Osteoporosis (and low bone mass) affects 50 percent of people over 50 years of age, or over 50 million people in the United States. Its primary impact, fractures (also called fragility or low-trauma fractures), occurs secondary to normal activity (e.g., bending, coughing, lifting, fall from a standing height), and eventually occurs in 50% of women and 20% of men. VCFs constitute one-quarter of osteoporotic fractures,6 often at the midthoracic (T7-T8) and thoracolumbar junction (T12-L1). They may cause significant acute and chronic pain, leading to complications of impaired mobility (comparable to a hip fracture, pneumonia, loss of bone and muscle mass, incidental falls, deep venous thrombosis, depression, and isolation).10 Medicare claims data shows a 85% 10 year mortality following a VCF diagnosis.11 Under-diagnosis and under-treatment may exacerbate morbidity and mortality.10 Vertebral augmentation provides a significant mortality benefit over nonsurgical management with a low number needed to treat (NNT).
Treatment options for symptomatic osteoporotic VCF range from NSM (anti-osteoporosis therapy, analgesics, limited activity/bed rest, back brace, physical therapy) to PVA (PVP and PKP). PVP involves the percutaneous injection of bone cement under image guidance into the VCF. PKP adds balloon tamponade within the fractured vertebral body to create a low pressure cavity prior to cement injection. Both treatments aimed to immobilize the fracture, reduce pain, and improve alignment.
Successful small European series introduced PVP into the United States in 1993; by 2007 encouraging preliminary observational data led to medical society endorsement and clinical acceptance in painful osteoporotic VCFs refractory to medical management. Subsequent early open-label randomized controlled trials (RCTs), including the Vertebroplasty for Painful Chronic Osteoporotic Vertebral Fractures (VERTOS) trial,21 the Fracture Reduction Evaluation (FREE) trial,22,23 VERTOS II,14 and others, found a benefit of vertebral augmentation over non-surgical management.
VERTOS II was a multicenter RCT that compared PVP and NSM of acute (< 6 weeks) osteoporotic VCF in patients with moderate to severe pain (VAS ≥ 5).14 Among 202 patients, the primary endpoint of pain relief at one month and one year was greater after PVP (-5.2/-5.7) than after NSM (-2.7/-3.7) (p < 0.001). Secondary outcomes, including RDQ and Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO), were similarly improved. The main limitation in the VERTOS II trial was the lack of blinding. Subsequent analysis of the medical cohort showed that 60% achieved sufficient (VAS ≤ 3) pain relief, most within 3 months.15 The authors acknowledged that despite the VERTOS II results, “clinicians still do not know how to best treat their patients,” but conclude that, pending further RCTs, PVP may be justified in patients with insufficient pain relief after 3 months of conservative treatment.15
The lack of blinding made the early open-label RCTs, vulnerable to placebo effect. However, in 2009, two high profile, methodologically controversial (e.g., non-rigorous patient selection) double-blinded, RCTs found no benefit of PVP over a “sham” procedure (pedicle periosteal bupivacaine injection).12,13 Ever since, there has been a lack of consensus on the appropriate management of osteoporotic VCF, particularly the role of PVA.6,10 Medicare claims data shows that among over 2 million VCF patients, PVA was performed in 20% in 2005, peaked at 24% in 2007-2008, and declined to 14% in 2014, a 42% decrease.11 Lower PVA utilization was associated with a 4% increase in propensity-adjusted mortality risk (p < 0.001). A secondary analysis gave a number needed to treat (NNT) at one year to save a life of 22.8 and 14.8 for vertebroplasty and kyphoplasty, respectively.26 Both studies noted the potential for selection bias despite propensity scoring. Subsequent major RCTs, described below, have attempted to address the perceived shortcomings of these two negative studies (primarily more stringent selection criteria and choice of control).
The Vertebroplasty for Acute Painful Osteoporotic Fractures (VAPOUR) double-blinded RCT was designed to compare acute fracture (< 6 weeks) PVP with a sham procedure (subcutaneous, not periosteal, infiltration) for patients with severe pain (NRS ≥ 7).5 Among 120 randomized patients, the primary endpoint (NRS score < 4 by 14 days) was achieved in 44% and 21% of PVP and sham patients, respectively (p = 0.011), and durable to 6 months. Mean height loss at 6 months was 36% greater in the control group (63% vs. 27%). Hospital inpatients constituted 57% of study patients; among this group, median length of stay was reduced by 5.5 days in the PVP group. In addition to a focus on the acute, severely painful VCF, this study also concentrated on delivering greater cement volumes than prior studies. The authors conclude that PVP is superior to true placebo control of severe pain in VCFs of less than 6 weeks.
VERTOS IV used the same inclusion criteria as VERTOS II, but was a double-blinded comparison of PVP with a sham procedure (pedicle periosteal infiltration).7 Among the 180 randomized patients, although the reduction in VAS score was clinically (> 1.5 points) and statistically significant up to 12 months in both groups (5.00 at 12 months in the PVP group vs. 4.75 in the sham group), reductions in VAS scores did not differ between groups (p = 0.48). The authors conclude, “the results suggest that periosteal infiltration alone in the early phase provides enough pain relief with no need for additional cementation.” They recommend the “pragmatic approach” of first use of “periosteal infiltration during natural healing” and “cementation only in a selected subgroup of patients with insufficient pain relief after this early phase.” They also highlight a subgroup that may warrant earlier PVP per the VAPOUR trial (hospital inpatients with more comorbidity and severe pain).
