Percutaneous kyphoplasty with or without posterior pedicle screw fixation for the management of severe osteoporotic vertebral compression fractures with nonunion.

OBJECTIVE: To assess the radiographic outcomes, clinical outcomes and complications of percutaneous kyphoplasty (PKP) with and without posterior pedicle screw fixation (PPSF) in the treatment of severe osteoporotic vertebral compression fractures (sOVCF) with nonunion. METHODS: This study involved 51 patients with sOVCF with nonunion who underwent PKP or PPSF + KP. The operation time, intraoperative blood loss, volume of injected bone cement, operation costs and hospital stays were all recorded. In addition, the Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) were assessed separately for each patient before and after surgery. RESULTS: Compared with the PPSF + KP group, the PKP group had shorter operation time, less intraoperative blood loss, shorter hospital stays and fewer operation costs. However, cobb's angle improvement (13.4 ± 4.3° vs. 21.4 ± 5.3°), VWR improvement ratio (30.4 ± 11.5% vs. 52.8 ± 12.7%), HA (34.9 ± 9.0% vs. 63.7 ± 7.6%) and HM (28.4 ± 11.2% vs. 49.6 ± 7.7%) improvement ratio were all higher in PPSF + KP group than that in PKP group. In addition, the ODI index and VAS score in both groups were significantly decreased at the postoperative and final follow-up. PKP group's postoperative VAS score was significantly lower than that in PPSF + KP group, but there was no statistically significant difference in VAS score at the last follow-up. CONCLUSION: PKP and PPSF + KP can both effectively relieve the pain associated with sOVCF with nonunion. PPSF + KP can achieve more satisfactory vertebral reduction effects compared to PKP. However, PKP was less invasive and it has more advantages in shortening operation time and hospital stay, as well as decreasing intraoperative blood loss and operation costs.

Pre-existing osteoporosis and serum vitamin D levels in patients with distal radius fractures: are we missing something?

INTRODUCTION: Given the significant therapeutic gap for osteoporosis, this study aims to investigate the most common osteoporosis-related fracture. The analysis will also consider patients' serum vitamin D levels and the indications for basic osteoporosis diagnostic tests and osteoporosis therapy prior to fracture. MATERIALS AND METHODS: This prospective clinical trial included patients with distal radius fractures who underwent surgery at our hospital between 1 April 2021 and 7 April 2022. Blood samples were taken from all participants and existing risk factors for osteoporosis were recorded. In addition, the indication for a guideline-based osteoporosis diagnosis was assessed and the risk of another future fracture with FRAX® was calculated. This information was used to decide whether there was an indication for specific osteoporosis therapy. RESULTS: A diagnosis gap of 53% and a treatment gap of 84% were identified among the 102 patients investigated. The patients' ages ranged from 46 to 91 years, with an average vitamin D level of 57 nmol/l, which was below the recommended level of 75 nmol/l. It was noted on a monthly basis that the vitamin D level (without substitution) never exceeded the recommended value of 75 nmol/l in any month. Three-quarters of patients had indications for a baseline osteoporosis diagnosis, yet less than 50% received one. According to FRAX® data, 57% of patients had indications for specific osteoporosis treatment before experiencing the fracture. CONCLUSION: Even without a previous distal radius fracture, many patients are in need of osteoporosis diagnosis or treatment. Our research suggests that patients with distal radius fractures should have their vitamin D levels checked via a blood test and be evaluated for osteoporosis. As endogenous vitamin D levels are often inadequate, year-round vitamin D supplementation should be considered for the prevention of osteomalacia and as a basis for the treatment of osteoporosis. GERMAN CLINICAL TRIAL REGISTER ID: DRKS00028085.

Abaloparatide promotes bone repair of vertebral defects in ovariectomized rats by increasing bone formation.

Osteoporotic vertebral fracture (OVF) is the most common type of osteoporotic fracture and is associated with immobility and mortality. Bone anabolic agents, such as abaloparatide (ABL), are usually administered to patients with OVF to prevent subsequent fractures. Although several studies have shown that bone anabolic agents promote healing of long bone fractures, there is little evidence of their healing effect on vertebral bone fractures. In the present study, we investigated the effect of ABL on vertebral bone defects using ovariectomized (OVX) rats with vertebral body drill-hole defects, an animal model of OVF. Eight-week-old female Sprague-Dawley rats were subjected to OVX, followed by the 32-36 days of bone depletion period, once-daily subcutaneous ABL was administered to OVX rats at a dose of 30 µg/kg for a maximum of 6 weeks from the day of the vertebral defect surgery. We found that ABL significantly increased bone mineral content and improved trabecular structural parameters at the vertebral defect site. Moreover, ABL significantly increased bone strength of the defected vertebrae. Bone histochemical analysis revealed formation of thick trabecular bone networks at the defect site after ABL administration, consistent with an improvement in trabecular structural parameters by ABL. ABL increased ALPase- and PHOSPHO1-positive osteoblastic cells and ALPase/PCNA double-positive cells, indicating enhanced preosteoblast proliferation as well as bone formation at the defect site. On the other hand, ABL did not affect the number of cathepsin K-positive osteoclasts per bone surface, suggesting that ABL did not promote excessive bone resorption. Our findings suggest that ABL is useful not only for preventing secondary vertebral fractures but also for promoting bone healing in OVF.

