Introduction: Bisphosphonates (BP) used in osteoporosis management can induce an acute phase response, their short-term endocrine effects remain unclear. This study hypothesized that initial BP exposure elicits a non-thyroidal illness syndrome (NTIS)-like pattern and that thyroid autoimmunity may amplify this response. Methods: In this prospective cohort at a tertiary centre, 336 adults (93% postmenopausal women) were enrolled: 168 received first-dose BP therapy (zoledronic acid (ZA) =129; oral alendronate (ALN) = 39) and 168 matched controls (calcium/vitamin D). FT3, FT4, TSH, and erythrocyte sedimentation rate (ESR) were measured at baseline and on days 1, 2, 3, 7, and 42 with baseline anti-TPO Ab. Linear mixed-effects models with random intercepts evaluated group × time interactions, adjusting for age, sex, and body mass index. Results: BP recipients demonstrated a clear temporal pattern, FT3 declined significantly, reaching a nadir on Day 2 (mean difference −0.47 pg/mL vs controls, P < 0.001), FT4 fell modestly (mean difference −0.07 ng/dL), and TSH was transiently suppressed before rebounding above baseline by Day 42 (mean difference +0.39 mIU/L). ESR peaked on Day 2 and normalized by Day 7, paralleling hormonal recovery. Group × time interactions were significant for all parameters ( P < 0.05). Anti-TPO Ab positive individuals exhibited deeper FT3 suppression and greater TSH rebound. ALN effects were directionally similar but underpowered. Conclusion: First-dose BP therapy, particularly ZA, induces a short-lived, reversible NTIS-like response amplified by thyroid autoimmunity. Early post-infusion thyroid testing may mimic hypothyroidism, re-evaluation after six to eight weeks is recommended.
Kumar et al. (2026) studied this question.