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10. Osteoporosis in a population from medieval Norway

Author

Mays, S., Turner-Walker, G., and Syversen, U.

Subjects
Norway -- Demographic aspects, England -- Demographic aspects, Osteoporosis -- Evaluation, Anthropology/archeology/folklore
Abstract

Modern populations from Norway and England differ in their experience of osteoporosis, the former showing lower bone mineral density (BMD) and a higher fragility fracture rate. The aim of the present work was to investigate whether this was also the case during the Middle Ages. Age-dependent loss of BMD in the proximal femur was assessed using dual X-ray absorptiometry (DXA) in male and female adult skeletons from a cemetery in the medieval town of Trondheim, Norway. Fracture prevalence was also investigated. Results were compared with those previously reported for a skeletal series from Wharram Percy, a deserted medieval village in England. Results indicate that peak BMD and patterns of age-related loss of BMD in the Norwegian and the English group were similar. Among females, the prevalence of osteoporotic fractures was greater in the Norwegian than in the English population. The BMD results suggest that differences in BMD between English and Norwegians are of recent origin, although given the fairly modest sample sizes, further work is needed to confirm this. Reasons for the greater prevalence of osteoporotic fractures in women in the Norwegian skeletal series are unclear, but the colder climate and greater frequency of hard surfaces may have meant that falls were more frequent, and when they occurred, were more likely to result in fractures than in the rural English group.

Published
2006

21. Serum gastrin and gastric enterochromaffin-like cells during estrous cycle, pregnancy and lactation, and in response to estrogen-like agents in rats

Author

Ra, Vigen, Chen D, Syversen U, Astrid Kamilla Stunes, Hakanson R, and Cm, Zhao

Subjects
Male, endocrine system, Time Factors, Enterochromaffin-like Cells, Estrous Cycle, lactation, Pharmacology and Toxicology, Histidine Decarboxylase, Rats, Sprague-Dawley, Parietal Cells, Gastric, Pregnancy, Stomach Neoplasms, gastrin, Gastrins, sex, Animals, Lactation, Rats, Wistar, Toxaphene, Dieldrin, enterochromaffin-like cells, dieldrin, Estrogens, histidine, histamine, Rats, toxaphene, Gastric Mucosa, decarboxylase, Female, pregnancy, hormones, hormone substitutes, and hormone antagonists, Histamine
Abstract

Histamine-containing enterochromaffin-like (ECL) cells are numerous in the gastric mucosa. They operate under the. control of gastrin. ECL-cell tumors (gastric carcinoids) may arise as a consequence of sustained hypergastrinemia. For reasons unknown, such tumors have a female preponderance both in laboratory animals and humans. The present study consisted of four experiments exploring the possibility that gender-related factors might affect rat ECL cells. 1) A gender difference in terms of serum gastrin concentration and oxyntic mucosal histidine decarboxylase (HDC) activity appeared in Sprague-Dawley but not Wistar rats. Ultrastructural appearance of the ECL cells did not differ between genders. 2) During the different phases of the estrous cycle, the serum gastrin concentration, HDC activity and histamine concentration did not change. 3) During pregnancy, the serum gastrin concentration was suppressed, while it was increased during lactation. The HDC activity and the histamine concentration of the oxyntic mucosa were correlated with the levels of circulating gastrin. 4) Twelve-month treatment with estrogen-like agents, dieldrin and/or toxaphene (alone or in combination) was without any effect on the ECL cells neither in male nor in female rats. In conclusion, the ECL cells are under the control of gastrin, but probably not hormones that involve in the estrous cycle and pregnancy and lactation in rats. Possible gender-related factors behind the female preponderance of ECL-cell tumors remain unknown.

