Biomedical subjects

Jill E Shea

Publications and source records attributed to Jill E Shea.

5 recordsLinked to original sources

PubMed2005

Skeletal function and structure: implications for tissue-targeted therapeutics.

Osteoporosis, arthritis, and periodontal disease are common diseases of the skeleton, all of which could benefit from new therapeutic strategies, including targeted drug delivery. While bone is a rigid structure, it is not inert, with the cells of the skeleton being able to repair damage and respond to alterations in mechanical stimuli and various endocrine agents. Several important factors related to bone physiology that could influence the success of a pharmacological treatment include heterogeneity in bone remodeling activities throughout the skeleton, differences in blood supply and local vascularization, and the "blood-bone" barrier. The structural qualities of bone, especially the presence of hydroxyapatite crystals in the bone mineral and the established binding of certain molecules to this mineral phase, including tetracyclines, bisphosphonates, and other chelators, provide unique opportunities to treat skeletal diseases using targeted drug delivery. Additional opportunities exist in targeting sites with contrasting bone surface activities, including surfaces that are inactive, forming new bone or being resorbed. The ultimate key to developing new bone-targeted therapies is to understand and exploit the physiological characteristics at the desired target sites.

Bone Diseases↗

PubMed2004

Age-related mineralization heterogeneity changes in trabecular bone of the proximal femur.

Although there is extensive documentation in the literature regarding the importance of trabecular bone for proximal femoral integrity and fracture resistance, there remain gaps in our understanding of the basic mineral changes that may occur in trabecular bone attributable to aging. It is unclear what age-related changes take place in the trabecular bone of the proximal femur, a common fracture site in the elderly. It has been suggested that some explanation for conflicting reports on cancellous bone may be found at a microscopic level. The goal of this study was to document age-related changes in micromineralization in the proximal femur of Caucasian females using backscattered electron imaging technology. Proximal femurs were obtained from 11 young and 11 elderly females. Sections of bone from the superior and inferior neck and superior and inferior trochanter were analyzed in a scanning electron microscope using the backscatter technique to determine ash percent. Mean ash percent did not change with age in any of the four regions (P > 0.05). However, while the mean ash percent did not change, there was a dramatic increase in variability elderly age group and loss of mineral heterogeneity. This indicates that there are subpopulations with higher or lower ash percents than the mean in the elderly study group in this investigation. While variance changed dramatically, variance within individuals did not change significantly with age (P > 0.05). The results of this study suggest that changes in micromineralization may occur within an individual, adding a possible new dimension to our understanding of fracture risk in the elderly. Future studies should examine a longer population base to confirm this observation.

Adolescent↗

PubMed2003

Cortical bone dynamics, strength, and densitometry after induction of emphysema in hamsters.

Recent evidence suggests that patients suffering from chronic obstructive pulmonary disease are also at an increased risk of developing osteoporosis. The pathophysiological mechanism(s) linking these progressive diseases is unknown. The goal of this investigation was to determine whether there were alterations in bone mineral density and content, cortical bone structure and strength, and indexes of bone formation and resorption in the elastase-induced emphysematous hamster. At 3 wk after induction of emphysema, the femoral bone mineral content was 8% less (P = 0.026) and the femoral fracture strength was 6% less (P = 0.032) in the emphysematous hamster than in controls. The cortical area was 8.4% less (P = 0.013) and the periosteal mineral appositional rate was 27% less (P = 0.05) than in controls. Additionally, the endocortical eroded surface in the emphysematous group was about twice that in the control group (P = 0.003). Differences in some indexes of bone formation and resorption, paralleled by differences in bone structure and strength, were observed 3 wk after induction of emphysema. These differences in skeletal metabolism and strength may help explain some of the skeletal changes associated with chronic obstructive pulmonary disease in humans.

Animals↗

PubMed2002

Microvascularization of the hypermineralized calcified fibrocartilage and cortical bone in the sheep proximal femur.

It is well known that the incidence of hip fractures is increasing as the population ages, and that vascularity is one of the most important characteristics for any tissue (the proximal femur being no exception). Additionally, calcified fibrocartilage from tendon and ligament insertions comprises a significant portion of the fractional area of the proximal femur's cortical shell. The goal of the present investigation was to quantify and compare the microvascularity of the cortical bone and calcified fibrocartilage of the proximal femur in a sheep model. There were no regional differences in the vascular density of the cortical bone. However, the calcified fibrocartilage from tendon and capsular insertions were determined to be avascular, and regions of the proximal femur with insertions lacked a vascularized periosteum. If a vessel was present in the calcified fibrocartilage, it was located within an isolated region of bone tissue or osteoid. Since blood vessels appear to be a significant contributor to the health and remodeling of mineralized tissue, it is hypothesized that the large areas of avascular calcified fibrocartilage present on the elderly femoral neck may predispose these regions to damage accumulation. Therefore future research should examine the role of the vascularity to the proximal femur in the mechanisms of numerous pathological conditions, such as avascular necrosis, osteopenia, and hip fractures.

Animals↗

PubMed2002

Experimental confirmation of the sheep model for studying the role of calcified fibrocartilage in hip fractures and tendon attachments.

Research has shown that there is a dramatic increase in the fractional area of calcified fibrocartilage from tendon and capsular insertions on the human femoral neck (Vajda and Bloebaum, 1999; Shea et al., 2001b). Additional information regarding the properties of the proximal femur's cortical shell, gained from the use of an animal model, may result in a better understanding of elderly hip fracture since the cortical shell is a significant contributor to the strength of the proximal femur. The objective of the present study was to determine if the greater trochanter's tendon insertions of the human, rat, and sheep differ in terms of morphology and mineralization. The tendons of the greater trochanter of the human, rat, and sheep were observed to insert via a fibrocartilage insertion. The mineral content of the human and sheep calcified fibrocartilage was significantly higher than that of the rat calcified fibrocartilage (P < 0.01). Additionally, the mineral content of the rat cortical bone was significantly higher than that of the human cortical bone (P < 0.01). The mineral content of the calcified fibrocartilage and bone of the human and sheep were not statistically different from each other. There were also more similarities between the bone structure and lacunae density of the human and sheep than between the human and the rat. This suggests that the tendon insertions of the sheep are a better model than the tendon insertions of the rat for the investigation of calcified fibrocartilage in elderly hip fractures.

Aged↗