Current Osteoporosis Reports

, Volume 15, Issue 2, pp 110–119 | Cite as

Parathyroid Hormone and Parathyroid Hormone-Related Protein Analogs in Osteoporosis Therapy

  • Benjamin Z. LederEmail author
Therapeutics and Medical Management (S Jan de Beur and B Clarke, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Therapeutics and Medical Management


Purpose of Review

The purpose is to review the efficacy and optimal use of parathyroid hormone and parathyroid hormone-related protein analogs in osteoporosis treatment.

Recent Findings

The parathyroid hormone analog teriparatide, a potent stimulator of bone remodeling, increases hip and spine bone mineral density and reduces the risk of vertebral and non-vertebral fractures in postmenopausal osteoporotic women. The parathyroid hormone-related protein analog, abaloparatide, also reduces fracture incidence but has pharmacological effects that differ from teriparatide, particularly in cortical bone. These analogs provide maximal benefit when their use is followed by a potent antiresorptive medication. Moreover, studies have shown that the combination of teriparatide and the RANK-ligand inhibitor, denosumab, increase bone density and estimated strength more than monotherapy and more than any currently available regimen.


Parathyroid hormone and parathyroid hormone-related protein analogs, whether as monotherapy, in combination with antiresorptive agents or in sequence with antiresorptive agents, will likely play an expanding role in osteoporosis management.


Parathyroid hormone Teriparatide Abaloparatide Osteoporosis Anabolic agents Combination therapy Bone mineral density 


Compliance with Ethical Standard

Conflict of Interest

Benjamin Leder reports grants and personal fees from Amgen; grants from Lilly, during the conduct of the study; and personal fees from Lilly, outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: •Of importance ••Of major importance

