Calcified Tissue International

, Volume 90, Issue 3, pp 165–173 | Cite as

Effects of Increasing Age, Dosage, and Duration of PTH Treatment on BMD Increase—A Meta-analysis

  • Peter Schwarz
  • Niklas Rye Jorgensen
  • Leif Mosekilde
  • Peter Vestergaard
Original Research

Abstract

We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present), or Embase (1974 to present). The search date was November 16, 2010. All studies comparing PTH treatment to either placebo or antiresorptive drugs—for example, bisphosphonates or hormone replacement therapy—were included. A total of 214 studies were identified in the initial search, and 15 of these trials were included. By metaregression analysis, we found that the increase in spine BMD (Z-score) after PTH treatment was blunted by increasing age (R2 = 0.27; 2p = 0.01, slope −0.023 Z-scores per year, 11 studies). By increasing PTH dosage (μg/d), spine BMD increased significantly (2p = 0.002) with a slope of +0.011 Z-scores/μg/d of teriparatide. Furthermore, the duration of treatment was positively correlated to spine BMD (P < 0.001) with a slope of +0.043 Z-score for each extra month of treatment. We evaluated the BMD effect in hips and found no age dependency (R2 = 0.04; P = 0.66; 8 studies). However, for the spine, we found a significant relation to daily dosage (P = 0.011), Z-score coefficient 0.0051 ± 0.0020 (2p < 0.01). The treatment duration also correlated positively by a Z-score coefficient of 0.0170 ± 0.0053, 2p < 0.01 per extra month of treatment. PTH treatment alone seems to be able to improve BMD significantly. However, the BMD increase was significantly lower with increasing age in the spine. No age dependency was observed in the hips. In general the effect of treatment was improved with increasing dosage and duration of treatment from 6 to 36 months.

