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New Targets and Emergent Therapies for Osteoporosis

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Bone Regulators and Osteoporosis Therapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 262))

Abstract

The 11 existing FDA-approved osteoporosis drug treatments include hormone replacement therapy, 2 SERMs (raloxifene and bazedoxifene), 5 inhibitors of bone-resorbing osteoclasts (4 bisphosphonates and anti-RANKL denosumab), 2 parathyroid hormone analogues (teriparatide and abaloparatide), and 1 WNT signaling enhancer (romosozumab). These therapies are effective and provide multiple options for patients and physicians. As the genomic revolution continues, potential novel targets for future drug development are identified. This review takes a wide perspective to describe potentially rewarding topics to explore, including knowledge of genes and pathways involved in bone cell metabolism, the utility of animal models, targeting drugs to bone, and ongoing advances in drug design and delivery.

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References

  • Agholme F, Isaksson H, Kuhstoss S, Aspenberg P (2011) The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions. Bone 48:988–996

    CAS  PubMed  Google Scholar 

  • Allen JG, Lee MR, Han CY, Scherrer J, Flynn S, Boucher C, Zhao H, O’Connor AB, Roveto P, Bauer D et al (2009) Identification of small molecule inhibitors of proline-rich tyrosine kinase 2 (Pyk2) with osteogenic activity in osteoblast cells. Bioorg Med Chem Lett 19:4924–4928

    CAS  PubMed  Google Scholar 

  • Allen JG, Fotsch C, Babij P (2010) Emerging targets in osteoporosis disease modification. J Med Chem 53:4332–4353

    CAS  PubMed  Google Scholar 

  • Andrews EB, Gilsean AW, Midkiff K, Sherrill B, Wu Y, Mann BH, Masica D (2012) The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years. J Bone Miner Res 27:2429–2437

    CAS  PubMed  PubMed Central  Google Scholar 

  • Anonymous (2018) Osteoporosis: a roadmap to close the treatment gap. Lancet Diabetes Endocrinol 6:833

    Google Scholar 

  • Ansari N, Ho PW, Crimeen-Irwin B, Poulton IJ, Brunt AR, Forwood MR, Divieti Pajevic P, Gooi JH, Martin TJ, Sims NA (2018) Autocrine and paracrine regulation of the murine skeleton by osteocyte-derived parathyroid hormone-related protein. J Bone Miner Res 33:137–153

    CAS  PubMed  Google Scholar 

  • Ayturk U (2019) RNA-seq in skeletal biology. Curr Osteoporos Rep 17:178–185

    PubMed  Google Scholar 

  • Bergen DJM, Kague E, Hammond CL (2019) Zebrafish as an emerging model for osteoporosis: a primary testing platform for screening new osteo-active compounds. Front Endocrinol (Lausanne) 10:6

    Google Scholar 

  • Bodine PV, Stauffer B, Ponce-de-Leon H, Bhat RA, Mangine A, Seestaller-Wehr LM, Moran RA, Billiard J, Fukayama S, Komm BS et al (2009) A small molecule inhibitor of the Wnt antagonist secreted frizzled-related protein-1 stimulates bone formation. Bone 44:1063–1068

    CAS  PubMed  Google Scholar 

  • Borah B, Dufresne TE, Chmielewski PA, Gross GJ, Prenger MC, Phipps RJ (2002) Risedronate preserves trabecular architecture and increases bone strength in vertebra of ovariectomized minipigs as measured by three-dimensional microcomputed tomography. J Bone Miner Res 17:1139–4117

    CAS  PubMed  Google Scholar 

  • Boudin E, Yorgan T, Fijalkowski I, Sonntag S, Steenackers E, Hendrickx G, Peeters S, De Maré A, Vervaet B, Verhulst A et al (2017) The Lrp4R1170Q homozygous knock-in mouse recapitulates the bone phenotype of sclerosteosis in humans. J Bone Miner Res 32:1739–1749

    CAS  PubMed  Google Scholar 

  • Boyce RW, Paddock CL, Franks AF, Jankowsky ML, Eriksen EF (1996) Effects of intermittent hPTH(1-34) alone and in combination with 1,25(OH)(2)D(3) or risedronate on endosteal bone remodeling in canine cancellous and cortical bone. J Bone Miner Res 11:600–613

    CAS  PubMed  Google Scholar 

  • Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346:1513–1521

    CAS  PubMed  Google Scholar 

  • Brommage R (2001) Perspectives on using nonhuman primates to understand the etiology and treatment of postmenopausal osteoporosis. J Musculoskelet Neuronal Interact 1:307–325

    CAS  PubMed  Google Scholar 

  • Brommage R, Ohlsson C (2018) Translational studies provide insights for the etiology and treatment of cortical bone osteoporosis. Best Pract Res Clin Endocrinol Metab 32:329–340

    CAS  PubMed  Google Scholar 

  • Brommage R, Liu J, Hansen GM, Kirkpatrick LL, Potter DG, Sands AT, Zambrowicz B, Powell DR, Vogel P (2014) High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes. Bone Res 2:14034

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brommage R, Liu J, Vogel P, Mseeh F, Thompson AY, Potter DG, Shadoan MK, Hansen GM, Jeter-Jones S, Cui J et al (2019) NOTUM inhibition increases endocortical bone formation and bone strength. Bone Res 7:2

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bullock WA, Pavalko FM, Robling AG (2019) Osteocytes and mechanical loading: the Wnt connection. Orthod Craniofac Res 22(Suppl 1):175–179

