Osteoporosis International

, Volume 21, Issue 6, pp 1041–1045

Of mice and men: divergent risks of teriparatide-induced osteosarcoma

  • V. Subbiah
  • V. S. Madsen
  • A. K. Raymond
  • R. S. Benjamin
  • J. A. Ludwig
Short Communication



Since approval by the U.S. Food and Drug Administration (FDA) in December 2002, teriparatide (recombinant 1-34 PTH; Forteo®) has been safely used by more than 430,000 patients. Prior to FDA approval, however, there was concern that teriparatide might increase the risk for patients to develop osteosarcoma, as almost 45% of the rats treated with this drug at the highest-tested dose level developed this aggressive form of bone cancer. Balancing the proven benefits of teriparatide shown by clinical trials with the theoretical risk for teriparatide-induced human osteosarcoma, the FDA mandated both a ‘black-box’ warning of this potential side-effect and a company-sponsored postmarketing surveillance program. As a participating institute of that surveillance program, we report upon the second person with potential teriparatide-induced osteosarcoma, in this case, complicated by a history of pelvic radiation.


Given the theoretic risk of the drug teriparatide and the known risk of radiation in inducing osteosarcoma, we raise the issue of whether teriparatide magnified the risk of radiation-induced osteosarcoma in our patient and try to determine which factor played the predominant role in the development of his disease.


We analyzed preclinical rat data, human clinical experience with teriparatide, and our patient’s clinical history to assess the human risk of teriparatide and radiation exposure.


After the first case of suspected osteosarcoma was reported in December 2005, we encountered a second possible teriparatide-induced osteosarcoma less than a year later. Review of the preclinical animal data would suggest that teriparatide is safe for human use when used as recommended by the manufacturer. Given the location of the sarcoma within the field of radiation and the limited exposure to teriparatide before diagnosis, it is unlikely that teriparatide played the predominant role in the emergence of this patient’s osteosarcoma. We cannot, however, exclude the possibility that teriparatide magnified the carcinogenic effect of radiation therapy to induce the osteosarcoma.


Of more than 430,000 persons who have received teriparatide for treatment of severe osteoporosis, we report the second patient to develop osteosarcoma. Although teriparatide reduces osteoporosis-related fractures in select patient populations, important contraindications, such as prior radiation exposure, should be considered before use.


Bone cancer Osteoporosis Osteosarcoma Recombinant 1-34 PTH Sarcoma Teriparatide 


  1. 1.
    Services USDoHaH. (U.S. Dept. of Health and Human Services, Office of the Surgeon General). Bone Health and Osteoporosis: A Report of the Surgeon General. 2004.Google Scholar
  2. 2.
    Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57(1):43–66CrossRefPubMedGoogle Scholar
  3. 3.
    Huvos AG, Butler A, Bretsky SS (1983) Osteogenic sarcoma associated with Paget's disease of bone. A clinicopathologic study of 65 patients. Cancer 52(8):1489–1495CrossRefPubMedGoogle Scholar
  4. 4.
    Rosemann M, Kuosaite V, Nathrath M, Atkinson MJ (2002) The genetics of radiation-induced and sporadic osteosarcoma: a unifying theory? J Radiol Prot 22(3A):A113–A116CrossRefPubMedGoogle Scholar
  5. 5.
    Vahle JL, Sato M, Long GG et al (2002) 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 30(3):312–321CrossRefPubMedGoogle Scholar
  6. 6.
    Vahle JL, Long GG, Sandusky G, Westmore M, Ma YL, Sato M (2004) Bone neoplasms in F344 rats given teriparatide [rhPTH(1–34)] are dependent on duration of treatment and dose. Toxicol Pathol 32(34):426–438PubMedGoogle Scholar
  7. 7.
    Harper KD, Krege JH, Marcus R, Mitlak BH (2006) Comments on initial experience with teriparatide in the United States. Curr Med Res Opin 22(10):1927CrossRefPubMedGoogle Scholar
  8. 8.
    Harper KD, Krege JH, Marcus R, Mitlak BH (2007) Osteosarcoma and teriparatide? J Bone Miner Res 22(2):334CrossRefPubMedGoogle Scholar
  9. 9.
    Burr DB, Hirano T, Turner CH, Hotchkiss C, Brommage R, Hock JM (2001) Intermittently administered human parathyroid hormone(1–34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys. J Bone Miner Res 16(1):157–165CrossRefPubMedGoogle Scholar
  10. 10.
    Dempster DW, Cosman F, Parisien M, Shen V, Lindsay R (1993) Anabolic actions of parathyroid hormone on bone. Endocr Rev 14(6):690–709PubMedGoogle Scholar
  11. 11.
    Jolette J, Wilker CE, Smith SY et al (2006) Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1–84 in a 2-year study in Fischer 344 rats. Toxicol Pathol 34(7):929–940CrossRefPubMedGoogle Scholar
  12. 12.
    Divieti P, Geller AI, Suliman G, Juppner H, Bringhurst FR (2005) Receptors specific for the carboxyl-terminal region of parathyroid hormone on bone-derived cells: determinants of ligand binding and bioactivity. Endocrinology 146(4):1863–1870CrossRefPubMedGoogle Scholar
  13. 13.
    Tashjian AH, Gagel RF (2006) Teriparatide [human PTH(1–34)]: 2.5 years of experience on the use and safety of the drug for the treatment of osteoporosis. J Bone Miner Res 21(3):388–365CrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2009

Authors and Affiliations

  • V. Subbiah
    • 1
  • V. S. Madsen
    • 1
  • A. K. Raymond
    • 2
  • R. S. Benjamin
    • 1
  • J. A. Ludwig
    • 1
  1. 1.Department of Sarcoma Medical OncologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of PathologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

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