Cora Bow

Bone loss during menopausal transition among southern Chinese women

OBJECTIVES Estrogen deficiency during menopausal transition is associated with rapid bone loss. The purpose of this study was to examine the time of onset, the rate, and predictors of menopausal bone loss. STUDY DESIGN Prospective data were analyzed from 160 Chinese women between the ages of 45 to 55 years who participated in the Hong Kong Osteoporotic Study. MAIN OUTCOME MEASURES All participants were studied yearly for 4 years. Demographic information, menstrual status according to the Stages of Reproductive Aging Workshop (STRAW), and lifestyle habits were recorded as well as bone mineral density (BMD) measured every visit. Baseline follicular stimulating hormone, sex hormone binding globulin, parathyroid hormones, C-terminal telopeptides of type 1 collagen, estradiol and testosterone were also measured. RESULTS There was no significant bone loss at the spine, femoral neck and total hip in premenopausal women. Maximal bone loss occurred within the STRAW stage -2 and -1. Age at menopause, baseline age, body weight and FSH were independent predictors of bone loss. Subjects in the lowest quartile of baseline body weight (<50 kg) lost bone 2 times faster at spine compared with those in the highest quartile (>61 kg). Subjects in the highest quartile of baseline FSH (>40 IU/l) lost bone 1.3-2.3 times faster at all 3 sites compared with those in the lowest quartile (<5.8 IU/l). CONCLUSION Strategies to retard bone loss should be stressed to middle aged women, especially those with lean body built or with early menopause, to prevent osteoporosis later on in life.

Reducing radiation exposure in early-onset scoliosis surgery patients: novel use of ultrasonography to measure lengthening in magnetically-controlled growing rods

BACKGROUND CONTEXT Magnetically-controlled growing rod (MCGR) technology has been reported for the treatment of early-onset scoliosis (EOS). Such technology allows for regular and frequent outpatient rod distractions without the need for additional surgery. However, pre- and postdistraction spine radiographs are required to verify the amount of lengthening. This increased exposure to ionizing radiation in developing children significantly increases their risk profile for radiation-induced cancer and noncancerous morbidity. PURPOSE This study addressed the first and novel application and reliability of the use of ultrasonography, that has no ionizing radiation exposure, as an alternative to plain radiographs in the visualizing and confirming of rod distractions. STUDY DESIGN A prospective study. PATIENT SAMPLE Six EOS patients who underwent surgical treatment with MCGRs were prospectively recruited. OUTCOME MEASURES Imaging measurements based on ultrasound and plain radiographs. METHODS All patients were imaged via ultrasound, ease of rod identification was established, and the reliability and reproducibility of optimal reference point selection assessed blindly by three individuals. The clinical algorithm, using ultrasound, was subsequently implemented. Plain radiographs served as controls. RESULTS Assessment of the rods neck distance on ultrasound demonstrated a high degree of interrater reliability (a=0.99; p<.001). Intrarater reliability remained high on repeat measurements at different time intervals (a=1.00; p<.001). Satisfactory interrater reliability was noted when measuring the rods neck (a=0.73; p=.010) and high reliability was noted in assessing the housing of the rod (a=0.85; p=.01) on plain radiographs. Under blinded conditions, 2 mm rod distraction measured on radiographs corresponded to 1.7 mm distraction on the ultrasound (standard deviation: 0.24 mm; p<.001). Subsequently, the clinical algorithm using ultrasound, instead of radiographs, has been successfully implemented. CONCLUSIONS This is the first study to report the use of a novel technique using noninvasive, nonionizing ultrasound to reliably document rod distractions in EOS patients. A high level of inter- and intrarater reliabilities were noted. More importantly, the use of ultrasonography may result in fewer whole spine radiographs from being taken in patients who have had MCGRs implanted for EOS; thereby decreasing their exposure to ionizing radiation and the potential risk of future radiation-induced diseases.

