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Biomedical subjects

W S Jee

Publications and source records attributed to W S Jee.

At least 127 records · Page 7Linked to original sources
PubMed1991

Adaptation of diaphyseal structure with aging and increased mechanical usage in the adult rat: a histomorphometrical and biomechanical study.

The experimental increase in mechanical usage or overloading of the left hindlimb was produced by immobilization of the contralateral hindlimb. The right hindlimb was placed in a flexed position against the body and was immobilized using an elastic bandage. Some control animals were sacrificed initially at time zero and increased mechanical usage and age-matched control animals were sacrificed after 2, 10, 18, and 26 weeks of treatment. All animals received double bone fluorochrome labeling prior to sacrifice. Cortical bone histomorphometry and cross-sectional moments of inertia were determined. Marrow cavity enlargement and total cross-sectional area expansion represented the age-related cortical bone changes. Increased mechanical usage enhanced periosteal bone modeling in the formation mode and dampened endocortical bone remodeling and bone modeling in the resorption mode (resorption drift) to create a slight positive bone balance. These observations are in general agreement with Frost's postulate for mechanical effects on bone modeling and remodeling (Frost, H.M. 1987b. Bone "mass" and the "mechanostat." A proposal. Anat. Rec. 219: 1-9). The maximum moment of inertia did not change significantly in either control or overloaded tibial shafts. The minimum and polar moment of inertias in overloaded bones increases over those of controls at 18 and 26 weeks of the experiment.

Adaptation, Biological↗
PubMed1991

Long-term anabolic effects of prostaglandin-E2 on tibial diaphyseal bone in male rats.

The effects of long-term prostaglandin E2 (PGE2) on tibial diaphyseal bone were studied in 7-month-old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg/day for 60, 120 and 180 days. The tibial shaft was measured by single photon absorptiometry and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial diaphyseal bone samples. Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: 1) increased bone width and mineral density; 2) increased total tissue and total bone areas; 3) decreased marrow area; 4) increased periosteal and corticoendosteal lamellar bone formation; 5) activated corticoendosteal lamellar and woven trabecular bone formation and 6) activated intracortical bone remodeling. A new steady-state of increased tibial diaphyseal bone mass and elevated bone activities were observed from day 60 onward. The elevated bone mass level attained after 60 days of PGE2 treatment was maintained at 120 and 180 days. These observations indicate that the powerful anabolic effects of PGE2 will increase both periosteal and corticoendosteal bone mass and sustain the transient increase in bone mass with continuous daily administration of PGE2.

Absorptiometry, Photon↗
PubMed1991

Partial loss of anabolic effect of prostaglandin E2 on bone after its withdrawal in rats.

The object of this study was to determine the fate of PGE2-induced new bone mass after withdrawal of PGE2 administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3, and 6 mg PGE2/kg/d for 60 days and then withdrawn for 60 and 120 days. Histomorphometric analyses were performed on double fluorescent labeled undecalcified proximal tibial bone specimens. After 60 days of PGE2 treatment, a new steady state of increased trabecular bone area (+67% and +81% with 3 and 6 mg PGE2/kg/d) from woven bone and stimulated lamellar bone formation, elevated bone turnover, and shortened remodeling periods were achieved compared to age-matched controls. In contrast, after 60 and 120 days withdrawal of PGE2, a new steady state characterized by less trabecular bone area (+40% to +60% of controls with 3 and 6 mg/kg/d doses), normal lamellar bone formation, no woven bone formation from controls, and eroded surface greater than those seen in controls and previously in 60-day PGE2 treated rats. The decrease in new bone mass after withdrawal of PGE2 was due to a further elevation of bone resorption above that induced by the PGE2 treatment and a reduction in PGE2 stimulated bone formation activities. Although there is more trabecular bone than in controls after 120 days' withdrawal of PGE2, we postulate that the skeletal adaptation to mechanical usage will eventually reduce the bone mass to control levels. Thus, it is conservative to conclude that the anabolic effect of PGE2 was dependent upon continuous daily administration of PGE2 in these older rats.