  1. 1.
    Polyzos SA, Makras P, Efstathiadou Z, Anastasilakis AD. Investigational parathyroid hormone receptor analogs for the treatment of osteoporosis. Expert Opin Investig Drugs. 2015;24(2):145–57.CrossRefPubMedGoogle Scholar
  2. 2.
    Silva BC, Bilezikian JP. Parathyroid hormone: anabolic and catabolic actions on the skeleton. Curr Opin Pharmacol. 2015;22:41–50.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kousteni S, Bilezikian JP. The cell biology of parathyroid hormone in osteoblasts. Curr Osteoporos Rep. 2008;6(2):72–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Finkelstein JS, Leder BZ, Burnett SM, Wyland JJ, Lee H, de la Paz AV, et al. Effects of teriparatide, alendronate, or both on bone turnover in osteoporotic men. J Clin Endocrinol Metab. 2006;91(8):2882–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Glover SJ, Eastell R, McCloskey EV, Rogers A, Garnero P, Lowery J, et al. Rapid and robust response of biochemical markers of bone formation to teriparatide therapy. Bone. 2009;45(6):1053–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Greenspan SL, Bone HG, Ettinger MP, Hanley DA, Lindsay R, Zanchetta JR, 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(5):326–39.CrossRefPubMedGoogle Scholar
  7. 7.
    McClung MR, San Martin J, Miller PD, Civitelli R, Bandeira F, Omizo M, et al. Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med. 2005;165(15):1762–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, 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(19):1434–41.CrossRefPubMedGoogle Scholar
  9. 9.
    Hansen S, Hauge EM, Jensen JE, Brixen K. Differing effects of PTH 1-34, PTH 1-84 and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis. An 18 month open-labeled observational study using HR-pQCT. J Bone Miner Res. 2012.Google Scholar
  10. 10.
    Macdonald HM, Nishiyama KK, Hanley DA, Boyd SK. Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis. Osteoporos Int. 2011;22(1):357–62.CrossRefPubMedGoogle Scholar
  11. 11.
    • Tsai JN, Uihlein AV, Burnett-Bowie SM, Neer RM, Derrico NP, Lee H, et al. Effects of two years of teriparatide, denosumab, or both on bone microarchitecture and strength (DATA-HRpQCT study). J Clin Endocrinol Metab. 2016:jc20161160. This study demonstrates that 2 years of combined teriparatide and denosumab improves bone microarchitecture and estimated strength more than the individual treatments. Google Scholar
  12. 12.
    Gardella T. Interactions of PTH with receptors and signaling. In: Bilezikian J, editor. The Parathyroids. 3rd ed. New York, NY: Elsevier; 2015. p. 65–80.CrossRefGoogle Scholar
  13. 13.
    Frolik CA, Black EC, Cain RL, Satterwhite JH, Brown-Augsburger PL, Sato M, et al. Anabolic and catabolic bone effects of human parathyroid hormone (1-34) are predicted by duration of hormone exposure. Bone. 2003;33(3):372–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Martin TJ. Bone biology and anabolic therapies for bone: current status and future prospects. Journal of bone metabolism. 2014;21(1):8–20.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Dempster DW, Cosman F, Zhou H, Nieves JW, Bostrom M, Lindsay R. Effects of daily or cyclic teriparatide on bone formation in the iliac crest in women on no prior therapy and in women on alendronate. J Bone Miner Res. 2016a;31(8):1518–26.CrossRefPubMedGoogle Scholar
  16. 16.
    Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF. Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res. 2003;18(11):1932–41.CrossRefPubMedGoogle Scholar
  17. 17.
    Nishiyama KK, Cohen A, Young P, Wang J, Lappe JM, Guo XE, et al. Teriparatide increases strength of the peripheral skeleton in premenopausal women with idiopathic osteoporosis: a pilot HR-pQCT study. J Clin Endocrinol Metab. 2014:jc20141041.Google Scholar
  18. 18.
    Parfitt AM. Parathyroid hormone and periosteal bone expansion. J Bone Miner Res. 2002;17(10):1741–3.CrossRefPubMedGoogle Scholar
  19. 19.
    Hansen S, Hauge EM, Beck Jensen JE, Brixen K. Differing effects of PTH 1-34, PTH 1-84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: an 18-month open-labeled observational study using HR-pQCT. J Bone Miner Res. 2013;28(4):736–45.CrossRefPubMedGoogle Scholar
  20. 20.
    Keaveny TM, Donley DW, Hoffmann PF, Mitlak BH, Glass EV, San Martin JA. 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(1):149–57.CrossRefPubMedGoogle Scholar
  21. 21.
    Keaveny TM, McClung MR, Wan X, Kopperdahl DL, Mitlak BH, Krohn K. Femoral strength in osteoporotic women treated with teriparatide or alendronate. Bone. 2012;50(1):165–70.CrossRefPubMedGoogle Scholar
  22. 22.
    •• Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316(7):722–33. This study reports that the PTHrP analog, abaloparatide, reduces the risk of new vertebral and nonvertebral fractures in postmenopausal osteoporotic women CrossRefPubMedGoogle Scholar
  23. 23.
