Ovariectomy does not induce osteopenia through interleukin-6 in rhesus monkeys (Macaca mulatta)

Area of Science:

• Endocrinology
• Bone Biology
• Immunology

Background:

• Estrogen deficiency is a major cause of bone loss, particularly in postmenopausal women.
• Interleukin-6 (IL-6) is a cytokine implicated in bone metabolism and inflammation.
• The precise role of IL-6 in estrogen-depletion bone loss remains incompletely understood.

Purpose of the Study:

• To investigate the role of IL-6 in estrogen (E2)-depletion-induced bone loss using a nonhuman primate model.
• To determine if IL-6 levels or signaling are altered during estrogen deficiency and if these changes correlate with bone loss.

Main Methods:

• Adult female rhesus monkeys underwent sham-operation, ovariectomy (ovx), or ovx with E2 replacement.
• Bone mineral density (BMD) of the lumbar spine and radius was measured over 9 months.
• Serum and bone marrow levels of IL-6 and its soluble receptor were analyzed.
• Peripheral blood mononuclear cells and bone marrow cells were cultured to assess IL-6 production.

Main Results:

• Ovariectomy led to significant decreases in lumbar spine and radius BMD, which were prevented by E2 replacement.
• Serum osteocalcin and skeletal-specific alkaline phosphatase were elevated in the ovx group, indicating increased bone turnover.
• No significant differences in serum or bone marrow IL-6 levels were observed between ovx and ovx + E2 groups.
• Bone marrow plasma soluble IL-6 receptor levels were transiently increased in the ovx group at 3 months post-ovx.

Conclusions:

• Estrogen deprivation in rhesus monkeys leads to bone loss and altered bone remodeling markers.
• Despite the presence of bone loss, IL-6 levels and signaling do not appear to be significantly modulated by estrogen deficiency.
• These data suggest that IL-6 modulation is not the primary mechanism driving estrogen-depletion bone loss in this primate model.