Dr. David Roodman of the University of Pittsburgh presented these findings at the International Myeloma Workshop (IMW) on May 6 in Paris.

Most multiple myeloma patients develop bone disease, which can cause bone fractures that are extremely painful and debilitating. The current gold standard for treating myeloma bone disease is bisphosphonates, a class of drugs that slow the breakdown of bone, thereby reducing the number of fractures.

Patients diagnosed with either smoldering myeloma or monoclonal gammopathy of undetermined significance, which are both asymptomatic diseases that can progress to myeloma, may also experience bone complications. According to Dr. Roodman, it is unclear whether these patients should be treated with bisphosphonates.  For now, the guidelines recommend that patients with these conditions should only use bisphosphonates if diagnosed with osteoporosis from a DEXA scan, which measures bone density and strength. However, all patients with high-risk smoldering myeloma and bone loss should consider bisphosphonate treatment.

Solitary plasmacytoma is another precursor disease in which the patient has a single mass of myeloma cells that often result in a bone lesion.  The guidelines do not recommend bisphosphonate treatment for this type of patient.

For myeloma patients with multiple lesions, the guidelines recommend treatment with a bisphosphonate.  For myeloma patients without evidence of bone disease, it is unclear whether they should be treated with bisphosphonates. Some research has shown bisphosphonate use may have a clinical benefit even in patients without bone disease.

Some bisphosphonates are administered orally, while others are administered through intravenous injections. The guidelines recommended that patients use intravenous bisphosphonates, such as Zometa (zoledronic acid), due to results from a recent clinical trial that suggested this bisphosphonate may extend survival. In addition, they recommended that physicians administer standard doses of bisphosphonates every three to four weeks.

It is still unclear how long bisphosphonates should be used.  There is currently no randomized data on bisphosphonate use for more than two years. As a result, physicians should assess a patient’s risk and benefit of using bisphosphonate treatment after two years.

For instance, researchers have speculated that long-term use of bisphosphonates increases one’s risk of developing osteonecrosis of the jaw, a rare but serious side effect of bisphosphonate use in which there is a loss of blood supply to the jaw, causing jawbone tissue to die. To prevent osteonecrosis of the jaw, patients treated with bisphosphonates should maintain good dental hygiene and should stop bisphosphonate treatment for 90 days before and after invasive dental procedures.

Rare fractures of the upper leg and in the feet have also been reported after long-term use of bisphosphonates.

The guidelines also recommend that myeloma patients make sure to get enough vitamin D and calcium, nutrients essential for strong and healthy bones.  This is a concern because sixty percent of myeloma patients are vitamin D and calcium deficient. The guidelines say that patients may use vitamin D and calcium supplements with bisphosphonate treatment, but calcium supplementation should be used cautiously for patients with kidney problems.

Minimally invasive surgery can also be used to reduce pain associated with a spinal compression fracture and to improve a patient’s functional ability. In particular, the guidelines recommended kyphoplasty, a procedure in which a physician inserts and inflates a small balloon into the fractured vertebra, creating a space that is then filled with an acrylic cement to stabilize the spinal cord. However, there is conflicting evidence as to the benefits of vertebroplasty, a procedure in which the cement is injected directly into the fractured vertebra.

Radiation therapy may also be used for pain reduction and localized improvements in function. However, it should only be used in urgent cases, depending on a patient’s prior treatment history and response, due to its impact on bone marrow function.

For more information, please see the full guidelines (pdf), which are available on the IMW website.

Based on these findings, the study authors suggested that balloon kyphoplasty be considered as an early treatment option for cancer patients with vertebral compression fractures.

One of the hallmarks of multiple myeloma is bone disease, which is noted by bone pain, bone fractures or lesions, and increased calcium levels. Myeloma bone disease often causes bone loss or weakening, which may result in bone fractures in the spine due to compression of the vertebrae. These vertebral compression fractures may cause back pain, partial paralysis of limbs, decreased sensation, and poor urinary control.

Patients with spinal fractures may be treated with non-surgical methods, such as medication and bed rest to reduce pain, back braces and walking aids to improve functional ability, and anti-bone degradation therapy to prevent future fractures.