Aging↗
PubMed1990

Adaptation of cancellous bone to aging and immobilization in the rat: a single photon absorptiometry and histomorphometry study.

Nine-month-old female rats were double-labeled with bone markers and subjected to right hindlimb immobilization or served as control for 0, 2, 10, 18, or 26 weeks. The right limb was immobilized against the abdomen, thus unloading it, while the left limb was overloaded during ambulation. Single photon absorptiometry and cancellous bone histomorphometry were performed on dissected intact femur and 20-microns-thick undecalcified specimens of the proximal tibial metaphysis. In the unloaded limb, immobilization-induced muscle and cancellous bone loss occurred rapidly before 10 weeks and stabilized at 50% less bone mass after 18 weeks. Unloading caused a negative bone balance from a combination of elevated bone resorption and depressed bone formation. At 2, 10, and 18 weeks of immobilization, the ratios of bone resorption to bone formation surfaces were 1.6, 1.5, and 1.3, respectively; at 26 weeks, the ratio was 1. The bone loss was accompanied by poorer trabecular architecture (trabecular number decreased and trabecular separation increased), reaching the maximum at 18 weeks and stabilizing thereafter. These observations are in general agreement with Frost's postulate for mechanical effects on lamellar bone remodeling, and the findings on disuse osteoporosis in man. Therefore, the one-legged immobilization model can be useful in studies of the mechanisms of structural adaptation to mechanical usage.

Absorptiometry, Photon↗
PubMed1990

Adaptation of cancellous bone to overloading in the adult rat: a single photon absorptiometry and histomorphometry study.

Nine-month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 2, 10, 18, and 26 weeks and were double-labeled with bone markers. The right limb was immobilized against the abdomen and considered unloaded, while the left limb was overloaded during ambulation. Single-photon absorptiometry was performed on intact femur; static and dynamic histomorphometry were performed on 20 microns thick undecalcified frontal sections of the proximal tibial metaphysis. Changes in the continuously overloaded limb was compared to that in both limbs of age-matched control animals. Single-photon absorptiometry detected increases of bone mineral density of +6%, +6%, and +5% in the proximal and +9%, +7%, and +10% in the distal femoral metaphyses after 10, 18, and 26 weeks of continuous overloading. Morphometrically, significant changes occurred in proximal tibial metaphyses compared to age-matched controls: trabecular area increased +41% and +45%, trabecular number increased +31% and +32%, and trabecular separation decreased -30% and -31% after 18 and 26 weeks of overloading. A significant increase in mineral apposition rate (+38%) was found only at 26 weeks of overloading. Insignificant decreases in both eroded and labeled bone surfaces occurred at all time periods. The histomorphometric changes indicated that increased cancellous bone mass was caused by an increase in bone formation activity (i.e., increases in mineral apposition and bone formation rates) and a decrease in remodeling space (i.e., decrease in bone eroded surface). These findings indicate that the adult skeleton can quickly adapt to the increased biomechanical needs by increasing its cancellous bone mass with an adequate structural pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1990

A model of osteon closure in cortical bone.

A model of osteon closure is presented that incorporates some physiologic features of cortical bone remodeling, such as matrix synthesizing activity of osteoblasts, their burial as osteocytes, and elimination of cells. A simplified version of the model assumes a constant osteoblast activity throughout radial closure. An extended version allows for variable osteoblasts activity and is based on Lee's law of radial closure kinetics. The model calculations (extended model) show that both in humans and beagle dogs osteoblast activity steadily decreases during radial closure of the osteon. The potential of the model is also illustrated by calculating the dynamic change of the geometrical shape of the closing cone and the time dependence of the osteoid seam width, number of osteoblasts and bone formation rate in the closing cone.

Animals↗
PubMed1990

The role of prostaglandins in bone in vivo.