Published
2011

22. Once-yearly zoledronic acid and days of disability, bed rest, and back pain: Randomized, controlled HORIZON Pivotal Fracture Trial

Author

Cauley, J. a., Dennis, Black, Steven, Boonen, Cummings, Steven R., Peter, Mesenbrink, Lisa, Palermo, Zulema, Man, Peyman, Hadji, Horizon Pivotal Fracture Group Horowitz, Reid Ir Z., Orloff, J., Black, D., Cummings, S., Delmas, P., Eastell, R., Reid, Ian R., Boonen, S., Cauley, J., Cosman, F., Lakatos, P., Leung, P. c., Man, Z., Lau, E., Jasqui, S., Mautalen, C., Rosario Jansen, T., Caminis, J., Eriksen, E. f., Mesenbrink, P., Raisz, L., Bauer, P., Compston, J., Demets, D., Hirschberg, R., Johnell, O., Ralston, S., Wallace, R., Farkough, M., Flood, M., Bauer, D., Palermo, L., Lang, T., Kerzberg, E., Ridruejo, M., Tate, G., Velasco, J., Hooper, M., Kotowicz, M., Nash, P., Prince, R., Roberts, A., Sambrook, P., Dobnig, H., Finkenstedt, G., Hoefle, G., Klaushofer, K., Pecherstorfer, M., Peichl, P., Body, J., Devogelaer, J. p., Geusens, P., Kaufman, J., Brenol, J., Kochen, J., Lederman, R., Radominski, S., Szejnfeld, V., Zerbini, C., Adachi, J., Brown, J., Choquette, D., Hanley, D., Josse, R., Kendler, D., Kremer, R., Morin, F., Olszynski, W., Papaioannou, A., Kinyuen, C., Chen, B., Lin, S., Casas, N., Chalem, M., Jaller, J., Molina, J., Aro, H., Heikkinen, J., Kroger, H., Makinen, L., Saltevo, J., Salmi, J., Valimaki, M., Benhamou, C. l., Fardellone, P., Werhya, G., Allolio, B., Felsenberg, D., Happ, J., Hartard, M., Hensen, J., Kaps, P., Kekow, J., Moericke, R., Ortloff, B., Schneider, P., Wassenberg, S., Balogh, A., Gomor, B., Hidvegi, T., Koranyi, L., Poor, G., Tulassay, Z., Pollak, R. d., Eshed, V., Foldes, A. j., Ish Shalom, S., Vered, I., Weiss, M., Adami, S., Barone, A., Bianchi, G., Giannini, S., Isaia, G. c., Luisetto, G., Minisola, Salvatore, Molea, N., Nuti, R., Ortolani, S., Passeri, M., Rubinacci, A., Seriolo, B., Sinigaglia, L., Choi, W. h., Kang, M. i., Kim, G. s., Kim, H. s., Kim, Y. k., Lim, S. k., Son, H. y., Yoon, H. k., Abud, C., Garcia, P., Ochoa, L., Orozco, J., Santos, J., Reid, I., Elle, S., Halse, J., Høiseth, A., Olav, H., Røed, H. i., Skag, A., Stakkestad, J., Syversen, U., Badurski, J., Czerwinski, E., Lorenc, R., Marcinowska Suchowierska, E., Sawicki, A., Supronik, J., Ailamazyan, E., Benevolenskaya, L., Dreval, A., Dvoretsky, L., Dyomina, R., Mazurov, V., Melnichenko, G., Mkrtoumyan, A., Orlov Morozov, A., Ostroumova, O., Pikhlak, E., Shemerovskaya, T., Shostak, N., Skripnikova, I., Smetnik, V., Tsyrlina, E., Usova, G., Zalevskaya, A., Zazerskaya, I., Zotkin, E., Ljunggren, O., Lofgren, J., Palmer, M., Saaf, M., Stenstrom, M., Hasler, P., Lamy, O., Lippuner, K., Merlin, C., Rizzoli, R., Theiler, R., Tyndall, A., Uebelhart, D., Chen, J. f., Chen, P. q., Chin, L. s., Hwang, J. s., Yang, T. s., Jirapinyo, M., Sattaya, R., Sriussadaporn, S., Supasin, S., Taechakraichana, N., Wilawan, K., Donnachie, H., Fraser, W., Mclellan, A., Reid, D., Abruzzo, J., Ackerman, R., Adler, R., Aloia, J., Birbara, C., Bode, B., Bone, H., Brandon, D., Dionne, D., Jr Downs, R., Dreyfus, J., Elinoff, V., Emkey, R., Fanciullo, J., Fiske, D., Genaro, P., Gollapudi, M., Gordon, R., Hennessey, J., Howard, P., Johnson, K., Johnston, C., Kagan, R., Kafka, S., Kaine, J., Klein, T., Koltun, W., Leboff, M., Levine, B., Lewiecki, E. m., Lewis, C. e., Licata, A., Lillestol, M., Lubin, B., Malamet, R., Mangione, A., Matkovic, V., Mehta, D., Miller, P., Miller, S., Murphy, F. t., Nattrass, S., Podlecki, D., Recknor, C., Rosen, C., Rowe, D., Rude, R., Schnitzer, T., Sherrer, Y., Silverman, S., Stephenson, K., Troupin, B., Tucci, J., Villareal, R., Watts, N., Weinstein, R., Weitz, M., and White, R.