However, there are several disadvantages to treating spinal fractures exclusively with non-surgical practices, including limitations in efficacy and serious side effects that accompany some pain-relieving medications.

As a result, researchers are currently investigating whether vertebral compression fractures can be treated more effectively and safely with a surgical procedure known as balloon kyphoplasty. During the procedure, a small balloon is inserted into the fractured vertebra and inflated, creating a space that is later filled with an acrylic cement to stabilize and strengthen the vertebral structure.

The study included 134 cancer patients, 49 of whom had multiple myeloma. The patients were randomly assigned to receive treatment with balloon kyphoplasty or non-surgical methods. Patients who received non-surgical care had the opportunity to undergo balloon kyphoplasty after one month of non-surgical care.

In order to assess changes in a patient’s back-specific mobility, researchers used a 24-point questionnaire called RDQ. A score of 0 indicated no disability, whereas a score of 24 signified maximum disability.

At one month, the average RDQ score for patients assigned to the kyphoplasty group improved from 17.6 to 9.1, whereas the average RDQ score for patients assigned to the non-surgical care group did not change significantly (from 18.2 to 18.0).

The researchers also found that patients treated with kyphoplasty experienced a significant improvement in back pain seven days after the procedure, which continued through the one-month assessment mark. At one month, fewer patients in the kyphoplasty group used medication for pain relief than in the non-surgical care group.

Researchers also evaluated the patient’s ability to care for oneself. Of the patients treated with kyphoplasty, 75 percent had scores that indicated an ability to care for oneself, compared to 39 percent of the patients treated with non-surgical methods.

Patients in the kyphoplasty treatment group additionally reported improvement in quality of life. 

Of the patients who received non-surgical treatment, 73 percent opted to cross over to the kyphoplasty treatment group. These patients had similar outcomes to the original kyphoplasty group.

The most common side effects experienced within the first month include back pain and symptomatic spinal fractures. The rate of side effects was comparable for both treatment groups.

Although the study’s findings suggest that balloon kyphoplasty improves functional ability and back pain, the study authors pointed out that the significance of their findings is somewhat limited because the patients who received non-surgical care could cross over to the kyphoplasty treatment group after one month of treatment.

According to the study authors, however, the long-term effects of kyphoplasty can only be assessed in a controlled clinical trial that does not allow for patient cross over, which is unlikely to be conducted with cancer patients with limited life expectancy.

For more information on the study, please see the journal The Lancet (abstract).

Weakening of the vertebrae, the bones that make up the spine, can result in vertebral compression fractures. Though the most common cause of vertebral compression fractures is osteoporosis, they may also be caused by multiple myeloma tumors.

Patients with vertebral compression fractures often suffer from debilitating pain and may experience changes in their height. Non-surgical treatments for vertebral fractures include radiation, pain medication, short periods of bed rest, calcium and vitamin D supplementation, as well as the use of external back braces. Patients whose compression fractures do not respond to medical treatment can undergo surgical procedures to treat their fractures.

ArthroCare’s Contour device uses a movable, curved needle to displace soft bone, creating a space into which bone cement can be delivered to stabilize the fracture. It is used with vertebroplasty or kyphoplasty procedures, in which physicians use image guidance to inject bone cement through a hollow needle into the fractured bone.

The Contour device would most likely be used as an alternative to balloon kyphoplasty, in which an inflatable balloon is inserted through a needle into the fractured bone, creating a space for bone cement to be delivered after removal of the balloon.

Leakage of the cement out of the vertebrae is a potential complication of these procedures. In a new procedure, known as vesselplasty, a small bag is placed inside the vertebra before the addition of the bone cement to reduce the risk of cement leakage.

For more information, please see the ArthroCare press release.

Spinal fractures, also known as collapsed vertebrae or vertebral compression fractures, can develop in multiple myeloma patients who suffer from bone weakening.

Vesselplasty is a minimally invasive, image-guided surgical procedure that has emerged as an alternative to the conventional treatments of vertebroplasty and kyphoplasty.  A major advantage of vesselplasty is that it reduces leakage of cement out of the vertebral body, which is known to occur in both conventional treatments.  Leakage can trigger additional fractures in adjacent vertebral bodies.

