Melatonin increases oestradiol‐induced bone formation in ovariectomized rats

Abstract

: To assess the effect of melatonin on bone metabolism in ovariectomized rats, receiving oestradiol therapy or not, melatonin was administered in the drinking water (25 μg/mL water) and oestradiol (10 μg/kg body weight) or vehicle was given subcutaneously 5 days/week for up to 60 days after surgery. Urinary deoxypyridinoline (a marker of bone resorption) and circulating levels of bone alkaline phosphatase activity (a marker of bone formation), as well as serum calcium and phosphorus levels, were measured every 15 days. Bone area (BA), bone mineral content (BMC), bone mineral density (BMD) and total body fat (expressed as 100 g body weight) were measured by dual‐energy X‐ray absorptiometry at the end of the experiment. Body weight and total body fat were augmented after ovariectomy, and decreased after melatonin or oestradiol treatment. The effect of melatonin on body weight was seen in sham‐operated rats only. Ovariectomy augmented, and melatonin or oestradiol lowered, urinary deoxypyridinoline excretion. This effect of melatonin and oestradiol was seen mainly in ovariectomized rats. The efficacy of oestradiol to counteract ovariectomy‐induced bone resorption was increased by melatonin. Melatonin or oestradiol lowered serum bone alkaline phosphatase activity. Melatonin inhibition was seen mainly on the increase of bone alkaline phosphatase activity that followed ovariectomy. Serum phosphorus levels decreased after melatonin administration and were augmented after oestradiol injection; overall, melatonin impaired the increase of serum phosphorus caused by oestradiol. Ovariectomy decreased, and oestradiol increased, serum calcium levels while melatonin augmented serum calcium in sham‐operated rats only. On day 60 after surgery, BMD and content decreased after ovariectomy and were increased after oestradiol injection. Melatonin augmented BA of spine and BMC of whole of the skeleton and tibia. The highest values observed were those of rats treated concurrently with oestradiol and melatonin. The present results indicate that: (i) melatonin treatment restrained bone remodelling after ovariectomy; (ii) the effect of melatonin required adequate concentrations of oestradiol; (iii) melatonin augmented oestradiol effects on bone in ovariectomized rats; (iv) a counter‐regulation by melatonin of the increase in body fat caused by ovariectomy was uncovered. The melatonin doses employed were pharmacological in terms of circulating melatonin levels but not necessarily for some other fluids or tissues.

Parathyroid hormone 1 (1–34) acts on the scales and involves calcium metabolism in goldfish

“…Moreover, we were the first to find that melatonin, a major hormonal product of the pineal gland, functioned negatively in both osteoclasts and osteoblasts [18]. The action of melatonin on bone has also subsequently been reported in in vivo studies in the rat [23]. Moreover, we indicated that osteogenesis in the regenerating scale is very similar to that seen in mammalian membranous bone and that regenerating scales have estrogen receptors which respond to estrogen in the same manner as mammalian osteoblasts [24].…”

Melatonin regulates human bone sialoprotein gene transcription

“…It has a variety of physiological actions such as control of circadian rhythm, sexual development, inflammation and hormone secretion (3,8,10,13,15). Melatonin promotes osteoblast differentiation and bone formation (38,39), and can protect the oral cavity from tissue damage (40,41).…”

“…Furthermore, melatonin regulates various physiological and pathophysiological processes such as control of body temperature, sexual development, inflammation, the immune reponse and cell proliferation (8)(9)(10)(11)(12)(13). Melatonin also regulates bone remolding, prevents osteoporosis, and induces dentine formation and osseointegration of dental implants (14)(15)(16)(17)(18).…”

Effects of Melatonin on Tibia Bone Defects in Rats

“…The investigation and applications of melatonin in the hard tissues, bone and tooth, have received great attention. Melatonin has been investigated relative to bone remolding osteoporosis, osseointegration of dental implants and dentine formation Ladizesky et al, 2003;Cutando et al, 2007Cutando et al, , 2008Kotlarczyk et al, 2012;Liu et al, 2013). Osteopontin is one of the major non-collagen proteins in extracellular bone matrix, it has a role in osteoclast-mediated bone resorption.…”