Multiscale physiology-based modeling of mineral bone disorder in patients with impaired kidney function.
A physiologically based, multiscale model of calcium homeostasis and bone remodeling was used to describe the impact of progressive loss of kidney function over a typical 10-year course of chronic kidney disease (CKD), including the evolution of secondary hyperparathyroidism (HPT) caused by diminished renal phosphate clearance and increased plasma phosphate. An important sequela of HPT is marked elevations in bone resorption and loss of bone mineral density (BMD). Clinically, this CKD-related disease state is described as mineral bone disorder, or CKD-MBD. A multiscale physiologic model previously had been shown to describe CKD-MBD-related clinical changes in phosphate, parathyroid hormone (PTH), and calcitriol. The authors have extended the model to link bone remodeling markers with BMD elimination (0.000145 h(-1)) and formation rates. The composite model predicted lumbar spine BMD losses, relative to baseline, at months 28 (glomerular filtration rate = 58 mL/min), 50 (39 mL/min), and 120 (16 mL/min) of approximately -0.98%, -3.0%, and -6.5%, respectively, compared to the observed BMD values in corresponding renal function groups, scaled to a 100-mL/min baseline, of -0.5%, -4.0%, and -8.1%, respectively. In addition, simulated interventions with a hypothetical calcimimetic agent and calcitriol are provided to show the utility of this model as a platform for evaluating therapeutics.
Metrum Research Group LLC, Tariffville, Tariffville, CT 06081, USA. mattr@metrumrg.com
Matthew M
MM
Riggs
Mark C
MC
Peterson
Marc R
MR
Gastonguay
D015519:Bone Density; D001847:Bone Diseases / Q000378:metabolism / Q000503:physiopathology*; D016723:Bone Remodeling; D002118:Calcium / Q000378:metabolism*; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology*; D008954:Models, Biological; D010710:Phosphates / Q000378:metabolism
D010710:Phosphates; D002118:Calcium