Recent advances in models for screening potential osteoporosis drugs

References

• Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet. 2011;377:1276–1287.
   PubMed Web of Science ®Google Scholar
• Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts and prospects. J Clin Invest. 2005;115:3318–3325.
   PubMed Web of Science ®Google Scholar
• Seeman E, Delmas PD. Bone quality – the material and structural basis of bone strength and fragility. N Engl J Med. 2006;354:2250–2261.
   PubMed Web of Science ®Google Scholar
• Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res. 2007 Mar 1;22(3):465–475.
   PubMed Web of Science ®Google Scholar
• Hernlund E, Svedbom A, Ivergård M, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8:136.
   PubMed Web of Science ®Google Scholar
• Kanis JA, Cooper C, Rizzoli R, et al.; European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Identification and management of patients at increased risk of osteoporotic fracture: outcomes of an ESCEO expert consensus meeting. Osteoporos Int. 2017;28(7):2023–2034.
   PubMed Web of Science ®Google Scholar
• Bliuc D, Nguyen ND, Milch VE, et al. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. 2009;301(5):513–521.
   PubMed Web of Science ®Google Scholar
• Martin TJ, Seeman E. Bone remodeling: its local regulation and the emergence of bone fragility. Best Pract Res Clin Endo Endocrinol Metab. 2008;22:701–722.
   PubMed Web of Science ®Google Scholar
• Bellido T. Osteocyte-driven bone remodeling. Calcif Tissue Int. 2014;94:25–34.
   PubMed Web of Science ®Google Scholar
• Riggs BL, Khosla S, Melton LJ 3rd. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002;23:279–302.
   PubMed Web of Science ®Google Scholar
• Black DM, Rosen CJ. Postmenopausal osteoporosis. N Engl J Med. 2016;374:254–262.
   PubMed Web of Science ®Google Scholar
• Siris ES, Adler R, Bilezikian J, et al. The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int. 2014;25:1439–1443.
   PubMed Web of Science ®Google Scholar
• Cummings SR, Black DM, Nevitt MC, et al. Bone density at various sites for prediction of hip fractures. Lancet. 1993;341:72–75.
   PubMed Web of Science ®Google Scholar
• Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement. 2000 Mar 27–29;17(1):1–45.
   Google Scholar
• Lorentzon M, Cummings SR. Osteoporosis: the evolution of a diagnosis. J Intern Med. 2015;277:650–661.
   PubMed Web of Science ®Google Scholar
• Kanis JA, Johnell O, Oden A, et al. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int. 2008;19(4):385–397.
   PubMed Web of Science ®Google Scholar
• Gennari L, Merlotti D, Nuti R. Perspectives in the treatment and prevention of osteoporosis. Drugs Today (Barc). 2009;45:629–647.
   PubMed Web of Science ®Google Scholar
• Gennari L, Rotatori S, Bianciardi S, et al. Treatment needs and current options for postmenopausal osteoporosis. Expert Opin Pharmacother. 2016;17(8):1141–1152.
   PubMed Web of Science ®Google Scholar
• Office of Freedom of Information. Guidelines for the clinical evaluation of drugs used in the treatment of osteoporosis. Rockville (MD): Department of Health and Human Services; 1979.
   Google Scholar
• Colman EG; Food and Drug Administration. The Food and Drug Administration’s osteoporosis guidance document: past, present, and future. J Bone Miner Res. 2003;18(6):1125–1128.
   PubMed Web of Science ®Google Scholar
• Colman E, Hedin R, Swann J, et al. A brief history of calcitonin. Lancet. 2002;359:885–886.
   PubMed Web of Science ®Google Scholar
• Office of Freedom of Information. Guidelines for the clinical evaluation of drugs used in the treatment or prevention of osteoporosis. Rockville (MD): Department of Health and Human Services; 1984.
   Google Scholar
• Fleisch H, Russell RGG, 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
• Russell RG. Bisphosphonates: the first 40 years. Bone. 2011;49:2–19.
   PubMed Web of Science ®Google Scholar
• Riggs BL, Hodgson SF, O’Fallon WM, et al. Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med. 1990;322:802–809.
   PubMed Web of Science ®Google Scholar
• Office of Freedom of Information. Guidelines for preclinical and clinical evaluation of agents used in the prevention or treatment of postmenopausal osteoporosis. Rockville (MD): Department of Health, and Human Services; 1994.
   Google Scholar
• Rissanen JP, Halleen JM. Models and screening assays for drug discovery in osteoporosis. Expert Opin Drug Discov. 2010 Dec;5(12):1163–1174.
   PubMed Web of Science ®Google Scholar
• Rissanen JP, Ylipahkala H, Fagerlund KM, et al. Improved methods for testing antiresorptive compounds in human osteoclast cultures. J Bone Miner Metab. 2009;27(1):105–109.
