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Treatment of bone defects caused by trauma or disease is a major burden on human healthcare systems. Although autologous bone grafts are considered as the gold standard, they are limited in availability and are associated with post-operative complications. Minimally invasive alternatives using injectable bone cements are currently used in certain clinical procedures, such as vertebroplasty and balloon kyphoplasty. Nevertheless, given the high incidence of fractures and pathologies that result in bone voids, there is an unmet need for injectable materials with desired properties for minimally invasive procedures. This paper provides an overview of the most common injectable bone cement materials for clinical use. The emphasis has been placed on calcium phosphate cements and acrylic bone cements, while enabling the readers to compare the opportunities and challenges for these two classes of bone cements. This paper also briefly reviews antibiotic-loaded bone cements used in bone repair and implant fixation, including their efficacy and cost for healthcare systems. A summary of the current challenges and recommendations for future directions has been brought in the concluding section of this paper.

AbstractObjectiveTo assess whether percutaneous vertebroplasty results in more pain relief than a sham procedure in patients with acute osteoporotic compression fractures of the vertebral body.DesignRandomised, double blind, sham controlled clinical trial.SettingFour community hospitals in the Netherlands, 2011-15.Participants180 participants requiring treatment for acute osteoporotic vertebral compression fractures were randomised to either vertebroplasty (n=91) or a sham procedure (n=89).InterventionsParticipants received local subcutaneous lidocaine (lignocaine) and bupivacaine at each pedicle. The vertebroplasty group also received cementation, which was simulated in the sham procedure group.Main outcome measuresMain outcome measure was mean reduction in visual analogue scale (VAS) scores at one day, one week, and one, three, six, and 12 months. Clinically significant pain relief was defined as a decrease of 1.5 points in VAS scores from baseline. Secondary outcome measures were the differences between groups for changes in the quality of life for osteoporosis and Roland-Morris disability questionnaire scores during 12 months’ follow-up.ResultsThe mean reduction in VAS score was statistically significant in the vertebroplasty and sham procedure groups at all follow-up points after the procedure compared with baseline. The mean difference in VAS scores between groups was 0.20 (95% confidence interval −0.53 to 0.94) at baseline, −0.43 (−1.17 to 0.31) at one day, −0.11 (−0.85 to 0.63) at one week, 0.41 (−0.33 to 1.15) at one month, 0.21 (−0.54 to 0.96) at three months, 0.39 (−0.37 to 1.15) at six months, and 0.45 (−0.37 to 1.24) at 12 months. These changes in VAS scores did not, however, differ statistically significantly between the groups during 12 months’ follow-up. The results for secondary outcomes were not statistically significant. Use of analgesics (non-opioids, weak opioids, strong opioids) decreased statistically significantly in both groups at all time points, with no statistically significant differences between groups. Two adverse events occurred in the vertebroplasty group: one respiratory insufficiency and one vasovagal reaction.ConclusionsPercutaneous vertebroplasty did not result in statistically significantly greater pain relief than a sham procedure during 12 months’ follow-up among patients with acute osteoporotic vertebral compression fractures.Trial registrationClinicalTrials.gov NCT01200277.

Critical-sized bone defects are defined as those that will not heal spontaneously within a patient’s lifetime. Current treatment options include vascularized bone grafts, distraction osteogenesis, and the induced membrane technique. The induced membrane technique is an increasingly utilized method with favorable results including high rates of union. Tissue engineering holds promise in the treatment of large bone defects due to advancement of stem cell biology, novel biomaterials, and 3D bioprinting. In this review, we provide an overview of the current operative treatment strategies of critical-sized bone defects as well as the current state of tissue engineering for such defects.