Prostaglandins of the E series, primarily E2 and E1, have the greatest activity in bone. Following discovery of their potent ability to stimulate bone resorption in vitro, clinical investigations have placed prostaglandins at sites of localized bone resorption associated with inflammatory or space occupying lesions in vivo. These studies have shown that prostaglandin production at such sites may be increased by cytokines such as interleukin-1 but the mechanisms by which prostaglandins stimulate bone resorption are not yet known. Observation of periosteal bone formation in patients given, pharmacological doses of prostaglandin has led to investigation of its bone forming activity. Young, growing rats have increased metaphyseal bone formation and this is accompanied by increased periosteal and endocortical bone formation in older animals. In the mature animals there is a generalized activation of remodelling with increased formation in the remodeling cycle. This is also seen in oophorectomized rats and results in repletion of the lost bone in this model of osteoporosis. In animal models of localized disuse osteopenia, prostaglandins are found to be elevated at the site of bone loss and prostaglandin inhibitors at least partially protect against the exaggerated resorption that occurs. This is also seen in models of orthodontic tooth movement, periodontitis and osteomyelitis. Prostaglandin synthesis inhibitors have been shown to delay healing of bone and this has led to limitations on their use clinically in some situations. Exogenously administered prostaglandins have been found to enhance periosteal callus formation, but healing is not uniformly enhanced. Prostaglandins have also been associated with hypercalcemia in certain animal tumors that model human hypercalcemia of malignancy but are probably most important in this condition as mediators in the localized resorption of bone at tumor sites. These in vivo studies have shown that prostaglandins are involved with increases in both bone formation and bone resorption. In vitro studies have shown that prostaglandins stimulate osteoblasts as well as osteoclastic bone resorption but understanding these effects under in vivo conditions will require further investigation.

Animals↗
PubMed1990

Effects of prostaglandin E2 on production of new cancellous bone in the axial skeleton of ovariectomized rats.

The effects of prostaglandin E2 (PGE2) were histomorphometrically evaluated in cancellous bone of the axial skeleton of ovariectomized, osteopenic rats. Four months following bilateral ovariectomy (OVX) and sham-ovariectomy (SHAM) at 3 months of age, rats received daily subcutaneous injections of PGE2 at 0, 0.3, 1.0, 3.0 and 6.0 mg/kg/day for 30 days. The undecalcified fourth lumbar vertebral bodies (LVB) were processed for static and dynamic bone histomorphometry. The OVX rats possessed a slightly osteopenic LVB (17% vs. 24% cancellous bone mass). In rats given PGE2 at 3 and 6 mg/kg/day for 30 days, bone turnover, lamellar bone mass, and formation of new woven bone trabeculae were increased. Observations supported the conclusion that PGE2 activates bone modeling and remodeling, and shifts bone balance in favor of formation. In OVX rats given 6 mg PGE2/kg/day, cancellous bone mass and trabecular numbers were restored to levels found in untreated SHAM rats. Cancellous bone mass in the LVB of SHAM rats given 3 and 6 mg PGE2/kg/day increased by 16% and 30% over that of control rats. In addition, PGE2 stimulated longitudinal bone growth in both OVX and SHAM rats, a response that differed from male rats.

Aging↗
PubMed1990

Prostaglandin E2 enhances cortical bone mass and activates intracortical bone remodeling in intact and ovariectomized female rats.