    PubMed  Google Scholar 

  • Cacheiro P, Haendel MA, Smedley D, International Mouse Phenotyping Consortium and the Monarch Initiative (2019) New models for human disease from the International Mouse Phenotyping Consortium. Mamm Genome 30:143–150

    CAS  PubMed  PubMed Central  Google Scholar 

  • Capulli M, Maurizi A, Ventura L, Rucci N, Teti A (2015) Effective small interfering RNA therapy to treat CLCN7-dependent autosomal dominant osteopetrosis type 2. Mol Ther Nucleic Acids 4:e248

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, LeBoff M, Lewis CE, McGowan J, Neuner J et al (2003) Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA 290:1729–1738

    CAS  PubMed  Google Scholar 

  • Chang MK, Kramer I, Huber T, Kinzel B, Guth-Gundel S, Leupin O, Kneissel M (2014) Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels. Proc Natl Acad Sci U S A 111:E5187–E5195

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H, Ji X, Lee WC, Shi Y, Li B, Abel ED, Jiang D, Huang W, Long F (2019) Increased glycolysis mediates Wnt7b-induced bone formation. FASEB J 33:7810–7821

    CAS  PubMed  PubMed Central  Google Scholar 

  • Clemmensen C, Finan B, Müller TD, DiMarchi RD, Tschöp MH, Hofmann SM (2019) Emerging hormonal-based combination pharmacotherapies for the treatment of metabolic diseases. Nat Rev Endocrinol 15:90–104

    PubMed  Google Scholar 

  • Codrons V, Vanderbist F, Verbeeck RK, Arras M, Lison D, Préat V, Vanbever R (2003) Systemic delivery of parathyroid hormone (1-34) using inhalation dry powders in rats. J Pharm Sci 92:938–950

    CAS  PubMed  Google Scholar 

  • Cole LE, Vargo-Gogola T, Roeder RK (2016) Targeted delivery to bone and mineral deposits using bisphosphonate ligands. Adv Drug Deliv Rev 99(Pt A):12–27

    CAS  PubMed  Google Scholar 

  • Coleman PJ, Brashear KM, Askew BC, Hutchinson JH, McVean CA, Duong LT, Feuston BP, Fernandez-Metzler C, Gentile MA, Hartman GD et al (2004) Nonpeptide alphavbeta3 antagonists. Part 11: discovery and preclinical evaluation of potent alphavbeta3 antagonists for the prevention and treatment of osteoporosis. J Med Chem 47:4829–4837

    CAS  PubMed  Google Scholar 

  • Collet C, Ostertag A, Ricquebourg M, Delecourt M, Tueur G, Isidor B, Guillot P, Schaefer E, Javier RM, Funck-Brentano T et al (2017) Primary osteoporosis in young adults: genetic basis and identification of novel variants in causal genes. JBMR Plus 2:12–21

    PubMed  PubMed Central  Google Scholar 

  • Cosman F, Lane NE, Bolognese MA, Zanchetta JR, Garcia-Hernandez PA, Sees K, Matriano JA, Gaumer K, Daddona PE (2010) Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women. J Clin Endocrinol Metab 95:151–158

    CAS  PubMed  Google Scholar 

  • Cosman F, Gilchrist N, McClung M, Foldes J, de Villiers T, Santora A, Leung A, Samanta S, Heyden N, McGinnis JP 2nd et al (2016) A phase 2 study of MK-5442, a calcium-sensing receptor antagonist, in postmenopausal women with osteoporosis after long-term use of oral bisphosphonates. Osteoporos Int 27:377–386

    CAS  PubMed  Google Scholar 

  • Crooke ST, Witztum JL, Bennett CF, Baker BF (2018) RNA-targeted therapeutics. Cell Metab 27:714–739

    CAS  PubMed  Google Scholar 

  • Cross R (2017) The RNA drug hunters. Chem Eng News 95:16–18

    Google Scholar 

  • Cui Y, Niziolek PJ, MacDonald BT, Zylstra CR, Alenina N, Robinson DR, Zhong Z, Matthes S, Jacobsen CM, Conlon RA et al (2011) Lrp5 functions in bone to regulate bone mass. Nat Med 17:684–691

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, Verweij P, Mol-Arts M, Kloosterboer L, Mosca L, Christiansen C et al (2008) The effects of tibolone in older postmenopausal women. N Engl J Med 359:697–708

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cummings SR, Ensrud K, Delmas PD, LaCroix AZ, Vukicevic S, Reid DM, Goldstein S, Sriram U, Lee A, Thompson J et al (2010) Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med 362:686–696

    CAS  PubMed  Google Scholar 

  • Delgado-Calle J, Bellido T (2017) New insights into the local and systemic functions of sclerostin: regulation of quiescent bone lining cells and beige adipogenesis in peripheral fat depots. J Bone Miner Res 32:889–891

    PubMed  PubMed Central  Google Scholar 

  • DeLuca HF, Bedale W, Binkley N, Gallagher JC, Bolognese M, Peacock M, Aloia J, Clagett-Dame M, Plum L (2011) The vitamin D analogue 2MD increases bone turnover but not BMD in postmenopausal women with osteopenia: results of a 1-year phase 2 double-blind, placebo-controlled, randomized clinical trial. J Bone Miner Res 26:538–545

    CAS  PubMed  Google Scholar 

  • Dobnig H, Turner RT (1995) Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136:3632–3638

    CAS  PubMed  Google Scholar 

  • Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME, Maliszewski CR et al (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424

    CAS  PubMed  PubMed Central  Google Scholar 

  • Drake MT, Clarke BL, Oursler MJ, Khosla S (2017) Cathepsin K inhibitors for osteoporosis: biology, potential clinical utility, and lessons learned. Endocr Rev 38:325–350