Keywords

Bone mineral density Fracture Meta-analysis Parathyroid hormone 

References

  1. 1.
    Johnell O (1997) The socioeconomic burden of fractures: today and in the 21st century. Am J Med 103:20S–25SPubMedCrossRefGoogle Scholar
  2. 2.
    Kannus P, Niemi S, Parkkari J, Palvanen M, Vuori I, Järvinen M (1999) Hip fractures in Finland between 1970 and 1997 and predictions for the future. Lancet 353:802–805PubMedCrossRefGoogle Scholar
  3. 3.
    Meunier PJ, Slosman DO, Delmas PD, Sebert JL, Brandi ML, Albanese C, Lorenc R, Pors-Nielsen S, De Vernejoul MC, Roces A, Reginster JY (2002) Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis—a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 87:2060–2066PubMedCrossRefGoogle Scholar
  4. 4.
    Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel EM, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster JY (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–468PubMedCrossRefGoogle Scholar
  5. 5.
    Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441PubMedCrossRefGoogle Scholar
  6. 6.
    Orwoll ES, Scheele WH, Paul S, Adami S, Syversen U, Diez-Perez A, Kaufman JM, Clancy AD, Gaich GA (2003) The effect of teriparatide [human parathyroid hormone (1–34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 18:9–17PubMedCrossRefGoogle Scholar
  7. 7.
    Reginster JY, Meunier PJ (2003) Strontium ranelate phase 2 dose-ranging studies: PREVOS and STRATOS studies. Osteoporosis Int 14:56–65CrossRefGoogle Scholar
  8. 8.
    Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, Devogelaer JP, Curiel MD, Sawicki A, Goemaere S, Sorensen OH, Felsenberg D, Meunier PJ (2005) Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: treatment of Peripheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab 90:2816–2822PubMedCrossRefGoogle Scholar
  9. 9.
    Cranney A, Guyatt G, Krolicki N, Welch V, Griffith L, Adachi JD, Shea B, Tugwell P, Wells G, Osteoporosis Research Advisory Group (ORAG) (2001) A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis. Osteoporosis Int 12:140–151CrossRefGoogle Scholar
  10. 10.
    Cranney A, Welch V, Adachi JD, Guyatt G, Krolicki N, Griffith L, Shea B, Tugwell P, Wells G (2001) Etidronate for treating and preventing postmenopausal osteoporosis. Cochrane Database Syst Rev 2001;(4):CD003376Google Scholar
  11. 11.
    Cranney A, Wells G, Willan A, Griffith L, Zytaruk N, Robinson V, Black D, Adachi J, Shea B, Tugwell P, Guyatt G, Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group (2002) Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 23:508–516PubMedCrossRefGoogle Scholar
  12. 12.
    Cranney A, Tugwell P, Adachi J, Weaver B, Zytaruk N, Papaioannou A, Robinson V, Shea B, Wells G, Guyatt G, Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group (2002) Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocr Rev 23:517–523PubMedCrossRefGoogle Scholar
  13. 13.
    Cranney A, Tugwell P, Zytaruk N, Robinson V, Weaver B, Adachi J, Wells G, Shea B, Guyatt G, Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group (2002) Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis. Endocr Rev 23:524–528PubMedCrossRefGoogle Scholar
  14. 14.
    Torgerson DJ, Bell-Syer SEM (2001) Hormone replacement therapy and prevention of nonvertebral fractures. A meta-analysis of randomized trials. JAMA 285:2891–2897PubMedCrossRefGoogle Scholar
  15. 15.
    Torgerson DJ, Bell-Syer SEM (2001) Hormone replacement therapy and prevention of vertebral fractures: a meta-analysis of randomised trials. BMC Musculoskelet Disord 2:7–10PubMedCrossRefGoogle Scholar
  16. 16.
    Cranney A, Tugwell P, Zytaruk N, Robinson V, Weaver B, Shea B, Wells G, Adachi J, Waldegger L, Guyatt G, Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group (2002) Meta-analyses of therapies for postmenopausal osteoporosis. VI. Meta-analysis of calcitonin for the treatment of postmenopausal osteoporosis. Endocr Rev 23:540–551PubMedCrossRefGoogle Scholar
  17. 17.
    Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765Google Scholar
  18. 18.
    Maraldo M, McMurdor MTF, Vestergaard P, Schwarz P (2010) Evidence of effect of anti-resorptive medicine in the elderly and old. Eur Geriatr Med 1:279–292CrossRefGoogle Scholar
  19. 19.
    Schwarz P, Jørgensen NR, Mosekilde L, Vestergaard P (2011) The evidence for efficacy of osteoporosis treatment in men—a systematic review and meta-analysis of anti-resorptive and anabolic treatment in men. J Osteoporos 2011:259818PubMedGoogle Scholar
  20. 20.
    Greenspan SL, Bone HG, Marriott TB et al (2005) Preventing the first vertebral fracture in postmenopausal women with low bone mass using PTH(1–84): results from the TOP Study. J Bone Miner Res 20:S56CrossRefGoogle Scholar
  21. 21.
    Vestergaard P, Jørgensen NR, Mosekilde L, Schwarz P (2007) Effects of parathyroid hormone on bone mineral density and fracture risk—a metaanalysis. Osteoporosis Int 18:45–57CrossRefGoogle Scholar
  22. 22.
    Vestergaard P, Mollerup CL, Frøkjaer VG, Christiansen P, Blichert-Toft M, Mosekilde L (2000) Cohort study of risk of fracture before and after surgery for primary hyperparathyroidism. BMJ 321:598–602PubMedCrossRefGoogle Scholar
  23. 23.
    Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, Dempster D, Cosman F (1997) Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 350:550–555PubMedCrossRefGoogle Scholar
  24. 24.
    Böhning D (2000) Computer-assisted Analysis of Mixtures and Applications: Meta-analysis, Disease Mapping and Others. Chapman & Hall/CRC Press, Boca RatonGoogle Scholar
  25. 25.
    Lane NE, Sanchez S, Modin GW, Genant HK, Pierini E, Arnaud CD (1998) Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. J Clin Invest 102:1627–1633PubMedCrossRefGoogle Scholar
  26. 26.
    Body JJ, Gaich GA, Scheele WH, Kulkarni PM, Miller PD, Peretz A, Dore RK, Correa-Rotter R, Papaioannou A, Cumming DC, Hodsman AB (2002) 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 87:4528–4535PubMedCrossRefGoogle Scholar
  27. 27.
    Cosman F, Nieves J, Woelfert L, Formica C, Gordon S, Shen V (2001) Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of boen mass after parathyroid hormone withdrawal. J Bone Miner Res 16:925–931PubMedCrossRefGoogle Scholar
  28. 28.
    Cosman F, Nieves J, Zion M, Woelfert L, Luckey M, Lindsay R (2005) Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med 353:566–575PubMedCrossRefGoogle Scholar
  29. 29.
    Finkelstein JS, Klibanski A, Arnold AL, Toth TL, Hornstein MD, Neer RM (1998) Prevention of estrogen deficiency-related bone loss with human parathyroid hormone-(1–34). JAMA 280:1067–1073PubMedCrossRefGoogle Scholar
  30. 30.
    Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM (2003) The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 349:1216–1226PubMedCrossRefGoogle Scholar
  31. 31.
    Finkelstein JS, Arnold AL (1999) Increases in bone mineral density after discontinuation of daily human parathyroid hormone and gonadotropin-releasing hormone analog administration in women with endometriosis. J Clin Endocrinol Metab 84:1214–1219PubMedCrossRefGoogle Scholar
  32. 32.
    Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP (2000) Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 85:3069–3076PubMedCrossRefGoogle Scholar
  33. 33.
    McClung MR, San Martin J, Miller PD, Civitelli R, Bandeira F, Omizo M, Donley DW, Dalsky GP, Eriksen EF (2005) Opposite bone remodeling effects of Teriparatide and alendronate in increasing bone mass. Arch Intern Med 165:1762–1768PubMedCrossRefGoogle Scholar
  34. 34.
    Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ, PaTH Study Investigators (2003) The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 349:1207–1215PubMedCrossRefGoogle Scholar
  35. 35.
    Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, Lang TF, McGowan JA, Rosen CJ, PaTH Study Investigators (2005) One year of alendronate after one year of parathyroid hormone (1–84) for osteoporosis. N Engl J Med 353:555–565PubMedCrossRefGoogle Scholar
  36. 36.
    Hodsman AB, Hanley DA, Ettinger MP, Bolognese MA, Fox J, Metcalfe AJ, Lindsay R (2003) Efficacy and safety of human parathyroid hormone-(1–84) in increasing bone mineral density in postmenopausal osteoporosis. J Clin Endocrinol Metab 88:5212–5220PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Peter Schwarz
    • 1
    • 3
  • Niklas Rye Jorgensen
    • 2
  • Leif Mosekilde
    • 4
  • Peter Vestergaard
    • 4
  1. 1.Department of Medicine, Research Center of Aging and OsteoporosisGlostrup University HospitalGlostrupDenmark
  2. 2.Department of Clinical Biochemistry, Research Center of Aging and OsteoporosisGlostrup University HospitalGlostrupDenmark
  3. 3.Faculty of Health ScienceCopenhagen UniversityCopenhagenDenmark
  4. 4.Department of Medicine and Endocrinology MEAAarhus University HospitalAarhusDenmark

Personalised recommendations