Risk of Osteosarcoma with Anabolic Therapy

Unfolding the Truth

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Burden of Osteoporosis
Global Prevalence
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> 200 million individuals suffer from osteoporosis globally1

Indian Prevalence
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1 out of 5 Indians suffer from osteoporosis2

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References:

  1. Sozen T et al. European journal of rheumatology.2017;4(1):46-56
  2. Available at: https://ijoro.org/index.php/ijoro/article/view/1881. Accessed on 17th June,2021 at 5:45pm IST
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Need of Anabolic Therapy in Osteoporosis

T-score

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Anabolic therapy is indicated for the patients who are at a very high-risk1

(Multiple vertebral fractures in addition to a bone mineral desity T-score of > -2.5)

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References:

  1. https://www.endocrineweb.com/professional/meetings/anabolic-agents-superior-first-line-therapy-highest-risk-patients
  2. Accessed on 25th June, 2021 at 1:34pm IST
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Approved Anabolic therapies1
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Teriparatide

Abaloparatide

Romosozumab (under reviewby the USFDA)

Impact of Anabolic therapy in Osteoporosis2

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Daily PTH injections or PTH1-34

↑Serum PTH concentration

Bone formation Bone resorption to minor extent

↑Bone mass ↑Bone microarchitecture ↑Mechanical strength

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USFDA: United States Food and Drug Administration | PTH Parathyroid Hormone

References:

  1. Haas AV et al. Journal of the Endocrine Society.2018;2(8):922-932
  2. Russow G et al. International journal of molecular sciences.2019;20(1):83-100
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Contraindications of Teriparatide and Abaloparatide

(Food and drug Administration and European Medicines Agency study)1

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A history of bone cancer (primary or metastatic)

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Risk of Osteosarcoma

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Children and young adults with open epiphysis

Reference:

  1. Vahle JL et al. Toxicologic pathology.2002;30:312-321
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Clinical Evidence: Risk vs No Risk of Osteosarcoma with Teriparatide(1/3)
Outdated evidence on use of anabolic therapy1
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An animal study conducted in 2012 concluded that: ~26% incidence of osteosarcoma was associated with anabolic therapy administered for a period of > 18-24 months

Reference:

  1. Capriani C et al. Journal of bone and mineral research.2012;27(12):2419-2428
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Clinical Evidence: Risk vs No Risk of Osteosarcoma with Teriparatide(2/3)
Latest Post-marketing surveillance of osteosarcoma in patients receiving Teriparatide

8 years

No incidence of osteosarcoma1

10 years

No incidence of osteosarcoma2

15 years

No difference in incidence3

8 years

No incidence of osteosarcoma1

10 years

No incidence of osteosarcoma2

15 years

No difference in incidence3

References:

  1. Gilsenan A el al. Osteoporosis International.2018;29(10):2335-2343.
  2. Gilsenan A el al. 2021;32(4):645-651.
  3. Miller PD el al. Current Medical Research and Opinion.2020;36(11):1861-1872.
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Clinical Evidence: Risk vs No Risk of Osteosarcoma with Teriparatide(3/3)
Studies Type of study Drugs with dosage Study population / Sample size Follow up period Incidence of Osteosarcoma
Gilsenan1 Prospective study Teriparatide 2.4 lakhs 8 years No incidence
Gilsenan2 Prospective study Teriparatide 75 thousands 10 years No incidence
Gilsenan3 Population based comparative-cohort study Teriparatide 1.5 lakhs; >= 65 years 8 years 0.3.2 times incidence
Miller4 Post marketing surveillance Abaloparatide 2 years No incidence
Gilsenan5 Post marketing surveillance Teriparatide >=40years 15 years No difference in incidence
Osteosarcoma surveillance safety studies6 Teriparatide

3.7 lakhs

1.5 lakhs

 7 years Three and zero osteosarcoma

References:

  1. Gilsenan A et al. Osteoporosis International.2018;29(10):2335-2343.
  2. Gilsenan A et al. 2021;32(4):645-651.
  3. Gilsenan A et al. Pharmacoepidemiol Drug Safety.2020;29:1616-1626.
  4. Miller PD et al. Current Medical Reasearch.2021;36(2):244-251
  5. Gilsenan A et al. Journal of Bone and Mineral Reasearch.2021;36(2):244-251.
  6. Available at https://pi.lilly.com/us/forteo-pi.pdf Accessed on 17th June,2021 at 5:45pm IST
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Dosage Recommendations of Anabolic agents
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Use of Teriparatide for > 2 years should only be considered if a patient remains at or has returned to having a high risk for fracture2

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Abaloparatide*

  • 80-µg daily subcutaneous injection
  • Periumbilical region
  • Discontinued after 24 months1

*Not available in India

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Removal of Black Box Warning for Osteosarcoma1

References:

  1. Hass AV et al. Journal of the Endocrine Society.2018;2(8):922-932
  2. Available at https://pi.lilly.com/us/forteo-pi.pdf. Accessed on 17th June,2021 at 5:45pm IST.
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Conclusion
  • Anabolic agents are highly effective at increasing bone mineral density and reducing incidence of both vertrbral and nonvertebral fractures
  • Anabolic therapy resulting in osteosarcoma continues to be a theoretical issue, however, the clinical experience with both forms of PTH has not substantiated such concerns

PTH: Parathyroid hormone

Reference:

Capriani C et al. Journal of bone and mineral research.2012;27(12):2419-2428

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Disclaimer

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