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Published in: BMC Musculoskeletal Disorders 1/2011

Open Access 01-12-2011 | Research article

Pinealectomy affects bone mineral density and structure - an experimental study in sheep

Authors: Marcus Egermann, Christian Gerhardt, Alain Barth, Georges J Maestroni, Erich Schneider, Mauro Alini

Published in: BMC Musculoskeletal Disorders | Issue 1/2011

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Abstract

Background

Osteoporosis and associated fractures are a major public health burden and there is great need for a large animal model. Melatonin, the hormone of the pineal gland, has been shown to influence bone metabolism. This study aims to evaluate whether absence of melatonin due to pinealectomy affects the bone mass, structure and remodeling in an ovine animal model.

Methods

Female sheep were arranged into four groups: Control, surgically ovariectomized (Ovx), surgically pinealectomized (Px) and Ovx+Px. Before and 6 months after surgery, iliac crest biopsies were harvested and structural parameters were measured using μCT. Markers of bone formation and resorption were determined. To evaluate long term changes after pinealectomy, bone mineral density (BMD) was analyzed at the distal radius at 0, 3, 9, 18 and 30 months.

Results

Cancellous bone volume (BV/TV) declined after 6 months by -13.3% Px and -21.5% OvxPx. The bone loss was due to increased trabecular separation as well as decreased thickness. The histomorphometric quantification and determination of collagen degradation products showed increased bone resorption following pinealectomy. Ovariectomy alone results in a transient bone loss at the distal radius followed by continuous increase to baseline levels. The bone resorption activity after pinealectomy causes a bone loss which was not transient, since a continuous decrease in BMD was observed until 30 months.

