Outcomes of Balloon Kyphoplasty for Vertebral Compression Fractures in Patients with Diffuse Idiopathic Skeletal Hyperostosis at the Distal End or Adjacent Vertebra of the Fused Segments.

STUDY DESIGN: A retrospective cohort study. PURPOSE: To investigate the outcomes of balloon kyphoplasty (BKP) for vertebral compression fractures (VCFs) at the distal end or adjacent vertebra of the fused segments in patients with diffuse idiopathic skeletal hyperostosis (DISH). OVERVIEW OF LITERATURE: Vertebral fractures in the midportion of the fused segments in patients with DISH are generally unstable; thus, immobilization is recommended. However, VCFs classified as type A in the AO classification are observed at the distal end and adjacent vertebra of the fused segments, and treatment strategies for VCFs associated with DISH remain controversial. METHODS: The outcomes of 72 patients who underwent BKP for VCFs between 2015 and 2021 were retrospectively investigated. Patients with DISH were assigned to group D (n=21), whereas those without DISH were assigned to group ND (n=51). Back pain, incidence of subsequent adjacent fractures, reoperation rates, and local kyphosis were statistically analyzed. RESULTS: VCFs in group D occurred at the distal end or adjacent vertebra of the fused segments, and no fractures occurred in the midportion of the fused segment. Back pain improved in both groups, with no significant differences between them. Subsequent adjacent fractures were observed in three of the 21 patients in group D and 11 of the 51 patients in group ND, with no significant difference between them. Reoperation was performed in one patient each in groups D and ND, with no significant difference between the groups. Postoperatively, local kyphosis progressed significantly in group D. CONCLUSIONS: Although local kyphosis is more advanced in patients with DISH, BKP is effective for VCFs at the distal end or adjacent vertebra of the fused segments and may be useful in older patients with high complication rates.

Negative Effects of Diffuse Idiopathic Skeletal Hyperostosis on Bone Fusion after Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: This study adopted a retrospective cohort study design. PURPOSE: This study aimed to clarify the influence of diffuse idiopathic skeletal hyperostosis (DISH) on bone fusion after transforaminal lumbar interbody fusion (TLIF). OVERVIEW OF LITERATURE: The negative effects of DISH on lumbar degenerative diseases have been reported, and DISH may be involved in the onset and severity of lumbar spinal canal stenosis. Patients with DISH have significantly more reoperations after posterior lumbar fusion, including TLIF. However, the effects of DISH on bone fusion after TLIF have not been reported. METHODS: The medical records of patients with intervertebral TLIF from 2012 to 2018 were retrospectively examined. The patients were divided into those with fusion and those with pseudoarthrosis, and the following data were compared: age, sex, DISH, diabetes mellitus, smoking, drinking, albumin levels, body mass index ≥30 kg/m2, and L5/S fixation. Statistical analyses were performed using regression models. RESULTS: In this study, 180 patients (78.6%) had fusion and 49 patients (21.4%) had pseudoarthrosis. The number of patients with DISH was significantly higher in the pseudoarthrosis group than in the fusion group (36.7% and 21.7%, respectively; univariate p=0.031, multivariate p =0.019). No significant differences in age, sex, diabetes mellitus, smoking, drinking, albumin levels, body mass index ≥30 kg/m2, and L5/S fixation were observed between the two groups. The risk factors for bone fusion were statistically analyzed in 57 patients with DISH. DISH with a caudal end below Th11 was an independent risk factor for pseudoarthrosis (univariate p=0.011, multivariate p=0.033). CONCLUSIONS: DISH is an independent risk factor for pseudoarthrosis after one intervertebral TLIF, and DISH with a caudal end below Th11 is associated with a higher risk of pseudoarthrosis than DISH without a caudal end below Th11.

Severe cervical kyphosis in a young adult with fixed dropped head syndrome, dysphagia, and myelopathy: A case report.

BACKGROUND: Several reports exist on syndromic cervical kyphosis in the elderly, including dropped head syndrome, degenerative spondylosis, and neurological diseases; however, it is rarely reported in young patients especially with complications. CASE PRESENTATION: We describe a case of a 25-year-old man who presented severe cervical kyphosis with dropped head syndrome, horizontal-gaze disorder, dysphagia, and myelopathy. The etiology of this cervical kyphosis was suspected to be as a result of a combination of an underlying developmental disorder and habitual, long-term cervical flexion postures while engaging in smartphone games. Combined anterior and posterior surgeries resulted in good outcomes and improved the patient's quality of life remarkably. CONCLUSION: Cervical kyphosis awareness in young patients is crucial. Moreover, combined anterior and posterior approach provides secure, good results, and with less sequelae.

