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Osteoporosis: HELP
Articles by Russell T. Turner
Based on 14 articles published since 2010
(Why 14 articles?)
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Between 2010 and 2020, R. T. Turner wrote the following 14 articles about Osteoporosis.
 
+ Citations + Abstracts
1 Review Influence of body weight on bone mass, architecture and turnover. 2016

Iwaniec, Urszula T / Turner, Russell T. ·Skeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA Center for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USA urszula.iwaniec@oregonstate.edu. · Skeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA Center for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USA. ·J Endocrinol · Pubmed #27352896.

ABSTRACT: Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating the development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. Although the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size.

2 Review Alcohol: A Simple Nutrient with Complex Actions on Bone in the Adult Skeleton. 2016

Gaddini, Gino W / Turner, Russell T / Grant, Kathleen A / Iwaniec, Urszula T. ·Skeletal Biology Laboratory, School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon. · Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon. · Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon. ·Alcohol Clin Exp Res · Pubmed #26971854.

ABSTRACT: BACKGROUND: Alcohol is an important nonessential component of diet, but the overall impact of drinking on bone health, especially at moderate levels, is not well understood. Bone health is important because fractures greatly reduce quality of life and are a major cause of morbidity and mortality in the elderly. Regular alcohol consumption is most common following skeletal maturity, emphasizing the importance of understanding the skeletal consequences of drinking in adults. METHODS: This review focuses on describing the complex effects of alcohol on the adult skeleton. Studies assessing the effects of alcohol on bone in adult humans as well as skeletally mature animal models published since the year 2000 are emphasized. RESULTS: Light to moderate alcohol consumption is generally reported to be beneficial, resulting in higher bone mineral density (BMD) and reduced age-related bone loss, whereas heavy alcohol consumption is generally associated with decreased BMD, impaired bone quality, and increased fracture risk. Bone remodeling is the principal mechanism for maintaining a healthy skeleton in adults and dysfunction in bone remodeling can lead to bone loss and/or decreased bone quality. Light to moderate alcohol may exert beneficial effects in older individuals by slowing the rate of bone remodeling, but the impact of light to moderate alcohol on bone remodeling in younger individuals is less certain. The specific effects of alcohol on bone remodeling in heavy drinkers are even less certain because the effects are often obscured by unhealthy lifestyle choices, alcohol-associated disease, and altered endocrine signaling. CONCLUSIONS: Although there have been advances in understanding the complex actions of alcohol on bone, much remains to be determined. Limited evidence implicates age, skeletal site evaluated, duration, and pattern of drinking as important variables. Few studies systematically evaluating the impact of these factors have been conducted and should be made a priority for future research. In addition, studies performed in skeletally mature animals have potential to reveal mechanistic insights into the precise actions of alcohol and associated comorbidity factors on bone remodeling.

3 Article Sclerostin antibody treatment rescues the osteopenic bone phenotype of TGFβ inducible early gene-1 knockout female mice. 2020

Gingery, Anne / Subramaniam, Malayannan / Pitel, Kevin S / Li, Xiaodong / Ke, Hua Z / Turner, Russell T / Iwaniec, Urszula T / Hawse, John R. ·Department of Orthopedics, Mayo Clinic, Rochester, Minnesota. · Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota. · Department of Metabolic Disorders, Amgen, Inc., Thousand Oaks, California. · UCB Pharma, Slough, UK. · Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon. ·J Cell Physiol · Pubmed #31975377.

