Effects of Combined Treatment With Selective Androgen and Estrogen Receptor Modulators Ostarine and Raloxifen on Bone...

Area of Science:

• Endocrinology
• Pharmacology
• Bone Biology

Background:

• Hormone replacement therapy often focuses on estrogen and progesterone, neglecting age-related androgen decline in women.
• Decreased estrogen and androgen levels contribute to bone loss, and traditional hormone therapy can cause adverse effects.
• Selective receptor modulators (SRMs) offer a potential alternative for hormone-related bone loss.

Purpose of the Study:

• To investigate the efficacy and safety of a combined treatment with a selective estrogen receptor modulator (raloxifene, RAL) and a selective androgen receptor modulator (ostarine, OST) in preventing bone loss.
• To evaluate the effects of RAL and OST, alone and in combination, on bone structure, biomechanics, and systemic parameters in an ovariectomized rat model.

Main Methods:

• Ovariectomized (OVX) Sprague-Dawley rats were treated orally with OST, RAL, or a combination of both for 13 weeks.
• Control groups included non-ovariectomized (NON-OVX) and untreated OVX rats.
• Lumbar vertebrae and femora were analyzed for structural and biomechanical properties. Serum and tissue parameters were also assessed.

Main Results:

• Combined OST+RAL treatment improved bone structural and biomechanical parameters, showing advantages over RAL alone.
• RAL demonstrated antiresorptive effects without negative systemic effects.
• OST alone was less effective for bone protection and increased osteoblast number, serum phosphorus, bone magnesium, and organ/uterus weight.
• The combination therapy raised safety concerns, including increased serum phosphorus and luteinizing hormone, decreased serum magnesium and calcium, and no attenuation of organ/uterus weight increase.

Conclusions:

• Combined selective estrogen and androgen receptor modulator therapy shows promise for bone health but requires careful safety evaluation.
• While RAL is effective and safe, OST alone has limited bone protective effects and potential adverse systemic impacts.
• Further research is needed to develop alternative compounds with improved safety profiles for osteoporosis treatment.