Micromechanical Modeling Using Low Magnitude Mechanical Stimulation

Weightbearing exercise has an osteogenic effect by reducing bone resorption and enhancing bone formation. During the past several years a number of articles have appeared demonstrating that low-magnitude mechanical stimulation (LMMS) is osteogenic in animals and also in humans. Preclinical studies have also demonstrated an effect of decrease in adiposity. The mechanobiology underlying these phenomena is beginning to emerge in terms of expression of genes stimulated by the action of the vibrations to which osteocytes and adipocytes are subjected.

If successful, LMMS treatment, a non-pharmacologic intervention, could prevent bone loss and potentially stimulate bone formation and decreased adipocyte production resulting in increased bone strength and reduced fracture susceptibility in subjects at risk of developing osteoporosis. The proposed project focuses directly on measures of strength by evaluating the therapeutic response in terms of magnetic resonance (MR) image-based micro finite-element (FE) assessment of bone stiffness and failure strength, along with quantifying treatment-induced changes in marrow adiposity, as part of a single, integrated examination, conducted at baseline and 12 months of treatment in a double-blinded, randomized, placebo-controlled study of early postmenopausal women.

Inclusion criteria

• Females, ages 45-65 years and post menopausal, as defined by a history of amenorrhea for a minimum of 24 months and a serum FSH (follicle-stimulating hormone) concentration of 25 mIU/mL (milli-International unit per milliliter) and negative pregnancy test.

Exclusion criteria

• Current or prior use of medications known to affect bone (e.g. bisphosphonates, calcitonin, selective estrogen receptor modulators, denosumab, diphenylhydantoin, recent systemic glucocorticoid use), bone mineral density T score of less than -2.5 and greater than +2, Vitamin D level less then 12 ng/ml, BMI (body mass index) of greater than 32, current alcohol or drug abuse: more than 3 alcoholic beverages per day or current abuse of illicit drugs or prescription medication, uncontrolled or untreated cardiac or pulmonary disease liver disease: history of hepatitis or ALT (alanine aminotransferase) or AST (aspartate aminotransferase) greater than 2x ULN (upper limit of normal), renal disease: history of renal disease or serum creatinine greater than 2x ULN diabetes, pacemaker or metallic implants considered a contraindication to MR scanning.