Clinical risk factor assessment had better discriminative ability than bone mineral density in identifying subjects with vertebral fracture

SummaryThis study evaluated the characteristics of patients with vertebral fractures and examined the discriminative ability of clinical risk factors. The findings provide further insights into possible development of a simple, cost-effective scheme for fracture risk assessment using clinical risk factors to identify high-risk patients for further evaluation.IntroductionVertebral fractures are the most common complication of osteoporosis. The aim of this study was to evaluate the characteristics of patients with vertebral fractures and to determine the discriminative ability of bone mineral density (BMD) and other clinical risk factors.MethodsPostmenopausal Southern Chinese women (2,178) enrolled in the Hong Kong Osteoporosis Study since 1995 were prospectively followed up for fracture outcome. Subjects (1,372) with lateral spine radiographs were included in this study. Baseline demographic, BMD, and clinical risk factor information were obtained from a structured questionnaire.ResultsSubjects (299; 22%) had prevalent vertebral fractures. The prevalence of vertebral fractures increased with increasing age, number of clinical risk factors, and decreasing BMD. The odds of having a prevalent vertebral fracture per SD reduction in BMD after adjustment for age in Hong Kong Southern Chinese postmenopausal women was 1.5 for the lumbar spine and femoral neck. Analysis of the receiver operating characteristic curve revealed that bone mineral apparent density did not enhance fracture risk prediction. Subjects with ≥4 clinical risk factors had 2.3-fold higher odds of having a prevalent vertebral fracture while subjects with ≥4 clinical risk factors plus a low BMD (i.e., femoral neck T-score <−2.5) had 2.6-fold. Addition of BMD to clinical risk factors did not enhance the discriminative ability to identify subjects with vertebral fracture.ConclusionsBased on these findings, we recommend that screening efforts should focus on older postmenopausal women with multiple risk factors to identify women who are likely to have a prevalent vertebral fracture.

Novel diagnostic and prognostic methods for disc degeneration and low back pain

Low back pain (LBP) is the world’s leading debilitating condition [1]. It is estimated that 80% of the general population in the United States will develop LBP at one point in time [2,3]. Such pain can lead to diminished daily function and quality of life and work disability [4,5]. Not surprisingly, spine surgery to address LBP is one of the top five surgeries performed in the United States [6] where approximately 90-billion US dollars in health-care expenses are used annually to treat LBP [7]. As data indicate, LBP is clearly related with detrimental socioeconomic and health-care consequences that motivate efforts to identify LPB risk factors to develop improved prevention and treatment strategies. Although the etiology of LBP is multifaceted, disc degeneration (DD) has been suggested to be one of the most prominent risk factors [8–11]. However, whether DD is synonymous with LBP continues to be a topic of immense controversy. In this article, we review the current data regarding pain generating pathways and epidemiological evidence associating DD with LBP. In further support of this association, we review novel disc imaging techniques that may increase LBP diagnostic sensitivity and specificity. Finally, we discuss relevant aspects of the field of pain genes that may shed further light as to the links between DD and pain.

Refined Phenotyping of Modic Changes: Imaging Biomarkers of Prolonged Severe Low Back Pain and Disability

AbstractLow back pain (LBP) is the worlds most disabling condition. Modic changes (MC) are vertebral bone marrow changes adjacent to the endplates as noted on magnetic resonance imaging. The associations of specific MC types and patterns with prolonged, severe LBP and disability remain speculative. This study assessed the relationship of prolonged, severe LBP and back-related disability, with the presence and morphology of lumbar MC in a large cross-sectional population-based study of Southern Chinese.We addressed the topographical and morphological dimensions of MC along with other magnetic resonance imaging phenotypes (eg, disc degeneration and displacement) on the basis of axial T1 and sagittal T2-weighted imaging of L1-S1. Prolonged severe LBP was defined as LBP lasting ≥30 days during the past year, and a visual analog scale severest pain intensity of at least 6/10. An Oswestry Disability Index score of 15% was regarded as significant disability. We also assessed subject demographics, occupation, and lifestyle factors.In total, 1142 subjects (63% females, mean age 53 years) were assessed. Of these, 282 (24.7%) had MC (7.1% type I, 17.6% type II). MC subjects were older (P = 0.003), had more frequent disc displacements (P < 0.001) and greater degree of disc degeneration (P < 0.001) than non-MC subjects. In adjusted models, any MC (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.01–2.18), MC affecting whole anterior-posterior length (OR 1.62, 95% CI 1.04–2.51), and MC affecting 2/3 posterior length (OR 2.79, 95% CI 1.17–6.65) were associated with prolonged severe LBP. Type I MC tended to associate with pain more strongly than type II MC (OR 1.80, 95% CI 0.94–3.44 vs OR 1.36, 95% CI 0.88–2.09, respectively). Any MC (OR 1.47, 95% CI 1.04–2.10), type II MC (OR 1.56, 95% CI 1.06–2.31), MC affecting 2/3 posterior length (OR 2.96, 95% CI 1.27–6.89), and extensive MC (OR 1.95, 95% CI 1.21–3.15) were associated with disability. The strength of the associations increased with the number of MC.This large-scale study is the first to definitively note MC types and specific morphologies to be independently associated with prolonged severe LBP and back-related disability. This proposed refined MC phenotype may have direct implications in clinical decision-making as to the development and management of LBP. Understanding of these imaging biomarkers can lead to new preventative and personalized therapeutics related to LBP.

