Glucocorticoids Affect Bone Mineral Density and Bone Remodelling in OVX Sheep: A Pilot Study

Overview

Journal Bone Rep

Date 2018 Nov 28

PMID 30480061

Citations 5

Authors

Diana Cabrera

Frances M Wolber

Keren Dittmer

Chris Rogers

Anne Ridler

Danielle Aberdein

Tim Parkinson

Paul Chambers

Karl Fraser

Nicole C Roy

Marlena Kruger

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to validate the combination of ovariectomy and glucocorticoid treatment in sheep as a large animal model for osteoporosis by measuring the concentration of specific biomarkers in the blood of the sheep and measuring bone loss over five months. Aged Merino ewes were randomly allocated into four groups: control, ovariectomy (OVX), and two OVX groups receiving glucocorticoids-one group once-monthly for five months (OVXG), and the other for two months followed by no treatment for three months (OVXG2). Parameters measured were biochemical markers of bone turnover, areal bone mineral density, volumetric bone mineral density, and total and trabecular bone parameters. Ovariectomy increased the concentrations of bone resorption marker C-terminal telopeptides of type 1 collagen (CTx-1) and bone turnover marker serum osteocalcin (OC) concentrations in the OVX group compared to control sheep. The combination of ovariectomy and glucocorticoid treatment increased the concentrations of CTx-1 and decreased serum OC concentrations in the OVXG group compared to OVXG2. Femur and lumbar spine bone density were lower in experimentally treated groups when compared with the control group. Total and trabecular BMD in the proximal tibia were significantly lower in the treatment groups when compared with the control group. A significant negative correlation between femoral bone density and CTx-1 was found. The results of this study suggest that the combination of OVX and glucocorticoids induces bone loss in a short period of time in sheep.

Citing Articles

Effects of restraint stress and surface treatments on the stability of titanium dental implant osseointegration in dogs: An in vivo comparative study.

Abdulla M, Hasan R, Al-Hyani O J Taibah Univ Med Sci. 2024; 19(3):461-472.

PMID: 38544871 PMC: 10965825. DOI: 10.1016/j.jtumed.2024.03.004.

Osteoporosis Preclinical Research: A Systematic Review on Comparative Studies Using Ovariectomized Sheep.

Salamanna F, Contartese D, Veronesi F, Martini L, Fini M Int J Mol Sci. 2022; 23(16).

PMID: 36012173 PMC: 9408715. DOI: 10.3390/ijms23168904.

Expression of Renal Vitamin D and Phosphatonin-Related Genes in a Sheep Model of Osteoporosis.

Dittmer K, Chernyavtseva A, Marshall J, Cabrera D, Wolber F, Kruger M Animals (Basel). 2022; 12(1).

PMID: 35011173 PMC: 8749731. DOI: 10.3390/ani12010067.

Effects of short- and long-term glucocorticoid-induced osteoporosis on plasma metabolome and lipidome of ovariectomized sheep.

Cabrera D, Kruger M, Wolber F, Roy N, Fraser K BMC Musculoskelet Disord. 2020; 21(1):349.

PMID: 32503480 PMC: 7275480. DOI: 10.1186/s12891-020-03362-7.

Engineering bone phenotypes in domestic animals: Unique resources for enhancing musculoskeletal research.

Suva L, Westhusin M, Long C, Gaddy D Bone. 2019; 130:115119.

PMID: 31712131 PMC: 8805042. DOI: 10.1016/j.bone.2019.115119.

References

Johnson R, Gilbert J, Cooper R, Parsell D, Stewart B, Dai X . Effect of estrogen deficiency on skeletal and alveolar bone density in sheep. J Periodontol. 2002; 73(4):383-91. DOI: 10.1902/jop.2002.73.4.383. View

Harvey N, Dennison E, Cooper C . Osteoporosis: impact on health and economics. Nat Rev Rheumatol. 2010; 6(2):99-105. DOI: 10.1038/nrrheum.2009.260. View

Compston J . Management of glucocorticoid-induced osteoporosis. Nat Rev Rheumatol. 2010; 6(2):82-8. DOI: 10.1038/nrrheum.2009.259. View

Engelke K, Adams J, Armbrecht G, Augat P, Bogado C, Bouxsein M . Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD Official Positions. J Clin Densitom. 2008; 11(1):123-62. DOI: 10.1016/j.jocd.2007.12.010. View