Robot-assisted percutaneous vertebroplasty for osteoporotic vertebral compression fracture treatment and risk factor screening for postoperative refracture.

Osteoporotic vertebral compression fracture (OVCF) is a serious complication of osteoporosis, and percutaneous vertebroplasty (PVP) is a major therapeutic method for OVCF. This study aimed to evaluate the clinical efficacy and postoperative complications of robot-assisted targeted PVP for the treatment of OVCF. The data from 202 OVCF patients were analyzed in this study, including 72 cases received traditional PVP (PVP group), 68 cases received robot-assisted PVP (R-PVP group), and 62 cases underwent robot-assisted PVP combined with targeted plugging (R-PVP + TP group). The fluoroscopic exposure conditions, operative duration, lengths of stay, postoperative bone cement leakage, refracture, Visual Analog Scale (VAS) score, and Oswestry Disability Index (ODI) score were obtained and compared between the three groups. The Kaplan-Meier method and logistic regression model were adopted to screen the risk factors related with postoperative refracture. R-PVP and R-PVP + TP group had significantly reduced fluoroscopic frequency and radiation dose, and reduced cement leakage compared with PVP group. R-PVP + TP not only showed more obvious advantages in these aspects, but also had a lower probability of postoperative refracture. In addition, BMD, fracture vertebral distribution, cement leakage, and surgery methods were independent related with refracture. All the results demonstrated robot assistance could improve the application of PVP in the treatment of OVCF, and robot-assisted PVP combined with targeted plugging showed significantly reduced fluoroscopic exposure, bone cement leakage, and rate of postoperative refracture. BMD, fracture vertebral distribution, cement leakage, and operation methods were identified as four risk factors for the onset of refracture after PVP.

Application of an in-hospital, surgeon-led anti-osteoporotic medication algorithm in patients with hip fractures improves persistence to medication and can prevent the second fragility fracture.

INTRODUCTION: Secondary fracture prevention is an essential part of hip fracture treatment. Despite this, many patients are discharged without the appropriate anti-osteoporotic medication. The aim of this study is to report the outcomes of the application of an in-hospital, surgeon-led anti-osteoporotic medication algorithm to patients with hip fractures. MATERIALS AND METHODS: This prospective cohort study followed patients with hip fractures who were treated at a tertiary referral hospital between 2020 and 2022. At discharge, anti-osteoporotic medication according to the Arbeitsgemeinschaft für Osteosynthesefragen (AO) Foundation algorithm was prescribed to all patients. Multivariate Cox regression analysis was used to investigate the risks of non-persistence to medication and of secondary fracture. RESULTS: Two hundred thirteen consecutive patients were prospectively followed. Mean follow-up was 17.2 ± 7.1 months. Persistence to medication at 2 years was 58% (95%CI 51-65%). A secondary osteoporotic fracture occurred in 1/126 (0.8%) persistent patients and 9/87 (11.4%) non-persistent patients. Multivariable Cox regression analysis confirmed that persistence to medication was significantly associated with a lower risk of secondary fracture (cause-specific hazard ratio [csHR] 0.05; 95%CI 0.01-0.45; p = 0.007). CONCLUSION: The application of the surgeon-led AO Foundation algorithm enables the in-hospital initiation of anti-osteoporotic treatment, leading to better persistence to medication and decreased incidence of secondary osteoporotic fractures.

Optimizing percutaneous vertebroplasty: extra-facet puncture for osteoporotic vertebral compression fractures.

PURPOSE: To assess the safety and efficacy of the extra-facet puncture technique applied in unilateral percutaneous vertebroplasty (PVP) for treating osteoporotic vertebral compression fractures. METHODS: Demographics (age, gender, body mass index and underlying diseases) were recorded for analyzing. Visual analog scale (VAS) and Oswestry Disability Index (ODI) scores as well as their corresponding minimal clinically important difference (MCID) were used to evaluate clinical outcomes. The segmental kyphotic angle, the vertebral compression ratio and bone cement distribution pattern were evaluated by the plain radiographs. The facet joint violation (FJV) was defined by the postoperative computed tomography scan. Binary logistic regression analysis was performed to investigate relationships between multiple risk factors and residual back pain. RESULTS: VAS and ODI scores in both traditional puncture group and extra-facet puncture group were significantly decreased after PVP surgery (p < 0.05). However, no significant difference was observed between the two groups according to VAS and ODI scores. The proportion of patients achieving MCID of VAS and ODI scores was higher in extra-facet puncture group as compared to traditional puncture group within a month (p < 0.05). Finally, multivariate logistic regression analysis showed that FJV (odds ratio 16.38, p < 0.001) and unilateral bone cement distribution (OR 5.576, p = 0.020) were significant predictors of residual back pain after PVP surgery. CONCLUSIONS: Extra-facet puncture percutaneous vertebroplasty can decrease the risk of FJV and it also has the advantage of more satisfied bone cement distribution.

