Fluoride levels and osteosarcoma
Simmi Kharb2012, South Asian Journal of Cancer
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Context: Osteosarcoma is a rare malignant bone tumor, commonly occurring in the age group of 10 to 24 years. Recent reports have indicated that there is a link between fluoride exposure and osteosarcoma. Aims: The present study was planned to analyze serum levels of fluoride in patients of osteosarcoma and fluoride content of their drinking water. Settings and Design: The present study was carried out comparing 10 patients of osteosarcoma and 10 healthy volunteers (who served as controls). Materials and Methods: Serum and drinking water fluoride levels were estimated by ion selective electrode. Statistical analysis used: The data were computed as mean ± SD and Student’s t test was applied. Results: Both, the serum and drinking water fluoride levels, were significant by higher in patients with osteosarcoma as compared to controls (P < 0.05, P < 0.001, respectively). Conclusions: These results suggest a link between fluoride exposure and osteosarcoma.
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Published online: 2020-12-30
Original Article
Fluoride levels and osteosarcoma
Simmi Kharb, Ravindra Sandhu, Zile Singh Kundu1
Abstract
Context: Osteosarcoma is a rare malignant bone tumor, commonly occurring in the age group of 10 to 24 years. Recent reports
have indicated that there is a link between fluoride exposure and osteosarcoma. Aims: The present study was planned to analyze
serum levels of fluoride in patients of osteosarcoma and fluoride content of their drinking water. Settings and Design: The present
study was carried out comparing 10 patients of osteosarcoma and 10 healthy volunteers (who served as controls). Materials and
Methods: Serum and drinking water fluoride levels were estimated by ion selective electrode. Statistical analysis used: The
data were computed as mean ± SD and Student’s t test was applied. Results: Both, the serum and drinking water fluoride levels,
were significant by higher in patients with osteosarcoma as compared to controls (P < 0.05, P < 0.001, respectively). Conclusions:
These results suggest a link between fluoride exposure and osteosarcoma.
Key words: Fluoride, osteosarcoma, serum, water
Introduction
Osteosarcoma is a rare malignant bone tumor, commonly
occurring in the age group of 10 to-24 years. Bone is
the principal site of fluoride accumulation. [1,2] In several
parts of India, particularly Haryana, incidence of fluorosis
is high in certain areas.[3] Recent reports have indicated
that there is a direct link between fluoride exposure and
osteosarcoma.[4,5] Studies have also linked high incidence
of bone cancer to fluoridation in drinking water.[5-7] On the
other hand, a few reports have also indicated that fluoride
exposure has no role in osteosarcoma.[2,8,9]
To the best of our knowledge, we could not come across
any study where fluoride levels have been estimated in
serum and drinking water of osteosarcoma patients. Hence,
the present study was planned to analyze serum levels of
fluoride in patients of osteosarcoma and fluoride content of
their drinking water.
Materials and Methods
The present study was conducted in 10 patients of
osteosarcoma and 10 healthy volunteers, who served as
Departments of Biochemistry and 1Orthopedics, Pt.BDS PGIMS,
Rohtak, India
Correspondence to: Dr. Simmi Kharb,
E-mail: [email protected]
Access this article online
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Website:
www.sajc.org
DOI:
10.4103/2278-330X.103717
76
controls. 2 ml venous blood was collected aseptically
from antecubital vein, and serum was separated by
centrifugation. Also, 10 ml drinking water samples brought
by these subjects from their home were also evaluated.
Serum and fluoride levels were estimated by ion selective
electrode.[11] The data were computed as mean ± SD and
Student’s t test was applied.
Results
Serum fluoride levels were significant by higher in patients
with osteosarcoma as compared to controls (P < 0.05,
Table 1). Also, drinking water fluoride levels were
significantly higher in osteosarcoma group as compared
to controls (P < 0.001, Table 1). There was also a
positive correlation between drinking water fluoride and
serum fluoride levels in the osteosarcoma group patients
(r = 0.855, P < 0.01).
Discussion
Fluoride influences bone growth by acting as mitogenic
agent for Osteoblasts. [12] Recent studies have indicated
relationship of high fluoride levels in drinking water with
incidence of osteosarcoma.[4] There are no reports available
in literature where serum and drinking water fluoride
levels have been correlated in osteosarcoma. We have
recently reported on serum fluoride and sialic acid levels
in osteosarcoma.[13]
In the present study, significantly higher serum fluoride
levels were documented in osteosarcoma patients as
compared to healthy controls (Table 1, P < 0.05). Also,
samples of drinking water from the homes of these patients
also showed a higher fluoride content.
Fluoride gets incorporated into bone lattice by forming
fluoroapatite, which is more stable than hydroxyapatite.
South Asian Journal of Cancer ♦ October-December 2012 ♦ Volume 1 ♦ Issue 2
Kharb, et al.: Fluoride/osteosarcoma
Table 1: Fluoride levels in two groups
(mean ± SD, mg/L)
Control group
Serum fluoride
Water fluoride
0.042 ± 0.035
0.475 ± 0.243
Osteosarcoma
patients
0.183 ± 0.105
1.302 ± 0.760
P value
6.
