Characterization of bone mineral composition in the proximal tibia of cynomolgus monkeys: Effect of ovariectomy and nandrolone decanoate treatment

R. Y. Huang, L. M. Miller, C. S. Carlson, M. R. Chance

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Abstract

Life postmenopausal women, ovariectomized cynomolgus monkeys (Macaca fascicularis) experience accelerated loss of bone mass. Treatment of ovariectomized monkeys with nandrolone decanoate results in an increase in bone mass to levels comparable to those of intact animals. The changes in bone composition that occur with these treatments, however, are less well characterized. In the present study, we used synchrotron Fourier-transform infrared microspectroscopy (FT-IRM) and curve-fitting methods to monitor specific changes at cortical, subchondral, and trabecular bone regions in the proximal tibia. Four groups were studied: (1) sham-operated (sham); (2) ovariectomized and treated with placebo for 2 years (ovx); (3) ovx + nandrolone decanoate for 2 years (NAN); and (4) ovx + nandrolone decanoate beginning 1 year after ovx (dNAN). The results demonstrate that ovariectomy and nandrolone treatment did not affect the degree of mineralization as defined by the phosphate/protein ratio, but acid phosphate content (HPO42-) in cortical and subchondral bone was increased by ovariectomy, suggesting this bone to be less mature due to increased remodeling that occurs after ovariectomy. In the subchondral and cortical bone regions, ovariectomized monkeys showed a lower total carbonate content (CO32-/matrix ratio) than sham controls, specifically due to the decrease in labile carbonate content. In the trabecular region, no change of carbonate content was observed. Treatment with nandrolone decanoate was found to restore the loss in carbonate, where the resulting mineral had a larger quantity of type B carbonate. Finally, we correlated carbonate content with dual-energy X-ray absorptiometry measurements, and found a positive correlation between bone mineral density and type A carbonate in bone, which is stoichiometrically related to the amount of calcium in bone. Therefore, the results presented herein identify significant differences in bone chemistry after ovariectomy and nandrolone treatment, which may help explain previous findings that, although nandrolone decanoate treatment increased bone mass, it could not reverse the decrease in bone strength due to ovariectomy (Aerssens et al., Calcif Tissue Int 53:269-277; 1993).

Original languageEnglish (US)
Pages (from-to)492-497
Number of pages6
JournalBone
Volume30
Issue number3
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
The authors thank Nebojsa Marinkovic, Michael Sullivan, Kevin Kovacs, and John Toomey for their technical assistance at Beamline U2B, and Hermina Borgerink and Miranda Oliver for their assistance in cutting the sections of undecalcified bone. This research was supported by the Biomedical Technology Program of the NCRR, P41-RR01633 (M.R.C); the American Federation for Aging Research, A98087 (L.M.M.); and the National Institutes of Health, RR-14099 (C.S.C). The NSLS was supported by the United States Department of Energy under contract DE-AC02-98CH10886.

Keywords

  • Bone mineral
  • Cynomolgus macaques
  • Infrared microspectroscopy
  • Nandrolone decanoate
  • Ovariectomy
  • Postmenopausal osteoporosis

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