AbstractThere is little debate that mechanical feedback is a key factor in the regulation and maintenance of adult bone structure, following the principles of the mechanostat hypothesis. The factors that drive early ontogenetic change in skeletal microarchitecture are less easily discerned, however, and appear to include not only functional interactions, but also genetic and epigenetic components that may form a blueprint for future development.
The increasingly sophisticated capabilities of imaging technologies provide a platform through which ontogenetic patterns in skeletal development can be studied. When these patterns are considered in conjunction with major physiological, motor and sociological milestones, it may be possible to identify the factors that drive specific phases of development. In particular, digital radiography and micro-computed tomography are regarded as the gold standard imaging modalities for respective qualitative and quantitative studies of skeletal architecture. In this research, these techniques were applied to a sample of juvenile ischia across a developmental spectrum to identify changes in structure with increasing maturity.
The human ischium presents a suitable region for early ontogenetic investigation. During post-natal maturation, it develops load-bearing functions associated with bipedal locomotion and is primarily responsible for weight transmission through the pelvis in a seated posture. However, it reportedly experiences less pronounced mechanical strains and may therefore allow a greater exploration of the non-mechanical stimuli involved in early skeletal development.
The qualitative investigation of ischial development between the late fetal period and 14 years of age, identified 6 progressive phases of ischial development. In the fetal and perinatal period, bone intensity was found to increase rapidly to form a robust, radiopaque structure. Between 5 months and 2 years of age, there was a substantial decrease in the radiographic intensity of the ischium. This early period of bone loss may be linked to the dual action of the infant growth spurt, a period of enhanced growth of both the trunk and limbs, and the weaning period, which may restrict the availability of ingested dietary calcium and therefore demand the release of stored skeletal calcium to facilitate growth. Beyond this period, however, this pattern of loss reversed and radiopacity was found to increase, with the most pronounced increases seen in the regions associated with the acetabulum and ischial spine.
To further explore the period of apparent bone accrual and subsequent loss that characterised the infant developmental period, micro-computed tomography was used to document the perinatal trabecular and cortical architecture and investigate changes in the internal structure with increasing maturity, up to 3 years of age.
Analysis of the perinatal ischium revealed statistically significant differences in regional trabecular bone characteristics and cortical thickness. The metaphyseal regions were defined by relatively immature bone indicative of modelling activities, regions of growth, while the central body of the ischium contained a more mature trabecular architecture that was consistent with accommodating the presence of a proliferating vascular centre.
It was subsequently confirmed that the loss of bone intensity observed qualitatively was the result of a significant decrease in bone volume fraction and cortical thickness across the ischium between 5 months and 2 years of age. Associated architectural changes included a significant decrease in trabecular number and an incremental increase in trabecular thickness. These changes suggest that there is a paradigm shift during infancy which prompts a rapid resorption of mineralised tissue within the ischium, perhaps to release sufficient stored calcium to facilitate the rapid growth of the child which is characteristic of this period. However, the changes are not exclusively deleterious, as the trabecular tissue which remains appears to undergo remodelling to increase trabecular thickness and perhaps prevent mechanical failure during routine use.
The identification of a period of skeletal overproduction and subsequent constructive regression may be of great significance in understanding early bone development at a whole-bone level and any subsequent failure. It is further proposed that the end of this transitory period may signal a biological switch between genetically-programmed skeletal growth in-utero and a functionally adaptive growth guided primarily by biomechanical stimuli.
|Date of Award
|Sue Black (Supervisor) & Craig Cunningham (Supervisor)
- Skeletal development
- Microcomputed tomography
- Gradient map