ABSTRACT: Deletion of TGFβ inducible early gene-1 (TIEG) in mice results in an osteopenic phenotype that exists only in female animals. Molecular analyses on female TIEG knockout (KO) mouse bones identified increased expression of sclerostin, an effect that was confirmed at the protein level in serum. Sclerostin antibody (Scl-Ab) therapy has been shown to elicit bone beneficial effects in multiple animal model systems and human clinical trials. For these reasons, we hypothesized that Scl-Ab therapy would reverse the low bone mass phenotype of female TIEG KO mice. In this study, wildtype (WT) and TIEG KO female mice were randomized to either vehicle control (Veh, n = 12/group) or Scl-Ab therapy (10 mg/kg, 1×/wk, s.c.; n = 12/group) and treated for 6 weeks. Following treatment, bone imaging analyses revealed that Scl-Ab therapy significantly increased cancellous and cortical bone in the femur of both WT and TIEG KO mice. Similar effects also occurred in the vertebra of both WT and TIEG KO animals. Additionally, histomorphometric analyses revealed that Scl-Ab therapy resulted in increased osteoblast perimeter/bone perimeter in both WT and TIEG KO animals, with a concomitant increase in P1NP, a serum marker of bone formation. In contrast, osteoclast perimeter/bone perimeter and CTX-1 serum levels were unaffected by Scl-Ab therapy, irrespective of mouse genotype. Overall, our findings demonstrate that Scl-Ab therapy elicits potent bone-forming effects in both WT and TIEG KO mice and effectively increases bone mass in female TIEG KO mice.

4 Article Effects of Alcohol and Estrogen Receptor Blockade Using ICI 182,780 on Bone in Ovariectomized Rats. 2019

Wagner, Lindsay / Howe, Kathy / Philbrick, Kenneth A / Maddalozzo, Gianni F / Kuah, Amida F / Wong, Carmen P / Olson, Dawn A / Branscum, Adam J / Iwaniec, Urszula T / Turner, Russell T. ·Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon. · Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon. · Center for Healthy Aging Research, Oregon State University, Corvallis, Oregon. ·Alcohol Clin Exp Res · Pubmed #31479513.

ABSTRACT: BACKGROUND: Estrogen signaling is essential for the sexual dimorphism of the skeleton, is required for normal bone remodeling balance in adults, and may influence the skeletal response to alcohol. High levels of alcohol consumption lower bone mass in ovary-intact but not ovariectomized (ovx) rats. However, the extremely rapid rate of bone loss immediately following ovx may obscure the effects of alcohol. We therefore determined (i) whether heavy alcohol consumption (35% caloric intake) influences bone in sexually mature ovx rats with established cancellous osteopenia and (ii) whether ICI 182,780 (ICI), a potent estrogen receptor signaling antagonist, alters the skeletal response to alcohol. METHODS: Three weeks following ovx, rats were randomized into 5 groups, (i) baseline, (ii) control + vehicle, (iii) control + ICI, (iv) ethanol (EtOH) + vehicle, or (v) EtOH + ICI, and treated accordingly for 4 weeks. Dual-energy X-ray absorptiometry, microcomputed tomography, blood measurements of markers of bone turnover, and gene expression in femur and uterus were used to evaluate response to alcohol and ICI. RESULTS: Rats consuming alcohol had lower bone mass and increased fat mass. Bone microarchitecture of the tibia and gene expression in femur were altered; specifically, there was reduced accrual of cortical bone, net loss of cancellous bone, and differential expression of 19/84 genes related to bone turnover. Furthermore, osteocalcin, a marker of bone turnover, was lower in alcohol-fed rats. ICI had no effect on weight gain, body composition, or cortical bone. ICI reduced cancellous bone loss and serum CTX-1, a biochemical marker of bone resorption; alcohol antagonized the latter 2 responses. Neither alcohol nor ICI affected uterine weight or gene expression. CONCLUSIONS: Alcohol exaggerated bone loss in ovx rats in the presence or absence of estrogen receptor blockade with ICI. The negligible effect of alcohol on uterus and limited effects of ICI on bone in alcohol-fed ovx rats suggest that estrogen receptor signaling plays a limited role in the action of alcohol on bone in a rat model for chronic alcohol abuse.

5 Article Polyethylene particles inserted over calvarium induce cancellous bone loss in femur in female mice. 2018

Philbrick, Kenneth A / Wong, Carmen P / Kahler-Quesada, Arianna M / Olson, Dawn A / Branscum, Adam J / Turner, Russell T / Iwaniec, Urszula T. ·Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA. · Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA. · Center for Healthy Aging Research, Oregon State University, Corvallis, OR 97331, USA. ·Bone Rep · Pubmed #30094298.