Conclusions

The changes after pinealectomy in sheep are indicative of bone loss. Overall, these findings suggest that the pineal gland may influence bone metabolism and that pinealectomy can be used to induce bone loss in sheep.
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Literature
1.
go back to reference Barrios C, Brostrom LA, Stark A, Walheim G: Healing complications after internal fixation of trochanteric hip fractures: the prognostic value of osteoporosis. J Orthop Trauma. 1993, 7: 438-442. 10.1097/00005131-199310000-00006.CrossRefPubMed Barrios C, Brostrom LA, Stark A, Walheim G: Healing complications after internal fixation of trochanteric hip fractures: the prognostic value of osteoporosis. J Orthop Trauma. 1993, 7: 438-442. 10.1097/00005131-199310000-00006.CrossRefPubMed
2.
go back to reference Cornell CN: Internal fracture fixation in patients with osteoporosis. J Am Acad Orthop Surg. 2003, 11: 109-119.CrossRefPubMed Cornell CN: Internal fracture fixation in patients with osteoporosis. J Am Acad Orthop Surg. 2003, 11: 109-119.CrossRefPubMed
3.
go back to reference Food and Drug Administration: Guidelines for Preclinical and Clinical Evaluation of Agents Used in the Prevention or Treatment of Postmenopausal Osteoporosis. 1994, Washington D C: FDA Division of Metablism and Endocrine Drug Products Food and Drug Administration: Guidelines for Preclinical and Clinical Evaluation of Agents Used in the Prevention or Treatment of Postmenopausal Osteoporosis. 1994, Washington D C: FDA Division of Metablism and Endocrine Drug Products
4.
go back to reference Egermann M, Goldhahn J, Schneider E: Animal models for fracture treatment in osteoporosis. Osteoporos Int. 2005, 16 (Suppl 2): S129-S138.CrossRefPubMed Egermann M, Goldhahn J, Schneider E: Animal models for fracture treatment in osteoporosis. Osteoporos Int. 2005, 16 (Suppl 2): S129-S138.CrossRefPubMed
5.
go back to reference Miller SC, Wronski TJ: Long-term osteopenic changes in cancellous bone structure in ovariectomized rats. Anat Rec. 1993, 236: 433-441. 10.1002/ar.1092360303.CrossRefPubMed Miller SC, Wronski TJ: Long-term osteopenic changes in cancellous bone structure in ovariectomized rats. Anat Rec. 1993, 236: 433-441. 10.1002/ar.1092360303.CrossRefPubMed
6.
go back to reference Thompson DD, Simmons HA, Pirie CM, Ke HZ: FDA Guidelines and animal models for osteoporosis. Bone. 1995, 17: 125S-133S.CrossRefPubMed Thompson DD, Simmons HA, Pirie CM, Ke HZ: FDA Guidelines and animal models for osteoporosis. Bone. 1995, 17: 125S-133S.CrossRefPubMed
7.
go back to reference Turner AS: The sheep as a model for osteoporosis in humans. Vet J. 2002, 163: 232-239. 10.1053/tvjl.2001.0642.CrossRefPubMed Turner AS: The sheep as a model for osteoporosis in humans. Vet J. 2002, 163: 232-239. 10.1053/tvjl.2001.0642.CrossRefPubMed
8.
go back to reference Turner AS, Alvis M, Myers W, Stevens ML, Lundy MW: Changes in bone mineral density and bone-specific alkaline phosphatase in ovariectomized ewes. Bone. 1995, 17: 395S-402S.CrossRefPubMed Turner AS, Alvis M, Myers W, Stevens ML, Lundy MW: Changes in bone mineral density and bone-specific alkaline phosphatase in ovariectomized ewes. Bone. 1995, 17: 395S-402S.CrossRefPubMed
9.
go back to reference Chavassieux P, Garnero P, Duboeuf F, Vergnaud P, Brunner-Ferber F, Delmas PD, et al: 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. 10.1359/jbmr.2001.16.1.89.CrossRefPubMed Chavassieux P, Garnero P, Duboeuf F, Vergnaud P, Brunner-Ferber F, Delmas PD, et al: 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. 10.1359/jbmr.2001.16.1.89.CrossRefPubMed
10.
go back to reference Sigrist IM, Gerhardt C, Alini M, Schneider E, Egermann M: The long-term effects of ovariectomy on bone metabolism in sheep. J Bone Miner Metab. 2007, 25: 28-35.CrossRefPubMed Sigrist IM, Gerhardt C, Alini M, Schneider E, Egermann M: The long-term effects of ovariectomy on bone metabolism in sheep. J Bone Miner Metab. 2007, 25: 28-35.CrossRefPubMed
11.
go back to reference Cardinali DP, Ladizesky MG, Boggio V, Cutrera RA, Mautalen C: Melatonin effects on bone: experimental facts and clinical perspectives. J Pineal Res. 2003, 34: 81-87. 10.1034/j.1600-079X.2003.00028.x.CrossRefPubMed Cardinali DP, Ladizesky MG, Boggio V, Cutrera RA, Mautalen C: Melatonin effects on bone: experimental facts and clinical perspectives. J Pineal Res. 2003, 34: 81-87. 10.1034/j.1600-079X.2003.00028.x.CrossRefPubMed
12.
