Filling in those lines

By Shari Roan

Aug. 25, 2003 12 AM PT

Times Staff Writer

Botox was just the beginning. The popularity of the injectable toxin overwhelmingly proved that people wanted wrinkle cures without surgery.

So as hundreds of thousands of Americans rushed to get the muscle-paralyzing treatment -- even those who had never before sought cosmetic procedures -- plastic surgeons and drug manufacturers were working to come up with other simple tricks to smooth aging skin. They seem to have succeeded.

A new generation of injectable substances -- used to treat facial lines, scars and depressions -- has begun hitting the market. The products, which actually fill in deep wrinkles and small imperfections, are expected to lure the sizable Botox crowd even farther down the path toward eternally youthful skin. Two fillers have recently been approved by the Food and Drug Administration, and several more are awaiting approval. They work in slightly different ways, but all are an improvement over bovine collagen, the filler of choice for the past decade, doctors say.

Not only do the new fillers last longer than traditional collagen injections -- some are even permanent -- they don’t pose the risk of headaches the way Botox injections do.”Botox has drawn a lot of people into the cosmetic dermatologist’s office who hadn’t come in before, and I think the new fillers will draw even more people in,” says Dr. Leslie Baumann, a Miami dermatologist who has investigated several of the new fillers. “People who are used to paying $500 for Botox won’t have sticker shock.”

The botulinum toxin -- Botox for short -- is used primarily to prevent expression lines from forming during facial movement, such as the smile lines around the mouth and those that form between the eyebrows. Fillers actually plump up deeper lines (at least temporarily), most notably the folds that run from nose to mouth and mouth to chin.

Fillers also are used for lip augmentation and to fill acne scars and sunken areas of the face, such as under the eyes. Neither they nor Botox are generally used to treat fine lines and wrinkles, such as those around the eyes.

Soft implants can also be used to fill in deep lines and folds, but those products require surgery and are costly. Injectable fillers require no surgery, little recovery time and they’re significantly cheaper.

Although studies haven’t been completed on all of the substances -- and some doctors are wary of the permanent fillers -- most appear to pose little risk. Moreover, many of the new fillers are synthetic and, like Botox, don’t require allergy testing in advance of treatment. Bovine collagen required one or more allergy tests six weeks before treatment.

“Sales of collagen in the late ‘90s became relatively flat,” says Dr. Douglas Hamilton, a dermatologist and assistant clinical professor at UCLA. “Consumers became increasingly disillusioned that you had to keep going back and redoing the treatment. Consumers started to really push for something more permanent. There was nothing, up until now, in the American market, and the pent-up demand is tremendous.”

Now the sheer range of new products demands that savvy consumers spend some time considering their options -- not only which product to choose, but where to get it.

Some people already have obtained the fillers, even those not yet approved by the FDA, through clinical trials, off-label use and illegal use.

They’re often smuggled from other places in which they’ve been used for years, such as Europe, Canada and Latin America, Baumann says. “We see a lot of illegal fillers in Miami,” she adds, “and I know it’s going to continue to be a problem.”

Tough to detect illegal ones

People who are receiving illegal fillers have no way of knowing the purity of the product and how it has been stored (high temperatures will change the chemical composition of some fillers), she says. In addition, U.S. studies on many of the products haven’t been completed, which should make consumers think carefully about possible unknown risks before opting to have an experimental treatment.

Also, the popularity of the new dermal fillers could trigger problems similar to those surrounding Botox, such as shots being given by untrained practitioners and outside medical offices. In March, the American Society for Dermatologic Surgery announced plans to form a task force to develop guidelines for using facial fillers and cautioned that the treatments should only be administered by trained doctors.

“It’s not something people should approach cavalierly,” Hamilton says. “Botox you can turn over to a registered nurse who has been well-trained and not have problems. But only doctors, he added, should be injecting the permanent wrinkle fillers. Some doctors may rely on nurses, however, to administer the temporary ones. The new fillers differ in composition and durability. Two approved by the FDA in March, CosmoDerm and CosmoPlast, are made of collagen derived from human cells. Doctors say they last slightly longer than bovine collagen.

