title: Ovariectomy does not induce osteopenia through interleukin-6 in rhesus monkeys (Macaca mulatta).
abstract: To characterize the role of interleukin-6 (IL-6) in estrogen (E2)-depletion bone loss, we utilized a nonhuman primate model of human skeletal physiology. Adult female rhesus monkeys were sham-operated (S; n = 5), ovariectomized (ovx; n = 10), or ovx followed by E2 replacement (ovx + E2; n = 10) and evaluated for the indicated parameters at 0, 3, 6, and 9 months post-ovx. Lumbar spine bone mineral density (BMD) decreased by 3 months and continued to decline through 9 months in the ovx, but not in the ovx + E2 or S groups. Middle and distal radius BMD was decreased at 9 months in the ovx, but not in the ovx + E2 or S groups. The S group had marked fluctuations in bone remodeling parameters, and cytokine levels in S animals were consistent with menstrual cycling, and therefore only those values in the ovx and ovx + E2 groups are reported. Serum osteocalcin and skeletal-specific alkaline phosphatase were elevated in the ovx group compared with the ovx + E2 group. There was no difference in serum or bone marrow plasma IL-6 levels between the ovx and ovx + E2 groups. Similarly, there was no difference in basal or phorbol ester-stimulated IL-6 levels of peripheral blood mononuclear cell or bone marrow cell culture supernatants between groups. There was no difference in serum or bone marrow soluble IL-6 receptor between groups. However, the bone marrow plasma soluble IL-6 receptor levels were transiently increased from baseline at 3 months in the ovx but not in the ovx + E2 group. In summary, there was no bone loss in the ovx + E2 group, although the serum and bone marrow IL-6 levels were similar to those of the ovx group. These data suggest that modulation of IL-6 is not the key mechanism through which estrogen deprivation mediates bone loss in rhesus monkeys.
authors.affiliation: Department of Pathology, School of Medicine and Institute of Gerontology, University of Michigan, Ann Arbor, USA. etkeller@umich.edu
authors.forename: E T
authors.initials: ET
authors.lastname: Keller
authors.forename: N C
authors.initials: NC
authors.lastname: Binkley
authors.forename: B A
authors.initials: BA
authors.lastname: Stebler
authors.forename: D M
authors.initials: DM
authors.lastname: Hall
authors.forename: G M
authors.initials: GM
authors.lastname: Johnston
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: W B
authors.initials: WB
authors.lastname: Ershler
mesh_terms: D000818:Animals; D015415:Biomarkers; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000378:metabolism / Q000503:physiopathology*; D016723:Bone Remodeling; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008253:Macaca mulatta; D010052:Ovariectomy
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D015232:Dinoprostone