Testosterone treatment and the risk of osteonecrosis: a pharmacovigilance analysis in Vigibase

Clémentine Vabre; Kyle Johnson; François Montastruc; Delphine Vezzosi; Oriana H Yu; Christel Renoux

doi:10.1007/s00228-022-03440-w

Testosterone treatment and the risk of osteonecrosis: a pharmacovigilance analysis in Vigibase

Eur J Clin Pharmacol. 2023 Mar;79(3):383-388. doi: 10.1007/s00228-022-03440-w. Epub 2023 Jan 5.

Authors

Clémentine Vabre^{1

2}, Kyle Johnson^{3

4}, François Montastruc^{5

6}, Delphine Vezzosi⁷, Oriana H Yu^{4

8}, Christel Renoux^{3

4

9}

Affiliations

¹ Department of Medical and Clinical Pharmacology, Centre of Pharmaco Vigilance and Pharmacoepidemiology, Toulouse University Hospital, Faculty of Medicine, 37 Allées Jules Guesde, Toulouse, 31000, France.
² Centre d'Investigation Clinique CIC 1436 - INSERM, University Paul Sabatier Toulouse, Toulouse University Hospital, Toulouse, France.
³ Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada.
⁴ Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, McGill University, Montreal, Québec, Canada.
⁵ Department of Medical and Clinical Pharmacology, Centre of Pharmaco Vigilance and Pharmacoepidemiology, Toulouse University Hospital, Faculty of Medicine, 37 Allées Jules Guesde, Toulouse, 31000, France. francois.montastruc@univ-tlse3.fr.
⁶ Centre d'Investigation Clinique CIC 1436 - INSERM, University Paul Sabatier Toulouse, Toulouse University Hospital, Toulouse, France. francois.montastruc@univ-tlse3.fr.
⁷ Department of Endocrinology, Larrey Hospital, CardioMet Institute, University Hospital Centre of Toulouse, Toulouse, France.
⁸ Division of Endocrinology, Jewish General Hospital, Montreal, Québec, Canada.
⁹ Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.

PMID: 36602591
DOI: 10.1007/s00228-022-03440-w

Abstract

Purpose: Recent reports have raised concerns about a potential risk of osteonecrosis associated with testosterone treatment (TT). The aim of this pharmacovigilance study was to assess the risk of reporting osteonecrosis associated with the use of TT compared with use of any other medication.

Methods: We performed a disproportionality analysis to investigate the risk of reporting osteonecrosis with TT using the WHO database VigiBase^®. We estimated the reporting odds ratio (ROR) and 95% confidence interval (CI) of reporting osteonecrosis with use of TT vs all other drugs, and the adjusted ROR with use of TT vs use of drugs for benign prostatic hyperplasia (BPH).

Results: Among men at least 18 years of age between January 1, 2000, and December 31, 2019, we identified 3479 reports of osteonecrosis, 84 of which were associated with TT use, out of a total of 4,667,754 adverse event reports. Reports of osteonecrosis in TT users occurred with both transdermal and injectable forms, and the mean age at report was 55.4 years. TT use was associated with a greater risk of reporting osteonecrosis compared to all other drugs (ROR, 5.13; 95% CI, 4.13-6.37) and compared with use of drugs for BPH (ROR, 3.00; 95% CI, 2.08-4.30). Half of the osteonecrosis reports associated with TT indicated concomitant use of corticosteroids.

Conclusion: TT was associated with a greater risk of reports of osteonecrosis compared to use of any other drug and use of drugs for BPH. This signal should be confirmed in complementary studies.

Keywords: Clinical pharmacology; Hypogonadism; Osteonecrosis; Testosterone.

MeSH terms

Adverse Drug Reaction Reporting Systems
Databases, Factual
Humans
Male
Middle Aged
Osteonecrosis*
Pharmacovigilance
Prostatic Hyperplasia*
Testosterone

Substances

Testosterone