MON-LB72 Multicentric Carpotarsal Osteolysis Syndrome (MCTO) Has a Generalized High Turnover Bone Phenotype, High S RANKL and Responds to Denosumab
Bibliographic record
Abstract
Abstract Background:MCTO is a rare disorder, caused by mutations in the MABF gene, a negative regulator of RANKL. Manifestations include carpal tarsal osteolysis and subsequent renal failure in some. Pathophysiology is poorly understood, and no effective treatment is available. Clinical case:A 5y old boy presented (2011) with R wrist pain and diffuse swelling. MRI showed pan-carpal synovitis with joint effusion. He did not respond to different anti-inflammatory medications. Plain films showed central loss of the proximal row of carpal bones. His mother was followed as an adolescent with presumed juvenile rheumatoid arthritis. Genetic testing confirmed MAFB gene mutation (c.206C>T,p.Ser69Leu) in both patient and mother.At 7y, skeletal survey showed diffuse osteopenia and mild height loss in T1. DXA (L1-4) Z-score was -0.7. Calcium phosphate metabolism indices were within reference ranges. Bone Specific Alk Pi was modestly increased and C-telopeptide markedly increased.He received Denosumab (0.5-0.75 mg/Kg) 4-monthly for two years and experienced less pain and increased daily activities with improved R wrist function. Osteolysis stabilized and none was noted in the L wrist or ankles. BMD Z-score was -0.2. A year following treatment (2016) he received two more injections of Denosumab following pain and movement restriction of R elbow, R knee and L ankle. In 2019 (13y) he fell and radiology showed, R knee osteopenia, R wrist almost complete destruction of the carpal bones. Neither ankle nor L wrist showed osteolysis. R upper limb musculature was wasted when compared with the left. Shoulder and elbow strength were preserved. BMD Z-score was -1.2. Serum calcium, 25(OH)Vitamin D and PTH were normal. Bone specific alkaline phosphatase and C-Telopeptide were elevated. Serum creatinine was normal, eGFR 150 ml/min/1.73m2, ACR (6.6 [normal< 3.5] mg/mmol)) with no hypercalciuria or nephrocalcinosis. He was normotensive.High resolution peripheral quantitative computerized tomography (HRpQCT) of the L distal radius and distal tibia compared with 7 age-matched healthy males showed reduced total volumetric BMD (186.4;198.2-306.4), normal trabecular volumetric BMD and markedly reduced cortical volumetric BMD (320.4;636.5-792.5). Cortical thickness was below the expected range. HRpQCT measurements of the R wrist and tibia were similar. sRANKL, 6 weeks after Denosumab were markedly increased in both undiluted (35.4 pmol/L) and averaged diluted samples (83.73 pmol/L) when compared with healthy age-matched children (0.21-0.41pmol/L). Conclusions/Clinical Lessons:MCTO (MAFB, mutation c.206C>T,p.Ser69Leu), has a generalized high turnover skeletal phenotype (osteoporosis), likely driven by very high levels of sRANKL. Denosumab is a targeted treatment for the osteoporosis, which may help stabilize the osteolysis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".