    PubMed  PubMed Central  Google Scholar 

  • Dudley HR, Spiro D (1961) The fine structure of bone cells. J Biophys Biochem Cytol 11:627–649

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ebeling PR, Akesson K, Bauer DC, Buchbinder R, Eastell R, Fink HA, Giangregorio L, Guanabens N, Kado D, Kallmes D et al (2019) The efficacy and safety of vertebral augmentation: a second ASBMR task force report. J Bone Miner Res 34:3–21

    PubMed  Google Scholar 

  • Erben RG (2015) Hypothesis: coupling between resorption and formation in cancellous bone remodeling is a mechanically controlled event. Front Endocrinol (Lausanne) 6:82

    Google Scholar 

  • Fan L, Pei S, Lucas Lu X, Wang L (2016) A multiscale 3D finite element analysis of fluid/solute transport in mechanically loaded bone. Bone Res 4:16032

    CAS  PubMed  PubMed Central  Google Scholar 

  • Farr JN, Xu M, Weivoda MM, Monroe DG, Fraser DG, Onken JL, Negley BA, Sfeir JG, Ogrodnik MB et al (2017) Targeting cellular senescence prevents age-related bone loss in mice. Nat Med 23:1072–1079

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fitzpatrick LA, Dabrowski CE, Cicconetti G, Gordon DN, Papapoulos S, Bone HG 3rd, Bilezikian JP (2011) The effects of ronacaleret, a calcium-sensing receptor antagonist, on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mineral density. J Clin Endocrinol Metab 96:2441–2449

    CAS  PubMed  Google Scholar 

  • Fleming A, Sato M, Goldsmith P (2005) High-throughput in vivo screening for bone anabolic compounds with zebrafish. J Biomol Screen 10:823–831

    CAS  PubMed  Google Scholar 

  • Florio M, Gunasekaran K, Stolina M, Li X, Liu L, Tipton B, Salimi-Moosavi H, Asuncion FJ, Li C, Sun B et al (2016) A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair. Nat Commun 7:11505

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frost HM, Jee WS (1992) On the rat model of human osteopenias and osteoporoses. Bone Miner 18:227–236

    CAS  PubMed  Google Scholar 

  • Gafni RI, Brahim JS, Andreopoulou P, Bhattacharyya N, Kelly MH, Brillante BA, Reynolds JC, Hua Z, Dempster DW, Collins MT (2012) Daily parathyroid hormone 1-34 replacement therapy for hypoparathyroidism induces marked changes in bone turnover and structure. J Bone Miner Res 27:1811–1820

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gardinier JD, Daly-Seiler C, Rostami N, Kundal S, Zhang C (2019) Loss of the PTH/PTHrP receptor along the osteoblast lineage limits the anabolic response to exercise. PLoS One 14:e0211076

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gilsenan A, Harding A, Kellier-Steele N, Harris D, Midkiff K, Andrews E (2018) The Forteo Patient Registry linkage to multiple state cancer registries: study design and results from the first 8 years. Osteoporos Int 29:2335–2343

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ginsburg GS (2019) A global collaborative to advance genomic medicine. Am J Hum Genet 104:407–409

    CAS  PubMed  PubMed Central  Google Scholar 

  • Glantschnig H, Hampton RA, Lu P, Zhao JZ, Vitelli S, Huang L, Haytko P, Cusick T, Ireland C, Jarantow SW et al (2010) Generation and selection of novel fully human monoclonal antibodies that neutralize Dickkopf-1 (DKK1) inhibitory function in vitro and increase bone mass in vivo. J Biol Chem 285:40135–40147

    CAS  PubMed  PubMed Central  Google Scholar 

  • Glüer CC, Scholz-Ahrens KE, Helfenstein A, Delling G, Timm W, Açil Y, Barkmann R, Hassenpflug J, Stampa B, Bauss F, Schrezenmeir J (2007) Ibandronate treatment reverses glucocorticoid-induced loss of bone mineral density and strength in minipigs. Bone 40:645–655

    PubMed  Google Scholar 

  • Goldberg DR, De Lombaert S, Aiello R, Bourassa P, Barucci N, Zhang Q, Paralkar V, Stein AJ, Holt M, Valentine J et al (2017) Optimization of spirocyclic proline tryptophan hydroxylase-1 inhibitors. Bioorg Med Chem Lett 27:413–419

    CAS  PubMed  Google Scholar 

  • Graham S, Gamie Z, Polyzois I, Narvani AA, Tzafetta K, Tsiridis E, Helioti M, Mantalaris A, Tsiridis E (2009) Prostaglandin EP2 and EP4 receptor agonists in bone formation and bone healing: in vivo and in vitro evidence. Expert Opin Investig Drugs 18:746–766

    PubMed  Google Scholar 

  • Gregson CL, Wheeler L, Hardcastle SA, Appleton LH, Addison KA, Brugmans M, Clark GR, Ward KA, Paggiosi M, Stone M et al (2016) Mutations in known monogenic high bone mass loci only explain a small proportion of high bone mass cases. J Bone Miner Res 31:640–649

    CAS  PubMed  Google Scholar 

  • Gregson CL, Newell F, Leo PJ, Clark GR, Paternoster L, Marshall M, Forgetta V, Morris JA, Ge B, Bao X et al (2018) Genome-wide association study of extreme high bone mass: contribution of common genetic variation to extreme BMD phenotypes and potential novel BMD-associated genes. Bone 114:62–71

