-
- Jan Andreason used to get slightly rattled every day
-- all in the name of science.
-
- Though in her mid-50s, Andreason has the thin, fragile
bones seldom found in women under 70. Hoping to fight off further ravages
of osteoporosis, she had volunteered in late 1997 as a subject in a year-long
trial of a treatment for the brittle-bone disease.
-
- Participation wasn't difficult. All Andreason had to
do was submit to twice-daily bouts on a 75-pound contraption installed
in her guest bedroom by the Creighton University School of Medicine in
Omaha, Neb. Resembling an upright bathroom scale with handlebars, the vibrating
machine sent a gentle buzzing through every bone in her body.
-
- Most mornings, Andreason read the newspaper or blow-dried
her hair while putting in 10 minutes on the device. Before bedtime, she'd
step on the platform for a second 10-minute buzz.
-
- This shaky therapy may represent the future of bone health.
Preliminary data from Andreason and 51 other postmenopausal recruits suggest
that in some cases, the platform's vibrations may be able to halt the rapid
bone loss that occurs in most older women, says Kenneth J. McLeod, a co-inventor
of the device.
-
- [bone-growth stimulator]
-
- Women at risk for osteoporosis got a daily buzz on this
prototype bone-growth stimulator in a Creighton University study. (McLeod)
-
- Even newer data from a 2-year study of sheep suggest
that scientists might be able to tailor the regimen to increase the mass
of the bones most vulnerable to age-related thinning.
-
- The vibrating platform appears to work by triggering
bones to generate tiny electric fields, explains McLeod of the State University
of New York at Stony Brook, who directed the sheep experiments. These tiny
currents may turn on genes that affect bone remodeling and growth.
-
- The experimental osteoporosis-fighting machine represents
just one technology in a wave of new applications of electric and magnetic
fields (EMFs) to bone injuries and related problems. All build on decades
of work by physicists and surgeons. Though much of this work remains experimental,
the Food and Drug Administration acknowledges that when properly applied,
EMFs can make for good medicine.
-
- [---]
-
- Most news reports about EMFs have focused on emanations
from power lines, building wiring, and appliances. They have chronicled
the continuing controversy over whether these fields have unhealthy effects,
such as perturbed sleep patterns (SN: 1/10/98, p. 29), altered heart rhythms
(SN: 1/30/99, p. 70), and cancer (SN: 2/21/98, p. 119). Yet while these
risks have grabbed headlines, EMFs have been quietly edging into medicine.
-
- Over the past 20 years, FDA has approved EMF generators
for two medical uses. The devices are used frequently to treat bone fractures
that have stopped healing. EMF treatment is also increasingly being applied
to fuse spinal vertebrae in people with intractable back pain.
-
- [ewe]
-
- In a just-completed 2-year study, researchers put the
hind legs of aging ewes -- a model for osteoporosis in people -- on this
vibrating platform for a daily shake. The vibrated legs lost less bone
than the animals' untreated forelegs. Depending on the frequency of the
vibrations, some bones gained mass. (Simon Turner, Colorado State University)
-
- The first inkling of potential benefits from EMFs emerged
during the 1950s, McLeod notes. That's when a series of experiments showed
that bone is piezoelectric, meaning that bending or deforming its crystal
structure creates local electric currents. Physiologists quickly linked
these currents to bone growth in studies that seemed to explain why exercise
strengthens bones and immobilization weakens them. This link suggested
that electric currents could be applied as therapy.
-
- From the beginning of EMFs' ascendancy to medical respectability,
Carl Brighton has been an active player. An orthopedic surgeon at the University
of Pennsylvania School of Medicine in Philadelphia, he was the first doctor
to treat a fracture with EMFs.
-
- In 1971, Brighton was faced with the case of a Camden,
N.J., woman whose 9-month-old ankle fracture steadfastly refused to heal.
