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Biomedical subjects

Y F Ma

Publications and source records attributed to Y F Ma.

At least 37 records · Page 2Linked to original sources
PubMed1997

Impact of antihypertensive therapy on the skeleton: effects of moexipril and hydrochlorothiazide on osteopenia in spontaneously hypertensive ovariectomized rats.

Skeletal effects of moexipril, an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide (HCTZ), a thiazide diuretic, were studied in ovariectomized (OVX) spontaneously hypertensive rats (SHR). Moexipril (10 mg/kg per day), HCTZ (10 mg/kg per day), alone or in combination, as well as 17 alpha-estradiol (30 micrograms/kg per day) were given to OVX SHR immediately after surgery and studied for short- and long-term effects (14 and 56 days respectively). All drugs were given orally. Histomorphometric data on the secondary spongiosa of proximal tibial metaphyses (cancellous bone) and tibiofibular junctions of tibial shafts (cortical bone) were analyzed. Ovariectomy induced cancellous bone loss in SHR by inducing negative bone balance. Estrogen prevented ovariectomy-induced cancellous bone loss in the SHR by reducing bone turnover and partially suppressing the coupling of bone formation to resorption on the endocortical surface. HCTZ reduced blood pressure after 1 week of treatment, yet this effect was no lower than that seen in controls after 3 weeks of treatment. Two weeks of HCTZ transiently prevented ovariectomy-induced increases in bone turnover rate and eroded surface. This delayed ovariectomy induced trabecular bone loss in the proximal tibial metaphysis, but had no effect on the tibial shaft. Like HCTZ, moexipril also reduced blood pressure after the first week of treatment but it had no apparent effect on either the proximal tibial metaphysis or the tibial shaft. A combination of moexipril and HCTZ exhibited a much more potent hypotensive effect and had the same effect on bone mass and dynamic end-points as HCTZ alone. Our data indicate that (1) HCTZ treatment has some transient beneficial effects on both antihypertension and osteoprotection in hypertensive osteopenic rats, (2) the combination of moexipril with HCTZ improved the antihypertensive effect but did not potentiate or hamper the osteoprotective effect of HCTZ, and (3) the skeletal effect of estrogen is not impacted by the hypertensive state. These findings are relevant for the use of ACE inhibitor and thiazide diuretics, alone or in combination, in antihypertensive therapy in postmenopausal women.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Raloxifene analog (LY117018 HCL) ameliorates cyclosporin A-induced osteopenia in oophorectomized rats.

Cyclosporin A (CsA) administered to the oophorectomized (Ox) rat exacerbates the high turnover osteopenia associated with estrogen deficiency. 17 beta-estradiol replacement therapy prevent this bone loss. The aim of this study was to see whether an estrogen-like compound, Raloxifene analog (LY117018 HCL, Ral) could likewise ameliorate CsA-induced osteopenia in the Ox rat. Sixty 6-month-old Sprague-Dawley rats, divided into five groups, underwent oophorectomy. One group acted as a basal group and the others received either vehicle (group B), CsA 15 mg/kg/day (group C), Ral 3 mg/kg/day (group D), or CsA 15 mg/kg/day and Ral 3 mg/kg/day (group E) for 28 days by gavage. A sixth sham operated group of 12 rats received vehicle only (group A). Rats were weighed and bled on days 0, 14, and 28 for measurement of ionized calcium, glucose, osteocalcin (BGP), 17 beta-estradiol, and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Tibiae were removed on day 28 for bone histomorphometry after double tetracycline and calcein labeling. Oophorectomy caused a significant gain in weight in groups B and C which was prevented by Ral in groups D and E. Randomized blood glucose levels and 1,25(OH)2D3 levels were elevated in both CsA-treated groups. Blood ionized calcium levels were lower in vehicle (group B) compared with sham (group A) on day 28. Ox (group B) had significantly higher serum BGP levels compared with sham-operated rats. Serum BGP levels were further elevated in group C compared with vehicle and were lowered in both Ral-treated groups to vehicle levels by day 28. Bone histomorphometry revealed a high turnover osteopenia with increased parameters of bone formation and resorption and loss of cancellous bone volume postoophorectomy (group B). CsA (group C) exacerbated the effects of oophorectomy. Ral (group D) completely prevented the high turnover osteopenia caused by oophorectomy and was able to attenuate substantially the effects of CsA in the Ox rat (group E). Ral therapy ameliorated CsA-induced osteopenia in the Ox rat and might prove a useful agent in preventing bone loss in postmenopausal women receiving CsA.