To assess the efficacy of prostaglandin E2 (PGE2) in augmenting cortical bone mass, graded doses of PGE2 were subcutaneously administered for 30 days to seven-month old sham-ovariectomized (SHAM) and ovariectomized (OVX) rats. Both groups were operated at three months of age. Histomorphometric analyses of double fluorescent labeled tibial shafts were performed on basal control, OVX, and SHAM rats treated with 0, 0.3, 1, 3, and 6 mg PGE2/kg/d for 30 days. Baseline aging data showed increased cortical tissue and cortical bone area and reduced bone formation parameters at the periosteal and endocortical bone envelopes between three and eight months of age. The tibial shafts of OVX rats compared to SHAM controls showed elevated periosteal mineral apposition rate and endocortical bone formation parameters. PGE2 administration to OVX and SHAM rats increased cortical bone by the addition of new circumferential bone on the endocortical and periosteal surfaces, as well as woven cancellous bone in the marrow region. Stimulated osteoblastic recruitment and activity enhanced bone formation at all bone surfaces. The new bone was both lamellar and woven in nature. PGE2 treatment also activated intracortical bone remodeling (not seen in untreated eight-month old rats), creating a porous cortex. Thus, PGE2 administration activated cortical bone modeling in the formation mode (A----F), as well as intracortical bone remodeling (A----R----F). PGE2 administration to OVX rats resulted in more intracortical bone remodeling, periosteal bone formation, and new cancellous bone production than observed in PGE2 treated controls. The findings that PGE2 administration to OVX and intact female rats increases cortical bone mass, coupled with observations that mouse, rat, dog, and man respond similarly to PGE2, suggest that PGE2 administration may be useful in the prevention and treatment of postmenopausal osteoporosis.

Aging↗
PubMed1990

Transient effects of subcutaneously administered prostaglandin E2 on cancellous and cortical bone in young adult dogs.

The transient effects of prostaglandin E2 (PGE2) on cancellous and cortical bone in iliac crests and mid-tibial shafts of nine intact young adult dogs were evaluated following 31 days of treatment. Histomorphometric bone changes were characterized from in vivo fluorescent double-labeled undecalcified bone specimens. PGE2 caused an increase in cancellous bone remodeling evidence by increased in activation frequency; increased percent eroded and formation surfaces; increased mineral apposition and bone formation rates; and shortened resorption, formation, and total bone remodeling periods. Activated cancellous bone remodeling did not lead to decreased cancellous bone mass, indicating an imbalance between bone resorption and formation in favor of formation (activation----resorption----stimulated formation; A----R----F increases) at remodeling sites. The PGE2 treatment activated bone modeling in the formation mode (activation----formation; A----F) at the periosteal and endocortical surfaces and increased activation frequency of intracortical bone remodeling in the tibial shaft. Increased modeling activation converted quiescent bone surfaces to formation surfaces with stimulated osteoblastic activity (i.e., increased percent labeled periosteal and endocortical surfaces, mineral apposition rates, and woven and lamellar trabecular bone formation) leading to 9- to 26-fold increases in newly formed bone mass in subperiosteal, subendosteal, and marrow regions, compared to controls. However, increased intracortical bone remodelling elevated remodeling space (i.e., increased cortical porosity), producing a bone loss that partially offsets the bone gain. The combined events lead to a positive bone balance in PGE2-treated cortical bone, compared to a negative bone balance in control bones. Collectively our data suggest that in vivo PGE2 is a powerful activator of cancellous and cortical bone formation, which may be able to build a peak bone mass to prevent and/or correct the skeletal defects to cure osteoporosis.

Alkaline Phosphatase↗
PubMed1989

Flurbiprofen enhances growth and cancellous and cortical bone accumulation in rapidly growing long bones.

The effects of flurbiprofen, a non-steroidal anti-inflammatory drug, on bone growth was studied by static and dynamic histomorphometry in immature (28 days old) male Sprague-Dawley rats. Flurbiprofen at 0, 0.02, 0.1, 0.5 or 2.5 mg/kg/d doses was given subcutaneously daily for 21 days. The 0.1 and 0.5 mg/kg/d doses were most effective in stimulating longitudinal and radial bone growth and enhancing the accumulation of cancellous and cortical bone. Proximal tibial longitudinal bone growth rate, growth plate thickness, and periosteal bone formation rate were increased 30-40%, while cortical bone (tibial shaft) and cancellous bone (proximal tibial metaphysis) accumulated 12% and 90% more bone than controls, respectively. Enhanced accumulation of cortical bone was attributed to stimulated periosteal bone formation without accompanying marrow cavity enlargement. Enhanced accumulation of cancellous hard tissue was postulated to be due to reduced trabecular bone resorption and no effect on bone formation. The cell counts support these conclusions. There was a decrease in osteoclast numbers (-62 to -70%), an insignificant decrease in osteoblast numbers (-5 to -30%) per mm of bone surface and a decrease in osteoclast to osteoblast ratio (-35 to -56%). The findings presented are compatible with the conclusion that flurbiprofen, induced changes in rapidly growing long bones by reducing osteoclast activity and recruitment, stimulating longitudinal and radial growth, increasing the cortical bone mass by stimulated periosteal bone growth and depressed endosteal resorption, and increasing cancellous bone mass by depressed trabecular bone resorption without affecting bone formation.