In this study, 29 patients underwent vesselplasty treatment, seven of which had multiple fractures.  Of the 37 procedures performed, spinal fractures were caused by osteoporosis in 27 cases (73 percent), high-impact trauma in five (13.5 percent), multiple myeloma in three (8 percent), and metastatic fracture in two (5.4 percent).

Patients were scored before and after treatment on pain, mobility, and the need for painkillers.  Pain decreased from 8.72 to 3.38 after treatment, mobility impairment dropped from 2.31 to 0.59, and use of painkillers fell from 3.07 to 1.86.  All values were statistically significant, and no clinical complications arose.

The results of this study suggest that vesselplasty offers considerable improvements in pain, mobility, and use of painkillers in patients with spinal fractures.  The authors assert that the procedure is a safe and effective alternative to conventional spinal fracture treatments.

For more information, please see the study in the American Journal of Roentgenology (abstract).

Balloon kyphoplasty involves inserting an inflatable balloon into the fractured vertebra of the spinal column. The balloon is then filled with bone cement to return the vertebra to its correct position. Afterwards, patients typically have reduced pain and can move easier.

“Myeloma patients frequently have this specific problem,” said Dr. Carl Freter, an oncologist and hematologist at the University of Missouri-Columbia. He is an advocate of balloon kyphoplasty and for the past fifteen years, he has seen it improve patient quality of life.

“It has a number of advantages – relieves pain and gets patients off sedentary pain medications,” Dr. Freter said. “I have a handful of patients with remarkable results.”

Spinal fractures are the most common type of bone lesion in multiple myeloma patients. Nearly 90 percent of myeloma patients endure these kinds of lesions, which happen when cells that breakdown bones go into overdrive or cells that build bones cannot form or function properly. The fractures usually occur in the lower back because the weakened bones cannot withstand the pressure.

Treatment methods include radiation, which reduces pain, and vertebroplasty, which involves injecting bone cement directly into the broken vertebra. But balloon kyphoplasty results in lower cement leakage than vertebroplasty and can provide pain relief for two years.

Furthermore, the study reported no serious complications as a result of balloon kyphoplasty. The procedure reduces spinal deformity and improves social function and mental health, according to a quality of life survey administered to patients.

“The study is convincing and impressive,” Freter said, adding he hopes it will lead to wider application.

The authors of the study looked at seven different articles about the safety and effectiveness of balloon kyphoplasty and analyzed the outcomes. Fifty-seven percent of the total patients suffered from multiple myeloma.

Each of the studies followed up with patients, ranging from three months to two years after their procedure. Balloon kyphoplasty improved height loss and spinal deformity. However, these effects were only temporary.

For more information, please see the study in BMC Palliative Care (pdf).

DVT involves blood clot formation in the deep veins of the body, and if a clot dislodges, it may travel to other areas and block blood flow to vital organs. Researchers estimate that approximately 70 percent of all critical blockages of lung blood vessels originate from DVT in the pelvis or lower extremities.

Multiple myeloma patients face a higher risk of DVT, both because of molecular abnormalities intrinsic to myeloma and because of side effects from the newer class of treatment agents. In the era before these drugs emerged, approximately two to three percent of elderly myeloma patients experienced DVT during treatment. This risk, albeit higher than that in the general population, nevertheless remained low enough that broadscale clot-preventative measures were unwarranted.

With the advent of new immunomodulatory agents, including Revlimid (lenalidomide), Velcade (bortezomib), and thalidomide (Thalomid), DVT incidence has risen to between 10 percent and 30 percent. For many myeloma patients, guidelines now advocate daily aspirin intake, which acts as a blood thinner and helps to prevent clots. Patients with a higher DVT risk, including those who are immobilized or are overweight or diabetic, should usually receive a prescription blood thinner.

These preventative measures have greatly reduced the incidence of DVT, allowing patients to continue more safely with their treatment regimens. As Dr. Sundar Jagannath explains, “Nowadays we can mitigate or prevent the occurrence of blood clot and still the patient can benefit from a life-saving drug.”