ABSTRACT: Focal bone resorption (osteolysis) induced by wear particles contributes to long-term orthopedic joint failure. However, the impact of focal osteolysis on remote skeletal sites has received less attention. The goal of this study was to determine the effects of polyethylene particles placed over calvaria on representative axial and appendicular skeletal sites in female mice. Because recent work has identified housing temperature as an important biological variable in mice, response to particle treatment was measured in animals housed at room (22 °C) and thermoneutral (32 °C) temperature. Osteolysis was evident in skeletal tissue adjacent to particle insertion. In addition, cancellous bone loss was observed in distal femur metaphysis. The bone loss was associated with lower osteoblast-lined perimeter and lower mineralizing perimeter in distal femur, lower osteocalcin gene expression in tibia, and lower serum osteocalcin, suggesting the response was due, at least in part, to reduced bone formation. Mild cold stress induced by sub-thermoneutral housing resulted in cancellous bone loss in distal femur and lumbar vertebra but did not influence skeletal response to particles. In summary, the results indicate that focal inflammation induced by polyethylene particles has the potential to result in systemic bone loss. This is significant because bone loss is a risk factor for fracture.

6 Article Skeletal and Uterotrophic Effects of Endoxifen in Female Rats. 2017

Gingery, Anne / Iwaniec, Urszula T / Subramaniam, Malayannan / Turner, Russell T / Pitel, Kevin S / McGovern, Renee M / Reid, Joel M / Marler, Ronald J / Ingle, James N / Goetz, Matthew P / Hawse, John R. ·Division of Orthopedic Research, Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota 55905. · Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905. · Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331. · Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905. · Department of Oncology, Mayo Clinic, Rochester, Minnesota 55905. · Department of Comparative Medicine, Mayo Clinic, Scottsdale, Arizona 85259. ·Endocrinology · Pubmed #28977607.

ABSTRACT: Endoxifen, the primary active metabolite of tamoxifen, is currently being investigated as a novel endocrine therapy for the treatment of breast cancer. Tamoxifen is a selective estrogen receptor modulator that elicits potent anti-breast cancer effects. However, long-term use of tamoxifen also induces bone loss in premenopausal women and is associated with an increased risk of endometrial cancer in postmenopausal women. For these reasons, we have used a rat model system to comprehensively characterize the impact of endoxifen on the skeleton and uterus. Our results demonstrate that endoxifen elicits beneficial effects on bone in ovary-intact rats and protects against bone loss following ovariectomy. Endoxifen is also shown to reduce bone turnover in both ovary-intact and ovariectomized rats at the cellular and biochemical levels. With regard to the uterus, endoxifen decreased uterine weight but maintained luminal epithelial cell height in ovariectomized animals. Within luminal epithelial cells, endoxifen resulted in differential effects on the expression levels of estrogen receptors α and β as well as multiple other genes previously implicated in regulating epithelial cell proliferation and hypertrophy. These studies analyze the impact of extended endoxifen exposure on both bone and uterus using a Food and Drug Administration-recommended animal model. Although endoxifen is a more potent breast cancer agent than tamoxifen, the results of the present study demonstrate that endoxifen does not induce bone loss in ovary-intact rats and that it elicits partial agonistic effects on the uterus and skeleton in ovariectomized animals.

7 Article High-Dietary Alpha-Tocopherol or Mixed Tocotrienols Have No Effect on Bone Mass, Density, or Turnover in Male Rats During Skeletal Maturation. 2017

Tennant, Katherine G / Leonard, Scott W / Wong, Carmen P / Iwaniec, Urszula T / Turner, Russell T / Traber, Maret G. ·1 Linus Pauling Institute, Oregon State University , Corvallis, Oregon, USA. · 2 Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University , Corvallis, Oregon, USA. ·J Med Food · Pubmed #28384008.