Animals↗
PubMed1996

Short-term systemic insulin-like growth factor-1 is unable to prevent cyclosporin A-induced osteopenia in the rat.

Immunosuppression with cyclosporin A (CsA) is effective in a number of immune-mediated diseases and in preventing rejection following organ transplantation. We have repeatedly demonstrated that CsA in the rat model produces accelerated bone remodelling with net bone loss, best characterized in trabecular bone. IGF-I holds promise as a treatment for various osteopenic conditions. Although currently a subject of much controversy, various studies have suggested that in vivo it is anabolic to cortical as well as trabecular bone. The purpose of this study was, in part, to further characterize the effects of CsA and IGF-I on trabecular and cortical bone, and to see whether systemic IGF-I is able to modulate CsA's deleterious skeletal effects. Sixty 10 week-old, male, Sprague-Dawley rats were randomized to receive the following daily for 3 weeks: (1) CsA vehicle (veh) per os (po) + recombinant human (rh) IGF-1 veh subcutaneously (sc); (2) CsA 15 mg/kg po + rhIGF-I-veh; (3) CsA-veh + rhIGF-I 200 microg/kg sc; (4) CsA-veh + rhIGF-I 600 microg/kg sc; (5) CsA 15 mg/kg + rhIGF-I 200 microg/kg, and (6) CsA 15 mg/kg + rhIGF-I 600 microg/kg. Rats were weighed and venous blood was sampled serially for determination of glucose, ionized calcium (Ca2+), PTH, vitamin D, and osteocalcin. Following sacrifice on day 20, histomorphometry was performed on double calcein-labeled tibial metaphysis and diaphysis. All rats receiving CsA had elevated levels of blood glucose and osteocalcin by day 9 and vitamin D at day 20. PTH was similar in all groups, and Ca2+ was only raised in the CsA and CsA + IGF-I 200 microg/kg groups. Rats receiving IGF-I 200 microg/kg and IGF-I 600 microg/kg gained more weight than either vehicle- or CsA-treated animals, attesting to IGF-1's anabolic properties. CsA caused severe trabecular bone loss, not prevented by IGF-I; it even further increased the eroded surface. CsA and IGF-I had little effect on cortical bone volume or marrow area. IGF-I increased endocortical matrix synthesis, as evidenced by the increases in the percent endocortical osteoid perimeter, an effect negated by the addition of CsA. This experiment demonstrates that trabecular bone is more susceptible than cortical bone to the deleterious effects of CsA and indicates little role for IGF-1 in the pathophysiology or treatment of CsA-induced bone disease at the given doses and duration of treatment.

Animals↗
PubMed1996

Time responses of cancellous and cortical bones to sciatic neurectomy in growing female rats.

