SATB2-associated syndrome: characterization of skeletal features and of bone fragility in a prospective cohort of 19 patients.

BACKGROUND: Individuals with pathogenic variants in SATB2 display intellectual disability, speech and behavioral disorders, dental abnormalities and often features of Pierre Robin sequence. SATB2 encodes a transcription factor thought to play a role in bone remodeling. The primary aim of our study was to systematically review the skeletal manifestations of SATB2-associated syndrome. For this purpose, we performed a non-interventional, multicenter cohort study, from 2017 to 2018. We included 19 patients, 9 females and 10 males ranging in age from 2 to 19 years-old. The following data were collected prospectively for each patient: clinical data, bone markers and calcium and phosphate metabolism parameters, skeletal X-rays and bone mineral density. RESULTS: Digitiform impressions were present in 8/14 patients (57%). Vertebral compression fractures affected 6/17 patients (35%). Skeletal demineralization (16/17, 94%) and cortical thinning of vertebrae (15/17) were the most frequent radiological features at the spine. Long bones were generally demineralized (18/19). The distal phalanges were short, thick and abnormally shaped. C-telopeptide (CTX) and Alkaline phosphatase levels were in the upper normal values and osteocalcin and serum procollagen type 1 amino-terminal propeptide (P1NP) were both increased. Vitamin D insufficiency was frequent (66.7%). CONCLUSION: We conclude that SATB2 pathogenic variants are responsible for skeletal demineralization and osteoporosis. We found increased levels of bone formation markers, supporting the key role of SATB2 in osteoblast differentiation. These results support the need for bone evaluation in children and adult patients with SATB2-associated syndrome (SAS).

Incidental 68Ga-Prostate-Specific Membrane Antigen Uptake in Compression Fracture of a Vertebral Body.

ABSTRACT: Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein, which is overexpressed in prostate cancer cells. With its wide use, there is a growing number of case reports describing non-prostate cancer-related benign and malignant lesions showing increased 68Ga-PSMA uptake. We herein present the case of an 89-year-old man with prostate cancer who was referred for 68Ga-PSMA PET/CT for restaging, which revealed incidental 68Ga-PSMA uptake in compression fracture of a vertebral body. This case demonstrates that PSMA expression may occur in acute compression fractures, and it can be a potential pitfall when reporting 68Ga-PSMA PET/CT images.

Vertebral compression fractures: Still an unpredictable aspect of osteoporosis

Vertebral compression fracture is a hallmark of osteoporosis (OP) and by far the most prevalent fragility fracture. It is well proven that patients who develop a vertebral compression fracture are at substantial risk for additional fractures. Diagnosis is based on adequate clinical evaluation, imaging, and laboratory tests. The imaging of OP and fragility fractures includes conventional radiology to evaluate spinal fractures, bone mineral density (BMD) testing by dual energy x-ray densitometry, quantitative computerized tomography, magnetic resonance imaging, bone scintigraphy (if necessary), and ultrasound. Screening and treatment of individuals with high risk of osteoporotic fracture are cost-effective, but approximately two-thirds of the vertebral compression fractures (VCF) that occur each year are not accurately diagnosed and, therefore, not treated. Evaluation of VCFs, even though they may be asymptomatic, seems essential to health-related and/or clinical research on OP.

Additional Magnetic Resonance or Nuclear Scintigraphy Imaging Influences Approach to Vertebral Augmentation: A Single Institution Experience.

STUDY DESIGN: Retrospective review. OBJECTIVE: To ascertain impact of preprocedural magnetic resonance imaging (MRI) or nuclear medicine Tc99m-DMP scintigraphy on the treatment plan when compared with plain films and/or computed tomography prior to vertebral augmentation procedures. SUMMARY OF BACKGROUND DATA: Over 1 million vertebral compression fractures (VCFs) occur in the United States annually with over 150,000 individuals hospitalized each year. Physical examination and history are essential to the workup of VCFs, but imaging remains necessary for confirming the diagnosis. VCFs can be imaged with various modalities and there is limited data on the comparative effectiveness of different imaging modalities. METHODS: Six hundred fifty consecutive patients treated with vertebral augmentation at a single institution between May of 2013 and April of 2018 were reviewed. Preprocedure imaging of the spine obtained within 30 days prior to the procedure were reviewed. Preprocedure imaging results were cross-referenced against the levels treated by vertebral augmentation to determine whether there was a change in the levels treated after receiving an MRI or NM imaging study. RESULTS: Three hundred sixty-three patients had adequate imaging for inclusion. One hundred fifty-four of these 363 patients (42.4%) had an alteration of their treatment plan based upon the MR or NM imaging. Fewer vertebral levels were treated in 33, different levels were treated in 41, and more levels were treated in 80 patients. CONCLUSION: MRI or nuclear medicine bone scan imaging prior to vertebral augmentation altered the location and number of levels treated in a large percentage of patients, adding specificity to treatment over findings on radiographs or computed tomography alone. LEVEL OF EVIDENCE: 3.

