Ovariectomized cynomolgus monkeys have previously been investigated as a nonhuman primate model of postmenopausal osteoporosis (Jerome et al., Bone Miner 9:527-540; 1994). In the present study, Fourier transform infrared microspectroscopy (FTIRM) was used to verify that differences in bone mineral quality and quantity in the vertebrae of mature intact (INT) and ovariectomized (ovx) monkeys were analogous to those seen in osteoporotic and nondiseased human bones. FTIRM spectra were acquired from 15 trabeculae per vertebra from three ovx and three INT adult monkeys (mean age 8 years). These spectra were compared with those of both trabecular and previously reported osteonal bone obtained from 3 'normal' and 11 postmenopausal osteoporotic human subjects. While variations in the mineral:matrix ratio (mineral content), carbonate:phosphate ratio, and crystallinity are typical for trabecular bone from iliac crests of normal human subjects, the values of these parameters were relatively static for trabecular bone from postmenopausal osteoporotic human subjects. In general, trabecular bone from postmenopausal osteoporotic human subjects exhibited decreased mineral content (1.0 ± 0.5 vs. 2.9 ± 0.6), increased crystallinity, and increased carbonate:phosphate relative to controls. Similarly, trabecular bone from ovariectomized monkeys exhibited lower mineral content (5.8 ± 0.2) compared with the INT group (6.2 ± 0.2; p ≤ 0.05) and contained larger/more perfect apatite crystals (increased crystallinity) with increased carbonate:phosphate ratios. Variations in absolute values were attributable to site differences (ilium vs. vertebrae). To appreciate the importance of mineral properties on mechanical properties, compression testing was performed using cores of monkey L-3 and L-4 vertebral bodies from a separate group of monkeys. Treating monkeys with the anabolic steroid nandrolone decanoate (ND) immediately after ovariectomy and for the next 24 months (ND group), or beginning 12 months after ovariectomy (dND group), increased the ultimate stress compared with an ovx treatment group, despite large interanimal variations in bone architecture and mechanical properties. These data support the hypothesis that ovariectomized adult monkeys are an excellent model for postmenopausal osteoporosis, and can be used for the evaluation of therapeutic modalities. Copyright (C) 2000 Elsevier Science Inc.
Bibliographical noteFunding Information:
This study was supported by grants from the NIH (AR01876 [C.R.], AG09827 [C.R.], AR0433125 [A.L.B., S.G., E.P.]), the Clark Foundation (C.L.R., F.M.), the Cornell Cooperative Education Program, the Max Kade Foundation (C.R.), and the Austrian National Bank Project (F.M.). The authors express their appreciation to Dr. S. B. Doty for his help in specimen preparation and Kevin Shea and John Afthnios for their help with mechanical testing and density measurements. Sergio Gadaleta performed all the analyses on monkey bones described herein, and wrote the first draft of the paper. Adele Boskey and Clare Rimnac designed the study, interpreted the data, edited the paper, and obtained the funds for the study. Eleftherios Paschalis performed the analysis of the human bones, and interpreted the data. Cathy Carlson provided the monkey bone specimens and reviewed and edited the manuscript. Franz Menshik and Todd Baldini were actively involved in the mechanical evaluation of the monkey spines, and assisted in data interpretation. Margaret Peterson was the statistician.
- Animal model
- Bone mineral crystallinity
- Compression testing
- Fourier transform infrared microspectroscopy (FTIRM)
- Nandrolone decanoate