From his experiments, Brighton knew that electric fields have the capacity
to knit unfused bones in animals. So, his team poked a metal pin into the
woman's leg, anchored the pin to the broken bone, and hooked it up to a
battery. Then, they put the leg in a cast and sent the woman home with
the battery connected.
-
- "Twelve weeks later, her bone was healed,"
Brighton recalls. The researchers' explanation was that the small current
delivered by the battery to the patient's ankle -- which they measured
at 10 microamps -- spurred specialized cells to grow new bone.
-
- Over the past quarter century, orthopedic researchers
have been refining their techniques. Brighton developed one of the earliest
of those modifications -- delivery of fields via electrodes placed on the
skin instead of on the bone. This method remains the only one that FDA
has approved for fusing spinal vertebrae, he notes.
-
- More recent techniques enable fields to be delivered
without electrodes touching the body. This is the most important therapeutic
advance in recent years, suggests Arthur A. Pilla. A biophysicist at the
Mount Sinai School of Medicine in New York City, he explains that the newer
devices transfer a field's energy into the body from wire coiled around,
but not touching, the injured area.
-
- For EMFs to penetrate the body, the coils must carry
a pulsing electric current, he explains -- not the simpler direct currents
associated with electrode-generated fields. In designing the waveform for
these oscillating fields -- their shape, amplitude, and frequency -- "we
were guided by measurements people were making of natural, mechanically
induced voltages in bone," Pilla recalls. The waveforms of these therapeutic
EMFs differ dramatically from those generated by power lines and indoor
wiring.
-
- His group won FDA approval in 1979 for the use of a pulsing
EMF device for fusing broken bones. Pilla adds that the major manufacturers
of EMF-generating bone-growth stimulators still rely on this basic waveform.
Twenty years later, researchers still argue whether therapeutic benefits
trace to the electric fields or the magnetic fields that these devices
induce.
-
- [---]
-
- To study joint disease, orthopedic surgeon Roy K. Aaron
has been working with a pulsed EMF technique. He and Deborah Ciombor, both
at Brown University School of Medicine in Providence, R.I. recently used
it to treat a strain of guinea pigs that ordinarily begin showing signs
of osteoarthritis of the knee by 1 year of age. The researchers began EMF
therapy on one group of animals on their first birthday and continued it
for 6 months. Another group received no treatment. At 18 months of age,
most of the treated guinea pigs had relatively mild disease and a few appeared
to be free of pain. All the untreated animals were crippled by the oseoarthritis.
-
- [turkey wing bones]
-
- Yellow dye highlights new growth in these sections of
wing bones from live turkeys. In contrast to the wing treated with coils
triggering a very tiny current in bone (left), the one placed in inactive
coils (right) shows no new tissue. (McLeod)
-
- "I was so surprised by the difference between the
[treated and untreated groups] that I repeated the experiment," Aaron
says. The results were the same. The data demonstrate that this treatment
does not simply reduce symptoms, such as swelling, but actually modifies
the development of disease, he says.
-
- EMF therapy also helps people with established joint
disease, Aaron says. This month, he's completing a clinical trial of EMF
therapy for men and women with advanced osteoarthritis in their knees.
-
- Two previous studies had found that EMFs reduce pain
and swelling. EMFs also have that effect in his new trial -- presumably,
he says, "by changing the chemistry of the joint." Studies by
his team and others indicate that these fields can increase a joint's production
of natural anti-inflammatory agents, such as transforming growth factor-beta.
-
- Not surprisingly, Aaron notes, medical supply companies
are now developing products, such as a glove with coils, to deliver EMFs
to arthritis-savaged joints.
-
- Softer tissues also respond to these fields. For instance,
Pilla observes that many people with bone breaks experience significant
pain in muscles around their injuries. Shortly after EMF therapy begins,
however, that pain disappears.
-
- Though the mechanism remains elusive, Pilla says, the
treatment seems to affect swelling, which can cause pain. If this proves
true, he says, EMFs might benefit people with carpal tunnel syndrome, where
swelling in the wrist pinches nerves going to the fingers.
