Evaluation of the efficacy and safety of romosozumab (evenity) for the treatment of osteoporotic vertebral compression fracture in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials (CDM-J).

PURPOSE: Osteoporotic vertebral compression fracture (OVCF) is a common fragile fracture resulting from osteoporosis. We compared the efficacy and safety of romosozumab and commonly used osteoporosis drug treatments for the treatment of OVCF in postmenopausal women. METHODS: Through searching and screening five databases, we included randomized controlled trials (RCTs) published through June 18, 2021 comparing different treatments. Following the Preferred Reporting Items for Systematic Reviews statement, the main objective was to evaluate the mean difference and risk ratio of the treatment effect. The primary measures of romosozumab efficacy used in this study were vertebral, non-vertebral, and clinical fracture events, and secondary outcomes were bone mineral density (BMD) changes at the lumbar spine, total hip, and femoral neck and the incidence of adverse events (AEs), RESULTS: Nine RCTs including 12 796 participants were included in the analysis, and romosozumab was compared with placebo, alendronate, and teriparatide in the treatment of osteoporosis in postmenopausal women. The incidence of fractures, low BMD, and AEs was analyzed. Compared with the controls, three doses of romosozumab were linked to evident advantages in the treatment of low BMD and fractures but associated with increased hypersensitivity and injection site reaction risks. Furthermore, fewer AEs were observed in the romosozumab arms (210 mg: risk ratio = 0.96, 95% confidence interval = 0.93-0.99; 140 mg: risk ratio = 0.28, 95% confidence interval = 0.08-0.98) than in the alendronate and placebo arms. CONCLUSIONS: Our meta-analysis revealed the evident advantages of romosozumab in the treatment of osteoporosis and low BMD in postmenopausal women and increased risks of hypersensitivity and injection site reactions.

Effectiveness of Neridronate in the Management of Bone Loss in Patients with Duchenne Muscular Dystrophy: Results from a Pilot Study.

INTRODUCTION: Bone loss is a major issue in patients affected by Duchenne muscular dystrophy (DMD), a rare musculoskeletal disorder, particularly in those treated with glucocorticoids (GCs). We aimed to assess the effectiveness of neridronate in terms of bone mineral density (BMD) changes in this population. METHODS: We retrospectively reviewed the records of patients affected by DMD receiving GCs referred to our outpatient from 2015 to 2020. All patients were treated with an intramuscular (IM) injection of neridronate (25 mg every month). Bone density was measured at the lumbar spine (LS; L1-L4 tract) using dual-energy x-ray absorptiometry (DXA) (GE Lunar), no more than 4 weeks before (T0) and after 1 year from neridronate treatment (T1). RESULTS: Eight boys with DMD were included with a mean age at diagnosis of 4.75 ± 2.81 years. Six of them were non-ambulant and two of them had previous low-trauma fractures (a distal femur fracture and a vertebral compression fracture, respectively). All patients were receiving deflazacort [median duration of therapy 11.5 years (interquartile range 2-25)]. At the DXA evaluation (T0), the mean L1-L4 BMD value was 0.716 ± 0.164 g/cm2. Six patients (75%) showed an L1-L4 Z-score height-adjusted of less than - 2. The mean age of neridronate initiation was 18.87 ± 6.81 years. All patients were supplemented with calcium carbonate and vitamin D at baseline. After 12 months of treatment (T1), the mean L1-L4 BMD value was 0.685 ± 0.190 g/cm2. Seven patients (87.5%) showed an L1-L4 Z-score of less than - 2. Changes in LS BMD and Z-score were not significant between T0 and T1 in our cohort (p = 0.674 and p = 0.208, respectively) as well as among non-ambulant patients with DMD without previous fragility fractures. CONCLUSIONS: In this study, we reported for the first time that neridronate may slow bone loss in GC-treated patients with DMD at 1-year follow-up.

A preliminary safety assessment of vertebral augmentation with32P brachytherapy bone cement.

