Treatment needs and current options for postmenopausal osteoporosis

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
• 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
• 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
• 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
• Lorentzon M, Cummings SR. Osteoporosis: the evolution of a diagnosis. J Intern Med. 2015;277:650–661.
   PubMed Web of Science ®Google Scholar
• Gennari L, Merlotti D, Nuti R. Perspectives in the treatment and prevention of osteoporosis. Drugs Today (Barc). 2009;45:629–4.
   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;10:1201–1216.
   PubMed Web of Science ®Google Scholar
• Boonen S, Laan RF, Barton IP, et al. Effect of osteoporosis treatments on risk of non-vertebral fractures: review and meta-analysis of intention-to-treat studies. Osteoporos Int. 2005;16:1291–1298.
   PubMed Web of Science ®Google Scholar
• Ferrari S. Future directions for new medical entities in osteoporosis. Best Pract Clin Endocrinol Metab. 2014;28:859–870.
   PubMed Web of Science ®Google Scholar
• Seeman E. Is a change in bone mineral density a sensitive and specific surrogate of anti-fracture efficacy? Bone. 2007;41:308–317.
   PubMed Web of Science ®Google Scholar
• Kleerekoper M. Osteoporosis prevention and therapy: preserving and building strength through bone quality. Osteoporos Int. 2006;17:1707–1715.
   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
• Bilezikian JP. Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Am J Med. 2009;122:S14–S21.
   Web of Science ®Google Scholar
• Maraka S, Kennel KA. Bisphosphonates for the prevention and treatment of osteoporosis. BMJ. 2015;351:h3783.
   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;356:1809–1822.
   PubMed Web of Science ®Google Scholar
• Khosla S, Bilezikian JP, Dempster DW, et al. Benefits and risks of bisphosphonate therapy for osteoporosis. J Clin Endocrinol Metab. 2012;97:2272–2282.
   PubMed Web of Science ®Google Scholar
• McClung M, Harris ST, Miller PD, et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med. 2013;126:13–20.
   PubMed Web of Science ®Google Scholar
• Black DM, Bauer DC, Schwartz AV, et al. Continuing bisphosphonate treatment for osteoporosis—for whom and for how long? N Engl J Med. 2012;366:2051–2053.
   PubMed Web of Science ®Google Scholar
• Khosla S, Oursler MJ, Monroe DG. Estrogen and the skeleton. Trends Endocrinol Metab. 2012;23:576–581.
   PubMed Web of Science ®Google Scholar
• Bord S, Beavan S, Ireland D, et al. Mechanisms by which high dose estrogen therapy produces anabolic skeletal effects in postmenopausal women: role of locally produced growth factors. Bone. 2001;29:216–222.
   PubMed Web of Science ®Google Scholar
• Christiansen C, Lindsay R. Estrogens, bone loss and preservation. Osteoporos Int. 1990;1:7–13.
   PubMedGoogle Scholar
• Cauley JA, Robbins J, Chen Z, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the women’s health initiative randomized trial. JAMA. 2003;290:1729–1738.
   PubMed Web of Science ®Google Scholar
• Jackson RD, Shidham S. The role of hormone therapy and calcium plus vitamin D for reduction of bone loss and risk for fractures: lessons learned from the women’s health initiative. Curr Osteoporos Rep. 2007;5:153–159.
   PubMedGoogle Scholar
• Gurney EP, Nachtigall MJ, Nachtigall LE, et al. The women’s health initiative trial and related studies: 10 years later: a clinician’s view. J Steroid Biochem Mol Biol. 2014 Jul;142:4–11.
   PubMed Web of Science ®Google Scholar
• Manson JE, Hsia J, Johnson KC, et al. Women’s health initiative investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523–534.
   PubMed Web of Science ®Google Scholar
• Prestwood KM, Kenny AM, Kleppinger A, et al. Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial. JAMA. 2003;290:1042–1048.
   PubMed Web of Science ®Google Scholar
• de Villiers TJ, Gass MLS, Haines CJ, et al. Global consensus statement on menopausal hormone therapy. Climacteric. 2013;16:203–204.