ABSTRACT: High levels of alpha-tocopherol, the usual vitamin E supplement, are reported to decrease bone mass in rodents; however, the effects of other vitamin E forms on the skeleton are unknown. To test the hypothesis that high intakes of various vitamin E forms or the vitamin E metabolite, carboxyethyl hydroxy chromanol, were detrimental to bone status, Sprague-Dawley rats (n = 6 per group, 11-week males) for 18 weeks consumed semipurified diets that contained adequate alpha-tocopherol, high alpha-tocopherol (500 mg/kg diet), or 50% Tocomin (250 mg mixed tocopherols and tocotrienols/kg diet). Vitamin E status was evaluated by measuring plasma, liver, and bone marrow vitamin E concentrations. Bone density, microarchitecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and cancellous bone volume fraction, trabecular number, thickness, and spacing), and cancellous bone formation were assessed in the tibia using dual-energy X-ray absorptiometry, microcomputed tomography, and histomorphometry, respectively. In addition, serum osteocalcin was assessed as a global marker of bone turnover; gene expression in response to treatment was evaluated in the femur using targeted (osteogenesis related) gene profiling. No significant differences were detected between treatment groups for any of the bone endpoints measured. Vitamin E supplementation, either as alpha-tocopherol or mixed tocotrienols, while increasing vitamin E concentrations both in plasma and tissues, had no effect on the skeleton in rats.

8 Article Hypothalamic Leptin Gene Therapy Reduces Bone Marrow Adiposity in ob/ob Mice Fed Regular and High-Fat Diets. 2016

Lindenmaier, Laurence B / Philbrick, Kenneth A / Branscum, Adam J / Kalra, Satya P / Turner, Russell T / Iwaniec, Urszula T. ·Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University , Corvallis, OR , USA. · Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University , Corvallis, OR , USA. · Department of Neuroscience, McKnight Brain Institute, University of Florida , Gainesville, FL , USA. · Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA; Center for Healthy Aging Research, Oregon State University, Corvallis, OR, USA. ·Front Endocrinol (Lausanne) · Pubmed #27579023.

ABSTRACT: Low bone mass is often associated with elevated bone marrow adiposity. Since osteoblasts and adipocytes are derived from the same mesenchymal stem cell (MSC) progenitor, adipocyte formation may increase at the expense of osteoblast formation. Leptin is an adipocyte-derived hormone known to regulate energy and bone metabolism. Leptin deficiency and high-fat diet-induced obesity are associated with increased marrow adipose tissue (MAT) and reduced bone formation. Short-duration studies suggest that leptin treatment reduces MAT and increases bone formation in leptin-deficient ob/ob mice fed a regular diet. Here, we determined the long-duration impact of increased hypothalamic leptin on marrow adipocytes and osteoblasts in ob/ob mice following recombinant adeno-associated virus (rAAV) gene therapy. Eight- to 10-week-old male ob/ob mice were randomized into four groups: (1) untreated, (2) rAAV-Lep, (3) rAAV-green fluorescent protein (rAAV-GFP), or (4) pair-fed to rAAV-Lep. For vector administration, mice were injected intracerebroventricularly with either rAAV-leptin gene therapy (rAAV-Lep) or rAAV-GFP (9 × 10(7) particles) and maintained for 30 weeks. In a second study, the impact of increased hypothalamic leptin levels on MAT was determined in mice fed high-fat diets; ob/ob mice were randomized into two groups and treated with either rAAV-Lep or rAAV-GFP. At 7 weeks post-vector administration, half the mice in each group were switched to a high-fat diet for 8 weeks. Wild-type (WT) controls included age-matched mice fed regular or high-fat diet. High-fat diet resulted in a threefold increase in MAT in WT mice, whereas MAT was increased by leptin deficiency up to 50-fold. Hypothalamic leptin gene therapy increased osteoblast perimeter and osteoclast perimeter with minor change in cancellous bone architecture. The gene therapy decreased MAT levels in ob/ob mice fed regular or high-fat diet to values similar to WT mice fed regular diet. These findings suggest that leptin plays an important role in regulating the differentiation of MSCs to adipocytes and osteoblasts, a process that may be dysregulated by high-fat diet. However, the results also illustrate that reducing MAT by increasing leptin levels does not necessarily result in increased bone mass.