    CAS  PubMed  PubMed Central  Google Scholar 

  • Halse J, Greenspan S, Cosman F, Ellis G, Santora A, Leung A, Heyden N, Samanta S, Doleckyj S, Rosenberg E et al (2014) A phase 2, randomized, placebo-controlled, dose-ranging study of the calcium-sensing receptor antagonist MK-5442 in the treatment of postmenopausal women with osteoporosis. J Clin Endocrinol Metab 99:E2207–E2215

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hämmerle SP, Mindeholm L, Launonen A, Kiese B, Loeffler R, Harfst E, Azria M, Arnold M, John MR (2012) The single dose pharmacokinetic profile of a novel oral human parathyroid hormone formulation in healthy postmenopausal women. Bone 50:965–973

    PubMed  Google Scholar 

  • Han CY, Wang Y, Yu L, Powers D, Xiong X, Yu V, Nguyen Y, Jean DJ Jr, Babij P (2009) Small molecules with potent osteogenic-inducing activity in osteoblast cells. Bioorg Med Chem Lett 19:1442–1445

    CAS  PubMed  Google Scholar 

  • Hariri H, Pellicelli M, Arnaud S (2017) New PTH signals mediating bone anabolism. Curr Mol Biol Rep 3:133–141

    Google Scholar 

  • Henriksen K, Andersen JR, Riis BJ, Mehta N, Tavakkol R, Alexandersen P, Byrjalsen I, Valter I, Nedergaard BS, Teglbjaerg CS et al (2012) Evaluation of the efficacy, safety and pharmacokinetic profile of oral recombinant human parathyroid hormone [rhPTH(1-31)NH(2)] in postmenopausal women with osteoporosis. Bone 53:160–166

    PubMed  Google Scholar 

  • High KA, Roncarolo MG (2019) Gene therapy. N Engl J Med 381:455–464

    CAS  PubMed  Google Scholar 

  • Hirano T, Burr DB, Turner CH, Sato M, Cain RL, Hock JM (1999) Anabolic effects of human biosynthetic parathyroid hormone fragment (1-34), LY333334, on remodeling and mechanical properties of cortical bone in rabbits. J Bone Miner Res 14:536–545

    CAS  PubMed  Google Scholar 

  • Horwitz MJ, Augustine M, Khan L, Martin E, Oakley CC, Carneiro RM, Tedesco MB, Laslavic A, Sereika SM, Bisello A et al (2013) A comparison of parathyroid hormone-related protein (1-36) and parathyroid hormone (1-34) on markers of bone turnover and bone density in postmenopausal women: the PrOP study. J Bone Miner Res 28:2266–2276

    CAS  PubMed  PubMed Central  Google Scholar 

  • Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, Collins JE, Humphray S, McLaren K, Matthews L et al (2013) The zebrafish reference genome sequence and its relationship to the human genome. Nature 496:498–503

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huang HX, Lin H, Lan F, Wu YF, Yang ZG, Zhang JJ (2018) Application of bone transgenic zebrafish in anti-osteoporosis chemical screening. Animal Model Exp Med 1:53–61

    PubMed  PubMed Central  Google Scholar 

  • Idris A (2019) Bone research protocols. Springer, New York

    Google Scholar 

  • Jee WS, Ma YF (1997) The in vivo anabolic actions of prostaglandins in bone. Bone 21:297–304

    CAS  PubMed  Google Scholar 

  • Jerome CP, Burr DB, Van Bibber T, Hock JM, Brommage R (2001) Treatment with human parathyroid hormone (1-34) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys (Macaca fascicularis). Bone 28:150–159

    CAS  PubMed  Google Scholar 

  • John MR, Harfst E, Loeffler J, Belleli R, Mason J, Bruin GJ, Seuwen K, Klickstein LB, Mindeholm L, Widler L et al (2014) AXT914 a novel, orally-active parathyroid hormone-releasing drug in two early studies of healthy volunteers and postmenopausal women. Bone 64:204–210

    CAS  PubMed  Google Scholar 

  • Jolette J, Wilker CE, Smith SY, Doyle N, Hardisty JF, Metcalfe AJ, Marriott TB, Fox J, Wells DS (2006) Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1-84 in a 2-year study in Fischer 344 rats. Toxicol Pathol 34:929–940

    CAS  PubMed  Google Scholar 

  • Jolette J, Attalla B, Varela A, Long GG, Mellal N, Trimm S, Smith SY, Ominsky MS, Hattersley G (2017) 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 86:356–365

    CAS  PubMed  Google Scholar 

  • Kao RS, Abbott MJ, Louie A, O’Carroll D, Lu W, Nissenson R (2013) Constitutive protein kinase A activity in osteocytes and late osteoblasts produces an anabolic effect on bone. Bone 55:277–287

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SW, Pajevic PD, Selig M, Barry KJ, Yang JY, Shin CS, Baek WY, Kim JE, Kronenberg HM (2012) Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts. J Bone Miner Res 27:2075–8204

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SW, Lu Y, Williams EA, Lai F, Lee JY, Enishi T, Balani DH, Ominsky MS, Ke HZ, Kronenberg HM et al (2017) Sclerostin antibody administration converts bone lining cells into active osteoblasts. J Bone Miner Res 32:892–901

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim H, Kim YG, Choi W, Moon JH, Hwang I, Kim K, Yadav VK, Karsenty G, Jeong JS, Kim H (2018) Generation of a highly efficient and tissue-specific tryptophan hydroxylase 1 knockout mouse model. Sci Rep 8:17642

    PubMed  PubMed Central  Google Scholar 

  • Kishnani PS, Rockman-Greenberg C, Rauch F, Bhatti MT, Moseley S, Denker AE, Watsky E, Whyte MP (2019) Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. Bone 121:149–162

