Combination of selective androgen and estrogen receptor modulators in orchiectomized rats

Roch, Paul Jonathan; Wolgast, V; Gebhardt, M-M; Böker, Kai Oliver; Hoffmann, Daniel Max; Saul, Dominik; Schilling, Arndt F.; Sehmisch, Stephan; Komrakova, Marina

doi:10.1007/s40618-022-01794-7

Cited by 6 publications

(13 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Orx reduced Ca and P levels. The Mg level in serum did not differ between groups (P > 0.05), with an average of 0.7 ± 0.1 mmol/L [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

“… 1 Differs from all other groups, a differs from Non-Orx, b differs from Orx, c differs from Orx + EN, d differs from Orx + RAL ( p < 0.05, Dunn’s test: spleen, kidney, and P; Tukey test: all other data) 2 data were published in Roch et al[ 19 ] …”

Section: Methodsmentioning

confidence: 99%

“…Raloxifene (RAL) is a SERM that is an approved treatment for postmenopausal osteoporosis, which has been reported to affect bone turnover markers in elderly men and prevent bone loss in men with prostate cancer without feminizing effects [ 16 , 17 ]. In our previous studies, we demonstrated the beneficial effects of RAL or EN applied as single treatments on bone and muscle tissue in an orchiectomized rat model [ 15 , 18 , 19 ]. Therefore, we hypothesized that the combination of EN and RAL would exert a favorable effect on bone tissue in male rats.…”

Section: Introductionmentioning

confidence: 99%

“…Furuya et al [ 20 ] reported positive additive effects of the application of a non-steroidal SARM (S-101479) combined with RAL on the bones of an ovariectomized rat model of postmenopausal osteoporosis. Our latest study showed improvement in muscle tissue under combined treatment of EN and RAL in male rats [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…The treatments were applied immediately after orchiectomy as an osteoporosis prophylaxis. Data on body weight, food intake and preliminary data of in-vivo computed tomography of the lumbar spine, as a part of this study, have been reported recently [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats

Komrakova¹,

Büchler²,

Böker³

et al. 2022

J Endocrinol Invest

Self Cite

View full text Add to dashboard Cite

Purpose Enobosarm (EN), a selective androgen receptor modulator and raloxifene (RAL), a selective estrogen receptor modulator, have been shown to improve bone tissue in osteoporotic males. The present study evaluated the effects of a combination therapy of EN and RAL on bone properties in orchiectomized rats compared to the respective single treatments. Methods Eight-month-old male Sprague–Dawley rats were either left intact (Non-Orx) or orchiectomized (Orx). The Orx rats were divided into four groups (n = 15 each): 1) Orx, 2) EN treatment (Orx + EN), 3) RAL treatment (Orx + RAL), 4) combined treatment (Orx + EN + RAL). EN and RAL (0.4 mg and 7 mg/kg body weight/day) were applied immediately after Orx with a soy-free pelleted diet for up to 18 weeks. The lumbar spine and femora were examined by micro-CT, biomechanical, histomorphological, ashing, and gene expression analyses. Results EN exhibited an anabolic effect on bone, improving some of its parameters in Orx rats, but did not affect biomechanical properties. RAL exhibited antiresorptive activity, maintaining the biomechanical and trabecular parameters of Orx rats at the levels of Non-Orx rats. EN + RAL exerted a stronger effect than the single treatments, improving most of the bone parameters. Liver weight increased after all treatments; the kidney, prostate, and levator ani muscle weights increased after EN and EN + RAL treatments. BW was reduced due to a decreased food intake in the Orx + RAL group and due a reduced visceral fat weight in the Orx + EN + RAL group. Conclusion The EN + RAL treatment appeared to be promising in preventing male osteoporosis, but given the observed side effects on liver, kidney, and prostate weights, it requires further investigation.

show abstract

“…The Orx reduced Ca and P levels. The Mg level in serum did not differ between groups (P > 0.05), with an average of 0.7 ± 0.1 mmol/L [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats

Komrakova¹,

Büchler²,

Böker³

et al. 2022

J Endocrinol Invest

Self Cite

View full text Add to dashboard Cite

show abstract

Treatment of osteoporosis using a selective androgen receptor modulator ostarine in an orchiectomized rat model

