The role of cement augmentation with percutaneous vertebroplasty and balloon kyphoplasty for the treatment of vertebral compression fractures in multiple myeloma: a consensus statement from the international myeloma working group (imwg)

ABSTRACT Multiple myeloma (MM) represents approximately 15% of haematological malignancies and most of the patients present with bone involvement. Focal or diffuse spinal osteolysis may

result in significant morbidity by causing painful progressive vertebral compression fractures (VCFs) and deformities. Advances in the systemic treatment of myeloma have achieved high

response rates and prolonged the survival significantly. Early diagnosis and management of skeletal events contribute to improving the prognosis and quality of life of MM patients. The

management of patients with significant pain due to VCFs in the acute phase is not standardised. While some patients are successfully treated conservatively, and pain relief is achieved

within a few weeks, a large percentage has disabling pain and morbidity and hence they are considered for surgical intervention. Balloon kyphoplasty and percutaneous vertebroplasty are

minimally invasive procedures which have been shown to relieve pain and restore function. Despite increasing positive evidence for the use of these procedures, the indications, timing,

efficacy, safety and their role in the treatment algorithm of myeloma spinal disease are yet to be elucidated. This paper reports an update of the consensus statement from the International

Myeloma Working Group on the role of cement augmentation in myeloma patients with VCFs. SIMILAR CONTENT BEING VIEWED BY OTHERS ROLE OF PERCUTANEOUS VERTEBROPLASTY WITH HIGH-VISCOSITY CEMENT

IN THE TREATMENT OF SEVERE OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES Article Open access 25 February 2021 CEMENT AUGMENTATION FOR TREATMENT OF HIGH TO MID-THORACIC OSTEOPOROTIC

COMPRESSION FRACTURES, HIGH-VISCOSITY CEMENT PERCUTANEOUS VERTEBROPLASTY VERSUS BALLOON KYPHOPLASTY Article Open access 12 November 2022 INCIDENCE AND RISK FACTORS OF ADJACENT VERTEBRAL

FRACTURE AFTER PERCUTANEOUS VERTEBROPLASTY OR KYPHOPLASTY IN POSTMENOPAUSAL WOMEN: A RETROSPECTIVE STUDY Article Open access 03 August 2024 INTRODUCTION Multiple myeloma (MM) is a

haematologic malignancy characterised by infiltration of the bone marrow by plasma cells which can be associated with lytic bone disease causing severe bone pain, pathological fractures and

neurological compromise including cauda equina/spinal cord compression. Up to 90% of the myeloma patients develop osteolytic lesions during the course of their disease1,2,3 and 70% of

patients are affected at some stage by osteolytic/osteopenic disease of the spine4. Several skeletal events over a patient’s lifetime result in substantial morbidity, mortality5 and

increased healthcare costs. The introduction of new targeted therapeutic agents in combination with stem cell transplantation has led to a remarkable evolution in the management of myeloma

over the last 2 decades6,7. Patients with myeloma are living much longer because of improved treatment of the primary disease. Haematological medical management aims at improving the

survival of these patients and maintaining their quality of life (QoL). It is thus especially important to treat the osteolytic bone disease and vertebral compression fractures (VCFs) of the

spine in a timely manner. Historically, haematologists treated the pain associated with VCFs with radiotherapy and strong opioids. However, these treatments have their own side effects and

do not stabilise the fracture. In many cases, pain remains disabling and some patients develop progressive deformities. Some of the fractures also fail to heal and may result in significant

chronic pain. Treatment of the spine is directed towards keeping the patient pain free, ambulatory and continent. A secondary aim should be to minimise any progressive kyphotic deformity

which can lead to a poor QoL. Vertebrae that are severely compressed can lose more than 50% of their original height8. Following a spinal fracture, there is an exponential risk of a

subsequent one due to an abnormal sagittal balance that ensues and the additional compressive forces on the anterior aspect of the spine9,10,11. Moreover, the patients adopt a kyphotic

posture to minimise pain from their VCFs and to compensate for the weakness of the spinal musculature12,13,14. Patients with multiple fractures have reduced activities of daily living,

pulmonary and gastric problems and have increased morbidity and mortality11,13. The kyphotic posture significantly reduces lung function15 and pulmonary disease is the commonest cause of

death in women with VCFs11,16,17. Another major consequence of the spinal deformities is the psychological impact to these patients who often suffer from depression, anxiety and low

self-esteem, with accompanying loss of QoL18,19,20. The introduction of minimally invasive procedures such as balloon kyphoplasty (BKP) and percutaneous vertebroplasty (PV) has enabled the

vast majority of the treated patients to return to a near normal level of function within a very short period of time with excellent pain relief21,22,23,24,25,26,27,28,29,30,31,32,33. In

2008, a consensus statement was published by the International Myeloma Working Group (IMWG) on the role of vertebral augmentation with cement in MM34. The aim of this paper is to update the

previous recommendations by the IMWG considering new published data. OVERVIEW OF VERTEBRAL CEMENT AUGMENTATION PROCEDURES (VCPS), PV AND BKP VERSUS ALTERNATE OPTIONS AS THERAPY FOR VCFS The

PV and BKP have been extensively used in the treatment of painful osteoporotic and cancer-related VCFs. The value of these modalities in treating osteoporotic VCFs was questioned because of

the results from two prospective randomised trials that showed no benefit when compared with a sham procedure in relieving pain35,36,37,38,39,40. Kallmes et al. had a simulated surgical

procedure as control group without cement augmentation, and in the study by Buchbinder et al., the patients had a sham procedure which entailed injection of a local anaesthetic into the

periosteum over the lamina and pedicle. Some of the criticisms of these two studies, the patients most in need of cement augmentation and therefore potentially the ones with the maximum

amount of benefit, were possibly excluded from the studies on the basis that they would not allow themselves to be randomised into one of the two groups. The patients enrolled in the studies

may have had facet joint-related pain and not the severe pain that one would usually associate with an acute VCF. This may explain why the patients did not show improvement following VP. It

is recognised clinically that the severe pain due to an acute VCF subsides if the fracture starts to heal but patients can experience residual pain related to a resultant deformity. The

deformity alters the facet joint mechanics and facet-related pain can ensue. Wilson et al. reported that a third of the patients technically suitable for VP for an osteoporotic fracture,

responded beneficially to a facet joint injection alone. In this study, the percentage of the enrolled patients may had facet-related pain rather pain from the original fracture41,42.

