Loss of anti-Müllerian hormone signaling in mice affects trabecular bone mass in a sex- and age-dependent manner.

Ovariectomy-induced osteoporosis in mice results from an abrupt loss of ovarian sex steroids. Anti-Müllerian hormone knockout (AMHKO) mice show a gradual but accelerated ovarian aging, and therefore may better resemble osteoporosis following natural menopause. To study the impact of AMH signaling deficiency on bone, we compared trabecular and cortical bone parameters in 2-, 4-, 10- and 16-month-old male and female wild type (WT), AMHKO and AMH type II receptor knockout (MRKI) mice using microCT. Goldner's staining was performed to confirm the observed bone phenotype. Both male and female AMHKO and MRKI mice showed an age-dependent loss of trabecular bone (P < 0.001). However, reproductive-aged female AMHKO and MRKI mice had a higher BV/TV compared to WT (P < 0.001), coinciding with increased growing follicle numbers (P < 0.05), increased estrus inhibin B levels (AMHKO: P < 0.001; MRKI: P < 0.05), but normal inhibin A, estrogen and progesterone levels. In aged female AMHKO and MRKI mice BV/TV did not differ from WT mice due to greater trabecular bone loss between 10 and 16 months compared to WT mice. At these ages, AMHKO and MRKI mice had reduced growing follicle numbers (P < 0.05), and reduced Inhibin B levels (P < 0.001). At 10 months of age, female MRKI mice had increased cortical bone parameters compared to WT mice (P < 0.01). Bone parameters of male AMHKO and MRKI mice did not differ from male WT mice. In conclusion, AMH signaling deficiency results in a sex- and age-dependent effect on predominantly trabecular bone. Our results further suggest that reproductive hormones beyond estrogen may contribute to bone homeostasis.