9 Article Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss. 2016

Iwaniec, U T / Philbrick, K A / Wong, C P / Gordon, J L / Kahler-Quesada, A M / Olson, D A / Branscum, A J / Sargent, J L / DeMambro, V E / Rosen, C J / Turner, R T. ·Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA. · Center for Healthy Aging Research, Oregon State University, Corvallis, OR, 97331, USA. · Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA. · College of Veterinary Medicine, Oregon State University, Corvallis, OR, 97331, USA. · Maine Medical Center Research Institute, Scarborough, ME, 04074, USA. · Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331, USA. russell.turner@oregonstate.edu. · Center for Healthy Aging Research, Oregon State University, Corvallis, OR, 97331, USA. russell.turner@oregonstate.edu. ·Osteoporos Int · Pubmed #27189604.

ABSTRACT: INTRODUCTION: Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18-23 °C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture. METHODS: Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 or 32 °C for up to 18 weeks. RESULTS: C57BL/6J mice housed at 22 °C experienced a 62 % cancellous bone loss from the distal femur metaphysis during the interval from 8 to 18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32 °C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption. CONCLUSIONS: Housing female mice at 22 °C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies utilizing mice as preclinical models for osteoporosis.

10 Article Evaluation of long-term vitamin E insufficiency or excess on bone mass, density, and microarchitecture in rodents. 2013

Iwaniec, Urszula T / Turner, Russell T / Smith, Brenda J / Stoecker, Barbara J / Rust, Allison / Zhang, Bo / Vasu, Vihas T / Gohil, Kishorchandra / Cross, Carroll E / Traber, Maret G. ·Skeletal Biology Laboratory, Oregon State University, Corvallis, OR 97331, USA; Center for Healthy Aging Research, Oregon State University, Corvallis, OR 97331, USA. · Department of Nutritional Sciences, College of Human Sciences, Oklahoma State University, Stillwater, OK 74078, USA. · Skeletal Biology Laboratory, Oregon State University, Corvallis, OR 97331, USA. · Biostatistics Core, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA. · Department of Internal Medicine, Genome and Biomedical Sciences Facility, University of California at Davis, Davis, CA 95616, USA. · Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. Electronic address: maret.traber@oregonstate.edu. ·Free Radic Biol Med · Pubmed #24051180.

ABSTRACT: High dietary α-tocopherol levels reportedly result in osteopenia in growing rats, whereas α-tocopherol deficiency in α-tocopherol transfer protein-knockout (α-TTP-KO) mice results in increased cancellous bone mass. Because osteoporosis is a disease associated primarily with aging, we hypothesized that age-related bone loss would be attenuated in α-TTP-KO mice. Cancellous and cortical bone mass and microarchitecture were assessed using dual-energy X-ray absorptiometry and micro-computed tomography in 2-year-old α-TTP-KO and wild-type (WT) male and female mice fed dl-α-tocopherol acetate. In contrast to our expectations, differences in cancellous bone were not detected between WT and α-TTP-KO mice of either gender, and α-TTP-KO males had lower (p<0.05) cortical bone mass than WT males. We therefore evaluated bone mass, density, and microarchitecture in proximal femur of skeletally mature (8.5-month-old) male Sprague-Dawley rats fed diets containing low (15 IU/kg diet), adequate (75 IU/kg diet), or high (500 IU/kg diet) dl-α-tocopherol acetate for 13 weeks. Low dietary α-tocopherol did not increase bone mass. Furthermore, no reductions in cancellous or cortical bone mass were detected with high dietary α-tocopherol. Failure to detect increased bone mass in aged α-TTP-KO mice or bone changes in skeletally mature rats fed either low or high levels of α-tocopherol does not support the hypothesis that α-tocopherol has a negative impact on bone mass, density, or microarchitecture in rodents.

11 Article Acute exposure to high dose γ-radiation results in transient activation of bone lining cells. 2013

Turner, Russell T / Iwaniec, Urszula T / Wong, Carmen P / Lindenmaier, Laurence B / Wagner, Lindsay A / Branscum, Adam J / Menn, Scott A / Taylor, James / Zhang, Ye / Wu, Honglu / Sibonga, Jean D. ·Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA; Center for Healthy Aging Research, Oregon State University, Corvallis, OR, USA. Electronic address: Russell.Turner@oregonstate.edu. ·Bone · Pubmed #23954507.