go back to reference Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni JM: Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res. 2000, 28: 193-202. 10.1034/j.1600-079X.2000.280401.x.CrossRefPubMed Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni JM: Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res. 2000, 28: 193-202. 10.1034/j.1600-079X.2000.280401.x.CrossRefPubMed
13.
go back to reference Roth JA, Kim BG, Lin WL, Cho MI: Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem. 1999, 274: 22041-22047. 10.1074/jbc.274.31.22041.CrossRefPubMed Roth JA, Kim BG, Lin WL, Cho MI: Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem. 1999, 274: 22041-22047. 10.1074/jbc.274.31.22041.CrossRefPubMed
14.
go back to reference Radio NM, Doctor JS, Witt-Enderby PA: Melatonin enhances alkaline phosphatase activity in differentiating human adult mesenchymal stem cells grown in osteogenic medium via MT2 melatonin receptors and the MEK/ERK (1/2) signaling cascade. J Pineal Res. 2006, 40: 332-342. 10.1111/j.1600-079X.2006.00318.x.CrossRefPubMed Radio NM, Doctor JS, Witt-Enderby PA: Melatonin enhances alkaline phosphatase activity in differentiating human adult mesenchymal stem cells grown in osteogenic medium via MT2 melatonin receptors and the MEK/ERK (1/2) signaling cascade. J Pineal Res. 2006, 40: 332-342. 10.1111/j.1600-079X.2006.00318.x.CrossRefPubMed
15.
go back to reference Koyama H, Nakade O, Takada Y, Kaku T, Lau KH: Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res. 2002, 17: 1219-1229. 10.1359/jbmr.2002.17.7.1219.CrossRefPubMed Koyama H, Nakade O, Takada Y, Kaku T, Lau KH: Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res. 2002, 17: 1219-1229. 10.1359/jbmr.2002.17.7.1219.CrossRefPubMed
16.
go back to reference Sandyk R, Anastasiadis PG, Anninos PA, Tsagas N: Is postmenopausal osteoporosis related to pineal gland functions?. Int J Neurosci. 1992, 62: 215-225.CrossRefPubMed Sandyk R, Anastasiadis PG, Anninos PA, Tsagas N: Is postmenopausal osteoporosis related to pineal gland functions?. Int J Neurosci. 1992, 62: 215-225.CrossRefPubMed
17.
go back to reference Iguchi H: [Age dependent changes in the serum melatonin concentrations in healthy human subjects and in patients with endocrine and hepatic disorders and renal failure (author's transl)]. Fukuoka Igaku Zasshi. 1981, 72: 423-430.PubMed Iguchi H: [Age dependent changes in the serum melatonin concentrations in healthy human subjects and in patients with endocrine and hepatic disorders and renal failure (author's transl)]. Fukuoka Igaku Zasshi. 1981, 72: 423-430.PubMed
18.
go back to reference Sack RL, Lewy AJ, Erb DL, Vollmer WM, Singer CM: Human melatonin production decreases with age. J Pineal Res. 1986, 3: 379-388. 10.1111/j.1600-079X.1986.tb00760.x.CrossRefPubMed Sack RL, Lewy AJ, Erb DL, Vollmer WM, Singer CM: Human melatonin production decreases with age. J Pineal Res. 1986, 3: 379-388. 10.1111/j.1600-079X.1986.tb00760.x.CrossRefPubMed
19.
go back to reference Ostrowska Z, Kos-Kudla B, Marek B, Swietochowska E, Gorski J: Assessment of the relationship between circadian variations of salivary melatonin levels and type I collagen metabolism in postmenopausal obese women. Neuro Endocrinol Lett. 2001, 22: 121-127.PubMed Ostrowska Z, Kos-Kudla B, Marek B, Swietochowska E, Gorski J: Assessment of the relationship between circadian variations of salivary melatonin levels and type I collagen metabolism in postmenopausal obese women. Neuro Endocrinol Lett. 2001, 22: 121-127.PubMed
20.
go back to reference Ladizesky MG, Cutrera RA, Boggio V, Somoza J, Centrella JM, Mautalen C, et al: Effect of melatonin on bone metabolism in ovariectomized rats. Life Sci. 2001, 70: 557-565. 10.1016/S0024-3205(01)01431-X.CrossRefPubMed Ladizesky MG, Cutrera RA, Boggio V, Somoza J, Centrella JM, Mautalen C, et al: Effect of melatonin on bone metabolism in ovariectomized rats. Life Sci. 2001, 70: 557-565. 10.1016/S0024-3205(01)01431-X.CrossRefPubMed
21.
go back to reference Ladizesky MG, Boggio V, Albornoz LE, Castrillon PO, Mautalen C, Cardinali DP: Melatonin increases oestradiol-induced bone formation in ovariectomized rats. J Pineal Res. 2003, 34: 143-151. 10.1034/j.1600-079X.2003.00021.x.CrossRefPubMed Ladizesky MG, Boggio V, Albornoz LE, Castrillon PO, Mautalen C, Cardinali DP: Melatonin increases oestradiol-induced bone formation in ovariectomized rats. J Pineal Res. 2003, 34: 143-151. 10.1034/j.1600-079X.2003.00021.x.CrossRefPubMed
22.
