Osteoporosis risk in patients with primary open-angle glaucoma using muscarinic and prostaglandin agonists: A retrospective cohort study

BackgroundGlaucoma is the leading cause of irreversible blindness worldwide, with primary open-angle glaucoma (POAG) arising as the most common subtype. Recent studies have shown that muscarinic and prostaglandin pathways can modulate bone remodeling under systemic, context-dependent conditions. M3 muscarinic receptor activation has been linked to increased bone formation and decreased resorption, whereas continuous prostaglandin E2 (PGE2) administration inhibits bone resorption, with intermittent use inducing bone formation. Given the minimal systemic findings of topical ophthalmic medications, the clinical relevance of bone remodeling effects for patients treated with glaucoma eye drops, particularly in regard to osteoporosis, remains uncertain and warrants evaluation.Patients and MethodsA retrospective cohort study was conducted using the TriNetX network with approximately 100 million de-identified electronic medical records. Cohorts included POAG patients prescribed either prostaglandin analogs (e.g. latanoprost, bimatoprost, travoprost, tafluprost) without muscarinic agonist use, or muscarinic M3 agonists (e.g. pilocarpine, carbachol) without prostaglandin analog use. Propensity score matching was performed for age, sex, comorbidities, and concurrent glaucoma medications to limit possible cofounders. The outcome was defined as a diagnosis of osteoporosis without current pathological fracture (ICD code M81). Risk ratios (RR), odd ratios (OR), and 95% confidence intervals (CI) were calculated.ResultsAfter matching, each cohort included 6,743 patients. The incidence of osteoporosis is 13.3% in the prostaglandin cohort and 8.9% in the muscarinic cohort. Prostaglandin agonist use was associated with a statistically significant increase in osteoporosis risk (RR = 0.67, 95% CI 0.60-0.73; OR = 0.63, 95% CI 0.57-0.71; p < 0.0001).ConclusionProstaglandin agonist use was associated with an increased risk of osteoporosis compared with muscarinic agonist therapy in POAG patients. These findings suggest potential systemic effects (e.g. changes to bone health) of prostaglandin agonist use beyond previously known local, ocular effects and highlight the importance of considering osteoporosis risk in glaucoma management.