Variations in the Histologic Distribution of Rat Bone Marrow Cells with Respect to Age and Anatomic Site

Abstract

Bone marrow cellularity in untreated Fischer 344/N rats was subjectively evaluated in hematoxylin and eosin (H & E)-stained histologic sections from femur, tibia, humerus, sternum, lumbar vertebrae, ribs, pelvis, and skull of 2-, 4-, 7-, 16-, and 24-month-old males. Marrow cellularity varied with age of the rat and bone site sampled. Hematopoietic cellularity was consistently higher in rats less than 4 months of age and less consistently higher in 24-month-old rats versus intermediate age groups examined. The 24-month-old rats had the greatest animal-to-animal variation in cellularity. Site differences in bone marrow cellularity were present and similar at 4, 7, and 16 months. Mean percentage of marrow space occupied by hematopoietic cells ranged from 33-75%. Categories for histologic grading of bone marrow cellularity are presented. Sternum, femur, and humerus are recommended sites for histologic evaluation of bone marrow cellularity from conventional H & E-stained sections. Definitive evaluation and assessment of hematopoietic perturbations should not be solely based on subjective evaluation of routine histologic sections.

Importance of Starting Age for Myelotoxicity Study in Dietary Restricted Rats

“…In fact, undernutrition during the rapid growth stage is thought to cause changes, such as hemocytopenia, that are nearly equal to those induced by immunotoxicants. Many reports concerning hematological changes in dietary restricted rats 4–9 or nontreated rats with age-related physiological data 10–13 have been published. However, few reports have examined age-related hematological changes in dietary restricted rats.…”

Skeletal dosimetry in a voxel‐based rat phantom for internal exposures to photons and electrons

“…Figure 3 shows the segmented results of the rat skeletal system, mineral bone, RBM, and YBM. The cellularity of different bones is presented in Table II along with those reported by Cline et al 32 Supplemental Tables 1 and 2 ͑Ref. 57͒ show the AF results for the mineral bone ͑including cortical bone and trabecular bone͒, the RBM, and the YBM in the 40 defined bone sites, calculated for photon and electron sources placed in 18 source organs and seven bone locations.…”

“…34 Generally, the youngest rats have the highest marrow cellularity. Cline et al 32 reported that, regardless of the site, the mean marrow cellularity was 80% at 2 months of age; by 2 yr of age, the cellularity decreased to a mean of 66%. Table II shows marrow cellularities of the rat phantom at 11 bone sites.…”

“…We identified 40 bone sites and then calculated the absorbed fraction ͑AF͒ of mineral bone, RBM, and YBM at these sites for monoenergetic photon and electron sources located in 18 organs and seven bone locations. The beta self-dose and cross-dose S-factors for 169 Er, 143 Pr, 89 Sr, 32 P, and 90 Y from the source organs to mineral bone, RBM, and YBM are also presented based on the AF.…”

Best Practices for Evaluation of Bone Marrow in Nonclinical Toxicity Studies

“…For small laboratory animal species (e.g., rat, mouse, guinea pig), samples of bone marrow for histological examination may be acquired from any one of several bones with hematopoietically active marrow (e.g., sternum, rib, humerus, and femur). Regardless of age, the distal tibia of the rat has a demonstrable lack of active hematopoiesis, suggesting that this site is unacceptable for histological bone marrow evaluations (Cline and Maronpot 1985). The sternum and distal femur are sites that have been routinely used for bone marrow histology in small laboratory animals.…”