Bone and Cellular Immune System of Multiparous Sows are Insensitive to Ovariectomy and Nutritive Calcium Shortage

Abstract

Research in osteoporosis, which is a complex systemic disease, demands suitable large animal models. In pigs, most research has been done in growing minipigs, which probably are not ideal models for postmenopausal osteoporosis. Therefore, our aim was to analyze the effects of ovariectomy (OVX) and nutritive calcium shortage on multiparous Large White sows. 32 animals were randomly assigned to 4 groups in a cross design with OVX vs. sham and physiological calcium supplementation (0.75% calcium) vs. dietary calcium shortage (0.3% calcium). The observation period was 10 months with blood sampling every 2 months for hematological, immunological, and biochemical bone marker measurements. At the termination of the experiment, animals were sacrificed. Samples of trabecular bone of distal radius, proximal tibia, and sixth lumbar vertebra were subjected to micro-computed tomography imaging and ashed afterwards. Dual X-ray absorptiometry scans of the proximal femora were performed with prepared bones being placed in a water bath for mimicking soft tissue. Analyses of bone marker and cytokine profile kinetics, distribution of leukocyte subpopulations, and morphometrical and densitometrical analyses showed no evidence of any impact of OVX or calcium shortage. In conclusion, the skeleton of adult sows of a conventional breed is seemingly protected from effects of OVX and calcium shortage.