Several others (Restylane, Perlane and Hylaform) are made from hyaluronic acid gel, a substance that is found naturally in the skin. Studies so far have shown that hyaluronic acid lasts about twice as long as bovine collagen.

“Just like collagen is part of the connective tissue, so is hyaluronic acid,” says Dr. Rhoda Narins, a clinical professor of dermatology at New York University Medical Center. “It provides a lot of volume because it binds to water. You can not only fill with it, but you can lift with it.”

Another filler in development, NuFill, is a poly-lactic acid that may last as long as two years because it stimulates the growth of new collagen.

Other fillers could have even more staying power.

A more durable ‘glue’

One of the most controversial substances is Artefill, which is awaiting FDA approval after receiving a vote of approval from an FDA advisory committee in February. Artefill, which is called Artecoll in Europe, consists of bovine collagen mixed with tiny synthetic microspheres. After injection, the collagen acts as a glue, holding the spheres in place. Eventually, the bovine collagen disintegrates but the body’s own collagen grows in to encapsulate the spheres, which remain in the skin permanently.

Cynthia Hunter, an actress and model in her mid-40s, received Artefill in a clinical trial six years ago and says the treatment has held up.

“I had collagen for years, but I was looking for something more permanent,” she says. “Collagen was really costly and time-consuming. [Artefill] made the biggest difference. I had it in 1997 and, to this day, it still looks as good.”

Other permanent injectable products include Radiance, which uses tiny synthetic spheres, and liquid silicone. Radiance has been approved for the treatment of vocal cord paralysis and is now in clinical trials for cosmetic use. Liquid silicone also has been approved for a different use, but is sometimes used as a cosmetic filler as well.

Some doctors say they are steering clear of all the permanent injectables. “When you have a permanent substance, you have the potential for permanent problems,” says Narins. For example, she won’t use Artefill, which has been linked in Europe to granulomas, permanent bumps under the skin.

Hamilton, who served as a clinical investigator for the product, says Artefill’s formula has been changed significantly since its early use in Europe and that side effects are now rare.

“I get calls from all over the United States about when it’s going to be available,” he says. “The permanent aspect is what people are looking for.”

Regardless of which new products prove most successful, Hamilton predicts consumers will continue to push for even more low-cost treatments that stave off the appearance of aging for as long as possible.

(BEGIN TEXT OF INFOBOX)

What’s next in cosmetic fillers

Several new fillers for facial scars, depressions, expression lines and folds, and for lip enhancement are expected to become available in the next few years.

CosmoDerm and CosmoPlast

Both are made of collagen derived from human cells grown in the lab.

Duration: Four to six months

Status: Approved in March.

Cost: Each about $500.

Restylane and Perlane

Both are made of hyaluronic acid, a type of natural sugar found in the body.

Duration: Six to eight months

Status: Restylane is awaiting FDA approval; Perlane is in clinical trials.

Cost: Has not been established. Each is expected to be $300 to $500 per syringe; one to two syringes are required depending on the size of the area treated.

Hylaform

Made of hyaluronic acid from rooster combs.

Duration: Three to 12 months

Status: Awaiting FDA approval

Cost: Has not been established, but is expected to be about $300 per syringe.

NuFill

Made of a synthetic substance, poly-lactic acid; provokes skin to generate collagen growth.

Duration: 18 to 24 months

Status: One use (wasting of soft tissue due to aging or illness) is awaiting FDA approval; clinical trials are to begin soon on expanded cosmetic uses.

Cost: Has not been established, but is expected to be about $300.

Artefill

Made of permanent plastic-like microspheres mixed with bovine collagen.

Duration: Effects are long-term; skin will continue to age, however.

Status: Awaiting FDA approval.

Cost: Has not been established, but doctors predict it will be about $1,500 per treatment.

Radiance

Made of calcium phosphate microspheres mixed with a polysaccharide gel.

Duration: Might last several years, but studies haven’t been completed.

Status: FDA has approved it for treating vocal cord paralysis; it’s in clinical trials for cosmetic use. It’s often used off-label.

Cost: Has not been established, but doctors predict it will be $750 to $1,500.

Silicone