Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis

Abstract

Selective androgen receptor modulators (SARMs) have shown beneficial effects on muscle wasting, general physical function and bone properties in male mammals. However, data on the effects of SARMs in postmenopausal osteoporotic bone are scarce. We evaluated the effects of the SARM drug ostarine on postmenopausal osteoporotic bone in a rat osteoporosis model. Ovariectomy was performed on 46 of 56 3-month-old female Sprague-Dawley rats. Eight weeks after ovariectomy, ostarine was orally administered daily for 5 weeks in dosages of 0.04 (low, OVX + Ost. 0.04), 0.4 (intermediate, OVX + Ost. 0.4), and 4 mg/kg (high, OVX + Ost. 4) body weight. Another ovariectomized group received no ostarine. Lumbar vertebrae and femora were removed for biomechanical, gene expression, ashing, and computer tomography analyses. Low dose showed no effects. The effects of intermediate and high doses were comparable overall. Improvements were mainly seen in structural properties such as bone mineral density and bone volume density. However, the effects in femora were superior to effects in vertebrae. Ostarine treatment for 5 weeks did not improve significantly biomechanical properties. mRNA expression of the receptor activator of NF-κB ligand decreased after treatment, and uterine weight increased. Serum levels of phosphorus increased following ostarine treatment in intermediate and high-dose groups. Short-term treatment of osteoporotic bone with ostarine leads to improvement of several microstructural bone indices. While we did not observe changes in biomechanics, it is conceivable that longer treatment may also improve biomechanical properties. Further studies are needed to characterize longer time effects and side effects of ostarine in osteoporosis.

Ostarine and Ligandrol Improve Muscle Tissue in an Ovariectomized Rat Model

“…The BW of the rats across all treatment groups was similar at the beginning of the study (244 ± 7.8 g) (32,33). Ovariectomy led to a significant enhancement of BW in all four OVX groups compared with the Non-OVX group from week 2 post ovariectomy.…”

“…Ovariectomy led to a significant enhancement of BW in all four OVX groups compared with the Non-OVX group from week 2 post ovariectomy. Treatment with OS did not have any influence on body weight (Table 1, Figure 2) (32,33).…”

“…Rats were randomly divided into five groups (Figure 1 , respectively). Data on BW, uterine weight, muscle weight, and OS dosages have been previously published (32,33).…”

“…Two independent experiments were conducted. The OS effect on bone tissue and animal model as a part of Experiment I has been recently published (32,33).…”

Bone‐protective effects of Lactobacillus plantarum B719‐fermented milk product

“…Phosphorus is an essential mineral that acts on bone formation. However, high serum levels of phosphorus are associated with vascular calcification and endothelial dysfunction (Hoffmann et al 2019). Furthermore, ALP is produced in liver, intestine, kidney and bone; however, approximately 50% of total ALP is produced from bone in healthy adults (Kuo and Chen 2017).…”