Preclinical
Safety Data
Rats
treated with near-life time daily injections had dose-dependent
exaggerated bone formation and increased incidence of osteosarcoma
most probably due to an epigenetic mechanism. Teriparatide did not
increase the incidence of any other type of neoplasia in rats. Due to
the differences in bone physiology in rats and humans, the clinical
relevance of these findings is probably minor. No bone tumours were
observed in ovariectomised monkeys treated for 18 months or during a
3-year follow-up period after treatment cessation. In addition, no
osteosarcomas have been observed in clinical trials or during the
post treatment follow-up study.1
Clinical
Experience
An
analysis conducted in 2012 found that in the more than 16,000
patients who received teriparatide in controlled clinical trials and
observational studies, there were no cases of osteosarcoma reported.2
Postmarketing
Experience
Cases
of bone tumor and osteosarcoma have been reported rarely in the
postmarketing period. The causality to teriparatide use is unclear.3
The
cumulative number of spontaneous reports with a pathology-confirmed
diagnosis of osteosarcoma in the teriparatide-treated population does
not exceed what would be predicted based on background incidence
alone.3
Osteosarcoma
continues to be the focus of long-term postmarketing surveillance
efforts. Any communication to Lilly that includes a potential report
of osteosarcoma is further investigated and reported expeditiously to
the FDA and to other regulatory authorities.
Treatment
considerations
In
rats, teriparatide caused a dose-dependent increase in the incidence
of osteosarcoma, a malignant bone tumor. Because of the uncertain
relevance of the rat osteosarcoma finding to humans, prescribe
teriparatide only for patients for whom potential benefits outweigh
potential risk.3
Teriparatide
should not be prescribed for patients at increased baseline risk for
osteosarcoma. Increased risks include:3
Paget’s
disease of bone
Unexplained
elevations of alkaline phosphatase (elevations in alkaline
phosphatase may signal undiagnosed Paget’s disease of bone)*
Pediatric
and young adult patients with open epiphyses
Prior
external beam or implant radiation therapy involving the skeleton
Teriparatide
treatment has been shown to elevate BSAP as part of its mechanism of
action; this elevation is expected.3
References
1.
Forsteo [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
2.
Andrews EB, Gilsenan AW, Midkiff K, et al. The US postmarketing
surveillance study of adult osteosarcoma and teriparatide: study
design and findings from the first 7 years. J Bone Miner Res.
2012;27(12):2429-2437. https://doi.org/10.1002/jbmr.1768
3.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Glossary
ALP
= bone alkaline phosphatase
BSAP
= bone-specific alkaline phosphatase
FDA
= Food and Drug Administration