Peterson-Riggs Calcium Homeostasis and Bone Remodeling Model

Where this model is curated

The entry card says what the model is for: which mechanism nodes it links to, how faithfully, and what it found. This page holds the model itself.

disorder CKD-Mineral Bone Disorder kb/disorders/CKD-Mineral_Bone_Disorder.yaml

Committed run

From exports/model_runs/BIOMD0000000613.json, regenerated by just gen-model-results. Scenario roots link to the mechanism node they drive on the entry page.

Simulation results — 11 scenarios run with dismech-perturb (tellurium / libRoadRunner CVODE) over 26280 h; baseline GFR = 6.0

Scenario	BMD (relative)	CaPO4_Product ((mg/dL)^2)	FGF23 (pg/mL)	Osteoblasts (relative)	Osteoclasts (relative)	Plasma_Ca (mg/dL)	Plasma_Calcitriol (pg/mL)	Plasma_PO4 (mg/dL)	Plasma_PTH (pg/mL)	Sclerostin (pmol/L)	Soluble_Klotho (pg/mL)	Vascular_Calcification (relative)	Activated phenotypes
Healthy baseline GFR = 6.0	18933.810946	573.722684	110.177227	0.005013	0.002063	33.656129	288.607712	17.046603	81.543379	835.161448	600.0	37.495963	reference
CASR loss-of-function drives Secondary Hyperparathyroidism	17435.456924 0.92× baseline	654.888818 1.14× baseline	203.180378 1.84× baseline	0.005013 1.00× baseline	0.002305 1.12× baseline	33.73051 1.00× baseline	77.529433 0.27× baseline	19.415325 1.14× baseline	92.861269 1.14× baseline	3108.712626 3.72× baseline	200.0 0.33× baseline	141.405532 3.77× baseline	Proximal muscle weakness · mild Arterial calcification · mild Left ventricular hypertrophy · mild
CYP27B1 loss-of-function drives Calcitriol Deficiency	17807.132 0.94× baseline	648.932921 1.13× baseline	203.073728 1.84× baseline	0.005013 1.00× baseline	0.002203 1.07× baseline	33.473026 0.99× baseline	77.90233 0.27× baseline	19.386742 1.14× baseline	85.982736 1.05× baseline	2894.467257 3.47× baseline	200.0 0.33× baseline	132.684558 3.54× baseline	Proximal muscle weakness · mild Arterial calcification · mild Left ventricular hypertrophy · mild
CYP24A1 loss-of-function drives Calcitriol Deficiency	19268.351915 1.02× baseline	645.956574 1.13× baseline	223.543096 2.03× baseline	0.005013 1.00× baseline	0.002106 1.02× baseline	33.625027 1.00× baseline	358.430566 1.24× baseline	19.210589 1.13× baseline	81.704222 1.00× baseline	2808.513843 3.36× baseline	200.0 0.33× baseline	129.298395 3.45× baseline	Arterial calcification · mild Left ventricular hypertrophy · mild
KLOTHO deficiency drives Phosphate Retention and FGF23 Axis	17812.834941 0.94× baseline	648.948435 1.13× baseline	203.074111 1.84× baseline	0.005013 1.00× baseline	0.002204 1.07× baseline	33.47355 0.99× baseline	77.898133 0.27× baseline	19.386902 1.14× baseline	85.97189 1.05× baseline	4251.332962 5.09× baseline	40.0 0.07× baseline	195.039613 5.20× baseline	Proximal muscle weakness · mild Arterial calcification · moderate Left ventricular hypertrophy · mild
SLC20A1 gain-of-function drives Vascular Calcification	17812.834851 0.94× baseline	648.948435 1.13× baseline	203.074111 1.84× baseline	0.005013 1.00× baseline	0.002204 1.07× baseline	33.47355 0.99× baseline	77.898133 0.27× baseline	19.386902 1.14× baseline	85.97189 1.05× baseline	8675.143252 10.39× baseline	200.0 0.33× baseline	397.988318 10.61× baseline	Proximal muscle weakness · mild Arterial calcification · severe Left ventricular hypertrophy · moderate Calcinosis cutis · calciphylaxis risk
SOST loss-of-function drives Bone-Vascular Paradox (Sclerostin/Wnt Axis)	17812.834709 0.94× baseline	648.948435 1.13× baseline	203.074111 1.84× baseline	0.005013 1.00× baseline	0.002204 1.07× baseline	33.47355 0.99× baseline	77.898133 0.27× baseline	19.386902 1.14× baseline	85.97189 1.05× baseline	291.290669 0.35× baseline	200.0 0.33× baseline	132.664369 3.54× baseline	Proximal muscle weakness · mild Arterial calcification · mild Left ventricular hypertrophy · mild
GPD1 loss-of-function drives Kidney Glycolysis-G3P Phosphate Sensing	18843.300911 1.00× baseline	646.67696 1.13× baseline	65.9649 0.60× baseline	0.005013 1.00× baseline	0.002127 1.03× baseline	33.589485 1.00× baseline	294.720957 1.02× baseline	19.252363 1.13× baseline	82.813551 1.02× baseline	2842.651477 3.40× baseline	200.0 0.33× baseline	130.418743 3.48× baseline	Arterial calcification · mild Left ventricular hypertrophy · mild
High-phosphate diet drives Phosphate Retention and FGF23 Axis	17619.134077 0.93× baseline	730.84001 1.27× baseline	209.676269 1.90× baseline	0.005013 1.00× baseline	0.002219 1.08× baseline	33.448603 0.99× baseline	34.348987 0.12× baseline	21.849642 1.28× baseline	86.582675 1.06× baseline	4389.130844 5.26× baseline	200.0 0.33× baseline	202.754688 5.41× baseline	Proximal muscle weakness · moderate Arterial calcification · moderate Left ventricular hypertrophy · moderate
Low-calcium diet drives Calcitriol Deficiency	17792.156667 0.94× baseline	648.947736 1.13× baseline	203.076557 1.84× baseline	0.005013 1.00× baseline	0.002204 1.07× baseline	33.472029 0.99× baseline	77.879588 0.27× baseline	19.387762 1.14× baseline	86.003448 1.05× baseline	2894.663606 3.47× baseline	200.0 0.33× baseline	132.696525 3.54× baseline	Proximal muscle weakness · mild Arterial calcification · mild Left ventricular hypertrophy · mild
Phosphate binder therapy drives Phosphate Retention and FGF23 Axis	17468.987881 0.92× baseline	685.106944 1.19× baseline	261.596937 2.37× baseline	0.005013 1.00× baseline	0.002255 1.09× baseline	33.40361 0.99× baseline	39.530871 0.14× baseline	20.509967 1.20× baseline	87.520513 1.07× baseline	4248.293313 5.09× baseline	100.0 0.17× baseline	199.667166 5.33× baseline	Proximal muscle weakness · moderate Arterial calcification · moderate Left ventricular hypertrophy · mild
Calcimimetic (cinacalcet) drives Secondary Hyperparathyroidism	17397.732522 0.92× baseline	765.818913 1.33× baseline	271.367761 2.46× baseline	0.005013 1.00× baseline	0.002246 1.09× baseline	33.337729 0.99× baseline	16.192413 0.06× baseline	22.971538 1.35× baseline	86.70348 1.06× baseline	5934.218003 7.11× baseline	100.0 0.17× baseline	281.703722 7.51× baseline	Proximal muscle weakness · moderate Arterial calcification · moderate Left ventricular hypertrophy · moderate Calcinosis cutis · calciphylaxis risk

