Influence of Aromatase Inhibition on the Bone-Protective Effects of Testosterone

Beck, Darren T.; Yarrow, Joshua F.; Beggs, Luke A.; Otzel, Dana M.; Ye, Fan; Conover, Christine F.; Miller, Jay James R.; Balaez, Alexander; Combs, Sarah M; Leeper, Alicia M.; Williams, Alyssa; Lachacz, Stephanie A; Zheng, Naiquan; Wronski, Thomas J.; Borst, Stephen E.

doi:10.1002/jbmr.2265

Cited by 27 publications

(24 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differences in LABC mass have been previously reported (Beck et al., ). Briefly, LABC mass was 45% lower in ORX compared with SHAM animals ( p < .001).…”

Section: Resultssupporting

confidence: 51%

“…a). There were no differences in LABC mass observed between TEST‐ and TREN‐treated groups ( p = .63; Beck et al., ).…”

Section: Resultsmentioning

confidence: 94%

“…For this study, we examined a subset of the LABC muscles from our previously published companion article (Beck et al., ). Briefly, rats ( n = 10–11/group) were stratified by initial weight and divided into the following groups: (i) Sham‐operated (SHAM), (ii) ORX, (iii) ORX + testosterone enanthate (ORX + TEST) and (iv) ORX + trenbolone enanthate (ORX + TREN).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle

Dalbo¹,

Roberts

Mobley

et al. 2016

Andrologia

View full text Add to dashboard Cite

The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats (n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week ) or ORX + trenbolone (TREN; 1.0 mg week ). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX (p < .001). ORX + TEST and ORX + TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively (p < .01), with no differences between conditions for myonuclear number per muscle fibre (p = .948). Mstn protein was increased 159% and 169% in the ORX + TEST and ORX + TREN compared to ORX (p < .01). pan-SMAD2/3 protein was ~30-50% greater in ORX compared to SHAM (p = .006), ORX + TEST (p = .037) and ORX + TREN (p = .043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM (p < .05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy.

show abstract

“…Differences in LABC mass have been previously reported (Beck et al., ). Briefly, LABC mass was 45% lower in ORX compared with SHAM animals ( p < .001).…”

Section: Resultssupporting

confidence: 51%

“…a). There were no differences in LABC mass observed between TEST‐ and TREN‐treated groups ( p = .63; Beck et al., ).…”

Section: Resultsmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle

Dalbo¹,

Roberts

Mobley

et al. 2016

Andrologia

View full text Add to dashboard Cite

show abstract

“…Testosterone (T) deficiency (ie, hypogonadism) may also exacerbate SCI-induced bone loss (18) because androgens modulate osteoblast differentiation (19) and influence cancellous bone maintenance in males. (20) After SCI, 40% to 80% of men exhibit hypogonadism, with a higher incidence and more severe T deficiency occurring closer to time of injury. (21) Supporting these findings in humans, we have recently developed a young (14-week-old, nonskeletally mature) male contusion rodent SCI model that exhibits T deficiency and severe cancellous bone loss 21 days after injury.…”

