Dimitri Filippiadis and Alexis Kelekis (both Department of Radiology II, Attikon University Hospital, Athens, Greece) here detail the history and future of percutaneous vertebroplasty and kyphoplasty, and discuss the findings of the 2016 VAPOUR trial. This demonstrated that patients with acute osteoporotic fractures suffering from severe pain benefit from percutaneous vertebroplasty (PVP) over the designed placebo treatment.
Typically, vertebral augmentation techniques for the treatment of compression fractures include percutaneous vertebroplasty and kyphoplasty; both are minimally invasive, imaging-guided percutaneous techniques applied for stabilisation of vertebral fractures. Additionally, there is also compound spinal augmentation, which involves additional materials to poly-methylmethacrylate (PMMA), an issue that is out of the scope of this article.
There is a wide variety of possible substrate vertebral fractures to be treated, including osteoporotic, pathologic, traumatic and malignant types. Common indications for percutaneous vertebroplasty include: symptomatic cases of osteoporotic vertebral fracture being refractory following a three to four week course of medical therapy, benign tumors, vertebra with extensive osteolysis or invasion secondary to malignant tumor, Kummel’s disease, traumatic fractures and need for anterior stabilisation prior to surgical operation performed in the spine’s posterior elements. Percutaneous kyphoplasty can also be proposed for the aforementioned indications, however, the technique seems to be more suitable for a recent (fewer than seven to 10 days) traumatic vertebral fracture (A1 type according the Magerl classification) with a kyphotic angle at the specific level >15°. Both techniques are governed by relatively high efficacy and safety profiles whilst single session multilevel treatments have been shown to be feasible without compromising safety and efficacy. Since not all vertebral compression fractures are the same, a tailor-based approach is necessary for optimum efficacy and safety results.
Vertebral compression fractures (VCF) result in a kyphotic deformity. The kyphotic-compensatory stance includes posterior pelvic tilt resulting in hamstring muscle foreshortening with consequent decreased gait velocity and distance, further affecting mobility. The constant paraspinal muscular contraction required to maintain this stance results in secondary chronic back pain. The kyphotic angle has been shown to be independently associated with decreased mobility, which is in turn correlated with an increased fall risk. In some cases, the evolution of the fracture and kyphotic angle might create medullar compression and neurological deficit, as depicted in the literature. The presence of a VCF will result in loss of pressure in the adjacent intervertebral disc and doubling of the stress on the adjacent vertebral body. Residual kyphosis post standard vertebral augmentation with vertebroplasty or balloon kyphoplasty potentially results in doubling the stress on the adjacent vertebral body, thus halving the force required to produce a subsequent compression fracture. It appears that the natural course of the additional fractures rate can be altered by treatment and reduction of existing fractures by vertebral augmentation techniques.
PMMA mixed to an opacifying agent is most commonly used in percutaneous spine augmentation with a wide variety of market products differing upon opacifying agent used (barium sulfate, zirconium, tantalum, or hydroxyapatite), viscosity (low, medium, high), working time (up to 40 minutes) and exothermic reaction (present or not). Recent alternatives to the original PMMA cement aim to improve application, delivery, and characteristics such as viscosity and working time. These alternatives include radiofrequency-targeted augmentation, radioactivated high-viscose bone cement injected into previously created channels, and compound techniques with implants such as stents, PEEK cages etc. Additional proposals include a synthetic bone substitute (calcium phosphate cement), capable of remodelling or integrating into the surrounding bone, which is expected to work as a carrier for osteoinductive proteins, or a radio-opaque silicon polymer which sticks to itself and adheres to bone, whilst its viscosity gradually increases, resulting in a longer working time and a stiffness close to that of the intact vertebrae. Next generation cements to be used in vertebral augmentation techniques will aim for superior handling properties, provision of immediate reinforcement, new bone formation and new bone in-growth, as well as the addition of anticancer drugs or bioactive additives for bone metabolism promotion.
The VAPOUR trial published in 2016 clearly showed that patients with acute osteoporotic fractures suffering from severe pain clearly benefit from percutaneous vertebroplasty (PVP) over the designed placebo treatment. In clear disparity to older studies, the VAPOUR trial, which is multi-centered, recruited patients with one or two osteoporotic vertebral fractures of less than six weeks’ duration and with a Numeric Rated Scale (NRS) back pain greater than or equal to seven out of 10. Patients were compared and randomly assigned to either a vertebroplasty or a placebo arm.
The VAPOUR trial concluded that PVP is superior to the placebo intervention for pain reduction in patients with acute osteoporotic spinal fractures of less than six weeks’ in duration. Additionally, this trial has showed that conservative management is not free of adverse events and complications, since fracture collapse and retropulsion led to spinal cord compression in two patients of the placebo group. The advantages of the VAPOUR trial over previous masked RCTs are clear and include earlier treatment of vertebral compression fractures in patients with severe pain (NRS ≥7) more than half of whom (57%) were hospitalised, with a 5.5 days reduction of hospital stay reported in the vertebroplasty group. Furthermore, the placebo intervention applied in the VAPOUR trial was much closer to a true sham procedure since the periosteal local anesthetic infiltration applied in the previous masked RCTs could have provided pain relied especially in cases of chronic fractures. Finally, the X-rays at six months post PVP illustrated a 30% greater vertebral height preservation without an increase in additional vertebral fractures.
The wide variety on fracture morphology and substrate in combination to each patient’s different characteristics and co-morbidities demand a tailored lesion and a patient centered approach. Next generation cements to be used in PVP and BKP aim to improve handling properties, reinforcement, osteoconductivity and osteoinductivity, biodegradability and to act as drug carriers. Vertebral augmentation techniques prolong survival and prevent morbidity in patients with vertebral compression fractures. The VAPOUR trial is a well-constructed, masked, randomised placebo-controlled trial clearly illustrating that PVP is a safe and effective procedure for symptomatic patients with acute osteoporotic fractures suffering from severe pain refractory to conservative management. These results are in accordance to the everyday clinical practice and the hundreds of articles published upon vertebroplasty during the last five years post the NEJM RCTs reporting high efficacy and safety rates.
Both PVP and BKP are more efficient than conservative therapy for the management of painful fractures; both techniques save and prolong life as well as prevent morbidity. Complications from performing vertebral augmentation may be less than complications from not performing the procedure. As far as osteoporotic fractures are concerned there is no clearly proven superiority of one technique over the other, however, BKP comes with a longer operation time and at a higher cost. It is evident that throughout the literature there is no clearly proven superiority of one technique over the other; all the aforementioned provocative results and conclusions could easily be related to selection biases. Ideally, a prospective, randomised, direct comparison of the two methods for the treatment of vertebral compression fractures in similar patient groups would provide the answers.