Changes of Bone Turnover Markers and Bone Tissue Content After Severe Osteoporotic Vertebral Compression Fracture.

BACKGROUND The incidence of osteoporotic vertebral fractures (OVCFs) has increased significantly in recent years. In order to assess osteoporotic fracture healing process, it is necessary to study the characteristics after this type of vertebral fracture. However, there are few researches on fracture healing process in severe OVCFs. We aim to investigate the histological healing process and the kinetics of bone turnover markers following severe OVCFs. MATERIAL AND METHODS There were 149 patients with severe OVCFs included in this study. Fasting blood samples were obtained to detect bone turnover markers levels. A transpedicular bone biopsy was performed to collect bone biopsy specimens during vertebroplasty surgery. Stratification of healing process was performed: stage I (1-3 days), stage II (4-10 days), stage III (11-20 days), stage IV (21-30 days), stage V (1-3 months), stage VI (3-6 months). RESULTS Quantitative analysis of bone histomorphometry showed that a large amount of necrotic bone tissue was observed in stage VI (12.92±3.66%). Bone turnover markers showed the concentration of ß-isomerized C-terminal telopeptide (ß-CTX) which reflects activity in osteoclast continued to increase in stage VI (0.9±0.33 ng/mL). These results differed from previous reports of other type vertebral fractures. CONCLUSIONS Bone histomorphometric analysis and bone turnover markers showed that severe osteoporotic vertebral compression fractures often associated with delayed union and nonunion during the healing process.

Combined intravoxel incoherent motion diffusion-weighted MR imaging and magnetic resonance spectroscopy in differentiation between osteoporotic and metastatic vertebral compression fractures.

PURPOSE: Our purpose was to combine intravoxel incoherent motion diffusion-weighted MR imaging (IVIM-DWI) and magnetic resonance spectroscopy (MRS) to differentiate osteoporotic fractures from osteolytic metastatic vertebral compression fractures (VCFs). METHODS: A total of 70 patients with VCFs were included and divided into two groups, according to their causes of fractures based on pathological findings or clinical follow-up. All patients underwent conventional sagittal T1WI, T2WI, STIR, IVIM-DWI, and single-voxel MRS. The diffusion coefficient (D), pseudo diffusion (D*), and perfusion fraction (f) parameters from IVIM-DWI and the lipid water ratio (LWR) and fat fraction (FF) parameters from MRS were obtained and compared among groups. Furthermore, the diagnostic performance of MRS, IVIM-DWI, and IVIM-DWI combined with MRS for differentiation between osteoporotic and osteolytic metastatic VCFs was assessed by using receiver operating characteristic (ROC) curve analysis. RESULTS: Compared with the osteoporotic group, the metastatic group had significantly lower values for f, D, and FF, but higher D* (all P < 0.05). The area under the receiver operating characteristic (ROC) curve of MRS, IVIM-DWI, and IVIM-DWI combined with MRS were 0.73, 0.88, and 0.94, respectively. Among these, the IVIM-DWI combined with MRS showed the highest sensitivity, specificity, and accuracy, which are 90.63% (29/32), 97.37 % (37/38), and 94.29% (66/70), respectively. CONCLUSIONS: IVIM-DWI combined with MRS can be more accurate and efficient for differentiation between osteoporotic and osteolytic metastatic VCFs than single MRS or IVIM-DWI.

The risk factors of vertebral refracture after kyphoplasty in patients with osteoporotic vertebral compression fractures: a study protocol for a prospective cohort study.