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Osteoporosis, Bed rest, Placebo, Drug Administration Schedule, Article, law.invention, postmenopausal osteoporosis, zoledronic acid, Randomized controlled trial, Risk Factors, law, Back pain, disability, fracture, Internal medicine, Prevalence, Humans, Medicine, Disabled Persons, Orthopedics and Sports Medicine, Probability, Bone Density Conservation Agents, Diphosphonates, business.industry, Imidazoles, medicine.disease, Back Pain, Female, Multivariate Analysis, Spinal Fractures, Bed Rest, Low back pain, Surgery, Zoledronic acid, Relative risk, medicine.symptom, business, medicine.drug
Abstract

The objective of this study was to determine the effect of once-yearly zoledronic acid on the number of days of back pain and the number of days of disability (ie, limited activity and bed rest) owing to back pain or fracture in postmenopausal women with osteoporosis. This was a multicenter, randomized, double-blind, placebo-controlled trial in 240 clinical centers in 27 countries. Participants included 7736 postmenopausal women with osteoporosis. Patients were randomized to receive either a single 15-minute intravenous infusion of zoledronic acid (5 mg) or placebo at baseline, 12 months, and 24 months. The main outcome measures were self-reported number of days with back pain and the number of days of limited activity and bed rest owing to back pain or a fracture, and this was assessed every 3 months over a 3-year period. Our results show that although the incidence of back pain was high in both randomized groups, women randomized to zoledronic acid experienced, on average, 18 fewer days of back pain compared with placebo over the course of the trial (p = .0092). The back pain among women randomized to zoledronic acid versus placebo resulted in 11 fewer days of limited activity (p = .0017). In Cox proportional-hazards models, women randomized to zoledronic acid were about 6% less likely to experience 7 or more days of back pain [relative risk (RR) = 0.94, 95% confidence interval (CI) 0.90–0.99] or limited activity owing to back pain (RR = 0.94, 95% CI 0.87–1.00). Women randomized to zoledronic acid were significantly less likely to experience 7 or more bed-rest days owing to a fracture (RR = 0.58, 95% CI 0.47–0.72) and 7 or more limited-activity days owing to a fracture (RR = 0.67, 95% CI 0.58–0.78). Reductions in back pain with zoledronic acid were independent of incident fracture. Our conclusion is that in women with postmenopausal osteoporosis, a once-yearly infusion with zoledronic acid over a 3-year period significantly reduced the number of days that patients reported back pain, limited activity owing to back pain, and limited activity and bed rest owing to a fracture.