ABSTRACT: The present studies investigated the cellular mechanisms for the detrimental effects of high dose whole body γ-irradiation on bone. In addition, radioadaptation and bone marrow transplantation were assessed as interventions to mitigate the skeletal complications of irradiation. Increased trabecular thickness and separation and reduced cancellous bone volume fraction, connectivity density, and trabecular number were detected in proximal tibia and lumbar vertebra 14days following γ-irradiation with 6Gy. To establish the cellular mechanism for the architectural changes, vertebrae were analyzed by histomorphometry 1, 3, and 14days following irradiation. Marrow cell density decreased within 1day (67% reduction, p<0.0001), reached a minimum value after 3days (86% reduction, p<0.0001), and partially rebounded by 14days (30% reduction, p=0.0025) following irradiation. In contrast, osteoblast-lined bone perimeter was increased by 290% (1day, p=0.04), 1230% (3days, p<0.0001), and 530% (14days, p=0.003), respectively. There was a strong association between radiation-induced marrow cell death and activation of bone lining cells to express the osteoblast phenotype (Pearson correlation -0.85, p<0.0001). An increase (p=0.004) in osteoclast-lined bone perimeter was also detected with irradiation. A priming dose of γ-radiation (0.5mGy), previously shown to reduce mortality, had minimal effect on the cellular responses to radiation and did not prevent detrimental changes in bone architecture. Bone marrow transplantation normalized marrow cell density, bone turnover, and most indices of bone architecture following irradiation. In summary, radiation-induced death of marrow cells is associated with 1) a transient increase in bone formation due, at least in part, to activation of bone lining cells, and 2) an increase in bone resorption due to increased osteoclast perimeter. Bone marrow transplantation is effective in mitigating the detrimental effects of acute exposure to high dose whole body γ-radiation on bone turnover.

12 Article The bone disease associated with factor VIII deficiency in mice is secondary to increased bone resorption. 2013

Recht, M / Liel, M S / Turner, R T / Klein, R F / Taylor, J A. ·The Hemophilia Center, Oregon Health & Science University, Portland, OR, USA. ·Haemophilia · Pubmed #23731369.

ABSTRACT: Osteopenia and osteoporosis have increasingly become a recognized morbidity of factor VIII (FVIII) deficiency. Recently, we demonstrated that FVIII knockout (KO) mice had significantly decreased bone mass and bone strength despite the fact that they did not have haemarthroses. The aim of this study was to explore the mechanism of bone disease associated with FVIII deficiency. We compared biochemical markers of bone formation and osteoclastogenesis, inflammatory cytokines, as well as static and dynamic histomorphometry of genetically engineered FVIII KO male mice to those of wild-type (WT) controls. At 20 weeks of age, FVIII KO mice, as well as WT controls, were sacrificed. Serum and bones were obtained at the time of sacrifice to study biochemical markers of bone formation (osteocalcin) and osteoclastogenesis (receptor activator of nuclear factor kappa-β and osteoprotegerin), levels of inflammatory cytokines (interleukin-1α and interferon-β) and to perform static and dynamic histomorphometry of tibia cancellous bone. There was no difference in the biochemical markers of bone formation or osteoclastogenesis. However, there were differences in the two bone-associated cytokines studied. In addition, histomorphometric examination revealed cancellous osteopenia in FVIII KO mice as evidenced by decreased bone area and trabecular number and increased trabecular separation. Bone formation parameters were normal in FVIII KO mice. In contrast, osteoclast-lined bone perimeter was increased. These data demonstrate that bone disease in FVIII KO mice is due to an increased rate of bone resorption.

13 Article Genistein administered as a once-daily oral supplement had no beneficial effect on the tibia in rat models for postmenopausal bone loss. 2013

Turner, Russell T / Iwaniec, Urszula T / Andrade, Juan E / Branscum, Adam J / Neese, Steven L / Olson, Dawn A / Wagner, Lindsay / Wang, Victor C / Schantz, Susan L / Helferich, William G. ·Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA. Russell.Turner@oregonstate.edu ·Menopause · Pubmed #23385720.

