Poster Presentation ANZBMS-MEPSA-ANZORS 2022

Serum sclerostin concentrations using the Diasorin assay correlate with renal function and physical activity (#240)

Shejil Kumar 1 , Lucy Ding 1 2 , Paul Bonnitcha 2 , Roderick Clifton-Bligh 1 , Cameron Wood 2 , Christian Girgis 1
  1. Endocrinology, Royal North Shore Hospital, Sydney, NSW, Australia
  2. Clinical Chemistry, Royal North Shore Hospital, Sydney, NSW, Australia

Background: Sclerostin is an osteocyte-derived inhibitor of bone formation (1). Skeletal loading and the osteoanabolic agent romosozumab increase bone density via sclerostin downregulation/inhibition (1, 2). Sclerostin concentrations have been associated with skeletal loading (3, 4), and inversely associated with renal function (5). Data is scarce regarding association with renal function using the recently validated Diasorin assay, which is more specific for intact sclerostin than degradation fragments (6).

Methods: We conducted a cross-sectional study of serum sclerostin concentrations in different groups approximating different degrees of loading: active laboratory staff (n = 40), patients with recent femoral fracture (n = 39) and acute (<3 months, n = 10) and chronic (1-3 years, n = 5) spinal cord injury (SCI). We used an automated chemiluminescent sclerostin assay (LIAISON®, DiaSorin). Patients with predominantly stage 4-5 chronic kidney disease (CKD) (n = 25) were included to determine sclerostin associations with renal function.

Results: Serum sclerostin concentrations (pg/mL) among cohorts were: staff (median 176, IQR 122), femoral fracture (median 451, IQR 211), acute SCI (median 295, IQR 146) and chronic SCI (median 126, IQR 111). Mean sclerostin concentrations significantly differed between fully ambulant staff and less ambulant patients with femoral fracture and acute (but not chronic) SCI. The CKD cohort had highest sclerostin concentrations (median 676, IQR 811). Sclerostin had a strong negative association with eGFR (r = -0.682, p <0.001), and strong positive association with creatinine (r = 0.752, p <0.001). Using multivariate linear regression, sclerostin associations with eGFR and creatinine remained significant (p <0.001).

Conclusions: Sclerostin concentrations are elevated in renal impairment using the Diasorin assay, suggesting elevated intact sclerostin rather than renally-excreted degradation products as the primary mechanism. This may represent impaired intact sclerostin excretion or a pathophysiological response to CKD. Use of this sclerostin assay should adjust for renal function.

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