Four questions motivated this work:​ 1) Is the zeta potential different comparing normal and osteoporotic bone? 2) Does the etiology producing osteoporosis affect zeta potential response? 3) Do zeta potential changes have physiologic significance? 4) Can a structural model be developed for the bone surface - bone fluid interface explaining changes in the zeta potential?

Stress generated potentials are electrokinetic in origin and proportional to the zeta potential. However, little attention has been directed toward understanding the fiducial zeta potential state at the physiologic bone surface - bone fluid interface using stress generated potential and particle microelectrophoresis protocols. To obtain physiologic values ofthe zeta potential in bone, the measurement must be performed using Neuman's fluid, which mimics bone extracellular fluid. Additionally, the zeta potential of bone is spatially heterogenous.

The following models of osteoporosis were studied:​ aging, disuse, estrogen deficiency, calcium deficiency, etidronate treatment, and clinical osteopenia. Statistically significant zeta potential changes occurred when statistically significant changes were produced in bone mineral density. The cause ofthe observed osteoporosis affects the amplitude and sign ofthe zeta potential response.

The positive hypothesis states that endogenous electrical fields have a physiologic role in the mechanism of bone remodeling. This field exhibits an amplitude dose-response relationship, and the zeta potential determines the amplitude ofthis field. An observation of no zeta potential change for all clinical factors causing osteoporosis would have argued against the hypothesis. However, statistically significant zeta potential changes were observed and are consistent with the hypothesis.

Results from the osteoporotic models and from controlled variations in calcium, phosphate, and fluoride concentration in physiologic bone extracellular fluid were used to propose a structural model ofthe electrical double layer in bone. In this model, the zeta potential depends on the bone substrate proper (composed of collagen, mineral, and boundary regions), stationary layer (wherein ions, ionic complexes, and proteins are adsorbed), and bone extracellular fluid. The zeta potential of calcium-deficient hydroxyapatite was negative in Neuman's fluid, and was consistent with this model. Zeta potential differences between normal and osteoporotic bone indicate a subtle structural difference between normal and osteoporotic bone.