Unilaterally extrapedicular versus transpedicular kyphoplasty in treating osteoporotic lumbar fractures: a randomized controlled study.

BACKGROUND: The unilaterally extrapedicular approach is adopted increasingly to perform balloon kyphoplasty in treating osteoporotic lumbar fractures, which is intended to improve radiological and clinical efficacy. We compared the efficacy and safety of this method with a unilaterally transpedicular approach. METHODS: We conducted a single-center, randomized controlled trial enrolling participants with a one-level osteoporotic lumbar fracture in less than 1 month. Patients were randomly assigned to undergo kyphoplasty via either a unilaterally extrapedicular approach (treatment group) or a unilaterally transpedicular approach (control group). The primary outcome was the difference in change from baseline to 1 month in visual analog scale (VAS) scores between the two groups. Secondary outcome measures included vertebral height ratio, operation time, fluoroscopic times, hemoglobin loss, and cement leakage between groups. Data were analyzed by intention to treat principle. RESULTS: A total of 80 participants were assigned to the treatment group (n = 40) and control group (n = 40), with three and two patients lost to follow-up during 12 months in the two groups, respectively. At 1 month postoperatively, the treatment group showed a greater reduction in VAS score from baseline, compared with the control group (mean difference between groups = 0.63, 95%CI 0.19-1.06). There were no significant between-group differences in restoration in anterior, middle, and posterior vertebral body (P > 0.05). No significant differences were found in the rate of cement leakage and perioperative hemoglobin loss (P > 0.05). CONCLUSION: Compared with balloon kyphoplasty via the unilaterally transpedicular approach in treating lumbar OVCFs, the unilaterally extrapedicular approach appears to be promising in achieving effective pain relief, adequate cement infusion, short operation time, less fluoroscopy exposure, and comparable risk of cement leakage and vessel injury. It is an alternative approach for lumbar OVCFs treated with kyphoplasty.

The relationship between pain relief and the amount and distribution of injected cement in kyphoplasty for osteoporotic vertebral fractures.

OBJECTIVE: This study aimed to compare the relationship of pain relief with the amount and distribution of injected cement in kyphoplasty for osteoporotic vertebral fractures. PATIENTS AND METHODS: This cohort study was conducted on 90 patients with osteoporotic vertebral fractures who needed chronic pain medication. Patients underwent kyphoplasty balloon surgery, and polymethylmethacrylate (PMMA) or bone cement was injected into the created cavities and the volume of injected cement was recorded. After the surgery, the distribution of cement was measured using a computed tomography (CT) scan in the coronal, sagittal, and axial axes of the vertebra, and the percentage of cement distribution was evaluated using Photoshop software in these three axes, followed by the pattern of cement distribution. The cement was measured in the entire vertebra. The patients were evaluated over a period of 6 months, and the amount of pain improvement was measured by the VAS scale in 24 hours, two weeks, six weeks, and six months after surgery. In this study, the data of 90 patients with a mean age of 72.5±10.9 years were included in the study. The mean volume of cement injected was 1.2±5.8 cc, followed by the mean percentage of cement distribution (47.7±7.4%); the mean pain score before the operation (8.7±1.3), the mean pain score 24 hours after the operation (7.7±1.4), the mean pain score 2 weeks after the operation (4.8±1.3), the mean pain score 6 weeks after the operation (3.6±1.2) and the mean pain score 6 months after the operation (3.5±1.4) were evaluated after collection. RESULTS: The pain intensity 24 hours after the operation had a significant positive correlation with the percentage of cement distribution and pain intensity before the operation. The intensity of pain 2 weeks after the operation was positively correlated with the age of the patients and the intensity of pain before the operation. The pain intensity 6 weeks after the operation was significantly correlated with the age of the patients and the pain intensity before the operation. The intensity of pain 6 months after the operation was positively linked to the age of the patients and negatively correlated with the percentage of cement distribution. The pain reduction has changed significantly in the 4 measured intervals, and during a period of 6 months, there was a significant improvement in the pain level of the patients continuously. It was found that the rate of recovery of the patient's pain has increased by increased distribution of injected cement. Although this reduction in pain during the 6-month period was not significantly related to the variables of gender, smoking, history of corticosteroid use, and the volume of injected cement. CONCLUSIONS: The balloon kyphoplasty is a safe and successful method for treating symptomatic vertebral fractures. Kyphoplasty is associated with significant pain relief, improved quality of life, and kyphosis correction. The volume of cement injected had no effect on reducing patients' pain after the operation, but a higher percentage of cement distribution was associated with a better response in patients.