BACKGROUND: Percutaneous kyphoplasty (PKP) is the first-line treatment for osteoporotic vertebral compression fractures (OVCFs) that can immediately relieve pain and allow the quick recovery of lost mobility. However, some studies reported that after PKP, the incidence of vertebral refracture, particularly adjacent vertebral fracture (AVF), was high. Our previous meta-analysis suggested that the risks for vertebral refracture and AVF did not increase after percutaneous vertebral augmentation in OVCF patients. Despite the negative results of our meta-analysis, there is still significant evidence regarding the relationship between kyphoplasty and AVF, so a new prospective cohort study is warranted. In addition, in our previous retrospective study, we found that advanced age, female sex and low oestradiol (E2) concentrations might be related to the occurrence of postoperative vertebral refracture after PKP. To sufficiently evaluate the probable factors involved in the occurrence of postoperative vertebral refracture, we designed this prospective study. METHODS: This is a prospective cohort study of patients admitted for PKP to treat painful OVCFs. The baseline data, including demographic information, lifestyle, bone metabolic status, sex hormone and sex hormone-binding globulin (SHBG) levels, and clinical characteristics will be collected at the time of enrolment. Surgical features of PKP will be recorded on the operation day. Lifestyle, bone metabolic status, sex hormone levels, and SHBG levels will be assessed during the follow-up period at 1 m, 3 m, 12 m, and 24 m postoperatively. Patients suffering from acutely aggravated back pain will be referred to an orthopaedist, and refractured vertebrae will be confirmed by magnetic resonance imaging and computed tomography. The primary outcome will be the incidence of vertebral refracture. Multivariate analyses will be carried out to evaluate the variables that are independently correlated with vertebral refracture. DISCUSSION: To evaluate the risk of postoperative refracture preoperatively and to identify the surgical points related to postoperative refracture, this study will explore the risk factors related to vertebral refracture after PKP. The results may provide new information about defining OVCF patients suitable for PKP treatment. TRIAL REGISTRATION: ChiCTR-ROC-17011562 . Registered on July 4th, 2017.

Polymethylmethacrylate distribution is associated with recompression after vertebroplasty or kyphoplasty for osteoporotic vertebral compression fractures: A retrospective study.

BACKGROUND: Osteoporotic vertebral compression fracture, always accompanied with pain and height loss of vertebral body, has a significant negative impact on life quality of patients. Vertebroplasty or kyphoplasty is minimal invasive techniques to reconstruct the vertebral height and prevent further collapse of the fractured vertebrae by injecting polymethylmethacrylate into vertebral body. However, recompression of polymethylmethacrylate augmented vertebrae with significant vertebral height loss and aggressive local kyphotic was observed frequently after VP or KP. The purpose of this study was to investigate the effect of polymethylmethacrylate distribution on recompression of the vertebral body after vertebroplasty or kyphoplasty surgery for osteoporotic vertebral compression fracture. METHODS: A total of 281 patients who were diagnosed with vertebral compression fracture (T5-L5) from June 2014 to June 2016 and underwent vertebroplasty or kyphoplasty by polymethylmethacrylate were retrospectively analyzed. The X-ray films at 1 day and 12 months after surgery were compared to evaluate the recompression of operated vertebral body. Patients were divided into those without recompression (non-recompression group) and those with recompression (recompression group). Polymethylmethacrylate distribution pattern, including location and relationship to endplates, was compared between the two groups by lateral X-ray film. Multivariate logistic regression analysis was performed to assess the potential risk factors associated with polymethylmethacrylate distribution for recompression. RESULTS: One hundred and six (37.7%) patients experienced recompression after surgery during the follow-up period. The polymethylmethacrylate distributed in the middle of vertebral body showed significant differences between two groups. In non-recompression group, the polymethylmethacrylate in the middle portion of vertebral body were closer to endplates than that in the recompression group (upper: t = 31.41, p<0.001; lower: t = 12.19, p<0.001). The higher percentage of the height of polymethylmethacrylate in the middle portion of vertebral body indicates the lower risk of recompression (odds ratio [OR]<0.01, p<0.001). The recompression group and non-recompression group showed significant difference in "contacted" polymethylmethacrylate distribution pattern (polymethylmethacrylate contacted to the both upper/lower endplates) (χ2 = 66.23, p<0.001). The vertebra with a "contacted" polymethylmethacrylate distribution pattern has lower risk of recompression (OR = 0.09, p<0.001). CONCLUSIONS: Either more polymethylmethacrylate in the middle portion of vertebral body or "contacted" polymethylmethacrylate distribution pattern had a significantly less incidence of recompression. The findings indicated that the control of polymethylmethacrylate distribution during surgery may reduce the risks of recompression after vertebroplasty or kyphoplasty.