Clinical utility of ultrasound to prospectively monitor distraction of magnetically controlled growing rods.

BACKGROUND CONTEXT Growing rods are commonly used for surgical treatment of skeletally immature patients with scoliosis, but require repeated surgeries for distractions and are fraught with complications. As an alternative, the use of magnetically controlled growing rods (MCGR) allows for more frequent non-invasive distractions to mimic normal growth. However, more plain radiographs are needed to monitor increased distraction frequency, thereby increasing ionizing radiation exposure to the developing child. The use of ultrasound, which emits no radiation, has been found in a cross-sectional study to be reliable in measuring MCGR distractions. PURPOSE The study aims to address the prospective clinical utility of ultrasound compared with plain radiographs for assessing MCGR distractions. STUDY DESIGN This is a prospective study. PATIENT SAMPLE The study includes patients with early-onset scoliosis undergoing distractions after MCGR implant. OUTCOME MEASURES The distraction length on plain radiographs and ultrasound was measured. METHODS This is a prospective study of patients treated with MCGR. Patients with both single- and dual-rod systems were included. Outpatient distractions were performed at monthly intervals, targeting 2 mm of distraction on each occasion. Assessment of distraction length was monitored by ultrasound at each visit; plain radiographs were taken every 6 months and were compared with ultrasound measurements. RESULTS Nine patients (5 female, 4 male), with a mean of 29 distractions (standard deviation [SD] ±14.3), were recruited. The mean distracted length per 6 months was 5.7 mm (SD ±3.6 mm) on plain radiographs and 5.2 mm (SD ±3.9 mm) on ultrasound for the concave rod, and 6.1 mm (SD ±3.6 mm) on plain radiographs and 5.9 mm (SD ±3.8 mm) on ultrasound for the convex rod. Excellent inter- and intra-rater reliabilities were observed for radiographic and ultrasound measurements. An excellent correlation was noted between the two imaging modalities (r=0.93; p<.0001). CONCLUSIONS This is the first prospective study to validate that ultrasound assessment of MCGR distraction lengths was highly comparable with that of plain radiographs. The present study has verified that ultrasound can be used to document length changes by distraction over time and that it had high clinical utility. Ultrasound can be a reliable alternative to plain radiographs, thereby avoiding radiation exposure and its potential detrimental sequelae in the developing child.

Frequent small distractions with a magnetically controlled growing rod for early-onset scoliosis and avoidance of the law of diminishing returns

Purpose To assess the effect of frequent small distractions with a magnetically controlled growing rod (MCGR) on spinal length gain and achieved distraction length in children with early-onset scoliosis (EOS), and to determine whether the law of diminishing returns applies to this group of patients with MCGR. Methods A consecutive series of 3 males and 4 females with EOS who underwent MCGR implantation at a mean age of 10.2 years and were followed up for a mean of 3.8 years were reviewed. Distraction was aimed at 2 mm monthly. The coronal Cobb angle, T1-S1 length gain, and achieved distraction length were measured at 6-monthly intervals. Results The mean total number of distractions was 31. Four of the patients had problems that may have affected distractions. The mean coronal Cobb angle improved post-operatively and was maintained throughout the follow-up period. The mean T1-S1 length gain and achieved distraction length varied over the follow-up period and did not diminish with repeated lengthening. Conclusions Frequent small distractions with the MCGR for EOS enable T1-S1 and achieved distraction length gain without significant reduction in gain after repeated lengthening.