Non-invasive skin autofluorescence, blood and urine assays of the advanced glycation end product (AGE) pentosidine as an indirect indicator of AGE content in human bone.

BACKGROUND: Bone mineral density (BMD) measurements are widely used to assess fracture risk. However, the finding that some fracture patients had high BMD together with the low contribution of drugs to osteoporosis suggests that bone strength factors other than BMD contribute to bone quality. We evaluated the amount of advanced glycation end products (AGEs) by non-invasive assays of serum and urine as well as by skin autofluorescence to measure the levels of a representative AGE, pentosidine, to investigate whether pentosidine can serve as an indirect indicator of AGEs formation in bone collagen. METHODS: A total of 100 spinal surgery patients without fragility fracture (54 males and 46 females) treated at our hospital were enrolled. The amount of pentosidine in blood, urine, skin and bone (lumbar lamina) samples from these patients was measured. AGE accumulation was assessed by measuring skin autofluorescence. We examined the correlation between pentosidine content in tissues and body fluid, as well as skin AGEs with age, height, body weight, BMI, and estimated glomerular filtration rate (eGFR). RESULTS: A significant age-related increase in pentosidine levels in tissues was observed, while there was a significant negative correlation between tissue pentosidine and eGFR. The amount of skin pentosidine was significantly and positively correlated with pentosidine content of the bone in those under 50 years of age. Urine pentosidine also correlated positively with bone pentosidine and skin pentosidine, but only in females. The total amount of AGEs in skin did not correlate with bone pentosidine. CONCLUSION: In this study, the strong correlation between the pentosidine content in each sample and eGFR may indicate that renal dysfunction with advancing age increases oxidative stress and induces AGEs formation in collagen-containing tissues. The correlation of skin pentosidine concentration and eGFR, with AGEs formation in bone collagen suggests that pentosidine would be a useful indirect index of decreased bone quality. Skin AGEs estimated by autofluorescence in clinical situations may not be suitable as an indirect assessment of bone quality. Because urine pentosidine correlated positively with bone pentosidine and skin pentosidine in females, urine pentosidine may be a candidate for an indirect assessment of bone quality.

Effects of 18-month treatment with bazedoxifene on enzymatic immature and mature cross-links and non-enzymatic advanced glycation end products, mineralization, and trabecular microarchitecture of vertebra in ovariectomized monkeys.

Bazedoxifene (BZA) is used for the treatment of post-menopausal osteoporosis. To elucidate changes in collagen, mineralization, and structural properties and their relationship to bone strength after treatment with BZA in ovariectomized (OVX) monkeys, the levels of collagen and enzymatic immature, mature, and non-enzymatic cross-links were simultaneously examined, as well as trabecular architecture and mineralization of vertebrae. Adult female cynomolgus monkeys were divided into 4 groups (n=18 each) as follows: Sham group, OVX group, and OVX monkeys given either 0.2 or 0.5mg/kg BZA for 18 months. Collagen concentration, enzymatic and non-enzymatic pentosidine cross-links, whole fluorescent advanced glycation end products (AGEs), trabecular architecture, mineralization, and cancellous bone strength of vertebrae were analyzed. The levels of enzymatic immature and mature cross-links, bone volume (BV/TV), and trabecular thickness (Tb.Th) in BZA-treated groups were significantly higher than those in the OVX control group. In contrast, the trabecular bone pattern factor (TBPf), the structure model index (SMI), the enzymatic cross-link ratio, and the levels of pentosidine and whole AGEs in BZA-treated groups were significantly lower than those in the OVX control group. Stepwise logistic regression analysis revealed that BV/TV, Tb.Th, TbPf, and pentosidine or whole AGEs independently affected ultimate load (model R(2)=0.748, p<0.001) and breaking energy (model R(2)=0.702). Stiffness was affected by Tb.Th, enzymatic immature cross-link levels and their ratio (model R(2)=0.400). Treatment with BZA prevented OVX-induced deterioration in the total levels of immature enzymatic cross-links and AGEs accumulation and structural properties such as BV/TV, Tb.Th, and TbPf, which contribute significantly to vertebral cancellous bone strength.

Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone.

Eldecalcitol (ELD), an active form of vitamin D analog approved for the treatment of osteoporosis in Japan, increases lumbar spine bone mineral density (BMD), suppresses bone turnover markers, and reduces fracture risk in patients with osteoporosis. We have previously reported that treatment with ELD for 6 months improved the mechanical properties of the lumbar spine in ovariectomized (OVX) cynomolgus monkeys. ELD treatment increased lumbar BMD, suppressed bone turnover markers, and reduced histomorphometric parameters of both bone formation and resorption in vertebral trabecular bone. In this study, we elucidated the effects of ELD on bone quality (namely, mineralization, microarchitecture, microdamage, and bone collagen crosslinks) in OVX cynomolgus monkeys in comparison with OVX-vehicle control monkeys. Density fractionation of bone powder prepared from lumbar vertebrae revealed that ELD treatment shifted the distribution profile of bone mineralization to a higher density, and backscattered electron microscopic imaging showed improved trabecular bone connectivity in the ELD-treated groups. Higher doses of ELD more significantly reduced the amount of microdamage compared to OVX-vehicle controls. The fractionated bone powder samples were divided according to their density, and analyzed for collagen crosslinks. Enzymatic crosslinks were higher in both the high-density (≥2.0 mg/mL) and low-density (<2.0 mg/mL) fractions from the ELD-treated groups than in the corresponding fractions in the OVX-vehicle control groups. On the other hand, non-enzymatic crosslinks were lower in both the high- and low-density fractions. These observations indicated that ELD treatment stimulated the enzymatic reaction of collagen crosslinks and bone mineralization, but prevented non-enzymatic reaction of collagen crosslinks and accumulation of bone microdamage. Bone anti-resorptive agents such as bisphosphonates slow down bone remodeling so that bone mineralization, bone microdamage, and non-enzymatic collagen crosslinks all increase. Bone anabolic agents such as parathyroid hormone decrease bone mineralization and bone microdamage by stimulating bone remodeling. ELD did not fit into either category. Histological analysis indicated that the ELD treatment strongly suppressed bone resorption by reducing the number of osteoclasts, while also stimulating focal bone formation without prior bone resorption (bone minimodeling). These bidirectional activities of ELD may account for its unique effects on bone quality.

[Bone metabolism and cardiovascular function update. The estimation of bone material quality in the concept of bone and vascular linkage].

It has become clear that a reduction in sex hormones from middle age onwards, increasing age, and an increase in oxidative stress related to lifestyle-related diseases can also reduce bone material properties in terms of collagen post-translational modification, crosslink formation. These changes lead to both qualitative and quantitative abnormalities in collagen, which is the major bone matrix protein. The intermolecular cross-link formation of collagen, which regulates bone-material attributes, is a mechanism independent of bone remodeling. In other words, cross-link formation is controlled by the environment surrounding the bone matrix, comprising cellular functions, oxidative stress, and glycation level. Because oxidative stress is also risk factor of arteriosclerosis and cardiovascular event, there is link between low bone quality and arteriosclerosis. High levels of pentosidine in urine or blood, or mild hyperhomocysteinemia which suggest bone collagen abnormalities, might be used as surrogate markers for evaluating bone quality, assessing the risk of bone fracture. Patients with osteoporosis can be divided into 3 types on the basis of bone density and with bone quality. We are entering an age in which the treatment of osteoporosis will be personalized, with drugs administered depending on these types.

Diabetes, collagen, and bone quality.

Diabetes increases risk of fracture, although type 2 diabetes is characterized by normal or high bone mineral density (BMD) compared with the patients without diabetes. The fracture risk of type 1 diabetes as well as type 2 diabetes increases beyond an explained by a decrease of BMD. Thus, diabetes may reduce bone strength without change in BMD. Whole bone strength is determined by bone density, structure, and quality, which encompass the micro-structural and tissue material properties. Recent literature showed that diabetes reduces bone material properties rather than BMD. Collagen intermolecular cross-linking plays an important role in the expression of bone strength. Collagen cross-links can be divided into beneficial enzymatic immature divalent and mature trivalent cross-links and disadvantageous nonenzymatic cross-links (Advanced glycation end products: AGEs) induced by glycation and oxidation. The formation pathway and biological function are quite different. Not only hyperglycemia, but also oxidative stress induces the reduction in enzymatic cross-links and the formation of AGEs. In this review, we describe the mechanism of low bone quality in diabetes and the usefulness of the measurement of plasma or urinary level of AGEs for estimation of fracture risk.

