Effects of combined treatment with eldecalcitol and alendronate on bone mass, mechanical properties, and bone histomorphometry in ovariectomized rats: A comparison with alfacalcidol and alendronate

A possible role of 5α-androstane-3α,17β-diol (3α-androstanediol) in the control of FSH secretion was studied at various ages in ovariectomized rats. In the rat strain used, vaginal opening, coincident with first ovulation, generally occurs between 37 and 42 days of age. If 3α-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 μg/100 g body wt) between 13 and 30 days of age; at 33–35 days of age only the 300 μg dose caused some inhibition of FSH release. Results were more complex if 3α-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3α-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3α-androstanediol was combined with oestradiol a clear decrease in effect, as compared to the effect of oestradiol alone, was found between 20 and 30 days of age. Also the effect of combined oestradiol and progesterone treatment was greater than the effect of combined treatment with oestradiol, progesterone and 3α-androstanediol. At all ages after day 20 none of the steroid combinations tested was capable of maintaining FSH levels in ovariectomized rats similar to those in intact rats. It is concluded that 3α-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3α-androstanediol on FSH secretion is limited in the presence of oestradiol.

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Zoledronic acid modulates osteoclast apoptosis through activation of the NF-κB signaling pathway in ovariectomized rats

Experimental Biology and Medicine ◽

10.1177/15353702211011052 ◽

2021 ◽

pp. 153537022110110

Author(s):

Yu-Ting Cheng ◽

Jian Liao ◽

Qian Zhou ◽

Hua Huo ◽

Lucas Zellmer ◽

...

Keyword(s):

Zoledronic Acid ◽

Bone Mass ◽

Mass Loss ◽

Ovariectomized Rats ◽

Therapeutic Effects ◽

Bone Mass Loss ◽

Cellular Effects ◽

Protein Levels ◽

Adverse Factor ◽

Osteoclast Apoptosis

Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls. Further evaluation with a TUNEL assay showed ovariectomized enhanced apoptosis of osteoblasts but inhibited apoptosis of osteoclasts in the mandible. Zoledronic acid given subcutaneously as a single low dose was shown to counteract both of these ovariectomized effects. Immunohistochemical staining showed that ovariectomized induced the protein levels of RANKL and the 65-kD subunit of the NF-κB complex mainly in osteoclasts, as confirmed by staining for TRAP, a marker for osteoclasts, whereas zoledronic acid inhibited these inductions. Western blotting showed that the levels of RANKL, p65, as well as the phosphorylated form of p65, and IκB-α were all higher in the ovariectomized group than in the sham and ovariectomized + zoledronic acid groups at both the 4th- and 12th-week time points in the mandible. These data collectively suggest that ovariectomized causes bone mass loss by enhancing apoptosis of osteoblasts and inhibiting apoptosis of osteoclasts. In osteoclasts, these cellular effects may be achieved by activating RANKL-NF-κB signalling. Moreover, zoledronic acid elicits its therapeutic effects in the mandible by counteracting these cellular and molecular consequences of ovariectomized.

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