Published
2011

24. Effects of the peroxisome proliferator-activated receptor (PPAR)-δ agonist GW501516 on bone and muscle in ovariectomized rats

Author

Mosti, M P, Stunes, A K, Ericsson, Madelene, Pullisaar, H, Reseland, J E, Shabestari, M, Eriksen, E F, Syversen, U, Mosti, M P, Stunes, A K, Ericsson, Madelene, Pullisaar, H, Reseland, J E, Shabestari, M, Eriksen, E F, and Syversen, U

Abstract

Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.

Published
2014
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25. Østrogen og hjerte

Author

Fink Eriksen E, Iversen Oe, and Syversen U

Subjects
Text mining, Estrogen, medicine.drug_class, business.industry, medicine, General Medicine, Bioinformatics, Psychology, business
Published
2013
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29. The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats

Author

Stunes, A.K. (Astrid), Westbroek, I., Gustafsson, B.I. (Björn), Fossmark, R. (Reidar), Waarsing, J.H. (Jan), Eriksen, E.F. (Erik), Petzold, C. (Christiane), Reseland, J.E., Syversen, U., Stunes, A.K. (Astrid), Westbroek, I., Gustafsson, B.I. (Björn), Fossmark, R. (Reidar), Waarsing, J.H. (Jan), Eriksen, E.F. (Erik), Petzold, C. (Christiane), Reseland, J.E., and Syversen, U.

Abstract

Background: Activation of peroxisome proliferator-activated receptor (PPAR)gamma is associated with bone loss and increased fracture risk, while PPARalpha activation seems to have positive skeletal effects. To further explore these effects we have examined the effect of the PPARalpha agonists fenofibrate and Wyeth 14643, and the PPARgamma agonist pioglitazone, on bone mineral density (BMD), bone architecture and biomechanical strength in ovariectomized rats.Methods: Fifty-five female Sprague-Dawley rats were assigned to five groups. One group was sham-operated and given vehicle (methylcellulose), the other groups were ovariectomized and given vehicle, fenofibrate, Wyeth 14643 and pioglitazone, respectively, daily for four months. Whole body and femoral BMD were measured by dual X-ray absorptiometry (DXA), and biomechanical testing of femurs, and micro-computed tomography (microCT) of the femoral shaft and head, were performed.Results: Whole body and femoral BMD were significantly higher in sham controls and ovariectomized animals given fenofibrate, compared to ovariectomized controls. Ovariectomized rats given Wyeth 14643, maintained whole body BMD at sham levels, while rats on pioglitazone had lower whole body and femoral BMD, impaired bone quality and less mechanical strength compared to sham and ovariectomized controls. In contrast, cortical volume, trabecular bone volume and thickness, and endocortical volume were maintained at sham levels in rats given fenofibrate.Conclusions: The PPARalpha agonist fenofibrate, and to a lesser extent the PPARaplha agonist Wyeth 14643, maintained BMD and bone architecture at sham levels, while the PPARgamma agonist pioglitazone exaggerated bone loss and negatively affected bone architecture, in ovariectomized rats.

Published
2011
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30. Serum gastrin and gastric enterochromaffin-like cells during estrous cycle, pregnancy and lactation, and in response to estrogen-like agents in rats

Author

Vigen, R. A., Chen, D., Syversen, U., Stunes, K., Håkanson, Rolf, Zhao, C. -M., Vigen, R. A., Chen, D., Syversen, U., Stunes, K., Håkanson, Rolf, and Zhao, C. -M.

