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New indications, studies on the way for bone growth stimulators

2006 Special Focus: Bone Grwoth StimulatorsFor decades orthopedic surgeons have used bone growth stimulation to treat fractures and nonunions, and to fuse lumbar spines. Support for these treatments came from a host of clinical studies that over the years have shown the devices work when used properly — even if no one knew exactly why.

However, some criticisms of the technology have lingered. Research into the science behind bone growth stimulation and its method of action has lagged behind adoption of the technology.

For various reasons, adoption has also come slowly in the United States, though more than 250,000 long bone nonunions that reportedly occur annually might benefit from the kind of kick-start bone growth stimulators are believed to provide. According to one estimate, the market for appendicular application of bone growth stimulation was expected to total around $400 million last year, far below the potential market size.

Experts also agree it will take many more studies to find whether these devices indeed lead to improved quality of life and quicker return to work, as some claim.

But, progress is being made. Device manufacturers and researchers at laboratories worldwide have started more in-depth studies into what happens when ultrasound, pulsed electromagnetic fields (PEMF), capacitive coupling, direct electrical current and combined magnetic fields (CMF) energy waves get applied to bone.

“All of the growth factors that are believed to regulate very early stages of, say, the fracture healing process, have been shown to be upregulated with the different bone growth stimulation technologies,” said James T. Ryaby, PhD, who has researched the science behind this technology since the 1970s. Ryaby and colleagues were the first to evaluate the role of growth factors in bone growth stimulation technologies, and published on CMF effects on the insulin-like growth factor pathway. CMF bone growth stimulation technology is marketed by DJ Ortho.

Interestingly, some studies conducted independently of one another have recently suggested bone growth stimulation technology isn’t just for bones any more. It may eventually prove effective for such soft tissue applications as ligament and tendon injuries, regenerating cartilage and healing other musculoskeletal tissues. The basis for that prediction: The energy apparently also helps upregulate growth factors related to soft tissue healing, like fibroblast growth factor-2 (FGF-2).

Quality-of-life issues

There are other indications that we’re pursuing, like osteoarthritis, disc repair and ulcer healing.
— Bruce Simon

At a more practical level, “The new clinical studies on the horizon are looking more at SF-36 and quality of life. We’re very aware that we need more health-economic information and better studies of that type,” said Neill Pounder, PhD, senior research project manager, Smith & Nephew, Memphis. Smith & Nephew manufactures the only FDA-approved ultrasound-based bone growth stimulator.

“I think the potential for these electromagnetic devices is still wide open,” said Bruce Simon, PhD, another scientist who has extensively researched this field. He is director of research at EBI, Parsippany, N.J., which manufactures a full line of bone growth stimulation products using direct current, capacitive coupling and pulsed electromagnetic fields (PEMF) waveforms.

“There are other indications that we’re pursuing, like osteoarthritis, disc repair and ulcer healing. There’s great potential wherever the body … has some type of trauma or wound, because it uses electrical fields as part of the healing mechanism. If you could understand how to stimulate the appropriate cells at the appropriate time to upregulate the growth factors, it’s a technology with tremendous potential,” Simon told Orthopedics Today.

New directions

A greater understanding of the mechanism of action behind these systems has helped investigators identify some new indications for bone growth stimulation. For example, the FDA recently approved the device solely indicated for use in cervical spine fusions, the Cervical-Stim product (Orthofix; Huntersville, N.C).

This year Orthofix plans to start a clinical trial to get a fresh fracture indication for its Physio-Stim long bone system, Orthofix president Gary Henley told Orthopedics Today. Canadian investigators at four centers are also now involved in a randomized controlled trial looking at the effects of ultrasound for healing fresh tibial fractures fixed with intramedullary nails.

Added to the push for new indications: Many manufacturers producing the dozen or so bone growth stimulation devices sold in the United States have redesigned their products to make them more patient-friendly. Some now tout lighter, more compact units and more ergonomic models. Others are powered by rechargeable batteries that manufacturers say promotes better patient compliance.

FDA approvals

The nonspinal bone growth stimulators have been FDA approved for long bone nonunions, defined as those that show lack of radiographic progression three months after treatment. Smith & Nephew’s Exogen system gained initial FDA approval for fresh, closed, posteriorly displaced distal radius fractures and fresh, close or Grade I open tibia diaphysis fractures in skeletally mature patients. It is currently the only bone growth stimulator indicated for fresh fractures. It later got clearance for a nonunion indication.

Already, the FDA has approved several devices for use in the spine to accelerate lumbar spine fusions.

Despite the promise these systems show in terms of accelerating bone healing, opponents argue they are expensive and might actually extend the overall treatment time in patients whose initial treatment failed. Criticism also centers on the fact that fractures targeted with electrical and other signals would likely have healed anyway through the body’s own reparative process.

The devices have “thin Level 1 evidence,” Randy Rosier, MD, PhD, Rochester, N.Y., said when he presented the “cons” of using electrical stimulation at a meeting. The devices should probably be considered alternative treatments, he said.

Bone growth stimulators work by sending electrical, electromagnetic or mechanical energy signals or waveforms to an area of bone that needs treatment. Depending on design, electrodes from the lead or other component from which that energy emanates may be implanted surgically for round-the-clock treatment or applied externally through a device worn by the patient for specific periods of time.

Technologies now being used include PEMF, CMF, capacitive coupling, implantable direct current and low-intensity ultrasound. The systems all use battery power. For nonimplantable units worn daily, usage times range from about 20 to 30 minutes through about 10 hours, according to information that manufacturers supplied to Orthopedics Today.

