Skip to main content

Advertisement

SpringerLink
Log in

Biologicals in Osteoporosis: Teriparatide and Parathyroid Hormone in Women and Men

  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Osteoporosis is characterized by the occurrence of a host of fractures. According to densitometric values, an operational definition for osteoporosis corresponds to a loss of 25% to 30% (−2.5 T-scores) compared with the mean values of bone mineral density of young premenopausal women. For years, research tried to develop drugs to improve the bone mineral density. According to the compounds, antiresorptive agents are able to decrease the fracture rate by about 30% to 70%, and to increase the bone mineral density. However, the agents increasing the most bone mineral density are not necessarily those that influence the most fracture rates. It has been known for years that parathyroid hormone (PTH) administered cyclically is able to increase bone mineral density. Two analogues of PTH have been developed: PTH (1-34) and PTH (1-84). Both of them are able to increase bone mineral density and reduce the rate of vertebral fracture but not of the hip, nor of nonvertebral fractures, the latter at least for PTH (1-84). Their exact place in the armamentarium of therapy of osteoporosis and their best time of administration are not yet definitely settled. New modes of administration (transdermal, intranasal, oral) will probably become available soon. With all the drugs available today and those still in development, it can be hoped that osteoporosis will become a disease of the past.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

  1. Consensus development conference: diagnosis, prophylaxis and treatment of osteoporosis [no authors listed]. Am J Med 1991, 90:107–110.

    Google Scholar 

  2. Watts NB, Cooper C, Lindsay R, et al.: Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk. J Clin Densitom 2004, 7:255–261.

    Article  PubMed  Google Scholar 

  3. Cummings SR, Karpf DB, Harris F, et al.: Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 2002, 112:281–289.

    Article  CAS  PubMed  Google Scholar 

  4. Sarkar S, Mitlak BH, Wong M, et al.: Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 2002, 17:1–10.

    Article  CAS  PubMed  Google Scholar 

  5. Bruyere O, Roux C, Detilleux J, et al.: Relationship between bone mineral density changes and fracture risk reduction in patients treated with strontium ranelate. J Clin Endocrinol Metab 2007, 92:3076–3081.

    Article  CAS  PubMed  Google Scholar 

  6. Selye H: On the stimulation of new bone-formation with parathyroid extract and irradiated ergosterol. Endocrinology 1932, 16:547–558.

    Article  CAS  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. Reeve J, Davis UM, Hesp R, et al.: Treatment of osteoporosis with human parathyroid hormone and observations on the effects of sodium fluoride therapy. Br Med J 1990, 301:314–318.

    Article  CAS  Google Scholar 

  10. Reeve J, Bradbeer JN, Arlot M, et al.: hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: Biochemical, kinetic and histological responses. Osteoporosis Int 1991, 1:162–170.

    Article  CAS  Google Scholar 

  11. Slovik DM, Rosenthal DI, Doppelt SH, et al.: Restoration of spinal bone in osteoporotic men by treatment with human parathyroid hormone (1-34) and 1,25-dihydroxyvitamin D. J Bone Miner Res 1986, 1:377–381.

    Article  CAS  PubMed  Google Scholar 

  12. Delmas PD, Vergnaud P, Arlot ME, et al.: The anabolic effect of human PTH (1-34) on bone formation is blunted when bone resorption is inhibited by the bisphosphonate tiludronate—Is activated resorption a prerequisite for the in vivo effect of PTH on formation in a remodeling system? Bone 1995, 16:603–610.

    Article  CAS  PubMed  Google Scholar 

  13. Shen V, Dempster DW, Birchman R, et al.: Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol. J Clin Invest 1993, 91:2479–2487.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. Vahle JL, Long GG, Sandusky G, et al.: Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. Toxicol Pathol 2004, 32:426–438.

    Article  CAS  PubMed  Google Scholar 

  16. • Watts NB, Miller PD, Kohlmeier LA, et al.: Vertebral fracture risk is reduced in women who lose femoral neck BMD with teriparatide treatment. J Bone Miner Res 2009, 24:1125–1131. Losing BMD when on TPTD therapy does not necessarily mean increase in fracture risk.

    Article  CAS  PubMed  Google Scholar 

  17. Nevitt MC, Chen P, Dore RK, et al.: Reduced risk of back pain following teriparatide treatment: a meta-analysis. Osteoporos Int 2006, 17:273–280.

    Article  PubMed  Google Scholar 

  18. •• Aspenberg P, Genant HK, Johansson T, et al.: Teriparatide for acceleration of fracture repair in humans: A prospective, randomized double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res 2010, 25:404–414. TPTD therapy could help to accelerate the fracture repair in humans.

    CAS  PubMed  Google Scholar 

  19. Tagil M, McDonald MM, Morse A, et al.: Intermittent PTH (1-34) does not increase union rates in open rat femoral fractures and exhibits attenuated anabolic effects compared to closed fractures. Bone 2010, 46:852–859.