   PubMed Web of Science ®Google Scholar
• Selander K, Lehenkari P, Väänänen HK. The effects of bisphosphonates on the resorption cycle of isolated osteoclasts. Calcif Tissue Int. 1994;55:368–375.
   PubMed Web of Science ®Google Scholar
• Gennari L, Merlotti D, Valleggi F, et al. Selective estrogen receptor modulators for postmenopausal osteoporosis: current state of development. Drugs Aging. 2007;24:361–379.
   PubMed Web of Science ®Google Scholar
• Komm BS, Mirkin S. An overview of current and emerging SERMs. J Steroid Biochem Mol Biol. 2014;143:207–222.
   PubMed Web of Science ®Google Scholar
• Russell G. Bisphosphonates from bench to bedside. Ann NY Acad Sci. 2006;1068:367–401.
   PubMed Web of Science ®Google Scholar
• Rogers MJ, Crockett JC, Coxon FP, et al. Biochemical and molecular mechanisms of action of bisphosphonates. Bone. 2011;49:34–41.
   PubMed Web of Science ®Google Scholar
• Kalu DN. The ovariectomized rat model of postmenopausal bone loss. Bone Miner. 1991;15:175–191.
   PubMedGoogle Scholar
• Guideline on the evaluation of medicinal products in the treatment of primary osteoporosis. European Medicines Agency. [cited 2018 May 21]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003405.pdf
   Google Scholar
• Osteoporosis: nonclinical evaluation of drugs intended for treatment guidance for industry. FDA. [cited 2018 May 21]. Available from: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM506366.pdf
   Google Scholar
• Binkley N, Kimmel D, Bruner J, et al. Zoledronate prevents the development of absolute osteopenia following ovariectomy in adult rhesus monkeys. J Bone Miner Res. 1998;13(11):1775–1782.
   PubMed Web of Science ®Google Scholar
• Hornby SB, Evans GP, Hornby SL, et al. Long-term zoledronic acid treatment increases bone structure and mechanical strength of long bones of ovariectomized adult rats. Calcif Tissue Int. 2003;72(4):519–527.
   PubMed Web of Science ®Google Scholar
• Glatt M, Pataki A, Evans GP, et al. Loss of vertebral bone and mechanical strength in estrogen-deficient rats is prevented by long-term administration of zoledronic acid. Osteoporos Int. 2004;15(9):707–715.
   PubMed Web of Science ®Google Scholar
• Black DM, Delmas PD, Eastell R, et al.; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809–1822.
   PubMed Web of Science ®Google Scholar
• Fleisch H, Russell RG, Simpson B, et al. Prevention by a diphosphonate of immobilization “osteoporosis” in rats. Nature. 1969;223(5202):211–212.
   PubMed Web of Science ®Google Scholar
• Peng Z, Tuukkanen J, Zhang H, et al. The mechanical strength of bone in different rat models of experimental osteoporosis. Bone. 1994;15(5):523–532.
   PubMed Web of Science ®Google Scholar
• Sakai A, Sakata T, Ikeda S, et al. Intermittent administration of human parathyroid hormone(1-34) prevents immobilization-related bone loss by regulating bone marrow capacity for bone cells in ddY mice. J Bone Miner Res. 1999;14(10):1691–1699.
   PubMed Web of Science ®Google Scholar
• Yao W, Cheng Z, Pham A, et al. Glucocorticoid-induced bone loss in mice can be reversed by the actions of parathyroid hormone and risedronate on different pathways for bone formation and mineralization. Arthritis Rheum. 2008;58(11):3485–3497.
   PubMedGoogle Scholar
• Gao W, Reiser PJ, Coss CC, et al. Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. Endocrinology. 2005;146(11):4887–4897.
   PubMed Web of Science ®Google Scholar
• Börjesson AE, Farman HH, Engdahl C, et al. The role of activation functions 1 and 2 of estrogen receptor-α for the effects of estradiol and selective estrogen receptor modulators in male mice. J Bone Miner Res. 2013;28(5):1117–1126.
   PubMed Web of Science ®Google Scholar
• Rinotas V, Niti A, Dacquin R, et al. Novel genetic models of osteoporosis by overexpression of human RANKL in transgenic mice. J Bone Miner Res. 2014;29(5):1158–1169.
   PubMed Web of Science ®Google Scholar
• Andersson N, Lindberg MK, Ohlsson C, et al. Repeated in vivo determinations of bone mineral density during parathyroid hormone treatment in ovariectomized mice. J Endocrinol. 2001;170(3):529–537.
   PubMed Web of Science ®Google Scholar
• Morello KC, Wurz GT, De Gregorio MW. SERMs: current status and future trends. Crit Rev Oncol Hematol. 2002;43:63–76.
