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Peer-reviewedCC BYDiseases (Basel, Switzerland)

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

10 affiliations
  1. 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia.
  2. 2General Hospital "Dr. Josip Bencević", Andrije Štamapara 42, 35000 Slavonski Brod, Croatia.
  3. 3University of Slavonski Brod, 35000 Slavonski Brod, Croatia.
  4. 4Department of Internal Medicine and History of Medicine, Faculty of Medicine Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia.
  5. 5Division of Internal Medicine, Health Center Zagreb Centar, Runjaninova 4, 10000 Zagreb, Croatia.
  6. 6Clinical Hospital Center "Sestre Milosrdnice", Vinogradska Cesta 29, 10000 Zagreb, Croatia.
  7. 7Faculty of Medicine Zagreb, 10000 Zagreb, Croatia.
  8. 8University Hospital for Infectious Diseases "Dr. Fran Mihaljević", 10000 Zagreb, Croatia.
  9. 9Department of Clinical Medicine, Faculty of Dental Medicine and Health Osijek, Crkvena Ulica 21, 31000 Osijek, Croatia.
  10. 10Division of Endocrinology, Department of Internal Medicine, University Hospital Centre Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia.

Abstract

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.

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BibTeX
@article{bosnic2026frailty,
  title = {{Frailty, Inflammaging, and Polypharmacy as Interacting Determinants of Falls in Older Women: A Clinical and Pharmacological Perspective in Primary Care Settings.}},
  author = {Zvonimir Bosnić and Hrvoje Pitlović and Ivana Šofić and Maja Miletić and Danijel Marinčić and Katarina Šarčević Ivić-Hofman and Ivan Lekić and Karlo Miličić Juhas and Valerija Miličić and Tatjana Bačun},
  journal = {Diseases (Basel, Switzerland)},
  year = {2026},
  month = oct,
  doi = {10.3390/diseases14100374},
  url = {https://europepmc.org/article/MED/42930001},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Frailty, Inflammaging, and Polypharmacy as Interacting Determinants of Falls in Older Women: A Clinical and Pharmacological Perspective in Primary Care Settings.
AU  - Zvonimir Bosnić
AU  - Hrvoje Pitlović
AU  - Ivana Šofić
AU  - Maja Miletić
AU  - Danijel Marinčić
AU  - Katarina Šarčević Ivić-Hofman
AU  - Ivan Lekić
AU  - Karlo Miličić Juhas
AU  - Valerija Miličić
AU  - Tatjana Bačun
PY  - 2026
DA  - 2026/10/12
JO  - Diseases (Basel, Switzerland)
DO  - 10.3390/diseases14100374
UR  - https://europepmc.org/article/MED/42930001
AB  - 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.
SN  - 2079-9721
ER  -