Bone Toolbox: Biomarkers, Imaging Tools, Biomechanics, and Histomorphometry

Abstract

Bone is a unique tissue with turnover, metabolic, and cellular activities that vary through development to aging and with a mineralized matrix in which the current state and the history of a bone coexist. Qualitative histopathology often lacks sensitivity to detect changes in bone formation, mineralization and resorption, which often requires chronic dosing to result in structural changes such as variation in bone mass and geometry. A large panel of modalities can be used to fully analyze the health of the skeleton, including biomarker evaluation in serum or urine, imaging techniques ranging from radiology to computed tomography, biomechanical testing, and undecalcified tissue processing with bone histomorphometry. The use of clinically relevant biomarkers provides an important noninvasive, sensitive, rapid, and real-time tool to monitor bone activity at the whole skeleton level when conducting safety assessments in a preclinical setting. Imaging modalities also allow in vivo longitudinal assessments with a powerful, noninvasive and clinically translatable tools to monitor drug effects. Different imaging modalities are used in the preclinical studies to evaluate the bone tissues: standard radiography, dual-energy X-ray absorptiometry, peripheral quantitative computed tomography (pQCT), micro-computed tomography, and high-resolution pQCT. Bone histomorphometry is an important tool that provides sensitive evaluation to detect effects of test articles on bone resorption, formation, mineralization, remodeling rates and growth to address a potential target- or class-related theoretical bone liability. Ultimately, the measurement of bone mechanical properties in pharmaceutical testing is critical to understand the potential effects of that pharmaceutical on bone health and fracture risk. Important considerations are required for including these different techniques in toxicology rodents and nonrodent studies, to actually integrate these into safety assessment.

Simvastatin induces adverse effects on proliferation and mineralization of human primary osteoblasts

“…2) and increased mineralization ( Fig. 4) beside nearly unaltered levels of the typical osteogenic marker ALP [42,43] imply a possible alternative pathway of mineralization beside the osteogenic effect of increased ALP conversion [42,43]. Regularly, a reduced cell count originated by decreased viability (Fig.…”

Effects of Therapy with Fibrin Glue combined with Mesenchymal Stem Cells (MSCs) on Bone Regeneration: A Systematic Review

“…In this way, histological analysis and the use of fluorochromes are useful to assess extracellular matrix deposition and mineralization. Additionally, biochemical analyzes allow the detection of biomarkers involved in bone metabolism and histomorphometry is a valuable technique to assess cell activity [ 56 , 57 ]. Other techniques have been extensively used to assess bone tissue density and microarchitecture, such as densitometry and microtomography, respectively.…”

Clinical Performance of Short Expandable Dental Implants for Oral Rehabilitation in Highly Atrophic Alveolar Bone: 3-year Results of a Prospective Single-Center Cohort Study

“…Long-term success in implantology depends on a sufficient quantity and quality of peri-implant bone, as well as healthy mucosa. A wide range of modalities can be used to fully describe bone health, including biomarkers in serum and urine, imaging techniques, biomechanical testing, and histomorphometry [ 44 ]. Furthermore, studies on dental implant treatment present ambiguous bone tissue characteristics.…”