Skeletal Dynamics in Man Measured by Nonradioactive Strontium*

Abstract

A great deal of useful information about calcium metabolism in man has been obtained by balance technics. Balance studies give only net changes in total body calcium and do not indicate whether changes in balance result from alterations of rates of movement into or out of bone. For example, positive balance could result from increased bone deposition or decreased bone resorption. Similarly, balance could be unchanged if increased resorption were matched by increased deposition. Rates of bone deposition have been measured in man using Ca45 and Ca47 as tracers (1-1 1). Isotopes of strontium have been similarly used (5,6,8,(11)(12)(13)(14)(15)(16), since strontium is a boneseeking element whose distribution in the body is similar to that of calcium. Accumulated experience suggests that cautious use of these boneseeking radionuclides in human subjects is without demonstrable risk. Nevertheless, this experience is still limited both in numbers of subjects and length of observation. In a study of Sr90 toxicity in mice, a direct linear relationship was noted between total internal radiation dose from Sr90 and decrease in survival time and tumor production (17 individual under varied conditions. This possibility is the subject of the present investigation. The results indicate that nonradioactive strontium can be used to detect alterations of skeletal metabolism in various defined physiological and pathological states. METHODSThe following subj ects were studied: 25 healthy persons at ordinary activity (including 11 inmates of San Quentin Prison; 31 studies) 14 athletes (all members of the San Quentin Prison football team) ; 11 patients with idiopathic nephrolithiasis; 28 with primary hyperparathyroidism (4 with skeletal disease shown by elevated serum alkaline phosphatase levels or roentgenographic evidence of skeletal involvement or both; 17 with normal phosphatase and X-ray appearance but with microscopic foci of resorption seen in bone biopsy; and 7 with normal phosphatase, X-ray appearance and bone biopsy); 7 with hyperthyroidism; 8 with acromegaly; 3 with hyperadrenocorticism; 26 with advanced, unequivocal postmenopausal or senile osteoporosis (40 studies); 5 with Paget's disease of bone; and 1 with chronic vitamin D overdose. The reproducibility of the method was tested by 21 duplicate tests in osteoporotic and normal subjects. All subjects were on diets free of milk and cheese except the prisoners, whose fare was unrestricted. All subjects were ambulatory.Significant dietary strontium was excluded by checking initial blood and urine specimens. Then 10.0 mEq of strontium gluconate' was infused intravenously over a period of 10 minutes. Blood samples were taken every 24 hours and 24-hour urine specimens were collected for 4 to 6 days.All specimens were collected in acid-washed glassware. All determinations were done in duplicate. Serum and urine calcium levels were determined on a flame spectrophotometer by the method of Maclntyre (18). Serum strontium was measured by diluting 1.0 ml of serum with 3 ml of an aqueo...

Direct Measurement of Osteolysis in Man

“…At least in the short term (the present study being conducted during the first 10 days of treatment) there is an elevation in Va noted in all four subjects; on the other hand, Wajchenberg, Pereira, Kieffer, and Ursic (23) noted a decrease in the fraction of dietary calcium absorbed after prolonged treatment (18 days) although their subjects varied their calcium intake between control and treatment periods and may have had an increased absolute value for Va. Also, there appears to be an increase in vt with treatment without any significant change in pool size (M1 + M2) being noted. No significant change in v,+ was apparent in the present studies, but Eisenberg (29) found it to be elevated after 6 wk of glucocorticoid therapy; however, Eisenberg and Gordan (21) Vw.. In any event, short-term glucocorticoid treatment did not increase the ratio of bone resorption to rapidly miscible pool turnover.…”

“…In early studies (19)(20)(21) Cae was often simplified to a single compartment, but it became apparent that at least two compartments were required to fit the first 10 days of data and compensate for excessive excretion of tracer during the intitial mixing phases (14). Three compartments have also been used (20, 22, (24) used PTA data for 20 days and included a slower fourth compartment in their analyses, as also considered by others (5,20).…”

Effect of sex hormones on bone in primary osteoporosis

“…By estimating the rate of resorption in the rib from knowledge of the bone formation rate and the rib porosity, Wu, Jett, and Frost (12) found an absolute increase in endosteal resorption rate (the process accounting for most of the resorption in the vertebrae), although the intracortical resorption rate was found to be lower than normal. Studies with bone-seeking isotopes have shown that skeletal mineral accretion is normal or is decreased in proportion to the decreased skeletal mass (13)(14)(15)(16)(17).…”

Strontium and Its Relation to Calcium Metabolism*

“…It was thought that radioactive strontium (Srr), which was more readily available and which can be detected more simply, might serve as a substitute tracer for Car. Early experiments (1)(2)(3) confirmed this notion in a general way, and several investigators (4)(5)(6)(7) have subsequently proceeded on the assumption that Sr behaves like Ca in the body. Although the urinary excretions of Sr and Ca were found to differ, it has been assumed or demonstrated that as far as the skeleton is concerned, differences in the biological behavior of Ca and Sr are small and perhaps negligible (4,(8)(9)(10)(11)(12)(13)(14)(15).…”

“…Sr occurs in the body in only very small quantities, and its concentration in various tissues is known with only moderate precision (22). Analytical techniques for precisely analyzing small quantities of Sr have been developed only recently (5,7,23). In contrast with Ca studies, Sr concentration in kinetic studies with Srr has generally not been expressed in terms of specific activity (units of radioactivity per unit of mass), the only valid independent parameter.…”