-
- Indeed, that's a possibility that Betty F. Sisken of
the University of Kentucky College of Medicine in Lexington would like
to explore. Currently, she's probing EMFs' direct influence on nerves.
-
- In their initial studies, she and her colleagues crushed
a nerve in the hind leg of rats and then treated the animals with EMFs
for 4 hours daily. In one 6-day-long experiment, the treatment speeded
the nerve's recovery by 22 percent. In follow-up tests -- where 16 rats
received EMFs for 40 days and an equal number were allowed to heal unaided
-- treated animals again showed an accelerated recovery.
-
- [---]
-
- Despite some exploration of EMFs to heal nerves and other
soft tissue, the majority of studies continue to focus on bone.
-
- James T. Ryaby, vice president of OrthoLogic, a medical
devices company in Tempe, Ariz., has been using what he calls combined
fields -- oscillating magnetic fields superimposed on a static magnetic
field. They appear to spur bone growth more quickly than the older type
of pulsed EMFs, Ryaby says.
-
- [treated bones]
-
- Sections of bone from healthy female rat (left) and two
whose ovaries were removed 6 weeks earlier to model women who lose bone
after menopause. Bone from animal treated with combined EMFs (middle) shows
less loss than one from untreated rat (right). (John H. Kinney, Lawrence
Livermore National Laboratory)
-
- What's more, the combined-field devices require just
a small percentage of the power used by typical pulsed EMF generators.
This means the combined-field devices can run on conventional batteries,
Ryaby says. His company is testing such a device for fusing vertebrae in
patients with back pain.
-
- More tantalizing, says Ryaby, are the data from a just
completed study with female rats suggesting that the combined fields can
reverse the kind of bone loss women experience after menopause. After removing
the rodents' ovaries to simulate a postmenopausal state, Ryaby's team watched
the animals quickly lose bone. Six weeks later, some of the rats began
receiving combined-field therapy for 30 minutes a day. Within a little
more than a month, he says, the treated animals were regaining lost bone
while their untreated counterparts continued to lose it.
-
- As exciting as the data are, Ryaby says his company has
no plans to develop the technology for human use. Women just aren't likely
to sign up for such therapy at menopause knowing that they would likely
have to continue it the rest of their lives.
-
- Indeed, McLeod says, "a fear factor associated with
EMFs clearly haunts the therapeutic field."
-
- Because of the stigma of EMFs, McLeod and Clint Rubin
have been looking for an alternative. The Stony Brook pair may have found
it in the bones themselves. Over the past 20 years, they have demonstrated
that during walking, jumping, or even just maintaining a balanced posture,
muscles exert enough strain on bones to generate microcurrents of electricity.
The discovery inspired the scientists to create a device to encourage the
body to make its own electric fields for building bones.
-
- [---]
-
- The resulting vibrating platform "is highly innovative
but not ready for prime time," says endocrinologist Robert Marcus
of the Veterans Affairs Medical Center in Palo Alto, Calif. Overall, the
benefit for women taking part in the Creighton study, led by Diane Cullen,
"was less than overwhelming," he says. He acknowledges, however,
that certain subgroups -- such as those, like Andreason, who started out
with the thinnest bones -- appeared to derive benefit. He's begun using
the device in a pilot project.
-
- The platform's commercial developer, Exogen of Piscataway,
N.J., will fine-tune the device's frequency and the recommended treatment
times before undertaking any study of a larger group in women, says Jack
T. Ryaby, the company's scientific director.
-
- McLeod says that in his newest tests with aging sheep,
platforms vibrating at 90 Hz increased bone mass. This suggests that tripling
the vibration frequency of the platform used for the Creighton trial might
build new bone, not just stabilize loss.
-
- Moreover, if the sheep data translate to people, he suspects
that women would need just 8 minutes a day on the faster-vibrating device.
"This is really exciting because 8 minutes is easy," he says.