Learning Curve in Monitoring Magnetically Controlled Growing Rod Distractions With Ultrasound

Study Design. Prospective study. Objective. To determine whether a learning curve exists for ultrasound measurement of magnetically controlled growing rod (MCGR) distractions. Summary of Background Data. For patients managed by MCGRs, close monitoring of interval distraction length gains is important to determine whether the distractions are translating into actual spine growth. Radiographs are the criterion standard for measuring length gains, but ultrasound has been shown to be effective in monitoring distraction lengths without radiation exposure. It is, however, an operator-dependent tool and thus the accuracy of ultrasound measurement of distracted length may improve with experience. Methods. This is a prospective correlation analysis of patients who underwent MCGR treatment for scoliosis. The study period was inclusive of 19th February 2013 to 31st March 2015. All subjects were consecutively recruited in a prospective manner. Data regarding date of the distraction visit, and the interval radiograph and ultrasound measurements of the distracted lengths were collected. Only those episodes with both radiograph and ultrasound performed were used for analysis. The mean differences in change of radiograph and ultrasound measurements were plotted to determine correlation differences and to observe for a learning curve. Results. A total of 379 distraction episodes were analyzed. The mean differences between ultrasound and radiograph measurements per distraction episode were −0.3 mm for the right rod and −0.1 mm for the left rod. For learning curve analysis, there were three distinct timepoints in which the difference of correlation became significantly better and were described as clusters. The correlation in the first cluster (19th February 2013 to 15th October 2013) was 0.612 (right rod) and 0.795 (left rod), the second cluster (16th October 2013 to 20th May 2014) was 0.879 (right rod) and 0.918 (left rod), and the third cluster (21st May 2014 to 31st March 2015) was 0.956 (right rod) and 0.932 (left rod). Thus, a plateau was observed at the second cluster, which translated to 97 to 146 rod measurements. Conclusion. Correlation between radiograph and ultrasound measurements is reasonable to begin with but improves with time. During initial use, successful distractions should correlate between the clinical feel and ultrasound confirmation. Although the absolute value may not be accurate and may require radiographs to confirm, with time and experience, ultrasound measurements can then be more reliable. Level of Evidence: 3

Heritability of Serum Osteoprotegerin

Serum osteoprotegerin (OPG) level is a key biomarker for numerous traits of clinical importance like diabetes, coronary artery disease, blood pressure, lipid profile, and cancers, but its genetic basis remains poorly understood. We estimated the heritability (h2) of serum OPG level in 1442 southern Chinese subjects from 306 families. The h2 for unadjusted OPG was 0.62 for females and 0.17 for males; and for age‐adjusted OPG, 0.75 for females and 0.37 for males. Adjustment for lifestyle factors including calcium and phytoestrogen intake, exercise, smoking, and alcohol consumption exerted only a modest effect on the h2. In conclusion, we confirmed that circulating OPG is a heritable trait and there is a significant difference in heritability between sexes.

The Ute Disc Sign on Mri: a novel imaging biomarker associated with degenerative spine changes, low back pain and disability

Study Design. Cross-sectional. Objective. To assess the distribution of the ultra-short time-to-echo (UTE) disc sign (UDS) and its association with disc degeneration, other magnetic resonance imaging (MRI) phenotypes, pain, and disability profiles. Summary of Background Data. Disc degeneration has been conventionally assessed by T2-weighted (T2W) signal intensity on MRI; however, its clinical utility has been questionable. UTE MRI assesses short T2 components. The authors have identified a new imaging biomarker on UTE—the UDS. Methods. One hundred eight subjects were recruited. T2W MRI assessed disc degeneration and other phenotypes, and T1-rho MRI values represented quantitative proteoglycan disc profiles of L1-S1. UDS was detected on UTE (i.e., hyper-/hypointense disc band). A UDS score (cumulative number of UDS levels) and T2W summated lumbar degenerated scores (cumulative disc degeneration score) were assessed. Subject demographics, chronic low back pain (LBP), and disability profiles (Oswestry Disability Index: ODI) were obtained. Results. UDS was noted in 39.8% subjects, 61.4% occurred at the lower lumbar spine and 39.5% had multilevel UDS. UDS subjects had significantly greater severity and extent of disc degeneration, and Modic changes (P < 0.05). By disc levels, a higher prevalence of disc degeneration/displacement, Modic changes, and spondylolisthesis were noted in UDS discs than non-UDS discs (P < 0.05). T1-rho values were also lower in UDS discs (P = 0.022). The majority of UDS could not be detected on T2W. The UDS score significantly correlated with worse ODI scores (r = 0.311; P = 0.001), whereas T2W cumulative disc degeneration score did not (r = 0.13; P = 0.19). LBP subjects exhibited more multilevel UDS (P < 0.015) but not on T2W MRI (P = 0.53). The UDS score was significantly related to LBP (P = 0.009), whereas T2W cumulative disc degeneration score was not (P = 0.127). Conclusion. This is the first study to report “UDS” in humans. UDS is a novel imaging biomarker that is highly associated with degenerative spine changes, chronic LBP, and disability than conventional T2W MRI. Level of Evidence: 2