October 11, 2002
A Critique of the Phipps Study on Hip Fracture
by Paul Connett
Professor of Chemistry
St. Lawrence University
The Phipps study published in the British Medical
Journal on Oct 6, 2000 (www.bmj.com/cgi/content/full/321/7265/860),
is one of the studies on hip fracture which I examined as part of my invited
peer review of the
York report (A summary of the York report was also published in the same
issue of the BMJ). The York team incorporated Kathy Phipps' data in their
meta-analysis of bone fracture. Phipps' paper is one of the 18 (3 unpublished
and one abstract) studies done since 1990. 10 of these studies show an association
between increased hip fracture and fluoridation and 8 do not. Phipps is
one that did not.
I am glad that Phipps does not hide her enthusiasm for water fluoridation, when she declares without a supporting reference that, "the benefit of fluoridation in the prevention of dental caries has been overwhelmingly substantiated". However, the notion that fluoride protects against hip fracture, in addition to the marginal benefits to teeth it may have, is a stretch in the context of the 10 studies which conflict with Phipps' results. While it is true that her study is superior to some because she controls for 13 variables, and she uses bone mineral density as an indirect confirmation that those who had more exposure to fluoridated water have accumulated more fluoride, she still lacks the actual levels of fluoride that have accumulated in the bones. Instead she relies for her comparisons on the number of years of exposure to fluoridated water. For the study period 1971-1990, the authors give the mean age of the women examined as 74.5, 74.2 and 73.9 years in the three groups observed: no exposure, mixed exposure and continuous exposure, respectively. If this was their age in 1990, then the mean age of those exposed at the beginning of the study in 1971 was 53.9 years. Thus most of their known exposure was after menopause, which according to some authors could make a difference with respect to fluoride's impacts (Danielsen, 1992), although not all agree on this point (Kurtio, 1999).
However, the most disturbing aspect of the report is how much attention is given to the DECREASE of hip fracture incidence and how little attention is given to the INCREASE in the incidence of wrist fracture in the group exposed for 20 years of water fluoridation. The ostensible reason for this is that the decrease in hip fracture incidence is deemed statistically significant while the increase in wrist fracture is deemed statistically insignificant. However, when one considers the basis of the claims of significance and insignificance the difference between the two results is very slender indeed. This is particularly important when it is recognized that the "significance" for the hip fracture decrease and the "non-significance" of the wrist fracture increase only emerges after adjustment for 12 variables. It raises the question of how accurate these adjustments were, if such fine distinctions are going to be made.
Here are the details. In Table 5, after age adjustment, the authors report a relative risk of 0.85 for hip fractures for the continuously exposed group, with a 95% confidence interval (CI) of 0.63 to 1.14 and a p-value of 0.287. Translated this indicates a statistically non-significant decrease of 15% in the incidence of hip fracture. It is statistically non-significant because the CI overlaps with 1.00 and the p-value is greater than 0.05. In the same table, the authors report the relative risk for hip fracture, after adjustment for 12 more variables, as 0.69, with a CI of 0.50 to 0.96 and a p-value of 0.028. This translates to a decrease in hip fracture of 31% and it is now statistically significant because the 95% confidence interval (0.55 to 0.96) no longer overlaps with 1.00 - but only just - and the p-value is less than 0.05.
If we now compare this with the wrist fracture figures we find the following. The age adjusted relative risk for wrist fracture for the women continuously exposed is 1.36 (CI: 1.07 - 1.73), p-value 0.012. This translates to a 36% increase in wrist fracture which is statistically significant, because the 95% CI does not include the value of 1.00, and the p-value is less than 0.05. After adjustment for 12 more variables, these figures become 1.32 (CI: 1.00 to 1.71) with a p-value of 0.051. This is now declared as a non-significant finding because, even though the relative risk has hardly changed, despite the consideration of 12 variables, the CI just overlaps with 1.00, in fact the lower value is actually at 1.00 and the p-value is just over 0.05 at 0.051! This is about as close as one can get to a significant result without actually calling it statistically significant. This is so close in fact, that this result must bring into question how accurately these adjustments, and the assumptions on which they were based, were performed.