Efficacy of percutaneous cement-augmented screw fixation plus percutaneous kyphoplasty in the management of unstable osteoporotic vertebral compression fractures.

OBJECTIVE: The present study was performed to compare the efficacy of percutaneous kyphoplasty (PKP) vs. percutaneous cement-augmented screw fixation plus PKP in the management of unstable osteoporotic vertebral compression fractures (OVCF). PATIENTS AND METHODS: A total of 197 patients with unstable OVCF treated in the Department of Spine Surgery, Lianyungang First People's Hospital from September 2019 to September 2021 were recruited and assigned via random number table method 1:1 to receive either PKP (group A, n=106) or PKP plus percutaneous cement-augmented screw fixation (group B, n=91). The outcome measures for the evaluation of different surgical methods included visual analogue scale (VAS), the height of the anterior-posterior border of the injured spine, Cobb angle of the posterior convexity, Oswestry disability index (ODI) scores, and Japanese Orthopaedic Association (JOA) scores. RESULTS: PKP exhibited shorter operative time and length of hospital stay and less intraoperative blood loss vs. PKP plus percutaneous cement-augmented screw fixation (p<0.05). Patients with PKP plus percutaneous cement-augmented screw fixation experienced milder postoperative pain vs. those with PKP alone at 7 days postoperatively, as evidenced by the lower VAS scores (p<0.05). PKP plus percutaneous cement-augmented screw fixation provided more restoration of anterior margin height and posterior convexity Cobb angle vs. PKP alone (p<0.05). Patients with PKP only showed slightly higher Japanese Orthopaedic Association (JOA) scores than those with combined surgery, while the postoperative clinical signs between the two arms were similar (p>0.05). CONCLUSIONS: Single PKP features the benefits of minimal trauma, simple operation, and rapid postoperative recovery in the treatment of OVCF. PKP plus percutaneous cement-augmented screw fixation for severe OVCF provided distinctly better performance than PKP alone in terms of early pain relief, restoration of vertebral body height, correction of posterior convexity deformity, and firm spinal stability.

Clinical efficacy of modified percutaneous kyphoplasty (PKP) vs. conventional PKP for osteoporotic vertebral compression fractures: a single-center retrospective study.

OBJECTIVE: To investigate the clinical efficacy of using a standardized modified percutaneous kyphoplasty (transverse process­pedicle approach to percutaneous kyphoplasty, TPKP) approach for the treatment of osteoporotic vertebral compression fractures (OVCFs) and to explore the possibility that it may become the preferred option in the future. PATIENTS AND METHODS: A retrospective analysis was conducted on a total of 81 patients (TPKP group, 43 cases; PKP group, 38 cases) with OVCFs who underwent TPKP and PKP at the Department of Spine Surgery, Wuhan Fourth Hospital, from May 2021 to October 2021. We evaluated the patients' demographic information, intraoperative data (volume of cement injection and, duration of surgery), clinical outcomes at different time points (Visual Analog Scale, Oswestry Dysfunction Index), and radiographic data (Cobb angle, anterior vertebral body height). Statistical analysis was performed to assess the efficacy of the procedure, both within and between the two groups before and after surgery. RESULTS: The difference in preoperative general information between the two groups of patients was non-statistically significant (p>0.05), and they were comparable. Additionally, no statistically significant difference (p>0.05) was found between the TPKP and PKP groups in terms of operative time, length of hospital stay, recovery of injured spine height, Cobb angle, and cement leakage rate. However, significant statistical differences (p<0.05) were noted between the two groups regarding cement volume, distribution pattern, 1-day postoperative VAS scores, 1-day postoperative ODI scores, and loss of height of the injured spine. TPKP demonstrated superior performance compared to PKP in these specific areas. CONCLUSIONS: TPKP offers the same surgical safety as the conventional approach, with better cement distribution and better pain relief, as well as the advantage of maintaining the height of the operated vertebral body. The technique is easy to master and use when guided by standard puncture procedures.

Analysis of Potential Risk Factors for Cement Leakage into Paraspinal Veins after Vertebroplasty for Acute Osteoporotic Vertebral Fractures Based on a 3D Reconstruction Technique: A Retrospective Matched Case-Control Study.