Height velocity curves in female patients with idiopathic scoliosis.

Following identification of peak height velocity (PHV) by a recent study as a possible prognostic factor for curve progression in patients with idiopathic scoliosis (IS), the aim of this study was to investigate PHV curves in Japanese female patients with IS. The study subjects were 20 skeletally immature IS patients who were followed until maturity. The mean age and the mean pubertal status at the initial visit were 9.8 years and 24 months before menarche, respectively, with a follow-up period of 5.2 years. Height measurements were recorded at each visit, and HV was calculated as the change in height (cm) divided by the time interval (yr.) between visits of 6 to 12 months. The PHV, age at PHV (APHV), height at PHV (HPHV), and final height (FH) were determined. Patient HV curves were plotted using their HV data, and growth periods (GPs) were calculated from the curves. PHVs and GPs of study patients were compared to standard data from unaffected girls. The median values and interquartile ranges in PHV, APHV, HPHV, and FH were 8.5 cm/yr. (7.9-9.7), 11.8 yr. (11.2-12.1), 153.2 cm (150.1-155.8), and 160.1 cm (157.4-162.4), respectively. The median GP was 27 months. The PHV and GP values in IS female patients were higher and shorter than those in unaffected girls. These findings indicate that the patterns of height velocity curves in IS patients are different from those in unaffected girls, suggesting that curve progression in IS patients is associated with the magnitude of PHV and duration of GP. Recently, we have developed an HV reader to easily and quickly identify the present HV in patients with scoliosis, applicable for the clinical setting or school screening. We conclude that risk assessments of curve progression in patients with IS should include HV along with measures of skeletal maturity such as the Risser sign and/or digital skeletal age using hand X-rays.

Anatomical considerations for cervical pedicle screw insertion: the use of multiplanar computerized tomography reconstruction measurements.

OBJECT: The purpose of this study was to evaluate the linear and angular parameters of the vertebral body (VB) required for cervical pedicle screw (CPS) insertion by using multiplanar computerized tomography (CT) reconstructions. METHODS: Three hundred fifteen vertebrae from C-3 to C-7 in 63 patients were studied. Pedicle dimensions such as pedicle transverse angle (PTA), pedicle sagittal angle (PSA), and pedicle outer width (POW) were measured on axial CT reconstructions, as were linear parameters including the lateral mass thickness (LMT), the anteroposterior (AP) and mediolateral distances between spinal canal and transverse foramen, and spinal canal longitudinal and transverse diameter. In addition, the correlations between PTA and other parameters were calculated using univariate linear regression analysis. The overall mean LMT ranged from 10.7 to 12.6 mm. The smallest mean AP spinal canal-transverse foramen distance was found at C-7 (1.1 mm),whereas the largest mean distance was at C-4 (3.1 mm). The smallest mean mediolateral spinal canal-transverse foramen distance was found at C-4 (1.2 mm), whereas the largest mean distance was at C-7 (4.7 mm). There were significant intergroup differences between male and female patients except for PTA and spinal canal longitudinal diameter. The PTA had a direct linear correlation with AP and mediolateral spinal canal-transverse foramen distances. The largest Pearson coefficient was 0.71 between the PTA and AP spinal canal-transverse foramen distance and the inverse one was -0.73 between the PTA and mediolateral spinal canal-transverse foramen distance. CONCLUSIONS: Analysis of the data obtained in this study suggests that not only pedicle dimensions but also linear and angular parameters of the VB can be useful data when inserting a CPS.

Solitary eosinophilic granuloma of the sternum.

We report a rare case of eosinophilic granuloma of the sternum in a 25-year-old woman, who presented with anterior chest pain and a tender mass over the sternum. Total-body bone scintigraphy and computed tomography scanning of the thorax revealed an isolated lytic lesion of the manubrium. An open biopsy showed the typical histologic appearance of an eosinophilic granuloma. Surgical curettage of the solitary lesion was performed, and the sternal defect was filled with a bone replacement material. At the 2-year follow-up, no local recurrence was found, and the patient was in good health.