Effects of unilateral sciatic neurectomy on the responses of both cancellous and cortical bones were studied in growing female rats at 0, 1, 4, 8, and 12 weeks after operation. Using double-fluorescent labeling techniques, histomorphometric analyses were performed on longitudinal sections of proximal tibial metaphyseal secondary spongiosa (PTM) and on cross sections of tibial shaft (TX). In PTM, sciatic neurectomy not only inhibited the age-related bone gain, but also reduced the trabecular bone mass by 46%, which was accompanied by decreases in trabecular number, thickness, and node to node density, and an increase in trabecular separation and free end to free end density. The bone loss occurred mainly between 1 and 4 weeks after operation. A sharp increase in bone formation indices was observed during the first week after nerve section. However, these endpoints quickly dropped to levels lower than those of sham-operated controls at 4 weeks, and were not different from the control levels at 8 weeks after operation. Eroded surface increased progressively after sciatic neurectomy during the 12 weeks experimental period. In TX, sciatic neurectomy inhibited the age-related increase in total tissue area that maintained it at the basal control level. However, the cortical bone area in neurectomized legs was lower than that in sham-operated controls. Sciatic neurectomy also stimulated the bone formation indices on both periosteal and endocortical surfaces during the first week after operation. These endpoints declined sharply between 1 and 4 weeks and then maintained at control levels between 8 and 12 weeks post surgery. Endocortical eroded surface increased 1 week after neurectomy, reached the peak at 8 weeks, and then decreased thereafter. These findings suggest that (1) sciatic neurectomy not only inhibited age-related bone gain but also induced marked bone loss in cancellous bone site and inhibited age-related bone gain in cortical bone site, which mainly resulted from the decrease in bone formation and the increase in bone resorption; (2) the changes in both cancellous and cortical bones responded to sciatic neurectomy occurred mostly within the first 4 weeks and stabilized between 8 and 12 weeks after surgical intervention. In conclusion, the unilateral sciatic neurectomized rat is a complex model in which to study osteopenia. Despite sciatic neurectomy being a simple operation, the interactions of skeletal responses to postsurgical regional acceleratory phenomenon (RAP) and disuse and adaptation changes cannot be clearly differentiated. Furthermore, the complications from growth and aging should be avoided.

Animals↗
PubMed1995

Prostaglandin E2 administration prevents bone loss induced by orchidectomy in rats.

The objects of this study were to investigate whether prostaglandin E2 (PGE2) can prevent orchidectomy (ORX)-induced cancellous bone loss in growing male rats, and to determine the differential effects of PGE2 on sham-operated (sham) and ORX male rats. Fourteen-week-old Sprague-Dawley male rats were divided into groups of basal, vehicle-treated sham, PGE2-treated sham, vehicle-treated ORX, and PGE2-treated ORX rats for either 3 or 9 weeks. PGE2 was given at 6 mg/kg body weight daily by subcutaneous injection. Static and dynamic cancellous bone histomorphometry were performed on double-fluorescent labeled undecalcified proximal tibial metaphyseal sections. No effect was observed by ORX on body weight or longitudinal bone growth rate when compared with sham-operated controls. However, androgen deficiency caused significant increases in percent eroded perimeter, mineral apposition rate, and bone turnover (bone-volume-referent-bone formation rate), which resulted in a significant decrease in trabecular bone number, increase in trabecular separation, and a nonsignificant decrease in trabecular bone area by 3 weeks of ORX. After 9 weeks of ORX, trabecular bone area and number were significantly decreased, and trabecular separation, percent eroded perimeter, and the index of bone turnover (bone-volume-referent-bone formation rate) remained significantly increased while the index of bone formation (tissue-volume-referent-bone formation rate) was nonsignificantly decreased when compared with sham controls. When 6 mg PGE2/kg/day was given for 3 and 9 weeks, similar anabolic effects were observed in sham and ORX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats.

The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. Immobilization for 30 days without treatment decreased trabecular bone area, number, and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1-38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, and restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of female rats with continuously immobilized right hindlimbs. These results suggest that PTH may be useful in treating disuse-induced osteoporosis in humans.

Animals↗
PubMed1995

Rapamycin: a bone sparing immunosuppressant?

