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Fibromyalgia as a Predictor of Complex Regional Pain Syndrome After Distal Radius Fracture.

ABSTRACT: Background: Complex regional pain syndrome (CRPS) can be a devastating complication following extremity injury, but risk factors are not well understood. The purpose of this study was to investigate the association between fibromyalgia and the development of CRPS after distal radius fracture. Methods: The PearlDiver Medicare database was queried using International Classification of Diseases, 9th Revision (ICD-9) and Current Procedural Terminology (CPT) codes for diagnoses and treatments of distal radius fractures. Patients were separated into fibromyalgia and control cohorts, and the prevalence of CRPS was measured at 3, 6, 9, and 12 months from the date of injury or procedure. Demographic factors, treatment modality, and comorbid conditions were analyzed by multivariable logistic regression to reduce confounding and identify additional risk factors. Results: Database queries yielded 853 186 patients diagnosed or treated for distal radius fracture, with 6% having previous diagnosis of fibromyalgia. The prevalence of CRPS following distal radius fracture was increased at 3, 6, 9, and 12 months in the fibromyalgia cohort compared with the control c, with a 1-year incidence of 0.51% compared with 0.20% (odds ratio [OR], 2.54, P < .001). Multivariable logistic regression supported the association, with estimated OR of 2.0 (P < .001). In addition, female gender, surgical or manipulative treatment, and anxiety were positively associated with CRPS, and age >65, diabetes, and heart failure were negatively associated. Conclusions: While the basis of the association between fibromyalgia and CRPS is unknown, our data suggest that it could serve as a useful predictor of CRPS risk, promoting increased vigilance for CRPS symptoms and earlier recognition and treatment, thereby improving patient outcomes.

SUBMITTER: Lipman MD

PROVIDER: S-EPMC6760091 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeCarpal tunnel syndrome (CTS) can present following distal radius fracture (DRF) and may progress to require carpal tunnel release (CTR). The primary aim of this study was to determine the incidence of CTS within 6 months of a DRF and the rate of CTR in this population.MethodsWe used the PearlDiver national insurance database to determine the incidence of CTS after DRF. Patients were identified by International Classification of Diseases-10 codes, and treatment modalities for DRF and CTS were determined by respective Current Procedural Terminology codes. Patients with less than 6 months of follow-up, bilateral DRF, or preexisting CTS were excluded. Patient demographic characteristics were recorded. The time from DRF diagnosis to CTS diagnosis and CTR was determined. A multivariable analysis was performed to determine the differences between patients who underwent a CTR compared with those who were treated conservatively.ResultsWe identified 23,733 patients (6,015 men; 17,718 women) who sustained a DRF. Of these patients, 79.1% were treated nonsurgically and 20.9% underwent surgical fixation. In total, 9.2% (N = 2,179) were diagnosed with CTS in their ipsilateral extremity within 6 months of sustaining the DRF. Of the patients whose DRF was treated nonsurgically, 6.3% (N = 1,198) developed CTS and 2.9% (N = 546) required CTR. Of those patients whose DRF was treated surgically, 19.8% (N = 981) developed CTS and 13.3% (N = 661) required CTR. Of those patients with symptoms severe enough to warrant CTR, 18.5% required a second surgical intervention for the CTR.ConclusionsDistal radius fractures severe enough to require surgical fixation are associated with a higher incidence of perioperative CTS. Accordingly, careful evaluation for and counseling on CTS during surgical fixation may decrease the chance of a second surgery. We have identified a cohort of patients with DRFs who may benefit from prophylactic CTR.Type of study/level of evidenceDiagnostic IV.