   PubMed Web of Science ®Google Scholar
• Parfitt AM, Drezner MK, Glorieux FH, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res. 1987;2:595–610.
   PubMed Web of Science ®Google Scholar
• Campbell GM, Sophocleous A. Quantitative analysis of bone and soft tissue by micro-computed tomography: applications to ex vivo and in vivo studies. Bonekey Rep. 2014;3:564.
   PubMedGoogle Scholar
• Movérare S, Venken K, Eriksson A-L, et al. Differential effects on bone of estrogen receptor alpha and androgen receptor activation in orchidectomized adult male mice. Proc Natl Acad Sci USA. 2003;100(23):13573–13578.
   PubMed Web of Science ®Google Scholar
• Tivesten A, Moverare S, Chagin A, et al. Additive effects of estrogen and androgen receptor activation on trabecular bone in ovariectomized rats. J. Bone Miner Res. 2004;19(11):1833–1839.
   PubMed Web of Science ®Google Scholar
• McLaughlin F, MacIntosh J, Hayes B, et al. Glucocorticoid induced osteopenia in the mouse as assessed by histomorphometry, micro CT and biochemical markers. Bone. 2002;30(6):924–930.
   PubMed Web of Science ®Google Scholar
• Sasov AY, Dewaele D. High resolution in vivo scanner for small animals. In: Bonse U, editor. Developments in X-ray tomography III. Vol. 4503, Proceedings of SPIE, Orlando, Florida, US; 2002. p. 256–264.
   Google Scholar
• Office of Freedom of Information 1994 Guidelines for Preclinical and Clinical Evaluation of Agents Used in the Prevention or Treatment of Postmenopausal Osteoporosis. Department of Health and Human Services, Rockville, MD, USA. Available from: https://www.fda.gov/OHRMS/DOCKETS/98fr/04d-0035-gdl0001.pdf
   Google Scholar
• Thompson DD, Simmons HA, Pirie CM, et al. FDA guidelines and animal models for osteoporosis. Bone. 1995;17(4Suppl):125S–133S.
   PubMedGoogle Scholar
• Available from: https://www.iofbonehealth.org/emea-revises-guidelines-evaluation-drugs-treatment-primary-osteoporosis
   Google Scholar
• Reginster J-Y, Abadie E, Delmas P, et al. Recommendations for an update of the current (2001) regulatory requirements for registration of drugs to be used in the treatment of osteoporosis in postmenopausal women and in men. Osteoporos Int. 2006;17(1):1–7.
   PubMed Web of Science ®Google Scholar
• Gennari L, Bilezikian JP. New and developing pharmacotherapy for osteoporosis in men. Expert Opin Pharmacother. 2018;19(3):253–264.
   PubMed Web of Science ®Google Scholar
• Schuitt SC, van der Klift M, Weel AE, et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam study. Bone. 2004;34:195–202.
   PubMed Web of Science ®Google Scholar
• Gennari L, Rotatori S, Bianciardi S, et al. Appropriate models for novel osteoporosis drug discovery and future perspectives. Expert Opin Drug Discov. 2015;10(11):1201–1216.
   PubMed Web of Science ®Google Scholar
• Manolagas SC. Wnt signaling and osteoporosis. Maturitas. 2014;78:233–237.
   PubMed Web of Science ®Google Scholar
• Gong Y, Slee RB, Fukai N, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001;107:513–523.
   PubMed Web of Science ®Google Scholar
• Little RD, Carulli JP, Del Mastro RG, et al. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet. 2002;70:11–19.
   PubMed Web of Science ®Google Scholar
• Boyden LM, Mao J, Belsky J, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002;346:1513–1521.
   PubMed Web of Science ®Google Scholar
• Balemans W, Ebeling M, Patel N, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Molec Genet. 2001;10:537–543.
   PubMed Web of Science ®Google Scholar
• Brunkow M, Gardner JC, Van Ness J, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001;68:577–589.
   PubMed Web of Science ®Google Scholar
• Balemans W, Patel N, Ebeling M, et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet. 2002;39:91–97.
   PubMed Web of Science ®Google Scholar
• Papapoulos SE. Targeting sclerostin as potential treatment of osteoporosis. Ann Rheum Dis. 2011;70:i119–i122.
   PubMed Web of Science ®Google Scholar
• Das S, Sakthiswary R. Bone metabolism and histomorphometric changes in murine models treated with sclerostin antibody: a systematic review. Curr Drug Targets. 2013;14:1667–1674.
   PubMed Web of Science ®Google Scholar
• Langdahl BL, Libanati C, Crittenden DB, et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet. 2017;390(10102):1585–1594.