OBJECTIVE: Pulmonary embolism, cardiac embolism, and even cerebral embolism due to paraspinal vein leakage (PVL) are increasingly reported, and their risk factors need to be adequately investigated for prevention. To this end, this study investigated the correlation of the distribution and morphological characteristics of fracture lines with the occurrence of PVL after percutaneous vertebroplasty (PVP), which has not been previously reported. METHODS: Patients with acute single-segment thoracolumbar osteoporotic vertebral compression fractures (OVCFs) treated with PVP at our institution from January 2019 to July 2022 were selected for a matched case-control study. The case and control groups included those with and without PVL, respectively, matched at a 1:1 ratio based on general clinical characteristics. Additionally, fracture map and heatmap analysis was performed in both groups. In addition to the general clinical characteristics, the vertebral height ratio, puncture angle, delivery rate, and indexes were assessed via the three-dimensional CT reconstruction fracture line mapping technique, namely, the distribution of fracture lines, fracture line length, main fracture line shape, location of fracture line involvement, and number of fracture line branches, were compared between the two groups. The Wilcoxon rank-sum test, t tests, analysis of variance, and conditional logistic regression were used for statistical analysis. RESULTS: Among 658 patients with OVCFs, 54 who did and 54 who did not develop PVL were included in this study. Significant differences in the puncture angle, fracture line distribution (MR-1, ML-2, MM-2, MR-2, ML-3, MM-3, LL-1, LM-1, LL-2, LM-2), fracture line involvement of the posterior wall, total fracture line length, and main fracture line length were found between the two groups (p < 0.05). Logistic univariate analysis showed significant differences in the puncture angle, fracture line distribution (MR-1, ML-2, MM-2, MR-2, ML-3, MM-3, LL-1, LL-2, LM-2, LL-3), total fracture line length, main fracture line length, and fracture line involvement of the posterior wall between the two groups (p < 0.05). Logistic multifactorial analysis showed that the fracture line distribution (UR-3, ML-3, LM-2, LR-2) and main fracture line length were independent risk factors for the development of PVL in both groups. In addition, the fracture maps and heatmaps showed a greater degree of fracture line encapsulation and more extensive involvement in the middle and lower regions of the vertebral body in the PVL group than in the control group. CONCLUSIONS: Through a three-dimensional computed tomography reconstruction-based fracture line mapping technique, this study revealed for the first time that the distribution of fracture lines (UR-3, ML-3, LM-2, LR-2) and main fracture line length were independent risk factors for PVL after PVP in patients with acute single-segment thoracolumbar OVCFs. In addition, we hypothesized that the fracture line-vein traffic branch that may appear within 2 weeks after injury in acute OVCF patients may be one of the mechanisms influencing the above potential independent risk factors associated with PVL.

Preoperative planning of compact zone trajectory is necessary in treating osteoporotic vertebral compression fracture with endplate involvement: A prospective randomized controlled study.

BACKGROUND: This prospective randomized controlled study compares the clinical and radiological outcomes between reduction methods with or without compact trabecular bone during percutaneous kyphoplasty in osteoporotic vertebral fractures. METHODS: The cohort of 100 patients who underwent percutaneous kyphoplasty was randomly divided into group A (guide pin and balloon introduced directly into fracture site) and group B (guide pin and balloon inserted away fracture site). The surgery duration, clinical and radiological outcomes postoperatively and at follow-up, and complications of cement leakage and adjacent fracture were recorded. Patients were followed up for an average of 20.18 months. The clinical outcomes were assessed using the Oswestry Disability Index and visual analog scale. RESULTS: The two groups had similar patient demographics, surgery times, and volume of cement injected. The method using elevation of the collapsed endplate indirectly had no significant influence on radiological outcomes but significantly decreased the occurrence of intradiscal cement leakage and improved 1- and 12-month postoperative functional outcomes. CONCLUSION: Elevating and reinforcing the collapsed endplate rather than just filling the defect during percutaneous kyphoplasty is safe and effective. This technique decreased pain and improved function with lower rates of further collapse of the osteoporotic vertebrae compared to defect-filling alone.

Factors associated with non-initiation of osteoporosis pharmacotherapy after hip fracture: analysis of claims data in Japan.

In an analysis of claims data from a city in Japan, male patients and patients with dementia were less likely to receive osteoporosis pharmacotherapy after hip fracture. Treatment initiation rate has improved between 2014 and 2017. PURPOSE: Older adults with recent hip fractures are at a high risk of recurrent fractures. However, the post-fracture care gap has been reported globally. This study examines factors associated with pharmacotherapy non-initiation within 1 year after hip surgery. METHODS: Using medical and long-term care (LTC) claims, and LTC needs certification data in Tsukuba City, Japan, we identified individuals aged 65 years or older who had hip fractures with subsequent surgical procedures between October 1, 2014, and December 31, 2017. Patient (age, sex, dementia, and comorbidities) and health service-related characteristics (fiscal year, type of hospital, number of hospital beds, and admission to recovery phase rehabilitation wards) were examined. The association of these factors with non-pharmacotherapy for osteoporosis within 1 year after hip fracture using multivariable logistic models was analyzed. RESULTS: We identified 275 patients with hip fractures who did not receive pharmacotherapy pre-fracture. Forty percent of them received pharmacotherapy within 1 year of post-fracture. Male sex (odds ratio (OR) = 4.49 [2.14-9.44]) and dementia (OR = 1.90 [1.03-3.52]) were associated with no pharmacotherapy, whereas later fiscal year (OR = 0.64 [0.48-0.87]) and admission to rehabilitation wards (OR = 0.25 [0.14-0.46]) were associated with pharmacotherapy initiation within 1 year of post-fracture. Comorbidities were not associated with the initiation of pharmacotherapy. CONCLUSION: Pharmacotherapy for osteoporosis was less likely to be initiated after a hip fracture in male patients and patients with dementia. These patients should be considered for pharmacotherapy because they are at high risk of recurrent fractures.

