title: High doses of caffeine reduce in vivo osteogenic activity in prepubertal rats.
abstract: Caffeine adversely affects endochondral ossification during fetal skeletal growth, and results in increased incidence of delayed and abnormal fetal skeletal development. Chronic caffeine intake also decreases growth hormone secretion. Thus, it is conceivable that caffeine may disrupt bone growth during the peripubertal period. This study aimed to investigate the impact of high-caffeine consumption on bone growth throughout puberty. A total of 51 male rats (21 days old) were divided randomly into three groups: a control group and two groups fed caffeine via gavage with 120 and 180 mg kg(-1)  day(-1) for 4 weeks. After death, the final length and weight of leg bones were measured, and the tibia processed for histomorphometric analysis. Caffeine caused a significant decrease in body mass gain. This was accompanied with proportional decreases in lean body mass and body fat. In addition, bone mass and osteogenic activity in vivo were assessed using dual-energy X-ray absorptiometry and (18) F-NaF positron emission tomography. The results showed significant decreases of bone mass and in vivo osteogenic activity in the caffeine-fed groups. Rats fed with caffeine showed a significantly shorter and lighter tibia and femur and the vertebral column compared with controls. In addition, caffeine does not increase the width of the growth plates (GPs), it slows the rate at which the GP closes due to a slower rate of growth. These results demonstrated that caffeine altered osteogenic activity, leading to delayed peripubertal longitudinal bone growth and maturation. Given that osteogenic cells undergo dynamic changes in metabolic activity and that the pubertal growth spurt is mainly stimulated by growth hormone/insulin-like growth factor-1 and sex steroids during pubertal development, caffeine could suppress ossification by interfering with both physiological changes in hormonal secretion and osteogenic activity during this critical period. Further study will be needed to investigate the cellular/molecular mechanism by which caffeine affects osteogenesis using in vitro experimental models.
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Jisook
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: A-Ram
authors.initials: AR
authors.lastname: Yu
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Ji-Soo
authors.initials: JS
authors.lastname: Shin
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Yun-Young
authors.initials: YY
authors.lastname: Choi
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Jaesook
authors.initials: J
authors.lastname: Roh
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D002110:Caffeine / Q000008:administration & dosage / Q000009:adverse effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D005269:Femur / Q000187:drug effects; D006132:Growth Plate / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D049268:Positron-Emission Tomography; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine; D007334:Insulin-Like Growth Factor I
keywords: 18F-NaF PET; DXA; caffeine; growth spurt; osteogenesis; puberty