Melatonin effect on bone metabolism in rats treated with methylprednisolone

Abstract

The present study was undertaken to examine the effect of melatonin (25 microg/mL of drinking water, about 500 microg/day) on a 10-wk long treatment of male rats with methylprednisolone (5 mg/kg s.c., 5 days/wk). Bone densitometry and mechanical properties, calcemia, phosphatemia and serum bone alkaline phosphatase activity and C-telopeptide fragments of collagen type I (CTX) were measured. Both melatonin and methylprednisolone decreased significantly body weight (BW) and the combination of both treatments resulted in the lowest BW values found. Consequently, all results were analyzed with BW as a covariate. Densitometrically, methylprednisolone augmented bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) in the entire skeleton, BMC in cortical bone, and BMC and BMD in trabecular bone. Melatonin increased BMC and BA in whole skeleton and BMC and BMD in trabecular bone. For BMC and BA of whole skeleton, BMC of cortical bone, and BMC and BMD of trabecular bone, the combination of glucocorticoids and melatonin resulted in the highest values observed. Femoral weight of rats receiving methylprednisolone or melatonin increased significantly and both treatments summated to achieve the greatest effect. In femoral biomechanical testing, methylprednisolone augmented ultimate load and work to failure significantly. Rats receiving the combined treatment of methylprednisolone and melatonin showed the highest values of work to failure. The circulating levels of CTX, an index of bone resorption, decreased after methylprednisolone or melatonin, both treatments summating to achieve the lowest CTX values found. Serum calcium increased after methylprednisolone and serum phosphorus decreased after treatment with methylprednisolone or melatonin while serum bone alkaline phosphatase levels remained unchanged. The results are compatible with the view that low doses of methylprednisolone or melatonin decrease bone resorption and have a bone-protecting effect.

Abnormal proliferation and differentiation of osteoblasts from girls with adolescent idiopathic scoliosis to melatonin

“…It has been documented that melatonin plays a crucial role in promoting bone formation in humans [24, 34] by enhancing the proliferation, differentiation, and matrix formation of osteoblasts [33, 34, 43]. In this study, melatonin‐induced proliferation of normal human osteoblasts was mediated in a dose‐dependent manner (Fig.…”

“…Melatonin has been detected probably in every examined species of the animal kingdom [11, 12] and in plants [13, 14]. This indoleamine is involved in many regulatory functions including embryo development [15], circadian rhythm [16], reproductive physiology [17, 18], seasonal reproductive changes [19, 20], tumor growth [21–23], and bone growth [24–27]. Moreover, melatonin has an antiaging potential owing to its free‐radical scavenging and powerful antioxidant activities [28, 29], as well as protective effects on nuclear and mitochondrial DNA [30].…”

Melatonin prevents glucocorticoid inhibition of cell proliferation and toxicity in hippocampal cells by reducing glucocorticoid receptor nuclear translocation

“…In fact, in other tissues the interaction of melatonin with glucocorticoids has been demonstrated. Melatonin inhibits in vitro the increased of calcium uptake in bone samples of rats treated with pharmacological amounts of corticosterone [43]. Also, it prevents glucocorticoid-induced apoptosis in thymocytes [44] and protects cerebellar neurons from apoptosis induced by glucocorticoids [31].…”

Melatonin Effects on Hard Tissues: Bone and Tooth

“…Melatonin is a significant free-radical scavenger and antioxidant. It can clear up the free radicals generated by osteoclast during the bone resorption process and protect bone cells from oxidative attacks [18,30,31]. …”