Significant reduction in mortality and morbidity using cement augmentation with BKP or VP versus nonsurgical management was reported in retrospective analyses25,43. However, these studies

reported outcomes on osteoporotic and not on cancer patients. In the cancer population, prospective and retrospective analyses reported favourable results in the treatment of painful

metastatic cancer and myeloma-related VCF’s with PV and BKP24,29,44,45,46,47,48,49. The prospective randomised controlled trial Cancer Patient Fracture Evaluation (CAFE), provided evidence

for the superiority of BKP versus non-surgical management (NSM) of painful VCFs. 134 cancer patients were enrolled, of whom 49 had MM. Of these, 22 were randomly assigned to BKP and 27 to

NSM33. BKP was found to be significantly more favourable than NSM offering rapid and sustained pain relief at 1 year, as well as improved back function, QoL, activity, reduced use of

analgesics and bed rest days. Similarly, other studies have reported beneficial results of BKP and PV in rapid pain control, functional and QoL in MM patients with

VCFs24,29,30,31,45,48,50,51,52. Additional kyphoplasty was more effective than additional radiation or systemic therapy in terms of pain relief, reduction of pain associated disability and

of fracture incidence of the entire thoracolumbar spine44. It is very important that we do not deny treatment in MM patients that may be very effective in relieving the pain from their acute

VCF. They may require VCP (VP or BKP) to give them rapid relief of their pain and return them to function as soon as possible. The pain relief from cement augmentation has been sustained

over long post-operative periods in patients with MM21,30,50,53,54. Many patients with myeloma who get over the acute fracture pain may benefit from facet joint injections for facet-related

pain due to the kyphotic deformity. The evidence on bracing in the management of osteoporotic VCFs is conflicting and the role of the use of external supportive devices including rigid

thoracolumbar spinal orthosis (TLSO) or hyperextension braces is yet to be defined55. Splinting of fractures and thermoplastic bracing of spinal deformities has been used for many years to

treat disability and pain. Bracing for 8–12 weeks has also been used for the treatment of VCF’s related to myeloma52. This may be all that is needed to give the patients pain relief from

their acute fracture pain. The thermoplastic brace may also give temporary stability to a fractured spine and to patients with sternal fracture56 while chemotherapy is initiated. The most

important treatment modality is the systemic anti-myeloma therapy to get the myeloma under control. After one or two cycles of systemic anti-myeloma therapy, cement augmentation (PV and BKP)

can be performed if in fact the acute fracture pain is still present. Often these patients have had relief of their acute fracture pain with the thermoplastic brace alone or with the

addition of 4–6 weeks of medical/conservative treatment. This means that the patients may not need cement augmentation. Instead if they have chronic pain of a lower intensity over their

kyphotic deformity they may benefit from some facet joint injections. A small group of myeloma patients present with a soft tissue myelomatous mass within the spinal canal that can result in

spinal cord or cauda equine compression. These patients often present with neurological deficits and each case needs to be assessed individually. MRI scanning is clearly imperative but a CT

scan with soft tissue windows will help to delineate whether the neural compression is due to bone or soft tissue. If the compression is due to a soft tissue mass with associated

neurological impairment, then this may be amenable to steroids/chemotherapy and immediate radiotherapy. Patients with cord compression and no neurological deficit may not need radiotherapy

because chemotherapy and steroids have been shown to result in excellent resolution of the soft tissue myelomatous mass. Ideally, if patients can be treated with steroids, radiotherapy and

chemotherapy and have a very good resolution of their symptoms in 24 h, then they may not need surgical decompression and stabilisation. All decisions regarding patients with spinal cord

compression need to be taken into conjunction with an experienced spinal surgeon. Clearly, if a patient has spinal cord or cauda equina compression and has significant neurological sequelae

then they may require urgent surgical decompression and associated fixation. The aim however in patients with haematological malignancies should be to try and avoid placement of

screws/fixation of the spine. The metalwork has a higher than normal risk of failure because the bone is very weak due to MM causing secondary osteoporosis. In addition, there is a higher

risk of metalwork infection because the patients are immunosuppressed during their conventional chemotherapy, immunotherapy and stem cell transplantation. After resolution of the intraspinal

mass with chemotherapy, radiotherapy and steroids the fractured vertebra may need to be augmented with cement to treat the acute fracture pain but also to give mechanical support to the

anterior and middle columns of the spine57 thereby preventing further collapse of the vertebral body. Further collapse, particularly into kyphosis, may lead to spinal cord compromise because

of the deformity. Patients that present with no intraspinal soft tissue mass, but overt bony destruction and dubious spinal stability are another important group of patients. A posterior

vertebral wall defect or pedicle/facet fracture may lead one to question the spinal stability in this patient group. Often all that is needed is a spinal brace to keep them out of pain while

the spine confers itself stability by producing bridging bony osteophytes58,59. This appearance is similar to diffuse idiopathic skeletal hyperostosis60. It is a phenomenon that may be

accelerated by or the result of treatment with bisphosphonates. This is a very interesting finding and warrants further research to see whether patients with myeloma present a completely

different clinical problem than patients with osteolytic metastases due to solid tumours. The following is the consensus statement for recommendations for spinal support and cement

augmentation from the International Myeloma Working Group. MM patients with significant pain at a fracture site should be offered a BKP or PV procedure and the procedure should be performed

within 4–8 weeks unless there are medical contraindications (Tables 1 and 2, Fig. 1a, b). IDENTIFICATION OF PATIENTS SUITABLE FOR VERTEBRAL AUGMENTATION * Careful assessment to determine the

severity and site of the pain61. Patients with acute fracture pain should be considered and not the patient with facet joint-related pain. The clinical picture should be confirmed with MRI

scanning. The most useful MRI images to show an acute or on-going painful fracture are the sagittal STIR and T1 weighted sequences. The T1 weighted images may be more helpful in diagnosing a