-
- For the larger range of problems, Pilla holds that applied
EMFs will be more useful. However, medical generators today produce fields
with a waveform that probably is far from optimal, he says. Though experiments
aimed at improving these generators and securing FDA approval for devices
with different waveforms would be costly, the payoff could be tremendous,
he believes.
-
- [---]
-
- To get to that payoff, scientists need to learn more
about why these fields work. Many of the researchers who are developing
new applications for these fields are therefore asking, What do cells of
the body see in EMFs?
-
- "These fields are too weak to power the biology
or biochemistry that is active here," Pilla says. "They only
deliver enough energy to trigger something" -- much like a pacemaker
triggers contractions in the heart.
-
- In Bioelectrochemistry and Bioenergetics last February,
he and his colleagues reported finding that pulsed EMFs appear to increase
the binding of ions to receptors on the surface of cells. For instance,
they've witnessed enhanced binding of calcium to the regulatory molecule
called calmodulin. This difference may prove important in stimulation of
bone-cell growth by EMFs, Pilla says.
-
- EMFs can also increase bone cells' production of insulinlike
growth factor II, according to test-tube experiments by Ryaby of OrthoLogic
and his colleagues. This hormonelike molecule plays a key role in bone
growth and may be regulated by calcium binding to calmodulin.
-
- At the BioElectromagnetics Society meeting last June,
Sisken's group reported on test-tube experiments showing that pulsed EMFs
can turn on a gene in damaged nerves. That gene plays a role in triggering
growth-related repair.
-
- Brighton is also working to elucidate which genes are
altered by EMFs. "This is to me what's most exciting," he says.
"We can turn genes on and off with this stuff."
-
- McLeod and his group tend to focus on physical effects
of fields on cells. Their data indicate that EMFs may bias the movement
of cell structures that are otherwise jostled by the random pushes and
pulls of chemical and physical processes, McLeod says. He also finds that
EMFs can alter the environment in which cells grow and move within the
body. For instance, electric fields may alter the stickiness of surrounding
proteins. Indeed, he argues that changes in a cell's behavior may trace
as much to environmental alterations as to the cell's gene activity or
membrane effects.
-
- Changes in cellular behavior may not be limited to the
fields being used in therapy today, however. Aaron, for instance, has examined
effects of the 60-Hz fields generated by power lines and home wiring.
-
- In the August Bioelectromagnetics, his group reports
that field strengths similar to those in the home and workplace increased
production of a protein that regulates proliferation and development of
cells destined to become bone. The EMFs also stimulated some maturation
in cells.
-
- Aaron concludes that fields associated with electric
power may exert a beneficial influence on such tissues rather than harm
them.
-
- All this basic research may add up to more effective
devices and ubiquitous applications. For instance, Pilla says he believes
generators might one day be miniaturized to the size of a dime and cost
next to nothing.
-
- He envisions disposable bandages incorporating a tiny
EMF device that would treat problems ranging from ankle sprains to bedsores.
-
-
- References:
-
- Aaron, R.K., D.M. Ciombor, et al. 1999. Power frequency
fields
- promote cell differentiation coincident with an increase
in
- transforming growth factor-b 1 expression. Bioelectromagnetics
- 20(August):453.
-
- Huang, R.P., C.T. Rubin, and K.J. McLeod. 1999. Changes
in
- postural muscle dynamics as a function of age. Journal
of
- Gerontology: Biological Sciences SUA 8(August).
-
- Longo, F.M. . . . and B.F. Sisken. 1999. Electromagnetic
- fields influence NGF activity and levels following sciatic
- nerve transection. Journal of Neuroscience Research 55:230.
-
- Markov, M.S., and A.A. Pilla. 1999. Static m T-level
magnetic
- fields modulate myosin phosphorylation via kinetic effects
on
- calcium binding to calmodulin. In Proceedings, 2nd World
- Congress on Electricity and Magnetism in Biology and
Medicine.
- Plenum Press, New York.