Drug adherence and treatment duration for denosumab and mortality risk among hip fracture patients.

This study aimed to assess the impact of drug adherence and treatment duration for denosumab on mortality risk after hip fracture surgery. Lower all-cause mortality risk was associated with drug intervals of 7 months or less and longer treatment duration. The study highlights the importance of proper denosumab administration. PURPOSE: Prescription of anti-osteoporotic medications (AOMs) after osteoporotic hip fracture may increase bone mineral density (BMD) and decrease mortality risk. However, few studies have been conducted on drug adherence and treatment duration for denosumab, a popular choice among AOMs. This study aimed to assess the impact of denosumab adherence and treatment duration on the mortality risk of hip fracture patients after surgery. METHODS: We conducted a cohort study using nationwide population data from National Health Insurance Research Database (NHIRD) in Taiwan. Patients newly diagnosed with osteoporosis and hip fracture between 2008 and 2019 who used denosumab after surgery were included. We assessed drug adherence, treatment duration, and other parameters associated with patient outcomes. RESULTS: A total of 21,316 patients diagnosed with osteoporotic hip fractures were included. Compared with a > 7-month drug interval for denosumab, an interval of ≤ 7 months led to lower all-cause mortality risk (hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.57 ~ 0.64). Patients with denosumab treatment for over 1, 2, and 3 years had lower all-cause mortality risk (HR&CI: 0.68 (0.64 ~ 0.73), 0.48 (0.43 ~ 0.53), 0.29 (0.26 ~ 0.33)) than those with treatment duration < 1 year. Analysis after excluding short-term death yielded similar results. Analysis of causes of death also showed that good adherence and longer duration were associated with reduced mortality due to cancer and cardiovascular disease. CONCLUSION: Better drug adherence and longer duration of denosumab treatment are associated with lower all-cause mortality risk among hip fracture patients after surgery. Our study highlights the benefits of a proper time interval of denosumab administration. These findings provide important insight into management of osteoporotic hip fractures and may inform clinical practice and development of guidelines.

Double Vertebrae Kümmell Disease: Five Cases Report and Literature Review.

Kümmell disease (KD) is a complication of osteoporotic vertebral compression fractures. There is a lot of literature on KD, but the reported cases are all single vertebrae. This study reports five double vertebrae KD cases (10 levels) and discusses the possible underlying mechanisms with a literature review. One hundred and thirty vertebrae KD were diagnosed from 2074 osteoporotic vertebral compression fractures patients treated in our hospital between 2015 and 2019. These vertebrae KD were divided into two groups, one-level vertebrae KD (n = 125) and double-level KD (n = 5). The diagnosis of KD is mainly based on the signs of intravertebral vacuum cleft on X-ray or CT scan. Double vertebrae KD cases were classified by using the KD staging system. The analysis was performed on KD to compare age, gender, femoral neck bone mineral density of femoral neck (BMD), vertebrae distribution, Cobb angle, and visual analog scale (VAS) between one-level KD and double-level by t-tests, Welch's t-test, or hypothesis testing. The mean age of the participants in the one-level KD group was 78.69 years, while the mean age in the double-level KD group was 82.4 years. The difference was statistically significant (t = 3.66, p = 0.0004). There were 89 females and 36 males in the one-level KD group, while the double-level KD group had five females and no males. The femoral neck BMD was significantly different between the two groups, with the one-level KD group having a mean BMD of -2.75 and the double-level KD group having a mean BMD of -4.2 (t = 2.99, p= 0.0061). The vertebrae distribution was different between the groups, with the one-level KD group having vertebrae from T7 to L4 and the double-level KD group having vertebrae from T11 to L1. The Cobb angle was also significantly different between the groups, with the one-level KD group having a mean angle of 20.58 and the double-level KD group having a mean angle of 31.54 (t = 6.22, p = 0.0001). Finally, the VAS scores were similar between the two groups, with the one-level KD group having a mean score of 8.63 and the double-level KD group having a mean score of 8.8 (t = 1.35, p = 0.1790). It is concluded that double vertebrae Kümmell disease has special clinical significance due to its potential to cause greater spinal instability and deformity, increased risk of neurological symptoms, more complex surgical management, and greater risk of complications.