   PubMed Web of Science ®Google Scholar
• Santen RJ, Kagan R, Altomare CJ, et al. Current and evolving approaches to individualizing estrogen receptor-based therapy for menopausal women. J Clin Endocrinol Metab. 2014;99:733–747.
   PubMed Web of Science ®Google Scholar
• Roehm E. A reappraisal of women’s health initiative estrogen-alone trial: long-term outcomes in women 50–59 years of age. Obstet Gynecol Int. 2015;2015:713295. doi:10.1155/2015/713295. Epub 2015 Jan 1.
   PubMedGoogle Scholar
• de Villiers TJ, Stevenson JC. The WHI: the effect of hormone replacement therapy on fracture prevention. Climacteric. 2012;15:263–266.
   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
• Mirkin S, Komm BS. Tissue-selective estrogen complexes for postmenopausal women. Maturitas. 2013;76:213–220.
   PubMed Web of Science ®Google Scholar
• Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89:309–319.
   PubMed Web of Science ®Google Scholar
• Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2008;29:155–192.
   PubMed Web of Science ®Google Scholar
• Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Mineral Res. 2004;19:1059–1066.
   PubMed Web of Science ®Google Scholar
• McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354:821–831.
   PubMed Web of Science ®Google Scholar
• Zaheer S, LeBoff M, Lewiecki EM. Denosumab for the treatment of osteoporosis. Expert Opin Drug Metab Toxicol. 2015;11:461–470.
   PubMed Web of Science ®Google Scholar
• Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–765.
   PubMed Web of Science ®Google Scholar
• Bone HG, Chapurlat R, Brandi M-L, et al. The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Metab. 2013;98:4483–4492.
   PubMed Web of Science ®Google Scholar
• Dempster DW, Cosman F, Parisien M, et al. Anabolic actions of parathyroid hormone on bone. Endocr Rev. 1993;14:690–709.
   PubMed Web of Science ®Google Scholar
• Reeve J, Hesp R, Williams D, et al. Anabolic effect of low doses of a fragment of human parathyroid hormone on the skeleton in postmenopausal osteoporosis. Lancet. 1976;1:1035–1038.
   PubMed Web of Science ®Google Scholar
• Reeve J, Meunier PJ, Parsons JA, et al. Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial. Br Med J. 1980;280:1340–1344.
   PubMed Web of Science ®Google Scholar
• Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:1434–1441.
   PubMed Web of Science ®Google Scholar
• Marcus R, Wang O, Satterwhite J, et al. The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis. J Bone Miner Res. 2003;18:18–23.
   PubMed Web of Science ®Google Scholar
• Delmas PD, Licata AA, Reginster JY, et al. Fracture risk reduction during treatment with teriparatide is independent of pre-treatment bone turnover. Bone. 2006;39:237–243.
   PubMed Web of Science ®Google Scholar
• Greenspan SL, Bone HG, Ettinger MP, et al. Effect of recombinant human parathyroid hormone (1–84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann Intern Med. 2007;146:326–339.
   PubMed Web of Science ®Google Scholar
• Pleiner-Duxneuner J, Zwettler E, Paschalis E, et al. Treatment of osteoporosis with parathyroid hormone and teriparatide. Calcif Tissue Int. 2009;84:159–170.
   PubMed Web of Science ®Google Scholar
• Chen P, Miller PD, Delmas PD, et al. Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis. J Bone Miner Res. 2006;21:1785–1790.
   PubMed Web of Science ®Google Scholar
• Canalis E, Giustina A, Bilezikian JP. Mechanisms of anabolic therapies for osteoporosis. N Engl J Med. 2007;357:905–916.
   PubMed Web of Science ®Google Scholar
• Keaveny TM, Donley DW, Hoffmann PF, et al. Effects of teriparatide and alendronate on vertebral strength as assessed by finite element modeling of QCT scans in women with osteoporosis. J Bone Miner Res. 2007;22:149–157.