Abstract

Histamine-containing enterochromaffin-like (ECL) cells are numerous in the gastric mucosa. They operate under the. control of gastrin. ECL-cell tumors (gastric carcinoids) may arise as a consequence of sustained hypergastrinemia. For reasons unknown, such tumors have a female preponderance both in laboratory animals and humans. The present study consisted of four experiments exploring the possibility that gender-related factors might affect rat ECL cells. 1) A gender difference in terms of serum gastrin concentration and oxyntic mucosal histidine decarboxylase (HDC) activity appeared in Sprague-Dawley but not Wistar rats. Ultrastructural appearance of the ECL cells did not differ between genders. 2) During the different phases of the estrous cycle, the serum gastrin concentration, HDC activity and histamine concentration did not change. 3) During pregnancy, the serum gastrin concentration was suppressed, while it was increased during lactation. The HDC activity and the histamine concentration of the oxyntic mucosa were correlated with the levels of circulating gastrin. 4) Twelve-month treatment with estrogen-like agents, dieldrin and/or toxaphene (alone or in combination) was without any effect on the ECL cells neither in male nor in female rats. In conclusion, the ECL cells are under the control of gastrin, but probably not hormones that involve in the estrous cycle and pregnancy and lactation in rats. Possible gender-related factors behind the female preponderance of ECL-cell tumors remain unknown.

Published
2011

31. [Diphosphonates--pharmacology and clinical use]

Author

Jan Aaseth, Syversen U, and Førre O

Subjects
Diphosphonates, Research, Humans, Female, Osteoporosis, Postmenopausal
Abstract

Based upon recent research, bisphosphonates have now attained a ranking as the first alternative to oestrogen replacement therapy in women with postmenopausal osteoporosis. The efficacy of these drugs has been clearly documented in recent years, particularly as a result of extensive clinical trials with alendronate. The studies have also confirmed the favourable risk/benefit ratio. The specific affinity of bisphosphonates for bone tissue has been recognized for many years, and explains the diagnostic use of radio-labelled species in skeleton scintigraphy. Bisphosphonates deposited in bone tissue reverse the osteoporotic process by inhibiting osteoclastic bone resorption. This mechanism also explains their role as the treatment of choice in patients with Paget's disease and cancer induced hypercalcaemia. In addition, the same drugs are useful adjuvants in the treatment of patients with multiple myeloma or bone metastases to lessen the pain and risk of fracture. A possible role of bisphosphonates in the management of cancer patients without detectable bone metastases or patients with rheumatoid arthritis has been discussed, but further research is needed in these areas.

Published
1998

33. Long-term fluoxetine administration does not result in major changes in bone architecture and strength in growing rats

Author

Westbroek, I., Waarsing, J. H., van Leeuwen, J. P. T. M., Waldum, H., Reseland, J. E., Weinans, H., Syversen, U., Gustafsson, B. I., Westbroek, I., Waarsing, J. H., van Leeuwen, J. P. T. M., Waldum, H., Reseland, J. E., Weinans, H., Syversen, U., and Gustafsson, B. I.

Abstract

Many studies have indicated that serotonin and its transporter play a role in bone metabolism. In this study we investigated the effect of selective serotonin re-uptake inhibitor (SSRI), fluoxetine (Prozac (R))) on bone architecture and quality in growing female rats. We therefore administrated rats with clinically relevant doses of fluoxetine for a period of 6 months. DXA scans were performed during the treatment period in order to follow parameters as body weight, fat percentage and BMD. After 6 months of treatment, femurs were used to analyze bone architecture and bone strength, by means of mu CT scans and three-point bending assays, respectively. We found a slightly diminished bone quality, reflected in a lower bone tissue strength, which was compensated by changes in bone geometry. As leptin and adiponectin could be possible factors in the serotonergic regulation of bone metabolism, we also determined the levels of these factors in plasma samples of all animals. Leptin and adiponectin levels were not different between the control group and fluoxetine-treated group, indicating that these factors were not involved in the observed changes in bone geometry and quality.

Published
2007

43. Serotonin and fluoxetine modulate bone cell function in vitro

Author

Gustafsson, B.I., primary, Thommesen, L., additional, Stunes, A.K., additional, Tommeras, K., additional, Westbroek, I., additional, Waldum, H.L., additional, Slørdahl, K., additional, Tamburstuen, M.V., additional, Reseland, J.E., additional, and Syversen, U., additional

Published
2006
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