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Review Article| Volume 37, ISSUE 3, P337-350, August 2011

Emerging Therapies for Osteoporosis

  • Chad Deal
    Affiliations
    Orthopedic and Rheumatology Institute, Department of Rheumatology, Center for Osteoporosis and Metabolic Bone Disease, Cleveland, OH, USA

    Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland Clinic, 9500 Euclid Avenue, A50, Cleveland, OH 44195, USA
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      References

        • Kogianni G.
        • Noble B.S.
        The biology of osteocytes.
        Curr Osteoporos Rep. 2007; 5: 81-86
        • Bonewald L.F.
        The amazing osteocyte.
        J Bone Miner Res. 2011; 26: 229-238
        • Khosla S.
        • Westendorf J.J.
        • Oursler M.J.
        Building bone to reverse osteoporosis and repair fractures.
        J Clin Invest. 2008; 118: 421-428
        • Vahle J.L.
        • Sato M.
        • Long G.G.
        • et al.
        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. 2002; 30: 312-321
        • Subbiah V.
        • Madsen V.S.
        • Raymond A.K.
        • et al.
        Of mice and men: divergent risks of teriparatide-induced osteosarcoma.
        Osteoporos Int. 2010; 21: 1041-1045
        • Russell R.G.
        • Xia Z.
        • Dunford J.E.
        • et al.
        Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy.
        Ann N Y Acad Sci. 2007; 1117: 209-257
        • Del Fattore A.
        • Peruzzi B.
        • Rucci N.
        • et al.
        Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment.
        J Med Genet. 2006; 43: 315-325
        • Vasiljeva O.
        • Reinheckel T.
        • Peters C.
        • et al.
        Emerging roles of cysteine cathepsins in disease and their potential as drug targets.
        Curr Pharm Des. 2007; 13: 387-403
        • Stoch S.A.
        • Wagner J.A.
        Cathepsin K inhibitors: a novel target for osteoporosis therapy.
        Clin Pharmacol Ther. 2008; 83: 172-176
        • Gelb B.D.
        • Shi G.P.
        • Chapman H.A.
        • et al.
        Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.
        Science. 1996; 273: 1236-1238
        • Gauthier J.Y.
        • 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
        • Bone H.G.
        • McClung M.R.
        • 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
        • Eisman J.A.
        • Bone H.G.
        • Hosking D.J.
        • 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
        • Bauer D.C.
        Discontinuation of odanacatib and other osteoporosis treatments: here today and gone tomorrow?.
        J Bone Miner Res. 2011; 26: 239-241
        • Henriksen D.B.
        • Alexandersen P.
        • Hartmann B.
        • et al.
        Disassociation of bone resorption and formation by GLP-2: a 14-day study in healthy postmenopausal women.
        Bone. 2007; 40: 723-729
        • Henriksen D.B.
        • Alexandersen P.
        • Hartmann B.
        • et al.
        GLP-2 significantly increases hip BMD in postmenopausal women: a 120-day study.
        J Bone Miner Res. 2007; 22: S37
        • Henriksen D.B.
        • Alexandersen P.
        • Hartmann B.
        • et al.
        GLP-2 acutely uncouples bone resorption and bone formation in postmenopausal women.
        J Bone Miner Res. 2008; 23: S474
        • Jamal S.
        • Hamilton C.
        • Black D.
        • et al.
        Nitroglycerine improves bone mineral density, bone geometry, and bone strength: results from a two-year randomized controlled trial.
        J Bone Miner Res. 2010; 25: S77
        • Jamal S.A.
        • Cummings S.R.
        • Hawker G.A.
        Isosorbide mononitrate increases bone formation and decreases bone resorption in postmenopausal women: a randomized trial.
        J Bone Miner Res. 2004; 19: 1512-1517
        • Cummings S.R.
        • Browner W.S.
        • Bauer D.
        • et al.
        Endogenous hormones and the risk of hip and vertebral fractures among older women. Study of Osteoporotic Fractures Research Group.