Comprehensive treatment for vertebral metastatic lesions commonly involves vertebral augmentation (vertebroplasty or kyphoplasty) to relieve pain and stabilize the spine followed by multiple sessions of radiotherapy. We propose to combine vertebral augmentation and radiotherapy into a single treatment by adding32P, aß-emitting radionuclide, to bone cement, thereby enabling spinal brachytherapy to be performed without irradiating the spinal cord. The goal of this study was to address key dosimetry and safety questions prior to performing extensive animal studies. The32P was in the form of hydroxyapatite powder activated by neutron bombardment in a nuclear reactor. We performedex vivodosimetry experiments to establish criteria for safe placement of the cement within the sheep vertebral body. In anin vivostudy, we treated three control ewes and three experimental ewes with brachytherapy cement containing 2.23-3.03 mCi32P ml-1to identify the preferred surgical approach, to determine if32P leaches from the cement and into the blood, urine, or feces, and to identify unexpected adverse effects. Ourex vivoexperiments showed that cement with 4 mCi32P ml-1could be safely implanted in the vertebral body if the cement surface is at least 4 mm from the spinal cord in sheep and 5 mm from the spinal cord in humans.In vivo, a lateral retroperitoneal surgical approach, ventral to the transverse processes, was identified as easy to perform while allowing a safe distance to the spinal cord. The blood, urine, and feces of the sheep did not contain detectable levels of32P, and the sheep did not experience any neurologic or other adverse effects from the brachytherapy cement. These results demonstrate, on a preliminary level, the relative safety of this brachytherapy cement and support additional development and testing.

Multiple vertebral compression fractures in a human immunodeficiency virus-positive patient with glucocorticoid-induced Cushing syndrome treated with percutaneous vertebroplasty: a case report.

The authors present a rare case of multiple vertebral compression fractures in a young female with iatrogenic glucocorticoid-induced Cushing syndrome and concomitant human immunodeficiency virus (HIV) infection. Both long-term steroid use and HIV infection may lead to osteopenia or even osteoporosis. Multiple vertebral fractures in young patients are very uncommon and should alert the examiner to investigate any underlying cause. Treatment choices include pharmacological agents such as bisphosphonates or parathyroid hormone and even surgical interventions such as percutaneous vertebroplasty.

Pregnancy-related osteoporotic vertebral compression fractures in two patients treated with low-molecular-weight heparin during pregnancy: case reports.

Pregnancy-related osteoporosis (PRO) is an uncommon metabolic bone disease that can result in vertebral fragility fractures. Here we report two cases of young women who had been previously treated with LMWH-enoxaparin and were diagnosed with PRO with vertebral fragility fractures after delivery. In first case report, a 33-year-old primigravid woman who was treated with 40 mg/day of enoxaparin for eight months to prevent venous thromboembolism was presented. After delivery, Dual energy X ray absorptiometry (DEXA) revealed osteoporosis in lumbar and femoral neck region. In magnetic resonance imaging (MRI), T4-T7 thoracic vertebral height losses were detected. In second case report, a 28-year-old primigravid woman which was treated with 40 mg/day enoxparin from the second month to the birth was presented. Osteoporosis in lumbar region was detected by DEXA. MRI revealed T12-L1 and L5 vertebral height losses. In conclusion, PRO can cause severe low back pain and should be considered in differential diagnosis. A detailed medical history should be essential to detect relationship between LMWH and PRO.