   PubMed Web of Science ®Google Scholar
• Graeff C, Chevalier Y, Charlebois M, et al. Improvements in vertebral body strength under teriparatide treatment assessed in vivo by finite element analysis: results from the EUROFORS study. J Bone Miner Res. 2009;24:1672–1680.
   PubMed Web of Science ®Google Scholar
• McClung MR, San Martin J, Miller PD, et al. Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med. 2005;165:1762–1768.
   PubMed Web of Science ®Google Scholar
• Black DM, Bilezikian JP, Ensrud KE, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med. 2005;353:555–565.
   PubMed Web of Science ®Google Scholar
• Leder BZ, Neer RM, Wyland JJ, et al. Effects of teriparatide treatment and discontinuation in postmenopausal women and eugonadal men with osteoporosis. J Clin Endocrinol Metab. 2009;94:2915–2921.
   PubMed Web of Science ®Google Scholar
• Bilezikian JP. Combination anabolic and antiresorptive therapy for osteoporosis: opening the anabolic window. Curr Osteoporos Rep. 2008;6:24–30.
   PubMedGoogle Scholar
• Deal C, Omizo M, Schwartz EN, et al. Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial. J Bone Miner Res. 2005;20:1905–1911.
   PubMed Web of Science ®Google Scholar
• Cosman F, Eriksen EF, Recknor C, et al. Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH (1-34)] in postmenopausal osteoporosis. J Bone Miner Res. 2011;26:503–511.
   PubMed Web of Science ®Google Scholar
• Tsai JN, Uihlein AV, Lee H, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet. 2013;382:50–56.
   PubMed Web of Science ®Google Scholar
• Neuprez A, Reginster JY. Bone-forming agents in the management of osteoporosis. Best Pract Res Clin Endocrinol Metab. 2008;22:869–883.
   PubMed Web of Science ®Google Scholar
• Gauthier JY, Chauret N, Cromlish W, et al. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008;18:923–928.
   PubMed Web of Science ®Google Scholar
• Costa AG, Cusano NE, Silva BC, et al. Cathepsin K: its skeletal actions and role as a therapeutic target in osteoporosis. Nat Rev Rheumatol. 2011;7:447–456.
   PubMed Web of Science ®Google Scholar
• Boonen S, Rosenberg E, Claessens F, et al. Inhibition of cathepsin K for treatment of osteoporosis. Curr Osteoporos Rep. 2012;10:73–79.
   PubMed Web of Science ®Google Scholar
• Masarachia PJ, Pennypacker BL, Pickarski M, et al. Odanacatib reduces bone turnover and increases bone mass in the lumbar spine of skeletally mature ovariectomized rhesus monkeys. J Bone Miner Res. 2012;27:509e23.
   Web of Science ®Google Scholar
• Cusick T, Chen CM, Pennypacker BL, et al. Odanacatib treatment increases hip bone mass and cortical thickness by preserving endocortical bone formation and stimulating periosteal bone formation in the ovariectomized adult rhesus monkey. J Bone Miner Res. 2012;27:524–537.
   PubMed Web of Science ®Google Scholar
• Eisman JA, Bone HG, Hosking DJ, et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res. 2011;26:242–251.
   PubMed Web of Science ®Google Scholar
• Langdahl B, Binkley N, Bone H, et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: five years of continued therapy in a phase 2 study. J Bone Miner Res. 2012;27:2251–2258.
   PubMed Web of Science ®Google Scholar
• Bonnick S, de Villiers T, Odio A, et al. Effects of odanacatib on BMD and safety in the treatment of osteoporosis in postmenopausal women previously treated with alendronate: a randomized placebo-controlled trial. J Clin Endocrinol Metab. 2013;98:4727–4735.
   PubMed Web of Science ®Google Scholar
• Bone HG, McClung MR, Roux C, et al. Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res. 2010;25:937–947.
   PubMed Web of Science ®Google 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
• Eastell R, Nagase S, Ohyama M, et al. Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the OCEAN study. J Bone Miner Res. 2011;26:1303e12.
