PubMed Health⌕ Search

Biomedical subjects

S Epstein

Publications and source records attributed to S Epstein.

At least 19 recordsLinked to original sources
PubMed2005

Biological properties and mechanism of action of ibandronate: application to the treatment of osteoporosis.

Bisphosphonates, with their proven efficacy and safety, are the most commonly prescribed treatment for women with postmenopausal osteoporosis; however, optimal efficacy is often not achieved due to poor patient adherence to medication. Poor adherence leads to an increased risk of fracture, which itself results in morbidity, elevated healthcare costs and potentially, mortality. Although weekly rather than daily dosing of bisphosphonates has improved adherence, there remains a significant problem, and dosing less frequently than weekly has been suggested as a possible means for further improving adherence. Ibandronate is a new bisphosphonate that has a specific structure and set of characteristics that enable less frequent dosing than currently available bisphosphonates. This review provides details of the general structural features of all bisphosphonates and how these are understood to contribute to their functions in osteoporosis treatment. From this, the unique structure of ibandronate is described, along with how this translates into the high antiresorptive potency, favorable bone-binding, persistence in bone, and good tolerability that permits less frequent dosing. Finally, the clinical evidence for ibandronate is briefly presented, demonstrating the viability of less frequent dosing, with its potential benefits for patient convenience and adherence to therapy.

Bone Resorption↗
PubMed2003

Disposition of cyclosporine after intravenous and multi-dose oral administration in cats.

The aim of this study was to evaluate the disposition of cyclosporine after intravenous (i.v.) and oral administration and to evaluate single sampling times for therapeutic monitoring of cyclosporine drug concentrations in cats. Six adult male cats (clinically intact) were used. Two treatments consisting of a single i.v. cyclosporine (1 mg/kg) and multiple oral cyclosporine (3 mg/kg b.i.d p.o. for 2 weeks) doses. Whole blood cyclosporine concentrations were measured at fixed times by high performance liquid chromatography and pharmacokinetic values were calculated. Mean values for the i.v. data included AUC (7413 ng/mL.h), t1/2 distribution and elimination (0.705 and 9.7 h, respectively), Cmax (1513 ng/mL), and Vd(ss) (1.71 L/kg). Mean values for the oral data included AUC (6243 ng/mL.h), t1/2 of absorption and elimination (0.227 and 8.19 h, respectively), and Cmax (480.0 ng/mL). Bioavailability of orally administered cyclosporine was 29 and 25% on days 7 and 14 respectively. Whole blood comment cyclosporine concentration 2 h after administration (C2) better correlated with AUC on days 7 and 14 than trough plasma concentration (C12). The rate of oral cyclosporine absorption was less than expected and there was substantial individual variation. Therapeutic drug monitoring strategies for cyclosporine in cats should be re-evaluated.

Administration, Oral↗
PubMed2003

Disintegration/dissolution profiles of copies of Fosamax (alendronate).

OBJECTIVE: Poor quality has been reported for some generics and other copies of original products. We performed a pilot study to compare the disintegration/dissolution profiles of FOSAMAX (alendronate) 70 mg tablets with those of copies of FOSAMAX that were manufactured outside the United States. RESEARCH DESIGN AND METHODS: We used the standard United States Pharmacopeia (USP) disintegration method to evaluate FOSAMAX 70 mg tablets and 13 copies. At least 12 (n = 12) dosage units were tested for each product (except Fosmin, n = 10). The dissolution profiles of FOSAMAX and one representative copy were also compared. RESULTS: Nine copies (Osteomax, Defixal, Fosmin, Endronax, Osteomix, Genalmen, Fixopan, Osteoplus, and Fosval) disintegrated two- to ten-fold faster than FOSAMAX. Three other copies (Neobon, Regenesis, and Ostenan) disintegrated at least five-fold slower than FOSAMAX. Neobon is a softgel capsule, so special consideration was given to this different dosage form. One copy (Arendal) did not fall into either category but exhibited potentially large inter- and intra-lot variability. Dissolution of alendronate from Regenesis lagged behind that from FOSAMAX. CONCLUSION: Slower disintegration may reduce efficacy because bisphosphonates must be taken in the fasting state and contact with food or even certain beverages severely reduces bioavailability. Faster disintegration (or the use of gel-caps or other alterations to the drug formulation) could increase the risk of esophagitis, an adverse event associated with prolonged contact of the esophagus with bisphosphonates. These disintegration and dissolution results suggest that important differences may exist between FOSAMAX and its copies with regard to bioavailability, pharmacokinetics, and clinical efficacy and safety profiles. Additional testing is warranted to evaluate the pharmacokinetics and clinical safety of these copies.

