Regulative and adaptive factors in craniofacial growth

ANNALS OF ANATOMY

Regulative and adaptive factors in craniofacial growth Gert-Horst Schumacher Department of Anatomy, University of Rostock, Gertrudenstraf3e 9, D-18055 Rostock, Germany

Summary. Generally speaking, the animal experimental models described here are of theoretical importance. They fall naturally into the area of formulating general trends. Following elucidation of a series of concerns in the future, theoretical growth research will be able to provide more directly clinically applicable tools. Since no experimental animals of the masticatory type analogous to humans exist, results from animal experiments should be considered as statements on the biological reactions of analogous biological systems. Last but not least, biomechanical model representations point to the growth controlling functions of the bony and muscular head system components. These may provide an example for the analysis of degenerative changes in other parts ot the body and serve as a theoretical basis for targeted therapeutic measures.

Key words: Craniofacial growth - Regulative factors Adaptation - Animal models

Osteogenesis of the skull The bones of the skull are known to develop by chondral and desmal ossification. Chondral ossification starts at the chondrocranium, which arises from the fusion of several cartilage elements at the anterior end of the notochord as well as from the cranial somites, the cartilaginous ear and cartilaginous nose capsules (Fig. 1). The ossification emanates from several centers which differentiate in all directions. Any cartilage remaining between the bones in the form of synchondroses acts as a growth center in a similar way to the epiphysial plates of hollow bones. By about the age of 20 years, the synchondroses have completely ossified. The desmocranium is that part of the skull which ossifies directly out of the connective tissue. The bones of the roof of the skull, the greater part of the nasal skeleton,

Ann Anat (1999) 181:9-13 © Urban & FischerVerlag

and the jaw apparatus, among other structures, arise from it. The bony nuclei proliferate, thereby reducing the amount of connective tissue remaining to small gaps, the sutures. Further bone growth can occur in the sutures up to young adulthood, as occurs similarly in the synchondroses, growth in thickness of the skull vault being from the periosteum.

Regulative factors Osteogenesis during craniofacial growth is controlled by a complicated mechanism based on a genetic program. The program may be influenced by exogenic factors. The extent to which this happens depends on the period of development and the intensity of the environmental influences. Factors affecting craniofacial growth can be divided into general and local factors (Fig. 2).

Head posture There are numerous references in the literature to the influence of head posture or changes in head posture on skull shape. The shaping of the skull in the course of phylogeny is related causally to the assumption of an upright mode of locomotion and posture, cerebralisation and reduction of the jaw (Fig. 3). Fanghfinel (1974) looked more closely into this phenomenon in a model study of the influence of statics on the shape of the skull in rats. The angle of inclination of the neuro- and viscerocranium to the base of the skull was taken to be the main reference value. In humans this is, relative to that of quadrupeds, fairly large, presumably because of the verticalization of the trunk, the increase in volume of the brain, and the frontal positioning of the eyes; this last being a consequence of stereotaxic vision.

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b Fig. 1. a) Ossification centers in a 5 cm embryo, b, c) Anlage and derivatives of the chondrocranium. 1 trabecular cartilage; 2 ala orbitalis; 3 hypophyseal cartilage; 4 ala temporalis; 5 labyrinthine capsule; 6 notochord; 7 parachordal cartilage; 8 occipital cartilage; 9 ethmoid bone; 10 lesser wing of sphenoid; 11 greater wing of sphenoid; 12 body of sphenoid; 13 basilar part of occipital bone; 14 petrous temporal bone (From G.-H. Schumacher 1997). In this model study the anterior extremities of newborn rats (Rattus norvegicus Berkenhout) were amputated under the shoulder joints and the animals thus forced to walk bipedally. The animals were then killed at post-operative intervals of from 5 to 130 days. The skulls were measured in all dimensions, indices cal-

culated, and various angles on the base of the skull determined. 320 operated animals and a similar number of controls were used and a homologously linear differential equation of the second order with a constant coefficient was set up to illustrate the growth processes. The lines describing longitudinal growth showed, in the case of control and operated animals, a constantly decreasing size towards the end of the period of observation. After the 70th day, a comparison of control and operated animals showed an increasing divergence of these lines. This arose as a result of a decrease in skull length of the operated animals in comparison with the controls. The lengths of the neuro- and viscerocranium Statics: p o s t u r e , body

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Fig. 2. Structural factors in ontogenetic development (After G.-H. Schumacher 1968). 10

Fig. 4. a) Typical posture of bipedal rats. b) Reduction of skull length following bending of the viscerocranium. (From J. Fangh~inel 1974).

b showed that the relationship of both skull segments to the greatest skull length in the operated animals remained constant. The cause of the post-operative brachycephaly lay in a larger scale deflection of the viscerocranium as compared to the neurocranium (Fig. 4).

afrontal CT-sections of the neurocranium showed no marked right-left differences (Henkel and Pienkos 1989). The cause of the increasing anterior deviation of the snout in dogs can be ascribed to the occlusional relationship, the stronger intercuspation allowing no lateral jaw movement. The stability of the neurocranium may be explained by the fact that it is mainly the brain which controls the growth of this part of the skull.

