Author(s): Anderson, Garnet L; Limacher, Marian; Assaf, Annlouise R; Bassford, Tamsen; Beresford, Shirley AA; Black, Henry; Bonds, Denise; Brunner, Robert; Brzyski, Robert; Caan, Bette; Chlebowski, Rowan; Curb, David; Gass, Margery; Hays, Jennifer; Heiss, Gerardo; Hendrix, Susan; Howard, Barbara V; Hsia, Judith; Hubbell, Allan; Jackson, Rebecca; Johnson, Karen C; Judd, Howard; Kotchen, Jane Morley; Kuller, Lewis; LaCroix, Andrea Z; Lane, Dorothy; Langer, Robert D; Lasser, Norman; Lewis, Cora E; Manson, JoAnn; Margolis, Karen; Ockene, Judith; O'Sullivan, Mary Jo; Phillips, Lawrence; Prentice, Ross L; Ritenbaugh, Cheryl; Robbins, John; Rossouw, Jacques E; Sarto, Gloria; Stefanick, Marcia L; Van Horn, Linda; Wactawski-Wende, Jean; Wallace, Robert; Wassertheil-Smoller, Sylvia; Women's Health Initiative Steering Committee | Abstract: Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States.A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity.Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo.The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects.In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years.The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.

/pdf/effects-of-conjugated-equine-estrogen-in-postmenopausal-56019yuhvy.pdf

Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial

Biodegradation and biocompatibility of PLA and PLGA microspheres

Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers

Background: Antiresorptive agents are widely used to treat osteoporosis. We report the results of a multinational randomized, double-blind study, in which postmenopausal women with osteoporosis were treated with alendronate for up to 10 years. Methods: The initial three-year phase of the study compared three daily doses of alendronate with placebo. Women in the original placebo group received alendronate in years 4 and 5 and then were discharged. Women in the original active-treatment groups continued to receive alendronate during the initial extension (years 4 and 5). In two further extensions (years 6 and 7, and 8 through 10), women who had received 5 mg or 10 mg of alendronate daily continued on the same treatment. Women in the discontinuation group received 20 mg of alendronate daily for two years and 5 mg daily in years 3, 4, and 5, followed by five years of placebo. Randomized group assignments and blinding were maintained throughout the 10 years. We report results for the 247 women who participated in all four phases of the study. Results: Treatment with 10 mg of alendronate daily for 10 years produced mean increases in bone mineral density of 13.7 percent at the lumbar spine (95 percent confidence interval, 12.0 to 15.5 percent), 10.3 percent at the trochanter (95 percent confidence interval, 8.1 to 12.4 percent), 5.4 percent at the femoral neck (95 percent confidence interval, 3.5 to 7.4 percent), and 6.7 percent at the total proximal femur (95 percent confidence interval, 4.4 to 9.1 percent) as compared with base-line values; smaller gains occurred in the group given 5 mg daily. The discontinuation of alendronate resulted in a gradual loss of effect, as measured by bone density and biochemical markers of bone remodeling. Safety data, including fractures and stature, did not suggest that prolonged treatment resulted in any loss of benefit. Conclusions: The therapeutic effects of alendronate were sustained, and the drug was well tolerated over a 10-year period. The discontinuation of alendronate resulted in the gradual loss of its effects.

/pdf/ten-years-experience-with-alendronate-for-osteoporosis-in-nvnuhued6j.pdf

Ten years' experience with alendronate for osteoporosis in postmenopausal women.