Alendronate↗
PubMed2001

Effect of the interaction of parathyroid hormone and cyclosporine a on bone mineral metabolism in the rat.

Cyclosporine A (CsA) induces high turnover osteopenia in the rat and there is evidence for this in humans. Recent studies suggest that increases in parathyroid hormone (PTH) may be involved in posttransplantation bone loss. However, human studies are difficult to interpret since transplant patients usually receive a cocktail of immunosuppressants and have underlying disease. Our aim was to try to resolve the influence of the absence or presence of PTH on CsA-induced bone disease. Male Sprague Dawley rats aged 7-9 months, either sham operated or parathyroidectomized (PTX), were randomly divided into vehicle and CsA groups. All PTX rats were given oral calcium supplementation ad libitum. The rats were divided into groups: basal, sham/vehicle, sham/CsA, PTX/vehicle, and PTX/CsA. Serial biochemistry was performed 0, 14, and 28 days after the start of the experimental period; bone histomorphometry was performed 28 days after the start of the experimental period. Statistical analysis consisted of group comparisons and factorial analyses. The results showed that CsA alone produced a high turnover osteopenia consistent with previous studies. In the PTX animals there was an increase in bone mass. PTX also decreased osteoblast activity and recruitment, and serum 1,25OH2D levels. Serum levels of osteocalcin (BGP) were unaffected by PTX. The combination group (PTX/CsA) did not differ statistically from the controls in most of the histomorphometric parameters measured, with the exception of reduced mineral apposition and bone formation rates, reflecting the effects of PTX. Serum BGP and 1,25OH2D levels did not differ, but PTH was reduced from the control. Explanations for these results are (1) CsA and PTX exert their effects via separate mechanisms, negating each other; (2) in the absence of PTH, CsA managed to cause bone loss, and thus PTH may not be essential for CsA-induced bone loss; or (3) the profound accelerated bone loss produced by CsA in normal rats requires PTH. These findings may help explain the discrepancies found in clinical studies where bone loss occurs with either elevated or normal PTH levels.

Animals↗
PubMed2001

The endothelin receptor antagonist, L-754,142 does not prevent cyclosporine A-induced osteopenia in rats.

Cyclosporine A (CsA) is a potent immunosuppressive agent widely used to prevent allograft rejection. In vivo administration of CsA is associated with the development of high-turnover osteopenia. Endothelin-1 (ET), a vasoconstrictive peptide, has been implicated in CsA-induced nephrotoxicity and hypertension. Recent evidence suggests that endothelin plays a pivotal role in bone metabolism. The present study was designed to investigate whether L-754,142 (ETRA), the combined endothelin A and B receptor antagonist, when given to rats, would favorably modify the bone loss caused by CsA. Fifty, 5-month-old male Sprague-Dawley rats were randomly divided into five groups of 10 rats each. The first group served as a basal control. The remaining four groups received, by daily gavage for 28 days, (1) a combined CsA and ETRA vehicle, (2) CsA, 10 mg/kg, (3) ETRA, 30 mg/kg, and (4) CsA, 10 mg/kg and ETRA, 30 mg/kg, respectively. Rats were weighed and venous blood was collected on days 0, 14, 28 for determination of BUN, creatinine, calcium, PTH, osteocalcin, and 1,25(OH)2 D. Tibiae, after double labeling, were removed following sacrifice for histomorphometry. Both CsA-treated rats and CsA/ETRA-treated rats demonstrated trabecular osteopenia with raised serum osteocalcin, and 1,25(OH)2D levels when compared to control animals (P < 0.05). Rats given CsA alone developed renal impairment, as shown by an increased BUN. The combination group did not develop renal impairment. The results suggest that endothelin may contribute to the development of CsA-induced nephrotoxicity, which was prevented by ETRA, but does not seem to play a role in CsA-induced osteopenia.