-
- McLeod, K.J. . . . and C.T. Rubin. 1999. Frequency and
- duration optimization of dynamic loading protocols for
the
- reversal of osteopenia. Meeting of the Orthopaedic Research
- Society. February. Anaheim, Calif.
-
- McLeod, K.J., C.T. Rubin, et al. 1998. Skeletal cell
stresses
- and bone adaptation. American Journal of the Medical
Sciences
- 316(September):176.
-
- Midkiff, P., and B.F. Sisken. 1999. Nerve regeneration
in
- vitro: Mechanism of stimulation with pulsed radiofrequency
- fields. Meeting of the Bioelectromagnetic Society. June.
Long
- Beach.
-
- Muehsam, D.J., and A.A. Pilla. 1999. The sensitivity
of cells
- and tissues to exogenous fields: Effects of target system
- initial state. Bioelectrochemistry and Bioenergetics
- 48(February):35.
-
- Pilla, A.A. 1999. State of the art in electromagnetic
- therapeutics: Soft tissue applications. In Proceedings,
2nd
- World Congress on Electricity and Magnetism in Biology
and
- Medicine. Plenum Press. New York.
-
- Pilla, A.A. . . . and B.F. Sisken. 1999. EMF signals
and
- ion/ligand binding kinetics: Prediction of bioeffective
- waveform parameters. Bioelectrochemistry and Bioenergetics
- 48(February):27.
-
- Ryaby, J.T. 1998. Clinical effects of electromagnetic
and
- electric fields on fracture healing. Clinical Orthopaedics
- 355(October):S205.
-
- Further Readings:
-
- Fitzsimmons, R.J., J.T. Ryaby, et al. 1995. Combined
magnetic
- fields increase insulin-like growth factor-II in TE-85
human
- osteosarcoma bone cell cultures. Endocrinology 136:3100.
-
- Koth, L.C. . . . A.A. Pilla, et al. 1999. Effect of pulsed
- radio frequency stimulation on wound healing: A double-blind
- pilot clinical study. In Proceedings, 2nd World Congress
on
- Electricity and Magnetism in Biology and Medicine. Plenum
- Press. New York.
-
- Markov, M.S., and A.A. Pilla. 1997. Weak static magnetic
field
- modulation of myosin phosphorylation in a cell-free
- preparation: Calcium dependence. Bioelectrochemistry
and
- Bioenergetics 43:233.
-
- McLeod, K.J., and C.T. Rubin. 1992. The effect of
- low-frequency electrical fields on osteogenesis. Journal
of
- Bone and Joint Surgery.
-
- ______. 1990. Frequency specific modulation of bone adaptation
- by induced electric fields. Journal of Theoretical Biology
- 145:385.
-
- Pilla, A.A. 1993. State of the art in electromagnetic
- therapeutics. In Electricity and Magnetism in Biology
and
- Medicine. Blank, M., ed. San Francisco Press.
-
- Pilla, A,A., D.J. Muehsam, and M.S. Markov. A dynamical
- systems/Larmor precession model for weak magnetic field
- bioeffects: Ion binding and orientation of bound water
- molecules. Bioelectrochemistry and Bioenergetics 43:239.
-
- Raloff, J. 1999. EMFs -- doubts linger over possible
risks.
- Science News 156(July 3):12.
-
- ______. 1999. Electromagnetic fields may damage hearts.
- Science News 155(Jan. 30):70.
-
- ______. 1998. Electromagnetic fields may trigger enzymes.
- Science News 153(Feb. 21):119.
-
- ______. 1998. EMFs, biological influences. Science News
- 153(Jan. 10):29.
-
- Rubin, C.T. . . . and K.J. McLeod. 1993. Optimization
of
- electric field parameters for the control of bone remodeling:
- Exploitation of an indigenous mechanism for the prevention
of
- osteopenia. Journal of Bone and Mineral Research 8:S573.
-
- Sisken, B.F., and J. Walker. 1995. Therapeutic aspects
of
|