Section: Introductionmentioning

confidence: 99%

Sclerostin Inhibition Prevents Spinal Cord Injury-Induced Cancellous Bone Loss

Beggs

Ghosh

et al. 2014

Journal of Bone and Mineral Research

Self Cite

View full text Add to dashboard Cite

Spinal cord injury (SCI) results in rapid and extensive sublesional bone loss. Sclerostin, an osteocyte-derived glycoprotein that negatively regulates intraskeletal Wnt signaling, is elevated after SCI and may represent a mechanism underlying this excessive bone loss. However, it remains unknown whether pharmacologic sclerostin inhibition ameliorates bone loss subsequent to SCI. Our primary purposes were to determine whether a sclerostin antibody (Scl-Ab) prevents hindlimb cancellous bone loss in a rodent SCI model and to compare the effects of a Scl-Ab to that of testosterone-enanthate (TE), an agent that we have previously shown prevents SCI-induced bone loss. Fifty-five (n ¼ 11-19/group) skeletally mature male Sprague-Dawley rats were randomized to receive: (A) SHAM surgery (T8 laminectomy), (B) moderate-severe (250 kilodyne) SCI, (C) 250 kilodyne SCI þ TE (7.0 mg/wk, im), or (D) 250 kilodyne SCI þ Scl-Ab (25 mg/kg, twice weekly, sc) for 3 weeks. Twenty-one days post-injury, SCI animals exhibited reduced hindlimb cancellous bone volume at the proximal tibia (via mCT and histomorphometry) and distal femur (via mCT), characterized by reduced trabecular number and thickness. SCI also reduced trabecular connectivity and platelike trabecular structures, indicating diminished structural integrity of the remaining cancellous network, and produced deficits in cortical bone (femoral diaphysis) strength. Scl-Ab and TE both prevented SCI-induced cancellous bone loss, albeit via differing mechanisms. Specifically, Scl-Ab increased osteoblast surface and bone formation, indicating direct bone anabolic effects, whereas TE reduced osteoclast surface with minimal effect on bone formation, indicating antiresorptive effects. The deleterious microarchitectural alterations in the trabecular network were also prevented in SCI þ Scl-Ab and SCI þ TE animals, whereas only Scl-Ab completely prevented the reduction in cortical bone strength. Our findings provide the first evidence indicating that sclerostin inhibition represents a viable treatment to prevent SCI-induced cancellous and cortical bone deficits and provides preliminary rationale for future clinical trials focused on evaluating whether Scl-Ab prevents osteoporosis in the SCI population.

show abstract

“…The parietal region of the calvaria and right femur were scanned ex vivo with a Bruker Skyscan 1172 lCT (Kontich, Belgium) to determine the effects of rhRLX on lesion closure and bone morphometry remote from the injury site, respectively, using our protocols that abide by guidelines of the American Society of Bone and Mineral Research (Bouxsein et al 2010;Beck et al 2014;Beggs et al 2015). Briefly, calvaria from Protocols 1-4 were scanned at 50kVP/200 lA with a 0.5 mm aluminum filter, 2k camera resolution, 10 lm voxel 0.7°rotation step, and 180°tomographic rotation.…”

Section: High-resolution Three-dimensional (3d) Microcomputed Tomogramentioning

confidence: 99%

Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice

et al. 2019

View full text Add to dashboard Cite

Bone fractures are associated with considerable morbidity and increased mortality. A major limitation to healing is lack of bone blood flow, which is impaired by physical disruption of intraskeletal and/or periosteal vasculature by the fracture. Thus, pharmacological interventions are needed to improve osseous blood flow, thereby accelerating bone fracture closure. Relaxin is secreted by the ovary and circulates in rodents and humans during pregnancy. Because relaxin might benefit bone fracture healing by stimulating angiogenesis, vasculogenesis (and potentially osteogenesis) through mobilization and activation of bone marrow progenitor cells, and by increasing blood flow via vasodilation, we investigated whether relaxin administration would accelerate closure of a calvarial defect in mice. Whether administered systemically by osmotic pump or locally by collagen scaffolds for ~2 week period after lesioning, relaxin did not accelerate bone healing. Despite implementing relaxin doses that reached plasma concentrations spanning the physiological to supraphysiological range, testing the closure of two different sizes of calvarial lesions, allowing for different intervals of time from instigation of cranial lesion to euthanasia, and investigating mice of different ages, we did not observe a significant benefit of relaxin in bone lesion healing. Nor did we observe stimulation of blood vessel formation in the bone lesion by the hormone. An incidental finding was that relaxin appeared to enhance trabecular bone growth in an uninjured control bone (femur). Although the results of this study were not supportive of a therapeutic benefit for relaxin on calvarial defect closure, future investigation is needed employing different animal species and experimental models of bone fracture.

show abstract

Influence of Aromatase Inhibition on the Bone-Protective Effects of Testosterone

Cited by 27 publications

References 43 publications

Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle

Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle

Sclerostin Inhibition Prevents Spinal Cord Injury-Induced Cancellous Bone Loss

Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice

Contact Info

Product

Resources

About