< 0.05
< 0.001
7.
During periods of rapid skeleton growth, fluoride uptakes
in bone increases since hydroxyapatite crystal are extremely
small in young age. Also, fluoride has been reported to
increase calcium absorption in intestine,[14] and this property
is exploited in treatment of osteoporosis.
We showed a correlation between drinking water fluoride
and serum fluoride in osteosarcoma patients. However,
a Chinese report documented no correlation between
drinking water fluoride and serum fluoride (correlation
coefficient was 0.855) where fluoride in drinking water is
safe and reasonable.[15]
In vitro studies have shown that exposure to fluoride causes
osteoblast proliferation and malignant transformation.[16]
Optimal dose of between 10-100 μmol/L is required to
stimulate bone cell proliferation and differentiation.[16] Also,
a link between p53 mutations and fluoride bone content has
been reported in tissue samples from osteosarcoma patients.[17]
Finding of high serum fluoride levels in osteosarcoma
patients along with high drinking water fluoride level in our
patients suggest a link between fluoride and osteosarcoma.
References
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Lav KH, Baylink DJ. Molecular mechanism of action of fluoride on
bone cells. J Bone Miner Res 1998;13:1660-7.
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control study of osteosarcoma in young persons. Am J Epidemiol
1987;126:118-9.
Susheela AK. A treatise on fluorosis. UNICEF 2003. Delhi. Fluorosis
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Bassin EB, Wypij D, Davis RB, Mittleman MA. Age specific fluoride
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Cohn PD. A brief report on the association of drinking water
fluoridation and the incidence of osteosarcoma among young males.
New Jersey: Department of Health: Environmental Health Service;
1992. p. 1-17.
Yiamouyiannis JA. Fluoridation and cancer. The biology and
epidemiology of bone and oral cancer related to fluoridation.
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Mcguire SM, Vanable ED, Mcguire MH, Buckwalter JA, Douglass CW.
Is there a link between fluoridated water and osteosarcoma? J Am
Dent Assoc 1991;122:39-45.
Gelberg KH, Fitzgerald EF, Synian H, Robert D. Fluoride exposure
and childhood osteosarcoma: A Case Control Study. Am J Public
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Freni SC, Gaylor DW. International trends in the incidence of bone
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Venkateswarlu P. Evaluation of analytical method for fluorine in
biological and related materials. J Dent Res 1990;69:514-21.
Caverzasio J, Palmer G, Suzuki A, Bonjour JP. Mechanism of the
mitogenic effect of fluoride on osteoblast-like cells; evidence for
a G-protein dependent tyrosine phosphorylation process. J Bone
Miner Res 1997;12:1975-83.
Sandhu R, Lal H, Kundu ZS, Kharb S. Serum fluoride and sialic
acid levels in osteosarcoma. Biol Trace Elem Res 2011;144:1-5
(accepted).
Pasquini GM, Davey RA, Michelangeli VP, Grill V, Kaczmarczyk SJ,
Zajac JD. Local secretion of parathyroid hormone related protein
by an osteoblastic osteosarcoma (UMR 106-01) cell line results in
growth inhibition. Bone 2002;31:598-605.
Xiang QY, Liang YX, Chen BH, Wang CS, Zhen LQ, Chan LS,
et al. Study on the application of benchmark dose and biological
monitoring indexes of fluoride in drinking water. Zhonghua Yu Fang
Yi Xue Za Zhi 2004;38:261-4.
Wergedal JE, Lau K-HW, Baylink DJ. Fluoride and bovine bone extract
influence cell proliferation and phosphatase activities in human bone
cell cultures. Clin Orthop Relat Res 1988;233:274-82.
Ramesh N, Vuayaraghavan AS, Desai BS, Natarajan M, Murthy PB,
Pillai KS. Low levels of p53 mutations in Indian patients with
osteosarcoma and the correlation with fluoride levels in bone.
J Environ Pathol Toxicol Oncol 2001;20:237-43.
How to cite this article: Kharb S, Sandhu R, Kundu ZS. Fluoride levels
and osteosarcoma. South Asian J Cancer 2012;1:76-7.
Source of Support: Nil. Conflict of Interest: None declared.
NEWS
The 17th Annual Symposium of the Hong Kong Cancer Institute Clinical Application of Biomarkers in Cancer
Therapy
Date: Saturday 24th November
Sunday 25th November 2012
Venue: Postgraduate Education Centre, Prince of Wales Hospital, Shatin, Hong Kong, China
Organized by: Hong Kong Cancer Institute & Department of Clinical Oncology
In conjunction with the State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong
For further information:
Dr. Brigette Ma
Email: [email protected]
South Asian Journal of Cancer ♦ October-December 2012 ♦ Volume 1 ♦ Issue 2
77
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