DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1302 enamel. Osteosclerosis is characterized by increased bone density Since its inception, regulation of the fluoride concentration of
community water supplies periodically has encountered vocal
opposition, including allegations of putative adverse health consequences
of fluoridated water. Careful examination of these issues
indicates that cancer and all-cause mortalities do not differ significantly
between communities with fluoridated and nonfluoridated
water (Richmond, 1985).
SECTION V
HORMONES AND HORMONE ANTAGONISTS
secondary both to elevated osteoblastic activity and to the replacement
of hydroxyapatite by the denser fluoroapatite. The degree of
skeletal involvement varies from changes that are barely detectable
radiologically to marked cortical thickening of long bones, numerous
exostoses scattered throughout the skeleton, and calcification of
ligaments, tendons, and muscle attachments. In its severest form, it
is a disabling and crippling disease.
Mottled enamel, or dental fluorosis, was first described >60
years ago. In very mild mottling, small, opaque, paper-white areas
are scattered irregularly over the tooth surface. In severe cases, discrete
or confluent, deep brown- to black-stained pits give the tooth
a corroded appearance. Mottled enamel results from a partial failure
of the enamel-forming ameloblasts to elaborate and lay down
enamel. Because mottled enamel is a developmental injury, fluoride
ingestion following the eruption of teeth has no effect.
Mottling is one of the first visible signs of excess fluoride intake
during childhood. Continuous use of water containing ~1 ppm of
fluoride may result in very mild mottling in 10% of children; at
4-6 ppm the incidence approaches 100%, with a marked increase
in severity.
Severe dental fluorosis formerly occurred in regions where
local water supplies had a very high fluoride content (e.g., Pompeii,
Italy, and Pike’s Peak, Colorado). Current regulations in the U.S.
require lowering the fluoride content of the water supply or providing
an alternative source of acceptable drinking water for affected
communities. Sustained consumption of water with a fluoride content
of 4 mg/L (4 ppm) is associated with deficits in cortical bone
mass and increased rates of bone loss over time (Sowers et al., 1991).
Fluoride and Dental Caries. After a new water supply was established,
children in Bauxite, Arkansas, had a much higher incidence of caries
than those who had been exposed to the former fluoride-containing
water. Subsequent studies established definitely that supplementation
of water fluoride content to 1.0 ppm is a safe and practical intervention
that substantially reduces the incidence of caries in
permanent teeth.
There are partial benefits for children who begin drinking
fluoridated water at any age; however, optimal benefits are obtained
at ages before permanent teeth erupt. Topical application of fluoride
solutions by dental personnel appears to be particularly effective on
newly erupted teeth and can reduce the incidence of caries by 30-40%.
Dietary fluoride supplements should be considered for children
<12 years of age whose drinking water contains <0.7 ppm fluoride.
Conflicting results have been reported from studies of fluoridecontaining
toothpastes.
Adequate incorporation of fluoride into teeth hardens the
outer layers of enamel and increases resistance to demineralization.
Fluoride deposition apparently involves exchange with hydroxyl or
citrate anions in the enamel apatite crystal surface. The mechanism
by which fluoride prevents caries is not completely understood.
There is no convincing evidence that fluoride from any source
reduces the development of caries after the permanent teeth are completely
formed (usually ~14 years of age).
The fluoride salts usually employed in dentifrices are sodium
fluoride and stannous fluoride. Sodium fluoride also is available in
a variety of preparations for oral and topical use, including tablets,
drops, rinses, and gels.
CLINICAL SUMMARY
Increasing evidence supports the concept that regular
physical activity, adequate calcium intake, and lifestyle
changes have a positive impact on bone remodeling, constrain
bone loss, and reduce fracture risk. Antiresorptive
agents such as bisphosphonates, estrogen, selective estrogen
response modulators (SERMs), and calcium slow
bone resorption. Recombinant human PTH is available
for the treatment of osteoporosis and provides significant
intervention for restoring normal bone mass.
Cinacalcet, a drug that acts directly on the
parathyroid calcium-sensing receptor, provides a novel
approach to decreasing PTH secretion in secondary
hyperparathyroidism and parathyroid carcinoma.
Improved assays for measuring biologically active and
inactive forms of PTH may facilitate the diagnosis and
treatment of diseases associated with PTH resistance.
Estrogen-replacement therapy, once a mainstay
treatment for osteoporosis in women, has been curtailed
by the findings of the Women’s Health Initiative:
Despite estrogen’s beneficial effects on bone and fracture
risk, alone or in combination with progestin, estrogen
promotes an array of serious adverse cardiovascular
consequences. The FDA now recommends that estrogen
be reserved for women at significant risk of osteoporosis
who cannot take other medications.
BIBLIOGRAPHY
Alon US, Levy-Olomucki R, Moore WV, et al. Calcimimetics as
an adjuvant treatment for familial hypophosphatemic rickets.
Clin J Am Soc Nephrol, 2008, 3:658–664.
Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated
equine estrogen in postmenopausal women with hysterectomy:
The Women’s Health Initiative randomized
controlled trial. JAMA, 2004, 291:1701–1712.
Anonymous. Drugs for postmenopausal osteoporosis. Treat
Guidel Med Lett, 2008, 6:67–74.
Anonymous. Drugs for prevention and treatment of postmenopausal
osteoporosis. Treat Guidel Med Lett, 2005, 3:69–74.
Balena R, Kleerekoper M, Foldes JA, et al. Effects of different
regimens of sodium fluoride treatment for osteoporosis on the
structure, remodeling and mineralization of bone. Osteoporos
Int, 1998, 8:428–435.