   Google Scholar
• Eastell R, Nagase S, Small M, et al. Effect of ONO-5334 on bone mineral density and biochemical markers of bone turnover in postmenopausal osteoporosis: 2-year results from the OCEAN study. J Bone Miner Res. 2014;29:458e66.
   Web of Science ®Google Scholar
• Kartner N, Manolson MF. Novel techniques in the development of osteoporosis drug therapy: the osteoclast ruffled-border vacuolar H(+)-ATPase as an emerging target. Expert Opin Drug Discov. 2014;9:505–522.
   PubMed Web of Science ®Google Scholar
• Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006;116:1202–1209.
   PubMed Web of Science ®Google Scholar
• Manolagas SC. Wnt signaling and osteoporosis. Maturitas. 2014;78:233–237.
   PubMed Web of Science ®Google Scholar
• Bodine PV, Komm BS. Wnt signaling and osteoblastogenesis. Rev Endocr Metab Disord. 2006;7:33–39.
   PubMed Web of Science ®Google Scholar
• Baron R, Rawadi G. Wnt signaling and the regulation of bone mass. Curr Osteoporos Rep. 2007;5:73–80.
   PubMedGoogle Scholar
• Moester MJ, Papapoulos SE, Lowik CW, et al. Sclerostin: current knowledge and future perspectives. Calcif Tissue Inter. 2010;87:99–107.
   PubMed Web of Science ®Google Scholar
• Van Lierop AH, Hamdy NA, Hamersma H, et al. Patients with sclerosteosis and disease carriers: human models of the effect of sclerostin on bone turnover. J Bone Min Res. 2011;26:2804–2811.
   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
• McClung MR, Grauer A, Boonen S, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014;370:412–420.
   PubMed Web of Science ®Google Scholar
• Recker RR, Benson CT, Matsumoto T, et al. A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density. J Bone Miner Res. 2015;30:216–224.
   PubMed Web of Science ®Google Scholar
• Okazaki M, Potts JT, Gardella TJ. Identification and optimization of residues in PTH and PTHrP that determine altered modes of binding to the PTH/PTHrP receptor. J Bone Miner Res. 2008;23:S103.
   PubMed Web of Science ®Google Scholar
• Trivedi R, Goswami R, Chattopadhyay N. Investigational anabolic therapies for osteoporosis. Expert Opin Investig Drugs. 2010;19:995–1005.
   PubMed Web of Science ®Google Scholar
• Dean T, Vilardaga JP, Potts JT Jr, et al. Altered selectivity of parathyroid hormone (PTH) and PTH-related protein (PTHrP) for distinct conformations of the PTH/PTHrP receptor. Mol Endocrinol. 2008;22:156e66.
   Web of Science ®Google Scholar
• Pioszak AA, Parker NR, Gardella TJ, et al. Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides. J Biol Chem. 2009;284:28382e91.
   Web of Science ®Google Scholar
• Feurer E, Chapurlat R. Emerging drugs for osteoporosis. Expert Opin Emeriging Drugs. 2014;19:1–11.
   PubMed Web of Science ®Google Scholar
• Cosman F. Abaloparatide: a new anabolic therapy on the horizon. Bonekey Rep. 2015;4:661.
   PubMed Web of Science ®Google Scholar
• Hattersley G, Dean T, Corbin BA, et al. Binding selectivity of abaloparatide for PTH-type-1-receptor conformations and effects on downstream signaling. Endocrinology. 2016;157:141–149.
   PubMed Web of Science ®Google Scholar
• Leder BZ, O’Dea LS, Zanchetta JR, et al. Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2015;100:697–706.
   PubMed Web of Science ®Google Scholar
• Adler RA, El-Hajj Fuleihan G, Bauer DC, et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American society for bone and mineral research. J Bone Miner Res. 2016;31:16–35.
   PubMed Web of Science ®Google Scholar
• Leder BZ, Tsai JN, Uihlein AV, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. 2015;386:1147–1155.
   PubMed Web of Science ®Google Scholar