A case of multiple vertebral compression fractures due to glucocorticoid-induced osteoporosis in a pediatric patient with nephrotic syndrome
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INTRODUCTION: Glucocorticoid therapy has a number of adverse effects, among which osteoporosis and bone fracture can be major complications. Immunosuppressive therapy for nephrotic syndrome is effective and can help to reduce the cumulative dose of glucocorticoids. Therefore, for this reason, the number of patients with nephrotic syndrome who develop glucocorticoid-related osteoporotic compression fracture is decreasing. Here we describe a pediatric case of multiple vertebral compression fractures due to glucocorticoid-induced osteoporosis during treatment for nephrotic syndrome. CASE PRESENTATION: A 12-year-old boy with nephrotic syndrome was treated with the standard corticosteroid regimen stipulated by the International Study of Kidney Disease in Children (ISKDC). Although he achieved complete remission, he suffered two episodes of relapse, and after the second such episode, the disease became resistant to the steroid therapy. Therefore, the patient received steroid pulse therapy followed by steroid tapering concomitant with cyclosporine administration. However, ~ 9 months after the start of steroid therapy, the patient developed multiple vertebral compression fractures with severe back pain. CONCLUSION: It is necessary to evaluate the state of bone at an early stage of treatment for nephrotic syndrome in children, even if the cumulative dose of glucocorticoid is not particularly high.
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Risk factors for vertebral compression fractures in preoperative chemoradiotherapy with gemcitabine for pancreatic cancer.

BACKGROUND AND PURPOSE: Preoperative chemoradiotherapy (CRT) with gemcitabine (GEM) for pancreatic cancer is often accompanied by vertebral compression fractures (VCFs). This study aimed to establish the incidence of VCFs and identify the related risk factors (RFs) to elucidate how to decrease the overall incidence of VCF. MATERIAL AND METHODS: We investigated 220 patients with resectable or borderline-resectable pancreatic cancers who had completed preoperative CRT between 2006 and 2011. The RFs associated with VCF were analyzed in a total of 1308 thoracolumbar vertebral bodies. RESULTS: Thirty-seven VCFs occurred in 25 patients (11%); the cumulative incidence at two years was 18.9%. Univariate analysis revealed female sex, age and high daily GEM concentration during radiotherapy as RFs for VCF. The multivariate mixed effects logistic regression model demonstrated that the most responsible factor was radiation dose (p<0.001). We estimated the radiation condition resulting in a fracture incidence of ⩽5% by counting the patient's number of the three RFs. For patients with three factors, the mean vertebral dose was 22.0 Gy. CONCLUSIONS: The RFs for VCF after CRT were identified. The side effect of VCF might be avoided by regulating the radiation dose to neighboring vertebral bodies after considering the RFs.

[Clinical research of percutaneous vertebroplasty or percutaneous kyphoplasty for treating osteoporotic vertebral compression fractures induced by glucocorticosteroid].

OBJECTIVE: To investigate the clinical characteristics of vertebral compression fracture (VCF) in glucocorticosteroid-induced osteoporosis (GIOP) and risk of vertebral refracture after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP). METHODS: In the study, 570 cases who received PVP or PKP as treatments of VCF from January 2010 to December 2013 were retrospective reviewed, of which 42 were GIOP and 21 were followed up as GIOP group, and the other 528 were primary osteoporosis and 391 were followed up, of which 84 were selected as Control group based on age and gender. The fracture location, ratio of single segment fracture and multiple segments fracture in the two groups were compared. In the final follow up, the reoperation rates for vertebral refractures by the Kaplan-Meier method in the two groups were compared. RESULTS: The follow up periods were (24.0± 13.1) months in GIOP group and (25.8±14.4) months in control group(P>0.05). In GIOP group, there were 11 cases with one-segment fracture, 2 with two-segments fracture, 3 with three-segments fracture, 2 with four-segments fracture, 2 with five-segments fracture and 1 with eight-segments fracture. In Control group, there were 67 cases with one-segment fracture, 12 with two-segments fracture, 3 with three-segment fracture, and 2 with four-segments fracture. The ratio of single segment fracture in GIOP group was significantly lower than that in Control group(52.4% vs. 79.8%,P=0.01). There were 50 fracture segments in GIOP group and 109 fracture segments in Control group. The ratios of fracture segments located in thoracic segments(T1-T10), thoracolumbar segments(T11-L1)and lumbar segments(L2-L5)were 18%, 46% and 36% in GIOP group and 11.9%, 58.7% and 29.4% in Control group (P>0.05). The refracture rate in GIOP group was higher than that in control group (23.8% vs. 6.0%). The survival rate was lower in GIOP group than that in control group (P<0.01). CONCLUSION: The predilection site of VCF was similar in GIOP and primary osteoporosis (thoracolumbar segments> thoracic segments> lumbar segments). The risk of multiple segments VCF was higher in GIOP than in primary osteoporosis. The risk of vertebral refractures after PVP or PKP was higher in GIOP than in primary osteoporosis.

