{
  "abstract": "Background Bone fragility is a highly prevalent non-AIDS comorbidity in people living with HIV (PLWH), even in the setting of sustained virological suppression. Accelerated aging, persistent immune activation, and antiretroviral therapy exposure contribute to reduced bone mineral density (BMD); however, the endocrine and metabolic mechanisms underlying this process remain poorly defined. Emerging regulators such as leptin and FGF23 play key roles in bone metabolism in the general population, but their contribution to bone loss in PLWH has not yet been clarified.Methods We enrolled 104 viro-suppressed PLWH, classified by BMD as normal (T-score ≥ -1; n=55) or low (T-score < -1, including osteopenia, n=39 and osteoporosis, n=10). Plasma levels of adrenocorticotropic hormone (ACTH), leptin, FGF23, Dickkopf-1 (DKK1), TNF-α, osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), sclerostin (SOST) and parathyroid hormone (PTH) were quantified using Luminex assay. Mann-Whitney, Kruskal-Wallis, and Dunn’s multiple comparison tests were used, and Spearman correlations with immunological parameters were assessed.Results The majority of PLWH were older than 50 years of age (67/104; 64%). PLWH with low BMD were older than those with normal BMD ( table 1; p=0.01). Plasma levels of DKK1, TNF-α, OPG, OC, OPN, SOST and PTH did not differ between groups. In contrast, PLWH with low BMD displayed significantly lower ACTH (8.2 vs 17.8 pg/mL, p=0.02; figure 1A), leptin (10.3 vs 15.5 ng/mL, p=0.03; figure 1B), and FGF23 (36.4 vs 56.3 pg/mL, p=0.02; figure 1C) compared to PLWH with normal BMD.When stratifying PLWH with low BMD into osteopenic and osteoporotic groups, no significant differences were observed in the analyzed markers between the two subgroups. However, leptin levels were significantly lower in osteopenic individuals compared to PLWH with normal BMD (9.7 ng/mL vs 15.5 ng/mL, p=0.02), while ACTH and FGF23 levels showed a trend toward reduction in the osteopenic group compared to those with normal bone density (p=0.08 and p=0.07, respectively).Finally, age was negatively correlated with leptin (r = –0.2; p = 0.01) and positively correlated with FGF23 (r = 0.2; p = 0.05; figure 1D-E), whereas neither current nor nadir CD4+ T-cell counts were significantly associated with any of the analyzed biomarkers.Conclusions Our findings indicate that endocrine and metabolic dysregulation may play a key role in HIV-associated bone fragility. PLWH with low BMD exhibited reduced ACTH, leptin, and FGF23 levels, reflecting an imbalance of the HPA axis, energy metabolism, and FGF23-mediated phosphate/vitamin D homeostasis, which may contribute to impaired bone remodeling and skeletal vulnerability.The correlation between age and these hormonal markers further highlights the interplay between HIV, aging, and bone loss. Overall, assessment of endocrine and metabolic biomarkers may help identify PLWH at higher risk of bone fragility and guide early preventive and therapeutic strategies.Abstract OC65 Table 1Abstract OC65 Figure 1Plasma levels of adrenocorticotropic hormone (ACTH), leptin, and fibroblast growth factor 23 (FGF23) in people living with HIV (PLWH) stratified by bone mineral density (BMD) as normal or low (A-C). Spearman correlation analysis between age and leptin and FGF23 levels (D-E)",
  "authors": [
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "V Bono"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "C Tincati"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "M Augello"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "R Rovito"
    },
    {
      "affiliations": [
        "Rehabilitation Unit, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "AM Previtera"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "V Sala"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "F Monti"
    },
    {
      "affiliations": [
        "Renal Division, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "M Cozzolino"
    },
    {
      "affiliations": [
        "Renal Division, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "P Ciceri"
    },
    {
      "affiliations": [
        "Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "G Marchetti"
    }
  ],
  "title": "OC65 Endocrine and metabolic alterations in aging PLWH with low bone mineral density",
  "uid": "f1587157-9f1c-562c-acda-c6358c5c1cb5"
}