Association between Onychogryphosis and Lower Extremity Complications: A Multicenter Cohort Study Using TriNetX

Abstract

Introduction

Onychogryphosis has been associated with chronic foot injury and vascular disease. We evaluated whether onychogryphosis is associated with increased 5-year risk of lower extremity complications.

Methods

Using TriNetX Research Network patients with onychogryphosis were propensity score matched 1:1 to controls for age, sex, race, obesity, type II diabetes, chronic kidney disease, and smoking. Cox proportional hazards models estimated 5-year hazard ratios (HRs) for lower extremity complications, with subgroup analyses for diabetes and peripheral artery disease (PAD).

Results

After matching (174,537 per cohort), onychogryphosis was associated with increased 5-year risk of foot/toe amputation procedures (HR 2.798, 95% CI: 2.516–3.111), ulcer (HR 2.108, 95% CI: 2.023–2.196), cellulitis (HR 1.743, 95% CI: 1.685–1.803), osteomyelitis (HR 1.673, 95% CI: 1.583–1.769), and gangrene (HR 1.485, 95% CI: 1.382–1.597) (all p < 0.0001). Associations remained significant in diabetes and PAD restricted analyses.

Conclusion

Onychogryphosis was associated with substantially increased 5-year risk of major lower extremity complications in a large matched cohort, with consistent findings among patients with type II diabetes and PAD. Identification of onychogryphosis should prompt focused lower extremity assessment and brief risk screening with a low threshold for vascular or primary care referral in high-risk patients.

Introduction

Onychogryphosis is characterized by a markedly thickened hypercurved nail plate often resembling a ram’s horn. Older adults and patients with impaired mobility and self-care are most often affected [1, 2]. Onychogryphosis has been associated with chronic foot injury and vascular disease, suggesting that it may reflect broader lower extremity pathology [3]. However, population level evidence linking onychogryphosis to lower extremity complications is limited. Given the morbidity of diabetic and vasculopathic foot events, we assessed whether onychogryphosis is associated with subsequent lower extremity complications using a large multicenter real-world database.

Methods

TriNetX, a research network of ≥100 healthcare organizations that applies data quality checks for internal validation, was queried on March 2, 2026, for patients with onychogryphosis and a control group without onychogryphosis presenting for a general medical encounter. The index date was the first recorded onychogryphosis diagnosis (and the corresponding matched date for controls). Cohorts were propensity score matched 1:1 for age, sex, race, ethnicity, type II diabetes, chronic kidney disease, obesity, and smoking. Cox proportional hazards models estimated 5 year hazard ratios (HRs) for clinically significant lower extremity outcomes, including nonpressure chronic ulcer of lower limb, cellulitis of limb, osteomyelitis, gangrene, and foot/toe amputation procedures. This study was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (online suppl. File 1; for all online suppl. material, see https://doi.org/10.1159/000551347).

Results

After matching, each cohort included 174,537 patients (mean age 61.05 years, 55.46% female for the entire cohort). Baseline characteristics were well balanced after matching (all standardized mean differences <0.10) (Table 1). Onychogryphosis was associated with risk of foot/toe amputation procedures (HR 2.798, 95% CI: 2.516–3.111), nonpressure chronic ulcer of the lower limb (HR 2.108, 95% CI: 2.023–2.196), cellulitis of the limb (HR 1.743, 95% CI: 1.685–1.803), osteomyelitis (HR 1.673, 95% CI: 1.583–1.769), and gangrene (HR 1.485, 95% CI: 1.382–1.597) (all p < 0.0001) (Table 2). These associations remained significant in subgroup analyses restricted to patients with type II diabetes and peripheral artery disease (PAD), indicating that onychogryphosis independently predicts complications beyond these established risk factors (Table 3).

Table 1.

Demographic data of patients with onychogryphosis vs. patients without onychogryphosis (controls)

Characteristic	Onychogryphosis (N = 174,537)	Matched controls (N = 174,537)	SMD
Demographics
Age at index, years	61.0±15.7	61.1±15.8	0.0102
Female sex, n (%)	96,249 (55.145)	97,360 (55.782)	0.0128
White race, n (%)	122,721 (70.312)	123,427 (70.717)	0.0089
Black or African American race, n (%)	30,955 (17.735)	30,791 (17.642)	0.0025
Hispanic or Latino ethnicity, n (%)	12,481 (7.151)	11,178 (6.404)	0.0297
Asian race, n (%)	4,350 (2.492)	4,547 (2.605)	0.0072
Diagnoses (selected comorbidities), n (%)
Obesity, unspecified (E66.9)	40,639 (23.284)	41,913 (24.014)	0.0172
Type II diabetes mellitus (E11)	62,920 (36.050)	62,997 (36.094)	0.0009
Personal history of nicotine dependence (Z87.891)	32,224 (18.463)	32,612 (18.685)	0.0057
Chronic kidney disease (N18)	27,832 (15.946)	28,769 (16.483)	0.0146

Values are presented as n (%) or mean ± standard deviation (SD). Standardized mean differences (SMDs) <0.10 indicate adequate balance between cohorts.

Table 2.