An injectable, biodegradable calcium phosphate cement containing poly lactic-co-glycolic acid as a bone substitute in ex vivo human vertebral compression fracture and rabbit bone defect models.

Purpose/Aim of the study: To evaluate the biomechanical characteristics and biocompatibility of an injectable, biodegradable calcium phosphate cement (CPC) containing poly lactic-co-glycolic acid (PLGA). MATERIALS AND METHODS: A vertebral compression fracture model was established using 20 human cadaveric vertebrae (T11-L3) divided into CPC/PLGA composite versus PMMA groups for biomechanical testing. In addition, 35 New Zealand rabbits were used to evaluate biodegradability and osteoconductive properties of CPC/PLGA using a bone defect model. In vitro cytotoxicity was evaluated by culturing with L929 cells. RESULTS: The CPC/PLGA composite effectively restored vertebral biomechanical properties. Compared with controls, the maximum load and compression strength of the CPC/PLGA group were lower, and stiffness was lower after kyphoplasty (all p <.05). Degradation was much slower in the control CPC compared with CPC/PLGA group. The bone tissue percentage in the CPC/PLGA group (44.9 ± 23.7%) was significantly higher compared with control CPC group (25.7 ± 10.9%) (p <.05). The viability of cells cultured on CPC/PLGA was greater than 70% compared with the blanks. CONCLUSIONS: Our biodegradable CPC/PLGA composite showed good biomechanical properties, cytocompatibility, and osteoconductivity and may represent an ideal bone substitute for future applications.

Vertebral compression fractures as the initial presentation of AL amyloidosis: case series and review of literature.

The clinical presentation of AL amyloidosis is highly variable. In this series, we describe five cases of AL amyloidosis with vertebral compression fractures as initial presentation. All five patients had evidence of bone marrow replacement on magnetic resonance imaging and bone marrow biopsies demonstrating diffuse interstitial amyloid deposition. Hepatomegaly and elevated liver enzymes, consistent with liver involvement with amyloidosis, were also seen in each case. All five patients responded well to anti-plasma cell chemotherapy, with normalization of serum free light chain levels, reduction in alkaline phosphatase and improvement in pain and functional status. Although rare, AL amyloidosis should be considered in the differential diagnosis of selected patients with spontaneous vertebral compression fractures. Moreover, there seems to be an association of vertebral compression fractures with liver involvement in AL amyloidosis.

Transient activation of an adaptor protein, disabled-2, in rat spinal cord injury.

We previously reported that disabled-2 (Dab-2), a cytosolic adaptor protein, was expressed in inflammatory and glial cells in the central nervous system (CNS) in experimental autoimmune encephalomyelitis and cerebral cryoinjury. Here, to determine the pattern of Dab-2 expression in a clip compression-induced rat spinal cord injury (SCI) model, the protein level and localization of Dab-2 in the spinal cord were investigated in rats with SCI using Western blotting and immunohistochemistry. Western blotting revealed that the expression of both the 75- and 100-kDa isoforms of Dab-2 peaked significantly in the spinal cord after clip compression injury 7 days post-injury compared to sham controls, and declined slightly thereafter. Immunohistochemistry revealed weak Dab-2 immunostaining in some neurons, glial cells, and ependymal cells in the spinal cords of the control animals, compared to staining in the macrophages and reactive astrocytes in lesions of the SCI animals. Overall, these findings suggest that both isoforms of Dab-2 are transiently upregulated in response to SCI and that the increased expression of Dab-2 is associated with the early activation of macrophages and astrogliosis in the course of CNS inflammation.

Mechanical stress-induced apoptosis of nucleus pulposus cells: an in vitro and in vivo rat model.