    CAS  PubMed  Google Scholar 

  • Kneissel M, Boyde A, Gasser JA (2001) Bone tissue and its mineralization in aged estrogen-depleted rats after long-term intermittent treatment with parathyroid hormone (PTH) analog SDZ PTS 893 or human PTH(1-34). Bone 28:237–250

    CAS  PubMed  Google Scholar 

  • Knowles HJ (2015) Hypoxic regulation of osteoclast differentiation and bone resorption activity. Hypoxia (Auckl) 3:73–82

    Google Scholar 

  • Knudsen LB, Lau J (2019) The discovery and development of liraglutide and semaglutide. Front Endocrinol (Lausanne) 10:155

    Google Scholar 

  • Ko FC, Van Vliet M, Ellman R, Grasso D, Brooks DJ, Spatz JM, Conlon C, Aguirre JI, Wronski TJ, Bouxsein ML (2017) Treatment with a soluble bone morphogenetic protein type 1A receptor (BMPR1A) fusion protein increases bone mass and bone formation in mice subjected to hindlimb unloading. JBMR Plus 1:66–72

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, Nakagawa N, Kinosaki M, Yamaguchi K, Shima N et al (2000) Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med 191:275–286

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kolata G (2008) Bone finding may point to hope for osteoporosis. New York Times. https://www.nytimes.com/2008/11/27/health/research/27bone.html

  • Kostenuik PJ, Nguyen HQ, McCabe J, Warmington KS, Kurahara C, Sun N, Chen C, Li L, Cattley RC, Van G et al (2009) 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 24:182–195

    CAS  PubMed  Google Scholar 

  • Kwon RY, Watson CJ, Karasik D (2019) Using zebrafish to study skeletal genomics. Bone 126:37–50

    CAS  PubMed  PubMed Central  Google Scholar 

  • Langdahl B, Ferrari S, Dempster DW (2016) Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis. Ther Adv Musculoskelet Dis 8:225–235

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lawson MA, Ebetino FH, Mazur A, Chantry AD, Paton-Hough J, Evans HR, Lath D, Tsoumpra MK, Lundy MW, Dobson RL et al (2017) The pharmacological profile of a novel highly potent bisphosphonate, OX14 (1-fluoro-2-(imidazo-[1,2-α]pyridin-3-yl)-ethyl-bisphosphonate). J Bone Miner Res 32:1860–1869

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee WC, Guntur AR, Long F, Rosen CJ (2017) Energy metabolism of the osteoblast: implications for osteoporosis. Endocr Rev 38:255–266

    PubMed  PubMed Central  Google Scholar 

  • Lewiecki EM, Binkley N (2017) DXA: 30 years and counting: introduction to the 30th anniversary issue. Bone 104:1–3

    PubMed  Google Scholar 

  • Li J, Sarosi I, Yan XQ, Morony S, Capparelli C, Tan HL, McCabe S, Elliott R, Scully S, Van G et al (2000) RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci U S A 97:1566–1571

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Grisanti M, Fan W, Asuncion FJ, Tan HL, Dwyer D, Han CY, Yu L, Lee J, Lee E et al (2011) Dickkopf-1 regulates bone formation in young growing rodents and upon traumatic injury. J Bone Miner Res 26:2610–2621

    CAS  PubMed  Google Scholar 

  • Li C, Wang W, Xie L, Luo X, Cao X, Wan M (2016) Lipoprotein receptor–related protein 6 is required for parathyroid hormone-induced Sost suppression. Ann N Y Acad Sci 1364:62–73

    CAS  PubMed  Google Scholar 

  • Lleras-Forero L, Winkler C, Schulte-Merker S (2019) Zebrafish and medaka as models for biomedical research of bone diseases. Dev Biol. https://doi.org/10.1016/j.ydbio.2019.07.009

  • Lorentzon M, Cummings SR (2015) Osteoporosis: the evolution of a diagnosis. J Intern Med 277:650–661

    CAS  PubMed  Google Scholar 

  • Lowery JW, Rosen V (2018) The BMP pathway and its inhibitors in the skeleton. Physiol Rev 98:2431–2452

    CAS  PubMed  Google Scholar 

  • Lui JC, Colbert M, Cheung CSF, Ad M, Lee A, Zhu Z, Barnes KM, Dimitrov DS, Baron J (2019) Cartilage-targeted IGF-1 treatment to promote longitudinal bone growth. Mol Ther 27:673–680

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mäkitie RE, Costantini A, Kämpe A, Alm JJ, Mäkitie O (2019) New insights into monogenic causes of osteoporosis. Front Endocrinol (Lausanne) 10:70

    Google Scholar 

  • Marcus R (2011) Present at the beginning: a personal reminiscence on the history of teriparatide. Osteoporos Int 22:2241–2248

    CAS  PubMed  Google Scholar 

  • Martin TJ (2016) Parathyroid hormone-related protein, its regulation of cartilage and bone development, and role in treating bone diseases. Physiol Rev 96:831–871

    CAS  PubMed  Google Scholar 

  • Matic I, Matthews BG, Wang X, Dyment NA, Worthley DL, Rowe DW, Grcevic D, Kalajzic I (2016) Quiescent bone lining cells are a major source of osteoblasts during adulthood. Stem Cells 34:2930–2942

    CAS  PubMed  PubMed Central  Google Scholar 

  • Maynard RD, Ackert-Bicknell CL (2019) Mouse models and online resources for functional analysis of osteoporosis genome-wide association studies. Front Endocrinol (Lausanne) 10:277