    Finkelstein JS, Wyland JJ, Lee H, Neer RM. Effects of teriparatide, alendronate, or both in women with postmenopausal osteoporosis. J Clin Endocrinol Metab. 2010;95(4):1838–45.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Dempster DW, Roschger P, Misof BM, Zhou H, Paschalis EP, Alam J, et al. Differential effects of teriparatide and zoledronic acid on bone mineralization density distribution at 6 and 24 months in the SHOTZ study. J Bone Miner Res. 2016b;31(8):1527–35.CrossRefPubMedGoogle Scholar
  25. 25.
    • Cosman F, Dempster DW, Nieves JW, Zhou H, Zion M, Roimisher C, et al. Effect of teriparatide on bone formation in the human femoral neck. J Clin Endocrinol Metab. 2016;101(4):1498–505. This study describes teriparatide’s ability to rapidly stimulate bone formation in cancellous and endocortical envelopes of the femoral neck in humans CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lindsay R, Zhou H, Cosman F, Nieves J, Dempster DW, Hodsman AB. Effects of a one-month treatment with PTH (1-34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium. J Bone Miner Res. 2007;22(4):495–502.CrossRefPubMedGoogle Scholar
  27. 27.
    Leder BZ, Neer RM, Wyland JJ, Lee HW, Burnett-Bowie SM, Finkelstein JS. Effects of teriparatide treatment and discontinuation in postmenopausal women and eugonadal men with osteoporosis. J Clin Endocrinol Metab. 2009;94(8):2915–21.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    •• Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet. 2013;382(9886):50–6. This is the first study to demonstrate that, unlike combinations utilizing bisphosphonates, combined teriparatide and denosumab increases hip and spine BMD in postmenopausal women more than either agent alone and more than has been reported with any approved therapy CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    • Leder BZ, Tsai JN, Uihlein AV, Burnett-Bowie SA, Zhu Y, Foley K, et al. Two years of denosumab and teriparatide administration in postmenopausal women with osteoporosis (the DATA extension study): a randomized controlled trial. J Clin Endocrinol Metab. 2014;99(5):1694–700. This study extends the results of reference 28 and reports that 2 years of concomitant teriparatide and denosumab therapy increases BMD more than either medication alone CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med. 2003;349(13):1207–15.CrossRefPubMedGoogle Scholar
  31. 31.
    Cosman F, Eriksen EF, Recknor C, Miller PD, Guanabens N, Kasperk C, et al. Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH (1-34)] in postmenopausal osteoporosis. J Bone Miner Res. 2011;26(3):503–11.CrossRefPubMedGoogle Scholar
  32. 32.
    Body JJ, Gaich GA, Scheele WH, Kulkarni PM, Miller PD, Peretz A, et al. A randomized double-blind trial to compare the efficacy of teriparatide [recombinant human parathyroid hormone (1-34)] with alendronate in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2002;87(10):4528–35.CrossRefPubMedGoogle Scholar
  33. 33.
    Reeve J, Meunier PJ, Parsons JA, Bernat M, Bijvoet OL, Courpron P, et al. Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial. Br Med J. 1980;280(6228):1340–4.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Dempster DW, Cosman F, Kurland ES, Zhou H, Nieves J, Woelfert L, et al. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2001;16(10):1846–53.CrossRefGoogle Scholar
  35. 35.
    Vahle JL, Long GG, Sandusky G, Westmore M, Ma YL, Sato M. Bone neoplasms in F344 rats given teriparatide [rhPTH (1-34)] are dependent on duration of treatment and dose. Toxicol Pathol. 2004;32(4):426–38.CrossRefPubMedGoogle Scholar
  36. 36.
    Vahle JL, Sato M, Long GG, Young JK, Francis PC, Engelhardt JA, 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(3):312–21.CrossRefPubMedGoogle Scholar
  37. 37.
    Nakamura T, Sugimoto T, Nakano T, Kishimoto H, Ito M, Fukunaga M, et al. Randomized Teriparatide [human parathyroid hormone (PTH) 1-34] Once-Weekly Efficacy Research (TOWER) trial for examining the reduction in new vertebral fractures in subjects with primary osteoporosis and high fracture risk. J Clin Endocrinol Metab. 2012;97(9):3097–106.CrossRefPubMedGoogle Scholar
  38. 38.
    Orwoll ES, Scheele WH, Paul S, Adami S, Syversen U, Diez-Perez A, et al. The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2003;18(1):9–17.CrossRefGoogle Scholar
  39. 39.
    Kaufman JM, Orwoll E, Goemaere S, San Martin J, Hossain A, Dalsky GP, et al. Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int. 2005;16(5):510–6.CrossRefPubMedGoogle Scholar
  40. 40.
    Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med. 2003;349(13):1216–26.CrossRefPubMedGoogle Scholar
  41. 41.
    Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP. Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab. 2000;85(9):3069–76.PubMedGoogle Scholar
  42. 42.
    Weinstein RS. Clinical practice. Glucocorticoid-induced bone disease. N Engl J Med. 2011;365(1):62–70.CrossRefPubMedGoogle Scholar
  43. 43.
    Saag KG, Shane E, Boonen S, Marin F, Donley DW, Taylor KA, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med. 2007;357(20):2028–39.CrossRefPubMedGoogle Scholar
  44. 44.
    Saag KG, Zanchetta JR, Devogelaer JP, Adler RA, Eastell R, See K, et al. Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum. 2009;60(11):3346–55.CrossRefPubMedGoogle Scholar
