Bone Parameters are Improved with Intermittent Dosing of Vitamin D3 and Calcitonin

Abstract

Intermittent combination of an anabolic agent to promote bone formation and an antiresorptive agent that would prevent further bone loss is a theoretically attractive approach for restoring bone mass. We tested the potential of intermittently dosed calcitriol and calcitonin (CT) to restore bone properties in ovariectomized (Ovx) rats. Rats had Ovx or sham surgery at 8 weeks old and 4 weeks later were assigned to experimental groups: (1) sham vehicle, (2) Ovx vehicle, (3) Ovx + parathyroid hormone (PTH, 40 microg/kg), and (4) Ovx + calcitriol (2 microg/kg) + CT (2 microg/kg). Group 3 received PTH every week throughout the study, and group 4 received calcitriol at weeks 1, 3, 5, and 7 and CT at weeks 2, 4, 6, and 8. Dosing was carried out for 8 weeks with serum, and micro-computed tomographic analysis was done at 0, 4, and 8 weeks. Femurs and tibias were used for radiological analyses and for mechanical testing. Dosing with PTH improved bone mass and structure of cancellous bone at metaphyses of tibias and femurs as well as properties of cortical bone including geometry and strength. Intermittent dosing with calcitriol and CT was less potent in correcting loss of cancellous bone relative to treatment with PTH and had no effect on cortical bone parameters. However, intermittent dosing with calcitriol and CT was robust enough to improve cancellous bone mass and structure through bone formation without causing deleterious side effects. Our data provide additional evidence that therapies can be devised to ameliorate the skeletal defects associated with established osteoporosis.

Calcitonin and vitamin D3 have high therapeutic potential for improving diabetic mandibular growth

“…In this experiment, the intermittent dosing of vitamin D 3 and calcitonin was adopted as a means to restore the detrimental effects of DM because these two hormones act on different cellular targets and could potentially have an additive beneficial effect. 9 Previous research work has shown that the administration of vitamin D 3 alone for prolonged periods or in high doses is not recommended due to the disturbances expected in calcemic activities; moreover, the application of calcitonin alone was found to be unable to restore detrimental effects on bone structure or mass caused by some systemic hormonal disturbances. 9 , 21 …”

“…The antiresorptive effect of calcitonin was previously suggested 9 , 10 , 21 , 29 and was considered safe and capable of stabilizing or increasing bone mineral density. In addition, calcitonin is a powerful inhibitor of osteoclast activity with only a transitory action because it is quickly eliminated from the skeleton, circulation and extravascular fluids, allowing normal remodelling to take place.…”

“…Among these treatments, a theoretically attractive approach was suggested that includes the intermittent administration of an anabolic agent to promote bone formation and an antiresorptive agent that would prevent further bone loss. 7 , 9 Evidence suggests that vitamin D 3 can serve as the anabolic agent because it has a direct anabolic effect on bone and it increases the survival of osteoblasts. 9 , 10 In contrast, calcitonin can be used as the antiresorptive agent through its action with its specific receptors, causing powerful inhibition of osteoclast activity; moreover, its role as a regulator of calcium homeostasis that involves bone resorption is well documented.…”

“… 7 , 9 Evidence suggests that vitamin D 3 can serve as the anabolic agent because it has a direct anabolic effect on bone and it increases the survival of osteoblasts. 9 , 10 In contrast, calcitonin can be used as the antiresorptive agent through its action with its specific receptors, causing powerful inhibition of osteoclast activity; moreover, its role as a regulator of calcium homeostasis that involves bone resorption is well documented. 9 , 11 Consequently, this may aid in improving the lines of treatment for the craniofacial growth deficiency observed in DM patients.…”

Osteoblast Response to Ovariectomy Is Enhanced in Intrinsically High Aerobic-Capacity Rats

“…Osteoblast activity is upregulated in the OVX rat [14, 30–32]. At 4 weeks post-OVX, all dynamic histomorphometric measures (i.e., MS/BS, MAR, and BFR/BS) were significantly increased on the periosteal surface of the femoral diaphysis and in the trabecular region of the proximal tibial metaphysis in HCR and LCR OVX relative to sham animals (Fig.…”