    Google Scholar 

  • McDonald MM, Morse A, Schindeler A, Mikulec K, Peacock L, Cheng T, Bobyn J, Lee L, Baldock PA, Croucher PI et al (2018) Homozygous Dkk1 knockout mice exhibit high bone mass phenotype due to increased bone formation. Calcif Tissue Int 102:105–116

    CAS  PubMed  Google Scholar 

  • Miao D, He B, Jiang Y, Kobayashi T, Sorocéanu MA, Zhao J, Su H, Tong X, Amizuka N, Gupta A et al (2005) Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH 1-34. J Clin Invest 115:2402–2411

    CAS  PubMed  PubMed Central  Google Scholar 

  • Miller VM, Harman SM (2017) An update on hormone therapy in postmenopausal women: mini-review for the basic scientist. Am J Physiol Heart Circ Physiol 313:H1013–H1021

    PubMed  PubMed Central  Google Scholar 

  • Miller SC, de Saint-Georges L, Bowman BM, Jee WS (1989) Bone lining cells: structure and function. Scanning Microsc 3:953–960

    CAS  PubMed  Google Scholar 

  • Miller MA, Bare SP, Recker RR, Smith SY, Fox J (2008) Intratrabecular tunneling increases trabecular number throughout the skeleton of ovariectomized rhesus monkeys treated with parathyroid hormone 1-84. Bone 42:1175–1183

    CAS  PubMed  Google Scholar 

  • Moorer MC, Riddle RC (2019) Regulation of osteoblast metabolism by Wnt signaling. Endocrinol Metab (Seoul) 33:318–330

    Google Scholar 

  • Morley P (2005) Delivery of parathyroid hormone for the treatment of osteoporosis. Expert Opin Drug Deliv 2:993–1002

    CAS  PubMed  Google Scholar 

  • Morris JA, Kemp JP, Youlten SE, Laurent L, Logan JG, Chai RC, Vulpescu NA, Forgetta V, Kleinman A, Mohanty S et al (2019) An atlas of genetic influences on osteoporosis in humans and mice. Nat Genet 51:258–266

    CAS  PubMed  Google Scholar 

  • Morse A, Cheng TL, Schindeler A, McDonald MM, Mohanty ST, Kneissel M, Kramer I, Little DG (2018) Dkk1 KO mice treated with sclerostin antibody have additional increases in bone volume. Calcif Tissue Int 103:298–310

    CAS  PubMed  Google Scholar 

  • Mortier GR, Cohn DH, Cormier-Daire V, Hall C, Krakow D, Mundlos S, Nishimura G, Robertson S, Sangiorgi L, Savarirayan R et al (2019) Nosology and classification of genetic skeletal disorders: 2019 revision. Am J Med Genet A. https://doi.org/10.1002/ajmg.a.61366

  • Mullard A (2019) First targeted protein degrader hits the clinic. Nat Rev Drug Discov 18:237–239

    Google Scholar 

  • Murphy MG, Cerchio K, Stoch SA, Gottesdiener K, Wu M, Recker R, L-000845704 Study Group (2005) Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab 90:2022–2028

    CAS  PubMed  Google Scholar 

  • Nakai Y, Okamoto K, Terashima A, Ehata S, Nishida J, Imamura T, Ono T, Takayanagi H (2019) Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis. Bone Res 7:1

    CAS  PubMed  PubMed Central  Google Scholar 

  • Niziolek PJ, MacDonald BT, Kedlaya R, Zhang M, Bellido T, He X, Warman ML, Robling AG (2015) High bone mass-causing mutant LRP5 receptors are resistant to endogenous inhibitors in vivo. J Bone Miner Res 30:1822–1830

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nuttall ME, Bradbeer JN, Stroup GB, Nadeau DP, Hoffman SJ, Zhao H, Rehm S, Gowen M (1998) Idoxifene: a novel selective estrogen receptor modulator prevents bone loss and lowers cholesterol levels in ovariectomized rats and decreases uterine weight in intact rats. Endocrinology 139:5224–5234

    CAS  PubMed  Google Scholar 

  • Oprea TI, Bologa CG, Brunak S, Campbell A, Gan GN, Gaulton A, Gomez SM, Guha R, Hersey A, Holmes J et al (2018) Unexplored therapeutic opportunities in the human genome. Nat Rev Drug Discov 17:317–332

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pandey AK, Lu L, Wang X, Homayouni R, Williams RW (2014) Functionally enigmatic genes: a case study of the brain ignorome. PLoS One 9:e88889

    PubMed  PubMed Central  Google Scholar 

  • Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610

    CAS  PubMed  Google Scholar 

  • Pead MJ, Skerry TM, Lanyon LE (1988) Direct transformation from quiescence to bone formation in the adult periosteum following a single brief period of bone loading. J Bone Miner Res 3:647–656

    CAS  PubMed  Google Scholar 

  • Pearson RG, Masud T, Blackshaw E, Naylor A, Hinchcliffe M, Jeffery K, Jordan F, Shabir-Ahmed A, King G, Lewis AL et al (2019) Nasal administration and plasma pharmacokinetics of parathyroid hormone peptide PTH 1-34 for the treatment of osteoporosis. Pharmaceutics 11:E265

    PubMed  Google Scholar 

  • Pennypacker B, Shea M, Liu Q, Masarachia P, Saftig P, Rodan S, Rodan G, Kimmel D (2009) Bone density, strength, and formation in adult cathepsin K (−/−) mice. Bone 44:199–207

    CAS  PubMed  Google Scholar 

  • Pennypacker BL, Duong LT, Cusick TE, Masarachia PJ, Gentile MA, Gauthier JY, Black WC, Scott BB, Samadfam R et al (2011) Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbits. J Bone Miner Res 26:252–262

