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Non-randomised trials have reported benefits of kyphoplasty in patients with cancer and vertebral compression fractures (VCFs). We aimed to assess the efficacy and safety of balloon kyphoplasty compared with non-surgical management for patients with cancer who have painful VCFs. The Cancer Patient Fracture Evaluation (CAFE) study was a randomised controlled trial at 22 sites in Europe, the USA, Canada, and Australia. We enrolled patients aged at least 21 years who had cancer and one to three painful VCFs. Patients were randomly assigned by a computer-generated minimisation randomisation algorithm to kyphoplasty or non-surgical management (control group). Investigators and patients were not masked to treatment allocation. The primary endpoint was back-specific functional status measured by the Roland-Morris disability questionnaire (RDQ) score at 1 month. Outcomes at 1 month were analysed by modified intention to treat, including all patients with data available at baseline and at 1 month follow-up. Patients in the control group were allowed to crossover to receive kyphoplasty after 1 month. This study is registered with ClinicalTrials.gov, NCT00211237. Between May 16, 2005, and March 11, 2008, 134 patients were enrolled and randomly assigned to kyphoplasty (n=70) or non-surgical management (n=64). 65 patients in the kyphoplasty group and 52 in the control group had data available at 1 month. The mean RDQ score in the kyphoplasty group changed from 17·6 at baseline to 9·1 at 1 month (mean change −8·3 points, 95% CI −6·4 to −10·2; p<0·0001). The mean score in the control group changed from 18·2 to 18·0 (mean change 0·1 points; 95% CI −0·8 to 1·0; p=0·83). At 1 month, the kyphoplasty treatment effect for RDQ was −8·4 points (95% CI −7·6 to −9·2; p<0·0001). The most common adverse events within the first month were back pain (four of 70 in the kyphoplasty group and five of 64 in the control group) and symptomatic vertebral fracture (two and three, respectively). One patient in the kyphoplasty group had an intraoperative non-Q-wave myocardial infarction, which resolved and was attributed to anaesthesia. Another patient in this group had a new VCF, which was thought to be device related. For painful VCFs in patients with cancer, kyphoplasty is an effective and safe treatment that rapidly reduces pain and improves function. Medtronic Spine LLC.

Balloon kyphoplasty is a minimally invasive procedure for the treatment of painful vertebral fractures, which is intended to reduce pain and improve quality of life. We assessed the efficacy and safety of the procedure. Adults with one to three acute vertebral fractures were eligible for enrolment in this randomised controlled trial at 21 sites in eight countries. We randomly assigned 300 patients by a computer-generated sequence to receive kyphoplasty treatment (n=149) or non-surgical care (n=151). The primary outcome was the difference in change from baseline to 1 month in the short-form (SF)-36 physical component summary (PCS) score (scale 0–100) between the kyphoplasty and control groups. Quality of life and other efficacy measurements and safety were assessed up to 12 months. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00211211. 138 participants in the kyphoplasty group and 128 controls completed follow-up at 1 month. By use of repeated measures mixed effects modelling, all 300 randomised participants were included in the analysis. Mean SF-36 PCS score improved by 7·2 points (95% CI 5·7–8·8), from 26·0 at baseline to 33·4 at 1 month, in the kyphoplasty group, and by 2·0 points (0·4–3·6), from 25·5 to 27·4, in the non-surgical group (difference between groups 5·2 points, 2·9–7·4; p<0·0001). The frequency of adverse events did not differ between groups. There were two serious adverse events related to kyphoplasty (haematoma and urinary tract infection); other serious adverse events (such as myocardial infarction and pulmonary embolism) did not occur perioperatively and were not related to procedure. Our findings suggest that balloon kyphoplasty is an effective and safe procedure for patients with acute vertebral fractures and will help to inform decisions regarding its use as an early treatment option. Medtronic Spine LLC.

To the Editor: Oncogenic osteomalacia is a rare syndrome that is usually driven by small, mesenchymal tumors that express phosphatonins, proteins that decrease the abundance of sodium–phosphate cotransporters in the proximal renal tubule. This decrease causes renal phosphate wasting and leads to the clinical features of oncogenic osteomalacia, which include hyperphosphaturia, hypophosphatemia, reduced or abnormal serum 1,25-dihydroxyvitamin D levels, and osteomalacia. 1 , 2 The standard treatment of oncogenic osteomalacia is surgical excision of the mesenchymal tumor, which rapidly and permanently abrogates all symptoms. However, tumor removal can be complicated, because the lesion is usually small and difficult to distinguish from the . . .

