Rebound-associated Vertebral Fractures Research Articles

Progression of multiple vertebral fractures after denosumab discontinuation under treatment with romosozumab. A case-report

IntroductionDenosumab (Dmab) is widely used for the treatment of post-menopausal osteoporosis. Its discontinuation is sometimes accompanied by multiple vertebral fractures. Romosozumab (Rmab) has not been tested for its ability to prevent the rebound phenomenon. Case presentationWe present the case of a 68-year-old female patient with post-menopausal osteoporosis under treatment with Rmab who presented with multiple vertebral fractures after denosumab discontinuation. The addition of Rmab did not prevent new-onset rebound-associated vertebral fractures. The patient discontinued Rmab and Dmab was re-initiated. After six months, no new vertebral fractures occurred, bone mineral density increased and bone turnover markers remained suppressed. DiscussionOur clinical case illustrates the ineffectiveness of Rmab to prevent the multiple vertebral fracture cascade attributable to discontinuation of Dmab. We believe that treatment with Rmab might not be enough to prevent this phenomenon. Treatment with Dmab or possibly combination treatment with Dmab and Rmab could be another treatment option.

Glucocorticoid-induced osteoporosis: an overview with focus on its prevention and management.

The widespread use of glucocorticoids (GCs) contributes to the effective management of several diseases and conditions. However, it comes at a price in the case of the bones causing glucocorticoid-induced osteoporosis (GIOP), the most common cause of secondary osteoporosis and fractures. Several scientific societies have issued comprehensive guidelines on the optimal management of patients receiving GCs with the aim of providing answers to three fundamental questions, namely, whom to treat, when to treat, and how to treat. Both common ground and different approaches exist among them. General preventive measures should start along with GC initiation, and the duration of GC therapy should be limited to the minimal effective range. A pre-existing fracture, age, gender, menopausal status, dose, and duration of GC treatment are key factors in the decision to initiate antiosteoporotic medication. Oral bisphosphonates are typically regarded as the first-line treatment choice for GIOP partly due to their cost-effectiveness. Denosumab is another valid option, but an "exit strategy" should be considered before its initiation due to the risk of rebound-associated vertebral fractures upon its discontinuation. Since impaired bone formation represents the main mechanism by which GCs negatively affect skeletal health, osteoanabolic therapies appear to be pathophysiologically the more appropriate and appealing option, although cost considerations currently limit their use to selected severe cases. Regardless of the agent selected to mitigate the impact of GCs on the skeleton, what is most crucial is that the treating physician correctly stratifies the risk and intervenes at the right time.

Twenty-four months of follow-up in women with rebound-associated vertebral fractures after discontinuation of denosumab: a single-centre case series.

To describe the densitometric and biochemical changes achieved with osteoactive treatment after 24months of follow-up in patients who suffered rebound-associated vertebral fractures (RAVFs) after Dmab discontinuation, and to report the occurrence of new vertebral and non-vertebral fractures. Patients with RAVFs who received retreatment (RT) for 24months were included. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH), along with C-terminal cross-linked telopeptide of type I collagen, osteocalcin, and bone alkaline phosphatase. Data were collected at the start of the RT and after 24months. Seven female patients were included. RT consisted in Dmab (n = 3), teriparatide (TPT) (n = 3) and zoledronate (Zol) (n = 1). At 24months, the mean BMD change was 2.2% at LS, 6.8% at FN and 3.8% at TH in the Dmab group, 7.5% at LS, 1.4% at FN and 3.7% at TH in the TPT group and, 5.0% at LS, 0.6% at FN and 3.9% at TH in the patient with Zol. After 24months of follow-up, no patient suffered new fractures. In this series of patients with RAVFs, we did not observe any new fractures and the BMD remained stable after 24months of RT. Future studies are needed to evaluate the most suitable treatment approach after RAVFs but these preliminary data suggest that all denosumab, zoledronate and teriparatide might be adequate options.

Similarities and Differences in the Management of Patients with Osteoporotic Vertebral Fractures and Those with Rebound-Associated Vertebral Fractures Following Discontinuation of Denosumab.

Rebound-associated vertebral fractures (RVFx) following denosumab discontinuation are typically multiple, are commonly associated with acute sharp pain, increase the risk of imminent fractures, and are pathogenetically different from common osteoporotic vertebral fractures (VFx). A clinically relevant question is whether patients with RVFx should be managed differently from patients with osteoporotic VFx. To address this question, we performed a systematic search of the PubMed database, and we reviewed current evidence on the optimal management of patients with RVFx. For pain relief of patients with RVFx, potent analgesics, often opioids, are essential. Information on the effectiveness of braces in these patients is scarce. Vertebroplasty and kyphoplasty are strongly contraindicated as they confer a substantial risk for new VFx. Exercise may be helpful, but again evidence is lacking. In contrast to patients with osteoporotic VFx, in whom initial treatment with bone-forming agents is recommended, patients with RVFx should initiate treatment with potent antiresorptives. To summarize, patients who have sustained RVFx following denosumab discontinuation are at a very high risk for new fractures, especially VFx. The management of such patients requires a multidisciplinary approach that should not be restricted to pain relief and administration of antiosteoporotic medication, but should also include back protection, early mobilization, and appropriate exercise.