Acetamides↗
PubMed2001

Transforming growth factor-beta administration modifies cyclosporine A-induced bone loss.

Cyclosporine A (CsA), a potent immunosuppressant used in transplantation, induces increased formation with excess resorption in the rat with resultant osteopenia. These findings are confirmed in the human model. Transforming growth factor-beta (TGF-beta) is reported to be involved in the coupling of bone formation with resorption and in vivo and in vitro stimulates osteoblasts, and in vitro inhibits osteoclasts. CsA stimulates secretion of TGF-beta1 in humans, which, while improving immunosuppression, may also contribute to renal toxicity. This study was performed determine whether exogenously administered TGF-beta would modify the bone effects of CsA. Male Sprague-Dawley rats, 6 months of age, were randomized to receive: TGF-beta and CsA vehicle (group A); TGF-beta 5 microg/kg three times per week and CsA vehicle (group B); TGF-beta vehicle and CsA 10 mg/kg (group C); or TGF-beta 5 microg/kg three times per week and CsA 10 mg/kg (group D). These were compared with control over 28 days. CsA, but not TGF-beta, increased serum 1,25(OH)(2)D levels throughout the study. CsA increased osteocalcin (BGP), but TGF-beta negated this effect. Histomorphometry confirmed the known effects of CsA, whereas TGF-beta alone had no effect. However, in combination, TGF-beta blocked CsA's effect and increased osteoblast recruitment and activity, as reflected by increased percent mineralizing surface, percent osteoid perimeter, bone formation rate (bone volume referent), and activation frequency. Thus, it appears as if TGF-beta administration may have potential in modulating the deleterious bone effects of CsA.

Animals↗
PubMed2001

Characterization of altered myocardial fatty acid metabolism in patients with inherited cardiomyopathy.

Inherited defects in myocardial long-chain fatty acid metabolism are increasingly recognized as a cause of cardiomyopathy and sudden death in children. To evaluate whether the phenotypic expression of these genetic diseases could be delineated using positron emission tomography (PET), 11 patients with inherited defects in fatty acid metabolism were evaluated and results were compared with those of 6 nonaffected siblings. Myocardial perfusion, myocardial oxygen consumption (MVO2), and long-chain fatty acid metabolism were determined noninvasively with PET using quantitative mathematical models. There were no differences in haemodynamics, perfusion, MVO2 or plasma substrate levels between groups. Patients with defects in enzymes of fatty acid beta-oxidation (acyl-CoA dehydrogenase and 3-hydroxyacyl-CoA dehydrogenase deficiencies) (n = 5) had diminished myocardial palmitate oxidation compared with healthy siblings (3.2 +/- 3.0 vs. 13.0 +/- 5.6 nmol/g per min, p < 0.03) and a decrease in the percentage of MVO2 accounted for by palmitate (2% +/- 3% vs. 9% +/- 5%, p < 0.04). In these patients, extracted palmitate was shunted into a slow-turnover compartment (predominantly reflecting esterification to triglycerides) with expansion of palmitate in that pool (185 +/- 246 compared with 27 +/- 67 nmol/g in healthy siblings,p < 0.02). In contrast, myocardium of patients with carnitine deficiency (n = 6) (all on oral carnitine therapy) had normal palmitate extraction but expansion of the interstitial/cytosolic fatty acid pool (617 +/- 399 vs. 261 +/- 73 nmol/g in healthy siblings, p < 0.04), suggesting different mechanisms for handling upstream fatty acyl intermediates. Thus, PET can be used to noninvasively assess abnormal myocardial handling of fatty acids in patients with inherited defects of metabolism. This approach should be useful in the assessment of altered myocardial fatty acid metabolism associated with cardiomyopathy as well as for evaluating the efficacy of therapeutic interventions in affected patients.