In this respect it is intriguing that when the York team considered these same results from Phipps et al they recorded the adjusted figure as 1.3 (1.02, 1.7) (see their appendix C8 "Bone Studies: Individual Study results") and this is the number reported in the final version of the York Review (Oct 6, 2000). This table can be examined on the web at www.york.ac.uk/inst/crd/fluores.htm. The table can be found in the appendix identified as appc8.doc.
The fact that this number makes the difference between a so-called significant result and a non-significant result, raises a serious question as to why two reports published on the same day have different values - one significant the other non-significant. How did this number get changed and by whom?
These issues need very careful evaluation because many news outlets and health wire services are broadcasting the "good news" (see article below) that water fluoridation is good for bones. In my view this promotion is reckless based upon such slender evidence, and in the context of several important factors: a) 50% of all fluoride ingested accumulates in our bones b) water fluoridation is not the only source of fluoride we are exposed to c) high doses of fluoride used to treat patients with osteoporosis in an effort to harden their bones has led to an increase not a decrease in hip fracture d) this study also indicates an increase in wrist fracture, as close to significance as you can get and e) there are 10 studies (3 unpublished) which indicate an increase in hip fracture associated with fluoride in water and f) one of these studies shows an almost dose-response increase above 1 ppm exposure (Li et al, 1999, unpublished).
All the references cited above can be found in articles I have authored or co-authored on our webpage http://www.fluoridealert.org
Dr. Paul Connett,
Professor of Chemistry,
St. Lawrence University,
Canton, NY 13617.
The following is an article on Phipps' Study from the Pittsburgh Post-Gazette
October 6, 2000
Fluoridated Water Reduces Hip Fracture Risk in Women: Risk of Fractures in Spine Also Drops, New Study Finds
By Anita Srikameswaran
Women whose drinking water contains fluoride have a lower risk of hip and spine fractures, new research shows.
According to a multicenter study published in this week's British Medical Journal, women who had used fluoridated water for 20 years had a 31 percent lower risk of hip fracture and a 27 percent lower risk of vertebral fracture than women who didn't.
Women who have osteoporosis, or a loss of bone density, are predisposed to develop such fractures. Those who were exposed to fluoridated water had more bone at key sites in the spine and hip than did the unexposed women.
Some previous studies suggested that fluoridation increases the risk for fractures while others found the risk was lowered, said senior investigator Jane Cauley, of the University of Pittsburgh's Graduate School of Public Health.
Such studies "basically compared hip fracture rates in one area that didn't get fluoridated water with another area that did get fluoridated water," she explained. "There's no individual data."
Nearly 6,000 women aged 65 and older participated in the new study. Factors associated with osteoporosis, such as smoking, body weight and use of estrogen replacement therapy, were accounted for in the analysis.
In addition to the findings about hip and spine fractures, researchers discovered that fluoride exposed women actually had a 32 percent higher risk for wrist fractures and that they had more bone loss at the end of the radius, one of the long bones of the forearm.
"We don't understand it completely," Cauley said. She added that there are two kinds of bone and the wrist combines them in a different proportion from the hips and vertebrae. The explanation may lie in that difference.
It is clear, though, that hip and spine fractures can lead to a poor quality of life or even to death. Wrist fractures are not associated with mortality, she added.
If more people use fluoridated water, the number of hip and wrist fractures could drop significantly.
Opponents of water fluoridation say that fluoride has been linked to gene damage and Alzheimer's disease, and causes cancer in rats and mice. An October 1999 report from the Centers for Disease Control and Prevention states that "no credible evidence supports an association between fluoridation and any of these conditions."
"Fluoridated water has had a major impact on lowering the incidence of dental cavities," Cauley said. "I view it as one of the public health successes of 20th century."
Separately, the Journal published the results of an examination of 50 years of research on the safety of adding fluoride to drinking water. It found no evidence of harm.
The review covered 214 studies.
Fluoride opponents dismissed the research, saying it ignored some studies showing adverse effects and did not account for fluoride from other sources.
The research was commissioned by the British government, which is contemplating a nationwide fluoridation program. Fluoride is added to the water in some British communities but not in others.
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