Quantification of histomorphometric and structural bone changes in a sheep model for fracture treatment in osteoporotic bone

Summary

The histomorphometrical cancellous bone parameters of osteoporotic ewes were examined to establish a large animal model for the investigation of fracture treatment and healing in osteoporotic bone. Eighteen animals were divided into 2 groups. Group 1 (n = 8, age 3 to 5 years) served as an untreated control. In Group 2 (n = 10, age 7 to 9 years) osteoporosis was induced by means of ovariectomy, methylprednisolone application (average dose 160 mg/week) and Ca./Vit.D restricted diet during 7 months. Biopsies from iliac crest, femoral head and lumbar spine were harvested. Structural parameters from the biopsies were determined using μCT. In order to investigate static and dynamic parameters of bone remodelling, undecalcified sections were digitized and evaluated by means of image analysing software. Morphologically, bone area and trabecular thickness were reduced in osteoporotic sheep. Bone perimeter (−20%), trabecular number (−16%) and separation (+39%) showed a significant change in the iliac crest. The structure model index indicated a shift from the plate-to the rodmodel. At different skeletal sites of osteoporotic sheep bone resorption was significantly increased (250-675%), and bone formation significantly decreased (77-89%). Osteoid thickness (O.Th) was reduced (28-62%). In osteoporotic sheep the mean length of single labels was significantly shortened (64-73%) and the mineralising surface showed a significant decrease (80-92%). The mineralisation of the osteoid was comparable to the control group. The histomorphometrical changes in this sheep model of osteoporosis are comparable to the human situation of a combined post-menopausal and steroid-induced osteoporosis.

Keywords

Osteoporosis - animal model - sheep - histomorphometry - bone structure

• References

• 1 Adinoff AD, Hollister JR. Steroid-induced fractures and bone loss in patients with with asthma. N Engl J Med 1983; 309: 265-8.
• 2 Ballanti P, Della CRocca, Bonucci E, Milani S, Lo Cascio V, Imbimbo B. Sensitivity of bone histomorphometry in the diagnosis of metabolic bone diseases. Path Res Pract 1989; 185: 78-69.
• 3 Boyce RW, Franks AF, Jankowsky ML. Sequential histomorphometric changes in cancellous bone from ovariohysterctomized dogs. J Bone Miner Res 1990; 05: 947-53.
• 4 Chavassieux P, Buffet A, Vergnaud P, Garnero P, Meunier PJ. Short-term effects on ewe bone remodeling of short-term sodium fluoride administration. A histomorphometric and biochemical study. Bone 1991; 12: 421-7.
• 5 Chavassieux P, Buffet A, Vergnaud P, Garnero P, Meunier PJ. Short-term effects of corticosteroids on trabecular bone remodeling in old ewes. Bone 1997; 20: 451-5.
• 6 Chavassieux P, Pastoureau P, Chapuy MC, Delmas PD, Meunier PJ. Glucocorticoid-induced inhibition of osteoblastic bone formation in ewes: a biochemical and histomorphometric study. Osteoporosis Int 1993; 03: 97-102.
• 7 Currey JD, Brear K, Zioupos P. The effect of ageing and changes in mineral content in degrading the toughness of human femora. J Biomech 1996; 29: 257-60.
• 8 Dempster DW. Bone histomorphometry in glucocorticoid-induced osteoporosis. J Bone Miner Res 1989; 04: 137-41.
• 9 Ding M, Hvid I. Quantification of age-related changes in the structure model type and trabecular thickness of human tibial cancellous bone. Bone 2000; 26: 291-5.
• 10 Hawker GA. The epidemiology of osteoporosis. J Rheumatol 1996; 23: 2-5.
• 11 Hildebrand T, Rüegsegger P. Quantification of bone microarchitecture with the Structure Model Index. CMBBE 1997; 01: 15-23.
• 12 Ito M, Nakamura T, Matsumoto T, Tsurusaki K, Hayashi K. Analysis of trabecular microarchitecture of human iliac bone using microcomputed tomography in patients with hip arthrosis with or without vertebral fracture. Bone 1998; 23: 163-9.
• 13 Jerome CP, Kimmel DB, McAlister JA, Weaver DS. Effects of ovariectomy on iliac trabecular bone in baboons. Calcif Tissue Int 1986; 39: 206-8.
• 14 Kragstrup J, Gundersen HJG, Mosekilde L, Melsen F. Estimation of the three dimensional wall thickness of completed remodeling sites in iliac trabecular bone. Metab Bone Dis Relat Res 1982; 04: 113-7.
• 15 Lauritzen JB, Schwarz P, Lund B, McNair P, Transbol I. Changing incidence and residual lifetime of common osteoporosis-related fractures. Osteoporosis Int 1993; 03: 127-32.
• 16 Lespessailles E, Roux JP, Benhamou CL, Arlot ME, Eynard E, Harba R, Padonou C, Meunier PJ. Fractal analysis of bone texture on os calcis radiographs compared with trabecular microarchitecture analyzed by histomorphometry. Calcif Tissue Int 1998; 63: 121-5.
• 17 Lespessailles E, Siroux V, Poupon S, Andriambelosoa N, Pothuaud L, Harba R, Benhamou CL. Long-term corticosteroid therapy induces mild changes in trabecular bone texture. J Bone Miner Res 2000; 15: 747-53.
• 18 Lill CA, Fluegel AK, Schneider E. Effect of ovariectomy, malnutrition, and glucocorticoid application on bone properties in sheep. A pilot study. Osteoporosis Int 2002; 13: 480-6.
• 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: 559-66.
• 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. Osteoporosis Int 2002; 13: 407-14.
• 21 Muller R, Van Campenhout H, Van Damme B, Van der Perre G, Dequeker J, Hildebrand T, Rüegsegger P. Morphometric analysis of human bone biopsies: a quantitative structural comparison of histological sections and microcomputed tomography. Bone 1998; 23: 59-66.
• 22 Newman E, Turner AS, Wark JD. The potential of sheep for the study of osteopenia: Current status and comparison with other animal models. Bone 1995; 16: 277-84.
• 23 Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR. Bone histomorphometry: Standardization of nomenclature, symbols, and units. J Bone Miner Res 1987; 02: 595-610.
• 24 Pastoureau P, Arlot ME, Caulin F, Barier JP, Meunier PJ, Delmas PD. Effects of oophorectomy on biochemical and histological indices of bone turnover in ewes. J Bone Miner Res 1989; 04 (Suppl. 01) 58.
• 25 Raisz LG. Physiology and pathophysiology of bone remodelling. Clin Chem 1999; 45: 1353-8.
• 26 Selby PL, Halsey JP, Adams KRH, Klimiuk P, Knight SM, Pal B, Stewart IM, Swinson DR. Corticosteroids do not alter the threshold for vertebral fracture. J Bone Miner Res 2000; 15: 952-6.
• 27 Turner AS, Villanueva AR. Static and dynamic histomorphometric data in 9-to 11-year-old ewes. Vet Comp Orthop Traumatol 1994; 07: 101-9.
• 28 Wronski TJ, Schenk PA, Cintron M, Walsh CC. Effect of bodyweight on osteopenia in ovariectomized rats. Calcif Tissue Int 1987; 40: 155-9.