Derived artifact, regenerated by just gen-model-results — not curated evidence. Values rounded to 6 decimals. Config e1f733a15766, model.xml c7382d2fa6c3. Phenotypes activate per the curated variable thresholds.

Phenotype thresholds

Phenotype	Variable	Direction	Threshold	Reading
Proximal muscle weakness	`Plasma_Calcitriol`	below	0.5	ratio of baseline
Reduced bone mineral density	`BMD`	below	0.85	ratio of baseline
Pathologic fracture	`BMD`	below	0.7	ratio of baseline
Short stature	`BMD`	below	0.75	ratio of baseline
Arterial calcification	`Vascular_Calcification`	above	50.0	absolute
Left ventricular hypertrophy	`Vascular_Calcification`	above	100.0	absolute
Calcinosis cutis	`Vascular_Calcification`	above	250.0	absolute

Gene effects

How config.yaml turns a gene perturbation into a model parameter change: the multiplier applied for a loss- or gain-of-function.

Gene	Parameter	Effect	Rationale
`CASR`	`T61`	LoF ×3.0, GoF ×0.3	CaSR controls PTH suppression floor (T61 = min PTH secretion rate). LoF raises floor → PTH stays high. GoF (calcimimetic) lowers floor → PTH suppressed.
`CYP27B1`	`None`	LoF ×0.3	1-alpha-hydroxylase initial activity
`CYP24A1`	`T69`	LoF ×0.2	Calcitriol degradation rate (B -> ; T69 * B)
`SLC20A1`	`kin_VascCa`	in_extension ×True, GoF ×3.0	Vascular phosphate uptake rate (Pit-1)
`KL`	`kin_Klotho`	in_extension ×True, LoF ×0.2	Klotho production rate
`SOST`	`kin_SOST`	in_extension ×True, LoF ×0.1	Sclerostin production rate
`GPD1`	`kin_FGF23`	in_extension ×True, LoF ×0.3	FGF23 production rate (G-3-P pathway)

Run it locally

uv run python -m dismech.perturb kb/disorders/CKD-Mineral_Bone_Disorder.yaml --alljust gen-model-results --id BIOMD0000000613

Files

config.yaml extension.ant model.xml