As part of our ongoing assessment of bone tissue composition and structure, we report the first experimental protocols of a prospective study to investigate the potential of using Raman spectroscopy to diagnose and predict skeletal fragility in postmenopausal osteoporosis patients. This multi-center study will assess several potential spectroscopic and X-ray based diagnostic techniques. One hundred and twenty participants will be enrolled in this five year study and the investigators will be blinded to information concerning patient history and status. Iliac crest bone biopsy specimens are provided with no identifying information except a patient study number. Our team will use micro-computed tomography (micro-CT) to identify regions of interest in both cortical and cancellous bone from specimens delivered to us. Raman mapping will be performed using a line-focused 785 nm laser in order to obtain local and averaged values on several spectroscopic metrics of bone quality. These metrics include carbonate/phosphate and phosphate/matrix ratios. Results from an initial set of biopsies will be presented. Protocols for obtaining measurements are discussed, with emphasis on the challenges presented by the use of fixed and polymer embedded specimens. These protocols are illustrated will data from a biopsy specimen.