BackgroundIn advanced cancer patients, pelvic bone metastasis often causes pain and gait disturbance. The use of percutaneous bone cement [polymethylmethacrylate (PMMA)] injection for pain management and strengthening in pelvic bone metastasis has rarely been reported. To evaluate this method, we aimed to determine surgical outcomes and complications over a long-term follow-up period using a large patient group.Patients and MethodsWe retrospectively collected data from 178 patients who underwent percutaneous cementoplasty for pelvic metastatic lesions, 201 in total. Surgical outcomes evaluated included pain reduction and improvement of ambulation. Mortality within 1 month after procedure and pulmonary embolism caused by thrombus, fat, tumor emboli, or bone cement were investigated as surgical complications. For long-term survivors, pain relapse and mechanical failure were analyzed. The mean follow-up period was 12.6 months, and there were 159 fatalities at last follow-up.ResultsThe mean regional pain numerical rating scale scores decreased from 6.1 preoperatively to 2.4 1 month after procedure (p < 0.01). Gait function was maintained, worsened, and uncheckable in 68%, 24%, and 8% of patients, respectively, 1 month after procedure. Of long-term survivors followed up for > 12 months (n = 53), there were no significant changes in serial plain radiographs, and regional pain aggravation was observed in 9%. Pulmonary cement embolism and bone cement implantation syndrome was observed in 11% and 10%, respectively. However, all patients with these complications were asymptomatic.ConclusionsPercutaneous cement injection into the pelvis is a feasible and safe palliative surgical option for patients with advanced malignancy in terms of pain reduction and maintenance of ambulatory function under regional anesthesia.

By virtue of its excellent bioactivity and osteoconductivity, calcium phosphate cement (CPC) has been applied extensively in bone engineering. Doping a trace element into CPC can change physical characteristics and enhance osteogenesis. The trace element lithium has been demonstrated to stimulate the proliferation and differentiation of osteoblasts. We investigated the fracture-healing effect of osteoporotic defects with lithium-doped calcium phosphate cement (Li/CPC) and the underlying mechanism. Li/CPC bodies immersed in simulated body fluid converted gradually to hydroxyapatite. Li/CPC extracts stimulated the proliferation and differentiation of osteoblasts upon release of lithium ions (Li + ) at 25.35 ± 0.12 to 50.74 ± 0.13 mg/l through activation of the Wnt/β-catenin pathway in vitro . We also examined the effect of locally administered Li + on defects in rat tibia between CPC and Li/CPC in vivo . Micro-computed tomography and histological staining showed that Li/CPC had better osteogenesis by increasing bone mass and promoting repair in defects compared with CPC (P < 0.05). Li/CPC also showed better osteoconductivity and osseointegration. These findings suggest that local release of Li + from Li/CPC may accelerate bone regeneration from injury through activation of the Wnt/β-catenin pathway in osteoporosis.

Background Many surgeons treat giant cell tumor of bone (GCT) with intralesional curettage. Wide resection is reserved for extensive bone destruction where joint preservation is impossible or when expendable sites (eg, fibular head) are affected. Adjuvants such as polymethylmethacrylate and phenol have been recommended to reduce the risk of local recurrence after intralesional surgery. However, the best treatment of these tumors and risk factors for recurrence remain controversial. Questions/purposes We evaluated the recurrence-free survival after surgical treatment of GCT to determine the influence of the surgical approach, adjuvant treatment, local tumor presentation, and demographic factors on the risk of recurrence. Methods We retrospectively reviewed 118 patients treated for benign GCT of bone between 1985 and 2005. Recurrence rates, risk factors for recurrence and the development of pulmonary metastases were determined. The minimum followup was 36 months (mean, 108.4 ± 43.7; range, 36–233 months). Results Wide resection had a lower recurrence rate than intralesional surgery (5% versus 25%). Application of polymethylmethacrylate decreased the risk of local recurrence after intralesional surgery compared with bone grafting; phenol application alone had no effect on the risk of recurrence. Pulmonary metastases occurred in 4%; multidisciplinary treatment including wedge resection, chemotherapy, and radiotherapy achieved disease-free survival or stable disease in all of these patients. Conclusion We recommend intralesional surgery with polymethylmethacrylate for the majority of primary GCTs. Because pulmonary metastases are rare and aggressive treatment of pulmonary metastases is usually successful, we believe the potential for metastases should not by itself create an indication for wide resection of primary tumors. Level of Evidence Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.

