Yonsei Med J.  2016 Nov;57(6):1386-1394. 10.3349/ymj.2016.57.6.1386.

Changes in Bone Metabolism in Young Castrated Male Rats

Affiliations
  • 1Department of Neurosurgery, The Spine and Spinal Cord Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. kuhsu@yuhs.ac

Abstract

PURPOSE
To determine the window of time during which osteoporosis affects the management of spinal surgery and the mechanism of bone metabolism changes in males with osteoporosis by examining changes in bone metabolism in young castrated male rats.
MATERIALS AND METHODS
A total of 30 Sprague-Dawley rats were randomly allocated into two study groups. Group 1 (control) received a sham surgery and Group 2 received bilateral orchiectomy to change bone mineral density (BMD). Serum osteocalcin, alkaline phosphatase (ALP), and collagen type 1 cross-linked C-telopeptide (CTX) were analyzed at postoperative date (POD) 8, 10, and 12 weeks. BMDs were measured using micro computed tomography scans.
RESULTS
Femoral and lumbar BMDs were decreased in the orchiectomy groups. BMDs in the sham and orchiectomy groups showed statistically differences at POD 8, 10, and 12 weeks for the femur (p=0.032, 0.008, 0.008) and lumbar spine (p=0.151, 0.008, 0.008, respectively). Serum osteocalcin, ALP, and CTX decreased gradually; however, N-terminal type 1 procollagen (P1NP) showed a slight increase yet no significant change.
CONCLUSION
In young castrated male rats, a significant decrease in BMD was observed after orchiectomy due to the mixture of two detrimental factors. Young castrated male rats did not reach peak BMD. Increased bone turnover causes bone resorption to exceed bone formation. This study may contribute to the creation of a valuable model for studies of male osteoporosis and the spinal surgery field.

Keyword

Osteoporosis; orchiectomy; bone mineral density; spine; femur

MeSH Terms

Alkaline Phosphatase/metabolism
Animals
Biomarkers/*blood
*Bone Density
Bone Remodeling
Bone Resorption
Collagen Type I/metabolism
Female
Femur/*metabolism
Humans
Lumbar Vertebrae/metabolism
Male
Orchiectomy/*adverse effects
Osteocalcin/metabolism
Osteogenesis
Osteoporosis/metabolism
Peptides
Random Allocation
Rats
Rats, Sprague-Dawley
*X-Ray Microtomography
Biomarkers
Collagen Type I
Peptides
Osteocalcin
Alkaline Phosphatase

Figure

  • Fig. 1 Time course and experimental groups. Thirty 10-week-old male rats were acclimated before the study. At POD 8, 10, and 12 weeks, five rats were euthanized, and their femurs and lumbar spines were removed for measurement of BMD. Cardiac puncture was performed in three rats to obtain serum at POD 0, 1, 4, 8, and 12 weeks serially (↑, time of serum bone marker measurements). *Statistically significant data. POD, postoperative date; Cp, cardiac puncture; OCX, orchiectomy; BMD, bone mineral density.

  • Fig. 2 BMD measurement using the NRecon software. BMD was measured in the femur and lumbar spine using micro computed tomography and NRecon software. BMD, bone mineral density.

  • Fig. 3 Changes in BMD of the femur. BMD is reported as g/cm3. Measured BMD was lowest at week 8 after OCX, with an increase to peak BMD at week 10 and a subsequent decrease at week 12. BMD, bone mineral density; OCX, orchiectomy; POD, postoperative date.

  • Fig. 4 Changes in BMD of the lumbar spine. BMD is reported as g/cm3. BMD of the OCX group decreased at POD 8, 10, and 12 weeks, and there was a statistically significant decrease at POD 10 and 12 weeks (*). BMD, bone mineral density; OCX, orchiectomy; POD, postoperative date.

  • Fig. 5 Micro CT axial images of the femur. A, B, and C shows sham group rats at POD 8 weeks, 10 weeks, and 12 weeks. D, E, and F shows OCX group rats at POD 8 weeks, 10 weeks, and 12 weeks. POD, postoperative date; OCX, orchiectomy.

  • Fig. 6 Micro CT axial images of the lumbar spine. A, B, and C shows sham group rats at POD 8 weeks, 10 weeks, and 12 weeks. D, E, and F shows OCX group rats at POD 8 weeks, 10 weeks, and 12 weeks. POD, postoperative date; OCX, orchiectomy.

  • Fig. 7 Comparison of serum bone markers at POD 12 weeks. The OCX group showed elevated levels of bone markers, and P1NP, osteocalcin, and CTX showed statistically significant differences (*). POD, postoperative date; OCX, orchiectomy; P1NP, N-terminal type 1 procollagen; CTX, C-telopeptide.

  • Fig. 8 Serial changes in serum bone markers. (A) Bone formation markers. (B) Bone resorption marker. P1NP, N-terminal type 1 procollagen; ALP, alkaline phosphatase; OCX, orchiectomy; CTX-1, C-telopeptide-1.


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