Bone Mineral Metabolism in Cancer (eBook)

Recent Results in Cancer Research

Janusz Szymendera (Autor)

V. G. Allfrey, M. Allgower, K. H. Bauer (Herausgeber)

eBook Download: EPUB

2013 | 1. Auflage
118 Seiten
Elsevier Science (Verlag)
978-1-4831-9305-2 (ISBN)

Infos

Recent Results in Cancer Research: Bone Mineral Metabolism in Cancer presents the clinical approach to bone tissue metabolism, which depends on studying the plasma state, renal handling, kinetics, and balance of calcium and inorganic phosphate. This book discusses the problems of bone mineral metabolism in patients with cancer. Organized into five chapters, this book begins with an overview of the two major phases of bone mineral, namely, amorphous calcium phosphate and crystalline bone apatite. This text then examines the plasma state and renal handling of calcium and inorganic phosphate under controlled metabolic conditions. Other chapters consider the variability of each parameter in the majority of patients without bone secondaries. This book discusses as well the normal remodeling of bone in fertile-age women. The final chapter deals with the plasma state, renal handling, and kinetics of calcium and phosphate in plasmacytoma patients. This book is a valuable resource for oncologists.

Textauszug

Chapter 2

General Outlines of a Clinical Approach to Bone Tissue Metabolism

Publisher Summary

The content of mineral relative to organic matrix in bone is remarkably constant under physiological and most pathological conditions as bone tissue is being formed and resorbed in toto. This chapter describes the major pathways of calcium metabolism. It illustrates general relations between absorption of ingested and digestive juice calcium and excretion of endogenous and exogenous faecal calcium. The study of the rate of calcium accretion cannot be carried out by conventional techniques and requires the use of tracer kinetics. Body calcium represents two distinct and essentially independent moieties: (1) an exchangeable calcium pool and (2) a nonexchangeable calcium pool. The chapter illustrates a two-compartmental open system model of calcium turnover, compatible with a two-exponential plasma disappearance curve of calcium tracer. Parathyroid hormone (PTH) and thyrocalcitonin (TCT) are the two parts of a dual hormonal mechanism in the homeostatic regulation of ionized calcium concentration in the blood plasma. The major pathways of inorganic phosphate metabolism resemble those of calcium metabolism, though they differ in several points quantitatively. The chapter presents the relationship between the various forms of collagen and the urinary excretion of hydroxyproline. In the living organism, pyrophosphate has the role of a calcification regulator.

The content of mineral relative to organic matrix in bone is remarkably constant under physiological and most pathological conditions, since bone tissue is being formed and resorbed in toto (BAUER et al., 1961). Theoretically, there should be no difference in quantifying the bone tissue metabolism, irrespective of whether the bone mineral or the organic matrix is studied. In practice, at least in man, only the bone calcium metabolism is readily available for quantitative measurements, owing to the lack of any significant calcium stores besides the skeleton that could influence the overall metabolism of this element (HEANEY, 1964). On the other hand, it is practically impossible to measure the bone metabolism of inorganic phosphate, the counter ion of calcium, since the large amounts of organic tissue phosphates strongly interfere (BAUER et al., 1961).

Also the metabolism of bone matrix cannot be strictly quantified, owing to interference of collagen from other stores of connective tissue. Hence, the urinary excretion of hydroxyproline is assumed to be an index only, and not the measure, of bone collagen metabolism (PROCKOP and KIVIRIKKO, 1967). The same goes for the urinary excretion of pyrophosphate, the anion regulating the process of mineralization (FLEISCH et al., 1966).

Some of the most important features of calcium metabolism (plasma state, renal handling, net absorption and faecal output), the major features of phosphate metabolism (plasma state and renal handling), and the urinary excretion of hydroxyproline and pyrophosphate—may be investigated by conventional techniques. The remaining data of prime importance, that is, the rates of new bone formation and bone resorption, the true absorption of calcium in the gastrointestinal tract, and the excretion of endogenous calcium in faeces—cannot be obtained by these techniques and require the application of methods making use of tracers. Tracer methodology depends on the assumption that the atoms of the injected isotope of calcium, or any other tracer, behave exactly like the atoms of natural element, the tracee (BROWNELL et al., 1968), and that the system under study cannot discriminate between them (SOLOMON, 1960).

1 Calcium Metabolism

The major pathways of calcium metabolism may be outlined as in Fig 8.

