Mechanism of osteoporosis in adolescent idiopathic scoliosis: experimental scoliosis in pinealectomized chickens

109

Melatonin is a signal molecule that modulates the biological circadian rhythms of vertebrates. Melatonin deficiency is thought to be associated with several disorders, including insomnia, cancer, and cardiovascular and neurodegenerative diseases. Accumulating evidence has also indicated that melatonin may be involved in the homeostasis of bone metabolism. Age‐related reductions in melatonin are considered to be critical factors in bone loss and osteoporosis with aging. Thus, serum melatonin levels might serve as a biomarker for the early detection and prevention of osteoporosis. Compared to conventional antiosteoporosis medicines, which primarily inhibit bone loss, melatonin both suppresses bone loss and promotes new bone formation. Mechanistically, by activating melatonin receptor 2 (MT2), melatonin upregulates the gene expression of alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2), BMP6, osteocalcin, and osteoprotegerin to promote osteogenesis while inhibiting the receptor activator of NF‐kB ligand (RANKL) pathway to suppress osteolysis. In view of the distinct actions of melatonin on bone metabolism, we hypothesize that melatonin may be a novel remedy for the prevention and clinical treatment of osteoporosis.

Section: Prospects and Conclusionmentioning

confidence: 93%

Melatonin: Another avenue for treating osteoporosis?

Tian

Jiang

et al. 2019

109

“…In keeping with this, a disruption in melatonin‐mediated signaling, whether it be through a suppression of nocturnal melatonin levels by light at night (LAN) or through impaired melatonin receptor signaling in osteoblasts, is thought to underlie, respectively, the increased risk of hip and wrist fracture and low BMD in shift workers and to the development of adolescent idiopathic scoliosis . Decreases in melatonin have been shown to alter bone morphology in various models including fish , chickens , and mice . In rodents and sheep, LAN or removal of the melatonin source through pinealectomy increases bone marker turnover and decreases bone mass .…”

Section: Melatonin and Bonementioning

confidence: 99%

“…Decreases in melatonin have been shown to alter bone morphology in various models including fish , chickens , and mice . In rodents and sheep, LAN or removal of the melatonin source through pinealectomy increases bone marker turnover and decreases bone mass . A restoration of the melatonin peak at night by limiting LAN or by supplementing nighttime levels with exogenous melatonin may prove to be of benefit .…”

Section: Melatonin and Bonementioning

confidence: 99%

Melatonin effects on bone: potential use for the prevention and treatment for osteopenia, osteoporosis, and periodontal disease and for use in bone‐grafting procedures

Maria

Witt‐Enderby

2014

164

159

An important role for melatonin in bone formation and restructuring has emerged, and studies demonstrate the multiple mechanisms for these beneficial actions. Statistical analysis shows that even with existing osteoporotic therapies, bone-related disease, and mortality are on the rise, creating a huge financial burden for societies worldwide. These findings suggest that novel alternatives need to be developed to either prevent or reverse bone loss to combat osteoporosis-related fractures. The focus of this review describes melatonin's role in bone physiology and discusses how disruption of melatonin rhythms by light exposure at night, shift work, and disease can adversely impact on bone. The signal transduction mechanisms underlying osteoblast and osteoclast differentiation and coupling with one another are discussed with a focus on how melatonin, through the regulation of RANKL and osteoprotegerin synthesis and release from osteoblasts, can induce osteoblastogenesis while inhibiting osteoclastogenesis. Also, melatonin's free-radical scavenging and antioxidant properties of this indoleamine are discussed as yet an additional mechanism by which melatonin can maintain one's bone health, especially oral health. The clinical use for melatonin in bone-grafting procedures, in reversing bone loss due to osteopenia and osteoporosis, and in managing periodontal disease is discussed. ; the female-to-male ratio for fracture is 1.6 [1]. In the European Union, approximately 22 million women and 5.5 million men (between 50 and 84 yr) are projected to have osteoporosis; this number will rise by 23% by 2025 [3]. In the United States, nearly 57 million adults over age 50 are affected by bone disease, 48 million adults have osteopenia, and 9 million adults have osteoporosis, which places these individuals at risk for developing bone fracture. If left unchanged, by 2030, the prevalence of osteoporosis will increase to 11.9 million and 64.3 million with osteopenia [4].In the United States, the annual fracture rate is 1.5 million per year (300,000 hip and 700,000 vertebral fractures), which is expected to increase by 3 million by 2025 [5,6]. In the United Kingdom, although it was expected that the 12-month survival rate after hip fracture would be 90-91%, the actual numbers were less than expected with 63.3% of men and 74.9% of women surviving [7]. In the United States, hip fracture is responsible for approximately 31,000 excess deaths within 6 months, which can start as early as age 50; this is significant, considering that one in every three women and one in five men in the United States will experience an osteoporosis-related fracture in their lifetime [6]. In addition to increasing morbidity and mortality rates, osteoporosis-related fractures are also creating huge economical burdens to societies worldwide. For example, osteoporosis treatment and related fracture cost in the United States (per year) is $19 billion, which is expected to increase to $25.3 billion by 2025 [6]. In 2010, osteoporosis-related costs amounted ...

“…Also, in children with Smith-Magenis syndrome, a genetic condition associated with bone abnormalities, perturbations in both their sleep and melatonin rhythms exist [6,7]. In rodents, reduction in nocturnal melatonin levels either by light at night (LAN) or by pinealectomy increases bone marker turnover [8,9] and adversely affects their bone health [10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Effects on bone by the light/dark cycle and chronic treatment with melatonin and/or hormone replacement therapy in intact female mice

Witt‐Enderby

Slater

Johnson

et al. 2012

In this study, the effects of the light/dark cycle, hormone replacement therapy (HRT), and nocturnal melatonin supplementation on osteogenic markers and serum melatonin levels were examined in a blind mouse model (MMTV-Neu transgenic mice). Melatonin levels in this mouse strain (FVB/N) with retinal degeneration (rd-/-) fluctuate in a diurnal manner, suggesting that these mice, although blind, still perceive light. Real-time RT-PCR analyses demonstrated that Runx2, Bmp2, Bmp6, Bglap, and Per2 mRNA levels coincide with melatonin levels. The effect of chronic HRT (0.5 mg 17β-estradiol + 50 mg progesterone in 1800 kcal of diet) alone and in combination with melatonin (15 mg/L drinking water) on bone quality and density was also assessed by histomorphometry and microcomputed tomography, respectively. Bone density was significantly increased (P < 0.05) after 1 yr of treatment with the individual therapies, HRT (22% increase) and nocturnal melatonin (20% increase) compared to control. Hormone replacement therapy alone also increased surface bone, decreased trabecular space, and decreased the number of osteoclasts without affecting osteoblast numbers compared to the control group (P < 0.05). Chronic HRT + melatonin therapy did not significantly increase bone density, even though this combination significantly increased Bglap mRNA levels. These data suggest that the endogenous melatonin rhythm modulates markers important to bone physiology. Hormone replacement therapy with or without nocturnal melatonin in cycling mice produces unique effects on bone markers and bone density. The effects of these therapies alone and combined may improve bone health in women in perimenopause and with low nocturnal melatonin levels from too little sleep, too much light, or age.