Acetates↗
PubMed2001

Microbiology of serous otitis media in children: correlation with age and length of effusion.

The purpose of this study was to correlate the microbiology of serous otitis media in children with the duration of the condition and the patient's age. Aspirates of serous ear fluids from 114 children were examined for aerobic and anaerobic bacteria. Bacterial growth was noted in 47 patients (41%). Aerobic organisms only were recovered in 27 aspirates (57% of the culture-positive aspirates); anaerobic bacteria only in 7 (15%); and mixed aerobic and anaerobic bacteria in 13 (28%). A total of 83 bacterial isolates were recovered, accounting for 1.8 isolates per specimen (1.2 aerobes and 0.6 anaerobe). There were a total of 57 aerobic isolates, including Haemophilus influenzae (15 isolates), Streptococcus pneumoniae (13), and Staphylococcus sp (12). Twenty-six anaerobes were recovered, including anaerobic gram-positive cocci (10), Prevotella spp (8), and Propionibacterium acnes (4). The rate of positive cultures (20 of 36; 56%) was higher in patients younger than 2 years of age than in those older than 2 years of age (27 of 78; 35%). Streptococcus pneumoniae and H influenzae were more often isolated in children younger than 2 years of age and those with effusion for 3 to 5 months, whereas anaerobes were recovered more often in those older than 2 years of age and those with effusion for 6 to 13 months. These data illustrate the effects of the length of effusion and age on the recovery of aerobic and anaerobic bacteria in serous otitis media.

Age Factors↗
PubMed2001

Immunosuppressant use without bone loss--implications for bone loss after transplantation.

Cyclosporine A (CsA) is associated with posttransplantation bone disease. Immunosuppressant drugs such as sirolimus (SRL), which are more potent and less deleterious than CsA, are being developed. Previous experiments have shown that SRL although immunosuppressive, is relatively bone sparing. The use of low doses of CsA and SRL in combination has displayed in vivo synergism. This study was initiated to examine the effect of low-dose CsA and SRL on bone metabolism, thereby hopefully providing a bone sparing immunosuppressive regimen for transplant recipients. One hundred and nineteen rats were divided into groups: basal, vehicle, CsA high dose, CsA low dose, SRL low dose, and combination low-dose CsA and SRL. The basal group was killed on day 0 for histomorphometry. The experimental groups were weighed and bled on days 0, 28, 56, and 84 and were killed on day 84 for histomorphometry. Serial assays for blood urea nitrogen (BUN), creatinine, and osteocalcin were performed. Osteocalcin was raised on days 28 and 56 in the high dose CsA group. Histomorphometry showed osteopenia with high-dose CsA. Low-dose CsA was relatively bone sparing, while low-dose SRL and combined low-dose CsA did not cause bone loss. In conclusion, the synergistic combination of low-dose CsA and SRL has the potential of providing both bone sparing and immunosuppressive benefits.

Animals↗
PubMed2001

Patient handling of a dry-powder inhaler in clinical practice.

BACKGROUND: Multi-dose dry-powder inhalers are perceived as being easier for patients to use than conventional pressurized aerosol inhalers; however, no study has determined whether patients handle such devices adequately and whether there is a need for patient education in this area. METHOD: We used trained observers to assess the handling of a specific multi-dose dry powder inhaler (Turbuhaler; AstraZeneca Canada; Mississauga, ON) by patients currently using the device for the management of their asthma. Fourteen discrete steps were scored independently by two observers simultaneously. Patients were divided into two groups for analysis: those who had received formal instruction in the use of the inhaler at The Asthma Centre and those who had received no formal instruction in the community. RESULTS: There was no significant difference between the formally trained groups and control groups in the percentage of handling steps performed correctly (79% vs 78%, respectively; p > 0.05). Fewer than 50% of patients in both groups demonstrated optimal breath-holding when using the device. CONCLUSION: Patient handling of Turbuhaler was generally good, with no evidence that a structured education intervention offered an advantage over the usual education incidental to the prescribing or dispensing process. The most common handling flaw, suboptimal breath-holding, is not specific to this device and is of uncertain clinical significance.

