Yonsei Med J.  2009 Jun;50(3):358-367. 10.3349/ymj.2009.50.3.358.

Influence of Ovariectomy on Bone Turnover and Trabecular Bone Mass in Mature Cynomolgus Monkeys

• Iwamoto J
• Seki A
• Matsuura M
• Sato Y
• Takeda T
• Matsumoto
• Yeh JK

• KMID: 1758563
• DOI: http://doi.org/10.3349/ymj.2009.50.3.358

Abstract

PURPOSE: To examine the influence of ovariectomy (OVX) on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites in mature cynomolgus monkeys.
MATERIALS AND METHODS
Six female cynomolgus monkeys, aged 17-21 years, were randomized into 2 groups by the stratified weight: the OVX and sham-operation groups (n = 3 in each group). The experimental period was 16 months. Lumbar bone mineral density (BMD) in vivo and serum and urinary bone turnover markers were longitudinally measured, and peripheral quantitative computed tomographic and bone histomorphometric analyses were performed on trabecular bone of the lumbar vertebra, femoral neck, and distal radius at the end of the experiment.
RESULTS
OVX induced in a reduction in lumbar BMD compared with the sham controls and the baseline, as a result of increased serum levels of bone-specific alkaline phosphatase and urinary levels of cross-lined N- and C-terminal telopeptides of type I collagen. Furthermore, OVX induced reductions in trabecular volumetric BMD and trabecular bone mass compared with the sham controls, with increased bone formation rate at the lumbar vertebra, femoral neck, and distal radius.
CONCLUSION
The results indicated that OVX in mature cynomolgus monkeys (17-21 years of age) increased bone turnover and induced trabecular bone loss at the three skeletal sites compared with the sham controls. Thus, mature cynomolgus monkeys could be utilized for preclinical studies to examine the effects of interventions on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites.

Keyword

Ovariectomy; monkey; bone turnover; trabecular bone; femoral neck; lumbar spine; radius

MeSH Terms

Alkaline Phosphatase/blood
Animals
*Bone Density
Collagen Type I/urine
Female
Femur Neck/metabolism
Lumbar Vertebrae/metabolism
Macaca fascicularis/*physiology
Ovariectomy/*adverse effects
Radius/metabolism
Random Allocation

Figure

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  Fig. 1 Changes in body weight. Data are expressed as means ± standard error. Body weight significantly increased in the Sham group, but did not in the OVX group {one-way analysis of variance (ANOVA) with repeated measurements, Table 2}. There was no significant difference in changes in body weight between the 2 groups (two-way ANOVA with repeated measurements, Table 2). OVX, ovariectomy.

• 

  Fig. 2 Changes in lumbar BMD and BMC. Data are expressed as means ± standard error. Lumbar BMD significantly decreased in the OVX group, but did not change in the Sham group {one-way analysis of variance (ANOVA) with repeated measurements, Table 2}. Lumbar BMC significantly increased in the Sham group, but did not significantly change in the OVX group (one-way ANOVA with repeated measurements, Table 2). There was a significant difference in changes in lumbar BMD and BMC between the 2 groups (two-way ANOVA with repeated measurements, Table 2). OVX: ovariectomy, BMD, bone mineral density; BMC, bone mineral content.

• 

  Fig. 3 Changes in serum and urinary levels of bone turnover markers. Data are expressed as means ± standard error. Serum and urinary NTX levels significantly increased and urinary CTX levels did not in both groups {one-way analysis of variance (ANOVA) with repeated measurements, Table 2}. Bone-specific ALP levels significantly increased in the OVX group, but significantly decreased in the Sham group (one-way ANOVA with repeated measurements, Table 2). There were significant differences in changes of urinary NTX and CTX levels and serum bone-specific ALP levels, but not in those in serum NTX levels, between the 2 groups (two-way ANOVA with repeated measurements, Table 2). OVX, ovariectomy; NTX, cross-linked N-terminal telopeptides of type I collagen; CTX, cross-linked C-terminal telopeptides of type I collagen; Cr, creatinine; ALP, alkaline phosphatase.

• 

  Fig. 4 Changes in serum levels of calcium, phosphorus, ALP, and iPTH. Data are expressed as means ± standard error. Serum calcium and phosphorus levels did not significantly change in the both groups {one-way analysis of variance (ANOVA) with repeated measurements, Table 2}. Serum ALP and iPTH levels significantly increased in the OVX group, but did not change in the Sham group (one-way ANOVA with repeated measurements, Table 2). There were no significant differences in changes in serum calcium, phosphorus, ALP and iPTH levels between the 2 groups (two-way ANOVA with repeated measurements, Table 2). OVX, ovariectomy; ALP, alkaline phosphatase; iPTH, intact parathyroid hormone.

• 

  Fig. 5 Changes in urinary levels of calcium and phosphorus. Data are expressed as means ± standard error. Urinary calcium/Cr and phosphorus/Cr did not significantly change in the both groups {one-way analysis of variance (ANOVA) with repeated measurements, Table 2}. There were no significant differences in changes in urinary calcium/Cr and phosphorus/Cr between the 2 groups (two-way ANOVA with repeated measurements, Table 2). OVX, ovariectomy; Cr, creatinine.

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