Elastic and Physiochemical Relationships Within Cortical Bone: Growth Hormone Treatment of a Dwarf Rat Model

This doctoral dissertation project examines the relationships between the elastic and physicochemical properties of cortical bone as well as the efficacy of the use of recombinant human growth hormone (hGH) as a treatment to counter the effects of hormonal growth disruption (dwarfism) in a rat model. The goals of the project are to refine the ultrasonic elasticity technique for use with small specimens (<1.0 mm) and determine if the administration of hGH can counter the degenerative elastic and physicochemical characteristics of cortical bone resulting from hormone-suppressed downregulation. Ultrasonic wave propagation and density measurements were used to determine the three-dimensional material properties of rat femoral cortical bone. X-ray powder diffraction, morphometry, and biochemical analysis techniques were used to describe physicochemical properties including mineral crystal size, cortical porosity, and mineral and nonmineral content. Microstructural characteristics were also explored via scanning electron microscopy. Mathematical relationships between the local physicochemical (independent variable) and elastic (dependent variable) properties have been formulated via linear and nonlinear regression analysis. Generally, apparent density was found as the highest correlate with most of the Young’s and shear moduli (R²=0.300 to 0.600). Concomitantly, mineral crystal width and porosity offered the closest descriptions of Poisson’s ratios (R² up to 0.600). These correlations contribute to the fundamental relationships between microstructure and material properties within cortical bone. Evaluation of the changes due to the treatment of dwarfism with hGH have also been quantified. Wilcoxon t-tests verified a significant decrease in the elastic properties in dwarf rat cortical bone after hGH treatments (p<0.05). Physicochemical measures of bone quality (density, crystal size) generally decreased while measures of bone quantity (cotical area, moments of inertia) generally increased (p<0.05) after hGH treatments. Some mineral and nonmineral properties were unchanged. The unique contributions of this project are determination of a quantifiable link between cortical bone elasticity and its composite construction and determination of elasticity and physicochemical changes between dwarf bone and hGH treated dwarf bone. The methodology for the measurement of orthotropic elastic constants of small bone specimens is proven to be a unique and valuable research tool. The clinical importance of this study determines that the treatment of pituitary dwarfism with hGH increases bone formation and alters bone elastic characteristics.

Year	Entry
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1988	Ashman RB, Rho JY. Elastic modulus of trabecular bone material. J Biomech. 1988;21(3):177-181.
1989	Ashman RB, Rho JY, Turner CH. Anatomical variation of orthotropic elastic moduli of the proximal human tibia. J Biomech. 1989;22(8-9):895-900.
1994	Zhu M, Keller TS, Spengler DM. Effects of specimen load-bearing and free surface layers on the compressive mechanical properties of cellular materials. J Biomech. 1994;27(1):57-66.
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Year

Entry

1983

Bonar LC, Roufosse AH, Sabine WK, Grynpas MD, Glimcher MJ. X-ray diffraction studies of the crystallinity of bone mineral in newly synthesized and density fractionated bone. Calcif Tiss Int. December 1983;35(2):202-209.

1988

Schaffler MB, Burr DB. Stiffness of compact bone: effects of porosity and density. J Biomech. 1988;21(1):13-16.

1988

Ashman RB, Rho JY. Elastic modulus of trabecular bone material. J Biomech. 1988;21(3):177-181.

1989

Ashman RB, Rho JY, Turner CH. Anatomical variation of orthotropic elastic moduli of the proximal human tibia. J Biomech. 1989;22(8-9):895-900.

1994

Zhu M, Keller TS, Spengler DM. Effects of specimen load-bearing and free surface layers on the compressive mechanical properties of cellular materials. J Biomech. 1994;27(1):57-66.