Immunosuppressant therpay is associated with osteoporosis both clinically, post-transplantation, and experimentally. In rats, cyclosporin A (CsA) and FK506 induce a state of high turnover rapid bone loss. After 14 days of administration in immunosuppressive doses, the more recently discovered immunosuppressant, rapamycin, resulted in no change of cancellous bone volume. A longer study over 28 days has now been carried out; contrasting the new drug with CsA and FK506. Sixty, 10-week-old Sprague-Dawley rats were randomly divided into five groups of 12 rats each. The first group served as an aging control. The remaining four groups received, by daily gavage, a combined vehicle placebo, CsA 15 mg/kg, FK506 5 mg/kg, and rapamycin 2.5 mg/kg, respectively. CsA- and FK506-treated rats, but not those treated with rapamycin, demonstrated high turnover osteoporosis with raised serum 1,25(OH)2D (p < 0.05) and elevated serum osteocalcin (p < 0.05). The trabecular bone area was decreased by 66% (p < 0.01) in the CsA group and 56% (p < 0.05) in the FK506-treated group compared with the control animals. The CsA- and the rapamycin-treated groups failed to gain weight and developed severe hyperglycemia (> 20 mmol/l, p < 0.001) by day 14 but which largely resolved by day 28. Unlike the groups treated with CsA and FK506, rapamycin-treated rats had no loss of trabecular bone volume but there was increased modeling and remodeling and a decreased longitudinal growth rate. Rapamycin may thus confer a distinct advantage over the established immunosuppressants in not reducing bone volume in the short term.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Extra cancellous bone induced by combined prostaglandin E2 and risedronate administration is maintained after their withdrawal in older female rats.

Prostaglandin E2 (PGE2) has been recognized for its marked anabolic effect on bone, but the bone gain is lost after the cessation of PGE2 treatment. In previous studies, we were successful in maintaining the new bone by administering a bisphosphonate after the withdrawal of PGE2 treatment. The objective of this study was to determine the fate of the extra bone induced by a combination with PGE2 and risedronate after discontinuing treatment. Ninety-six 9-month-old virgin female Sprague-Dawley rats were treated with 1 or 5 micrograms of risedronate/kg/twice weekly, 6 mg of PGE2/kg/day alone or 6 mg of PGE2/kg/day plus 1 or 5 micrograms of risedronate/kg/twice weekly for 60 days (day 0) and followed by 60 days without treatment (day 60). We have reported the results from the groups treated for 60 days previously. This report is restricted to the histomorphometric findings on the secondary spongiosa of the proximal tibial metaphysis in the groups after withdrawal for 60 days. We found that the only group that maintained the PGE2 induced new bone after withdrawal was the group treated with 6 mg of PGE2/kg/day plus 5 micrograms of risdronate/kg/twice a week. Withdrawal of this combined treatment depressed bone turnover (bone-based bone formation rate, activation frequency) and bone resorption (percent eroded perimeter). The tissue mechanisms responsible for the protection drew from the previously deposited risedronate.

Aging↗
PubMed1995

Droloxifene prevents ovariectomy-induced bone loss in tibiae and femora of aged female rats: a dual-energy X-ray absorptiometric and histomorphometric study.

Our previous studies indicated that droloxifene (DRO), a tissue-specific estrogen antagonist/agonist, prevented bone loss without causing uterine hypertrophy in growing ovariectomized (OVX) rats. Using dual-energy X-ray absorptiometry (DXA) and bone histomorphometry, the current study compared the efficacy of DRO to 17 beta-estradiol (E2) in preventing OVX-induced bone loss in tibiae and femora of 19-month-old rats to determine whether DRO had similar skeletal effects as E2 in aged female rats. Sprague-Dawley female rats were OVX or sham-operated (sham) at 19 months of age. The sham-operated rats were treated with vehicle (oral), while the OVX rats were treated with vehicle (oral), E2 at 30 micrograms/kg/day (sc), or DRO at 2.5, 5, or 10 mg/kg/day (oral) for 8 weeks. Bone mineral density (BMD) of whole femora (WF), distal femoral metaphyses (DFM), femoral shafts (FS), and proximal femora (PF) was determined using DXA. Static and dynamic cancellous bone histomorphometric analyses were performed in double-labeled undecalcified longitudinal sections from proximal tibial metaphyses. Ovariectomy for 8 weeks significantly reduced the BMD of WF, DFM, FS, and PF (from -6 to -15%). Treatment with E2 completely prevented the decreases in BMD of WF and DFM and had no significant effects in BMD of FS and PF in aged OVX rats. The decrease in BMD of DFM induced by OVX was prevented by treatment with DRO at all dose levels. In addition, DRO at 10 mg/kg/day prevented OVX-induced decreases in BMD of WF, FS, and PF.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Droloxifene inhibits cortical bone turnover associated with estrogen deficiency in rats.