Main analysis: 5-year risk of incident lower extremity complications in patients with onychogryphosis vs. propensity score-matched controls

Outcome	HR	95% Confidence interval	p value
Foot/toe amputation procedures	2.798	2.516–3.111	<0.0001
Nonpressure chronic ulcer of lower limb	2.108	2.023–2.196	<0.0001
Cellulitis of limb	1.743	1.685–1.803	<0.0001
Osteomyelitis	1.673	1.583–1.769	<0.0001
Gangrene	1.485	1.382–1.597	<0.0001

Cox proportional hazards models estimating the association between onychogryphosis and 5-year incidence of lower extremity complications in propensity score matched cohorts. HRs with 95% confidence intervals are shown; p values are two-sided.

Table 3.

Subgroup analyses

Subgroup	Outcome	HR	95% Confidence interval	p value
Type II diabetes	Foot/toe amputation procedures	2.804	2.51–3.133	<0.0001
Type II diabetes	Nonpressure chronic ulcer of lower limb	2.112	2.015–2.213	<0.0001
Type II diabetes	Cellulitis of limb	1.837	1.762–1.916	<0.0001
Type II diabetes	Osteomyelitis	1.797	1.688–1.913	<0.0001
Type II diabetes	Gangrene	1.578	1.455–1.712	<0.0001
Peripheral artery disease	Foot/toe amputation procedures	1.89	1.689–2.115	<0.0001
Peripheral artery disease	Nonpressure chronic ulcer of lower limb	1.593	1.499–1.692	<0.0001
Peripheral artery disease	Cellulitis of limb	1.582	1.495–1.674	<0.0001
Peripheral artery disease	Osteomyelitis	1.474	1.366–1.591	<0.0001
Peripheral artery disease	Gangrene	1.241	1.138–1.354	<0.0001

Subgroup analyses showing 5-year HRs and 95% confidence intervals for incident lower extremity complications among patients with onychogryphosis compared with matched controls, restricted to patients with type II diabetes and to patients with PAD. HRs were estimated using Cox proportional hazards models over a 5-year follow-up period. All p values are two-sided.

Discussion

We found that onychogryphosis was associated with increased 5 year risk of lower extremity complications, including amputation procedures, ulceration, infection, and gangrene. These findings corroborate and extend limited existing epidemiologic data using a propensity score matched, time to event design with consistent findings in diabetes and PAD restricted subgroups. Similarly, in a retrospective cohort study using the All of Us Research Program database including 5,679 patients, onychogryphosis was associated with type II diabetes, PAD, and lower extremity ulcer (all p < 1E−6). Prior evidence is otherwise largely limited to case reports.

Since normal keratinization depends on adequate blood flow and oxygen delivery, vascular disease may impair nail matrix repair from repetitive microtrauma and increase susceptibility to onychodystrophy [4]. Onychogryphosis therefore may be an indicator of underlying vascular disease, which is particularly important in patients with type II diabetes and PAD, who are at high risk for severe progressive complications. For example, in a retrospective cohort study including 8,905 patients with type I or II diabetes, 514 (5.8%) developed a foot ulcer, of which 77 (15%) developed osteomyelitis and 80 (15.6%) requiring amputation [5]. Several causal models may explain this association. Onychogryphosis may serve as a marker of underlying vascular disease (shared etiology), result from trauma that also causes subsequent complications (common cause), or directly contribute through soft tissue injury creating infection portals (direct causation). These models are not mutually exclusive and prospective studies are needed to elucidate mechanisms. Because onychogryphosis is a clinical diagnosis, and can be readily appreciated during physical examination, its identification should prompt focused lower extremity assessment, brief lower extremity risk screen (history of diabetes/PAD, prior ulceration or infection), with a low threshold for referral to vascular or primary care for preventive care and vascular risk optimization in high-risk patients.

Study limitations include retrospective cohort design, potential diagnostic and procedural miscoding, residual confounding (neuropathy severity, socioeconomic factors, footwear, and mobility limitations), and potential surveillance bias due to differential healthcare utilization. Nonetheless, consistent associations across type II diabetes and PAD restricted analyses support the robustness of the observed relationship. Correlation does not equal causation.

In sum, we found that onychogryphosis was associated with an increased 5 year risk of lower extremity complications in a large multicenter matched cohort. Therefore, we recommend that diagnosis of onychogryphosis prompts inspection of the feet and interdigital spaces, a brief lower extremity risk screen, and a low threshold for referral to vascular or primary care for preventive care and vascular risk optimization. Prospective studies are needed to confirm temporality and test whether targeted screening and early interventions reduce subsequent complications.

Statement of Ethics

This study was conducted in accordance with the principles of the Declaration of Helsinki. The study was based entirely on de-identified patient data obtained under license from the TriNetX research network. No individually identifiable patient information was accessed. Accordingly, Institutional Review Board review and written informed consent were note required, in accordance with applicable institutional and regulatory guidelines.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

N.V.C.: study concept and design, data acquisition, data analysis and interpretation, drafting of the manuscript. S.R.L.: study supervision, interpretation of data, and critical revision of the manuscript. All authors reviewed and approved the final manuscript.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

The data that support the findings of this study are available from the TriNetX research network. Restrictions apply to the availability of these data, which were used under license for this study and are not publicly available. Data may be available from the corresponding author upon reasonable request and with permission of TriNetX.