The results of VERTOS II and VERTOS IV showed that at 12-monthfollow-up patients from the conservative and sham group had more often high pain scores (VAS ≥ 5) than patients who underwent PV. There are four predictors found for the risk of high pain scores (VAS ≥ 5) after 12-monthfollow-up, namely female, baseline VAS > 8, pain > 3 weeks before procedure and new OVCFs. When these four predictors hold true, there is increased risk of high VAS after 12-month follow-up, with no significant pain outcome difference between conservative therapy, sham or PV (no policy difference). However, moderate vertebral body height loss was significantly more predictive of low pain scores at 12 months after PV than after other treatments.
OVCFs can cause severe back pain and kyphosis with a negative impact on morbidity and quality of life. The retrospective and sham trials conducted until present showed contradictory results [5, 6, 9,10,11]. Consequently, various and different recommendations are presented for patient selection and optimal treatment strategies for painful OVCFs [12, 13].
In daily practice, clinicians taking care of OVCF patients are faced with the dilemma of whether to treat an individual patient with augmentation or conservative therapy. This paper analysed data and identified factors from two previous published RCTs (VERTOS II and VERTOS IV) that can influence the clinical outcome (pain relief) at 12 months. This may help to identify the patients who most likely benefit from PV.
From the combined results of the two VERTOS trials, we found that significantly more patients in the sham and conservative group had a high pain score (VAS ≥ 5) at 12-month follow-up than those in the PV group (40.1 vs 20.7%). When investigating the demographic and clinical characteristics, we identified 5 predictors for sustained high local back pain: female gender, patients with a baseline VAS > 8, pain duration > 3 weeks until treatment, mild or severe fracture classification and new fractures during follow-up. Female gender is more predisposed to osteoporosis and subsequent new fractures. Severe fractures causing kyphosis, heal slower and probably are much more painful. These factors probably combine and result in a high pain score after 12 months. Neither the number of treated levels nor the fracture level were significant predictors of high VAS scores at 12 months.
Odds ratio effect sizes of two dichotomous predictors can be interpreted inversely [14]. Therefore, our results indicate that four predictors [male, < 3 weeks of pain before treatment, baseline 5 < VAS < 8, without new fractures during follow-up] provide higher probability of successful pain reduction at 12 months after treatment of (sub)acute OVCFs (both in conservative, sham and PV). In the case of moderate (sub)acute OVCF, there is also a higher probability of successful pain reduction, but only after PV and not after conservative or sham intervention. The practical implication is that patients with moderate (sub)acute OVCFs are particularly suited to PV and not conservative treatment or sham intervention. Although no definitive recommendation can be made for an individual patient based on these findings, the combined results of these two trials provide additional perspective and further nuance to the VERTOS IV conclusion.
In contrast to VERTOS II, VERTOS IV on average did not indicate any added value of PV regarding pain relief compared to sham. However, it may be important to identify individual characteristics of patients for whom PV does result in significant pain reduction. Indeed, we must realize that there seems to be a distinct subgroup of patients with (sub)acute OVCFs and certain baseline characteristics predictive of successful pain relief after PV as opposed to the general conclusion of VERTOS IV.
The VAPOUR trial showed clinical success for PV over placebo for patients meeting the inclusion criteria severe pain (VAS ≥ 7) at baseline, OVCFs of less than 6 weeks duration and OVCFs at the thoracolumbar spinal segment as predictors for clinical success [11]. Although these results suggest that patients with severe pain and younger fractures may benefit from a PV intervention, the current study provides a more nuanced perspective. First, younger fracture age was predictive of low pain at 12 months, yet this effect was found regardless of the received intervention. Second, we found that patients with severe pain (VAS > 8) at baseline showed a higher chance on having VAS of 5 or higher at 12 months, regardless of the received intervention. Although VAPOUR showed on average a clinical success for PV compared to sham in a population of patients with severe pain (VAS ≥ 7), the study did not investigate the characteristics of patients who benefited most from PV treatment. The currently study revealed that patients with a moderate vertebral fracture type benefit most from PV. Identification of such characteristics may contribute to better select patients with OVCFs for PV. This approach seems a rational step, balancing between the risk of overtreating or undertreating this fragile population.
Along with the worldwide discussion on PV, this paper discusses the selection of patients for PV. VERTOS IV was the 3rd negative placebo trial of PV in contrast to the VAPOUR trial [11], which was the only positive placebo trial for PV, and was contemporary with VERTOS IV. Among other differences, the key differences in patient selection between VERTOS IV and VAPOUR are (1) vertebral fracture duration at the time of PV, (2) pain severity at baseline and (3) inclusion of inpatients. Mean fracture duration in VAPOUR was 2.6 weeks compared to 6.1 weeks in VERTOS IV, and this may be the critical factor explaining the different outcomes in these two trials. The pain severity at baseline was 8.6 on VAS for VAPOUR whereas 7.8 for VERTOS IV. In VAPOUR, 59% of patients were hospitalized in contrast to 0% inpatients in VERTOS IV. These trial differences and more information are described in the publication by Diamond et al.[15]. Compared with the other RCTs, VAPOUR used a different clinical approach offering PV much earlier compared to a longer fracture duration up to 12 months in the Kallmes’ and Buchbinder studies and up to 12 weeks in VERTOS IV. In addition, VAPOUR used a different cementation technique to the trials by Kallmes and Buchbinder. The “vertebral fill” technique is designed to brace the whole vertebral body against instability, augmenting it and preventing further collapse. The mean volume of PMMA injected into the vertebral body was three times greater in VAPOUR (7.5 mL) than in the Kallmes (2.6 mL).