Droloxifene (DRO), an estrogen antagonist/agonist, has been shown to possess estrogen-like effects in inhibiting bone turnover leading to cancellous bone loss in ovariectomized (OVX) rats. The purpose of this study was to determine the effects of DRO on cortical bone turnover in OVX rats. Sprague-Dawley female rats at 5 months of age were sham-operated (sham, n = 8) and orally treated with vehicle, or OVX (n = 56) and orally treated with either vehicle, DRO at 0.1, 1, 5, or 10 mg/kg/day, or 17 alpha-ethynyl estradiol (EE) at 3 or 30 micrograms/kg/day for 4 weeks. Static and dynamic cortical bone histomorphometry was performed on double fluorescent labeled, undecalcified cross sections of tibial diaphyses (proximal to the tibiofibular junction). There were no significant differences in tibial diaphyseal cross sectional area, marrow cavity area, and cortical bone area between groups after 4 weeks of administration. Periosteal mineralizing surface, mineral apposition rate, and bone formation rate-surface referent and endocortical eroded surface increased significantly, while endocortical mineral apposition rate and bone formation rate-surface referent increased nonsignificantly in OVX controls compared to sham controls. Treatment with DRO at doses of 0.1 to 10 mg/kg/day dose-dependently attenuated the OVX-induced higher bone formation indices in both the periosteal and endocortical surfaces and higher bone resorption index in the endocortical surface. At the highest dose (10 mg/kg/day), DRO completely inhibited the increases in bone formation and resorption indices in OVX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Adaptation of non-growing former epiphysis and metaphyseal trabecular bones to aging and immobilization in rat.

No data exit for distal tibia (DT), a bone site with growth plate closure at 3 months of age and with very low trabecular bone turnover rate. The purpose of this study was to characterize the response of DT to aging and immobilization (IM) in 6 to 16.5 month-old female rats. One hundred and forty six 6 month-old Sprague-Dawley rats were divided into aging controls and right hindlimb immobilization (RHLI) groups. The right hindlimb was immobilized against the abdomen with elastic bandages. Rats were sacrificed serially from 6 to 16.5 months old at intervals of 2 to 8 weeks. The histomorphometric study was performed on areas of former epiphyseal and metaphyseal trabecular bone of DT. No changes on bone mass or architecture were found in aging controls throughout the study. There was a decrease in bone mass of the former epiphysis after 3.5 months of IM due to resorption exceeding formation. Then it reverted to the aging control level at 4 months post IM. At the former metaphyseal site, significant bone loss (-19%) was observed as early as two weeks after IM. The peak bone loss (-54%) was reached at 1.5 months after IM and plateaued thereafter. The bone loss was mainly due to the reduction of trabecular thickness although trabecular number decreased significantly after 3.5 months IM. These results suggest that both former epiphysis and metaphyseal trabecular bones in DT can quickly adapt by losing bone to immobilization.

Adaptation, Physiological↗
PubMed1995

Remobilization partially restored the bone mass in a non-growing cancellous bone site following long term immobilization.

