A nonlinear compartmental model of Sr metabolism. II. Its physiological relevance for Ca metabolism

Abstract

We have studied the peculiarities of the nonlinear compartmental model for human Sr metabolism (Staub JF, Foos E, Courtin B, Jochemsen R, and Perault-Staub AM. Am J Physiol Regul Integr Comp Physiol 284: R819-R834, 2003), including its physiological reliability in the context of Sr-Ca similarity-dissimilarity. We found it to be relevant to Ca metabolism, except for discrimination against Sr relative to Ca at urinary and intestinal levels. The main findings are as follows: 1) the saturable part of intestinal absorption, shared by Sr and Ca, does not seem to be responsible for the discrimination of the transcellular pathway; 2) although there is little discrimination in bone, the physicochemical behaviors of Sr and Ca at the bone surface differ, at least quantitatively; and 3) Sr behaves as a "tracer" for Ca metabolic pathways and, under non-steady-state conditions, can also reveal self-regulatory processes. It is suggested that they depend on Ca2+ (cationic)-sensing receptors that are apparently more sensitive to Sr than to Ca. Acting on gastrointestinal and osteoblast lineage cells, these slow processes might contribute to adaptive, rather than homeostatic, regulation of Ca metabolism. Understanding these features could help clarify the pharmacological and therapeutic effects of oral Sr.

Moderate Strontium Loading Induces Rickets in Rats with Mild Chronic Renal Failure

“…Intestinal and renal calcium-specific channels as well as a variety of intracellular Ca-binding proteins showed significantly lower affinity for Sr binding [22][23][24] . Beyond this, in the presence of normal Sr levels, the extracellular concentration of calcium exceeds Sr by several orders of magnitude, thereby lowering the probability for Sr uptake [22] . While under physiological conditions these mechanisms are sufficient to prevent Sr-related deleterious effects, they likely become exhausted under conditions of continuous Sr loading in combination with impaired renal excretion.…”

“…The utilization of Sr for this purpose is of special interest, as Sr is a natural constituent of food and beverages. Calcium and Sr belong to the alkaline earth series and both cations possess quite similar chemical properties (ionic radius, charge-to-size ratio, coordination number), which translate into rather comparable interactions with organic and inorganic components [22] . While their major metabolic pathways related to gastrointestinal uptake and excretion probably utilize similar if not at all identical processes, at the cellular level discrimination between both cations occurs [22] .…”

“…Calcium and Sr belong to the alkaline earth series and both cations possess quite similar chemical properties (ionic radius, charge-to-size ratio, coordination number), which translate into rather comparable interactions with organic and inorganic components [22] . While their major metabolic pathways related to gastrointestinal uptake and excretion probably utilize similar if not at all identical processes, at the cellular level discrimination between both cations occurs [22] . Intestinal and renal calcium-specific channels as well as a variety of intracellular Ca-binding proteins showed significantly lower affinity for Sr binding [22][23][24] .…”

“…While their major metabolic pathways related to gastrointestinal uptake and excretion probably utilize similar if not at all identical processes, at the cellular level discrimination between both cations occurs [22] . Intestinal and renal calcium-specific channels as well as a variety of intracellular Ca-binding proteins showed significantly lower affinity for Sr binding [22][23][24] . Beyond this, in the presence of normal Sr levels, the extracellular concentration of calcium exceeds Sr by several orders of magnitude, thereby lowering the probability for Sr uptake [22] .…”

“…Although Sr is grossly excluded from properly crystallized apatite, at high concentrations it may replace calcium secondary to heteroionic exchange [6] . This replacement will result in a slight deformation of the crystal lattice, which in turn will ease subsequent Sr incorporation [22,25,26] . In the long run, this may decrease skeletal calcium content.…”