SP345SECRETED PHOSPHOPROTEIN 24 (SPP24) IS A NOVEL BIOMARKER OF MINERAL METABOLISM: A CROSS-SECTIONAL EVALUATION
Bibliographic record
Abstract
INTRODUCTION AND AIMS: The 24kD form of secreted phosphoprotein (SPP24), a cytokine binding bone matrix protein with various truncated c-terminal products, is primarily synthesized in liver and bone. The C-terminal products of SPP24 bind to bone morphogenic protein 2 (BMP2) and attenuate BMP2-induced bone formation. There is experimental evidence to suggest that BMP2 is also implicated in extra-osseous mineral deposition, including calcification of the vasculature. SPP24 shares homology with fetuin-A, a potent vascular and soft tissue calcification inhibitor and SPP24 is one component of the circulating fetuin-mineral complex. The limited evidence to date suggests that SPP-24 may function, in part, as an inhibitor of bone formation and ectopic vascular calcification. There are few reports assessing serum SPP-24 in humans, and to the best of our knowledge, it has not been studied in relation to kidney function or in concert with markers of mineral metabolism. METHODS: SPP-24 was measured in the serum of total of 192 subjects using ELISA-based measurements (Cloud-Clone, USA). Subjects were either participants of a study of measured GFR (mGFR) using inulin urinary clearance (n=80) or a subset of community-dwelling participants of year 10 of the Canadian Multicentre Osteoporosis Study (n=112). Serum or plasma biomarkers were assessed using ELISA-based measurement, except serum phosphate, which was assessed using a colorimetric assay. RESULTS: In the combined cohort, the mean SPP-24 was 167.7 ± 101.1 ng/mL (range 33.4-633.6 ng/mL). The mean age was 66.5±11.3, 82(42.9%) males and mean eGFR (CKD-epi) was 59.9±27.0 mL/min/1.73m2 (range 8-122 mL/min/1.73m2). There was a strong inverse correlation between SPP-24 and eGFR (r=-0.58, p<0.001). There was no association between SPP-24 and serum phosphate or age but significant positive correlations were found with serum intact parathyroid hormone (r=0.45, p<0.001), log-scaled fibroblast growth factor-23 (r=-0.20, p=0.01) and with the Wnt-signalling inhibitors sclerostin (r=0.32, p<0.001) and dickkopf-related protein 1 (r=-0.35, p<0.001). All correlations remained significant after adjustment for age. In subjects with mGFR by inulin clearance (mean 45.1±30.45 mL/min, range 6.3-164.6 mL/min), SPP-24 remained inversely correlated with mGFR (n=80, r=-0.35, p=0.002) but was not associated with 25-hydroxyvitamin D or α-klotho. CONCLUSIONS: The results of this study indicate that SPP-24 is significantly altered by kidney function and is the first human data linking levels of SPP-24 to other biomarkers involved in mineral metabolism. Whether there is a role for circulating SPP-24 in bone formation and ectopic mineralization requires further study.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".