Scoliosis | |
Is decreased bone mineral density associated with development of scoliosis? A bipedal osteopenic rat model | |
Emre Acaroglu2  Ralph Marcucio1  Nadir Yalcin1  Gokhan Demirkiran3  Ibrahim Akel4  Ozgur Dede3  | |
[1] University of California San Francisco, San Francisco General Hospital, Department of Orthopedic Surgery, San Francisco, CA, USA;Ankara Spine Center, Kavaklidere, Ankara, Turkey;Hacettepe University Department of Orthopedics and Traumatology, Ankara, Turkey;Izmir Kent Hospital, Cigli, Izmir, Turkey | |
关键词: Rat model; Heparin; Osteoporosis; Idiopathic Scoliosis; | |
Others : 791901 DOI : 10.1186/1748-7161-6-24 |
|
received in 2011-04-30, accepted in 2011-10-31, 发布年份 2011 | |
【 摘 要 】
Background
An association between adolescent idiopathic scoliosis and osteopenia has been proposed to exist. It is still not clear whether there is such an association and if so, whether osteopenia is a causative factor or a consequence. Our previous pilot studies have suggested the presence of osteopenia in scoliotic animals. The aim of this study was to investigate the development of scoliosis in an unpinealectomized bipedal osteopenic rat model, implementing osteoporosis as a causative factor.
Methods
Fifty Sprague-Dawley rats were rendered bipedal at the 3rd postnatal week and separated into control (25 rats) and heparin (25 rats receiving 1 IU/gr body weight/day) groups. DEXA scans after 4 weeks of heparin administration showed low bone mass in the heparin group. Anteroposterior and lateral x-rays of the surviving 42 animals (19 in heparin and 23 in control groups) were taken under anesthesia at the 40th week to evaluate for spinal deformity. Additional histomorphometric analysis was done on spine specimens to confirm the low bone mass in heparin receiving animals. Results of the DEXA scans, histomorphometric analysis and radiological data were compared between the groups.
Results
Bone mineral densities of rats in the heparin group were significantly lower than the control group as evidenced by both the DEXA scans and histomorphometric analyses. However, the incidence of scoliosis (82% in heparin and 65% in control; p > 0.05) as well as the curve magnitudes (12.1 ± 3.8 in heparin versus 10.1 ± 4.3 degrees in control; p > 0.05) were not significantly different. Osteopenic rats were significantly less kyphotic compared to control specimens (p = 0.001).
Conclusions
This study has revealed two important findings. One is that bipedality (in the absence of pinealectomy) by itself may be a cause of scoliosis in this animal model. Further studies on animal models need to consider bipedality as an independent factor. Secondly, relative hypokyphosis in osteopenic animals may have important implications. The absence of sagittal plane analyses in previous studies makes comparison impossible, but nonetheless these findings suggest that osteopenia may be important in the development of 3D deformity in adolescent idiopathic scoliosis.
【 授权许可】
2011 Dede et al; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140705022538628.pdf | 669KB | download | |
Figure 3. | 170KB | Image | download |
Figure 2. | 48KB | Image | download |
Figure 1. | 32KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Lowe TG, Edgar M, Margulies JY, Miller NH, Raso VJ, Reinker KA, Rivard CH: Etiology of idiopathic scoliosis: current trends in research. J Bone Joint Surg Am 2000, 82-A:1157-1168.
- [2]Miller NH: Genetics of familial idiopathic scoliosis. Clin Orthop Relat Res 2002, 60-64.
- [3]Porter RW: The pathogenesis of idiopathic scoliosis: uncoupled neuro-osseous growth? Eur Spine J 2001, 10:473-481.
- [4]Roach JW: Adolescent idiopathic scoliosis. Orthop Clin North Am 1999, 30:353-365. vii-viii
- [5]Miller NH: Idiopathic scoliosis: cracking the genetic code and what does it mean? J Pediatr Orthop 2011, 31:S49-52.
- [6]Healey JH, Lane JM: Structural scoliosis in osteoporotic women. Clin Orthop Relat Res 1985, 216-223.
- [7]Thevenon A, Pollez B, Cantegrit F, Tison-Muchery F, Marchandise X, Duquesnoy B: Relationship between kyphosis, scoliosis, and osteoporosis in the elderly population. Spine (Phila Pa 1976) 1987, 12:744-745.
- [8]Bartal E, Gage JR: Idiopathic juvenile osteoporosis and scoliosis. J Pediatr Orthop 1982, 2:295-298.
- [9]Burner WL, Badger VM, Sherman FC: Osteoporosis and acquired back deformities. J Pediatr Orthop 1982, 2:383-385.
- [10]Sadat-Ali M, Al-Othman A, Bubshait D, Al-Dakheel D: Does scoliosis causes low bone mass? A comparative study between siblings. Eur Spine J 2008, 17:944-947.
- [11]Cheng JC, Guo X: Osteopenia in adolescent idiopathic scoliosis. A primary problem or secondary to the spinal deformity? Spine (Phila Pa 1976) 1997, 22:1716-1721.