Therapeutic Efficacy and Safety of Percutaneous Curved Vertebroplasty in Osteoporotic Vertebral Compression Fractures: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis is aimed to provide higher quality evidence regarding the efficacy and safety between PCVP and PVP/KP in OVCFs. We searched the Cochrane Library, PubMed, Web of Science, and Embase databases for all randomized controlled trials (RCTs) and observational studies (cohort or case-control studies) that compare PCVP to PVP/KP for OVCFs. The Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of the RCTs and non-RCTs, respectively. Meta-analysis was performed using RevMan 5.4 software. A total of seven articles consisting of 562 patients with 593 diseased vertebral bodies were included. Statistically significant differences were found in the postoperative visual analog scale (VAS) at 1 day (MD = -0.11; 95% CI: [-0.21 to -0.01], p = 0.03), but not at 3 months (MD = -0.21; 95% CI: [-0.41-0.00], p = 0.05) or 6 months (MD = 0.03; 95% CI: [-0.13-0.20], p = 0.70). There was no statistically significant difference in postoperative Oswestry disability index (ODI) at 1 day (MD = -0.28; 95% CI: [-0.62-0.05], p = 0.10), 3 months (MD = -1.52; 95% CI: [-3.11-0.07], p = 0.06), or 6 months (MD = 0.18; 95% CI: [-0.13-0.48], p = 0.25). Additionally, there were no statistically significant differences in Cobb angle (MD = 0.30; 95% CI: [-1.69-2.30], p = 0.77) or anterior vertebral body height (SMD = -0.01; 95% CI: [-0.26-0.23], p = 0.92) after surgery. Statistically significant differences were found in surgical time (MD = -8.60; 95% CI: [-13.75 to -3.45], p = 0.001), cement infusion volume (MD = -0.82; 95% CI: [-1.50 to -0.14], P = 0.02), and dose of fluoroscopy (SMD = -1.22; 95% CI: [-1.84 to -0.60], p = 0.0001) between curved and noncurved techniques, especially compared to bilateral PVP. Moreover, cement leakage showed statistically significant difference (OR = 0.40; 95% CI: [0.27-0.60], p < 0.0001). Compared with PVP/KP, PCVP is superior for pain relief at short-term follow-up. Additionally, PCVP has the advantages of significantly lower surgical time, radiation exposure, bone cement infusion volume, and cement leakage incidence compared to bilateral PVP, while no statistically significant difference is found when compared with unilateral PVP or PKP. In terms of quality of life and radiologic outcomes, the effects of PCVP and PVP/KP are not significantly different. Overall, this meta-analysis reveals that PCVP was an effective and safe therapy for patients with OVCFs.

Treatment of osteoporosis with denosumab in patients with decreased kidney function.

INTRODUCTION: Little is known about treatment of osteoporosis with denosumab (Prolia®) in patients with decreased kidney function. The aim of this retrospective case report study was to investigate effects and side-effects of such treatment. METHODS: Since 2012, 75 patients with osteoporosis and decreased kidney function had been treated with denosumab (Prolia®) in the osteoporosis outpatient clinic of the department of endocrinology, Bispebjerg Hospital, University of Copenhagen, Denmark, and data were retrospectively collected from the patient records of these patients in 2021. RESULTS: At baseline, the mean estimated glomerular filtration rate (eGFR) was 34 mL/min (range 9-50) and the median age was 85 years (range 45-103). 95% of the patients had had low-energy fractures, and the bone mineral density T score of the hips was on average - 2.7. All, but one, patients had normal/high parathyroid hormone (PTH) levels. The mean duration of the treatment with denosumab at the follow-up was 5.3 years (range 1.5-10). There was an annual increase of 12% and of 7% in the T score of in the lumbar spine and hip, respectively, compared to the T-scores prior to the denosumab treatment. 20% had a new fracture during the follow-up. 21% had biochemical hypocalcemia following denosumab injection, 7% developed symptoms of hypocalcemia, whereas 4% needed to be hospitalized acutely. CONCLUSION: Treatment with denosumab of osteoporosis in patients with decreased kidney function (eGFR 9-50 mL/min), with normal/high PTH, seems in general to be well tolerated, with improvement of bone and decreased risk of new fractures.

Determination of immune factor levels in serum and local hematoma samples of osteoporotic fracture patients and clinical study of the effect of active vitamin D3 treatment on immune factor levels.

