Earlier this month, researchers announced a new chemical fluoride compound that could help reverse the ravages of spinal osteoporosis in hundreds of thousands of American women.
This is the story of how the promising new treatment almost was not developed.Its future had been in doubt for years. It had fallen through the cracks in the nation's drug development program, a so-called orphan drug that might never have been researched and tested without some unusual - and sometimes heroic - efforts.
It was rescued by a researcher who likes to work with orphan drugs, the president of a small drug company who was looking for a treatment for his grandmother's osteoporosis and by a National Institutes of Health safety net to catch some drugs that fall through the cracks.
As a result, this story has a happy ending. But health experts fear that many other potentially significant orphan drugs, for which there is no real hope of profitability, are being overlooked by pharmaceutical companies and falling by the wayside, to the disadvantage of millions of sick and suffering Americans.
According to researchers in Dallas, the new treatment for osteoporosis, a slow-release sodium fluoride compound used in conjunction with calcium citrate, has provided the first safe and effective treatment for the spine-curving disorder that affects about 5 million women in the United States.
The timed-release compound, which significantly reduced the spinal fracture rate in treated women, still has to be approved for use by the federal Food and Drug Administration, a process that could take up to two years.
But the fact that the treatment has gotten this far is quite surprising.
Drug companies had turned their backs on fluoride because they didn't want to conduct expensive clinical trials to prove the mineral's worth. It was one of nature's drugs, without patent protection, and the companies feared development costs would never be made up.
Fluoride has languished in no man's land for more than 15 years. Some doctors have provided it in roundabout ways to osteoporosis patients - advising them, for example, to buy fluoride compounds that are available at drugstores.
Other doctors have been telling patients to take fluoride-containing pills sold to prevent dental cavities.
"Fluoride is available without a prescription," said Dr. Gretajo Northrop, an endocrinologist at Rush-Presbyterian-St. Luke's Medical Center. "I've been on the drug myself for the last eight or nine years. There's no problem in showing an increase in bone density. I must have 200 patients on the compound right now."
But fluoride has never been approved by the FDA as a treatment for spinal osteoporosis, a condition linked to a decline in estrogen production after menopause. The condition results in crush fractures in the spinal column, which causes curvature of the spine, or "widow's hump," shortened stature, protruding stomach, back pain and gastrointestinal disorders.
The reason the FDA hasn't approved fluoride is that no drug company has performed the types of clinical trials needed to prove that it is both safe and effective.
As a result, thousands of women are not getting any kind of fluoride treatment, and there have been major concerns about fluoride's frequent side effects.
Many people cannot take available fluoride because the compounds react with stomach acids to produce nausea, heartburn and other gas-trointestintal problems. Medical experts were also worried about whether the new bone is as strong as normal bone.
Doctors were in a quandary.
But in Dallas, some bright minds found a way out of the problem.
University of Texas Southwestern Medical Center researchers, headed by Dr. Charles Pak, chief of mineral metabolism, put fluoride on the fast track by showing that the slow-release form overcame the stomach complications and that the new bone formed was normal.
Pak has developed four other orphan drugs, including potassium citrate, which prevents kidney stone formation. He knew that, in some cases, the federal government will grant drug companies exclusive sales rights or special tax breaks to market an orphan drug. He also knew about Mission Pharmacal Co., a small San Antonio company involved in making orphan drugs.
"I was interested right away because my grandmother suffers from osteoporosis and I wanted to help her," said Neill Walsdorf, Mission's president. The company makes Urocit-K, Pak's anti-kidney-stone drug, which Walsdorf himself takes.
Mission Pharmacal developed a special capsule that allowed sodium fluoride to leak out slowly in the intestine, where it did not cause the side effects in the stomach.
At the same time, the FDA guided Pak's clinical studies to make sure that they would answer the safety and efficacy questions the agency was interested in.
But the key was the financial support to conduct the human trials with sodium fluoride, which was provided by the National Institutes of Health and the University of Texas Southwestern Medical Center.