ABSTRACT: OBJECTIVE: Estrogen deficiency after menopause results in rapid bone loss, predisposing women to osteoporotic fractures. Genistein, a phytoestrogen present in high concentrations in soy, is an ingredient in dietary supplements aggressively marketed for bone health. However, in a recent long-duration clinical trial in postmenopausal women, the efficacy of soy extracts in reducing bone loss was disappointing. To better understand the failure of soy extracts to consistently induce a robust skeletal response in women, we investigated the long-term (5 mo) efficacy of genistein, administered as a daily oral supplement, (1) in preventing cancellous bone loss in skeletally mature virgin Long-Evans rats ovariectomized at 7 months of age and (2) in improving cancellous bone mass and architecture in aged retired-breeder rats ovariectomized at 16 or 22 months of age. METHODS: Rats within each age group were randomly assigned into one of three treatment groups (n = 7-12 rats/group): (1) vehicle control, (2) genistein 485 μg/day, or (3) genistein 970 μg/day, resulting in mean (SE) serum genistein levels of 0.18 (0.10), 0.76 (0.15), and 1.48 (0.31) μM, respectively. Total tibia bone mass and density were evaluated using dual-energy x-ray absorptiometry, whereas cancellous bone mass and architecture in the tibial metaphysis, as well as cortical bone mass and architecture in the tibial diaphysis, were evaluated by micro-CT. RESULTS: Oral genistein administered as a dietary supplement did not influence the cumulative effects of ovariectomy, aging, and/or reproductive history on cancellous and cortical bone mass and architecture. CONCLUSIONS: Serum levels of genistein similar to those in women consuming a high-soy diet are ineffective in preventing or treating bone loss in rat models for postmenopausal osteoporosis.

14 Article Moderate alcohol intake lowers biochemical markers of bone turnover in postmenopausal women. 2012

Marrone, Jill A / Maddalozzo, Gianni F / Branscum, Adam J / Hardin, Karin / Cialdella-Kam, Lynn / Philbrick, Kenneth A / Breggia, Anne C / Rosen, Clifford J / Turner, Russell T / Iwaniec, Urszula T. ·Nutrition Division, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA. ·Menopause · Pubmed #22922514.

ABSTRACT: OBJECTIVE: Epidemiological studies indicate that higher bone mass is associated with moderate alcohol consumption in postmenopausal women. However, the underlying cellular mechanisms responsible for the putative beneficial effects of alcohol on bone are unknown. Excessive bone turnover, combined with an imbalance whereby bone resorption exceeds bone formation, is the principal cause of postmenopausal bone loss. This study investigated the hypothesis that moderate alcohol intake attenuates bone turnover after menopause. METHODS: Bone mineral density was determined by dual-energy x-ray absorptiometry in 40 healthy postmenopausal women (mean ± SE age, 56.3 ± 0.5 y) who consumed alcohol at 19 ± 1 g/day. Serum levels of the bone formation marker osteocalcin and the resorption marker C-terminal telopeptide (CTx) were measured by immunoassay at baseline (day 0) and after alcohol withdrawal for 14 days. Participants then consumed alcohol and were assayed on the following morning. RESULTS: Bone mineral density at the trochanter and total hip were positively correlated to the level of alcohol consumption. Serum osteocalcin and CTx increased after abstinence (4.1 ± 1.6%, P = 0.01 and 5.8 ± 2.6%, P = 0.02 compared with baseline, respectively). Osteocalcin and CTx decreased after alcohol readministration, compared with the previous day (-3.4 ± 1.4%, P = 0.01 and -3.5 ± 2.1%, P = 0.05, respectively), to values that did not differ from baseline (P > 0.05). CONCLUSIONS: Abstinence from alcohol results in increased markers of bone turnover, whereas resumption of alcohol reduces bone turnover markers. These results suggest a cellular mechanism for the increased bone density observed in postmenopausal moderate alcohol consumers. Specifically, the inhibitory effect of alcohol on bone turnover attenuates the detrimental skeletal consequences of excessive bone turnover associated with menopause.