There is no report in the rat of the effects of remobilization (RM) in an adult bone site. The aim of this study was to determine whether complete recovery from IM-induced bone loss will occur in a non-growing bone site, the distal tibia. Seventy-five 6-month-old virgin Sprague-Dawley female rats were used in this study. Their hindlimbs were immobilized against the abdomen with bandages for 18 weeks, then remobilized for 2, 10 or 20 weeks. Distal tibial sections were analyzed in the former epiphysis, 0.3 mm proximal from the calcified cartilage, and in trabecular bone of the former metaphysis between 0.3 mm and 1.92 mm proximal to the former epiphysis. A significant bone loss occurred in both former epiphyseal and metaphyseal trabeculae at 18 weeks after IM. The lost bone was partially recovered at 10 weeks of RM, but the bone mass was still lower than in aging controls by the end of the study. The partial recovery was characterized by decreasing former epiphyseal bone porosity and thickening of former metaphyseal trabeculae with no effect on trabecular number. We concluded that both distal tibia regions only partially recovered, during 20 weeks of RM from the long time IM.

Animals↗
PubMed1995

Parathyroid hormone therapy accelerates recovery from immobilization-induced osteopenia.

Previous reports have shown that bone mass and architecture will partially recover by remobilization (RM) in immobilization (IM)-induced osteopenia. The aim of this study was to test whether PTH can accelerate the recovery during RM from the IM-induced osteopenia. Six-month-old Sprague-Dawley female rats were divided into aging and IM groups. The right hindlimb of rats was immobilized against the abdomen by elastic bandages for 18 weeks, then groups of rats were further IM or RM for 2, 10 and 20 weeks and given 30 or 80 micrograms hPTH (1-38)/kg/d s.c. Secondary spongiosa of proximal tibial metaphyses (PTM) were studied. Immobilization reduced the trabecular area, number and thickness at the first 18 weeks post IM, then plateaued. Ten weeks of RM restored 40% trabecular bone from IM controls due to thickening of the trabeculae. However, the trabecular area was still -14% and -13% lower than that of aging controls at 10 and 20 weeks. Two weeks of 30 micrograms PTH/kg/d in IM rats restored the bone to aging control levels, two weeks of 30 micrograms PTH/kg/d in RM rats and of 80 micrograms PTH/kg/d in both RM and IM rats added extra bone. Extending the treatment to 10 and 20 weeks, the same amount of total bone was added to both IM and RM rats. These findings indicate PTH is a powerful agent that can accelerate the recovery and add extra bone to osteopenic cancellous bone in both IM and RM rats.

Analysis of Variance↗
PubMed1995

Tomographic (pQCT) and biomechanical effects of hPTH(1-38) on chronically immobilized or overloaded rat femurs.

Six-month old rats chronically submitted to right hindlimb immobilization (IM) with mechanical overload (OL) of the left leg were treated 1 month later with 200 micrograms/kg/d of hPTH(1-38) for 15 or 75 days. Peripheral quantitative computed tomography (pQCT) scans and bending tests showed that hPTH increased cortical mass and volumetric BMD (vCtBMD) in both legs. However, elastic modulus of cortical bone and diaphyseal load-bearing capacity were improved only in OL bones. Improvement of diaphyseal strength was attributable to that of cortical bone quality, yet a stronger mechanostatic response of cortical modeling to bone material quality was also observed in treated OL bones. Data support hPTH(1-38) use for improving cortical bone mass and strength and point out a physical activity interaction with therapeutic results.

Analysis of Variance↗
PubMed1995

An in-vivo model for the rapid assessment of skeletal effects of anabolic agents.