VCF in a MM patient than the STIR images. In addition, T1 images may also show the fracture line. * MRI is crucial to document any radiological nerve root/cauda equina or spinal cord

compression. * CT scan with sagittal and coronal reconstructions may be needed to assess if there is spinal instability. A SINS classification can be helpful when determining the stability

of the spine. If there is a posterior wall defect or pedicle/facet joint involvement, then CT can determine the safety of cement placement within the vertebral body. If patients get a

recurrence of pain after a successful cement augmentation, then sagittal T1 and STIR images of the spine should be repeated to see if there is a new fracture that could develop following

myeloma treatment. * Assessment of myeloma disease status and therefore risk related to anaesthetic and any cement augmentation procedure. This includes potential anti-myeloma treatment

requirements and risk for infection and bleeding. Coordination of procedure with treating haematologist/oncologist to avoid anaemia, leukopaenia and/or thrombocytopaenia related to systemic

anti-myeloma therapy. TIMING OF VERTEBRAL CEMENT AUGMENTATION (PV OR BKP) The CAFÉ Trial investigated early intervention in cancer patients who had VCF’s treated with BKP. The functional

outcome (RDQ) was superior for the patients having BKP in the 1st month compared to the patients who received non-surgical treatment. The patients in the BKP group showed a marked reduction

in back pain and required less pain relief. This is important for myeloma patients since most of them have a degree of renal impairment. In addition, improvement of function and mobility can

reduce thrombotic and infection risk. Therefore, early intervention within 4–8 weeks62,63 of VCF’s with cement augmentation not only treats the pain associated with the fracture but in

addition improves clinical outcome and QoL52 (Table 2). NUMBER OF LEVELS TO BE CONSIDERED FOR TREATMENT For patients with multiple VCF’s and significant pain, the maximum number of levels

that should be augmented at a time should be determined by the operator. There is no upper limit for total number of vertebrae that should be treated in one intervention. The panel’s

recommendation is that it is appropriate to treat up to 3 levels at a time and any decision treating more levels than this should be taken with caution. The reason for this is that cement

embolus to the lungs may occur compromising respiratory function. Cement augmentation without cement leakage into the disc above or below should not increase the risk of adjacent vertebral

body fracture. Cement leakage rates with BKP are reported to be less than with VP28,31. This is also the consensus of the panel. THE HIGHEST LEVEL OF CEMENT AUGMENTATION Cement augmentation

of the spine is possible at all spinal levels. The C2 vertebral body can be augmented via a trans-oral or submandibular route. The C3–C7 vertebral bodies can be accessed and augmented

through a standard open anterior cervical approach64,65,66 or percutaneously if the experience is available. The thoracic and lumbar vertebral bodies can be augmented with cement in the

standard transpedicular or extrapedicular approach. Pain due to fractures from T1 to T4 rarely needs to be treated with cement augmentation because the pain usually settles with conservative

management. Sarcroplasty can be performed if there is evidence of sacral insufficiency fractures. THE METHOD OF VERTEBRAL CEMENT AUGMENTATION Published studies report contradicting results

for cement augmentation38,39,40,48,67,68,69,70,71. Although there has been a change in emphasis from VP to BKP, the evidence for one procedure over the other is debatable. A meta-analysis of

randomised and non-randomised trials of VP, BKP and NSM in patients with VCF due to osteoporosis31 has found that BKP was better than VP or NSM in reducing disability. Both BKP and VP were

better for reducing pain (mostly during the first 8 weeks) and subsequent fracture risk (by about 50%) when compared to NSM. There was no difference between BKP and VP for these parameters.

Cement leakage into the canal, lungs or other major organs was less for BKP than for VP. BKP was better in restoring mid-vertebral height and in changing kyphotic angle than VP and was also

associated with less incidence of refracture. BKP, which involves inflation of a balloon tamp to create a void in the vertebral body, controls the delivery of cement better than PV. Patients

with multiple VCF’s may become very kyphotic in the thoracic and lumbar regions of the spine. A hyperkyphosis results in a positive sagittal alignment also termed sagittal imbalance.

Patients with a positive sagittal balance find it more difficult to stand in the upright posture and in attempting to do so expend more energy. Poor sagittal alignment has been shown to be a

strong predictor of disability72. There has been debate as to the potential for BKP and PV to restore vertebral body height following a VCF. Some papers however report an improvement in the

Cobb angle (degree of kyphosis) following BKP50,54,73,74 for VCF’s related to MM. Similar outcomes of KIVA implant to BKP vertebral augmentation were reported in patients with VCFs

secondary to cancer and osteoporosis75,76,77,78,79. More research is needed to answer this question definitively. In addition, direct comparison of the complications of NSM, VP and BKP and

the optimal timing for VCF treatment in MM patients are questions that could be answered in a prospective randomised, controlled clinical trial. USE OF RADIOTHERAPY The use of radiotherapy

for local disease control and palliation should be used judiciously and sparingly depending on the patient’s presentation, need for urgent response, and prior treatment history and response.

MRI and CT scans are crucial to differentiate between a soft tissue myelomatous mass in the spinal canal from bony encroachment. The reason for this is that radiation therapy is very

effective in reducing the size of a soft tissue myelomatous mass but not effective if there is bony neural compression and does not stabilise the VCF. Radiotherapy should be limited as much

as possible to spare the patient’s marrow function. Current systemic combination therapies of steroids with novel agents work rapidly and should decrease the need for palliative

radiotherapy. Radiation therapy may be appropriate for: * (1) Patients with a soft tissue mass or plasmacytoma that has not resolved with systemic therapy * (2) Patients who cannot receive

systemic therapy * (3) Relapsed refractory patients * (4) Palliative approach for poor performance status patients * (5) When mass is associated with severe pain * (6) Location of

plasmacytoma precluding use of BKP or PV; e.g. tumour impacting posterior part of the vertebral body close to spinal cord and nerves. Receiving radiotherapy and the dose of previous

radiotherapy are not contraindications for cement augmentation (PV or BKP) if it is needed. The need and timing of a cement augmentation procedure for patients that have been irradiated

depends on the patient’s pain (Fig. 2). The cement augmentation procedures are performed through small stab incisions and therefore the usual concerns over wound healing do not exist.