go back to reference Ostrowska Z, Kos-Kudla B, Marek B, Kajdaniuk D, Staszewicz P, Szapska B, et al: The influence of pinealectomy and melatonin administration on the dynamic pattern of biochemical markers of bone metabolism in experimental osteoporosis in the rat. Neuro Endocrinol Lett. 2002, 23 (Suppl 1): 104-109.PubMed Ostrowska Z, Kos-Kudla B, Marek B, Kajdaniuk D, Staszewicz P, Szapska B, et al: The influence of pinealectomy and melatonin administration on the dynamic pattern of biochemical markers of bone metabolism in experimental osteoporosis in the rat. Neuro Endocrinol Lett. 2002, 23 (Suppl 1): 104-109.PubMed
23.
go back to reference Dempsey RJ, Hopkins J, Bittman EL, Kindt GW: Total pinealectomy by an occipital parasagittal approach in sheep. Surg Neurol. 1982, 18: 377-380. 10.1016/0090-3019(82)90157-4.CrossRefPubMed Dempsey RJ, Hopkins J, Bittman EL, Kindt GW: Total pinealectomy by an occipital parasagittal approach in sheep. Surg Neurol. 1982, 18: 377-380. 10.1016/0090-3019(82)90157-4.CrossRefPubMed
24.
go back to reference Roche JF, Dziuk PJ: A technique for pinealectomy of the ewe. Am J Vet Res. 1969, 30: 2031-2035.PubMed Roche JF, Dziuk PJ: A technique for pinealectomy of the ewe. Am J Vet Res. 1969, 30: 2031-2035.PubMed
25.
go back to reference Hildebrand T, Ruegsegger P: Quantification of Bone Microarchitecture with the Structure Model Index. Comput Methods Biomech Biomed Engin. 1997, 1: 15-23. 10.1080/01495739708936692.CrossRefPubMed Hildebrand T, Ruegsegger P: Quantification of Bone Microarchitecture with the Structure Model Index. Comput Methods Biomech Biomed Engin. 1997, 1: 15-23. 10.1080/01495739708936692.CrossRefPubMed
26.
go back to reference Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, et al: Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987, 2: 595-610.CrossRefPubMed Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, et al: Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987, 2: 595-610.CrossRefPubMed
27.
go back to reference Turgut M, Basaloglu HK, Yenisey C, Ozsunar Y: Surgical pinealectomy accelerates intervertebral disc degeneration process in chicken. Eur Spine J. 2006, 15: 605-612. 10.1007/s00586-005-0972-9.CrossRefPubMed Turgut M, Basaloglu HK, Yenisey C, Ozsunar Y: Surgical pinealectomy accelerates intervertebral disc degeneration process in chicken. Eur Spine J. 2006, 15: 605-612. 10.1007/s00586-005-0972-9.CrossRefPubMed
28.
go back to reference Pogoda P, Egermann M, Schnell JC, Priemel M, Schilling AF, Alini M, et al: Leptin inhibits bone formation not only in rodents, but also in sheep. J Bone Miner Res. 2006, 21: 1591-1599. 10.1359/jbmr.060709.CrossRefPubMed Pogoda P, Egermann M, Schnell JC, Priemel M, Schilling AF, Alini M, et al: Leptin inhibits bone formation not only in rodents, but also in sheep. J Bone Miner Res. 2006, 21: 1591-1599. 10.1359/jbmr.060709.CrossRefPubMed
29.
go back to reference 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. 10.1007/s001980200047.CrossRefPubMed 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. 10.1007/s001980200047.CrossRefPubMed
30.
go back to reference Schorlemmer S, Gohl C, Iwabu S, Ignatius A, Claes L, Augat P: Glucocorticoid treatment of ovariectomized sheep affects mineral density, structure, and mechanical properties of cancellous bone. J Bone Miner Res. 2003, 18: 2010-2015. 10.1359/jbmr.2003.18.11.2010.CrossRefPubMed Schorlemmer S, Gohl C, Iwabu S, Ignatius A, Claes L, Augat P: Glucocorticoid treatment of ovariectomized sheep affects mineral density, structure, and mechanical properties of cancellous bone. J Bone Miner Res. 2003, 18: 2010-2015. 10.1359/jbmr.2003.18.11.2010.CrossRefPubMed
31.
go back to reference Egermann M, Goldhahn J, Holz R, Schneider E, Lill CA: A sheep model for fracture treatment in osteoporosis: benefits of the model versus animal welfare. Lab Anim. 2008, 42: 453-464. 10.1258/la.2007.007001.CrossRefPubMed Egermann M, Goldhahn J, Holz R, Schneider E, Lill CA: A sheep model for fracture treatment in osteoporosis: benefits of the model versus animal welfare. Lab Anim. 2008, 42: 453-464. 10.1258/la.2007.007001.CrossRefPubMed
Metadata
Title
Pinealectomy affects bone mineral density and structure - an experimental study in sheep
Authors
Marcus Egermann
Christian Gerhardt
Alain Barth
Georges J Maestroni
Erich Schneider
Mauro Alini
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2011
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-12-271

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