Osteoporosis International

, Volume 17, Issue 2, pp 273–280 | Cite as

Reduced risk of back pain following teriparatide treatment: a meta-analysis

  • Michael C. Nevitt
  • Peiqi Chen
  • Robin K. Dore
  • Jean-Yves Reginster
  • Douglas P. Kiel
  • Jose R. Zanchetta
  • Emmett V. Glass
  • John H. Krege
Original Article

Abstract

Vertebral fractures are the most common osteoporotic fracture and may result in back pain with functional limitations and diminished quality of life. Teriparatide [rhPTH (1–34)] has been shown to increase bone mass and reduce the risk of vertebral and other osteoporotic fractures. The aim of this study was to evaluate the effects of teriparatide on the risk of back pain in patients with osteoporosis. A systematic review of the literature was performed, and five trials were identified and included in our analyses. All trials were randomized, double-blinded, and parallel with either new vertebral fracture ( n =1) or bone mineral density as the primary endpoint ( n =4). Four studies were in postmenopausal women with osteoporosis, and one was in men with idiopathic or hypogonadal osteoporosis. Two trials were placebo controlled, two trials were alendronate controlled, and one trial involved teriparatide plus hormone replacement therapy versus hormone replacement therapy alone. Reports of back pain, defined as new or worsened back pain after initiating the study drug, were obtained from adverse event databases, and the risk of back pain was analyzed using a multivariate Cox proportional hazards model. Results were not statistically heterogeneous ( P =0.60) across trials, and there were no differences between groups administered teriparatide 20 or 40 mcg/day doses ( P =0.64). The rates of back pain, moderate or severe back pain, and severe back pain per 100 patient-years were numerically lower in the teriparatide versus comparator groups in each study. Compared with the pooled comparator, patients in the pooled teriparatide group had reduced risk for any back pain [relative risk, 0.66 (95% CI, 0.55–0.80)], moderate or severe back pain [relative risk, 0.60 (95% CI, 0.48–0.75)] and severe back pain [relative risk, 0.44 (95% CI, 0.28–0.68)]. Separate meta-analyses comparing teriparatide versus placebo or antiresorptive drugs gave similar results. In conclusion, patients randomized to teriparatide had a reduced risk of new or worsening back pain compared to patients randomized to placebo, hormone replacement therapy or alendronate.

Keywords

Alendronate Back pain Hormone replacement therapy Osteoporosis rhPTH 1–34 Teriparatide 

Notes

Acknowledgments

We are grateful to Mary Ellen Perron and Mindy Rance for assistance in the preparation of the figures. Funding was provided by Lilly Research Laboratories, Eli Lilly and Company.