    CAS  PubMed  Google Scholar 

  • Pennypacker BL, Chen CM, Zheng H, Shih MS, Belfast M, Samadfam R, Duong LT (2014) Inhibition of cathepsin K increases modeling-based bone formation, and improves cortical dimension and strength in adult ovariectomized monkeys. J Bone Miner Res 29:1847–1858

    CAS  PubMed  Google Scholar 

  • Peplow M (2019) Click chemistry targets antibody-drug conjugates for the clinic. Nat Biotechnol. https://doi.org/10.1038/d41587-019-00017-4

  • Podbesek R, Edouard C, Meunier PJ, Parsons JA, Reeve J, Stevenson RW, Zanelli JM (1983) Effects of two treatment regimes with synthetic human parathyroid hormone fragment on bone formation and the tissue balance of trabecular bone in greyhounds. Endocrinology 112:1000–1006

    CAS  PubMed  Google Scholar 

  • Rauner M, Baschant U, Roetto A, Pellegrino RM, Rother S, Salbach-Hirsch J, Weidner H, Hintze V, Campbell G, Petzold A et al (2019) Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signaling. Nat Metab 1:111–124

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ravn P, Nielsen TF, Christiansen C (2006) What can be learned from the levormeloxifene experience? Acta Obstet Gynecol Scand 85:135–142

    CAS  PubMed  Google Scholar 

  • Reginster JY, Christiansen C, Roux C, Fechtenbaum J, Rouillon A, Tou KP (2001) Intermittent cyclic tiludronate in the treatment of osteoporosis. Osteoporos Int 12:169–177

    CAS  PubMed  Google Scholar 

  • Rhodes CA, Pei D (2017) Bicyclic peptides as next-generation therapeutics. Chemistry 23:12690–12703

    CAS  PubMed  PubMed Central  Google Scholar 

  • Riggs BL, Parfitt AM (2005) Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res 20:177–184

    CAS  PubMed  Google Scholar 

  • Riggs BL, Hodgson SF, O’Fallon WM, Chao EY, Wahner HW, Muhs JM, Cedel SL, Melton LJ 3rd (1990) Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med 322:802–809

    CAS  PubMed  Google Scholar 

  • Rogers MJ, Crockett JC, Coxon FP, Mönkkönen J (2011) Biochemical and molecular mechanisms of action of bisphosphonates. Bone 49:34–41

    CAS  PubMed  Google Scholar 

  • Rubin MR, Zhou H, Cusano NE, Majeed R, Omeragic B, Gomez M, Nickolas TL, Dempster DW, Bilezikian JP (2018) The effects of long-term administration of rhPTH(1-84) in hypoparathyroidism by bone histomorphometry. J Bone Miner Res 33:1931–1939

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt A, Kimmel DB, Bai C, Scafonas A, Rutledge S, Vogel RL, McElwee-Witmer S, Chen F, Nantermet PV, Kasparcova V et al (2010) Discovery of the selective androgen receptor modulator MK-0773 using a rational development strategy based on differential transcriptional requirements for androgenic anabolism versus reproductive physiology. J Biol Chem 285:17054–17064

    CAS  PubMed  PubMed Central  Google Scholar 

  • Scudellari M (2019) Protein-slaying drugs could be the next blockbuster therapies. Nature 567:298–300

    CAS  PubMed  Google Scholar 

  • Shao Y, Wichern E, Childress PJ, Adaway M, Misra J, Klunk A, Burr DB, Wek RC, Mosley AL, Liu Y et al (2019) Loss of Nmp4 optimizes osteogenic metabolism and secretion to enhance bone quality. Am J Physiol Endocrinol Metab 316:E749–E772

    PubMed  PubMed Central  Google Scholar 

  • Smith SY, Jolette J, Turner CH (2009) Skeletal health: primate model of postmenopausal osteoporosis. Am J Primatol 71:752–765

    CAS  PubMed  Google Scholar 

  • Smith SY, Varela A, Samadfam R (2017) Bone toxicology. Springer, Cham

    Google Scholar 

  • Stoeger T, Gerlach M, Morimoto RI, Nunes Amaral LA (2018) Large-scale investigation of the reasons why potentially important genes are ignored. PLoS Biol 16:e2006643

    PubMed  PubMed Central  Google Scholar 

  • Styrkarsdottir U, Stefansson OA, Gunnarsdottir K, Thorleifsson G, Lund SH, Stefansdottir L, Juliusson K, Agustsdottir AB, Zink F, Halldorsson GH et al (2019) GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures. Nat Commun 10:2054

    PubMed  PubMed Central  Google Scholar 

  • Sun Y, Ye X, Cai M, Liu X, Xiao J, Zhang C, Wang Y, Yang L, Liu J, Li S et al (2016) Osteoblast-targeting-peptide modified nanoparticle for siRNA/microRNA delivery. ACS Nano 10:5759–5768

    CAS  PubMed  Google Scholar 

  • Sun X, Wei J, Lyu J, Bian T, Liu Z, Huang J, Pi F, Li C, Zhong Z (2019) Bone-targeting drug delivery system of biomineral-binding liposomes loaded with icariin enhances the treatment for osteoporosis. J Nanobiotechnol 17:10

    Google Scholar 

  • Tascau L, Gardner T, Anan H, Yongpravat C, Cardozo CP, Bauman WA, Lee FY, Oh DS, Tawfeek HA (2016) Activation of protein kinase A in mature osteoblasts promotes a major bone anabolic response. Endocrinology 157:112–126