BackgroundTo compare high- versus low-viscosity bone cement on the clinical outcomes and complications in patients with Osteoporotic vertebral compression fractures (OVCFs) who underwent percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP).MethodsPubMed, Embase, and the Cochrane Library were searched for papers published from inception up to February 2021 for potentially eligible studies comparing high- versus low-viscosity cement for PVP/PKP. The outcomes were the leakage rate, visual analog scale (VAS), and Oswestry Disability Index (ODI).ResultsEight studies (558 patients; 279 in each group) were included. The meta-analysis showed that the leakage rate was lower with high-viscosity cement than with low-viscosity cement (OR = 0.23, 95%CI 0.14–0.39, P < 0.001; I2 = 43.5%, Pheterogeneity = 0.088); similar results were observed specifically for the disk space, paravertebral space, and peripheral vein, but there were no differences regarding the epidural space and intraspinal space. The VAS was decreased more significantly with high-viscosity cement than with low-viscosity cement (WMD = − 0.21, 95%CI − 0.38, − 0.04, P = 0.015; I2 = 0.0%, Pheterogeneity = 0.565). Regarding the ODI, there was no difference between high- and low-viscosity cement (WMD = − 0.88, 95%CI − 3.06, 1.29, P = 0.426; I2 = 78.3%, Pheterogeneity < 0.001).ConclusionsThere were lower cement leakage rates in PVP/PKP with high-viscosity bone cement than low-viscosity bone cement. The two groups have similar results in ODI, but the VAS scores favor high-viscosity bone cement. Therefore, the administration of high-viscosity bone cement in PVP/ PKP could be a potential option for improving the complications of leakage in OVCFs, while the clinical efficacy of relieving pain is not certain.

Percutaneous vertebroplasty is increasingly used for treatment of pain in patients with osteoporotic vertebral compression fractures, but the efficacy, cost-effectiveness, and safety of the procedure remain uncertain. We aimed to clarify whether vertebroplasty has additional value compared with optimum pain treatment in patients with acute vertebral fractures. Patients were recruited to this open-label prospective randomised trial from the radiology departments of six hospitals in the Netherlands and Belgium. Patients were aged 50 years or older, had vertebral compression fractures on spine radiograph (minimum 15% height loss; level of fracture at Th5 or lower; bone oedema on MRI), with back pain for 6 weeks or less, and a visual analogue scale (VAS) score of 5 or more. Patients were randomly allocated to percutaneous vertebroplasty or conservative treatment by computer-generated randomisation codes with a block size of six. Masking was not possible for participants, physicians, and outcome assessors. The primary outcome was pain relief at 1 month and 1 year as measured by VAS score. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00232466. Between Oct 1, 2005, and June 30, 2008, we identified 431 patients who were eligible for randomisation. 229 (53%) patients had spontaneous pain relief during assessment, and 202 patients with persistent pain were randomly allocated to treatment (101 vertebroplasty, 101 conservative treatment). Vertebroplasty resulted in greater pain relief than did conservative treatment; difference in mean VAS score between baseline and 1 month was −5·2 (95% CI −5·88 to −4·72) after vertebroplasty and −2·7 (−3·22 to −1·98) after conservative treatment, and between baseline and 1 year was −5·7 (−6·22 to −4·98) after vertebroplasty and −3·7 (−4·35 to −3·05) after conservative treatment. The difference between groups in reduction of mean VAS score from baseline was 2·6 (95% CI 1·74–3·37, p<0·0001) at 1 month and 2·0 (1·13–2·80, p<0·0001) at 1 year. No serious complications or adverse events were reported. In a subgroup of patients with acute osteoporotic vertebral compression fractures and persistent pain, percutaneous vertebroplasty is effective and safe. Pain relief after vertebroplasty is immediate, is sustained for at least a year, and is significantly greater than that achieved with conservative treatment, at an acceptable cost. ZonMw; COOK Medical.

Background In this study, we try to investigate the effect of antibiotic bone cement in patients with infected diabetic foot ulcer (DFU). Methods This is a retrospective study, including fifty-two patients with infected DFU who had undergone treated between June 2019 and May 2021. Patients were divided into Polymethylmethacrylate (PMMA) group and control group. 22 patients in PMMA group received antibiotic bone cement and regular wound debridement, and 30 patients in control group received regular wound debridement. Clinical outcomes include the rate of wound healing, duration of healing, duration of wound preparation, rate of amputation, and frequency of debridement procedures. Results In PMMA group, twenty-two patients (100%) had complete wound healing. In control group, twenty-eight patients (93.3%) had wound healing. Compared with control group, PMMA group had fewer frequencies of debridement procedures and shorter duration of wound healing (35.32 ± 3.77 days vs 44.37 ± 7.44 days, P < 0.001). PMMA group had five minor amputation, while control group had eight minor amputation and two major amputation. Regarding the rate of limb salvage, there was no limb lose in PMMA group and two limb losses in control group. Conclusion The application of antibiotic bone cement is an effective solution for infected DFU treatment. It can effectively decreased the frequency of debridement procedures and shorten the healing duration in patients with infected DFU.