Background Clinical trial participants may be temporarily absent or withdraw from trials, leading to missing data. In intention-to-treat (ITT) analyses, several approaches are used for handling the missing information - complete case (CC) analysis, mixed-effects model (MM) analysis, last observation carried forward (LOCF) and multiple imputation (MI). This report discusses the consequences of applying the CC, LOCF and MI for the ITT analysis of published data (analysed using the MM method) from the Fracture Reduction Evaluation (FREE) trial. Methods The FREE trial was a randomised, non-blinded study comparing balloon kyphoplasty with non-surgical care for the treatment of patients with acute painful vertebral fractures. Patients were randomised to treatment (1:1 ratio), and stratified for gender, fracture aetiology, use of bisphosphonates and use of systemic steroids at the time of enrolment. Six outcome measures - Short-form 36 physical component summary (SF-36 PCS) scale, EuroQol 5-Dimension Questionnaire (EQ-5D), Roland-Morris Disability (RMD) score, back pain, number of days with restricted activity in last 2 weeks, and number of days in bed in last 2 weeks - were analysed using four methods for dealing with missing data: CC, LOCF, MM and MI analyses. Results There were no missing data in baseline covariates values, and only a few missing baseline values in outcome variables. The overall missing-response level increased during follow-up (1 month: 14.5%; 24 months: 28%), corresponding to a mean of 19% missing data during the entire period. Overall patterns of missing response across time were similar for each treatment group. Almost half of all randomised patients were not available for a CC analysis, a maximum of 4% were not included in the LOCF analysis, and all randomised patients were included in the MM and MI analyses. Improved estimates of treatment effect were observed with LOCF, MM and MI compared with CC; only MM provided improved estimates across all six outcomes considered. Conclusions The FREE trial results are robust as the alternative methods used for substituting missing data produced similar results. The MM method showed the highest statistical precision suggesting it is the most appropriate method to use for analysing the FREE trial data. Trial Registration This trial is registered with ClinicalTrials.gov (number NCT00211211 ).

An investigation was conducted into the effects of double-level T12-L2 posterior fixation on the mobility of neighboring unfused segments. The segmental mobility of adjacent segments above and below the fixation in ten cadaveric human thoracolumbar spine specimens was measured before and after fixation by biomechanical testing in flexion, extension, right lateral bending, and right rotation, and the data were compared. In flexion and extension, mobility of the segment above the double-level T12-L2 posterior fixation was significantly increased (P<0.05). In the adjacent segment below the fixation, there was no significant increased mobility after fixation for each moment applied. There is evidence that the adjacent segment above a double-level T12-L2 posterior fixation becomes more mobile, and this may lead to an accelerated degeneration in the facet joints due to increased stress at this point. This could be responsible for symptoms like low back pain after spinal surgery.

Multiple myeloma (MM) represents approximately 15% of haematological malignancies and most of the patients present with bone involvement. Focal or diffuse spinal osteolysis may result in significant morbidity by causing painful progressive vertebral compression fractures (VCFs) and deformities. Advances in the systemic treatment of myeloma have achieved high response rates and prolonged the survival significantly. Early diagnosis and management of skeletal events contribute to improving the prognosis and quality of life of MM patients. The management of patients with significant pain due to VCFs in the acute phase is not standardised. While some patients are successfully treated conservatively, and pain relief is achieved within a few weeks, a large percentage has disabling pain and morbidity and hence they are considered for surgical intervention. Balloon kyphoplasty and percutaneous vertebroplasty are minimally invasive procedures which have been shown to relieve pain and restore function. Despite increasing positive evidence for the use of these procedures, the indications, timing, efficacy, safety and their role in the treatment algorithm of myeloma spinal disease are yet to be elucidated. This paper reports an update of the consensus statement from the International Myeloma Working Group on the role of cement augmentation in myeloma patients with VCFs.

