Bone phenotype in familial partial lipodystrophy type 2: Insulin resistance and sclerostin - 03/05/26
, Arnaud Jannin a, Lucille Van Es a, Romain Vankemmel c, Olivier Ernst d, Pascal Pigny c, Georges Lion e, Benjamin Chevalier e, Bernard Cortet f, Stéphanie Espiard a, g, Marie-Christine Vantyghem a, b, g, 1 Highlights |
• | The bone phenotype in Type 2 Familial Partial Lipodystrophy (FPLD2), a rare insulin-resistant condition without obesity was studied. |
• | Despite normal bone density, FPLD2 patients showed high sclerostin levels, a bone hormone usually inhibiting bone formation. |
• | Sclerostin levels in FPLD2 patients correlated to insulin-resistance markers and bone-Z-score independently of fat mass. |
• | This suggests impaired bone regulation by insulin-resistance more than by adiposity. |
Abstract |
Background |
The impact of insulin-resistance on bone mineral density (BMD) remains unclear. Sclerostin inhibits bone formation, and increases with ageing, metabolic syndrome, and renal failure. Genetically-determined low sclerostin levels are associated with high BMD. Our aim was to determine the bone phenotype and the influence of insulin-resistance without obesity on sclerostin levels in Familial Partial Lipodystrophy type 2 (FPLD2).
Methods |
Demographic, metabolic, anthropometric, and bone parameters were compared after adjustment on age and menopausal status across four groups of women (19 FPLD2, 12 obese with diabetes, 14 obese without diabetes, 11 lean controls).
Results |
The FPLD2 group had significantly higher Intra-Abdominal/Total-Abdominal Fat (IAF/TAF) ratio and lower fat mass percentage compared to the other groups. Glucose parameters (Fasting blood glucose, C-peptide, HbA1c, HOMA2-IR CP ), and triglycerides were significantly higher in the FPLD2 group than in controls, with a higher sclerostin level. Sclerostin levels were positively associated with age, glucose parameters, Z-score, T-score, and negatively with osteocalcin. FPLD2 was the only subgroup in which the association between sclerostin and HOMA2-IR CP was maintained. In contrast, osteocalcin levels were negatively associated with age, glucose parameters, triglycerides, IAF/TAF, and bone parameters. Neither sclerostin or osteocalcin were associated with BMI, whole-body fat, or leptin.
Conclusion |
The association of sclerostin (positive) and osteocalcin (negative) with HOMA2-IR CP , but not with fat mass parameters, suggests a predominant role of insulin-resistance over fat mass in the regulation of osteokines. Insulin-resistance may uncouple the usual relationship between sclerostin and BMD. The sclerostin contribution in early atherosclerosis in FPLD2 remains to be studied.
Le texte complet de cet article est disponible en PDF.Keywords : Atherosclerosis, Insulin-resistance, Lipodystrophy syndrome, Osteoporosis, Sclerostin
Abbreviations : BMI, BMD, Ca c , DEXA, DO, eGFR, ELISA, FBG, FPLD2, HbA1c, HBP, HDLc, HOMA2-IR CP , IAF, iDPP4, iSGLT2, LRP5/6, MASLD, MRI, NDO, PTH, TAF, TGO, TGP, WNT
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Vol 52 - N° 3
Article 101762- mai 2026 Retour au numéro
Article précédent
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