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"1 hi°Constant tension of the muscles is known to promote the local formation of bone substance, and the transmission of the stimuli resulting from tension is also known to stimulate bone growth even in more remote parts of the bone concerned. The jaw muscles constitute the most powerful group of muscles in the head and should therefore have a great influence on the shaping of the skull. In a study conducted in our laboratory, partial lower jaw resection of 74 beagle dogs of varying ages was undertaken in order to release jaw action. The animals were killed after 1 year. Measurements were made on macerated skulls by means of a measuring microscope and computer tomography. Unilateral, partial resection resulted in a loss of the normal occlusion. In a similar manner, the balance between the tongue and muscles of the floor of the mouth was disturbed and, consequently, the basal arch of the lower jaw affected. The medial pull of the masticatory muscles led to a medial displacement of the unoperated lower jaw. As a consequence of lower jaw resection, the skulls of all age groups showed distinct scolioses with a convexity in the non-operated, that is on the mechanically relieved side. The extent of the scoliosis depended on when the animals were killed. A dorsal view clearly shows the deviation increased from posterior to anterior (Fig. 5). Par11

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Fig. 5. a) The dentition in a beagle following partial resection of the right side of the maxilla, b) Divergence in the asymmetric skull of a dog. The axis "a" (o-A) is drawn through the middle of the transverse diameter of the skull (m). The axis "b" (o-B) crosses this transverse line at n. The difference between a and b at the rostral extremity of the skull is "x". (From G.-H. Schumacher 1997).

atrophy in many areas of the neck. On the contralateral side an increase in caliber of the common carotid was established, and the vertebral artery presented luminal enlargement on the ligated side. Collateral vessel formations, as well as anastomoses between both vessel stumps, were observed in the corresponding arteries on both sides. Carotid ligation resulted in an increase in the rate of growth of the skull, especially during the first period. The growth dynamics of the increase in skull measurements as well as vectoral charts indicate that the greatest postnatal growth period takes place between the 42nd day of life and the fourth month (Fig. 6). These results are due to an overcompensation in blood supply after vessel occlusion. There are numerous references in the literature of hyperemia leading to a longitudinal increase in tubular bones. An unexpected growth interruption was observed from the 4th to the 8th months. The genetic, hormonal, and circulatory influences on growth ensure that an excessive increase in bone growth is impossible.

In another of our studies, the results obtained after partial masticatory muscle resection in 3- to 4-month-old sheep differ significantly in some respects from those of dogs (Schumacher 1968). Asymmetries after a post-operative interval of approximately 500 days were in general smaller than those in dogs. As there is no intercuspation in sheep between the upper and lower rows of teeth, lateral displacements of the lower jaw cannot affect the upper jaw. It is striking that the convexity of the skull deviation was on the mechanically released side, that is to say, in contrast to dogs, on precisely the opposite side. These observed differences should not in any case be held to call the mode of bone reaction into question. The morphological and functional priorities of the masticatory muscles differ appreciably between herbivores and carnivores. The specific patterns of movement make their own demands on the strength and direction of muscle pull.

Blood supply The vessels and nerves belong to the nutrient channels serving the metabolism and thus also affect skull growth. Model studies in rats (KOster and Mierzwa 1985), and rabbits (Beleites and Brehmer 1986) have investigated the influence of the blood supply on craniogenesis. K6ster and Mierzwa (1985) experimented on 395 albino rats (Rattus norvegicus Berkenhout) aged from 42 to 365 days. Operationally, the right common carotid artery was ligated in 42-day-old animals. The animals were then killed after 4, 8 and 12 months. Control animals from each age group were used as a comparison. The relatively long observation period of i year allowed a mathematical extension of the postnatal growth period as well as an observation of long-term operative effects. After only 4 months postocclusional changes were seen. The distal end of the ligated carotid artery showed

Regulation of bone remodeling At the conclusion of growth, bone undergoes a constant functional remodeling process. The developmental possibilities related to bone structure are represented at various levels (Fig. 7), the structural changes of bone during growth also are included. The upper general level deals with the endogenous genetic and hormonal control of bone growth. We ascribe a central role to genetic influence and have thus placed it at the peak of our scheme. The general level includes primarily metabolic factors (effects of nutrition including oxygen and hormones). Among other factors, the different organic dietary substances (carbohydrates, fats and proteins) determine the metabolic pathways.