    Article  PubMed  Google Scholar 

  20. Bone HG, Hosking D, Devogelaer JP, et al.: Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 2004, 350:1189–1199.

    Article  CAS  PubMed  Google Scholar 

  21. Kaufman JM, Orwoll E, Goemaere S, et al.: Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int 2005, 16:510–516.

    Article  CAS  PubMed  Google Scholar 

  22. • Finkelstein JS, Wyland JJ, Leder BZ, et al.: Effects of teriparatide retreatment in osteoporotic men and women. J Clin Endocrinol Metab 2009, 94:2495–2501. There is a possibility of having several courses of TPTD therapy separated by weaning periods.

    Article  CAS  PubMed  Google Scholar 

  23. Cosman F, Niewes JW, Zion M, et al.: Retreatment with teriparatide one year after the first teriparatide course in patients on continued long-term alendronate. J Bone Miner Res 2009, 24:1110–1115.

    Article  PubMed  Google Scholar 

  24. Eastell R, Nickelsen T, Marin F, 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, 24:726–736.

    Article  CAS  PubMed  Google Scholar 

  25. • 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. Contrary to postmenopausal women, in eugonadal males, there is no bone loss after stopping TPTD.

    Article  CAS  PubMed  Google Scholar 

  26. Lindsay R, Scheele WH, Neer R, et al.: Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch Intern Med 2004, 164:2024–2030.

    Article  PubMed  Google Scholar 

  27. Cosman F, Nieves S, Woelfert L, 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, 16:925–931.

    Article  CAS  PubMed  Google Scholar 

  28. Finkelstein JS, Hayes A, Hunzelman JL, et al.: The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 2003, 349:1216–1226.

    Article  CAS  PubMed  Google Scholar 

  29. Middleton ET, Steel SA, Doherty SM: The effect of prior bisphosphonate exposure on the treatment response to teriparatide in clinical practice. Calcif Tissue Int 2007, 81:335–340.

    Article  CAS  PubMed  Google Scholar 

  30. Obermayer-Pietsch BM, Marin F, McCloskey EV, et al.: Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res 2008, 23:1591–1600.

    Article  CAS  PubMed  Google Scholar 

  31. 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, 19:745–751.

    Article  CAS  PubMed  Google Scholar 

  32. • Miller PD, Delmas PD, Lindsay R, et al.: Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate. J Clin Endocrinol Metab 2008, 93:3785–3793. Contrary to what has been written, there is apparently no blunting effect of TPTD by previous BP therapy.

    Article  CAS  PubMed  Google Scholar 

  33. Boonen S, Marin F, Obermayer-Pietsch B, 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, 93:852–860.

    Article  CAS  PubMed  Google Scholar 

  34. • Keel C, Kraenzlin ME, Kraenzlin CA, et al.: Impact of bisphosphonate wash-out prior to teriparatide therapy in clinical practice. J Bone Miner Metab 2010, 28:68–76. It is therefore not necessary to have a washing-out period from BPs before starting TPTD.

    Article  CAS  PubMed  Google Scholar 

  35. Cosman F, Wermers RA, Recknor C, 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, 94:3772–3780.

    Article  CAS  PubMed  Google Scholar 

  36. Cosman F, Nieves J, Zion M, et al.: Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med 2005, 353:566–575.

    Article  CAS  PubMed  Google Scholar 

  37. Adami S, San Martin J, Munoz-Torres M, et al.: Effect of raloxifene after recombinant teriparatide [hPTH(1-34)] treatment in postmenopausal women with osteoporosis. Osteoporos Int 2008, 19:87–94.

    Article  CAS  PubMed  Google Scholar 

  38. Cosman F, Nieves JW, Zion M, et al.: Effect of prior and ongoing raloxifene therapy on response to PTH and maintenance of BMD after PTH therapy. Osteoporos Int 2008, 19:529–535.

    Article  CAS  PubMed  Google Scholar 

  39. Kurland ES, Cosman F, McMahon DJ, et al.: Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 2000, 85:3069–3076.

    Article  CAS  PubMed  Google Scholar 

  40. Orwoll ES, Scheele WH, Paul S, et al.: The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 2003, 18:9–17.

    Article  CAS  PubMed  Google Scholar 

  41. Devogelaer JP: Glucocorticoid-induced osteoporosis: mechanisms and therapeutic approach. Rheum Dis Clin N Am 2006, 32:733–757.

    Article  Google Scholar 

  42. Lane NE, Sanchez S, Modin GW, et al.: Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. J Clin Invest 1998, 102:1627–1633.

    Article  CAS  PubMed  Google Scholar 

  43. Lane NE, Sanchez S, Modin GW, et al.: Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial. J Bone Miner Res 2000, 15:944–951.

