Combination Treatment With a Selective Androgen Receptor Modulator q(SARM) and a Bisphosphonate Has Additive Effects in Osteopenic Female Rats

  title={Combination Treatment With a Selective Androgen Receptor Modulator q(SARM) and a Bisphosphonate Has Additive Effects in Osteopenic Female Rats},
  author={Eric G. Vajda and Aimee Hogue and Kimberly Griffiths and William Y. Chang and Kelven Burnett and Yanling Chen and Keith B. Marschke and Dale E. Mais and Bijan Pedram and Yixing Shen and Arjan van Oeveren and Lin Zhi and Francisco J. L{\'o}pez and Martin D. Meglasson},
  journal={Journal of Bone and Mineral Research},
Recent clinical trials with bisphosphonates and PTH have not supported the hypothesis that combination treatments with antiresorptive and anabolic agents would lead to synergistic activity. We hypothesized that combination treatment with a selective androgen receptor modulator (SARM), LGD‐3303, and a bisphosphonate would be beneficial. In vitro competitive binding and transcriptional activity assays were used to characterize LGD‐3303. LGD‐3303 is a potent nonsteroidal androgen that shows little… 

The novel non-steroidal selective androgen receptor modulator S-101479 has additive effects with bisphosphonate, selective estrogen receptor modulator, and parathyroid hormone on the bones of osteoporotic female rats.

Evaluated SARM S-101479 from tetrahydroquinoline libraries in ovariectomized (OVX) rats indicated additive effects with commercial anti-osteoporosis drugs and showed periosteal bone formation of the cortical area, like natural androgen.

Local delivery of a selective androgen receptor modulator failed as an anabolic agent in a rat bone marrow ablation model

This study suggests that intramedullary/endosteal osteogenesis had a negative, dose-dependent response to locally released SARM, and suggests that there are biological limits to the targeted local application of SARMs.

Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit.

This Award Address attempts to chronicle the landmark discoveries, organize the SARM landscape into clinically relevant bins, and provide insight into the clinical prospects for SARMs.

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

While the authors did not observe changes in biomechanics, it is conceivable that longer treatment with ostarine may also improve biomechanical properties, and further studies are needed to characterize longer time effects and side effects of o starine in osteoporosis.

Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials

There is an unmet clinical need for safe and effective anabolic compounds such as SARMs and there is a need to determine the effect of resistance exercise training and protein intake associated with SARMs in the treatment of patients with muscle wasting.

Deciphering the selective androgen receptor modulators paradigm

The aim of the present paper is to summarize the current standing of research and development of SARMs and plausible molecular mechanisms underlying the potential for selective modulation of androgen receptor (AR) by different ligands and provides an update on SARM discovery paradigms for preclinical evaluations.

Selective Androgen Receptor Modulators (SARMs) in Sports: A Review

Selective androgen receptor modulators (SARMs) are an exciting group of molecules with pronounced anabolic effects and very weak to missing androgenic ones and they tend to be a big promise for improving the treatment process in different socially significant diseases.

A selective androgen receptor modulator enhances male-directed sexual preference, proceptive behavior, and lordosis behavior in sexually experienced, but not sexually naive, female rats.

The concept that LGD-3303 can stimulate aspects of female sexual behavior and may serve as a potential therapeutic for women with sexual desire disorders is supported.

Ostarine and Ligandrol Improve Muscle Tissue in an Ovariectomized Rat Model

Beneficial effect on muscle vascularization was observed for both SARMs with a stronger impact for OS and LG, and a higher muscle weight and intramuscular fat content observed after LG treatment could be considered as an unfavorable side effects and might be a limitation for their application at these dosages.



Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis.

Collectively, this novel compound served as a prototype for SARMs, which had unique tissue selectivity with high potency for bone formation and lower impact upon sex accessory tissues.

An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate.

An androgen receptor (AR) ligand that maintains expected anabolic activities with substantially diminished activity in the prostate and demonstrates the important role of the AR and androgens in mediating a number of beneficial effects in bone, muscle, and sexual function independent from the conversion of androgens into estrogenic ligands.

Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats.

The potent oral activity and tissue selectivity exhibited by BMS-564929 are expected to yield a clinical profile that provides the demonstrated beneficial effects of T in muscle and other tissues with a more favorable safety window.

Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia.

Although S-1 and finasteride showed very similar suppressive effects in the prostate of intact male rats, they decreased prostate size via different mechanisms of action, indicating that SARMs may demonstrate clinical utility as single agent or combination therapy for BPH.

Selective Androgen Receptor Modulator (SARM) Treatment Prevents Bone Loss and Reduces Body Fat in Ovariectomized Rats

The data suggest that S-4 could reduce the incidence of fracture via two different mechanisms (i.e., via direct effects in bone and reducing the occurrence of falls through increased muscle strength).

The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs

  • K. KavanaghK. Guo U. Oppermann
  • Chemistry, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2006
High-resolution x-ray structures of the human enzyme in complexes with risedronate and zoledronate, two of the leading N-BPs in clinical use, reveal the molecular binding characteristics of an important pharmacological target and provide a route for further optimization of these important drugs.

A two-year, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles.

As compared to estrogen alone, E + A significantly improved BMD and was well tolerated in surgically menopausal women.

The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis.

Changes in the volumetric density of trabecular bone, the cortical volume at the hip, and levels of markers of bone turnover suggest that the concurrent use of alendronate may reduce the anabolic effects of parathyroid hormone.

Preclinical safety profile of alendronate.

  • C. PeterG. Rodan
  • Biology, Medicine
    International journal of clinical practice. Supplement
  • 1999
The evidence presented in these studies supports the conclusion that alendronate administered to humans at therapeutic doses is a safe drug for the treatment of postmenopausal osteoporosis.