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Fig. 6. a) A portrayal of vectors for increase in length and height of the skull of Rattus norvegicus Berkenhout between 6 weeks and 12 months of age. Lg increment of total length; L1 length increase between 6 weeks and 4 months; b2 length increase between 4 and 8 months; L3 length increase between 3 and 12 months: Hv increment of rostral height; Hj increment of caudal height; M midpoint of a circle with radius of 57.5 mm. b) A vector analysis of snout deviation by means of velocity vectors for increase of the dimensions for snout length and breadth, and their results. (After D. K6ster and J. Mierzwa 1985).

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the experimental object and must therefore be regarded as "third party relations between the subject, the object and the model". This definition gives rise to numerous interrelationships which must be taken into account in interpreting results from models. The most important thing, though, is not the creation of a model, but the creation of a theory. Numerous authors have expounded on the perceptual-theoretical aspects of experimental models. The genetic analogy of animal to human material has unanimously been regarded as valid. Schlienger (1986) postulated that growth control mechanisms are the same in all mammals. This does not, however, mean that our model may take into account biological components but not the human social environment, which also affects growth. Moreover, complete transfer of inferences about the maxillomandibular apparatus from models to humans is impossible as no other animal shares the same dentition as humans. As far as analogous structures and functions are concerned, there are numerous comparisons between humans and animals. All ossification and growth processes in the rat skull correspond to those in humans. The sutural, chondral, and periosteal growth mechanisms are just as effective in the animals used here as in humans.

References

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Beleites B, BrehmerA (1986) Kraniofaziales Wachstum beim Kaninchen nach einseitiger Unterbindung der A. carotis communis unter Beriicksichtigung des Geschlechtsdimorphisnms. Med. Diss. A, Rostock Fangh~inel J (1974) Der Einflug formgestaltender Faktoren auf das postnatale Wachstum mit besonderer Bertlcksichtigung der Statik; ein Beitrag zur quantitativen Effassung von Problemen des Wachstums und der Adaptation. Med. Diss. B, Rostock Henkel KO, Pienkos R (1989) Quantitative Asymmetrieuntersuchungen am Beagle-Hundeschadel nach unilateraler Unterkieferresektion mit Hilfe der Computertomographie. Med. Diss. A, Rostock Johnson LG (1964) Morphologic analysis in pathology. The kinetics of disease and general biology of bone. In: Frost HM (Ed) Bone Biodynamics. Little, Brown & Company, Boston, p 543 KOster D, Mierzwa J (1985) Das postnatale Kopfwachstum bei Rattus norvegicus Berkenhout nach rechtsseitiger Karotisligatur. Eine Tierexperimentelle morphogenetische Studie. Med. Diss. B, Rostock Schlienger A (1986) Einseitige vertikale Okklusionsebene - St6rung und Wachstumsrichtung und -geschwindigkeit des Kondylar-Knorpels. Nova Acta Leopoldina 58:93-101 Schumacher GH (1968) Der maxillo-mandibul~ire Apparat unter dem Einflul3 formgestaltender Faktoren. Nova Acta Leopoldina 33:1-186 Schumacher OH (1997) Principles of Skeletal Growth. In: Dixon AD, Hoyte DAN, R6nning O (Eds) Fundamentals of Craniofacial Growth. CRC Press, Boca Raton New York, pp 80-94 Schumacher GH (1997) Muscles, Blood Vessels, and Craniofacial Growth: Some experimental Approaches. In: Dixon AD, HoyteDAN, R6nning O (Eds) Fundamentals of Craniofacial Growth. CRC Press, Boca Raton New York, pp 140-152

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Fig. 7. The monitoring of adjustments in bone structure. (From G.-H. Schumacher 1997). At the regional level, the vascular system is the effective agent, supplying the bone cells with metabolic material. The blood supply is regulated by the autonomic innervation of the vessels. Changes in blood supply also influence the quality of the metabolites available for remodeling. Finally, the local level is the domain of action of mechanical factors. Johnson (1964) describes bone as an organ which adapts its shape by specific cell activities in a constant cycle of removal and restoration. The exterior shape and inner structure are characteristically brought about by static influences such as body weight and gravity, as well as by muscle stress and movement. Even though growth-dependent mass displacements of individual head components are genetically controlled, it is still not possible to postulate genes affecting shape in the absence of mechanical forces.

Animal models in craniofacial growth As ethical considerations make experiments on humans inconceivable, it is necessary to use animals as models to gain knowledge. Models are, of course, not identical to 13