Patients that have a posterior wall defect (associated with a soft tissue mass encroaching the spinal canal) or pedicle/facet joint involvement may need supplementary cement augmentation

despite having received radiotherapy to stabilise the anterior and middle columns of the spine. Planned vertebral augmentation 4–8 weeks later (or after the second cycle of chemotherapy) is

appropriate for patients with relative vertebral instability. The aim of the cement augmentation is to halt further collapse of the fractured vertebral body that could result in progressive

kyphosis and secondary neural compromise. Overall, the proposed algorithm for spinal support in myeloma presenting with VCFs or spinal cord compression is summarised in a flow diagram in

Fig. 1b. The first major decision point is the presence or absence of signs and/or symptoms of neurological deficit. Obviously, if there is, this is an urgent matter and recommendations

proceed accordingly. Once the situation has been assessed, stabilised and treated, then cement augmentation can be an option if there is persistent pain. For patients without neurologic

compromise, imaging and multi-disciplinary assessment are recommended as the basis for consideration of cement augmentation. Integration within the total treatment schema is the primary

plan. DISCUSSION The prognosis of patients with myeloma has improved considerably over the last 15 years because of the advances in Haematological Oncology. We therefore need to become more

proficient at treating the associated medical/surgical complications related to the disease. One such complication is one or more VCF’s of the spine. Patients may present with significant

spinal fracture pain or neurological compromise. These signs and symptoms may present at the time of the index procedure or when there is a relapse of the disease. Essentially, myeloma

patients that present with spinal symptoms and signs need to be assessed to establish the source and nature of their pain and presence/absence of neurological compromise and spinal

instability. Those that present with neurological compromise may have spinal cord, cauda equina or nerve root compression. It is imperative, in patients with neurological compromise, to get

not only an MRI scan with STIR and T1 weighted images but also a CT scan (with soft tissue windowing) to delineate whether it is bone or soft tissue compromising the neurological structures.

Soft tissue in the spinal canal due to a myelomatous deposit is usually very sensitive to treatment with chemotherapy/radiotherapy/steroids and therefore the neural compression can be

treated by these modalities without the need for surgical decompression. Ideally, one would like to avoid any instrumentation in myeloma patients if possible because of the risk of

subsequent metalwork/deep spinal infection during periods of immunocompromise. However, if there is significant spinal cord compromise/cauda equina compression then surgical decompression

may be needed as an emergency and an immediate spinal surgical consultation should be sought on all such patients. Once the spinal cord/cauda equine compression has been treated with

steroids/chemotherapy/radiotherapy, cement augmentation may be needed to alleviate the pain associated with the fracture or to restore spinal stability. It is uncommon for a myeloma patient

to present with neurological compromise because of bony encroachment but if it occurs, radiotherapy/chemotherapy/steroids will not be an effective treatment. Surgery may be needed in this

cohort of patients. Patients who present with spinal pain, but no neurological compromise should have an MRI scan performed with STIR and T1 weighted images to detect any spinal fractures.

The T1 weighted images may be better than the STIR images in highlighting the fracture line in vertebrae infiltrated with a myelomatous deposit. If one has concerns about the spinal

stability because of a posterior wall defect or pedicle/facet joint/pars involvement, then a CT scan with sagittal and coronal reconstructions can be very helpful. Patients can have quite

significant bony defects but still be structurally stable in an orthotic brace80. A brace may be all that is needed in patients with a spinal fracture if they can mobilise without

significant pain. The external orthosis will also keep the patients in the upright posture (and potentially prevent the development of a kyphotic deformity) while their fractures heal.

Patients who present with spinal pain and have a new diagnosis of myeloma may need, depending on systemic symptoms, to have their disease controlled with chemotherapy prior to any

consideration for cement augmentation. The chemotherapy immune-compromises the patients and therefore the correct timing of cement augmentation should be a multi-disciplinary decision.

Antibiotic prophylaxis in the peri-operative period is strongly advised to avoid infection. The orthotic brace can be a very useful tool to control the pain to an acceptable level while the

disease is being treated with the first couple of cycles of chemotherapy. Another important aspect of the treatment in myeloma patients involves bisphosphonate therapy. This drug treatment

clearly helps to stabilise the bone density in patients with myeloma but, in addition may have a positive effect in producing an external scaffold of bone around the vertebral bodies to

confer them extra stability. This external scaffold, which has been described as DISH in prior publications81 in patients with myeloma, may decrease the need for spinal fixation in patients

otherwise thought to be at risk of spinal instability because of involvement of all three bony spinal columns57. CONCLUSION The prognosis of MM is continually improving due to medical

advances. The treatment of myeloma with chemo- immunotherapeutic agents and autologous stem cell transplantation renders the patient immunocompromised for periods of time, exposing them to

infection. Spinal fixation has been employed traditionally to treat myeloma patients when decompression and stabilisation were deemed to be essential. However, it is well established that in

situ instrumentation is at risk of getting infected when the patients are in an immunocompromised state. If the metalwork gets infected, then the consequences can be catastrophic. Cement

augmentation is a very effective way of stabilising the anterior and middle spinal columns without the need for metalwork fixation. It is an excellent way to relieve the pain from a VCF. The

myeloma spine treated with bisphosphonates appears to produce an external scaffold of bone that stabilises even the most moth-eaten spinal elements once the disease process is under

control. An external orthosis can be very effective when trying to achieve pain relief from a fracture. It also helps to maintain the correct sagittal balance in patients with multiple

fractures while they heal or before they are treated with cement augmentation. The development of radiofrequency ablation in combination with cement augmentation procedures is currently

under investigation with encouraging results. REFERENCES * Terpos, E., Christoulas, D. & Gavriatopoulou, M. Biology and treatment of myeloma related bone disease. _Metabolism_ 80, 80–90