Newman E, Turner A, Wark J . The potential of sheep for the study of osteopenia: current status and comparison with other animal models. Bone. 1995; 16(4 Suppl):277S-284S. DOI: 10.1016/8756-3282(95)00026-a. View

Garnero P, Ferreras M, Karsdal M, Nicamhlaoibh R, Risteli J, Borel O . The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation. J Bone Miner Res. 2003; 18(5):859-67. DOI: 10.1359/jbmr.2003.18.5.859. View

Les C, Vance J, Christopherson G, Turner A, Divine G, Fyhrie D . Long-term ovariectomy decreases ovine compact bone viscoelasticity. J Orthop Res. 2005; 23(4):869-76. DOI: 10.1016/j.orthres.2004.12.001. View

MacLeay J, Olson J, Turner A . Effect of dietary-induced metabolic acidosis and ovariectomy on bone mineral density and markers of bone turnover. J Bone Miner Metab. 2004; 22(6):561-8. DOI: 10.1007/s00774-004-0524-0. View

Egermann M, Goldhahn J, Holz R, Schneider E, Lill C . A sheep model for fracture treatment in osteoporosis: benefits of the model versus animal welfare. Lab Anim. 2008; 42(4):453-64. DOI: 10.1258/la.2007.007001. View

10.

Chavassieux P, Pastoureau P, CHAPUY M, Delmas P, Meunier P . Glucocorticoid-induced inhibition of osteoblastic bone formation in ewes: a biochemical and histomorphometric study. Osteoporos Int. 1993; 3(2):97-102. DOI: 10.1007/BF01623380. View

11.

Chavassieux P, Buffet A, Vergnaud P, Garnero P, Meunier P . Short-term effects of corticosteroids on trabecular bone remodeling in old ewes. Bone. 1997; 20(5):451-5. DOI: 10.1016/s8756-3282(97)00016-1. View

12.

Zhang Y, Li Y, Gao Q, Shao B, Xiao J, Zhou H . The variation of cancellous bones at lumbar vertebra, femoral neck, mandibular angle and rib in ovariectomized sheep. Arch Oral Biol. 2014; 59(7):663-9. DOI: 10.1016/j.archoralbio.2014.03.013. View

13.

Kielbowicz Z, Piatek A, Biezynski J, Skrzypczak P, Kuropka P, Kuryszko J . The experimental osteoporosis in sheep--clinical approach. Pol J Vet Sci. 2015; 18(3):645-54. DOI: 10.1515/pjvs-2015-0083. View

14.

Drake M, Clarke B, Lewiecki E . The Pathophysiology and Treatment of Osteoporosis. Clin Ther. 2015; 37(8):1837-50. DOI: 10.1016/j.clinthera.2015.06.006. View

15.

Wilke H, Kettler A, Claes L . Are sheep spines a valid biomechanical model for human spines?. Spine (Phila Pa 1976). 1997; 22(20):2365-74. DOI: 10.1097/00007632-199710150-00009. View

16.

Yoon K, Cho D, Yu S, Kim K, Jeon Y, Sung J . The Change of Bone Metabolism in Ovariectomized Rats : Analyses of MicroCT Scan and Biochemical Markers of Bone Turnover. J Korean Neurosurg Soc. 2012; 51(6):323-7. PMC: 3424170. DOI: 10.3340/jkns.2012.51.6.323. View

17.

Newton B, Cooper R, Gilbert J, Johnson R, Zardiackas L . The ovariectomized sheep as a model for human bone loss. J Comp Pathol. 2004; 130(4):323-6. DOI: 10.1016/j.jcpa.2003.12.007. View

18.

Sigrist I, Gerhardt C, Alini M, Schneider E, Egermann M . The long-term effects of ovariectomy on bone metabolism in sheep. J Bone Miner Metab. 2006; 25(1):28-35. DOI: 10.1007/s00774-006-0724-x. View

19.

Allen M . Biochemical markers of bone metabolism in animals: uses and limitations. Vet Clin Pathol. 2003; 32(3):101-13. DOI: 10.1111/j.1939-165x.2003.tb00323.x. View

20.

Turner A, Alvis M, Myers W, Stevens M, Lundy M . Changes in bone mineral density and bone-specific alkaline phosphatase in ovariectomized ewes. Bone. 1995; 17(4 Suppl):395S-402S. DOI: 10.1016/8756-3282(95)00317-7. View