MH, Larijani B, et al. Identification of a novel phosphonocarboxylate inhibitor of Rab geranylgeranyl transferase that specifically prevents Rab prenylation in osteoclasts and macrophages. J Biol Chem. 2001;276:48213–48222.
   PubMed Web of Science ®Google Scholar
• Coxon FP, Ebetino FH, Mules EH, et al. Phosphonocarboxylate inhibitors of Rab geranylgeranyl transferase disrupt the prenylation and membrane localization of Rab proteins in osteoclasts in vitro and in vivo. Bone. 2005;37:349–358.
   PubMed Web of Science ®Google Scholar
• Lawson MA, Coulton L, Ebetino FH, et al. Geranylgeranyl transferase type II inhibition prevents myeloma bone disease. Biochem Biophys Res Commun. 2008;377:453–457.
   PubMed Web of Science ®Google Scholar
• Baron RA, Tavare R, Figueiredo AC, et al. Phosphonocarboxylates inhibit the second geranylgeranyl addition by Rab geranylgeranyl transferase. J Biol Chem. 2009;284:6861–6868.
   PubMed Web of Science ®Google Scholar
• Guo Z, Wu YW, Das D, et al. Structures of RabGGTase-substrate/product complexes provide insights into the evolution of protein prenylation. Embo J. 2008;27:2444–2456.
   PubMed Web of Science ®Google Scholar
• Basso AD, Kirschmeier P, Bishop WR. Lipid posttranslational modifications. Farnesyl transferase inhibitors. J Lipid Res. 2006;47:15–31.
   PubMed Web of Science ®Google Scholar
• Blazewska KM, Ni F, Haiges R, et al. Synthesis, stereochemistry and SAR of a series of minodronate analogues as RGGT inhibitors. Eur J Med Chem. 2011;46:4820–4826.
   PubMed Web of Science ®Google Scholar
• Coxon FP, Joachimiak L, Najumudeen AK, et al. Synthesis and characterization of novel phosphonocarboxylate inhibitors of RGGT. Eur J Med Chem. 2014;84:77–89.
   PubMed Web of Science ®Google Scholar
• Kazmierczak A, Kusy D, Niinivehmas SP, et al. Identification of the Privileged Position in the Imidazo[1,2-a]pyridine Ring of Phosphonocarboxylates for Development of Rab Geranylgeranyl Transferase (RGGT) Inhibitors. J Med Chem. 2017;60:8781–8800.
   PubMed Web of Science ®Google Scholar
• Joachimiak L, Marchwicka A, Gendaszewska-Darmach E, et al. Synthesis and biological evaluation of imidazole-bearing alpha-phosphonocarboxylates as inhibitors of rab geranylgeranyl transferase (RGGT). ChemMedChem. 2018;13:842–851.
   PubMed Web of Science ®Google Scholar
• Zhou X, Born EJ, Allen C, et al. N-Oxide derivatives of 3-(3-pyridyl)-2-phosphonopropanoic acids as potential inhibitors of Rab geranylgeranylation. Bioorg Med Chem Lett. 2015;25:2331–2334.
   PubMedGoogle Scholar
• Raje N, Terpos E, Willenbacher W, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018;19:370–381.
   PubMed Web of Science ®Google Scholar
• Henry DH, Costa L, Goldwasser F, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011;29:1125–1132.
   PubMed Web of Science ®Google Scholar
• Jolette J, Attalla B, Varela A, et al. Comparing the incidence of bone tumors in rats chronically exposed to the selective PTH type 1 receptor agonist abaloparatide or PTH(1-34). Regul Toxicol Pharmacol. 2017;86:356–365.
   PubMed Web of Science ®Google Scholar
• Cummings SR, Ensrud K, Delmas PD, et al. Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med. 2010;362:686–696.
   PubMed Web of Science ®Google Scholar
• Himelstein AL, Foster JC, Khatcheressian JL, et al. Effect of longer-interval vs standard dosing of zoledronic acid on skeletal events in patients with bone metastases: a randomized clinical trial. JAMA. 2017;317:48–58.
   PubMed Web of Science ®Google Scholar
• Anderson K, Ismaila N, Flynn PJ, et al. Role of bone-modifying agents in multiple myeloma: american society of clinical oncology clinical practice guideline update. J Clin Oncol. 2018;36:812–818.
   PubMed Web of Science ®Google Scholar