We recently developed an in vivo model which can be used to rapidly assess the local skeletal effects of anabolic agents. In this model, 160 g Sprague-Dawley (SD) rats were used. A stainless steel cannula was inserted into the marrow cavity of the proximal tibia through the anterior-medial cortex 6 mm distal to the knee joint. The outer opening of the cannula was covered by skin. Agents with known anabolic skeletal effects or vehicle were injected daily for 10 days into the marrow region by a small needle passing through the cannula. Rats were also injected subcutaneously with a fluorescent bone marker to label the newly formed bone. Injection sites were fixed, embedded, and sectioned for histomorphometric analysis of trabecular bone. PTH and PGE2 stimulated a large amount of new trabecular bone formation in regions proximal and distal to the injection site as measured by histomorphometry. Control groups showed minimal bone formation, limited to formation of a thin layer of bony shell immediately surrounding the cannula. The profound anabolic skeletal effects of PTH and PGE2 seen in this Local Injection Model are similar to those seen in systemic injection (i.e. subcutaneous injection in intact or castrated male and female rats) previously reported. This Local Injection Model combines numerous advantages of in vivo models (systemic injection) and in vitro models when assessing agents with anabolic skeletal activities. Compared to conventional in vivo systemic injection models, this model enables detection of anabolic skeletal effects using very small quantities (in microgram) of test agents in a short treatment period (< 10 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Early effects of prostaglandin E2 on bone formation and resorption in different bone sites of rats.

The aim of this study was to determine early effects of prostaglandin E2 (PGE2) on bone mass, formation and resorption in a growing cancellous bone site (the proximal tibial metaphysis, PTM), non-growing cancellous bone site (the distal tibial metaphysis, DTM), and cortical bone site (the tibial shaft, TX) with histomorphometric analysis. Six mg PGE2/kg/d was given s.c. to 6-month-old Sprague-Dawley female rats for 5, 10 or 16 days. Double fluorescent labels were given to 0, 10- and 16-day PGE2 treatment and 16-day control groups. Significant increase in bone mass was found after 16 days treatment in cancellous bone sites but not in the cortical bone site. Stimulated bone formation, indicated by the increase in osteoid perimeter, was observed as early as 5 days post-treatment in all 3 bone sites. Bone formation indices were increased after 10 days of treatment, however, there was no difference in selected bone formation indices between 10 and 16 days PGE2 treatments at all 3 bone sites. Significant increase in eroded surface and eroded surface covered with osteoid was observed in cancellous bone sites after 5 days, but decreased after 10 days of treatment. Although the eroded surface was not elevated in TX at the 5th day, the eroded surface covered with osteoid was increased on endocortical surface which indicated that PGE2 stimulated bone resorption on this surface prior to day 5. We concluded that PGE2 stimulated the bone formation and resorption as early as 5 days post-treatment. The levels of stimulated bone formation was TX > DTM > PTM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Risedronate pretreatment does not hamper the anabolic effects of prostaglandin E2 in ovx rats.

Pretreatment of an anti-resorptive agent on the anabolic effects of prostaglandin E2 (PGE2) was studied on the proximal tibia and tibial shaft of ovariectomy (ovx) rats. Two days after ovx, rats were treated with either risedronate (Ris, 5 micrograms/kg twice weekly) or vehicle (V) for 60 days and then switched to 3 or 6 mg/kg/d PGE2 for 21 or 90 days. Bone area of both proximal tibial metaphysis (PTM) and tibial shaft (TX) were measured. Pretreatment with Ris increased the bone mass in PTM but not in TX of ovx rats. In the PTM, PGE2 produced the same percentage of new bone mass in both V- and Ris-pretreated ovx rats. The amount of new bone was almost the same after 3 weeks and 12 weeks of PGE2 treatment. There was no difference in the anabolic effects of 3 and 6 mg PGE2/kg/d in V-pretreated rats; however, the effects in Ris-pretreated groups were greater with 6 mg PGE2/kg/d than with 3 mg PGE2/kg/d. In TX, only the 6mg PGE2/kg/d administration added new bone on endocortical surfaces of both V- or Ris-pretreatment rats which leads to thickening the minimal cortical width, decreasing the marrow cavity and increasing total bone area. Both doses of PGE2 created new trabecular bone in the marrow cavity of tibial shaft in both vehicle- and Ris-pretreated ovx rats. These results suggest that Ris-pretreatment did not hamper the anabolic effects of PGE2 on either PTM or TX in ovx rats.

Aging↗