BACKGROUND: Un-physiological loads play an important role in the degenerative process of inter-vertebral discs (IVD). In this study, we used an in vitro and in vivo rat model to investigate the mechanism of nucleus pulposus (NP) cells apoptosis induced by mechanical stress. METHODS: Static compressive load to IVDs of rat tails was used as the in vivo model. For the in vitro model, NP cells were tested under the physiological and un-physiological loading. For histological examination, apoptotic index study, and apoptotic gene expression, we also selected cytokines [bone morphogenetic protein (BMP)-2/7, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)] to be analyzed. RESULTS: Under mechanical loading, cellular density was significantly decreased, but there was an increase of TUNEL positive cells and apoptosis index. In a dose-dependent manner; the necrosis became apparent in the un-physiologic strain. The selected cytokines (BMP-2/7, IGF-1, PDGF) can significantly reduce the percentage of apoptotic and necrotic cells. CONCLUSIONS: We conclude that the intrinsic (mitochondrial) apoptotic pathway plays an important role in the compressive load-induced apoptosis of NP cells. Combination therapy reducing the mechanical load and selected cytokines (BMP-2/7, IGF-1 and PDGF) may have considerable promise in the treatment of spine disc degeneration.

Bone marrow fat quantification of osteoporotic vertebral compression fractures: comparison of multi-voxel proton MR spectroscopy and chemical-shift gradient-echo MR imaging.

BACKGROUND: Only a few studies have used in/opposed phase method for a quantitative evaluation of fat fraction in the spine. PURPOSE: To compare multivoxel proton MR spectroscopy and chemical-shift gradient-echo MR imaging for bone marrow fat quantification in vertebral compression fractures (VCF). MATERIAL AND METHODS: Vertebral marrow fat quantification in fifteen patients was measured at 3.0-T. Multi-voxel proton spectroscopy (MRS) and in/opposed-phase MR imaging using a fat map build with a triple-echo gradient-echo sequence was used. All the patients had benign vertebral collapse. Bone marrow fat content was evaluated by both techniques in compressed (acute or chronic) and in non-compressed vertebrae. RESULTS: The percentage of fat fraction measured by the triple-echo sequence was well correlated with those calculated by MRS (r(2) = 0.85; P < 10(-4)). There was a significant decrease of fat fraction in acute VCF versus both chronic VCF (P < 10(-9)) and non-fractured vertebrae (P < 10(-7)). There was no significant difference in fat fraction evaluated by both techniques between non-fractured vertebrae and chronic VCF. CONCLUSION: We have validated the in/opposed phase method compared with MRS for vertebral bone marrow fat quantification. The fat mapping using a triple-echo gradient-echo sequence allows distinguishing acute and chronic benign VCF.

Are persistently symptomatic vertebral compression fractures associated with abnormal inflammatory profiles? A prospective study.

STUDY DESIGN: A case-control study with prospectively collected samples for laboratory analysis in a series of patients with spinal fragility fractures and a series of patients without fracture who underwent fusion for LBP. OBJECTIVE: Was an exploratory data analysis for candidate cytokine biomarkers present in the fracture milieu of patients with persistent back pain associated with vertebral compression fracture. SUMMARY OF BACKGROUND DATA: Lumbar and thoracic compression fractures are common. Little is known about the presence of inflammatory mediators within fractured vertebra in the clinical setting. METHODS: Thirty patients diagnosed with a single thoracic or lumbar compression fracture were treated with single level vertebroplasty. At the time of intervention, needle aspiration was carried out at the fractured level. A multiplexed bead assay was used to assess the presence of 27 different cytokines and inflammatory mediators. A control group consisted of needle aspiration samples of 30 lumbar vertebra from 13 patients with chronic pain but no fracture undergoing open instrumented fusion. RESULTS: Thirty patients with 30 fractures consisted of 23 female and 7 male with a mean age of 77.5 years (SD 13.6; range 42 to 97) and a mean of 3.9 weeks of pain (SD 3.1; range 1 to 12). The highest levels of inflammatory mediators were (in order): IL-1 receptor antagonist, PDGF, RANTES, IP-10, IL-8, and eotaxin. These mediators were present at concentrations>200 pg/mL. Compared with controls with chronic pain, significant differences were present for 4 mediators: TNF, MIP-1b, IL-9, and IL-12. The panel of these 4 markers was 93.3% specific and 66.7% sensitive for fracture compared with the control group. CONCLUSIONS: Inflammatory mediators are present in needle aspirates of symptomatic vertebral compression fractures. Some of these mediators show different levels than in patients with chronic pain but no fracture. LEVEL OF EVIDENCE: Diagnostic level of evidence II.