   PubMed Web of Science ®Google Scholar
• Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417–1427.
   PubMed Web of Science ®Google Scholar
• Amgen and UCB announce increased cardiovascular risk in patients receiving romosozumab, an anti-sclerostin antibody. Rheumatology (Oxford). 2017;56(8):e21.
   PubMedGoogle Scholar
• Bone HG, Dempster DW, Eisman JA, et al. Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the long-term odanacatib fracture trial. Osteoporos Int. 2015;26:699–712.
   PubMed Web of Science ®Google Scholar
• Mullard A. Merck &Co. drops osteoporosis drug odanacatib. Nat Rev Drug Discov. 2016;15:669.
   Web of Science ®Google Scholar
• Drake MT, Clarke BL, Oursler MJ, et al. Cathepsin K inhibitors for osteoporosis: biology, potential clinical utility, and lessons learned. Endocr Rev. 2017;38:325–350.
   PubMed Web of Science ®Google Scholar
• Brommage R. Genetic approaches to identifying novel osteoporosis drug targets. J Cell Biochem. 2015;116(10):2139–2145.
   PubMed Web of Science ®Google Scholar
• Brommage R, Liu J, Hansen GM, et al. High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes. Bone Res. 2014;2:14034.
   PubMed Web of Science ®Google Scholar
• Rozman J, Rathkolb B, Oestereicher MA, et al. Identification of genetic elements in metabolism by high-throughput mouse phenotyping. Nat Commun. 2018;9(1):288.
   PubMedGoogle Scholar
• Kostenuik PJ, Nguyen HQ, McCabe J, et al. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res. 2009;24:182–195.
   PubMed Web of Science ®Google Scholar
• Pennypacker BL, Duong LT, Cusick TE, et al. Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbits. J Bone Miner Res. 2011;26:252–262.
   PubMed Web of Science ®Google Scholar
• Manolagas SC. The quest for osteoporosis mechanisms and rational therapies: how far we’ve come, how much further we need to go. J Bone Miner Res. 2018 Feb 5;33:371–385. [Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Khosla S, Farr JN, Kirkland JL. Inhibiting cellular senescence: a new therapeutic paradigm for age-related osteoporosis. J Clin Endocrinol Metab. 2018 Feb 7;103:1282–1290. [Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Piemontese M, Almeida M, Robling AG, et al. Old age causes de novo intracortical bone remodeling and porosity in mice. JCI Insight. 2017;2(17). pii:93771.
   PubMed Web of Science ®Google Scholar
• Strontium ranelate discontinued. Drug Ther Bull. 2017 Aug;55(8):93–94.
   Google Scholar
• Siris ES, Miller PD, Barrett-Connor E, et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment. JAMA. 2001;286:2815–2822.
   PubMed Web of Science ®Google Scholar
• Merlotti D, Gennari L, Dotta F, et al. Mechanisms of impaired bone strength in type 1 and 2 diabetes. Nutr Metab Cardiovasc Dis. 2010;20(9):683–690.
   PubMed Web of Science ®Google Scholar
• Sundh D, Mellström D, Nilsson M, et al. Increased cortical porosity in older men with fracture. J Bone Miner Res. 2015;30(9):1692–1700.
   PubMed Web of Science ®Google Scholar
• Sundh D, Nilsson AG, Nilsson M, et al. Increased cortical porosity in women with hip fracture. J Intern Med. 2017;281(5):496–506.
   PubMed Web of Science ®Google Scholar
• Patsch JM, Burghardt AJ, Yap SP, et al. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res. 2013;28(2):313–324.
   PubMed Web of Science ®Google Scholar
• Saito M, Marumo K. Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int. 2010;21(2):195–214.
   PubMed Web of Science ®Google Scholar
• Ahmed LA, Shigdel R, Joakimsen RM, et al. Measurement of cortical porosity of the proximal femur improves identification of women with nonvertebral fragility fractures. Osteoporos Int. 2015;26(8):2137–2146.
   PubMed Web of Science ®Google Scholar
• Diez-Perez A, Güerri R, Nogues X, et al. Microindentation for in vivo measurement of bone tissue mechanical properties in humans. J Bone Miner Res. 2010;25:1877–1885.
   PubMed Web of Science ®Google Scholar
• Güerri-Fernández RC, Nogués X, Quesada Gómez JM, et al. Microindentation for in vivo measurement of bone tissue material properties in atypical femoral fracture patients and controls. J Bone Miner Res. 2013;28:162–168.
   PubMed Web of Science ®Google Scholar
• Farr JN, Xu M, Weivoda MM, et al. Targeting cellular senescence prevents age-related bone loss in mice. Nat Med. 2017;23(9):1072–1079.
   PubMed Web of Science ®Google Scholar