Osteoclasts are essential for bone resorption, playing a crucial role in skeletal development, homeostasis, and remodeling. Their differentiation depends on the RANK receptor encoded by the TNFRSF11A gene, with defects in this gene linked to osteoclast-poor sclerosing skeletal dysplasias. This report presents a 37-yr-old woman with normal height, valgus deformities that were treated surgically, frequent fractures, scoliosis, mildly elevated BMD, sclerotic diaphyseal bone, and metaphyseal widening. Initially suspected of having dysosteosclerosis, her diagnosis shifted toward Pyle disease due to the valgus deformity and prominent metaphyseal widening and translucency. Genetic analysis identified 2 pathogenic TNFRSF11A variants: a nonsense mutation c.1093G>T, p.(Glu365*) and a frameshift mutation c.1266_1268delinsCC, p.(Leu422Phefs*104). Thus, genetic and clinical assessment converged on the diagnosis of a mild form of dysosteosclerosis. Both mutations introduced premature stop codons but escaped complete nonsense-mediated decay, potentially permitting residual protein function. Analysis of patient-derived osteoclasts cultured on glass surfaces showed partial differentiation. However, in vitro resorptive function was strongly impaired, which was clinically reflected by reduced serum concentration of the bone resorption marker CTx. Despite this impairment, the retained residual resorptive function likely explains the patient’s relatively mild clinical presentation. These findings underscore the complex genetic interactions that affect osteoclast function, leading to a spectrum of phenotypes in osteoclast-related bone disorders. Lay Summary Osteoclasts are vital for maintaining bone health by breaking down bone tissue. This report describes a 37-yr-old woman diagnosed with dysosteosclerosis; a condition caused by mutations in the TNFRSF11A gene that impair bone resorption. She experienced scoliosis and frequent fractures from minor injuries. Initially suspected of having Pyle disease due to specific bone defects, genetic testing confirmed dysosteosclerosis with 2 mutations identified. Despite her milder symptoms, she faced numerous fractures. This case provides insights into the link between genetic mutations and bone disorders, highlighting the complexity of bone remodeling mechanisms. Graphical Abstract Graphical Abstract

In the operative treatment of spinal injuries, the reconstruction of the anterior column of the thoracolumbar spine is still controversial. We conducted a prospective clinical study to investigate the clinical and radiological outcome of 50 patients treated with a vertebral body replacement of adjustable height (Synex). Fifty consecutive patients were evaluated during in-patient treatment and at 12 and 20 months post-operatively in clinical notes and radiographs. 38/50 patients were operated for traumatic fractures. Out of 50 patients 45 attended the follow-up clinic 1 year post-operatively and 39 of these patients were examined after 20 months. Twenty-five patients returned to pre-injury activities within 1 year. This number increased to 29/39 patients at 20 months. Seventy-three percent of the patients returned to their job. After 1 year 25/45 patients complained of little or no back pain and 6 months later six patients were limited in their back function. At 1 year only three patients complained of surgical site pain which was improved at their final follow-up at 20 months. Individual satisfaction was determined using a score on a visual analog scale containing 19 questions on back pain, and functional limitation of the spine that has to be filled in by the patients at three different points of time. The score decreased from 87/100 pre-operatively to 65/100 at 1 year follow-up (P<0.001). The average permanent correction of the injured vertebra was 16.8 degrees (88%) including 2.3 degrees (12%) loss of correction at 12 months after operation. Bony integration was obtained in 83%. Early and intermediate outcome with the Synex vertebral replacement device for reconstruction of the anterior column appears promising. The loss of correction or reduction was only minimal. On the basis of our results we recommend the Synex implant as an alternative for the fixation and stabilisation of thoracolumbar fractures. However, long-term results and a clinically random control study are still required.

By contrast, vertebroplasty simply cements the broken fragments together with little anatomical correction and less predict able cement delivery.2-4 The resulting safety difference in bone cement-related complications is supported by several systematic meta-analyses comparing the two technologies.2-4 Kallmes and Jarvik assume incorrectly that the positive outcomes of FREE support the validity of vertebroplasty, and that a negative outcome with the ongoing sham-controlled vertebroplasty study would bring FREE into question. DW has received honoraria for consulting from Medtronic Spine LLC, and Cryolife and has received research funding from Medtronic Spine LLC, Zimmer, Apatec, and Cryolife; JVM and LB have received honoraria for consulting from Medtronic Spine LLC; JR is employed by the Swedish National Competence Centre for musculoskeletal disorders at Lund University Hospital, Sweden, which has received compensation for work by Medtronic Spine LLC; SB has received honoraria for consulting from Medtronic Spine LLC and has received consulting or advisory board fees, lecture fees, and research funding or grant support from Amgen, Eli Lilly, Kyphon, Merck, Novartis, Procter & Gamble, Sanofi-Aventis, Servier, and Roche-GlaxoSmithKline. *Douglas Wardlaw, Jan Van Meirhaeghe, Leonard Bastian, Jonas Ranstam, Steven Boonen, for the Fracture Reduction Evaluation (FREE) Study Investigators d.wardlaw@nhs.net Woodend Hospital, Aberdeen AB15 6ZQ, UK (DW); Algemeen Ziekenhuis St Jan, Brugge, Belgium (JVM); Klinikum Leverkusen, Leverkusen, Germany (LB); Swedish National Competence Centre for Musculoskeletal Disorders at Lund University Hospital, Lund, Sweden (JR); and Leuven University Division of Geriatric Medicine, Katholieke Universiteit Leuven, Leuven, Belgium (SB) 1 Kallmes DF, Jarvik JG.