Establishment and validation of a nomogram and web calculator for the risk of new vertebral compression fractures and cement leakage after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures

Purpose The aim of this work was to investigate the risk factors for cement leakage and new-onset OVCF after Percutaneous vertebroplasty (PVP) and to develop and validate a clinical prediction model (Nomogram). Methods Patients with Osteoporotic VCF (OVCF) treated with PVP at Liuzhou People’s Hospital from June 2016 to June 2018 were reviewed and met the inclusion criteria. Relevant data affecting bone cement leakage and new onset of OVCF were collected. Predictors were screened using univariate and multi-factor logistic analysis to construct Nomogram and web calculators. The consistency of the prediction models was assessed using calibration plots, and their predictive power was assessed by tenfold cross-validation. Clinical value was assessed using Decision curve analysis (DCA) and clinical impact plots. Results Higher BMI was associated with lower bone mineral density (BMD). Higher BMI, lower BMD, multiple vertebral fractures, no previous anti-osteoporosis treatment, and steroid use were independent risk factors for new vertebral fractures. Cement injection volume, time to surgery, and multiple vertebral fractures were risk factors for cement leakage after PVP. The development and validation of the Nomogram also demonstrated the predictive ability and clinical value of the model. Conclusions The established Nomogram and web calculator (https://dr-lee.shinyapps.io/RefractureApp/) (https://dr-lee.shinyapps.io/LeakageApp/) can effectively predict the occurrence of cement leakage and new OVCF after PVP.

Effectiveness of Rehabilitative Intervention on Pain, Postural Balance, and Quality of Life in Women with Multiple Vertebral Fragility Fractures: A Prospective Cohort Study

Patients with vertebral fragility fractures often experience chronic pain, postural and balance disorders, and poor quality of life (QoL). Although several studies have investigated the role of rehabilitation in severe osteoporosis, the effectiveness of this intervention in patients with multiple vertebral fractures is poorly known. The aim of our longitudinal cohort study is to evaluate the effectiveness of rehabilitation, including postural training, resistance exercises, and visual stabilization exercises, for a 7-week period, on the pain, postural balance, and QoL of subjects with at least two vertebral fragility fractures receiving denosumab and vitamin D. We investigated, before (T0) and after (T1, at 7 weeks) rehabilitation, the following outcome measures on 28 patients: pain (Numerical Rating Scale (NRS)), self-perceived QoL (36-Item Short Form Survey (SF-36) and Mini-Osteoporosis Quality of Life Questionnaire (Mini-OQOL)), dizziness (Dizziness Handicap Inventory (DHI-I)), mobility (Timed-Up and Go (TUG) test), and instrumental posturographic assessment (FreeMed posturography system). At the end of the treatment, improvements of pain and QoL were recorded. Pain relief was highly obtained in patients with more than two vertebral fractures. Moreover, a significant functional improvement (TUG test) was found in those with two vertebral fractures, without any statistically significant change reported for other outcomes. Our findings suggest that combined intervention, including anti-osteoporotic drugs and postural rehabilitation, should be proposed to osteoporotic patients with multiple vertebral fractures.

Long-Term Follow-Up of Denosumab Discontinuers with Multiple Vertebral Fractures in the Real-World: A Case Series

Denosumab discontinuation is associated with rapid reversal of bone turnover suppression and with a considerable increase in fracture risk, including a risk for multiple vertebral fractures (MVF). Long-term follow-up of patients who sustained MVF after denosumab discontinuation has not been reported. This case-series was aimed to provide a long-term follow-up on the management and outcome of denosumab discontinuers who initially presented with multiple vertebral fractures. Denosumab discontinuers were identified from a computerized database of a large healthcare provider. Baseline and follow-up clinical, laboratory, and imaging data were obtained from the computerized database and electronic medical records. The post-denosumab discontinuers MVF patients consisted of 12 women aged 71±12. Osteoporotic fractures were prevalent before denosumab discontinuation in 6 of the patients. The majority received bisphosphonates before denosumab. MVF occurred 134±76 days after denosumab discontinuation. The patients were followed for a median of 36.5 (IQR 28.2, 42.5) months after MVF. Two patients passed-away. Two patients suffered recurrent vertebral fractures. Following MVF, patients were treated inconsistently with denosumab, teriparatide, oral, and intravenous bisphosphonates, in various sequences. Two patients underwent vertebroplasty/kyphoplasty. This long-term follow-up of real-world patients with MVF following denosumab discontinuation reveals that management is inconsistent, and recurrent fractures are not uncommon. It calls for clear management guidelines for patients with MVF after denosumab discontinuation and for special attention to this high-risk group.

Denosumab Discontinuation and the Rebound Phenomenon: A Narrative Review

Denosumab is a potent antiresorptive agent that substantially increases bone mineral density and reduces fracture rates at all skeletal sites for as long as it is administered. However, its favorable skeletal effects reverse quickly upon its discontinuation, because of a vast increase of osteoclast number and activity, which leads to a subsequent profound increase of bone turnover above pre-treatment values, a phenomenon commonly described as “rebound phenomenon”. More importantly, most patients experience rapid, profound bone loss due to this burst of bone resorption that may lead in a minority of these patients to occurrence of fractures, especially multiple vertebral fractures. Therefore, subsequent antiresorptive treatment is mandatory, although the optimal regimen is yet to be clarified. In the present review, we outline what is currently known regarding the negative effects of denosumab discontinuation on different aspects of bone status, the factors that may affect them, and strategies to prevent them.

Should denosumab treatment for osteoporosis be continued indefinitely?

Denosumab was approved for the treatment of postmenopausal osteoporosis in 2010, based on the FREEDOM study, which indicated a benefit in terms of increased bone mineral density and reduced risk of major osteoporotic fracture. In the initial clinical studies it was noted that discontinuation of denosumab can lead to a rebound of bone turnover markers and loss of accrued bone mineral density. An increased risk of fractures (multiple vertebral fractures in particular) associated with discontinuation was noted after approval and marketing of denosumab. For many patients experiencing gain in bone mineral density and fracture prevention while taking denosumab, there is no reason to stop therapy. However, discontinuation of denosumab may happen due to non-adherence; potential lack of efficacy in an individual; where reimbursement for therapy is limited to those with bone mineral density in the osteoporosis range, when assessment reveals this has been exceeded; or patient or physician concern regarding side effects. This review paper aims to discuss these concerns and to summarize the data available to date regarding sequential osteoporosis therapy following denosumab cessation to reduce the risk of multiple vertebral fracture.