Biomaterials play a pivotal role in field of tissue engineering. Biomimetic synthetic polymers have been created to elicit specific cellular functions and to direct cell-cell interactions both in implants that are initially cell-free, which may serve as matrices to conduct tissue regeneration, and in implants to support cell transplantation. Biomimetic approaches have been based on polymers endowed with bioadhesive receptor-binding peptides and mono- and oligosaccharides. These materials have been patterned in two- and three-dimensions to generate model multicellular tissue architectures, and this approach may be useful in future efforts to generate complex organizations of multiple cell types. Natural polymers have also played an important role in these efforts, and recombinant polymers that combine the beneficial aspects of natural polymers with many of the desirable features of synthetic polymers have been designed and produced. Biomaterials have been employed to conduct and accelerate otherwise naturally occurring phenomena, such as tissue regeneration in wound healing in the otherwise healthy subject; to induce cellular responses that might not be normally present, such as healing in a diseased subject or the generation of a new vascular bed to receive a subsequent cell transplant; and to block natural phenomena, such as the immune rejection of cell transplants from other species or the transmission of growth factor signals that stimulate scar formation. This review introduces the biomaterials and describes their application in the engineering of new tissues and the manipulation of tissue responses.

Biomaterials in tissue engineering.

Recombinant human bone morphogenetic protein- (rhBMP-) can be used to enhance the repair of congenital or acquired bone pathologies when formulated in the appropriate carrier. Poly [D, L-(lactide-co-glycolide)] (PLGA) has been shown to be an effective carrier of rhBMP-. We investigated several particle sizes PLGA and several doses of rhBMP- in a rat orthotopic model. We also investigated the effects of a fibrinolytic inhibitory agent, epsilon aminocaproic acid (EACA), on the healing response. Our data indicate that higher doses of rhBMP- resulted in increased failure torque (408 ± 70 N-mm or 60% of the intact value) and higher incidence of union (100%). The induced bone in femurs treated with the smaller particle size PLGA achieved the greatest torsional stiffness and strength. The presence of rhBMP- was necessary for new bone to form, but the presence of EACA did not change these results; the use of the PLGA carrier appeared to increase bone strength and stiffness. In fact, with higher doses of rhBMP- in PLGA, the stiffness of the new bone was equal to that of intact controls (64 ± 20 N-mm/deg [intact femurs] versus 45 ± 10 N-mm/degree [medium dose in small PLGA], 61 ± 17 N-mm/degree [high dose in small PLGA], and 36 ± 11 N-mm/degree [medium dose in large PLGA]; P > .05). In conclusion, PLGA implanted with rhBMP- effectively aided in healing large segmental defects in rat femurs. © 1994 John Wiley & Sons, Inc.

Healing of large segmental defects in rat femurs is aided by RhBMP-2 in PLGA matrix.

Fluoride stimulates trabecular bone formation, whereas bisphosphonates reduce bone resorption and turnover. Fracture prevention has not been convincingly demonstrated for either treatment so far. We compared the effects of 1-yr treatment of 9-mo-old minipigs with sodium fluoride (NaF, 2 mg/kg/d p.o.) or alendronate (ALN, 4 amino-1-hydroxybutylidene bisphosphonate monosodium, 1 mg/kg/d p.o.) on the biomechanical and histomorphometric properties of pig bones. As expected, NaF increased and ALN decreased bone turnover, but in these normal animals neither changed mean bone volume. NaF reduced the strength of cancellous bone from the L4 vertebra, relative to control animals, and the stiffness (resistance to deformation) of the femora, relative to the ALN group. In the ALN-treated animals, there was a strong positive correlation between bone strength and L5 cancellous bone volume, but no such correlation was observed in the NaF group. Furthermore, the modulus (resistance to deformation of the tissue) was inversely related to NaF content and there was a relative decrease in bone strength above 0.25 mg NaF/g bone. Moreover, within the range of changes measured in this study, there was an inverse correlation between bone turnover, estimated as the percentage of osteoid surface, and modulus. These findings have relevant implications regarding the use of these agents for osteoporosis therapy.

/pdf/comparison-of-alendronate-and-sodium-fluoride-effects-on-btox0lcv1q.pdf

Comparison of alendronate and sodium fluoride effects on cancellous and cortical bone in minipigs. A one-year study.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

M. A. Battle

Author Tools

Chat about Author

Papers

Healing of large segmental defects in rat femurs is aided by RhBMP-2 in PLGA matrix.

Comparison of alendronate and sodium fluoride effects on cancellous and cortical bone in minipigs. A one-year study.