A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health

Abstract

Bisphenol A (BPA) is an endocrine disruptor which can bind to the oestrogen receptor. It also possesses oestrogenic, antiandrogenic, inflammatory and oxidative properties. Since bone responds to changes in sex hormones, inflammatory and oxidative status, BPA exposure could influence bone health in humans. This review aimed to summarize the current evidence on the relationship between BPA and bone health derived from cellular, animal and human studies. Exposure to BPA (0.5-12.5 µM) decreased the proliferation of osteoblast and osteoclast precursor cells and induce their apoptosis. Bisphenol AF (10 nM) enhanced transforming growth factor beta signalling but bisphenol S (10 nM) inhibited Wnt signalling involved in osteoblast differentiation in vitro. In animals, BPA and its derivatives demonstrated distinct effects in different models. In prenatal/postnatal exposure, BPA increased femoral bone mineral content in male rats (at 25 ug/kg/day) but decreased femoral mechanical strength in female mice (at 10 µg/kg/day). In oestrogen deficiency models, BPA improved bone mineral density and microstructures in aromatase knockout mice (at very high dose, 0.1% or 1.0% w/w diet) but decreased trabecular density in ovariectomized rats (at 37 or 370 ug/kg/day). In contrast, bisphenol A diglycidyl ether (30 mg/kg/day i.p.) improved bone health in normal male and female rodents and decreased trabecular separation in ovariectomized rodents. Two cross-sectional studies have been performed to examine the relationship between BPA level and bone mineral density in humans but they yielded negligible association. As a conclusion, BPA and its derivatives could influence bone health and a possible gender effect was observed in animal studies. However, its effects in humans await verification from more comprehensive longitudinal studies in the future.

4-Hexylresorcinol Exhibits Different Characteristics to Estrogen

“…The warning for endocrine system disruptors has been increased annually [9,10]. Many types of endocrine disruptors have been introduced and tested for their potential biohazards [14].…”

“…These agents include pesticides, such as dichlorodiphenyltrichloroethane (DDT), its metabolites, and many common industrial chemicals, such as polychlorinated biphenyls and BPA [21,22]. Human health effects from exposure to xenoestrogen include: precocious puberty, increased incidence of breast cancer, testicular cancer, prostate cancer, and reduced sperm count [9,14,21]. Long-term uptake of low-dosage xenoestrogen is deposited in adipocytes and may be released in fasting conditions and show estrogen effects [21].…”

“…However, increased bone mass and angiogenesis by 4HR may be similar to the actions of estrogen. Estrogen-like materials have been studied as endocrine disruptor and breast cancer inducer [9,10]. Differentiation of 4HR from other xenoestrogens is important for usage of 4HR as immunomodulation agent.…”

“…Xenoestrogen is the chemical that mimics the action of estrogen and results in endocrine system disruption [9,10]. Xenoestrogen may pollute and destroy the natural endocrine system.…”

“…Xenoestrogen is a member of a group of organic phenolic compounds with a benzene ring [11]. Bisphenol A (BPA) is a representative chemical [9,10]. Global fear for xenoestrogen has sharply increased recently [12].…”