Bone and Joints

Gunson, Diane E.; Gropp, Kathryn E.; Varela, Aurore

doi:10.1016/b978-0-12-415759-0.00063-7

Cited by 26 publications

(21 citation statements)

References 145 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When performing 14-day toxicity studies in young rats, decreased longitudinal bone growth in these rapidly growing young animals is a common finding that could be secondary to either decreased food intake or a direct toxic effect of the test drug or the combination of the above (Gunson, Gropp, and Varela 2013). This is because the GPs of such young rats are known to respond sensitively to drugs that affect bone growth (Gunson, Gropp, and Varela 2013). GPs are known to play an important role in endochondral bone growth and are affected by a variety of hormones and dietary factors (Gunson, Gropp, and Varela 2013; Leininger and Riley 1990; Young and Heath 2000).…”

mentioning

confidence: 99%

“…This is because the GPs of such young rats are known to respond sensitively to drugs that affect bone growth (Gunson, Gropp, and Varela 2013). GPs are known to play an important role in endochondral bone growth and are affected by a variety of hormones and dietary factors (Gunson, Gropp, and Varela 2013; Leininger and Riley 1990; Young and Heath 2000). Indeed, identifying the cause of changes in toxicity studies can be difficult since GPs can be affected by secondary drug-related changes, such as decreased body weight or decreased food consumption, as well as direct toxic effects of the test drug (Gunson, Gropp, and Varela 2013).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of 5-Fluorouracil Daily Oral Dosing versus Dietary Restriction on Femoral Growth Plates in Rats

et al. 2018

View full text Add to dashboard Cite

We evaluated the growth plates (GPs) of rats after a 14-day reduction in food consumption caused by either daily oral dosing with 5-fluorouracil (5-FU: a positive control reducing food consumption and affecting the GPs) or a direct reduction in food consumption to determine whether the observed changes were attributable to a direct effect of drug toxicity. Histomorphometric analyses of the femoral GP were performed for a nontreated (NT) control group, three groups treated with 5-FU (12, 15, and 18 mg/kg/day) and three groups with food intake restricted to levels corresponding to those consumed by the rats in the three 5-FUtreated groups. Compared with the NT group, the GP widths and the number of chondrocytes in the proliferative zone decreased significantly in all the 5-FU-treated groups and the dietary restriction groups. Importantly, no significant differences between the 5-FU-treated groups and the groups with matched dietary restrictions were seen for most parameters. Thus, the 14-day dietary restriction caused significant changes in the proliferative zone of the GP, and similar changes observed in the 5-FU-treated groups were presumed to result from the comparable reduction in food intake rather than being a direct toxic effect of the drug.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Characterization of 5-Fluorouracil Daily Oral Dosing versus Dietary Restriction on Femoral Growth Plates in Rats

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Schematic diagram of bone turnover illustrating the generation of various bone biomarkers for resorptive and formative processes. Reproduced with permission from Gunson, Gropp, and Varela (2013).…”

Section: Biochemical Markers Of Bone Turnovermentioning

confidence: 99%

“…Occult bone production detected radiologically in the axial skeleton of a rat (A, black arrows) and corresponding microscopic findings (B) of an occult osteosarcoma affecting the last cervical vertebral body and spinous process, which compresses the spinal cord, hematoxylin, and eosin. Reproduced with permission from Gunson, Gropp, and Varela (2013).…”

Section: Skeletal Imagingmentioning

confidence: 99%

See 1 more Smart Citation

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

Varela¹,

Jolette²

2018

Toxicol Pathol

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Limitations of Pathology and Animal Models

Neef

2017

Pathology of Taxicologists

View full text Add to dashboard Cite

Bone and Joints

Cited by 26 publications

References 145 publications

Characterization of 5-Fluorouracil Daily Oral Dosing versus Dietary Restriction on Femoral Growth Plates in Rats

Characterization of 5-Fluorouracil Daily Oral Dosing versus Dietary Restriction on Femoral Growth Plates in Rats

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

Limitations of Pathology and Animal Models

Contact Info

Product

Resources

About