Anomalous bone changes in ovariectomized type 2 diabetic rats: inappropriately low bone turnover with bone loss in an estrogen-deficient condition

Author:

Aeimlapa Ratchaneevan12,Wongdee Kannikar13,Tiyasatkulkovit Wacharaporn14,Kengkoom Kanchana5,Krishnamra Nateetip12,Charoenphandhu Narattaphol1267

Affiliation:

1. Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok, Thailand

2. Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand

3. Faculty of Allied Health Sciences, Burapha University, Chonburi, Thailand

4. Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand

5. National Laboratory Animal Center, Mahidol University, Nakhon Pathom, Thailand

6. Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand

7. The Academy of Science, The Royal Society of Thailand, Bangkok, Thailand

Abstract

Estrogen deprivation accelerates bone resorption, leading to imbalance of bone remodeling and osteoporosis in postmenopausal women. In the elderly, type 2 diabetes mellitus (T2DM) frequently coexists as an independent factor of bone loss. However, little is known about the skeletal changes in a combined condition of estrogen deficiency and T2DM. Herein, we performed ovariectomy (OVX) in nonobese Goto-Kakizaki (GK) T2DM rats to examine changes associated with calcium and phosphate metabolism and bone microstructures and strength. As expected, wild-type (WT) rats subjected to ovariectomy (OVX-WT) had low trabecular bone volume and serum calcium with increased dynamic histomorphometric and serum bone markers, consistent with the high turnover state. T2DM in GK rats also led to low trabecular volume and serum calcium. However, the dynamic histomorphometric markers of bone remodeling were unaffected in these GK rats, indicating the distinct mechanism of T2DM-induced bone loss. Interestingly, OVX-GK rats were found to have anomalous and unique changes in bone turnover-related parameters, i.e., decreased osteoblast and osteoclast surfaces with lower COOH-terminal telopeptide of type I collagen levels compared with OVX-WT rats. Furthermore, the levels of calciotropic hormones, i.e., parathyroid hormone and 1,25(OH)2D3, were significantly decreased in OVX-GK rats. Although the OVX-induced bone loss did not further worsen in GK rats, a three-point bending test indicated that OVX-GK bones exhibited a decrease in bone elasticity. In conclusion, T2DM and estrogen deficiency both led to microstructural bone loss, the appearance of which did not differ from each factor alone. Nevertheless, the combination worsened the integrity and suppressed the turnover, which might eventually result in adynamic bone disease.

Funder

Cluster and Program Management Office, National Science and Technology Development Agency

The Thailand Research Fund through the TRF International Network Program

The Thailand Research Fund through the TRF International Research Network

TRF Senior Research Scholar

Mahidol University

the Faculty of Science, Mahidol University

Science Achievement Scholarship of Thailand

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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