The 2018 multicenter, prospective, uncontrolled, EVOLVE study of 354 Medicare-age patients with acute or subacute (≤ 4 mo.) painful (NRS ≥ 7) VCF (all but 8 osteoporotic), found statistical improvement in NRS, Oswestry Disability Index (ODI), Short Form-36 Questionnaire Physical Component Summary (SF-36v2 PCS), and EuroQol-5-Domain (EQ-SD) out to 12 months.24 The authors conclude that “kyphoplasty is a safe, effective, and durable procedure for treating patients with painful VCF due to osteoporosis.”
Hirsch, et al, is a claims-based analysis of national registries and insurance datasets that indicates a significant mortality benefit for patients with vertebral compression fractures who receive vertebral augmentation. Both vertebroplasty and kyphoplasty modalities conferred a prominent mortality benefit over nonsurgical management in the analysis of the US Medicare registry, with a low number needed to treat. The calculations based on this data base resulted in a low number needed to treat to save 1 life at 1 year and at 5 years. This analysis of >2,000,000 patients with vertebral compression fracture (VCF) revealed that only 15 patients need to be treated to save 1 life at 1 year. This large dataset analysis suggests that vertebral augmentation provides a significant mortality benefit over nonsurgical management with a low number needed to treat (NNT).
Multi-Jurisdictional Contractor Advisory Committee (CAC) Meeting
After review of highly graded evidence-based literature from the years 2004 -2018, the opinions amongst the CAC Advisory Committee (CAC) members and the Subject Matter Experts (SME) varied on many of the proposed questions regarding the strength of evidence for the treatment of osteoporotic vertebral compression fractures with vertebroplasty and kyphoplasty. Multiple pieces of literature were discussed to determine if osteoporotic vertebral compression fractures receiving intervention treatment during the acute or subacute timeframes were supported. Also discussed were if current literature and quality of evidence addressed an acute, subacute or chronic fracture time frame, and if highly graded evidence existed for supporting conservative, non-interventional treatment. Topics within the discussion reviewed strength of evidence regarding pain relief, overall opioid usage, quality of life, mobility as well as mortality risk. CAC members and SMEs discussed the need for further research trials to strengthen existing data as others felt the benefits of these procedures have been proven in evidence-based literature from trials that have already been performed.
Skeletal lytic lesions leading to bone pain are frequent in myeloma patients and can be present in other malignancies. Analgesic and analgesic adjuvants, in conjunction with chemotherapy, may control the pain from lytic lesions.30 In refractory or non-responsive pain, PVA has been utilized as a treatment option since the early 2000’s.31-33 A 2016 systematic review by the Ontario Health Technology Assessment Series reported the role of PVA for cancer-related VCF.34 They reviewed 111 clinical reports with 4,235 patients, including 14 systematic reviews and six RCTs evaluating the effectiveness of vertebroplasty or KYPHOPLASTY for patients with mixed primary spinal metastatic cancers, multiple myeloma, or hemangiomas. Due to the high heterogeneity of the clinical reports, the authors performed a narrative synthesis. They found the mean pain intensity scores, analgesia scores, and pain- related disability scores were significantly reduced after PVA. Asymptomatic cement leakage was common, but major adverse events were rare. This was consistent with the findings reported in an International, randomized, non- blinded trial called the Cancer Patient Fracture Evaluation (CAFÉ) study reported on 134 patients with cancer related painful VB fractures. Patients were randomized to KYPHOPLASTY (n=70) or non-surgical management (n=64). The mean RDQ score in the KYPHOPLASTY group changed from 17·6 at baseline to 9·1 at one month (mean change -8·3 points, 95% CI -6·4 to -10·2; p<0·0001), and the control group changed from 18·2 to 18·0 (mean change 0·1 points; 95% CI -0·8 to 1·0; p=0·83). At one month, the KYPHOPLASTY treatment effect for RDQ was -8·4 points (95% CI -7·6 to -9·2; p<0·0001). In an intention-to-treat analysis, KYPHOPLASTY resulted in a decrease in a back- specific disability measurement in one month. The KYPHOPLASTY group reported a significantly lower percentage of patients requiring walking aids (46 versus 25 percent), bracing (22 versus 2 percent), bed rest (46 versus 23 percent), and medications of any kind (82 versus 52 percent). Limitations included potential bias and small numbers; however, there were not significant adverse outcomes.35
For malignant PVC guidelines established by the International Society of Interventional Radiology, Standards of Practice Committee recommends referral and use of PVA for:
- For a patient rendered non-ambulatory as a result of pain from a weakened or fractured vertebral body, pain persisting at a level that prevents ambulation despite 24 hours of analgesic therapy;
- For a patient with sufficient pain from a weakened or fractured vertebral body that physical therapy is intolerable, pain persisting at that level despite 24 hours of analgesic therapy; or
- For any patient with a weakened or fractured vertebral body, unacceptable side effects such excessive sedation, confusion, or constipation as a result of the analgesic therapy necessary to reduce pain to a tolerable level. 36
The International Myeloma Working Group (IMWG) on the use of cement augmentation with percutaneous vertebroplasty and percutaneous KYPHOPLASTY for the treatment of vertebral compression fractures in multiple myeloma (MM) concludes the use of cement augmentation is an effective way to stabilize the spinal column and indicates balloon KYPHOPLASTY (BKP) and percutaneous vertebroplasty (PV) allows the majority of patients the ability to return to a near-normal level of function in a relatively short period by significantly reducing back pain and decreasing the use of pain relief. Further, the consensus statement from the IMWG states, “multiple myeloma patients with significant pain at a fracture site should be offered a balloon KYPHOPLASTY or percutaneous vertebroplasty procedure, and the procedure should be performed within 4-8 weeks unless there are medical contraindications”.37 The American College of Radiology ACR Appropriate Criteria for Management of VCFs considers PVA “Usually Appropriate” action for a pathological spinal fracture with severe and worsening pain.38