Postpartum osteoporosis and vertebral fractures in two patients treated with enoxaparin during pregnancy.

Postpartum osteoporosis (PPO) is a rare disease associated with pregnancy and lactation period. Here, we report severe PPO and multiple vertebral compression fractures in two patients treated with enoxaparin--low-molecular-weight heparin (LMWH)--throughout their pregnancy. A 34-year-old woman who has delivered her second baby 3 months ago presented with severe low-back pain. She was treated with enoxaparin 40 mg/day for 8 months during her pregnancy. Dual-energy X-ray absorptiometry (DEXA) showed low T- and Z-scores in lumbar (L) vertebras. In magnetic resonance imaging (MRI), severe height losses in thoracic (T) 12, L1, and L2 vertebras were detected. She was diagnosed to have severe PPO and multiple vertebral compression fractures and was prescribed risedronate 35 mg/week, calcium, and vitamin D. The other patient was a 36-year-old woman diagnosed with PPO and vertebral fractures at the third week postpartum. She was also treated with enoxaparin 60 mg/day during her pregnancy. Severe osteoporosis in L vertebras and height losses indicative for compression fractures in T5-8, T11-12, and L2-5 vertebras were detected by DEXA and MRI, respectively. She was treated with calcitonin 200 U/day, calcium, and vitamin D. These findings suggest that vertebral compression fractures and PPO may be one of the causes of severe back pain in postpartum patients. Treatment with LMWH during pregnancy might be considered as a new risk factor for this rare condition.

Sudden paraplegia following epidural lipomatosis and thoracal compression fracture after long-term steroid therapy: a case report.

Sudden paraplegia secondary to the posterior spinal epidural compression and vertebral compression fracture as a complication in corticosteroid treatment is extremely rare. The authors presented a case 49-year-old man with chronic relapsing attack of Still's disease. After the identification of pathology, the surgical evacuation of lipid tissue and pedicle-based instrumentation showed therapeutic success. To the authors' knowledge, this is the first case showing both vertebral fracture and paraplegia that required urgent surgery in the follow-up Still's disease.

Impact of cement leakage into disks on the development of adjacent vertebral compression fractures.

STUDY DESIGN: A retrospective study assessing new adjacent vertebral compression fracture (VCF) after percutaneous vertebroplasty (PV). OBJECTIVE: To evaluate the relationship between cement leakage into the disk during initial PV and development of subsequent new adjacent VCF. SUMMARY OF BACKGROUND DATA: Cement leakage outside the vertebral body during PV has been reported and usually responds to conservative treatment. Sometimes bone cement may leak into the intervertebral disk and result in painful new adjacent VCF that usually requires another PV for pain relief. METHODS: From January 2002 to December 2002, a total of 106 consecutive patients underwent PVs for osteoporotic VCFs. The risk of new fractures of adjacent vertebral bodies, the amount of cement injection, and the duration of development of new adjacent fractures in relation to cement leakage into the disk were retrospectively assessed and statistically compared. RESULTS: New adjacent VCFs occurred in 20 (18.9%) of 106 patients at 22 adjacent vertebral bodies after PVs during at least 24 months of follow-up. The difference in number of new adjacent fractures between both patients and vertebral bodies with cement leakage and those without leakage into the disk were statistically significant (P<0.001 and P<0.001). Amounts of cement injected and duration to development of new adjacent fractures differed between patients with or without cement leakage (P<0.001 and P=0.005, respectively). CONCLUSIONS: PV is a simple and effective, but not risk-free or complication-free procedure for the treatment of osteoporotic VCF. Patients undergoing PV should be informed of the possibility of new adjacent fractures and the higher risk if cement leaks into the disk.