Animals↗
PubMed1989

The effects of chronic vitamin A excess on bone remodeling in aged rats.

This study was conducted to assess the effects of long-term ingestion of moderate excesses of vitamin A on trabecular bone remodeling in the fifth lumbar vertebral body of aged rats. Eighteen-month-old rats were fed diets with vitamin A content equal to the daily requirement (DR), 2-fold, and 5-fold the DR along with calcium content of either the DR or 0.3-fold the DR, for 14 months each. As expected, serum concentrations of 1,25-dihydroxyvitamin D were higher in the reduced than in the normal calcium intake groups (65.1 +/- 2.4 SEM vs 47.8 +/- 2.1 pg/ml, P less than 0.001). Calcium balance was more positive at the higher than the lower calcium intake (5.7 vs 0.9 mg, P less than 0.001) but was unaffected by vitamin A intake. Histomorphometric analysis of the fifth lumbar vertebral body revealed that the 2-fold but not the 5-fold excess in vitamin A intake resulted in a 15% increase in percentage of trabecular bone (P less than 0.02). The low calcium diet depressed bone growth (total bone tissue) but did not affect percentage of trabecular bone. Several effects of the vitamin A excess and low calcium diet were noted along the trabecular surface including increased mineral apposition rate and resorption surfaces and decreased formation surfaces. The net effect of vitamin A on trabecular bone of the rat varies as intake begins to exceed the DR. At a 2-fold excess, a modest favorable effect on percentage of trabecular bone was observed.

Aging↗
PubMed1989

Ultrastructural features of osteoclasts in situ.

The morphology of in situ osteoclasts on endocortical surfaces of the femoral midshaft was examined by scanning electron microscopy. Mice were perfusion fixed and bone marrow plugs were flushed out of femoral diaphyseal cylinders. The bones were split longitudinally and the endocortical surfaces examined. This method left on the bone surface most of the endosteal cells in their natural, in situ shape and position. Most of the bone surface was lined by contiguous bone lining cells covering resting bone surfaces, making a clear physical barrier between the bone and marrow compartments. On resorption surfaces, which were characterized by excavation cavities, osteoclasts were very polymorphic and spread on the bone surface, extending large pseudopods. The in vivo morphology of individual osteoclasts appears somewhat similar to that described by other investigators on calvaria surfaces and for isolated osteoclasts adherent to artificial substrates. In the resorption domains, osteoclasts appeared to be connected with adjacent osteoclasts, suggesting that the cells form a functional syncytium in resorption areas.

Animals↗
PubMed1989

Bone lining cells: structure and function.

Bone lining cells (BLC's) cover inactive (nonremodeling) bone surfaces, particularly evident in the adult skeleton. BLC's are thinly extended over bone surfaces, have flat or slightly ovoid nuclei, connect to other BLC's via gap junctions, and send cell processes into surface canaliculi. BLC's can be induced to proliferate and differentiate into osteogenic cells and may represent a source of "determined" osteogenic precursors. BLC's and other cells of the endosteal tissues may be an integral part of the marrow stromal system and have important functions in hematopoiesis, perhaps by controlling the inductive microenvironment. Because activation of bone remodeling occurs on inactive bone surfaces, BLC's may be involved in the propagation of the activation signal that initiates bone resorption and bone remodeling. Evidence also suggests that BLC's are important in the maintenance of the bone fluids and the fluxes of ions between the bone fluid and interstitial fluid compartments for mineral homeostasis.