    CAS  PubMed  Google Scholar 

  • Taylor S, Ominsky MS, Hu R, Pacheco E, He YD, Brown DL, Aguirre JI, Wronski TJ, Buntich S, Afshari CA et al (2016) Time-dependent cellular and transcriptional changes in the osteoblast lineage associated with sclerostin antibody treatment in ovariectomized rats. Bone 84:148–159

    CAS  PubMed  Google Scholar 

  • Trajanoska K, Rivadeneira F (2019) The genetic architecture of osteoporosis and fracture risk. Bone 126:2–10

    PubMed  Google Scholar 

  • Vahle JL, Sato M, Long GG, Young JK, Francis PC, Engelhardt JA, Westmore MS, Linda Y, Nold JB (2002) Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety. Toxicol Pathol 30:312–321

    CAS  PubMed  Google Scholar 

  • Vahle JL, Long GG, Sandusky G, Westmore M, Ma YL, Sato M (2004) Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. Toxicol Pathol 32:426–348

    CAS  PubMed  Google Scholar 

  • Vahle JL, Zuehlke U, Schmidt A, Westmore M, Chen P, Sato M (2008) Lack of bone neoplasms and persistence of bone efficacy in cynomolgus macaques after long-term treatment with teriparatide [rhPTH(1-34)]. J Bone Miner Res 23:2033–2039

    CAS  PubMed  Google Scholar 

  • van Deursen JM (2019) Senolytic therapies for healthy longevity. Science 364:636–637

    PubMed  PubMed Central  Google Scholar 

  • Vickery BH, Avnur Z, Cheng Y, Chiou SS, Leaffer D, Caulfield JP, Kimmel DB, Ho T, Krstenansky JL (1996) RS-66271, a C-terminally substituted analog of human parathyroid hormone-related protein (1-34), increases trabecular and cortical bone in ovariectomized, osteopenic rats. J Bone Miner Res 11:1943–1951

    CAS  PubMed  Google Scholar 

  • Vogel P, Read RW, Hansen GM, Powell DR, Kantaputra PN, Zambrowicz B, Brommage R (2016) Dentin dysplasia in Notum knockout mice. Vet Pathol 53:853–862

    CAS  PubMed  Google Scholar 

  • Warden SJ, Mantila Roosa SM, Kersh ME, Hurd AL, Fleisig GS, Pandy MG, Fuchs RK (2014) Physical activity when young provides lifelong benefits to cortical bone size and strength in men. Proc Natl Acad Sci U S A 111:5337–5342

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wein MN, Liang Y, Goransson O, Sundberg TB, Wang J, Williams EA, O’Meara MJ, Govea N, Beqo B, Nishimori S et al (2016) SIKs control osteocyte responses to parathyroid hormone. Nat Commun 7:13176

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL et al (2008) Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 135:825–837

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang YS, Xie J, Wang D, Kim JM, Tai PWL, Gravallese E, Gao G, Shim JH (2019) Bone-targeting AAV-mediated silencing of Schnurri-3 prevents bone loss in osteoporosis. Nat Commun 10:2958

    PubMed  PubMed Central  Google Scholar 

  • Yao W, Jee WS, Zhou H, Lu J, Cui L, Setterberg R, Liang T, Ma Y (1999) Anabolic effect of prostaglandin E2 on cortical bone of aged male rats comes mainly from modeling-dependent bone gain. Bone 25:697–702

    CAS  PubMed  Google Scholar 

  • Yoshida K, Oida H, Kobayashi T, Maruyama T, Tanaka M, Katayama T, Yamaguchi K, Segi E, Tsuboyama T, Matsushita M et al (2002) Stimulation of bone formation and prevention of bone loss by prostaglandin E EP4 receptor activation. Proc Natl Acad Sci U S A 99:4580–4585

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zanchetta MB, Boailchuk J, Massari F, Silveira F, Bogado C, Zanchetta JR (2018) Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study. Osteoporos Int 29:41–47

    CAS  PubMed  Google Scholar 

  • Zhang L, Takahashi HE, Inoue J, Tanizawa T, Endo N, Yamamoto N, Hori M (1997) Effects of intermittent administration of low dose human PTH(1-34) on cancellous and cortical bone of lumbar vertebral bodies in adult beagles. Bone 21:501–506

    CAS  PubMed  Google Scholar 

  • Zhang G, Guo B, Wu H, Tang T, Zhang BT, Zheng L, He Y, Yang Z, Pan X, Chow H et al (2012) A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy. Nat Med 18:307–314

    PubMed  Google Scholar 

  • Zhang X, MacDonald BT, Gao H, Shamashkin M, Coyle AJ, Martinez RV, He X (2016) Characterization of Tiki, a new family of Wnt-specific metalloproteases. J Biol Chem 291:2435–2443

    CAS  PubMed  Google Scholar 

  • Zhang X, Dong S, Xu F (2018) Structural and druggability landscape of frizzled G protein-coupled receptors. Trends Biochem Sci 43:1033–1046

    CAS  PubMed  Google Scholar 

  • Zhao Q, Liu X, Zhang L, Shen X, Qi J, Wang J, Qian N, Deng L (2013) Bone selective protective effect of a novel bone-seeking estrogen on trabecular bone in ovariectomized rats. Calcif Tissue Int 93:172–183

    CAS  PubMed  PubMed Central  Google Scholar 

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    Robert Brommage

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    Paula H. Stern

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Brommage, R. (2019). New Targets and Emergent Therapies for Osteoporosis. In: Stern, P.H. (eds) Bone Regulators and Osteoporosis Therapy. Handbook of Experimental Pharmacology, vol 262. Springer, Cham. https://doi.org/10.1007/164_2019_329

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