Histochemical examination of the effects of high-dose 1,25(OH)2D3 on bone remodeling in young growing rats

Abstract

Vitamin D has an anabolic effect on bone developmental processes and is involved in maintaining skeletal integrity. In recent years, pediatric cases of vitamin D intoxication have attracted attention. Therefore, the aim of this study was to investigate the influence of long-term administration of physiologically-high-dose calcitriol (1,25(OH)2D3) on bone remodeling in young developing rats. Neonatal rats received once-daily subcutaneous injection of calcitriol (250 ng/kg body weight), or PBS only as a control, for 3 weeks. At 1, 2 and 4 weeks' post-administration, rats were sacrificed and fixed by transcardial perfusion with 4 % paraformaldehyde, following which tibiae were extracted for histochemical analysis. Compared with the control group, the number of tartrate-resistant acid phosphatase- and Cathepsin K-positive osteoclasts were significantly increased, and the expression of alkaline phosphatase in osteoblasts was decreased in trabecular bone of rats administered high-dose 1,25(OH)2D3, leading to decreased trabecular bone volume. In addition, the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) was increased, while that of osteoprotegerin was weaker in osteoblasts in the experimental group compared with the control group. Moreover, there was weaker immunoreactivity for EphrinB2 in osteoclasts and EphB4 in osteoblasts of trabecular bone in the experimental group compared with the control group. These findings suggest that long-term use of physiologically-high dose calcitriol may result in bone loss through RANKL/RANK/osteoprotegerin and EphrinB2-EphB4 signaling pathways, and that these negative effects could continue after drug withdrawal. Therefore, optimal limits for vitamin D administration need to be established for children and adolescents.

Vitamin D metabolism in growing pigs: influence of UVB irradiation and dietary vitamin D supply on calcium homeostasis, its regulation and bone metabolism

“…When mineralization subsequently takes place, BMD will increase (Dittmer et al., ). On the other side, 1,25‐(OH) 2 ‐D is known to inhibit bone mineralization (St‐Arnaud et al., ; Sun et al., ). Sun et al.…”

“…Sun et al. () found that subcutaneous injections of a physiologically high dose of 1,25‐(OH) 2 ‐D (250 ng/kg body weight, releasing a maximal physiological response in normal rats) over 3 weeks in newborn rats led to decreased trabecular bone volume measured in histologically sections of the tibial metaphysis. In contrast, piglets were reported to show serum levels of 25‐OH‐D up to 900 nmol/l without any changes in content of Ca and P of the bones (von Rosenberg et al., ).…”

“…These pigs were fed 500 μ g 25‐OH‐D/kg feed for 42 days (corresponding to 20 000 IU vitD/kg feed; Lauridsen et al., ). The effect of 1,25‐(OH) 2 ‐D on bone (stimulation or inhibition of bone resorption and mineralization) depends on dose and PTH level in blood (Sun et al., ). Reported values for 25‐OH‐D with negative effects on bone metabolism (reduced mineral contents) are rare and vary highly.…”

Effects of ultraviolet irradiation with a LED device on bone metabolism associated with vitamin D deficiency in senescence-accelerated mouse P6

“…UVR treatment with a UV-LED device has advantages for these problems of vitamin D supplementation and sun exposure. Regarding vitamin D medication, there are several potential risks of negative effects of high-dose vitamin D medication on bone metabolism [45,46] and hypercalcemia [47]. However, UVR for vitamin D supply could reduce those risks, because levels of active vitamin D [1,25(OH) 2 D] synthesized endogenously are regulated by renal 1α-hydroxylase and 24-hydroxylase through the homeostatic response to levels of the vitamin D hormone and calcium [11,13,48].…”

Az alacsony alkalikusfoszfatáz-aktivitás klinikai értékelése és differenciáldiagnosztikája

“…A magas D-vitamin-szint gátolja az osteogenesist, az osteo blastok aktivitását és csökkenti a csontképzést [13], így szintén a referenciaérték alatti mérési eredményekhez vezethet.…”