ReviewThe biological role of strontium
Introduction
Strontium (Sr) in human biology and pathology has attracted less attention than the other two important divalent metals calcium and magnesium, and over the years been an object of academic rather than clinical interest. Although this is still true, there is an increasing awareness of the biological role of Sr after the development of the drug strontium ranelate, which has recently been shown to reduce the incidence of fractures in osteoporotic patients [39], [40], [49]. Important contribution to the knowledge of Sr was obtained in the 1950s and 1960s. A comprehensive review on Sr was published 1964 [18]. The present updated review deals with normal functions of stable Sr, and covers areas of bone physiology in a broad sense inclusive of chemistry, toxicity, nutrition, intestinal absorption, renal excretion, homeostasis, and role in heart and muscle function. It summarises older and more recent publications relevant to medicine. Cellular and subcellular functions of Sr are not described in any detail.
Section snippets
Chemistry
Sr was discovered in 1790 in a mine near the Scottish village Strontian and was isolated 1808. Sr is one of the alkaline earth metals. It never occurs free in nature, because metallic Sr oxidises easily forming strontium oxide, which has a yellowish colour. Sr is well known from the minerals celestite (SrSO4) and strontianite (SrCO3). Natural Sr is a mixture of four stable isotopes: 84Sr (0.56%), 86Sr (9.86%), 87Sr (7.02%), and 88Sr (82.56%). The elements of group 2 of the periodic system, to
Strontium sources
Sr comprises 0.02–0.03% of the earth's crust, from where the Sr of water derives. Sr is widely available. Its concentration in soil and drinking water varies between 0.001 and 39 mg/l, and in the United States, the concentration of Sr in drinking water is <1 mg/l [60]. A normal diet contains 2–4 mg Sr/day, most of it derived from vegetables and cereals. Thus, the amount of Sr in food of Western countries is negligible compared to Ca. The intake of Sr depends on the Sr contents of the diet, and
Strontium deficiency
Sr has never been shown to be an essential element, that is, causing death when absent, but Sr may in some plants promote growth [6]. Caries prevalence is inversely related to Sr levels in water, plaque, and enamel [21]. Administration of Sr in moderate doses prevented caries in rats [22]. The complicated issue of Sr and caries was reviewed 1983 [57].
Since Sr given as strontium ranelate augments bone Ca in experimental animals and reduces fracture rate in osteoporotic patients, it could be
Strontium toxicity
Toxic symptoms due to overdosing of Sr have not been reported in man. However, intravenous administration of high doses of Sr induces hypocalcaemia due to increased renal excretion of Ca [41], [52]. Farm animals have been studied intensively. Clearly, dietary Sr can vary widely without toxic symptoms appearing. Young pigs fed 6700 ppm Sr and 0.16% Ca suffered from incoordination and weakness followed by posterior paralysis [2]. Mature hens seem more resistant, egg weight and egg production
Intestinal absorption
Normally, Ca/Sr discrimination occurs under physiological circumstances for the following functions: gastrointestinal absorption, renal excretion, placental transfer, and mammary secretion [17]. Generally, Sr is poorly absorbed in the intestinal tract. Intestinal Sr absorption in rats decreases with age, but whether this is the case with humans is unknown. Vitamin D promotes intestinal Sr absorption, and Ca inhibits it. Lactose and other carbohydrates can promote both Sr and Ca absorption. Most
Strontium in muscles
Ca directly activated the release of Sr from the sarcoplasmatic reticulum of rat cardiac ventricular myocytes [55] in studies of the effect of Sr ions on Ca-dependent feedback mechanisms during excitation–contraction coupling. In an investigation on the intracellular pathway of the acetylcholine-provoked contraction in cat detrusor muscle cells, Sr which depletes or blocks intracellular Ca release, inhibited acetylcholine-induced contraction [1]. Activation of smooth muscle is normally
Renal handling of strontium
Ca and Sr seem to share a common tubular transport path in the renal tubules [64]. Sr in suspended renal proximal tubular cells inhibited PTH-dependent cyclic AMP production, like did Ca, at concentrations up to 10 mM [37]. The renal clearance of Sr is around three times that of Ca, perhaps due to smaller tubular reabsorption, which again might be due the larger size of the Sr atom vs. that of Ca. This is one of many examples showing that studies with radiostrontium should be used and
Isolated systems
Sr in many pharmacological investigations using isolated cells or organs often mimics the actions of Ca, although the response to stimulation tends to be weaker. The following examples illustrate this: (A) Sr sustains secretion of insulin as a response to glucose in isolated systems of pancreatic islets, although to a lesser extent than Ca [34]; (B) Sr2+ is effective in restoring the insulin-mediated glucose cell uptake after deprivation of Ca2+ and Mg2+ from the medium in isolated fat cells,
Strontium in bone
The amount of Sr in the skeleton is only 0.035 of its Ca content [28]. Radiostrontium is cleared from the blood almost immediately after injection. 85Sr passes the walls of Haversian capillaries by diffusion to reach bone extracellular fluid [23]. Administered Sr is almost exclusively deposited in bone [43]. Na, Pb, and Sr can be substituted in the Ca positions of apatite [61]. Radiostrontium has been used as a tracer for Ca in kinetic studies although radiocalcium and radiostrontium behave
Homeostatic control
It appears from animal studies that Sr can substitute for Ca in many physiological processes. These include muscular contraction and blood clotting, which are provoked by Sr as well as by Ca, but to a lesser degree. It seems that whenever there is an active transport across biological membranes, for example, in gastrointestinal absorption, renal excretion, lactation, and placental passage, Ca is transported more easily than Sr [58].
Conversely to Ca, Sr is not under homeostatic control in the
References (66)
- et al.
Toxic effects of stable strontium in young pigs
J. Nutr
(1961) - et al.
The divalent strontium salt S 12911 enhances bone cell replication and bone formation in vitro
Bone
(1996) - et al.
Experimental epiphyseal cartilage anomalies by dietary strontium
Poult. Sci
(1972) - et al.
Long-term treatment with strontium ranelate increases vertebral bone mass without deleterious effect in mice
Metabolism
(2002) - et al.
Absorption of Ca45 and Sr85 from solid and liquid food at various levels of the alimentary tract of the rat
J. Nutr
(1962) - et al.
Effects of strontium on calcium metabolism in rats: I. A distinction between pharmacologic and toxic doses
Jpn. J. Pharmacol
(1994) - et al.
Effects of strontium on calcium metabolism in rats: II. Strontium prevents the increased rate of bone turnover in ovariectomised rats
Jpn. J. Pharmacol
(1995) - et al.
Rachitogenic activity of dietary strontium: distribution of intestinal calcium absorption and 1,25 dihydroxycholecalciferol synthesis
J. Biol. Chem
(1972) - et al.
Strontium causes osteomalacia in chronic renal failure rats
Kidney Int
(1998) - et al.
Dose-dependent effects of strontium on osteoblast function and mineralisation
Kidney Int
(2003)