Remodelling of the Bone Matrix 23 



dominant. The newly formed collagen molecules are degraded to a large extent 

 before their incorporation in organized fibers. This is represented schematically in 

 Fig. 1 by a pathway passing from Ij to N, and D^ . In remodelling tissues, the newly 

 synthesized molecules are used for building new fibers while the pre-existing old 

 fibers become solubilized and lysed. The net result is that the newly formed collagen 

 remains for a much longer time In the pool of the fibers. It is represented In Fig. 1 by 

 a metabolic pathway starting at Ij and passing from Ni to Ng to finish at D, . 



These metabolic pathways are based on the extractablllty of the collagen. This 

 property depends on the stability of the structured fibers which seems to be a func- 

 tion of Intermolecular bonds. Maturation processes occuring also at the molecular 

 level have been demonstrated by Orheckowitch et al. (1960) and PiEZ et al. (1961). 



Since the work of Neuberger and Slack (1953) It is known that bone has a 

 collagen metabolism as active as any other connective tissue. Further studies (Flana- 

 gan and Nichols, 1964) have shown that bone Is potentially capable of synthesizing 

 significant amounts of protein. This overall metabolic activity of bone has not been 

 analysed In the same way as that In soft connective tissue. Indeed the collagen of 

 normal bone cannot be usefully fractionated by salt solutions of different Ionic 

 strength or pH. 



Some metabolic studies using salt fractionation of the collagen have however been 

 made in animals treated with lathyrltlc drugs. In this experimental condition more 

 collagen Is extractable In cold hypertonic saline (Levene and Gross, 1959). This 

 seems to be related to some abnormality of the process of maturation of the collagen 

 molecule, which lacks Intramolecular bonds (Martin et al., 1961) and forms unstable 

 aggregates (Gross, 1963 a). Isotope Incorporation studies (Tanzer and Gross, 1964) 

 demonstrate that the collagen In lathyrltic bone Is heterogenous, suggesting that 

 lathyrltlc collagen originates from 2 or more collagen pools. 



The problem in studying the metabolism of bone arises from the complexity of 

 this biological material. It is composed of elements of different age. Each of them 

 consists of different layers of calcified collagen which have been formed by the pro- 

 gressive deposition of the matrix and the crystals. Obvious differences in the meta- 

 bolic activity of the mineral part of these units can be demonstrated either by mlcro- 

 radlographlc or autohlstoradiographic techniques (Marshall et al., 1959; McLean 

 and Rowland, 1963). Simultaneously with different degree of mineralization, the 

 density of the organic matrix Is also variable from one osteon to the other and 

 within the same element from the center to the periphery (Smith, 1963). In these 

 elementary units of bone the collagen layers vary In direction from the central cavity 

 to the compact peripheral tissue (Glimcher, 1959). These elementary units of bone 

 can be divided Into different regions according to their density of calcification 

 (Robinson, 1960). This author calculated for different regions of an osteon the 

 probable concentration of Its components. Fie proposed a model In which a unit 

 volume of bone of different degrees of calcification would have an amount of matrix 

 almost constant while the relative proportion of calcium and water would vary In 

 opposite direction one to the other. On this hypothesis, Herman and Richelle 

 (1961) have calculated that the density of bone from different regions would range 

 from 1.7 to 2.3. They designed a technique to separate these constituents of bone 

 according to their stage of calcification. Samples of bone are finely ground in a high 

 speed specially designed grinder. The fine particles (about 5 // large) are separated 



