Frailty, Inflammaging, and Polypharmacy as Interacting Determinants of Falls in Older Women: A Clinical and Pharmacological Perspective in Primary Care Settings

Background: Falls in older women are multifactorial events driven by the complex interaction of age-related loss of physiological reserve, frailty, sarcopenia, chronic low-grade inflammation, multimorbidity, and medication exposure. Older women represent a substantial proportion of fall-related injuries and fractures, yet available evidence is highly heterogeneous. Since many studies focus on mixed-sex cohorts, we must differentiate women-specific findings from general geriatric data. Methods: A structured narrative review was conducted to integrate biological, clinical, and pharmacological evidence on falls in older women, focusing particularly on primary care. The initial literature search covered PubMed, Scopus, Web of Science, and Embase from January 2000 to March 2025. To ensure the integration of recent high-level evidence, a supplementary search and backward citation tracking were subsequently executed through 31 August 2026, aligning with peer-review recommendations. Women-specific evidence was prioritized over mixed-sex cohorts. Given that the review aims for an interpretive synthesis rather than quantitative effect estimation, a meta-analysis and formal risk-of-bias assessments were omitted. Discussion: Frailty and sarcopenia are consistently associated with falls and functional decline in older adults. In contrast, inflammaging and metabolic dysregulation are more strongly supported as contributors to frailty, sarcopenia, and functional vulnerability than as independently established causal determinants of falls. Medication-related fall susceptibility may arise through several mechanisms, including sedation, impaired attention and psychomotor function, orthostatic hypotension, bradycardia, electrolyte and glucose disturbances, gait impairment, and adverse skeletal effects. Psychotropic agents, anticholinergic drugs, opioids, selected cardiovascular drugs, and other fall-risk-increasing drugs warrant particular attention in patients with reduced physiological reserve. Medication review and appropriate deprescribing should be considered components of multidomain fall-prevention strategies rather than stand-alone interventions. Conclusions: The principal contribution of this review is not the identification of new individual fall-risk factors, but the integration of established biological vulnerability, functional impairment, and pharmacological burden within a sex-sensitive primary-care framework. This approach may help clinicians consider frailty, medication exposure, and women-specific modifiers simultaneously during fall-risk assessment. The proposed framework is hypothesis-generating and should not be interpreted as a prospectively validated mechanistic or prediction model.