A Clinical--Metabolic Approach to Determining Calcium Requirements: Interplay of the Glucose Axis, PTH--Vitamin D Signalling and Bone Mineral Density

Calcium homeostasis is maintained by an endocrine network comprising parathyroid hormone (PTH), calcitriol and calcitonin, which defends serum calcium at the expense of skeletal reserves. Serum calcium is therefore an unreliable indicator of nutritional calcium status, and empirical supplementation remains common. This narrative review proposes a clinical–metabolic approach to estimating individual calcium requirements that integrates bone mineral density (BMD), vitamin D status and the compensatory PTH response. We make three contributions. First, we present a sigmoidal phosphate–PTH model in which a glucose-dependent gain term ($\mathrm{\Delta }{k}_{\mathrm{g}\mathrm{l}\mathrm{u}\mathrm{c}}$) captures the heightened parathyroid sensitivity associated with dysglycaemia, and we illustrate it with simulated values for healthy adults, women and individuals with gluco-osteoporosis. Second, we translate the model into a four-step decision algorithm that frames the intake gap as a net balance of intestinal absorption, renal excretion and bone turnover. Third, we incorporate the osteocyte–osteoblast bioenergetic axis (sclerostin/Wnt signalling, GLUT1-mediated glucose uptake, aerobic glycolysis and osteocalcin–insulin crosstalk) to explain why calcium supplementation may be ineffective when cellular energy supply or insulin sensitivity is impaired. The framework aims to prevent secondary hyperparathyroidism, avoid over supplementation and preserve skeletal integrity. The model values are simulated and require prospective clinical validation.