Rebound-Associated Vertebral Fractures Two Months After a Missed Dose of Denosumab

Introduction: Denosumab, an anti-resorptive medication approved for treatment of osteoporosis, increases bone mineral density and reduces fracture risk. Discontinuation of treatment is associated with bone turnover rebound and reduced bone mineral density. We report a case of a woman without prior history of fragility fractures who presented with multiple spontaneous vertebral fractures two months after a missed dose of Denosumab, which is earlier than current available literature. Clinical Case: A 54-year old female was diagnosed with osteoporosis at the age of 50 with a DXA revealing T-scores of LS -2.9 SD, LFN -0.6 SD, TH -0.5 SD. Ten-year probability of MOF evaluated by FRAX was 6%. Work-up for secondary causes of osteoporosis during the time was unremarkable. She was started on Denosumab 60 mg every 6 months from July 2016 to July 2019, receiving a total of 5 injections. She had missed her dose of Denosumab in January 2020. Two months after the missed dose, she presented to a local hospital with complaints of chest and epigastric pain. A CTA was performed as part of evaluation which was unremarkable aside from an incidental finding of thoracic compression fractures. An MRI of the spine was subsequently done which showed a recent-appearing moderate to severe wedge compression fracture and edema of the T7 and T6 vertebral bodies, and of the upper two-thirds of the T4.A biological and radiological work-up to exclude other causes of osteoporosis to explain the patient’s vertebral fractures was performed. The patient did not have renal failure, vitamin D deficiency, hyperthyroidism, primary hyperparathyroidism, Cushing’s disease, hypophosphatemia, multiple myeloma, Celiac disease, diabetes mellitus, or prior glucocorticoid treatment. During the time of treatment and discontinuation of Denosumab, the patient was on adequate supplementation of calcium and Vitamin D. The patient’s vertebral fractures were treated with kyphoplasty. To treat osteoporosis and prevent further risk of fractures, she was started on an anabolic agent Abaloparatide. Conclusion: This case demonstrates rebound vertebral fractures occurring very shortly after discontinuing Denosumab in a relatively young woman with low probability of major osteoporotic fracture. Further investigation must be done to determine pathophysiological process involved of vertebral fractures and treatment regimen after sudden discontinuation of Denosumab.

Efficacy of Antiosteoporotic Medications in Patients With Rebound-Associated Fractures After Denosumab Discontinuation

Denosumab discontinuation results in rapid bone loss and increased risk of multiple rebound-associated vertebral fractures (RAVFs). The optimal treatment for patients who have sustained such fractures is currently unknown. We aimed to investigate the bone mineral density (BMD) changes achieved with various regimens in postmenopausal women who had sustained RAVFs after denosumab discontinuation in everyday clinical practice. In this multicenter, retrospective observational study, 39 Greek postmenopausal women from six regional bone centers throughout Greece with RAVFs after denosumab discontinuation were included. We collected BMD and fracture data before and 1 year after treatment with denosumab (n = 20), teriparatide (n = 8), zoledronate (n = 8) or teriparatide/denosumab combination (n = 3). Both lumbar spine (LS)-- and femoral neck (FN)-BMD were preserved with all regimens used. With the exception of zoledronate, a trend towards increase was observed with all regimens in LS-BMD. Three patients sustained additional fractures despite treatment reinstitution (2 with zoledronate and 1 with teriparatide). Among patients with RAVFs following denosumab discontinuation both antiresorptive (zoledronate and denosumab) and anabolic (teriparatide) treatment as well as the combination of denosumab with teriparatide seem to be effective in terms of BMD response.

Progression of Rebound-Associated Vertebral Fractures Following Denosumab Discontinuation Despite Reinstitution of Treatment: Suppressing Increased Bone Turnover May Not Be Enough

Rebound-associated vertebral fractures (RAVFs) could occur in a minority of the patients who discontinue denosumab. In such patients, denosumab is often reinstituted to rapidly suppress bone turnover and avert the risk of additional fractures. Herein we report the cases of 2 patients who sustained RAVFs, and in whom resuming denosumab treatment did not avert the occurrence of new RAVFs a few months later, despite the suppression of bone turnover markers. It seems that denosumab reinstitution cannot completely eliminate the risk of new RAVFs and that the rebound of bone turnover may not be the sole mechanism to explain this phenomenon.

Magnetic resonance imaging has an advantage over conventional spine X-rays in the evaluation of rebound-associated vertebral fractures following denosumab discontinuation.

Patients discontinuing or neglecting denosumab treatment are at risk of sustaining rebound-associated vertebral fractures (RAVFs). In everyday clinical practice, conventional X-rays are used to diagnose such events in patients reporting acute back pain. Herein we report the cases of two patients, in whom magnetic resonance imaging (MRI) depicted more RAVFs or allowed earlier detection of RAVFs compared with conventional X-rays. It seems that, in the setting of RAVFs following denosumab discontinuation, MRI imaging provides better accuracy in the diagnostic process and in the classification assessment compared to conventional X-rays, thus allowing an earlier and clearer picture of the magnitude of spinal damage. This could have an impact on clinical decisions and improve patient's management.

Letter to the Editor: Severe Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: Nine Clinical Cases Report

Letter to the Editor: Severe Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: Nine Clinical Cases Report