Bone Mineral Metabolism in Cancer

Recent Results in Cancer Research

Janusz Szymendera, V. G. Allfrey, M. Allgöwer, K. H. Bauer, V. G. Allfrey, M. Allgöwer, K. H. Bauer

• Éditeur: Butterworth-Heinemann
• Année: 2013
• ISBN:
  9781483193052
• Sujet: Medicine
• Sous-sujet: Oncology

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.

Chapter 1

General Outlines of Bone Tissue Metabolism

Publisher Summary

This chapter focuses on bone tissue metabolism. Bones are organized on two levels: (1) as organs and (2) as a tissue. As organs, they are particular elements of the skeleton adapted to withstand stresses; as a tissue, they form a highly specialized connective tissue composed of cells embedded in an interstitial substance, which includes the organic framework or matrix and the mineral. The chapter discusses the molecular structure and metabolism of the major parts of bone, namely, cells, organic matrix, and inorganic salts. Bone cells are organized in three compartments: (1) proliferating, (2) functional, and (3) a final-stage compartment. The interstitial organic substance or matrix consists of two major components: (1) collagen and (2) ground substance. The degradation of bone collagen to peptides and amino acids is mediated by proteolytic enzymes. The ground substance in which the cells and collagen are embedded consists of proteoglycans and glycoproteins. The time-dependent changes in the content of proteoglycans are because of their half-lives. The catabolism of sulphated glycosaminoglycans depends on the desulphation processes, followed by the degradation of the desulphated polymer. The inorganic portion of bone contains two major mineral phases: (1) amorphous or noncrystalline calcium phosphate and (2) crystalline bone apatite. Both the amorphous calcium phosphate and crystalline apatite are strongly hydrated; the volume of hydration shell is several times greater than that of mineral.

Bones are organized on two levels: as organs and as a tissue. As organs, they are particular elements of the skeleton adapted to withstand stresses; as a tissue, they form a highly specialized connective tissue composed of cells embedded in an interstitial substance, which includes the organic framework or matrix and the mineral. A brief account of what is known about the molecular structure and metabolism of the major parts of bone—cells, organic matrix and inorganic salts—seems advisable.

1 Structure and Function of Bone Cells

Bone cells are organized in three compartments: a proliferating, a functional, and a final-stage compartment (OWEN, 1963). The first compartment cells, the preosteoblasts, are reproducing themselves, and the second compartment cells may be either osteoblasts or osteoclasts. The final-stage cell of an osteoblast is the osteocyte (OWEN, 1963).

Osteoblasts and osteocytes have much the same fine structure and reveal the cytoplasmatic features of intense metabolic activity: they control the metabolism of collagen, proteoglycans and glycoproteins, as well as the mineral elements of bone tissue (BAUD, 1966). Osteoclasts, giant cells with a variable number of nuclei, produce organic acids, the agents of the solubilization of bone mineral, as well as acid hydrolases—the enzymes that digest organic matrix (VAES, 1966). There is good evidence to suggest that bone cells of all functional states stem from the preosteoblast (OWEN, 1963).

The differences in structure and metabolic activities of bone cells are associated with their specific function: osteoblasts with formation, osteocytes with maintenance, and osteoclasts with resorption of bone (BAUER et al., 1961).

2 Structure and Function of Bone Matrix

The interstitial organic substance or matrix consists of two major components: collagen and ground substance.

2.1 Collagen

Composition and Structure of Collagen

The collagenous framework of the bone tissue is composed of typical fibres having characteristic low-angle X-ray diffraction patterns and banded patterns in the electron microscope with a periodicity of 64—70 nm (RAMACHANDRAN, 1963). Each collagen fibre is composed of basic tropocollagen molecules having a molecular weight of 300,000 (BORNSTEIN and PIEZ, 1964), a length of 300 nm, and a diameter of 1.5—1.6 nm in the wet state (BEAR, 1952).

Tropocollagen is composed of three polypeptide alpha chains having the same molecular weight of about 100,000 The alpha 2 chain differs in its amino acid composition and chromatographic behaviour from the two alpha 1 chains (BORNSTEIN and PIEZ, 1964). The amino acid composition of alpha 1 and alpha 2 chains of human skin collagen—there are about 1,100 amino acid residues in each chain—is shown in Fig. 1.

Fig. 1 A comparison of the amino acid composition of alpha chains from human skin collagen. The values used for constructing this diagram were taken from BORNSTEIN and PIEZ (1964). 1° = 2.78 amino acid residues per 1000 total residues; I = Imino acids; II = Hydroxy amino acids; III = Acidic amino acids; IV = Basic amino acids; V = Aromatic amino acids

Significant differences may be found in the contents of proline, hydroxyproline, alanine, lysine and glutamic acid (more in alpha 1 chain) and hydroxylysine, histidine, leucine, isoleucine, valine and tyrosine (more in alpha 2 chain) in comparing both chains (BORNSTEIN and PIEZ, 1964). The findings that collagen from codfish skin contains three different, chromatographically separable alpha chains (PIEZ, 1964), that the fragments produced by cleavage of the methionyl bonds in the alpha 1 chains demonstrate large variations in their amino acid composition (BORNSTEIN and PIEZ, 1965), and that the primary structure of collagen is heterogeneous as a consequence of the incomplete hydroxylation of individual prolyl residues in collagen (BORNSTEIN, 1967)—all indicate that alpha 1 chains are not identical. Moreover, the finding of large variations in amino acid composition in the fragments produced by cleavage of the methionyl bonds indicates that the amino acid sequence of each of the alpha chains is unique throughout its length (BORNSTEIN and PIEZ, 1965). It contradicts the model of collagen structure proposed by PETRUSKA and HODGE (1964) based on identical intrachain subunits.

The alpha chains of the tropocollagen molecule have a discernible recurrence of certain similar sequences of amino acids. These sequences are found in the crystalline or non-polar regions. The non-polar regions alternate with a large pol...