Fig. 8 General scheme of calcium metabolism. The gastrointestinal (GI) tract, exchangeable calcium in extracellular fluid, cells and bone, and nonexchangeable calcium in bone are represented

A fraction of the ingested calcium is absorbed in the small intestine, and the remainder passes through the gastrointestinal tract and is excreted in the faeces without having been absorbed. Similarly, of the calcium secreted with the digestive juices, a fraction is reabsorbed, and the remainder appears in the faeces. Calcium circulating in body fluids is maintained at a constant level in equilibrium with its levels in the intracellular fluid and in the exchangeable bone mineral. Calcium is accreted in bone tissue in the process of new bone formation or remodelling, and resorbed from bone tissue in the process of bone destruction. The loss of endogenous calcium in the urine and faeces is compensated for by an equivalent intake of this element.

 

Calcium Absorption

The fate of calcium in the gastrointestinal tract is indicated in Figure 9.

Fig. 9 General relations between absorption of ingested and digestive juice calcium and excretion of endogenous and exogenous faecal calcium

Daily ingested calcium Vi and that entering the gut with digestive juices Vd, both being only partially absorbed from the intestinal lumen, add to the unabsorbed element that appears in faeces VF. The difference between the rates of intake and faecal output, the net absorption rate Va(net), is given by the formula:

(1)

It may be obtained by simple determination of calcium in the food and faeces sampled on a time basis, that is, over an appropriate balance periode timed with time-markers (REIFENSTEIN et al., 1945).

By subtracting the excretion rate of endogenous faecal calcium Vf from the excretion rate of total faecal calcium, the excretion rate of exogenous faecal calcium β Vi is obtained:

(2)

The endogenous faecal calcium denotes calcium secreted into the gut with digestive juices and then excreted in the faeces, excluding that secreted into the gut and then reabsorbed. The excretion rate of endogenous faecal calcium is calculated from the amount of tracer excreted in faeces following its intravenous administration, since, being administered intravenously, all tracer in faeces is endogenous. Assuming the specific activity of calcium secreted into the gut and excreted in urine at the same time interval to be identical, the excretion rate of endogenous faecal calcium may be obtained by the formula of AUBERT and MILHAUD (1960):

(3)

where Vu = excretion rate of urinary calcium, ffaeces = fraction of tracer excreted in faeces, and furine = fraction excreted in urine, both accurately timed with a correction for faecal lag (cf. BRONNER et al., 1962):

(4)

Calcium secreted into the gut and then reabsorbed cannot be obtained in vivo, since its fractional reabsorption rate β Vd is not observable even with the aid of isotopes (MARSHALL, 1964).

The rate of entry of the radioisotope from the intestinal tract into the vascular system is usually given as the integrated steady state rate of absorption from the entire gut. Recently, HART and SPENCER (1967) studied the initial entry rate of the tracer, i. e. entry of the tracer from one compartment into another compartment of the system, without consideration of recirculation or feedback; this reflects the gradual passage of the remaining unabsorbed dose of tracer through different portions of the intestinal tract, exhibiting different transport activity (HART and SPENCER, 1967). The appearance of the tracer in the vascular space can be expressed by the Volterra integral equation:

(5)

in which G(t) is the plasma activity curve following an oral tracer dose at time t0 = 0; B(τ) is the rate of initial entry at time τ following an oral tracer dose, at which the tracer first appears in the vascular system; F(t) is the plasma activity curve following intravenous tracer administration (HART and SPENCER, 1967). Since G(t) and F(t) are determined experimentally, the integral equation can be solved by standard means, and B(τ) determined either analytically (BERKOWITZ et al., 1963; HART and SPENCER, 1967) or by a computer (HART and SPENCER, 1967).

Figure 10 illustrates a typical result for the initial entry functions from the intestine into the vascular system for 15 minutes intervals employed in the calculations (HART and SPENCER, 1967). The integrated area under the curve gives the cumulative absorption for tracer, identical with that obtained in above test on true absorption.

Fig. 10 Rate of initial entry of radiocalcium from the intestine into the vascular space. (From HART and SPENCER, 1967)

Detailed studies on the transport of calcium across the intestinal wall have led to the conclusion that calcium absorption is not due solely to passive diffusion, but that there is an...

Produkt-Details

• Erscheint lt. Verlag: 22.10.2013
• Sprache: englisch
• Themenwelt: Medizinische Fachgebiete ► Chirurgie ► Unfallchirurgie / Orthopädie
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Onkologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• ISBN-10: 1-4831-9305-5 / 1483193055
• ISBN-13: 978-1-4831-9305-2 / 9781483193052