Decreased bone mineral density and vertebral compression fractures in a young adult male with 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH): is CAH an unrecognized population at risk for glucocorticoid-induced osteoporosis?

BACKGROUND: CAH, most often due to a molecular defect in the 21-OH enzyme, results in inadequate cortisol production and subsequent life-long GC replacement. AIMS: To heighten awareness for risk of GIO in children with CAH including (1) ongoing assessment of GC dosing, (2) screening for bone health, and (3) prophylactic measures/early intervention once GIO is identified. PATIENT: 23 year-old male with 21OHD CAH referred for osteopenia. METHODS: Chart review; radiological, serological and urine assessment. RESULTS: Patient has old vertebral compression fractures and diminished BMD, the onset of which likely corresponds to excessive GC dosing during adolescence. CONCLUSION: As with other GC-dependent conditions, children with CAH may represent a previously unrecognized population at risk for GIO. Physicians need to be cognizant of the consequences of excessive GC dosing on bone health, especially during infancy and adolescence, critical periods for both linear growth as well as bone accretion.

Sequential changes of bone metabolism in normal and delayed union of the spine.

UNLABELLED: Time-dependent changes in bone markers in delayed or nonunion of vertebral fracture were compared with those of normal union. Thirty-three patients with a fresh vertebral fracture were enrolled. Urinary Type I collagen C-terminal telopeptide, pyridinoline, deoxypyridinoline, serum C-terminal telopeptide, and N-midportion of osteocalcin (OC(N-mid)) were determined at the time of hospital admission (within 24 hours after the fracture event in all cases) and at 2, 4, 12, 24, and 48 weeks thereafter. Subjects were divided into two groups according to the results of MR images taken 48 weeks after fracture. Twenty-four were normally united (Group N) and nine had delayed or nonunion (Group D) of the spine. No differences between values of bone resorption markers in Group N and Group D were observed at any time. Serum OC(N-mid) in Group N started to increase at 2 weeks and reached the peak value at 24 weeks (180%); however, serum OC(N-mid) in Group D increased at most 120% from baseline to 4 weeks. Values of serum OC(N-mid) in Group N were higher at 24 and 48 weeks than those in Group D. Impairment of fracture healing was strongly associated with a deficit in the increase of osteocalcin in the later stage of fracture repair. LEVEL OF EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Nonprogression of vertebral area or bone mineral content on DXA does not predict compression fractures.

The 2003 International Society for Clinical Densitometry consensus guidelines recommend exclusion of vertebral bodies for lack of increase in bone area (BA) or bone mineral content (BMC), or an unusual T-score discrepancy (>1 standard deviation [SD]) between adjacent vertebrae. It is unclear how often nonprogression in BA, BMC, and T-score discrepancies predicts abnormal vertebral morphology, such as compression fractures. We prospectively studied 101 individuals sent for clinical dual-energy X-ray absorptiometry (DXA) scanning, including 20.8% males and 79.2% females. The population was 85% Caucasian, 13% African-American, and 3% Hispanic. The mean age was 65.6 yr; 20.2% were currently on steroids and 22.7% were taking drugs for osteoporosis. All subjects underwent the usual posteroanterior (PA) spine DXA scan PA and lateral vertebral fracture analysis (VFA). The presence of vertebral compression fractures and/or scoliosis of the lumbar spine by VFA were correlated with nonprogression of area or BMC, and/or a difference of >1 SD in T-scores using Fisher's exact test. By VFA, we detected 22 lumbar compression fractures among 101 subjects, which was 16% of the population. Nonprogression of BA, BMC, and T-score discrepancy were not statistically associated with the presence of vertebral compression fracture as assessed by VFA. Thirty percent of subjects had lumbar spine scoliosis. The presence of scoliosis was significantly related to a T-score discrepancy at L1-L4.