        N Engl J Med. 1998; 339: 733-738
        • Wimalawansa S.J.
        Nitric oxide and bone.
        Ann N Y Acad Sci. 2010; 1192: 391-403
        • Wimalawansa S.J.
        Nitric oxide: new evidence for novel therapeutic indications.
        Expert Opin Pharmacother. 2008; 9: 1935-1954
        • Wimalawansa S.J.
        Rationale for using nitric oxide donor therapy for prevention of bone loss and treatment of osteoporosis in humans.
        Ann N Y Acad Sci. 2007; 1117: 283-297
        • Pouwels S.
        • Lalmohamed A.
        • van Staa T.
        • et al.
        Use of organic nitrates and the risk of hip fracture: a population-based case-control study.
        J Clin Endocrinol Metab. 2010; 95: 1924-1931
        • Wimalawansa S.J.
        • Grimes J.P.
        • Wilson A.C.
        • et al.
        Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss.
        J Clin Endocrinol Metab. 2009; 94: 3356-3364
        • Jamal S.A.
        • Hamilton C.J.
        • Eastell R.
        • et al.
        Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: a randomized trial.
        JAMA. 2011; 305: 800-807
        • Neer R.M.
        • Arnaud C.D.
        • Zanchetta J.R.
        • 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
        • McClung M.R.
        • San Martin J.
        • Miller P.D.
        • et al.
        Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass.
        Arch Intern Med. 2005; 165: 1762-1768
        • Glass 2nd, D.A.
        • Karsenty G.
        In vivo analysis of Wnt signaling in bone.
        Endocrinology. 2007; 148: 2630-2634
        • Baron R.
        • Rawadi G.
        Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton.
        Endocrinology. 2007; 148: 2635-2643
        • Gardner J.C.
        • van Bezooijen R.L.
        • Mervis B.
        • et al.
        Bone mineral density in sclerosteosis; affected individuals and gene carriers.
        J Clin Endocrinol Metab. 2005; 90: 6392-6395
        • Padhi D.
        • Stouch B.
        • Fang L.
        • et al.
        Anti-sclerostin antibody increases markers of bone formation in healthy postmenopausal women.
        J Bone Miner Metab. 2007; 22: S37
        • Williams B.O.
        • Insogna K.L.
        Where Wnts went: the exploding field of Lrp5 and Lrp6 signaling in bone.
        J Bone Miner Res. 2009; 24: 171-178
        • Yadav V.K.
        • Balaji S.
        • Suresh P.S.
        • et al.
        Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis.
        Nat Med. 2010; 16: 308-312
        • Richards J.B.
        • Papaioannou A.
        • Adachi J.D.
        • et al.
        Effect of selective serotonin reuptake inhibitors on the risk of fracture.
        Arch Intern Med. 2007; 167: 188-194
        • Ducy P.
        • Amling M.
        • Takeda S.
        • et al.
        Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass.
        Cell. 2000; 100: 197-207
        • Rosen C.J.
        Bone: serotonin, leptin and the central control of bone remodeling.
        Nat Rev Rheumatol. 2009; 5: 657-658
        • Rosen C.J.
        Serotonin rising–the bone, brain, bowel connection.
        N Engl J Med. 2009; 360: 957-959
        • Brown E.M.
        The calcium-sensing receptor: physiology, pathophysiology and CaR-based therapeutics.
        Subcell Biochem. 2007; 45: 139-167
        • Amizuka N.
        • Karaplis A.C.
        • Luz A.
        • et al.
        Haploinsufficiency of parathyroid hormone-related peptide results in abnormal postnatal bone development.
        Dev Biol. 1996; 175: 166-176
        • Horwitz M.J.
        • Tedesco B.
        • Gundberg C.
        • et al.
        Short-term parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis.
        J Clin Endocrinol Metab. 2003; 88: 569-575
        • Horwitz M.J.
        • Tedesco B.
        • Garcia-Ocana A.
        • et al.
        Parathyroid hormone-related protein for the treatment of postmenopausal osteoporosis: defining the maximal tolerable dose.
        J Clin Endocrinol Metab. 2010; 95: 1279-1287