OBJECTIVE: The aim of this study was to investigate changes in systemic and local immune factors, namely, interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, in patients with and without osteoporotic fractures and to explore the effects of active vitamin D3 treatment on immune function and fracture prognosis in patients with osteoporotic fractures. METHOD: The mRNA expression levels of IL-1ß, IL-6 and TNF-α were measured before the operation. After the operation, the patients in the control group were treated with conventional fracture treatment and calcium supplementation, and the patients in the treatment group were treated with calcium plus active vitamin D3 in addition to conventional fracture treatment. The serum of each patient was collected on the seventh day after the operation. RESULTS: The expression levels of the three immune factors (IL-1ß, IL-6 and TNF-α) in the fracture end hematoma samples were significantly positively correlated with those in the serum samples (P < 0.05). The mean values of the serums of IL-1ß, IL-6 and TNF-α in the osteoporosis group were significantly higher than those in the non-osteoporosis group (P < 0.05). The average number of hematomas in the osteoporosis group was significantly higher than that in the non-osteoporosis group (P < 0.05). The results for the active vitamin D3 treatment group were significantly lower than those for the control group (P < 0.05). The mean wrist function score of the active vitamin D3 treatment group was significantly better than that of the control group (P < 0.05). The average fracture healing time of the treatment group was significantly shorter than that of the control group (P < 0.05). CONCLUSION: The relative expression of IL-1ß, IL-6, and TNF-α in the fracture end hematoma samples was positively correlated with the corresponding levels of these immune factors in the serum samples. The levels of IL-1ß, IL-6 and TNF-α in the serum and fracture end hematoma samples of the osteoporotic fracture patients were higher than those of the non-osteoporotic fracture patients. Active vitamin D3 treatment promoted fracture healing by affecting the levels of these immune factors.

Asfotase alfa improved skeletal mineralization and fracture healing in a child with MCAHS.

Tissue non-specific alkaline phosphatase (TNSALP) is an enzyme that is tethered to the cell membrane by glycosylphosphatidylinositol (GPI) and converts inorganic pyrophosphate to inorganic phosphate. Inorganic phosphate combines with calcium to form hydroxyapatite, the main mineral in the skeleton. When TNSALP is defective, conversion of inorganic pyrophosphate to inorganic phosphate is impaired and the skeleton is at risk of under-mineralization. Phosphatidylinositol glycan anchor biosynthesis class N (PIGN) is one of more than 20 genes in the GPI-biosynthesis family. Pathogenic variants in PIGN have been identified in multiple congenital anomalies-hypotonia-seizures syndrome (OMIM 614080), although a metabolic bone disease or skeletal fragility phenotype has not been reported. We describe a female child with multiple congenital anomalies-hypotonia-seizures syndrome due to a compound heterozygous pathogenic variant in PIGN who sustained a low-trauma distal femur fracture at age 7.4 years. We hypothesized that the GPI synthesis defect may result in metabolic bone disease from inadequate anchoring of TNSALP in bone and initiated asfotase alfa, a human bone-targeted recombinant TNSALP-Fc-deca-aspartate peptide, as it could bypass the PIGN genetic defect that possibly caused her skeletal fragility. Asfotase alfa was begun at 8.5 years. Baseline X-rays revealed mild rachitic findings of wrists and knees, which resolved by 5 months of treatment. Bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) showed mild improvement in spine, hip and total body less head after 16 months of treatment, while radius declined. She sustained additional low trauma fractures at right tibia and left humeral neck at 11 and 15 months into treatment, which healed quickly. Calcium, phosphorus, and parathyroid hormone levels have remained within the normal range over the 18 months of treatment. For adverse effect, she experienced a rash and discomfort in the first week of treatment which resolved with ibuprofen and diphenhydramine. She also developed subcutaneous fat atrophy. Overall, in this child with a compound pathogenic variant in PIGN, off-label use of asfotase alfa has been generally well tolerated with minimal side effects and resolution of rickets, but she continues to remain skeletally fragile.

Deciphering the protective effect of Buzhong Yiqi Decoction on osteoporotic fracture through network pharmacology and experimental validation.

BACKGROUND: Osteoporotic fracture (OPF) is one of the most common skeletal diseases in an aging society. The Chinese medicine formula Buzhong Yiqi Decoction (BZYQD) is commonly used for treating OPF. However, the essential bioactive compounds and the underlying molecular mechanisms that promote fracture repair remain unclear. METHODS: We used network pharmacology and experimental animal validation to address this issue. First, 147 bioactive BZYQD compounds and 32 target genes for treating OPF were screened and assessed. A BZYQD-bioactive compound-target gene-disease network was constructed using the Cytoscape software. Functional enrichment showed that the candidate target genes were enriched in oxidative stress- and inflammation-related biological processes and multiple pathways, including nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, an OPF rat model was established and treated with BZYQD. RESULTS: The results revealed that BZYQD ameliorated OPF characteristics, including femoral microarchitecture, biomechanical properties, and histopathological changes, in a dose-dependent manner. Results of enzyme-linked immunosorbent assay showed that BZYQD reduced the serum's pro-inflammatory cytokines [Tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-1ß, and IL-6] and improved oxidative stress-related factors [glutathione (GSH) and superoxide dismutase (SOD)]. BZYQD significantly decreased the protein expression of NF-κB in OPF rat femurs, suppressed NF-κB activation, and activated the nuclear factor-erythroid factor 2-related factor (Nrf2)/heme oxygenase 1 (HO-1) and p38 MAPK as well ERK pathways. CONCLUSIONS: Our results suggest that BZYQD could improve inflammation and oxidative stress during fracture repair by suppressing NF-κB and activating Nrf2/MAPK signaling pathways.