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Published on: April 7, 2023
Eldecalcitol prevents muscle loss by suppressing PI3K/AKT/FOXOs pathway in orchiectomized mice
Haichao Zhang1, Zheng Ke2, Shuangshuang Dong2
1Department of Osteoporosis and Bone Disease, Research Section of Geriatric Metabolic Bone Disease, Shanghai Geriatric Institute, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
Abstract:
Elderly male patients are susceptible to develop osteoporosis and sarcopenia, especially those with fragility fractures, hypogonadism, and prostate cancer with androgen deprivation therapy. However, at present, very few treatments are available for men with sarcopenia. Previous preclinical studies in ovariectomized rats have shown the promising effects of eldecalcitol in ameliorating the bone strength and muscle atrophy. We thus investigated the effects of eldecalcitol on androgen-deficient male mice. Six-week-old male mice underwent orchiectomy (ORX) or sham surgery. Mice were randomly divided into 4 groups (n = 12/per group), including 1) sham mice, 2) ORX group, 3) ORX eldecalcitol 30 ng/kg, and 4) ORX eldecalcitol 50 ng/kg. Eldecalcitol increased bone mass and strength of femur in ORX mice. Eldecalcitol 30 ng/kg dose completely rescued ORX-induced muscle weakness. The RT-qPCR showed that eldecalcitol enhanced the mRNA levels of type I and IIa fibers. The expression levels of MuRF1 and Atrogin-1 of gastrocnemius in the eldecalcitol groups were much lower than that of the ORX group. It is assumed that eldecalcitol potentially acts via PI3K/AKT/FOXOs signaling pathway. These findings provide evidence for evaluating eldecalcitol as an investigational treatment for male patients with sarcopenia and osteoporosis.
Insights
Eldecalcitol shows promise in treating osteoporosis and sarcopenia in male mice by improving bone strength and muscle mass. This study suggests its potential as a therapeutic option for aging men with these conditions.
Area of Science:
- Gerontology
- Endocrinology
- Muscle Physiology
Background:
- Elderly men, particularly those with fragility fractures, hypogonadism, or prostate cancer undergoing androgen deprivation therapy, are at high risk for osteoporosis and sarcopenia.
- Currently, limited treatment options exist for sarcopenia in men.
- Preclinical studies in ovariectomized rats indicated eldecalcitol's efficacy in improving bone strength and mitigating muscle atrophy.
Purpose of the Study:
- To investigate the effects of eldecalcitol on androgen deficiency-induced bone and muscle loss in male mice.
- To evaluate eldecalcitol as a potential therapeutic agent for male sarcopenia and osteoporosis.
Main Methods:
- Male mice underwent orchiectomy (ORX) or sham surgery and were divided into four groups: sham, ORX, ORX with 30 ng/kg eldecalcitol, and ORX with 50 ng/kg eldecalcitol.
- Bone mass and strength were assessed.
- Muscle weakness was evaluated, and RT-qPCR was used to analyze mRNA levels of muscle fiber types (I and IIa) and muscle-specific ubiquitin ligases (MuRF1 and Atrogin-1).
Main Results:
- Eldecalcitol administration significantly increased femur bone mass and strength in ORX mice.
- A dose of 30 ng/kg eldecalcitol completely reversed ORX-induced muscle weakness.
- Eldecalcitol treatment upregulated mRNA levels of type I and IIa muscle fibers and decreased the expression of MuRF1 and Atrogin-1 in the gastrocnemius muscle compared to the ORX group.
Conclusions:
- Eldecalcitol effectively improves bone and muscle health in a mouse model of androgen deficiency.
- The drug's mechanism may involve the PI3K/AKT/FOXOs signaling pathway.
- These findings support the further evaluation of eldecalcitol for treating sarcopenia and osteoporosis in men.
