Effects of alfacalcidol on muscle strength, muscle fatigue, and bone mineral density in normal and ovariectomized rats

Abstract

Vitamin D affects not only bone but also muscle to prevent falls and osteoporotic fractures. However, these effects on muscle and the mechanisms of fall prevention are still unclear. The purpose of this study was to investigate the effects of alfacalcidol [1α(OH)D 3 ] on muscle strength, muscle fatigue, and bone mineral density (BMD) in ovariectomized rats. Seven-month-old female Wistar rats were orally administered 1α(OH)D 3 or its vehicle everyday for 4 weeks after ovariectomy (OVX) or sham operation. Calf muscle strength and fatigue were evaluated by electrical stimulation of the sciatic nerve under general anesthesia. 1α(OH)D 3 administration significantly increased the maximum muscle strength in the sham-operated (P < 0.01) and the OVX (P < 0.01) groups compared to their respective control groups. However, 1α(OH)D 3 administration did not significantly affect muscle fatigue in these groups. The BMD of the femur in the 1α(OH)D 3 -treated OVX group was significantly higher than that in the vehicle-treated OVX group (P = 0.04). These results suggested that 1α(OH)D 3 increases muscle strength but does not affect muscle fatigue in this rat model. The effectiveness of activated vitamin D in preventing bone fractures may be partly owing to its effect on muscle strength in addition to its known effect on bone metabolism.The active, hormonal form of vitamin D 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 or calcitriol] and its prodrug 1α-hydroxyvitamin D 3 [1α(OH)D 3 or alfacalcidol] have been widely used to treat a variety of metabolic bone diseases, such as rickets/osteomalacia, renal osteodystrophy, and osteoporosis (8, 41). Activated vitamin D can prevent fractures by improving bone quality, bone metabolism, and bone mineral density (BMD) (7,22,40,45,50). However, its preventive effects on fractures were more significant than its effects on bone quality or BMD. Several recent meta-analyses have demonstrated that native or activated vitamin D has preventive effects on falls (2, 16). This preventive effect on falls contributes to a partial reduction of fractures by vitamin D in elderly osteoporotic individuals (3, 37). However, the mechanisms by which activated vitamin D prevents falls remain unknown. Several factors have been reported as physical risk factors for falls, including decreased muscle strength or function of lower extremity, impaired physical function such as single-leg standing, and postural imbalance with aging (26,28,34,36). Vitamin D may act directly on muscle tissue to exert its preventive effect on falls. It has been known that osteomalacia and rickets cause muscular atrophy and decrease muscle strength and that the muscular symptoms associated with these diseases quickly improve with vitamin D treatment (39, 43). These findings indicate a potential association between vitamin D and muscle tissue. Therefore, the effects of vitamin D on muscle tissue with regard to fall prevention have been of focus in aged and osteoporotic patients. Muscle function is defined by several factors, including mu...

Association of hypovitaminosis D with triceps brachii muscle fatigability among older women: Findings from the EPIDOS cohort

“…To the best of our knowledge, only two studies have examined this issue [16,17]. The first one, an animal study by Kasukawa et al [16], examined the effects of vitamin D supplementation on calf muscle fatigue in 12 ovariectomized rats.…”

Effects of a vitamin D analog, alfacalcidol, on bone and skeletal muscle in glucocorticoid-treated rats

“…Several limitations in the present study warrant attention. First, the duration of treatment with alfacalcidol was only 4 weeks, although the length of treatment was determined based on previous studies (24). Duration of treatment appears to represent an important factor, and the effects of vitamin D treatment on muscles in glucocorticoid-treated animals should be further clarified in future studies by increasing the duration of administration.…”

“…At euthanasia, the right femur was harvested for BMD measurement. BMD at the proximal, middle, and distal thirds of the femur and total BMD of the femur were measured using dualenergy X-ray absorptiometry (QDR-4500 Delphi; Hologic, Bedford, MA, USA) (24). Protocols for all animal experiments were approved in advance by the Animal Research Committee of Akita University, and all subsequent animal experiments adhered to the "Guidelines for Animal Experimentation" of the university.…”

Kwas zoledronowy stosowany przez dwa lata u Chinek z osteoporozą pomenopauzalną zwiększa gęstość mineralną tkanki kostnej i poprawia jakość życia związaną ze stanem zdrowia

“…In addition, all the patients received daily calcium (1,000-1,500 mg) and vitamin D (400-1,200 IU) during the study. Muscle strength, balance, and functional mobility depend on vitamin D serum levels [34,35]. Several previous studies have noted that treatment with vitamin D (alfacalcidol or calcitriol) can significantly reduce the risk of falls and of fall-associated fractures [34,36,37].…”

“…Muscle strength, balance, and functional mobility depend on vitamin D serum levels [34,35]. Several previous studies have noted that treatment with vitamin D (alfacalcidol or calcitriol) can significantly reduce the risk of falls and of fall-associated fractures [34,36,37]. Hua Lin [23,38] reported that 5 mg zoledronic acid and calcitriol can significantly reduce the risk of falls in patients with postmenopausal osteoporosis.…”