(2018). CAS  PubMed  Google Scholar  * Terpos, E., Ntanasis-Stathopoulos, I., Gavriatopoulou, M. & Dimopoulos, M. A. Pathogenesis of bone disease in multiple myeloma: from bench to

bedside. _Blood Cancer J._ 8, 7 (2018). PubMed  PubMed Central  Google Scholar  * Terpos, E., Christoulas, D., Gavriatopoulou, M. & Dimopoulos, M. A. Mechanisms of bone destruction in

multiple myeloma. _Eur. J. Cancer Care_ 26, e12761–12771 (2017). Google Scholar  * Callander, N. S. & Roodman, G. D. Myeloma bone disease. _Semin. Hematol._ 38, 276–285 (2001). CAS 

PubMed  Google Scholar  * Eda, H., Santo, L., Roodman, G. D. & Raje, N. Bone disease in multiple myeloma. _Cancer Treat. Res._ 169, 251–270 (2016). CAS  PubMed  Google Scholar  *

Landgren, O. & Rajkumar, S. V. New developments in diagnosis, prognosis, and assessment of response in multiple myeloma. _Clin. Cancer Res._ 22, 5428–5433 (2016). CAS  PubMed  PubMed

Central  Google Scholar  * Rajkumar, S. V. Myeloma today: disease definitions and treatment advances. _Am. J. Hematol._ 91, 90–100 (2016). CAS  PubMed  PubMed Central  Google Scholar  *

Genant, H. K., Wu, C. Y., van Kuijk, C. & Nevitt, M. C. Vertebral fracture assessment using a semiquantitative technique. _J. Bone Miner. Res._ 8, 1137–1148 (1993). CAS  PubMed  Google

Scholar  * Lindsay, R. et al. Risk of new vertebral fracture in the year following a fracture. _JAMA_ 285, 320–323 (2001). CAS  PubMed  Google Scholar  * Heggeness, M. H. Spine fracture with

neurological deficit in osteoporosis. _Osteoporos. Int._ 3, 215–221 (1993). CAS  PubMed  Google Scholar  * Kado, D. M. et al. Incident vertebral fractures and mortality in older women: a

prospective study. _Osteoporos. Int._ 14, 589–594 (2003). CAS  PubMed  Google Scholar  * Huang, M. H., Barrett-Connor, E., Greendale, G. A. & Kado, D. M. Hyperkyphotic posture and risk

of future osteoporotic fractures: the Rancho Bernardo study. _J. Bone Miner. Res._ 21, 419–423 (2006). PubMed  Google Scholar  * Kado, D. M. et al. Hyperkyphosis predicts mortality

independent of vertebral osteoporosis in older women. _Ann. Intern. Med._ 150, 681–687 (2009). PubMed  PubMed Central  Google Scholar  * Katzman, W. B., Vittinghoff, E. & Kado, D. M.

Age-related hyperkyphosis, independent of spinal osteoporosis, is associated with impaired mobility in older community-dwelling women. _Osteoporos. Int._ 22, 85–90 (2011). CAS  PubMed 

Google Scholar  * Schlaich, C. et al. Reduced pulmonary function in patients with spinal osteoporotic fractures. _Osteoporos. Int._ 8, 261–267 (1998). CAS  PubMed  Google Scholar  * Katzman,

W. B., Vittinghoff, E., Ensrud, K., Black, D. M. & Kado, D. M. Increasing kyphosis predicts worsening mobility in older community-dwelling women: a prospective cohort study. _J. Am.

Geriatr. Soc._ 59, 96–100 (2011). PubMed  PubMed Central  Google Scholar  * Kado, D. M., Lui, L. Y. & Cummings, S. R., Study of Osteoporotic Fractures Research Group. Rapid resting heart

rate: a simple and powerful predictor of osteoporotic fractures and mortality in older women. _J. Am. Geriatr. Soc._ 50, 455–460 (2002). PubMed  Google Scholar  * Lyles, K. W. et al.

Association of osteoporotic vertebral compression fractures with impaired functional status. _Am. J. Med._ 94, 595–601 (1993). CAS  PubMed  Google Scholar  * Silverman, S. L. The clinical

consequences of vertebral compression fracture. _Bone_ 13, S27–S31 (1992). PubMed  Google Scholar  * Gold, D. T. The clinical impact of vertebral fractures: quality of life in women with

osteoporosis. _Bone_ 18, 185S–189S (1996). CAS  PubMed  Google Scholar  * Dudeney, S., Lieberman, I. H., Reinhardt, M. K. & Hussein, M. Kyphoplasty in the treatment of osteolytic

vertebral compression fractures as a result of multiple myeloma. _J. Clin. Oncol._ 20, 2382–2387 (2002). CAS  PubMed  Google Scholar  * Bouza, C., Lopez-Cuadrado, T., Cediel, P.,

Saz-Parkinson, Z. & Amate, J. M. Balloon kyphoplasty in malignant spinal fractures: a systematic review and meta-analysis. _BMC Palliat. Care_ 8, 12 (2009). PubMed  PubMed Central 

Google Scholar  * Boonen, S. et al. Balloon kyphoplasty for the treatment of acute vertebral compression fractures: 2-year results from a randomized trial. _J. Bone Miner. Res._ 26,

1627–1637 (2011). PubMed  Google Scholar  * Burton, A. W. et al. Vertebral compression fracture treatment with vertebroplasty and kyphoplasty: experience in 407 patients with 1,156 fractures

in a tertiary cancer center. _Pain Med._ 12, 1750–1757 (2011). PubMed  Google Scholar  * Edidin, A. A., Ong, K. L., Lau, E. & Kurtz, S. M. Morbidity and mortality after vertebral

fractures: comparison of vertebral augmentation and nonoperative management in the medicare population. _Spine_ 40, 1228–1241 (2015). Google Scholar  * Evans, A. J. et al. Randomized

controlled trial of vertebroplasty versus kyphoplasty in the treatment of vertebral compression fractures. _J. Neurointerv. Surg._ 8, 756–763 (2016). PubMed  Google Scholar  * Ha, K. Y. et

al. Bone cement augmentation procedures for spinal pathologic fractures by multiple myeloma. _J. Korean Med. Sci._ 30, 88–94 (2015). PubMed  Google Scholar  * Health Quality Ontario.

