Impaired WNT signaling and the spine-Heterozygous WNT1 mutation causes severe age-related spinal pathology

Background: WNT signaling plays a major role in bone and cartilage metabolism. Impaired WNT/beta-catenin signaling leads to early-onset osteoporosis, but specific features in bone and other tissues remain inadequately characterized. We have identified two large Finnish families with early-onset osteoporosis due to a heterozygous WNT1 mutation c.652T>G, p.C218G. This study evaluated the impact of impaired WNT/beta-catenin signaling on spinal structures. Methods: Altogether 18 WNT1 mutation-positive (age range 11-76 years, median 49 years) and 14 mutation negative subjects (10-77 years, median 43 years) underwent magnetic resonance imaging (MRI) of the spine. The images were reviewed for spinal alignment, vertebral compression fractures, intervertebral disc changes and possible endplate deterioration. The findings were correlated with clinical data. Results: Vertebral compression fractures were present in 78% (7/9) of those aged over 50 years but were not seen in younger mutation-positive subjects. All those with fractures had several severely compressed vertebrae. Altogether spinal compression fractures were present in 39% of those with a WNT1 mutation. Only 14% (2/14) mutation -negative subjects had one mild compressed vertebra each. The mutation-positive subjects had a higher mean spinal deformity index (4.0 +/- 7.3 vs 0.0 +/- 0.4) and more often increased thoracic kyphosis (Z-score > + 2.0 in 33% vs 0%). Further, they had more often Schmorl nodes (61% vs 36%), already in adolescence, and their intervertebral discs were enlarged. Conclusion: Compromised WNT signaling introduces severe and progressive changes to the spinal structures. Schmorl nodes are prevalent even at an early age and increased thoracic kyphosis and compression fractures become evident after the age of 50 years. Therapies targeting the WNT pathway may be an effective way to prevent spinal pathology not only in those harboring a mutation but also in the general population with similar pathology. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Association between changes in lumbar Modic changes and low back symptoms over a two-year period

Background: The association of Modic changes (MC) with low back pain (LBP) is unclear. The purpose of our study was to investigate the associations between the extent of Type 1 (M1) and Type 2 (M2) MC and low back symptoms over a two-year period. Methods: The subjects (n = 64, mean age 43.8 y; 55 [86%] women) were consecutive chronic LBP patients who had M1 or mixed M1/M2 on lumbar spine magnetic resonance imaging (MRI). Size and type of MC on sagittal lumbar MRI and clinical data regarding low back symptoms were recorded at baseline and two-year follow-up. The size (%) of each MC in relation to vertebral size was estimated from sagittal slices (midsagittal and left and right quarter), while proportions of M1 and M2 within the MC were evaluated from three separate slices covering the MC. The extent (%) of M1 and M2 was calculated as a product of the size of MC and the proportions of M1 and M2 within the MC, respectively. Changes in the extent of M1 and M2 were analysed for associations with changes in LBP intensity and the Oswestry disability index (ODI), using linear regression analysis. Results: At baseline, the mean LBP intensity was 6.5 and the mean ODI was 33%. During follow-up, LBP intensity increased in 15 patients and decreased in 41, while ODI increased in 19 patients and decreased in 44. In univariate analyses, change in the extent of M1 associated significantly positively with changes in LBP intensity and ODI (beta 0.26, p = 0.036 and beta 0.30, p = 0.017; respectively), whereas the change in the extent of M2 did not associate with changes in LBP intensity and ODI (beta -0.24, p = 0.054 and beta -0.13, p = 0.306; respectively). After adjustment for age, gender, and size of MC at baseline, change in the extent of M1 remained significantly positively associated with change in ODI (beta 0.53, p = 0.003). Conclusion: Change in the extent of M1 associated positively with changes in low back symptoms.Peer reviewe

Association of Abdominal Obesity with Lumbar Disc Degeneration - A Magnetic Resonance Imaging Study

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Association of Abdominal Obesity with Lumbar Disc Degeneration - A Magnetic Resonance Imaging Study

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Body mass index is associated with lumbar disc degeneration in young Finnish males: subsample of Northern Finland birth cohort study 1986

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The death of King Charles XII of Sweden revisited

The death of King Charles XII of Sweden has remained as a mystery for more than three centuries. Was he assassinated by his own men or killed by the enemy fire? Charles was killed by a projectile perforating his skull from left to right. In this study, we utilized a Synbone ballistic skull phantom and modern radiological imaging to clarify the factors behind the observed head injuries. We examined whether a musket ball fired from the enemy lines would be the most potential projectile. Our experiments with a leaden 19.5mm musket ball demonstrated that at velocities of 200 to 250m/s, it could cause similar type of injuries as observed in the remains of Charles. The radiological imaging supported the theory that the projectile was not a leaden but of some harder metal, as we could detect remnants of lead inside the wound channel unlike in Charles' case. In addition, our experiments showed that a 19.5mm musket ball produces max. 17mm hole into a felt material. The main evidence supporting 19.5mm projectile size has been a 19-19.5mm bullet hole in a hat that Charles was wearing during his death. Additional experiments with a 25.4mm steel ball produced approximately 20mm hole in the felt. As our musket ball experiments also resulted in considerably smaller cranial injuries than those in Charles' case, we can conclude that the deadly projectile wasn't leaden and was more than 19.5mm in diameter, potentially an iron cartouche ball that was shot from the enemy lines.Peer reviewe

Modic changes associated with greater pain relief following anesthetization of the adjacent lumbar intervertebral disc:a retrospective study of chronic low back pain patients

Abstract Purpose: To assess the correlation between the degree of pain relief following discoblock and the presence and type of adjacent Modic changes (MC). Method: We retrospectively analyzed chronic low back pain (LBP) patients whose pain was suspected to originate from a specific lumbar intervertebral disc (IVD) based on a spine orthopedist’s clinical evaluation and magnetic resonance imaging (MRI). Thus, patients were selected to undergo discoblock. We calculated the degree of pain relief following discoblock on Numerical Rating Scale (ΔNRS) and analyzed the MRIs on the basis of MC presence and type on the lumbar spinal segment in question. We assessed the differences in ΔNRS between the groups with absent and present MC and the groups of MC subtypes. Results: Forty-five patients were included in the present study, all of whom underwent discoblock at a single level. The total MC prevalence was 77.8 % (35 patients); pure or dominant MC type 1 (MC1 group) 35.6 % (16 patients); and pure or dominant MC type 2 (MC2 group) 42.2 % (19 patients). ΔNRS was significantly greater in the group with MC compared to the group without MC (median ΔNRS −5.0 vs −2.5, respectively, P = 0.043). In pairwise comparisons, a significant difference in ΔNRS was found between the MC1 group and the group without MC (median ΔNRS −5.0 vs −2.5, respectively, P = 0.012). Conclusions: We propose that MC type 1 are associated with lumbar spinal pain, and that the pain arises at least partly from the adjacent IVD or endplate