  45. 45.
    Gluer CC, Marin F, Ringe JD, Hawkins F, Moricke R, Papaioannu N, et al. Comparative effects of teriparatide and risedronate in glucocorticoid-induced osteoporosis in men: 18-month results of the EuroGIOPs trial. J Bone Miner Res. 2013;28(6):1355–68.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Lane NE, Sanchez S, Modin GW, Genant HK, Pierini E, Arnaud CD. Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. J Clin Invest. 1998;102(8):1627–33.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Seno T, Yamamoto A, Kukida Y, Hirano A, Kida T, Nakabayashi A, et al. Once-weekly teriparatide improves glucocorticoid-induced osteoporosis in patients with inadequate response to bisphosphonates. SpringerPlus. 2016;5(1):1056.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Karras D, Stoykov I, Lems WF, Langdahl BL, Ljunggren O, Barrett A, et al. Effectiveness of teriparatide in postmenopausal women with osteoporosis and glucocorticoid use: 3-year results from the EFOS study. J Rheumatol. 2012;39(3):600–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Reeve J, Davies UM, Hesp R, McNally E, Katz D. Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride. BMJ. 1990;301(6747):314–8.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Reeve J, Bradbeer JN, Arlot M, Davies UM, Green JR, Hampton L, et al. hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: biochemical, kinetic and histological responses. Osteoporos Int. 1991;1(3):162–70.CrossRefPubMedGoogle Scholar
  51. 51.
    Reeve J, Arlot ME, Bradbeer JN, Hesp R, McAlly E, Meunier PJ, et al. Human parathyroid peptide treatment of vertebral osteoporosis. Osteoporos Int. 1993;3(Suppl 1):199–203.CrossRefPubMedGoogle Scholar
  52. 52.
    Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, et al. Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet. 1997;350(9077):550–5.CrossRefPubMedGoogle Scholar
  53. 53.
    Cosman F, Nieves J, Woelfert L, Formica C, Gordon S, Shen V, et al. Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal. J Bone Miner Res. 2001;16(5):925–31.CrossRefPubMedGoogle Scholar
  54. 54.
    Ste-Marie LG, Schwartz SL, Hossain A, Desaiah D, Gaich GA. Effect of teriparatide [rhPTH (1-34)] on BMD when given to postmenopausal women receiving hormone replacement therapy. J Bone Miner Res. 2006;21(2):283–91.CrossRefPubMedGoogle Scholar
  55. 55.
    Deal C, Omizo M, Schwartz EN, Eriksen EF, Cantor P, Wang J, 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(11):1905–11.CrossRefPubMedGoogle Scholar
  56. 56.
    • Muschitz C, Kocijan R, Fahrleitner-Pammer A, Lung S, Resch H. Antiresorptives overlapping ongoing teriparatide treatment result in additional increases in bone mineral density. J Bone Miner Res. 2013;28(1):196–205. This study reports that alendronate, when added to 9 months of teriparatide in postmenopausal women, increases BMD more than continuing teriparatide monotherapy CrossRefPubMedGoogle Scholar
  57. 57.
    Reszka AA, Rodan GA. Mechanism of action of bisphosphonates. Curr Osteoporos Rep. 2003;1(2):45–52.CrossRefPubMedGoogle Scholar
  58. 58.
    Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, et al. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006;38(5):617–27.CrossRefPubMedGoogle Scholar
  59. 59.
    Delmas PD, Munoz F, Black DM, Cosman F, Boonen S, Watts NB, et al. Effects of yearly zoledronic acid 5 mg on bone turnover markers and relation of PINP with fracture reduction in postmenopausal women with osteoporosis. J Bone Miner Res. 2009;24(9):1544–51.CrossRefPubMedGoogle Scholar
  60. 60.
    Cosman F, Wermers RA, Recknor C, Mauck KF, Xie L, Glass EV, et al. Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the antiresorptive agent. J Clin Endocrinol Metab. 2009;94(10):3772–80.CrossRefPubMedGoogle Scholar
  61. 61.
    Muschitz C, Kocijan R, Fahrleitner-Pammer A, Pavo I, Haschka J, Schima W, et al. Overlapping and continued alendronate or raloxifene administration in patients on teriparatide: effects on areal and volumetric bone mineral density The CONFORS study. J Bone Miner Res. 2014.Google Scholar
  62. 62.
    Walker MD, Cusano NE, Sliney Jr J, Romano M, Zhang C, McMahon DJ, et al. Combination therapy with risedronate and teriparatide in male osteoporosis. Endocrine. 2013;44(1):237–46.CrossRefPubMedGoogle Scholar
  63. 63.
    Schafer AL, Sellmeyer DE, Palermo L, Hietpas J, Eastell R, Shoback DM, et al. Six months of parathyroid hormone (1-84) administered concurrently versus sequentially with monthly ibandronate over two years: the PTH and ibandronate combination study (PICS) randomized trial. J Clin Endocrinol Metab. 2012;97(10):3522–9.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756–65.CrossRefPubMedGoogle Scholar
  65. 65.
    Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165–76.CrossRefPubMedGoogle Scholar
  66. 66.
    Prince R, Sipos A, Hossain A, Syversen U, Ish-Shalom S, Marcinowska E, et al. Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res. 2005;20(9):1507–13.CrossRefPubMedGoogle Scholar