Vertebral augmentation involving vertebroplasty or kyphoplasty for cancer-related vertebral compression fractures: a systematic review. _Ont. Health Technol. Assess. Ser._ 16, 1–202 (2016).

PubMed Central  Google Scholar  * Julka, A., Tolhurst, S. R., Srinivasan, R. C. & Graziano, G. P. Functional outcomes and height restoration for patients with multiple myeloma-related

osteolytic vertebral compression fractures treated with kyphoplasty. _J. Spinal Disord. Tech._ 27, 342–346 (2014). PubMed  Google Scholar  * Khan, O. A., Brinjikji, W. & Kallmes, D. F.

Vertebral augmentation in patients with multiple myeloma: a pooled analysis of published case series. _Am. J. Neuroradiol._ 35, 207–210 (2014). CAS  PubMed  Google Scholar  * Papanastassiou,

I. D. et al. Comparing effects of kyphoplasty, vertebroplasty, and non-surgical management in a systematic review of randomized and non-randomized controlled studies. _Eur. Spine J._ 21,

1826–1843 (2012). PubMed  PubMed Central  Google Scholar  * Lieberman, I. H., Dudeney, S., Reinhardt, M. K. & Bell, G. Initial outcome and efficacy of “kyphoplasty” in the treatment of

painful osteoporotic vertebral compression fractures. _Spine_ 26, 1631–1638 (2001). CAS  PubMed  Google Scholar  * Berenson, J. et al. Balloon kyphoplasty versus non-surgical fracture

management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. _Lancet Oncol._ 12, 225–235 (2011). PubMed 

Google Scholar  * Hussein, M. A. et al. The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement. _Leukemia_ 22, 1479–1484 (2008). CAS

  PubMed  Google Scholar  * Buchbinder R., et al. Percutaneous vertebroplasty for osteoporotic vertebral compression fracture. _Cochrane Database Syst. Rev._ 4, CD006349 (2015). * Comstock,

B. A. et al. Investigational vertebroplasty safety and efficacy trial (INVEST): patient-reported outcomes through 1 year. _Radiology_ 269, 224–231 (2013). PubMed  PubMed Central  Google

Scholar  * Kallmes, D. F. & Comstock, B. A. Commentary: No comparison: conservative management of painful spontaneous osteoporotic compression fractures is the way to go. _Spine J._ 12,

1006–1007 (2012). PubMed  Google Scholar  * Staples, M. P. et al. Effectiveness of vertebroplasty using individual patient data from two randomised placebo controlled trials: meta-analysis.

_BMJ_ 343, d3952 (2011). PubMed  PubMed Central  Google Scholar  * Kallmes, D. F. et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. _N. Engl. J. Med._ 361,

569–579 (2009). CAS  PubMed  PubMed Central  Google Scholar  * Buchbinder, R. & Kallmes, D. F. Vertebroplasty: when randomized placebo-controlled trial results clash with common belief.

_Spine J._ 10, 241–243 (2010). PubMed  Google Scholar  * Wilson, D. J., Owen, S. & Corkill, R. A. Coblation vertebroplasty for complex vertebral insufficiency fractures. _Eur. Radiol._

23, 1785–1790 (2013). PubMed  Google Scholar  * Wilson, D. R. et al. Effect of augmentation on the mechanics of vertebral wedge fractures. _Spine_ 25, 158–165 (2000). CAS  PubMed  Google

Scholar  * Edidin, A. A., Ong, K. L., Lau, E. & Kurtz, S. M. Mortality risk for operated and nonoperated vertebral fracture patients in the medicare population. _J. Bone Miner. Res._ 26,

1617–1626 (2011). PubMed  Google Scholar  * Kasperk, C. et al. Kyphoplasty in patients with multiple myeloma a retrospective comparative pilot study. _J. Surg. Oncol._ 105, 679–686 (2012).

PubMed  Google Scholar  * Mendoza, T. R. et al. Changes in pain and other symptoms in patients with painful multiple myeloma-related vertebral fracture treated with kyphoplasty or

vertebroplasty. _J. Pain_ 13, 564–570 (2012). PubMed  PubMed Central  Google Scholar  * La Maida, G. A. et al. Cement leakage: safety of minimally invasive surgical techniques in the

treatment of multiple myeloma vertebral lesions. _Eur. Spine J._ 21, S61–S68 (2012). PubMed  Google Scholar  * Simony, A., Hansen, E. J., Gaurilcikas, M., Abildgaard, N. & Andersen, M.

O. Pain reduction after percutaneous vertebroplasty for myeloma-associated vertebral fractures. _Dan. Med. J._ 61, A4945 (2014). PubMed  Google Scholar  * Anselmetti, G. C. et al.