Adult↗
PubMed2001

Predicting success in weaning from mechanical ventilation.

We identified 65 observational studies of weaning predictors that had been reported in 70 publications. After grouping predictors with similar names but different thresholds, the following predictors met our relevance criteria: heterogeneous populations, 51; COPD patients, 21; and cardiovascular ICU patients, 45. Many variables were of no use in predicting the results of weaning. Moreover, few variables had been studied in > 50 patients or had results presented to generate estimates of predictive power. For stepwise reductions in mechanical support, the most promising predictors were a rapid shallow breathing index (RSBI) < 65 breaths/min/L (measured using the ventilator settings that were in effect at the time that the prediction was made) and a pressure time product < 275 cm H2O/L/s. The pooled likelihood ratios (LRs) were 1.1 (95% confidence interval [CI], 0.95 to 1.28) for a respiratory rate [RR] of < 38 breaths/min and 0.32 (95% CI, 0.06 to 1.71) for an RR of > 38 breaths/min, which indicate that an RR of < 38 breaths/min leaves the probability of successful weaning virtually unchanged but that a value of > 38 breaths/min leads to a small reduction in the probability of success in weaning the level of mechanical support. For trials of unassisted breathing, the most promising weaning predictors include the following: RR; RSBI; a product of RSBI and occlusion pressure < 450 cm H2O breaths/min/L; maximal inspiratory pressure (PImax) < 20 cm H2O; and a knowledge-based system for adjusting pressure support. Pooled results for the power of a positive test result for both RR and RSBI were limited (highest LR, 2.23), while the power of a negative test result was substantial (ie, LR, 0.09 to 0.23). Summary data suggest a similar predictive power for RR and RSBI. In the prediction of successful extubation, an RR of < 38 breaths/min (sensitivity, 88%; specificity, 47%), an RSBI < 100 or 105 breaths/min/L (sensitivity, 65 to 96%; specificity, 0 to 73%), PImax, and APACHE (acute physiology and chronic health evaluation) II scores that are obtained at hospital admission appear to be the most promising. After pooling, two variables appeared to have some value. An RR of > 38 breaths/min and an RSBI of > 100 breaths/min/L appear to reduce the probability of successful extubation, and PImax < 0.3, for which the pooled LR is 2.23 (95% CI, 1.15 to 4.34), appears to marginally increase the likelihood of successful extubation. Judging by areas under the receiver operator curve for all variables, none of these variables demonstrate more than modest accuracy in predicting weaning outcome. Why do most of these tests perform so poorly? The likely explanation is that clinicians have already considered the results when they choose patients for trials of weaning.

APACHE↗
PubMed2001

Trials of miscellaneous interventions to wean from mechanical ventilation.

We found eight randomized controlled trials (RCTs) of miscellaneous interventions that were designed to facilitate the process of weaning from mechanical ventilation. The two RCTs of high-fat/low-carbohydrate enteral nutrition found favorable physiologic effects on CO2 production and respiratory quotient, rendering this type of nutrition potentially useful in patients with impaired ventilatory reserve; however, no conclusions can be made about the outcomes of the duration of ventilation and weaning success. The two RCTs of postextubation use of noninvasive ventilation are conflicting, showing potential short-term physiologic benefit in one study, but no benefit in terms of reintubation rates or other morbidity. These RCTs are less promising than other applications of noninvasive ventilation such as those in patients with COPD exacerbations. One RCT showed no improvement in success of weaning with exogenous growth hormone administration. In the setting of very frequent baseline blood gas analyses, one RCT of oximetry and capnography was associated with significantly fewer blood gas analyses. Biofeedback to enhance safe and rapid weaning showed a dramatically lower duration of ventilation in one RCT that did not report the weaning methods used. One RCT of preextubation acupuncture showed lower rates of laryngospasm in the acupuncture group. Overall, these studies were underpowered for clinically important outcomes. Multidisciplinary, patient-centered, holistic, and non-pulmonary approaches to weaning may provide additional safe, effective adjunctive methods of hastening liberation from mechanical ventilation.

