"Clinical Application of Synchrotron FTIR Microspectroscopy to Evaluate Alterations in Skeletal Mineralization in Response to Therapeutic Agents Used for the Treatment of Osteoporosis"

Robyn Fuchs, Indiana University

Two frequently prescribed interventions for the prevention and treatment of osteoporosis are load-bearing exercise and pharmaceutical agents which function to maintain or restore bone mass. An important question to evaluate with any treatment regimen is how bone at the tissue level may change in response to a prescribed therapy. Our laboratory has utilized synchrotron radiation from the U10B and X27A beam lines to evaluate the effectiveness of drugs used for the treatment of osteoporosis at the tissue level. Alterations in the collagen (protein) and mineral components of bone tissue can compromise the structural integrity of bone tissue, resulting in a weaker structure with a greater than normal propensity to fracture. Synchrotron FTIRM performed at the U10B beamline provides data on ratios of collagen to mineral (overall matrix mineralization) within discrete moieties of bone. Changes in matrix mineralization can have a profound effect on bone strength and the susceptibility for a bone to fracture. Overall matrix mineralization is calculated by performing area integrations on collagen (Amide I: 1688-1623 cm -1), carbonate (v2CO2-3: 905-825 cm-1) and phosphate (v4PO3-4 : 650-500 cm-1) IR bands. Data will be presented from two studies which examined alterations in collagen and mineral in response to therapeutic intervention. First, data will be presented comparing bone tissue from animals administered a vehicle control (saline) against animals treated with two different bisphosphonates (alendronate and risedronate) which were administered at clinically equivalent dosages. Secondly, data will be presented from a study which examined the lifelong benefits of exercise on bone health, including overall matrix mineralization. In addition, data acquired from the X27A beam line will be presented for a study which examined the skeletal effects of strontium ranelate on tissue level properties of bone in rats administered a low and normal calcium diet. Strontium content in bone tissue was quantified using X-ray fluorescence microprobe. Strontium has emerged as a new treatment option for postmenopausal osteoporosis in several countries; however it is uncertain how strontium alters the mineral properties of bone tissue, particularly in response to varied calcium intake. Bone tissue in the form of hydroxyapatite [Ca10(PO4)6(OH)2] is susceptible to ionic substitutions. For example, carbonate can replace phosphate and hydroxide ions (OH-), and strontium can replace calcium in bone tissue.