In addition to DVT, multiple myeloma patients may also experience bone disease and its complications. Specifically, many patients develop soft spots where the myeloma has damaged bone structure, which causes pain and increases fracture risk. Guidelines suggest treating patients for a year with bisphosphonates, such as Aredia (pamidronate) or Zometa (zoledronic acid), which help inhibit bone breakdown. Individuals in remission may discontinue this bone therapy but resume it if their cancer returns.

Presently, the available bone treatments can only inhibit further bone deterioration, rather than stimulate bone regrowth. Promising drugs on the horizon, however, may actually restore weakened bone areas.

Already, evidence suggests that Velcade, a drug for directly treating multiple myeloma, may also function to restore bone loss; in this regard, the drug simultaneously fights the bone disease and the underlying cancer. New experimental drugs, including RANK ligand inhibitors and Wnt signaling pathway drugs, have also proved encouraging for promoting bone regrowth. One RANK ligand inhibitor, Amgen’s denosumab, is currently in the final stages of FDA review, and the company expects a decision on approval by October 2009.

Physicians may also perform surgery for myeloma patients experiencing acute spinal pain from compressed vertebrae and fractures. The procedure, kyphoplasty, involves inserting a small balloon to separate compressed vertebrae and applying bone cement to stabilize the spinal column. Although not all patients are appropriate candidates, kyphoplasty can often restore lost height and, perhaps most importantly, provide instantaneous pain relief to the affected area. In contrast, non-invasive, localized radiation cannot immediately relieve spinal pain, because it functions through the slower process of destroying the underlying myeloma.

For more information, see the IMW presentation transcript (pdf) provided by the MMRF.

The most common type of lesions that develop in myeloma patients are in the spinal column. Patients may mistake pain from the lesion, often in the lower back and ribs, to be general back pain. One possible cause for the pain is vertebral compression fractures, also known as spinal fractures. This happens because the bone in the spine is too weak to withstand pressure. Multiple fractures in the spine can cause a hunchback condition from shortening of the spine.

While over-the-counter and prescription medication could reduce pain, radiation therapy, vertebroplasty, and kyphoplasty are alternative treatments to consider.

About 70 percent of myeloma patients with bone lesions receive radiation therapy to relieve pain. Patients receive fairly low doses of radiation to destroy myeloma cells and relief is felt a few days after treatment. Radiation therapy can be used alone or with other therapies to treat bone disease. Higher doses are not given because they could compromise future myeloma treatments. Too much radiation therapy may have an adverse effect on a patient’s bone marrow, which is important for maintaining the immune system.

Vertebroplasty is a minimally invasive procedure in which bone cement is injected into the fracture to stabilize the spinal column. The procedure is done under local or general anesthesia. Patients must remain in bed for one hour after the procedure to let the cement harden, and an overnight stay is required.

Another treatment option is kyphoplasty. This is a technique similar to vertebroplasty that uses orthopedic balloons to expand the fracture before bone cement is injected into the cavity. Local or general anesthesia is used, and the procedure takes less than one hour per fracture. Kyphoplasty is minimally invasive and uses only two small one-centimeter incisions. Patients recover overnight and can return to daily activities by the next day. Pain is usually decreased, and the treatment is compatible with other myeloma treatments.

A common complication with both vertebroplasty and kyphoplasty is cement leakage to areas outside of the fracture. Balloon kyphoplasty has a low risk of heart attacks, stroke, and clots (blood, fat, or cement) that migrate to the lungs.

Patients who have unstable spinal fractures or a history of blood clots are not recommended to have kyphoplasty done. Myeloma patients considering any of these procedures are advised to consult a doctor to find out if they qualify as candidates.

For more information on myeloma bone disease and these treatments, see the full article in the American Society of Hematology’s 2008 Education Program Book, Hematology. Also see other Beacon articles related to myeloma bone disease: skeletal imaging, bisphosphonate treatment, and novel therapies. Information on vertebral compression fractures can be found on the International Myeloma Foundation Web site.