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Causality assessment · Causality: well established

Tenofovir disoproxil fumarate and Bone loss: is the FAERS signal real?

n=7,079 co-reports · PRR 563.0 · ROR 717.3
Tenofovir disoproxil fumarate side-effect profileAll assessmentsSee in the full list
A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.
Causality: well established

Tenofovir disoproxil fumarate ↔ Bone loss

n=7,079 co-reports · PRR 563.0 · ROR 717.3 Emtricitabine/TDF ↔ bone density decreased: n=16,608 · PRR 516.1

Reporting over time (stimulated-reporting check)

2004: 0 reports (0.00% of the drug's reports)2005: 1 reports (0.16% of the drug's reports)2006: 3 reports (0.57% of the drug's reports)2007: 1 reports (0.18% of the drug's reports)2008: 0 reports (0.00% of the drug's reports)2009: 0 reports (0.00% of the drug's reports)2010: 1 reports (0.21% of the drug's reports)2011: 2 reports (0.36% of the drug's reports)2012: 0 reports (0.00% of the drug's reports)2013: 3 reports (0.57% of the drug's reports)2014: 2 reports (0.21% of the drug's reports)2015: 7 reports (0.58% of the drug's reports)2016: 5 reports (0.41% of the drug's reports)2017: 9 reports (0.68% of the drug's reports)2018: 23 reports (1.53% of the drug's reports)2019: 389 reports (20.07% of the drug's reports)2020: 8,208 reports (67.38% of the drug's reports)2021: 1,156 reports (42.17% of the drug's reports)2022: 450 reports (25.97% of the drug's reports)2023: 174 reports (15.92% of the drug's reports)2024: 139 reports (18.51% of the drug's reports)2025: 85 reports (14.51% of the drug's reports)05081114172023

Reporting spiked in 2019, 2020, 2021, 2022, 2023, 2024, 2025 — 88% of all 10,658 reports arrived in two years (2020–2021). A burst like this usually follows a regulatory communication, media coverage or litigation advertising rather than a change in the drug's effect; it inflates disproportionality for those years.

Bars: reports per year as a share of all FAERS reports for this drug, 2004–2025; amber = spike year (>3× the median share, ≥50 reports). Source: openFDA count=receivedate, retrieved 2026-10-09.

Tenofovir disoproxil fumarate (TDF) is an antiretroviral used to treat HIV and hepatitis B, and its renal and bone toxicities are precisely why the newer prodrug TAF was developed. TDF reduces bone mineral density and raises markers of bone turnover, with the steepest declines in the first year of therapy and a persistently lower density thereafter; the FDA label carries explicit bone and renal warnings. The very high FAERS PRR reflects an established, mechanism-linked effect (proximal tubular dysfunction with phosphate wasting), though the term "bone loss" aggregates several coded MedDRA terms, so the raw count overshoots the specificity.

Regulatory basis: tenofovir disoproxil fumarate prescribing information (warnings on decreases in bone mineral density and renal toxicity); TAF developed specifically to mitigate these effects.

Bradford Hill viewpointStatusNote
Temporality (necessary)metBMD falls after therapy starts, largest in the first year
StrengthmetPRR 563 here; consistent, measurable BMD differences in trials
ConsistencymetReplicated across randomized trials and cohorts
SpecificitypartialClass-related (some other NRTIs share it); the FAERS term aggregates several codes
Biological gradientpartialRelated to cumulative exposure and baseline risk
PlausibilitymetProximal tubulopathy with phosphate wasting is a named mechanism
CoherencemetCoheres with the drug's renal toxicity and with the TAF redesign
ExperimentmetBMD improves after switching TDF to TAF — a clean substitution experiment
AnalogypartialShared with certain other antiretrovirals (e.g. some NRTIs)

This page's own qualitative read, not an automated/citation-gated assessment.

✗ Searched, nothing relevant found. The trial that surfaced (NCT01352715) captured only a lipid term. Bone-density declines are measured as continuous densitometry endpoints in HIV trials, not as a coded "bone loss" adverse event, so a disproportionality count and a trial AE table are simply measuring different things here.