Abnormal Trabecular and Cortical Bone Microarchitecture in Chronic Hepatitis C Infection and Associations With Select Inflammatory Cytokines

Erica J Weinstein; Dean M Carbonari; Craig W Newcomb; Jessie Torgersen; Shanae M Smith; Katherine L Brecker; X Sherry Liu; Jay R Kostman; Stacey Trooskin; Rebecca A Hubbard; Joshua F Baker; Babette S Zemel; Mary B Leonard; Vincent Lo Re 3rd

doi:10.1093/ofid/ofaf102

Abnormal Trabecular and Cortical Bone Microarchitecture in Chronic Hepatitis C Infection and Associations With Select Inflammatory Cytokines

Open Forum Infect Dis. 2025 Apr 29;12(5):ofaf102. doi: 10.1093/ofid/ofaf102. eCollection 2025 May.

Authors

Erica J Weinstein¹, Dean M Carbonari², Craig W Newcomb², Jessie Torgersen^{1

2}, Shanae M Smith², Katherine L Brecker², X Sherry Liu^{3

4}, Jay R Kostman⁵, Stacey Trooskin⁶, Rebecca A Hubbard⁷, Joshua F Baker⁸, Babette S Zemel⁹, Mary B Leonard¹⁰, Vincent Lo Re 3rd^{1

2}

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
² Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Center for Real-World Effectiveness and Safety of Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³ Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴ Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵ Philadelphia FIGHT, Philadelphia, Pennsylvania, USA.
⁶ Mazzoni Center, Philadelphia, Pennsylvania, USA.
⁷ Department of Biostatistics, School of Public Health, Brown University, Providence, Rhode Island, USA.
⁸ Division of Rheumatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁹ Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁰ Department of Pediatrics and Medicine, Stanford University School of Medicine, Palo Alto, California, USA.

Abstract

Background: Hepatitis C virus (HCV) infection is associated with reduced bone mineral density (BMD) and increased fracture risk. The structural underpinnings for skeletal fragility with HCV and contributions of inflammatory cytokines remain unknown. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to compare skeletal parameters by chronic HCV.

Methods: We conducted a cross-sectional study among 58 participants with chronic HCV and 58 participants without HCV. Volumetric BMD and cortical dimensions of the radius and tibia were determined by HR-pQCT; visceral fat area and appendicular lean mass were assessed by whole body dual-energy x-ray absorptiometry; serum levels of tumor necrosis factor α (TNF-α), interleukin 6, and interleukin 18 were measured. Multivariable linear regression was used to estimate group differences in bone measurements and cytokines.

Results: Participants with chronic HCV had lower radius trabecular volumetric BMD (-24.2 mg hydroxyapatite [HA]/cm³) and lower tibia trabecular volumetric BMD (-20.5 mg HA/cm³), cortical area (-20.9 mm²), and cortical thickness (-0.47 mm) than participants without HCV (all P < .05), independent of age, sex, visceral fat area, appendicular lean mass, and smoking. Mean log TNF-α was higher with chronic HCV (+0.1-log pg/mL; P < .001), but no differences in mean log interleukin 6 or interleukin 18 were observed. Higher log TNF-α was associated with lower radius trabecular volumetric BMD (-99.7 mg HA/cm³), lower tibia cortical volumetric BMD (-91.6 mg HA/cm³), and higher tibia cortical porosity (+1.39%) by HR-pQCT (all P < .05).

Conclusions: Patients with chronic HCV had decreased trabecular volumetric BMD and cortical dimensions and higher TNF-α than individuals without infection, suggesting that HCV-associated inflammation might contribute to bone deficits.

Keywords: bone; cytokines; dual-energy x-ray absorptiometry; hepatitis C virus; peripheral quantitative computed tomography.

Abstract

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