Unravelling the pandemic: impaired bone metabolism and risk of SARS-CoV-2 infection
Creators: name: Pariente, Emilio
name: Martín-Millán, Marta
name: Nan, Daniel
name: Martínez-Revuelta, Daniel
name: Basterrechea, Hector
name: Pardo, Javier
name: Bonome, Merelyn
name: Solares, Sandra
name: Ramos, Carmen
name: Olmos-Martinez, Jose-Manuel
name: Pascua, Raquel
name: Martínez-Taboada, Victor M.
name: Hernández, José Luis
Publisher: name: Taylor & Francis
Year: 2025
Subjects: subject: Biochemistry
subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Physiology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Hematology

description: While the impact of COVID-19 on bone metabolism has been extensively studied, the inverse relationship remains less understood. This study investigates whether impaired bone metabolism is associated with an increased risk of COVID-19 infection. We conducted a nested case-control study within a population-based cohort, incorporating Kaplan-Meier analysis (KMA) to assess time to infection (TTI) differences. Propensity score matching (1:2) was performed and validated through standardized mean differences (&lt;0.10), variance ratio (=1), and McFadden’s pseudo-<i>R</i><sup>2</sup> (=0), ensuring balanced covariates. Bone status was evaluated using a composite index (AOMI), which included five components: P1NP and CTX (bone turnover markers), total hip bone mineral density (BMD-TH), trabecular bone score (TBS), and integral volumetric BMD (IvBMD). Inflammation and insulin resistance (IR) were assessed by albumin-to-globulin ratio (AGR &lt;1.50) and the TG/HDL ratio (&gt;2.50 in women and &gt;2.80 in men), respectively. We analysed 294 COVID-19 cases and 528 controls. AOMI+ individuals had a higher prevalence of COVID-19 (41.5% vs. 33.2%; <i>p</i> = 0.031), an adverse lipid pattern (“A” profile: high ApoB, LDL and TC) and pronounced bone changes (higher P1NP and CTX, lower BMD-TH, TBS, and IvBMD). AOMI − individuals were more likely to have metabolic syndrome, displayed a different lipid profile (“B” profile: elevated TG, AIP, and TG/HDL ratio), fewer bone alterations, and lower COVID-19 prevalence. TG/HDL ratio was 1.66 ± 1 in “A” profile, while it was 2.85 ± 1.4 in “B” profile individuals (<i>p</i> = 0.0001). Age acted as an effect modifier, and lowest tercile significantly increased COVID-19 risk associated with AOMI+ [Mantel-Haenszel OR = 1.42 (95%CI: 1.08–1.9); <i>p</i> = 0.022]. KMA identified AOMI+ men and individuals of both sexes in lowest age tercile, as groups with shorter TTI: These younger individuals had high CTX (women), low TBS (men), and high ApoB (both). In multivariable analyses, plasma CTX levels negatively correlated with TTI (adjusted β= −0.325; <i>p</i> = 0.0001). AOMI+ status was associated with increased COVID-19 risk after controlling for confounders, including IR (adjusted OR = 1.51; 95%CI: 1.04–2.10; <i>p</i> = 0.027), although this association weakened when adjusting for AGR (95%CI: 0.99–2.28; <i>p</i> = 0.055). ANCOVA-estimated adjusted TBS means were lower in COVID-19 cases compared to controls (1.259 vs. 1.294; <i>p</i> = 0.013). Impaired bone metabolism was found to be associated with increased COVID-19 risk, in a relationship potentially mediated by underlying inflammation. Elevated osteoclastic activity and a defined lipid profile with high ApoB, TC, LDL levels, played a crucial role in the results. Bone quality parameters more accurately captured COVID-19-related bone changes than BMD.