Percutaneous vertebroplasty in multiple myeloma: prospective long-term follow-up in 106 consecutive patients. _Cardiovasc. Intervent. Radiol._ 35, 139–145 (2012). PubMed  Google Scholar  *

Anselmetti, G. C. et al. Percutaneous vertebroplasty: multi-centric results from EVEREST experience in large cohort of patients. _Eur. J. Radiol._ 81, 4083–4086 (2012). PubMed  Google

Scholar  * Zou, J., Mei, X., Gan, M. & Yang, H. Kyphoplasty for spinal fractures from multiple myeloma. _J. Surg. Oncol._ 102, 43–47 (2010). PubMed  Google Scholar  * Astolfi, S.,

Scaramuzzo, L. & Logroscino, C. A. A minimally invasive surgical treatment possibility of osteolytic vertebral collapse in multiple myeloma. _Eur. Spine J._ 18, 115–121 (2009). PubMed 

PubMed Central  Google Scholar  * Malhotra, K. et al. Spinal disease in myeloma: cohort analysis at a specialist spinal surgery centre indicates benefit of early surgical augmentation or

bracing. _BMC Cancer_ 16, 444 (2016). PubMed  PubMed Central  Google Scholar  * Pflugmacher, R. et al. [A prospective two-year follow-up of thoracic and lumbar osteolytic vertebral fractures

caused by multiple myeloma treated with balloon kyphoplasty]. _Z. Orthop. Ihre Grenzgeb._ 145, 39–47 (2007). CAS  PubMed  Google Scholar  * Pflugmacher, R. et al. [Comparative findings of

balloon kyphoplasty in patients with vertebral fractures due to osteoporosis, metastases and myeloma]. _Z. Orthop. Unf._ 150, 198–204 (2012). CAS  Google Scholar  * Goodwin, V. A., Hall, A.

J., Rogers, E. & Bethel, A. Orthotics and taping in the management of vertebral fractures in people with osteoporosis: a systematic review. _BMJ Open._ 6, e010657 (2016). PubMed  PubMed

Central  Google Scholar  * Butler, J. S. et al. Pathologic sternal involvement is a potential risk factor for severe sagittal plane deformity in multiple myeloma with concomitant thoracic

fractures. _Spine J._ 15, 2503–2508 (2015). PubMed  Google Scholar  * Denis, F. The three column spine and its significance in the classification of acute thoracolumbar spinal injuries.

_Spine_ 8, 817–831 (1983). CAS  PubMed  Google Scholar  * Molloy, S. & Kyriakou, C. Expert’s comment concerning Grand Rounds case entitled “total spondylectomy for solitary bone

plasmacytoma of the lumbar spine in a young woman. A case report and review of the literature” (by N. von der Hoeh, S.K. Tschoeke, J. Gulow, A. Voelker, U. Siebolts and C.-E. Heyde). _Eur.

Spine J._ 23, 40–42 (2014). PubMed  Google Scholar  * Malhotra, K., Lui, D. F., Butler, J. S., Selvadurai, S. & Molloy, S. Successful nonsurgical treatment for highly unstable fracture

subluxation of the spine secondary to myeloma. _Spine J._ 16, e547–e551 (2016). PubMed  Google Scholar  * Mata, S. et al. A controlled study of diffuse idiopathic skeletal hyperostosis.

Clinical features and functional status. _Medicine_ 76, 104–117 (1997). CAS  PubMed  Google Scholar  * Langdon, J., Way, A., Heaton, S., Bernard, J. & Molloy, S. Vertebral compression

fractures—new clinical signs to aid diagnosis. _Ann. R. Coll. Surg. Engl._ 92, 163–166 (2010). PubMed  PubMed Central  Google Scholar  * Papanastassiou, I. D. & Vrionis, F. D. Is early

vertebroplasty/kyphoplasty justified in multiple myeloma given the rapid vertebral fracture progression? _Spine J._ 16, 833–834 (2016). PubMed  Google Scholar  * Papanastassiou, I. D. et al.

Adverse prognostic factors and optimal intervention time for kyphoplasty/vertebroplasty in osteoporotic fractures. _Biomed. Res. Int._ 2014, 925683 (2014). PubMed  PubMed Central  Google

Scholar  * Smith, G. R. & Hotchkiss, R. N. Radial head and neck fractures: anatomic guidelines for proper placement of internal fixation. _J. Shoulder Elbow Surg._ 5, 113–117 (1996). CAS

  PubMed  Google Scholar  * Guzik, G. Quality of life of patients after surgical treatment of cervical spine metastases. _BMC Musculoskelet. Disord._ 17, 315 (2016). PubMed  PubMed Central 

Google Scholar  * Druschel, C., Schaser, K. D., Melcher, I., Haas, N. P. & Disch, A. C. Minimally invasive combined anterior kyphoplasty for osteolytic C2 and C5 metastases. _Arch.

Orthop. Trauma Surg._ 131, 977–981 (2011). CAS  PubMed  Google Scholar  * Buchbinder, R., Kallmes, D. & Glasziou, P. Vertebroplasty versus conservative treatment for vertebral fractures.

_Lancet_ 376, 2070 (2010). PubMed  Google Scholar  * Gray, L. A., Rad, A. E., Gaughen, J. R. Jr., Kaufmann, T. J. & Kallmes, D. F. Efficacy of percutaneous vertebroplasty for multiple

synchronous and metachronous vertebral compression fractures. _Am. J. Neuroradiol._ 30, 318–322 (2009). CAS  PubMed  Google Scholar  * Jarvik, J. G. & Kallmes, D. F. Point of view.

Efficacy of vertebroplasty and kyphoplasty. _Spine_ 34, 613–614 (2009). PubMed  Google Scholar  * Kallmes, D. F., Buchbinder, R. & Miller, F. G. Viewpoint: Randomised controlled trials

using invasive control interventions should be included in Cochrane Reviews. _Cochrane Database Syst. Rev._ 8, ED000030 (2011). * Anselmetti, G. C., Muto, M., Guglielmi, G. & Masala, S.

Percutaneous vertebroplasty or kyphoplasty. _Radiol. Clin. North Am._ 48, 641–649 (2010). CAS  PubMed  Google Scholar  * Glassman, S. D. et al. The impact of positive sagittal balance in

adult spinal deformity. _Spine_ 30, 2024–2029 (2005). PubMed  Google Scholar  * Pflugmacher, R., Beth, P., Schroeder, R. J., Schaser, K. D. & Melcher, I. Balloon kyphoplasty for the

treatment of pathological fractures in the thoracic and lumbar spine caused by metastasis: one-year follow-up. _Acta Radiol._ 48, 89–95 (2007). CAS  PubMed  Google Scholar  * Pflugmacher, R.

et al. Percutaneous balloon kyphoplasty in the treatment of pathological vertebral body fracture and deformity in multiple myeloma: a one-year follow-up. _Acta Radiol._ 47, 369–376 (2006).