Acupuncture↗
PubMed2001

Measurement of myocardial blood flow with PET using 1-11C-acetate.

UNLABELLED: 11C-acetate has been used extensively for the noninvasive assessment of myocardial oxygen consumption and viability with PET. The use of early uptake of acetate by the heart to measure myocardial perfusion has been proposed. This study evaluated the application of 11C-acetate for absolute measurement of myocardial blood flow using a simple compartmental model that does not require blood sampling. METHODS: Eight healthy volunteers and 13 subjects with concentric left ventricular hypertrophy were studied under resting conditions with both 11Cacetate and 15O-water. Myocardial blood flow with 11C-acetate was obtained by fitting the first 3 min of the blood and tissue tracer activity curves to a two-compartment model. Flows obtained were compared with a validated approach using 15O-water. RESULTS: In healthy volunteers, regional myocardial perfusion at rest estimated with 11C-acetate was comparable with values obtained with 15O-water (1.06 +/- 0.25 and 0.96 +/- 0.12 mL/g/min, respectively). Perfusion in subjects with left ventricular hypertrophy was also comparable if the recovery coefficient (FMM) used was corrected for ventricular mass. If a fixed FMM was used, flow was greatly overestimated. FMM could be estimated from left ventricular mass (FMM = 0.46 + 0.002 x mass, r = 0.86, P < 0.0001). CONCLUSION: The results of this study suggest that 11C-acetate can be applied to quantitatively estimate myocardial perfusion under resting conditions using a two-compartment model without the need for blood sampling, provided that an appropriate FMM is chosen. This approach should increase the usefulness of this tracer and obviate administration of a separate tracer to independently measure perfusion.

Acetates↗
PubMed2000

Prevalence of coronary artery disease, complex ventricular arrhythmias, and silent myocardial ischemia and incidence of new coronary events in older persons with chronic renal insufficiency and with normal renal function.

In a prospective study of 98 persons > or = 65 years of age with chronic renal insufficiency (serum creatinine > 3.0 mg/dl) for > 1 year and 98 age- and sex-matched persons with normal renal function (serum creatinine < or = 1.2 mg/dl), new coronary events developed at 23-month follow-up in 69 persons (70%) with chronic renal insufficiency and at 48-month follow-up in 24 persons (24%) with normal renal function (p < 0.0001). Significant independent risk factors for new coronary events were age (risk ratio 1.1), prior coronary artery disease (risk ratio 3.5), complex ventricular arrhythmias diagnosed by 24-hour ambulatory electrocardiography (risk ratio 2.5), silent myocardial ischemia diagnosed by 24-hour ambulatory electrocardiography (risk ratio 1.9), and chronic renal insufficiency (risk ratio 3.4).

Aged↗
PubMed2000

Postmenopausal osteoporosis: fracture consequences and treatment efficacy vary by skeletal site.

At least half of all postmenopausal women will experience fractures during their lifetime, and the consequences are often serious, but most women at risk are not receiving adequate treatment. The objective of this paper is to summarize the literature concerning the consequences of osteoporotic fractures, and the effectiveness of pharmacologic agents for preventing fractures and their consequences, emphasizing a systematic, evidence-based summary of treatment results from randomized, controlled trials that were published previously. Osteoporosis is associated with increased risk of fractures at most skeletal sites. Hip fractures have much greater prognostic significance in terms of health than any other single type of fracture. However, symptomatic vertebral fractures and other non-hip fractures also represent enormous morbidity and economic burdens, and signal increased risk of future fractures of all types, including the hip. There is convincing evidence that two bisphosphonates (alendronate and risedronate) reduce the risk of both spine and non-spine fractures. The evidence for reducing hip fracture risk is greater for alendronate, with a consistent approximately 50% reduction in hip fractures across studies. Alendronate has also been demonstrated to maintain quality of life by reducing outcomes such as hospitalization and bed rest related to back pain. Among other agents, raloxifene reduces the risk of vertebral fractures by approximately 30%; the published evidence for most other agents is inconclusive. Osteoporosis should be regarded as seriously as other important chronic disorders such as hypertension and hyperlipidemia. Postmenopausal patients with a high risk of fractures--such as those with prior fractures or osteoporosis as measured by BMD--need to be treated. Although other therapeutic modalities are available, the evidence is most convincing for the bisphosphonates, alendronate and risedronate.