Key words

osteoporosis - osteoimmunology - pig

References

• 1 Pietschmann P, Rauner M, Sipos W, Kerschan-Schindl K. Osteoporosis: an age-related and gender-specific disease – a mini-review.  Gerontology. 2008;  55 3-12
• 2 Guidelines for Preclinical and Clinical Evaluation of Agents Used for the prevention or Treatment of Postmenopausal osteoporosis . Division of Metabolism and Endocrine Drug Products, Food and Drug Administration.  1994; 
• 3 Mori R, Kodaka T, Soeta S, Sato J. Preliminary study of histological comparison on the growth patterned of long-bone cortex in young calf, pig, and sheep.  J Vet Med Sci. 2005;  67 1223-1229
• 4 Mosekilde L, Weisbrode SE, Safron JA, Stills HF, Jankowsky ML, Ebert DC, Danielsen CC, Sogaard CH, Franks F, Stevens ML, Paddock CL, Boyce RW. Evaluation of the skeletal effects of combined mild dietary calcium restriction and ovariectomy in Sinclair S-1 minipigs: a pilot study.  J Bone Miner Res. 1993;  8 1311-1321
• 5 Scholz-Ahrens KE, Delling G, Jungblut PW, Kallweit E, Barth CA. Effect of ovariectomy on bone histology and plasma parameters of bone metabolism in nulliparous and multiparous sows.  Z Ernährungswiss. 1996;  35 13-21
• 6 Rauner M, Sipos W, Pietschmann P. Osteoimmunology.  Int Arch Allergy Immunol. 2007;  143 31-48
• 7 Allen MJ. Biochemical markers of bone metabolism in animals: uses and limitations.  Vet Clin Pathol. 2003;  32 101-113
• 8 Sipos W, Duvigneau JC, Hofbauer G, Schmoll F, Baravalle G, Exel B, Harth R, Dobretsberger M, Pietschmann P. Characterization of the cytokine pattern of porcine bone marrow derived cells treated with 1α,25(OH)₂D₃.  J Vet Med A. 2005;  52 382-387
• 9 Palme R, Möstl E. Biotin-streptavidin enzyme immunoassay for the determination of oestrogens and androgens in boar faeces.. In: Görög S (ed). Advances of Steroid Analysis ’93 Budapest: Akadémiai Kiadó; 1994: 111-117
• 10 Sipos W, Duvigneau J, Sterz F, Weihs W, Krizanac D, Bayegan K, Graf A, Hartl R, Janata A, Holzer M, Behringer W. Changes in interleukin-10 mRNA expression are predictive for 9-day survival of pigs in an emergency preservation and resuscitation model.  Resuscitation. 2010;  81 603-608
• 11 Sipos W, Duvigneau CJ, Hartl RT, Schwendenwein I. Exploratory reference intervals on hematology and cellular immune system of multiparous Large White sows.  Vet Immunol Immunopathol. 2011;  141 307-311
• 12 Sipos W, Schmoll F, Stumpf I. Minipigs and Potbellied Pigs as Pets in the Veterinary Practice – a Retrospective Study.  J Vet Med A. 2007;  54 504-511
• 13 Klopfenstein C, Farmer C, Martineau G-P. Diseases of the Mammary Gland.. In: Straw BE, Zimmerman JJ, D’Allaire S, Taylor DJ (eds). Diseases of Swine Iowa: Blackwell Publishing; 2006: 57-86
• 14 Turner AS, Mallinckrodt CH, Alvis MR, Bryant HU. Dose-response effects of estradiol implants on bone mineral density in ovariectomized ewes.  Bone. 1995;  17 421-427
• 15 MacLeay JM, Olson JD, Enns RM, Les CM, Toth CA, Wheeler DL, Turner AS. Dietary-induced metabolic acidosis decreases bone mineral density in mature ovariectomized ewes.  Calcif Tissue Int. 2004;  75 431-437
• 16 Chavassieux P, Garnero P, Duboeuf F, Vergnaud O, Brunner-Ferber F, Delmas PD, Meunier PJ. Effects of a new selective estrogen receptor modulator (MDL 103,323) on cancellous and cortical bone in ovariectomized ewes: A biochemical, histomorphometric, and densitometric study.  J Bone Miner Res. 2001;  16 89-96
• 17 Giavaresi G, Fini M, Torricelli P, Giardino R. The ovariectomized ewe model in the evaluation of biomaterials for prosthetic devices in spinal fixation.  Int J Artif Organs. 2001;  24 814-820
• 18 Pogoda P, Egermann M, Schnell JC, Priemel M, Schilling AF, Alini M, Schinke T, Rueger JM, Schneider E, Clarke I, Amling M. Leptin inhibits bone formation not only in rodents but also in sheep.  J Bone Miner Res. 2006;  21 1591-1599
• 19 Lill CA, Fluegel AK, Schneider E. Sheep model for fracture treatment in osteoporotic bone: a pilot study about different induction regimens.  J Orthop Trauma. 2000;  14 559-566
• 20 Lill CA, Gerlach UV, Eckhardt C, Goldhahn J, Schneider E. Bone changes due to glucocorticoid application in an ovariectomized animal model for fracture treatment in osteoporosis.  Osteoporos Int. 2002;  13 407-414
• 21 Pacifici R. Postmenopausal osteoporosis: how the hormonal changes of menopause cause bone loss.. In: Marcus R, Feldman D, Nelson DA, Rosen CF. (eds). Osteoporosis Amsterdam: Elsevier; 2008: 1041-1054
• 22 Pietschmann P, Grisar J, Thien R, Willheim M, Kerschan-Schindl K, Preisinger E, Peterlik M. Immune phenotype and intracellular cytokine production of peripheral blood mononuclear cells from postmenopausal patients with osteoporotic fractues.  Exp Gerontol. 2001;  36 1749-1759
• 23 Zheng SX, Vrindts Y, Lopez M, De Groote D, Zangerle PF, Collette J, Franchimont N, Geenen V, Albert A, Reginster JY. Increase in cytokine production (IL-1β, IL-6, TNF-α but not IFN-γ, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis.  Maturitas. 1997;  26 63-71
• 24 Scholz-Ahrens KE, Delling G, Stampa B, Helfenstein A, Hahne HJ, Açil Y, Timm W, Barkmann R, Hassenpflug J, Schrezenmeir J, Glüer CC. Glucocorticosteroid-induced osteoporosis in adult primiparous Göttingen miniature pigs: effects on bone mineral and mineral metabolism.  Am J Physiol Endocrinol Metab. 2007;  293 E385-E395
• 25 Boyce RW, Ebert DC, Youngs TA, Paddock CL, Mosekilde L, Stevens ML, Gundersen HJG. Unbiased estimation of vertebral trabecular connectivity in calcium-restricted ovariectomized minipigs.  Bone. 1995;  16 637-642
• 26 McGee LME, Wojda SJ, Barlow LN, Drummer TD, Castillo AB, Kennedy O, Condon KW, Auger J, Black HL, Nelson OL, Robbins CT, Donahue SW. Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).  Bone. 2009;  45 1186-1191

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