Animals↗
PubMed1989

Bone structural parameters, dosimetry, and relative radiation risk in the beagle skeleton.

A variety of morphometric and histomorphometric parameters such as the mass of bone and marrow, bone surface areas, percentage of bone volume, percentage of the surface that is trabecular, and percentage of surfaces that are forming and resting are calculated for all major parts of the beagle skeleton. The total bone surface of the beagle is estimated at 2.9 m2 with 53.7% of the surface area being associated with trabecular bone. There are about 4.5 x 10(9) bone-lining cells and about 1 x 10(9) osteoblasts. From the fractional retention in each part of the skeleton, the initial surface concentration of 239Pu after a single injection of 592 Bq/kg body wt (0.016 microCi/kg) on resting surfaces and at sites of bone formation is calculated for various values of the affinity ratios of trabecular/cortical and forming/resting surfaces. These estimated concentrations then yield dose rates as well as cumulative and collective doses to bone-lining cells and osteoblasts in the different parts of the skeleton. On the assumption that the relative risk of tumor induction is proportional to the collective dose to either bone-lining cells or osteoblasts, the frequency of tumor occurrence is calculated and compared to observed frequencies. Both hypotheses yield approximate agreement with experimental data for different ratios of trabecular/cortical radiation sensitivity, although the differences between some bones are statistically significant.

Animals↗
PubMed1988

Effects of N,N,N',N'-ethylenediaminetetramethylene phosphonic acid on cortical bone remodeling in the adult dog.

Phosphonic acids are of interest because of their potential usefulness in the treatment of disorders of bone and mineral metabolism, as a treatment for dental calculus, and as skeletal imaging agents. The effects of oral doses of N,N,N',N'-ethylenediaminetetramethylene phosphonic acid (EDITEMPA) on cortical bone remodeling and histology of adult dogs were determined. After treatment for 3 and 6 months, there were dose-related changes observed in cortical bone as measured using histomorphometric methods. With higher doses, EDITEMPA treatment resulted in the accumulation of osteoid due to impaired or delayed mineralization of bone. There was an increased mineralized and osseous tissue porosity suggesting an early increase in bone resorption perhaps due to an increased activation of bone remodeling.

Animals↗
PubMed1988

Flurbiprofen-induced stimulation of periosteal bone formation and inhibition of bone resorption in older rats.

The skeletal effects of flurbiprofen (Fb), a nonsteroidal anti-inflammatory drug, was studied by histomorphometry in 9-month-old retired female breeder, Sprague-Dawley rats. Flurbiprofen was given subcutaneously at 0, 0.2, 0.1, 0.5, 2.5, or 5 mg/kg/d for 21 days. Flurbiprofen had no effect on longitudinal growth, but stimulated radial growth (+200%) over controls. In the tibial shaft, Fb stimulated the mineral apposition rate (+25%), mineral bone formation rate (+100%), and periosteal labeling length (+64%) at the 2.5 and 5.0 mg Fb/kg dose levels, and had no effect on marrow cavity size compared to controls. However, these changes were insufficient to increase cortical bone mass. In the proximal tibial metaphysis, Fb suppressed osteoclasts/mm2 of metaphyseal tissue (-47%), osteoclasts/mm of bone surface (-46%), and the osteoclast/osteoblast ratio (-50%), increased the calcified cartilage core population (+100%), and had no effect on osteoblast numbers at all dose levels. There was an insignificant increase in metaphyseal cancellous bone mass. The current study leads to the conclusion that flurbiprofen-stimulated periosteal bone growth was due to direct stimulation of osteoblast recruitment and activity independent of longitudinal bone growth. Further, it confirms early findings in young rats that flurbiprofen induced depressed bone resorption without lowering bone formation. However, because of insufficient treatment time, the older rat did not accumulate bone as the young rats did.

Age Factors↗