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

Abstract

Glucocorticoids cause secondary osteoporosis and myopathy. The efficacy of vitamin D on osteoporotic fractures is thought to be through direct effects on bone and indirect effects on muscles that help to prevent falls. However, effects of vitamin D on muscles under glucocorticoid treatment remain unclear. Six-month-old female Wistar rats were randomized to four groups: vehicletreated controls; a prednisolone (PSL)-administered group (PSL group); an alfacalcidol-administered group (D group); and a group administered both PSL and alfacalcidol (PSL+D group). After a 4-week treatment period, maximum contractile strength and strength decrement index (SDI), an indicator of muscle fatigue, were measured in the calf muscle by electrical stimulation of the sciatic nerve. Cross-sectional area (CSA) of muscle fibers in the tibialis anterior muscle and bone mineral density (BMD) of the femur were evaluated. The PSL group showed significantly lower muscle strength, BMD and CSA of muscle fibers, and significantly higher SDI compared to the other three groups (P < 0.05). No significant differences were observed in any of these parameters among control, D, and PSL+D groups. These results suggest that in glucocorticoid-treated rats, alfacalcidol preserved not only BMD, but also muscle strength and muscle volume, and prevented muscle fatigue.

Effects of eldecalcitol on bone and skeletal muscles in glucocorticoid-treated rats

“…Our previous studies have shown that alfacalcidol increased muscle strength, but did not affect muscle fatigue, in ovariectomized rats [15], whereas it preserved both BMD and muscle strength and volume and prevented muscle fatigue in glucocorticoid-treated rats [16]. Similarly, in the present study, eldecalcitol increased muscle strength and volume in glucocorticoid-treated rats, but did not affect muscle fatigue.…”

“…Prednisolone (PSL) (Predonine; Shionogi Pharmaceutical, Osaka, Japan) was dissolved in 0.9 % saline, and 10 mg/kg/day was injected subcutaneously every day for 2 or 4 weeks. This dose was determined previously to cause steroid myopathy [16]. Eldecalcitol (Chugai Pharmaceutical, Tokyo, Japan) at a dose of 0.05 µg/kg/day dissolved in medium-chain triglyceride (MCT) or MCT alone was administered orally every day for 2 or 4 weeks.…”

“…The distal end of the Achilles tendon was exposed and cut at the insertion to the calcaneus. A transducer (ZPS-DPU; Imada, Aichi, Japan) was attached and fixed next to the stump with a load of 0.3 N [16]. Signals transmitted from the force transducer during isometric muscular contraction were digitally recorded on a forcetime curve (ZP-Recorder; Imada).…”

“…In addition, several recent meta-analyses have demonstrated that both native vitamin D and activated vitamin D 3 offer preventive effects against falls [13,14]. Alfacalcidol, a type of activated vitamin D 3 , also increased muscle strength in ovariectomized rats [15], and increased muscle strength and prevented muscle fatigue in glucocorticoid-treated rats [16]. However, this treatment had little effect on BMD [17,18].…”

Do diseases cause entheseal changes at fibrous entheses?

“…The results (Table 1) show that of 141 searches performed in PubMed only 16 yielded results totalling 35 papers. Of these, seven related to the periodontal ligament (Albair et al, 1982;Bragger et al, 1990;Fernyhough and Page, 1983;Isidor et al, 1985;Karring et al, 1985;Luder and Zappa, 1998;Nishimura et al, 1989), and four related to experiments in non-human animals (Harris et al, 2002;Hashimoto et al, 2007;Miyakoshi et al, 2010;Suliman et al, 1997). Of the remaining papers, seven focus on one specific condition: calcific tendinitis (Cahir and Saifuddin, 2005;Chadwick, 1989;Dürr et al, 1997;El-Essawy and Vanhoenacker, 2012;Fritz et al, 1994;Hayes et al, 1987a;Ikegawa, 1996).…”