2006 Special Focus: Bone Grwoth StimulatorsFor decades orthopedic surgeons have used bone growth stimulation to treat fractures and nonunions, and to fuse lumbar spines. Support for these treatments came from a host of clinical studies that over the years have shown the devices work when used properly — even if no one knew exactly why.

However, some criticisms of the technology have lingered. Research into the science behind bone growth stimulation and its method of action has lagged behind adoption of the technology.

For various reasons, adoption has also come slowly in the United States, though more than 250,000 long bone nonunions that reportedly occur annually might benefit from the kind of kick-start bone growth stimulators are believed to provide. According to one estimate, the market for appendicular application of bone growth stimulation was expected to total around $400 million last year, far below the potential market size.

Experts also agree it will take many more studies to find whether these devices indeed lead to improved quality of life and quicker return to work, as some claim.

But, progress is being made. Device manufacturers and researchers at laboratories worldwide have started more in-depth studies into what happens when ultrasound, pulsed electromagnetic fields (PEMF), capacitive coupling, direct electrical current and combined magnetic fields (CMF) energy waves get applied to bone.

“All of the growth factors that are believed to regulate very early stages of, say, the fracture healing process, have been shown to be upregulated with the different bone growth stimulation technologies,” said James T. Ryaby, PhD, who has researched the science behind this technology since the 1970s. Ryaby and colleagues were the first to evaluate the role of growth factors in bone growth stimulation technologies, and published on CMF effects on the insulin-like growth factor pathway. CMF bone growth stimulation technology is marketed by DJ Ortho.

Interestingly, some studies conducted independently of one another have recently suggested bone growth stimulation technology isn’t just for bones any more. It may eventually prove effective for such soft tissue applications as ligament and tendon injuries, regenerating cartilage and healing other musculoskeletal tissues. The basis for that prediction: The energy apparently also helps upregulate growth factors related to soft tissue healing, like fibroblast growth factor-2 (FGF-2).

Quality-of-life issues

There are other indications that we’re pursuing, like osteoarthritis, disc repair and ulcer healing.
— Bruce Simon

At a more practical level, “The new clinical studies on the horizon are looking more at SF-36 and quality of life. We’re very aware that we need more health-economic information and better studies of that type,” said Neill Pounder, PhD, senior research project manager, Smith & Nephew, Memphis. Smith & Nephew manufactures the only FDA-approved ultrasound-based bone growth stimulator.

“I think the potential for these electromagnetic devices is still wide open,” said Bruce Simon, PhD, another scientist who has extensively researched this field. He is director of research at EBI, Parsippany, N.J., which manufactures a full line of bone growth stimulation products using direct current, capacitive coupling and pulsed electromagnetic fields (PEMF) waveforms.

“There are other indications that we’re pursuing, like osteoarthritis, disc repair and ulcer healing. There’s great potential wherever the body … has some type of trauma or wound, because it uses electrical fields as part of the healing mechanism. If you could understand how to stimulate the appropriate cells at the appropriate time to upregulate the growth factors, it’s a technology with tremendous potential,” Simon told Orthopedics Today.

New directions

A greater understanding of the mechanism of action behind these systems has helped investigators identify some new indications for bone growth stimulation. For example, the FDA recently approved the device solely indicated for use in cervical spine fusions, the Cervical-Stim product (Orthofix; Huntersville, N.C).

This year Orthofix plans to start a clinical trial to get a fresh fracture indication for its Physio-Stim long bone system, Orthofix president Gary Henley told Orthopedics Today. Canadian investigators at four centers are also now involved in a randomized controlled trial looking at the effects of ultrasound for healing fresh tibial fractures fixed with intramedullary nails.

Added to the push for new indications: Many manufacturers producing the dozen or so bone growth stimulation devices sold in the United States have redesigned their products to make them more patient-friendly. Some now tout lighter, more compact units and more ergonomic models. Others are powered by rechargeable batteries that manufacturers say promotes better patient compliance.

FDA approvals

The nonspinal bone growth stimulators have been FDA approved for long bone nonunions, defined as those that show lack of radiographic progression three months after treatment. Smith & Nephew’s Exogen system gained initial FDA approval for fresh, closed, posteriorly displaced distal radius fractures and fresh, close or Grade I open tibia diaphysis fractures in skeletally mature patients. It is currently the only bone growth stimulator indicated for fresh fractures. It later got clearance for a nonunion indication.

Already, the FDA has approved several devices for use in the spine to accelerate lumbar spine fusions.

Despite the promise these systems show in terms of accelerating bone healing, opponents argue they are expensive and might actually extend the overall treatment time in patients whose initial treatment failed. Criticism also centers on the fact that fractures targeted with electrical and other signals would likely have healed anyway through the body’s own reparative process.

The devices have “thin Level 1 evidence,” Randy Rosier, MD, PhD, Rochester, N.Y., said when he presented the “cons” of using electrical stimulation at a meeting. The devices should probably be considered alternative treatments, he said.

Bone growth stimulators work by sending electrical, electromagnetic or mechanical energy signals or waveforms to an area of bone that needs treatment. Depending on design, electrodes from the lead or other component from which that energy emanates may be implanted surgically for round-the-clock treatment or applied externally through a device worn by the patient for specific periods of time.

Technologies now being used include PEMF, CMF, capacitive coupling, implantable direct current and low-intensity ultrasound. The systems all use battery power. For nonimplantable units worn daily, usage times range from about 20 to 30 minutes through about 10 hours, according to information that manufacturers supplied to Orthopedics Today.