TABLE 2.

Skeletal effects of Mel in preclinical models of bone loss.

Disease model	Effects	References
PNX	a) In newborn chicks, it caused vertebral (scoliotic) deformity and reduced spinal BMD	Turgut et al. (2005), Aota et al. (2013), Egermann et al. (2011)
	b) In young chickens, it caused high turnover bone loss and loss of trabecular microarchitecture in the vertebra
	c) In adult sheep, it caused trabecular bone loss at the iliac crest equivalent to OVX animals
Tph1 deletion in the pineal gland	Low bone mass phenotype and exogenous Mel restored bone mass	Sharan et al. (2017)
Mel receptor deletion	MT2R but not MT1R deletion has osteopenic phenotype	Sharan et al. (2017)
OVX	a) In mice, OVX caused bone loss at both tissue and serum marker levels and Mel reversed both	Zhang et al. (2021), Zhou et al. (2020b), Xu et al. (2018)
	b) In rats, OVX caused osteopenia and Mel maintained bone mass	Han et al. (2021), Da et al. (2020)
Prosthesis model developed in OVX rats	Mel in a composite hydrogel system was applied at the distal femur around titanium implant for the sustained release of the hormone, resulting in the increased osteogenesis around prosthesis	Xiao et al. (2020)
Aging	a) In 20-month-old rats, Mel treatment for 12 weeks increased bone mass and bone formation markers	Chu et al. (2017)
	b) In 22-month-old rats, Mel treatment for 10 weeks preserved bone mass and strength	Tresguerres et al. (2014)
	c) Long duration Mel (starting at 4 months until 20 months) maintained bone mass equivalent to adult animals	Igarashi-Migitaka et al. (2020)
Streptozotocin-induced diabetes	Mel protected diabetes-induced bone loss	Gong et al. (2021), Zhang et al. (2016)