CAS  PubMed  Google Scholar  * Korovessis, P., Vardakastanis, K., Repantis, T. & Vitsas, V. Balloon kyphoplasty versus KIVA vertebral augmentation—comparison of 2 techniques for

osteoporotic vertebral body fractures: a prospective randomized study. _Spine_ 38, 292–299 (2013). PubMed  Google Scholar  * Korovessis, P., Repantis, T., Miller, L. E. & Block, J. E.

Initial clinical experience with a novel vertebral augmentation system for treatment of symptomatic vertebral compression fractures: a case series of 26 consecutive patients. _BMC

Musculoskelet. Disord._ 12, 206 (2011). PubMed  PubMed Central  Google Scholar  * Korovessis, P., Vardakastanis, K., Vitsas, V. & Syrimpeis, V. Is Kiva implant advantageous to balloon

kyphoplasty in treating osteolytic metastasis to the spine? Comparison of 2 percutaneous minimal invasive spine techniques: a prospective randomized controlled short-term study. _Spine_ 39,

E231–E239 (2014). PubMed  Google Scholar  * Anselmetti, G. C. et al. Percutaneous vertebral augmentation assisted by PEEK implant in painful osteolytic vertebral metastasis involving the

vertebral wall: experience on 40 patients. _Pain Physician_ 16, E397–E404 (2013). PubMed  Google Scholar  * Tutton, S. M. et al. KAST Study: the Kiva system as a vertebral augmentation

treatment—a safety and effectiveness trial: a randomized, noninferiority trial comparing the Kiva system with balloon kyphoplasty in treatment of osteoporotic vertebral compression

fractures. _Spine_ 40, 865–875 (2015). PubMed  Google Scholar  * Molloy, S. et al. Is balloon kyphoplasty safe and effective for cancer-related vertebral compression fractures with posterior

vertebral body wall defects? _J. Surg. Oncol._ 113, 835–842 (2016). PubMed  Google Scholar  * Scutellari, P. N., Orzincolo, C., Spanedda, R. & Piva, N. Plasma cell dyscrasias and

diffuse idiopathic skeletal hyperostosis. Is it a merely accidental association?. _Radiol. Med._ 81, 625–632 (1991). CAS  PubMed  Google Scholar  * Fourney, D. R. et al. Spinal instability

neoplastic score: an analysis of reliability and validity from the spine oncology study group. _J. Clin. Oncol._ 29, 3072–3077 (2011). PubMed  Google Scholar  * Fisher, C. G. et al. A novel

classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. _Spine_ 35, E1221–E1229 (2010).

PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * University College London and Northwick Park Hospitals, London, UK Charalampia Kyriakou * Royal

National Orthopedic Hospital, Stanmore, UK Charalampia Kyriakou & Sean Molloy * Moffitt Cancer Center, University of South Florida, Tampa, FL, USA Frank Vrionis * Roswell Park Cancer

Center, Buffalo, NY, USA Ronald Alberico * Klinikum Leverkusen, Leverkusen, Germany Leonard Bastian * Karmanos Cancer Institute, Detroit, MI, USA Jeffrey A. Zonder * Memorial Sloan-Kettering

Cancer Center, New York, NY, USA Sergio Giralt * Massachusetts General Hospital, Boston, MA, USA Noopur Raje * Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN,

USA Robert A. Kyle * Indiana University, Indianapolis, IN, USA David G. D. Roodman * University of Athens School of Medicine, Athens, Greece Meletios A. Dimopoulos & Evangelos Terpos *

Mayo Clinic, Rochester, MN, USA S. Vincent Rajkumar * Cedars-Sinai Samuel Oschin Cancer Center, Los Angeles, CA, USA Brian B. G. Durie Authors * Charalampia Kyriakou View author publications

You can also search for this author inPubMed Google Scholar * Sean Molloy View author publications You can also search for this author inPubMed Google Scholar * Frank Vrionis View author

publications You can also search for this author inPubMed Google Scholar * Ronald Alberico View author publications You can also search for this author inPubMed Google Scholar * Leonard

Bastian View author publications You can also search for this author inPubMed Google Scholar * Jeffrey A. Zonder View author publications You can also search for this author inPubMed Google

Scholar * Sergio Giralt View author publications You can also search for this author inPubMed Google Scholar * Noopur Raje View author publications You can also search for this author

inPubMed Google Scholar * Robert A. Kyle View author publications You can also search for this author inPubMed Google Scholar * David G. D. Roodman View author publications You can also

search for this author inPubMed Google Scholar * Meletios A. Dimopoulos View author publications You can also search for this author inPubMed Google Scholar * S. Vincent Rajkumar View author

publications You can also search for this author inPubMed Google Scholar * Brian B. G. Durie View author publications You can also search for this author inPubMed Google Scholar * Evangelos

Terpos View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Charalampia Kyriakou. ETHICS DECLARATIONS CONFLICT OF

INTEREST The authors declare that they have no conflict of interest. ADDITIONAL INFORMATION PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in

published maps and institutional affiliations. RIGHTS AND PERMISSIONS OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use,

sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative

Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated

otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds

the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kyriakou, C., Molloy, S., Vrionis, F. _et al._ The role of cement augmentation with percutaneous vertebroplasty and balloon kyphoplasty for

the treatment of vertebral compression fractures in multiple myeloma: a consensus statement from the International Myeloma Working Group (IMWG). _Blood Cancer J._ 9, 27 (2019).

https://doi.org/10.1038/s41408-019-0187-7 Download citation * Received: 03 June 2018 * Revised: 09 September 2018 * Accepted: 31 October 2018 * Published: 26 February 2019 * DOI:

https://doi.org/10.1038/s41408-019-0187-7 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative