Clin Orthop Surg.  2012 Sep;4(3):234-241. 10.4055/cios.2012.4.3.234.

Effect of Combined Sex Hormone Replacement on Bone/Cartilage Turnover in a Murine Model of Osteoarthritis

• Yang JH
• Kim JH
• Lim DS
• Oh KJ

• KMID: 1392987
• DOI: http://doi.org/10.4055/cios.2012.4.3.234

Abstract

BACKGROUND
Estrogens act on estrogen receptors distributed in articular cartilages, synovial membrane, and ligaments, which are thought to be related with degenerative changes. Meanwhile, progesterone is known to have a weak anabolic action on bone formation This study evaluates the effects of estrogen and progesterone hormone on bone/cartilage turnover in ovariectomized (OVX) rats.
METHODS
Thirty-five 7-month-old female Sprague-Dawley rats were randomly divided into 5 groups and then ovariectomized bilaterally except the sham control group. The first and the second group acting as controls did not receive hormonal therapy, the third group received estrogen, the fourth group received progesterone, and the fifth group received combination of both hormones 10 weeks after surgery. Evaluations were done using the serum levels of cartilage oligomeric matrix protein (COMP) for cartilage turnover, collagen type I C-telopeptide (CTX-1) and osteocalcin (OC) for bone turnover at 11, 15, 19 weeks after OVX and histology using the Osteoarthritis Research Society International (OARSI) osteoarthritis (OA) cartilage histopathology assessment system.
RESULTS
Significantly less cartilage degradation (decreased levels of COMP) was found in the combined hormone treated group in comparison with OVX group. Similarly, both hormonal treatment resulted in increased bone formation and decreased bone resorption i.e., a low overall bone turnover status (decrease in the serum OC and CTX-1 levels).
CONCLUSIONS
Combined estrogen and progesterone therapy was found to be convincing in terms of reducing the severity of OA in this experimental model.

Keyword

Estrogen; Progesterone; Cartilage oligomeric matrix protein; Collagen type I C-telopeptide; Osteocalcin

MeSH Terms

Animals
Biological Markers/blood/metabolism
Bone Remodeling/*drug effects
Bone and Bones/chemistry/drug effects
Cartilage/chemistry/*drug effects
Collagen Type I/blood/metabolism
Disease Models, Animal
Estrogens/*pharmacology
Extracellular Matrix Proteins/blood/metabolism
Female
Glycoproteins/blood/metabolism
Histocytochemistry
Hormone Replacement Therapy/*methods
Osteoarthritis/blood/*drug therapy
Osteocalcin/blood/metabolism
Ovariectomy
Progesterone/*pharmacology
Rats
Rats, Sprague-Dawley

Figure

• 

  Fig. 1 Changes in serum levels in biochemical markers of bone and cartilage turnover in the cohort study. Cartilage turnover was assessed using cartilage low polymer substrate (COMP) (A) as a marker. The serum levels of collagen type I C-telopeptide (CTX-1) (B) and osteocalcin (OC) (C) were measured for bone turnover. Assessments were made 11, 15, and 19 weeks after OVX (equivalent to 1, 5, and 9 weeks after the hormone administration). Data show the average serum levels. F-sham: control group treated the same, OVX: ovariectomy, OVX-EL: estrogen group, OVX-P: progesterone group, OVX-E-P: estrogen and progesterone combination group.

• 

  Fig. 2 Findings on tissue examination. (A) The OVX group showed severe OA to a level of statistically significance (Safranin O stain, ×400). (B) Osteoarthritis Research Society International (OARSI) cartilage OA histopathology grading assessment graph of each group. OVX: ovariectomy, OA: osteoarthritis, F-sham: control group treated the same, OVX-E: estrogen group, OVX-P: progesterone group, OVX-E-P: estrogen and progesterone combination group.

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