Osteoporosis patients could soon ditch daily injection pens for an implantable microchip that releases medication at the push of a remote-controlled button, according to a new study appearing 15 February in the journal Science Translational Medicine.

The clinical trial, composed of a group of seven women with osteoporosis in Denmark, is the first to test a wirelessly-controlled microchip capable of releasing drugs into the body at any time.

The women received only 19 to 20 doses of the drug in the trial, but at news briefing today at the AAAS Annual Meeting, the researchers discussed their plans to develop a chip that delivers 365 days' worth of medicine.

"Patients will be freed from having to remember to take their medication and don't have to experience the pain of multiple injections," said Robert Farra, president and CEO of Microchips Inc., the Massachusetts-based company behind the device. Farra is a co-author of the study, along with colleagues from MIT, Harvard Medical School, OnDemand Therapeutics Inc., and Case Western Reserve University.

Unlike most drug delivery devices, which release small amounts of drug slowly over time, the microchip releases medication on command from an external wireless device. This controlled system gets medicine into the bloodstream quickly, similar to an injection. "Physicians will be able to seamlessly adjust their patients' therapy using a computer or cell phone," said Farra.

The authors think the microchip may be a more appealing and possibly cheaper alternative to long-term use of prefilled daily injection pens. Patients with severe osteoporosis often have to give themselves daily injections of medication that requires refrigeration. Aside from the psychological burden of daily injections, older people may have arthritis or other health problems that make injections physically difficult.

Moreover, since osteoporosis is a "silent" disease--affected individuals don't feel better or worse as their bone density decreases--many patients simply stop taking medication to avoid the hassle of daily injections.

The implant could help circumvent the high drop-off in patient compliance, Farra said. "In everyday medical practice," he noted, "adherence to drug treatment regimes is one of the major problems of health care."

Roughly the size of a pacemaker, the device holds daily doses of a drug inside tiny wells that pop open either on a pre-programmed schedule or via a wireless signal.



Adapting microchip technology for human use was no small feat. The team first had to figure out a way to seal each reservoir to be airtight at room temperature. They developed a special compression welding process designed to provide a long-term seal. The researchers also developed a metal layer, which is strong enough to protect the contents of each well, but thin enough to dissolve on command.

At the news briefing, the researchers said they are developing microchips with wells holding up to a milligram dose of medicine. This means that most of the drugs that could be delivered by the device would need to be small dose, potent medications. Drugs to treat multiple sclerosis, heart disease, and perhaps cancer would be good candidates for chip delivery, while large-dose medications such as insulin or antibiotics would not work in the device.

Despite the microchip's proven ability to deliver drugs in the lab, a fibrous collagen-based membrane tended to develop around the device once it was implanted into animals. The researchers were concerned that this fibrous tissue potentially could slow down the absorption of medication, and one of the aims of the study was to determine if the membrane decreased the device's effectiveness.

The researchers implanted the microchip just below the waistline into seven women between the ages of 65 and 70. The procedure can be performed in a doctor's office with local anesthetic.

Tracking the women for 12 months, the team showed that the implant delivered the osteoporosis drug teriparatide (sold under the brand name Forteo) just as effectively as daily injections. A fibrous membrane did form around the device, but it did not interfere with drug delivery and was "thin enough to read the microchip label through," Farra said.

Treatment improved bone formation and reduced the risk of bone fracture, as evidenced by the presence of biochemical markers signaling bone formation, bone mass, and bone resorption. "And there is much less variation from dose to dose than injections," Langer said, "so it's safer and more effective in that sense."

Farra said the cost of the device, the drug, and the implantation procedure for a year's worth of osteoporosis medicine would be comparable to the price of a year's worth of Forteo injections. The company hopes to make the device available for mainstream osteoporosis treatment in five years.

In the meantime, they envision a host of other uses for the device, including using it to deliver several different drugs at once, weaning a patient on and off a certain medication by releasing different concentrations of a drug over time, or even replacing a lifetime of vaccination injections with one chip.