Published: Apr 11, 2013
By Kristina Fiore , Staff Writer, MedPage Today

Action Points

• This is a double-blind, placebo controlled trial designed to evaluate the bone effects of several doses of fluoride in postmenopausal women with osteopenia.
• The study found no effect of fluorides compared with placebo on bone mineral density.

Low-dose fluoride didn’t improve bone mineral density (BMD) in postmenopausal women with osteopenia, researchers found.

In a randomized controlled trial, none of three doses of fluoride — 2.5 mg, 5 mg, or 10 mg — significantly raised BMD of the lumbar spine to a greater extent than placebo over the course of a year, Andrew Grey, MD, of the University of Auckland in New Zealand, and colleagues reported online in the Journal of Clinical Endocrinology and Metabolism.

Fluoride supplementation “is unlikely to be an effective therapy for osteoporosis,” they wrote.

Carol Levy, MD, of the Icahn School of Medicine at Mount Sinai in New York, who was not involved in the study, said the findings are in line with endocrinologists’ expectations.

“Most of us hadn’t believed that fluoride was a major tool in terms of treating osteoporosis,” Levy told MedPage Today. “This study is important, however, because it does confirm that finding, and reassures endocrinologists that our instincts were correct on this.”

Most treatments for preventing fracture work by decreasing bone resorption, but researchers also have been interested in therapies such as fluoride that primarily increase bone formation. The element has long been known to stimulate osteoblast growth and build bone.

However, findings from several trials have not been clear about fluoride’s efficacy in preventing fracture. Some studies of high-dose fluoride have shown increased bone formation and bone mineral density — at a cost of impaired bone mineralization and the possibility of adverse effects on fracture risk, the researchers noted.

On the other hand, a meta-analysis suggested that lower doses of fluoride may increase BMD and reduce fracture risk.

Grey and colleagues conducted a randomized, double-blind, placebo-controlled trial of 180 postmenopausal women with osteopenia at their academic research center. The women, who were recruited between June 2009 and March 2010, were at least 5 years past menopause.

They received either placebo or one of 3 doses of fluoride: 2.5 mg, 5 mg, or 10 mg.

The primary endpoint was change in lumbar spine BMD at 1 year. Secondary endpoints included changes in hip and total BMD, and markers of bone turnover.

Grey and colleagues found that none of the three doses of fluoride altered lumbar BMD at a significantly greater rate than placebo. Mean changes from baseline were as follows:

• Placebo: -0.4%
• 2.5 mg fluoride: -0.7%
• 5 mg fluoride: 0%
• 10 mg fluoride: 0.2%

Nor were there any significant differences between groups in total hip or total body BMD, the researchers reported.

However, these lower doses of fluoride did appear to “weakly activate bone remodeling,” with significant changes in at least one marker of bone formation.

Levels of procollagen type-I N-terminal propeptide (P1NP) increased significantly in the 5-mg and 10-mg fluoride groups compared with placebo. Levels rose by 7.5% (P=0.04) and 14.8% (P=0.005), respectively.

Yet there were no differences between placebo and any of the fluoride groups in levels of beta-C-terminal telopeptide type I collagen (beta-CTX), they reported.

There were no fractures in the placebo group, one metatarsal fracture in the 2.5-mg fluoride group, two fractures in the 5-mg group (one in the ankle and one in the calcaneus), and two fractures in the 10-mg group (one in the rib and one in the humerus).

Grey and colleagues warned that the trial wasn’t powered to evaluate fracture risk, but the “weak effects we observed on surrogates for skeletal health suggest that low-dose fluoride is unlikely to substantially reduce fracture risk,” they wrote.

They also noted that five patients in fluoride groups stopped treatment because of gastrointestinal symptoms, and concluded that the results “do not support the establishment of trials to investigate the effects of low-dose fluoride on fracture risk.”