Adjacent vertebral body fracture following vertebroplasty with polymethylmethacrylate or calcium phosphate cement: biomechanical evaluation of the cadaveric spine.

STUDY DESIGN: A biomechanical study using human cadaveric thoracolumbar spinal columns. OBJECTIVE: To compare the effect of treatment by vertebroplasty (VP) with polymethylmethacrylate cement and VP with calcium phosphate cement on the creation of adjacent vertebral body fracture following VP. SUMMARY OF BACKGROUND DATA: Adjacent vertebral body fractures have been reported as a complication following VP. METHODS: Twenty-four spinal columns (T10-L2) from human cadavers were subjected to dual energy radiograph absorptiometry to assess bone mineral density. They were divided into the P group and C group, and experimental vertebral compression fractures were created at T12 vertebrae. T12 vertebrae were augmented with polymethylmethacrylate and calcium phosphate cement in the P group and C group, respectively. Each spinal column was compressed until a new fracture occurred at any vertebra, and the location of newly fractured vertebra and failure load was investigated. RESULTS: There was no significant difference in bone mineral density at each level within each group. In the P group, a new fracture occurred at T10 in 2 specimens, T11 in 8, and L1 in 2. In the C group, it occurred at T10 in 1 specimen, T11 in 2, L1 in 1, and T12 (treated vertebra) in 8. The failure loads of the spinal column were 1774.8+/-672.3 N and 1501.2+/-556.5 N in the P group and C group, respectively. There was no significant difference in the failure load of the spinal column between each group. CONCLUSION: New vertebral fractures occurred at the vertebra adjacent to augmented vertebrae in the P group and in the augmented vertebrae in the C group. The difference in the fractured site may be because of the difference in strength between the 2 bone filler materials. Therefore, the strength of bone filler materials is considered a risk factor in developing adjacent vertebral body fractures after VP.

Symptomatic refractures after vertebroplasty in patients with steroid-induced osteoporosis.

BACKGROUND AND PURPOSE: Refracture after percutaneous vertebroplasty in patients receiving oral glucocorticoid therapy has caused some patients and referring physicians to have negative perceptions concerning the efficacy of the initial vertebroplasty treatment. The purpose of this study was to analyze symptomatic refractures after vertebroplasty in patients on oral steroid therapy. We hypothesized that the higher refracture rate of patients on oral glucocorticoid therapy after percutaneous vertebroplasty is due not to an inadequacy of the procedure but rather to a naturally higher predisposition of these patients to refracture compared with patients with primary osteoporosis. METHODS: A retrospective analysis was performed on all osteoporosis patients having initial vertebroplasty from August 1999 to August 2003. The follow-up period was limited to 1 year after initial vertebroplasty session, with the last follow-up date ending in August 2004. Data were collected on 387 osteoporosis patients. RESULTS: Of the patients with primary osteoporosis, 20.6% patients refractured whereas 37.8% of the patients with steroid-induced osteoporosis had symptomatic refractures within 1 year of initial vertebroplasty. Relative risk of refracture within 1 year for the patients with steroid-induced osteoporosis was 1.84 compared with the patients with primary osteoporosis. In addition, the patients with steroid-induced osteoporosis were more likely to refracture after their second treatment session (within 1 year of initial vertebroplasty) than those with primary osteoporosis. CONCLUSION: Patients presenting on oral steroid therapy at their initial vertebroplasty are almost twice more likely to have symptomatic refractures than primary osteoporosis patients within 1 year of initial vertebroplasty.

Severe osteoporosis and multiple fractures in an AIDS patient treated with short-term steroids for lymphoma: a need for guidelines.

An HIV-1 infected patient on dual protease inhibitor treatment developed spontaneous vertebral fractures and avascular necrosis of the femoral bone after receiving combined chemotherapy for Burkitt's lymphoma including short-term prednisolone. The factors involved in the pathogenesis of osteopaenia and osteoporosis in this case are discussed and we propose the need for guidelines in order to reduce the incidence of such events in HIV-infected patients in the future.