Böker¹,

Komrakova²,

Fahrendorff³

et al. 2023

Endocrine

Self Cite

View full text Add to dashboard Cite

Purpose The selective androgen receptor modulator ostarine has been shown to have advantageous effects on skeletal tissue properties, reducing muscle wasting and improving physical function in males. However, data on effects in male osteoporosis remain limited. In this study, the effects of ostarine on osteoporotic bone were evaluated in a rat model of male osteoporosis and compared with those of testosterone treatments. Methods Eight-month-old male Sprague-Dawley rats were either non-orchiectomized to serve as a healthy control (Non-Orx, Group 1) or orchiectomized (Orx, Groups 2–6) and then grouped (n = 15/group): (1) Non-Orx, (2) Orx, (3) Ostarine Therapy, (4) Testosterone Therapy, (5) Ostarine Prophylaxis and (6) Testosterone Prophylaxis. Prophylaxis treatments started directly after orchiectomy and continued for 18 weeks, whereas Therapy treatments were initiated 12 weeks after Orx. Ostarine and Testosterone were applied orally at daily doses of 0.4 and 50 mg/kg body weight, respectively. The lumbar vertebral bodies and femora were analyzed using biomechanical, micro-CT, ashing, and gene expression analyses. Results Ostarine Prophylaxis showed positive effects in preventing osteoporotic changes in cortical and trabecular bone (femoral trabecular density: 26.01 ± 9.1% vs. 20.75 ± 1.2% in Orx and in L4: 16.3 ± 7.3% vs 11.8 ± 2.9% in Orx); biomechanical parameters were not affected; prostate weight was increased (0.62 ± 0.13 g vs 0.18 ± 0.07 g in Orx). Ostarine Therapy increased solely the cortical density of the femur (1.25 ± 0.03 g/cm3 vs. 1.18 ± 0.04 g/cm3 in Orx); other bone parameters remained unaffected. Testosteron Prophylaxis positively influenced cortical density in femur (1.24 ± 0.05 g/cm3 vs. 1.18 ± 0.04 g/cm3 in Orx); Test. Therapy did not change any bony parameters. Conclusion Ostarine Prophylaxis could be further investigated as a preventative treatment for male osteoporosis, but an androgenic effect on the prostate should be taken into consideration, and combination therapies with other anti-osteoporosis agents could be considered.

show abstract

Advantage of ostarine over raloxifene and their combined treatments for muscle of estrogen-deficient rats

Roch,

Noisser,

Böker

et al. 2023

J Endocrinol Invest

View full text Add to dashboard Cite

Purpose Selective androgen (ostarine, OST) and estrogen (raloxifene, RAL) receptor modulators with improved tissue selectivity have been developed as alternatives to hormone replacement therapy. We investigated the combined effects of OST and RAL on muscle tissue in an estrogen-deficient rat model of postmenopausal conditions. Methods Three-month-old Sprague Dawley rats were divided into groups: (1) untreated non-ovariectomized rats (Non-OVX), (2) untreated ovariectomized rats (OVX), (3) OVX rats treated with OST, (4) OVX rats treated with RAL, (5) OVX rats treated with OST and RAL. Both compounds were administered in the diet. The average dose received was 0.6 ± 0.1 mg for OST and 11.1 ± 1.2 mg for RAL per kg body weight/day. After thirteen weeks, rat activity, muscle weight, structure, gene expression, and serum markers were analyzed. Results OST increased muscle weight, capillary ratio, insulin-like growth factor 1 (Igf-1) expression, serum phosphorus, uterine weight. RAL decreased muscle weight, capillary ratio, food intake, serum calcium and increased Igf-1 and Myostatin expression, serum follicle stimulating hormone (FSH). OST + RAL increased muscle nucleus ratio, uterine weight, serum phosphorus, FSH and luteinizing hormone and decreased body and muscle weight, serum calcium. Neither treatment changed muscle fiber size. OVX increased body and muscle weight, decreased uterine weight, serum calcium and magnesium. Conclusion OST had beneficial effects on muscle in OVX rats. Side effects of OST on the uterus and serum electrolytes should be considered before using it for therapeutic purposes. RAL and RAL + OST had less effect on muscle and showed endocrinological side effects on pituitary–gonadal axis.

show abstract

Combination of selective androgen and estrogen receptor modulators in orchiectomized rats

Cited by 6 publications

References 66 publications

A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats

A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats

Treatment of osteoporosis using a selective androgen receptor modulator ostarine in an orchiectomized rat model

Advantage of ostarine over raloxifene and their combined treatments for muscle of estrogen-deficient rats

Contact Info

Product

Resources

About