- [12]Akel I, Demirkiran G, Alanay A, Karahan S, Marcucio R, Acaroglu E: The effect of calmodulin antagonists on scoliosis: bipedal C57BL/6 mice model. Eur Spine J 2009, 18:499-505.
- [13]Akel I, Kocak O, Bozkurt G, Alanay A, Marcucio R, Acaroglu E: The effect of calmodulin antagonists on experimental scoliosis: a pinealectomized chicken model. Spine (Phila Pa 1976) 2009, 34:533-538.
- [14]Szalay EA, Bosch P, Schwend RM, Buggie B, Tandberg D, Sherman F: Adolescents with idiopathic scoliosis are not osteoporotic. Spine (Phila Pa 1976) 2008, 33:802-806.
- [15]Cheng JC, Tang SP, Guo X, Chan CW, Qin L: Osteopenia in adolescent idiopathic scoliosis: a histomorphometric study. Spine (Phila Pa 1976) 2001, 26:E19-23.
- [16]Cook SD, Harding AF, Morgan EL, Nicholson RJ, Thomas KA, Whitecloud TS, Ratner ES: Trabecular bone mineral density in idiopathic scoliosis. J Pediatr Orthop 1987, 7:168-174.
- [17]Machida M, Murai I, Miyashita Y, Dubousset J, Yamada T, Kimura J: Pathogenesis of idiopathic scoliosis. Experimental study in rats. Spine (Phila Pa 1976) 1999, 24:1985-1989.
- [18]Goff CW, Landmesser W: Bipedal rats and mice; laboratory animals for orthopaedic research. J Bone Joint Surg Am 1957, 39-A:616-622.
- [19]Matzsch T, Bergqvist D, Hedner U, Nilsson B, Ostergaard P: Heparin-induced osteoporosis in rats. Thromb Haemost 1986, 56:293-294.
- [20]Monreal M, Vinas L, Monreal L, Lavin S, Lafoz E, Angles AM: Heparin-related osteoporosis in rats. A comparative study between unfractioned heparin and a low-molecular-weight heparin. Haemostasis 1990, 20:204-207.
- [21]Muir JM, Andrew M, Hirsh J, Weitz JI, Young E, Deschamps P, Shaughnessy SG: Histomorphometric analysis of the effects of standard heparin on trabecular bone in vivo. Blood 1996, 88:1314-1320.
- [22]Thompson RC Jr: Heparin osteoporosis. An experimental model using rats. J Bone Joint Surg Am 1973, 55:606-612.
- [23]Turhan E, Acaroglu E, Bozkurt G, Alanay A, Yazici M, Surat A: Unilateral enucleation affects the laterality but not the incidence of scoliosis in pinealectomized chicken. Spine (Phila Pa 1976) 2006, 31:133-138.
- [24]Majoor CL: Heparin and osteoporosis. Lancet 1965, 2:641.
- [25]Dintenfass L: Heparin and Osteoporosis. Lancet 1965, 2:376.
- [26]Griffith GC, Nichols G Jr, Asher JD, Flanagan B: Heparin Osteoporosis. JAMA 1965, 193:91-94.
- [27]Kingery FA: Osteoporosis, Fractures, and Heparin Therapy. JAMA 1965, 193:152.
- [28]Chigot P, De Gennes C, Samama MM: [Osteoporosis induced either by unfractionated heparin or by low molecular weight heparin]. J Mal Vasc 1996, 21:121-125.
- [29]Mazanec DJ, Grisanti JM: Drug-induced osteoporosis. Cleve Clin J Med 1989, 56:297-303.
- [30]Shaughnessy SG, Hirsh J, Bhandari M, Muir JM, Young E, Weitz JI: A histomorphometric evaluation of heparin-induced bone loss after discontinuation of heparin treatment in rats. Blood 1999, 93:1231-1236.
- [31]Cheng JC, Guo X, Sher AH: Persistent osteopenia in adolescent idiopathic scoliosis. A longitudinal follow up study. Spine (Phila Pa 1976) 1999, 24:1218-1222.
- [32]Cheng JC, Qin L, Cheung CS, Sher AH, Lee KM, Ng SW, Guo X: Generalized low areal and volumetric bone mineral density in adolescent idiopathic scoliosis. J Bone Miner Res 2000, 15:1587-1595.
- [33]Park WW, Suh KT, Kim JI, Kim SJ, Lee JS: Decreased osteogenic differentiation of mesenchymal stem cells and reduced bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J 2009, 18:1920-1926.
- [34]Li XF, Li H, Liu ZD, Dai LY: Low bone mineral status in adolescent idiopathic scoliosis. Eur Spine J 2008, 17:1431-1440.
- [35]Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group World Health Organ Tech Rep Ser 1994, 843:1-129.
- [36]Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N: The diagnosis of osteoporosis. J Bone Miner Res 1994, 9:1137-1141.
- [37]Srivastava M, Mandal SK, Sengupta S, Arshad M, Singh MM: Quantification of bone mineral density to define osteoporosis in rat. J Endocrinol Invest 2008, 31:393-399.
- [38]Niles LP, Harjivan C, Nanji A: Heparin inhibits melatonin binding and signal transduction in chick brain. Biol Signals 1994, 3:26-33.