Fractures, Bone↗
PubMed2000

Drug-induced bone loss.

Bone loss leading to osteoporosis is common after the menopause and in the elderly but uncommon in normal young adults without predisposing factors. The risk factors usually associated with osteoporosis include a family history of osteoporosis or fractures, aging, prior diseases, sedentary lifestyle, low calcium intake, hypogonadism, vitamin D deficiency, smoking, and excessive alcohol consumption. However, the issue of drugs has to be considered in 'normal' individuals who present with osteoporosis or bone loss without predisposing genetic or other environmental factors. The list of drugs is extensive and includes, amongst others, glucocorticoids, thyroid hormone (excess), alcohol, medroxyprogesterone acetate, luteinizing hormone-releasing hormone agonists, anti-seizure medications, cyclosporine A, aluminium, lithium, and exchange resins. This paper reviews the pathophysiology and mechanisms of drug-induced bone loss, which includes osteoporosis and osteomalacia, and treatment concepts. Undoubtedly, physician awareness, appropriate investigation, careful prescribing, monitoring, and proper therapy for this eminently preventable side effect can preserve bone in the patients receiving bone-losing drugs.

Adult↗
PubMed2000

Influence of estrogen deficiency and replacement on T-cell populations in rat lymphoid tissues and organs.

Estrogen deficiency following ovariectomy or menopause results in bone loss. Although evidence strongly suggests that the immune system is involved in the pathogenesis of estrogen-deficient osteoporosis, it is not clear what role, if any, the T-lymphocyte plays in this process. Therefore, we examined the distribution of T-cell subsets in lymphoid organs and tissues, under varying estrogenic states in the rat. Six-month-old female Sprague-Dawley rats, ovariectomized (Ovx) and sham-operated, were randomized 5 d post-surgery into six groups to receive the following treatments: (A) sham/placebo; (B) sham/low-dose E2; (C) sham/high-dose E2; (D) Ovx/placebo; (E) Ovx/low-dose E2; (F) Ovx/high-dose E2. Half of the treated rats (groups A-F) were sacrificed on d 14; the remainder on d 28. Following euthanasia, mononuclear cells were isolated from the thymus, peripheral blood, spleen, lymph node and bone marrow, and were labeled for flow cytometric analysis using mouse anti-rat monoclonal antibodies directed against CD5, CD4, and CD8 antigenic markers. In the thymus, ovariectomy caused a dramatic increase and E2 treatment caused a dose-dependent decrease in weight that was proportional to the number of thymocytes. In the bone marrow, ovariectomy caused a significant reduction in the percentage of all T-cell subsets examined and this effect persisted throughout the duration of the study. Estrogen replacement therapy at the low-dose reversed the effects of ovariectomy and high-dose E2 treatment caused an increase in T-cell subsets in both the sham and Ovx groups, an effect that was more pronounced at d 14 compared with d 28. Although the percentages of some T-cell subsets in the other lymphoid organs/tissues were altered by ovariectomy or E2 treatment at d 0 and 14, all these changes had normalized by d 28 except for CD5 and CD4 cells in peripheral blood. In summary, with the exception of T-lymphocytes in the bone marrow, the effects of varying estrogenic states on T-cells were variable and transient. The influence of estrogen status on bone marrow T-lymphocytes suggests that these cells may play a role in mediating the effects of estrogen on bone turnover and warrant additional studies focusing on the functional role of T-cells in the bone marrow compartment.

Animals↗