    Article  CAS  PubMed  Google Scholar 

  44. Saag KG, Shane E, Boonen S, et al.: Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 2007, 357:2028–2039.

    Article  CAS  PubMed  Google Scholar 

  45. Saag KG, Zanchetta JR, Devogelaer J-P, 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, 60:3346–3355.

    Article  CAS  PubMed  Google Scholar 

  46. Devogelaer JP, Adler RA, Recknor C, et al.: Baseline glucocorticoid dose and bone mineral density response with teriparatide or alendronate therapy in patients with glucocorticoid-induced osteoporosis. J Rheumatol 2010, 37:141–148.

    Article  CAS  PubMed  Google Scholar 

  47. Eastell R, Chen P, Saag KG, et al.: Bone formation markers in patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate. Bone 2010, 46:929–934.

    Article  CAS  PubMed  Google Scholar 

  48. Hodsman AB, Hanley DA, Ettinger MP, et al.: Efficacy and safety of human parathyroid hormone-(1-84) in increasing bone mineral density in postmenopausal osteoporosis. J Clin Endocrinol Metab 2003, 88:5212–5220.

    Article  CAS  PubMed  Google Scholar 

  49. 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  Google Scholar 

  50. Fogelman I, Fordham JN, Fraser WD, et al.: Parathyroid hormone (1-84) treatment of postmenopausal women with low bone mass receiving hormone replacement therapy. Calcif Tissue Int 2008, 83:85–92.

    Article  CAS  PubMed  Google Scholar 

  51. Recker RR, Bare SP, Smith SY, et al.: Cancellous and cortical bone architecture and turnover at the iliac crest of postmenopausal osteoporotic women treated with parathyroid hormone 1-84. Bone 2009, 44:113–119.

    Article  CAS  PubMed  Google Scholar 

  52. Black DM, Bouxsein ML, Palermo L, et al.: Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling. J Clin Endocrinol Metab 2008, 93:2166–2172.

    Article  CAS  PubMed  Google Scholar 

  53. 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.

    Article  CAS  PubMed  Google Scholar 

  54. Garnero P, Bauer DC, Mareau E, et al.: Effects of PTH and alendronate on type I collagen isomerization in postmenopausal women with osteoporosis: the PATH study. J Bone Miner Res 2008, 23:1442–1448.

    Article  CAS  PubMed  Google Scholar 

  55. • Recker RR, Marin F, Ish-Shalom S, et al.: Comparative effects of teriparatide and strontium ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis. J Bone Miner Res 2009, 24:1358–1368. This paper shows the differing mechanisms of action between two promotors of bone formation.

    Article  CAS  PubMed  Google Scholar 

  56. Feng J, Liu Y, Xing Y, et al.: A novel human parathyroid hormone (1-34) analog for the treatment of osteoporosis. Peptides 2009, 30:1173–1180.

    Article  CAS  PubMed  Google Scholar 

  57. • Cosman F, Lane LE, Bolognese MA, et al.: Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women. J Clin Endocrinol Metab 2010, 95:151–158. This paper discusses a new mode of administration of PTH.

    Article  CAS  PubMed  Google Scholar 

  58. Ameri M, Daddona PE, Maa YF: Demonstrated solid-state stability of parathyroid hormone PTH (1-34) coated on a novel transdermal microprojection delivery system. Pharm Res 2009, 26:2454–2463.

    Article  CAS  PubMed  Google Scholar 

  59. Everhart-Caye M, Inzucchi SE, Guinness-Henry J, et al.: Parathyroid hormone (PTH)-related protein (1-36) is equipotent with PTH (1-34) in humans. J Clin Endocrinol Metab 1996, 81:199–208.

    Article  CAS  PubMed  Google Scholar 

  60. Horwitz MJ, Tedesco MB, 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.

    Article  CAS  PubMed  Google Scholar 

  61. Kumar S, Matheny CJ, Hoffman SJ, et al.: An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation. Bone 2010, 46:534–542.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

We thank the expert technical assistance of Mrs. Marie-Christine Hallot.

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Université Catholique de Louvain, UCL 5390, St-Luc University Hospital, Avenue Hippocrate 10, 1200, Brussels, Belgium

    Jean-Pierre Devogelaer & Daniel H. Manicourt

  2. Department of Rheumatology, Université Catholique de Louvain, Clinique Universitaire de Mont-Godinne, 5530, Yvoir, Belgium

    Yves Boutsen

Authors
  1. Jean-Pierre Devogelaer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yves Boutsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel H. Manicourt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jean-Pierre Devogelaer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Devogelaer, JP., Boutsen, Y. & Manicourt, D.H. Biologicals in Osteoporosis: Teriparatide and Parathyroid Hormone in Women and Men. Curr Osteoporos Rep 8, 154–161 (2010). https://doi.org/10.1007/s11914-010-0024-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-010-0024-1

Keywords

Search

Navigation