  67. 67.
    Lindsay R, Scheele WH, Neer R, Pohl G, Adami S, Mautalen C, et al. Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch Intern Med. 2004;164(18):2024–30.CrossRefPubMedGoogle Scholar
  68. 68.
    Rittmaster RS, Bolognese M, Ettinger MP, Hanley DA, Hodsman AB, Kendler DL, et al. Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J Clin Endocrinol Metab. 2000;85(6):2129–34.PubMedGoogle Scholar
  69. 69.
    Kurland ES, Heller SL, Diamond B, McMahon DJ, Cosman F, Bilezikian JP. The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone (1-34)]. Osteoporos Int. 2004;15(12):992–7.CrossRefPubMedGoogle Scholar
  70. 70.
    Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med. 2005;353(6):555–65.CrossRefPubMedGoogle Scholar
  71. 71.
    Eastell R, Nickelsen T, Marin F, Barker C, Hadji P, Farrerons J, et al. Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final results of the randomized, controlled European study of Forsteo (EUROFORS). J Bone Miner Res. 2009;24(4):726–36.CrossRefPubMedGoogle Scholar
  72. 72.
    • Leder BZ, Tsai JN, Uihlein AV, Wallace PM, Lee H, Neer RM, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. 2015a;386(9999):1147–55. This study demonstrates that in postmenopausal women, while switching from teriparatide or combined teriparatide/densoumab to densoumab monotherapy results in additional BMD gains, switching from denosumab to teriparatide results in accelerated bone turnover and signficant bone loss, particularly at the hip and distal radius CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Boonen S, Marin F, Obermayer-Pietsch B, Simoes ME, Barker C, Glass EV, et al. Effects of previous antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2008;93(3):852–60.CrossRefPubMedGoogle Scholar
  74. 74.
    Miller PD, Delmas PD, Lindsay R, Watts NB, Luckey M, Adachi J, et al. Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate. J Clin Endocrinol Metab. 2008;93(10):3785–93.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Ettinger B, San Martin J, Crans G, Pavo I. Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res. 2004;19(5):745–51.CrossRefPubMedGoogle Scholar
  76. 76.
    Cosman F, Nieves JW, Zion M, Garrett P, Neubort S, Dempster D, et al. Daily or cyclical teriparatide treatment in women with osteoporosis on no prior therapy and women on alendronate. J Clin Endocrinol Metab. 2015;100(7):2769–76.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Recknor C, Beck Jensen JE, Gilchrist N, Wang A, Pannacciuli N, Smith S, et al. Discontinuation of denosumab and associated fracture incidence: analysis from FREEDOM and its extension. Annual Meeting of the American Society of Bone and Mineral Research; Houston, TX2016.Google Scholar
  78. 78.
    Popp AW, Zysset PK, Lippuner K. Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics. Osteoporos Int. 2016;27(5):1917–21.CrossRefPubMedGoogle Scholar
  79. 79.
    Lamy O, Gonzalez-Rodriguez E, Stoll D, Hans D, Aubry-Rozier B. Severe rebound-associated vertebral fractures after denosumab discontinuation: nine clinical cases report. J Clin Endocrinol Metab. 2016:jc20163170.Google Scholar
  80. 80.
    Aubry-Rozier B, Gonzalez-Rodriguez E, Stoll D, Lamy O. Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports. Osteoporos Int. 2016;27(5):1923–5.CrossRefPubMedGoogle Scholar
  81. 81.
    Anastasilakis AD, Makras P. Multiple clinical vertebral fractures following denosumab discontinuation. Osteoporos Int. 2016;27(5):1929–30.CrossRefPubMedGoogle Scholar
  82. 82.
    Hattersley G, Dean T, Corbin BA, Bahar H, Gardella TJ. Binding selectivity of abaloparatide for PTH-type-1-receptor conformations and effects on downstream signaling. Endocrinology. 2016;157(1):141–9.CrossRefPubMedGoogle Scholar
  83. 83.
    Leder BZ, O'Dea LS, Zanchetta JR, Kumar P, Banks K, McKay K, 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. 2015b;100(2):697–706.CrossRefPubMedGoogle Scholar
  84. 84.
    Sato M, Vahle J, Schmidt A, Westmore M, Smith S, Rowley E, et al. Abnormal bone architecture and biomechanical properties with near-lifetime treatment of rats with PTH. Endocrinology. 2002;143(9):3230–42.CrossRefPubMedGoogle Scholar
  85. 85.
    Jolette J, Wilker CE, Smith SY, Doyle N, Hardisty JF, Metcalfe AJ, et al. Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1-84 in a 2-year study in Fischer 344 rats. Toxicol Pathol. 2006;34(7):929–40.CrossRefPubMedGoogle Scholar
  86. 86.
    Hattersley G, Attalla B, Varela A, Smith S. Comparison of osteosarcoma incidence between abaloparatide (BA058) and PTH (1-34) in long term rat studies. European Calcified Tissue Society Congress Oct 17; Prague, Czech Republic 2014.Google Scholar
  87. 87.
    Andrews EB, Gilsenan AW, Midkiff K, Sherrill B, Wu Y, Mann BH, et al. The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years. J Bone Miner Res. 2012;27(12):2429–37.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Harvard Medical School, Endocrine UnitMassachusetts General HospitalBostonUSA

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