Project description:Complex Regional Pain Syndrome (CRPS) is a multifactorial and disabling disorder with complex etiology and pathogenesis. Goals of therapy in CRPS should be pain relief, functional restoration, and psychological stabilization, but early interventions are needed in order to achieve these objectives. Several drugs have been used to reduce pain and to improve functional status in CRPS, despite the lack of scientific evidence supporting their use in this scenario. They include anti-inflammatory drugs, analgesics, anesthetics, anticonvulsants, antidepressants, oral muscle relaxants, corticosteroids, calcitonin, bisphosphonates, calcium channel blockers and topical agents. NSAIDs showed no value in treating CRPS. Glucocorticoids are the only anti-inflammatory drugs for which there is direct clinical trial evidence in early stage of CRPS. Opioids are a reasonable second or third-line treatment option, but tolerance and long term toxicity are unresolved issues. The use of anticonvulsants and tricyclic antidepressants has not been well investigated for pain management in CRPS. During the last years, bisphosphonates have been the mostly studied pharmacologic agents in CRPS treatment and there are good evidence to support their use in this condition. Recently, the efficacy of intravenous (IV) administration of neridronate has been reported in a randomized controlled trial. Significant improvements in VAS score and other indices of pain and quality of life in patients who received four 100 mg IV doses of neridronate versus placebo were reported. These findings were confirmed in the open-extension phase of the study, when patients formerly enrolled in the placebo group received neridronate at the same dosage, and these results were maintained at 1 year follow-up. The current literature concerning sympathetic blocks and sympathectomy techniques lacks evidence of efficacy. Low evidence was recorded for a free radical scavenger, dimethylsulphoxide (DMSO) cream (50%). The same level of efficacy was noted for vitamin C (500 mg per day for 50 days) in prevention of CRPS in patients affected by wrist fracture. In conclusion, the best available therapeutic approach to CRPS is multimodal and is based on the use of several classes of drugs, associated to early physiotherapy. Neridronate at appropriate doses is associated with clinically relevant and persistent benefits in CRPS patients.

Project description:BackgroundBisphosphonates are used to prevent the bone loss and fractures associated with osteoporosis, bone metastases, multiple myeloma, and osteogenesis deformans. Distal limb fractures cause regional bone loss with cutaneous inflammation and pain in the injured limb that can develop into complex regional pain syndrome (CRPS). Clinical trials have reported that antiresorptive bisphosphonates can prevent fracture-induced bone loss, inhibit serum inflammatory cytokine levels, and alleviate CRPS pain. Previously, we observed that the inhibition of inflammatory cytokines or adaptive immune responses attenuated the development of pain behavior in a rat fracture model of CRPS, and we hypothesized that bisphosphonates could prevent pain behavior, trabecular bone loss, postfracture cutaneous cytokine upregulation, and adaptive immune responses in this CRPS model.MethodsRats underwent tibia fracture and cast immobilization for 4 weeks and were chronically administered either subcutaneously perfused alendronate or oral zoledronate. Behavioral measurements included hindpaw von Frey allodynia, unweighting, warmth, and edema. Bone microarchitecture was measured by microcomputed tomography, and bone cellular activity was evaluated by static and dynamic histomorphometry. Spinal cord Fos immunostaining was performed, and skin cytokine (tumor necrosis factor, interleukin [IL]-1, IL-6) and nerve growth factor (NGF) levels were determined by enzyme immunoassay. Skin and sciatic nerve immunoglobulin levels were determined by enzyme immunoassay.ResultsRats with tibia fractures developed hindpaw allodynia, unweighting, warmth, and edema, increased spinal Fos expression and trabecular bone loss in the lumbar vertebra and bilateral distal femurs as measured by microcomputed tomography, increased trabecular bone resorption and osteoclast surface with decreased bone formation rates, increased cutaneous inflammatory cytokine and NGF expression, and elevated immunocomplex deposition in skin and nerve. Alendronate (60 μg/kg/d subcutaneously [s.c.]) or zoledronate (3 mg/kg/d orally) treatment for 28 days, started at the time of fracture, completely inhibited the development of hindpaw allodynia and reduced hindpaw unweighting by 44% ± 13% and 58% ± 5%, respectively. Orally administered zoledronate (3 mg/kg/d for 21 days) treatment also completely reversed established allodynia and unweighting when started at 4 weeks postfracture. Histomorphometric and microcomputed tomography analysis demonstrated that both the 3 and 60 μg/kg/d alendronate treatments reversed trabecular bone loss (an 88% ± 25% and 188% ± 39% increase in the ipsilateral distal femur BV/TV, respectively) and blocked the increase in osteoclast numbers and erosion surface observed in bilateral distal femurs and in L5 vertebra of the fracture rats. Alendronate treatment inhibited fracture-induced increases in hindpaw inflammatory mediators, reducing postfracture levels of tumor necrosis factor by 43% ± 9%, IL-1 by 60% ± 9%, IL-6 by 56% ± 14%, and NGF by 37% ± 14%, but had no effect on increased spinal cord Fos expression, or skin and sciatic nerve immunocomplex deposition.ConclusionsCollectively, these results indicate that bisphosphonate therapy inhibits pain, osteoclast activation, trabecular bone loss, and cutaneous inflammation in the rat fracture model of CRPS, data supporting the hypothesis that bisphosphonate therapy can provide effective multimodal treatment for CRPS.

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Fibromyalgia as a Predictor of Complex Regional Pain Syndrome After Distal Radius Fracture.

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