References

  1. 1.
    Riggs BL, Melton LJ III (1995) The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone 17 [Suppl 5]:505S–511SGoogle Scholar
  2. 2.
    Melton LJ III, Lane AW, Cooper C, Eastell R, O’Fallon WM, Riggs BL (1993) Prevalence and incidence of vertebral deformities. Osteoporos Int 3:113–119CrossRefPubMedGoogle Scholar
  3. 3.
    Clark S (2002) Osteoporosis—the disease of the 21st century? Lancet 359:1714CrossRefPubMedGoogle Scholar
  4. 4.
    Cooper C, Atkinson EJ, O’Fallon WM, Melton LJ III (1992) Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989. J Bone Miner Res 7:221–227PubMedGoogle Scholar
  5. 5.
    Gold DT (1996) The clinical impact of vertebral fractures: quality of life in women with osteoporosis. Bone 18 [Suppl 3]:185S–189SGoogle Scholar
  6. 6.
    Nevitt MC, Ettinger B, Black DM, Stone K, Jamal SA, Ensrud K, Segal M, Genant HK, Cummings SR (1998) The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med 128:793–800PubMedGoogle Scholar
  7. 7.
    Ismail AA, Cooper C, Felsenberg D, Varlow J, Kanis JA, Silman AJ, O’Neill TW (1999) Number and type of vertebral deformities: epidemiological characteristics and relation to back pain and height loss. European Vertebral Osteoporosis Study Group. Osteoporos Int 9:206–213CrossRefPubMedGoogle Scholar
  8. 8.
    Ettinger B, Black DM, Nevitt MC, Rundle AC, Cauley JA, Cummings SR, Genant HK (1992) Contribution of vertebral deformities to chronic back pain and disability. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 7:449–456PubMedGoogle Scholar
  9. 9.
    Matthis C, Weber U, O’Neill TW, Raspe H (1998) Health impact associated with vertebral deformities: results from the European Vertebral Osteoporosis Study (EVOS). Osteoporos Int 8:364–372CrossRefPubMedGoogle Scholar
  10. 10.
    Oleksik A, Lips P, Dawson A, Minshall ME, Shen W, Cooper C, Kanis J (2000) Health-related quality of life in postmenopausal women with low BMD with or without prevalent vertebral fractures. J Bone Miner Res 15:1384–1392PubMedGoogle Scholar
  11. 11.
    Silverman SL, Minshall ME, Shen W, Harper KD, Xie S (2001) The relationship of health-related quality of life to prevalent and incident vertebral fractures in postmenopausal women with osteoporosis: results from the Multiple Outcomes of Raloxifene Evaluation Study. Arthritis Rheum 44:2611–2619CrossRefPubMedGoogle Scholar
  12. 12.
    Lyles KW, Gold DT, Shipp KM, Pieper CF, Martinez S, Mulhausen PL (1993) Association of osteoporotic vertebral compression fractures with impaired functional status. Am J Med 94:595–601CrossRefPubMedGoogle Scholar
  13. 13.
    Mazanec DJ, Podichetty VK, Mompoint A, Potnis A (2003) Vertebral compression fractures: manage aggressively to prevent sequelae. Cleve Clin J Med 70:147–156PubMedGoogle Scholar
  14. 14.
    Edmond SL, Kiel DP, Samelson EJ, Kelly-Hayes M, Felson DT (2005) Vertebral deformity, back symptoms, and functional limitations among older women: The Framingham Study. Osteoporos Int 16:1086-1095CrossRefPubMedGoogle Scholar
  15. 15.
    Ray NF, Chan JK, Thamer M, Melton LJ III (1997) Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res 12:24–35PubMedGoogle Scholar
  16. 16.
    Gehlbach SH, Burge RT, Puleo E, Klar J (2003) Hospital care of osteoporosis-related vertebral fractures. Osteoporos Int 14:53–60CrossRefPubMedGoogle Scholar
  17. 17.
    Finnern HW, Sykes DP (2003) The hospital cost of vertebral fractures in the EU: estimates using national datasets. Osteoporos Int 14:429–436CrossRefPubMedGoogle Scholar
  18. 18.
    Lyles KW (1999) Management of patients with vertebral compression fractures. Pharmacotherapy 19:21S–24SCrossRefPubMedGoogle Scholar
  19. 19.
    Lieberman IH, Dudeney S, Reinhardt MK, Bell G (2001) Initial outcome and efficacy of “kyphoplasty” in the treatment of painful osteoporotic vertebral compression fractures. Spine 26:1631–1638PubMedGoogle Scholar
  20. 20.
    Watts NB, Harris ST, Genant HK (2001) Treatment of painful osteoporotic vertebral fractures with percutaneous vertebroplasty or kyphoplasty. Osteoporos Int 12:429–437CrossRefPubMedGoogle Scholar
  21. 21.
    Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535–1541PubMedGoogle Scholar
  22. 22.
    Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW Jr, Dequeker J, Favus M (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 333:1437–1443CrossRefGoogle Scholar
  23. 23.
    Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280:2077–2082CrossRefPubMedGoogle Scholar
  24. 24.
    Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282:1344–1352CrossRefPubMedGoogle Scholar
  25. 25.
    Chesnut CH 3rd, Silverman S, Andriano K, Genant H, Gimona A, Harris S, Kiel D, LeBoff M, Maricic M, Miller P, Moniz C, Peacock M, Richardson P, Watts N, Baylink D (2000) A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med 109:267–276PubMedGoogle Scholar
  26. 26.
    Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282:637–645PubMedGoogle Scholar
  27. 27.
    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 344:1434–1441PubMedGoogle Scholar
  28. 28.
    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 87:4528–4535PubMedGoogle Scholar
  29. 29.
    Fujita T, Inoue T, Morii H, Morita R, Norimatsu H, Orimo H, Takahashi HE, Yamamoto K, Fukunaga M (1999) Effect of an intermittent weekly dose of human parathyroid hormone (1–34) on osteoporosis: a randomized double-masked prospective study using three dose levels. Osteoporos Int 9:296–306CrossRefPubMedGoogle Scholar
  30. 30.
    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 18:9–17PubMedGoogle Scholar
  31. 31.
    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 165:1762-1768CrossRefPubMedGoogle Scholar
  32. 32.
    Ste-Marie LG, Scheele WH, Jasqui S, Schwartz SL, Pohl G, Gaich GA (2001) Effect of ly333334 [recombinant human parathyroid hormone (1–34), rhPTH(1–34)] on bone density when given to postmenopausal women receiving hormone replacement therapy (HRT). Program and abstracts. The Endocrine Society’s 83rd Annual Meeting June 20–23, abstract #OR42–5, p 125Google Scholar
  33. 33.
    Genant HK, Mitlak B, Myers S, Wertz B, Wang O (2000) Radiographic fracture grade is related to clinical disease severity. Results from the rhpth (1–34) fracture prevention study. Arthritis Rheum 43 [Suppl 9]:S383Google Scholar
  34. 34.
    Genant HK, Halse J, Briney WG, Xie L, Glass EV, Krege JH (2005) The effects of teriparatide on the incidence of back pain in postmenopausal women with osteoporosis. Curr Med Res Opin 21:1027–1034CrossRefPubMedGoogle Scholar
  35. 35.
    Nakajima A, Shimoji N, Shiomi K, Shimizu S, Moriya H, Einhorn TA, Yamazaki M (2002) Mechanisms for the enhancement of fracture healing in rats treated with intermittent low-dose human parathyroid hormone (1–34). J Bone Miner Res 17:2038–2047PubMedGoogle Scholar
  36. 36.
    Andreassen TT, Ejersted C, Oxlund H (1999) Intermittent parathyroid hormone (1–34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res 14:960–968PubMedGoogle Scholar
  37. 37.
    Nevitt MC, Thompson DE, Black DM, Rubin SR, Ensrud K, Yates AJ, Cummings SR (2000) Effect of alendronate on limited-activity days and bed-disability days caused by back pain in postmenopausal women with existing vertebral fractures. Fracture Intervention Trial Research Group. Arch Intern Med 160:77–85CrossRefPubMedGoogle Scholar
  38. 38.
    Musgrave DS, Vogt MT, Nevitt MC, Cauley JA (2001) Back problems among postmenopausal women taking estrogen replacement therapy: The Study of Osteoporotic Fractures. Spine 26:1606–1612CrossRefPubMedGoogle Scholar
  39. 39.
    Brynhildsen JO, Bjors E, Skarsgard C, Hammar ML (1998) Is hormone replacement therapy a risk factor for low back pain among postmenopausal women? Spine 23:809–813CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2005

Authors and Affiliations

  • Michael C. Nevitt
    • 1
  • Peiqi Chen
    • 2
  • Robin K. Dore
    • 3
  • Jean-Yves Reginster
    • 4
  • Douglas P. Kiel
    • 5
    • 6
  • Jose R. Zanchetta
    • 7
  • Emmett V. Glass
    • 2
  • John H. Krege
    • 2
  1. 1.University of California San FranciscoSan FranciscoUSA
  2. 2. Lilly Research LaboratoriesEli Lilly and CompanyIndianapolisUSA
  3. 3.University of California Los AngelesAnaheimUSA
  4. 4.University of LiègeLiègeBelgium
  5. 5.Hebrew Rehabilitation Center for the AgedBostonUSA
  6. 6.Harvard Medical SchoolHarvard UniversityBostonUSA
  7. 7.Instituto de Investigaciones MetabólicasBuenos AiresArgentina

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