Headache in a patient with Klinefelter's syndrome and hyperostosis frontalis interna.

Hyperostosis frontalis interna (HFI) has been reported in older women, but reports in men are rare. We present a novel case of migraine headache in a gentleman with Klinefelter's syndrome and HFI, along with a discussion of possible pathophysiologic mechanisms underlying both the headache and the HFI

Earliest Porotic Hyperostosis on a 1.5-Million-year-old Hominin, olduvai gorge, Tanzania.

Meat-eating was an important factor affecting early hominin brain expansion, social organization and geographic movement. Stone tool butchery marks on ungulate fossils in several African archaeological assemblages demonstrate a significant level of carnivory by Pleistocene hominins, but the discovery at Olduvai Gorge of a child's pathological cranial fragments indicates that some hominins probably experienced scarcity of animal foods during various stages of their life histories. The child's parietal fragments, excavated from 1.5-million-year-old sediments, show porotic hyperostosis, a pathology associated with anemia. Nutritional deficiencies, including anemia, are most common at weaning, when children lose passive immunity received through their mothers' milk. Our results suggest, alternatively, that (1) the developmentally disruptive potential of weaning reached far beyond sedentary Holocene food-producing societies and into the early Pleistocene, or that (2) a hominin mother's meat-deficient diet negatively altered the nutritional content of her breast milk to the extent that her nursing child ultimately died from malnourishment. Either way, this discovery highlights that by at least 1.5 million years ago early human physiology was already adapted to a diet that included the regular consumption of meat

The Use of Bone Morphogenetic Protein in the Intervertebral Disk Space in Minimally Invasive Transforaminal Lumbar Interbody Fusion

Study Design: Retrospective Cohort. Objective: The objective of this study was to characterize one surgeon’s experience over a 10-year period using rhBMP-2 in the disk space for minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). Summary of Background Data: MIS TLIF has been utilized as a technique for decreasing patients’ immediate postoperative pain, decreasing blood loss, and shortened hospital stays. Effectiveness and complications of rhBMP-2’s use in the disk space is limited because of its off-label status. Methods: Retrospective analysis of consecutive MIS TLIFs performed by senior author between 2004 and 2014. rhBMP-2 was used in the disk space in all cases. Patients were stratified based on the dose of rhBMP-2 utilized. Patients had 9 to 12 month computerized tomography scan to evaluate for bony fusion and continued follow-up for 18 months. Results: A total of 688 patients underwent a MIS TLIF. A medium kit of rhBMP-2 was utilized in 97 patients, and small kit was used in 591 patients. Fusion rate was 97.9% and this was not different between the 2 groups with 96/97 patients fusing in the medium kit group and 577/591 patients fusing in the small kit group. Five patients taken back to the operating room for symptomatic pseudoarthrosis, 4 reoperated for bony hyperostosis, and 10 radiographic pseudoarthroses that did not require reoperation. A statistically significant difference in the rate of foraminal hyperostosis was found when using a medium sized kit of rhBMP-2 was 4.12% (4/97 patients), compared with a small kit (0/591 patients, P=0.0004). Conclusions: Utilization of rhBMP-2 in an MIS TLIF leads to high fusion rate (97.9%), with an acceptable complication profile. The development of foraminal hyperostosis is a rare complication that only affected 0.6% of patients, and seems to be a dose related complication, as this complication was eliminated when a lower dose of rhBMP-2 was utilized

DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS (DISH) OF THE SHOULDER: A CAUSE OF SHOULDER PAIN?

Shoulder pain is a common complaint and shoulder hyperostosis a frequent radiological condition. However, little is known about the association between the clinical and radiological findings. To evaluate the clinical relevance of shoulder hyperostosis we performed a controlled, blind study of 99 hospitalized probands with and without thoracospinal hyperostosis on lateral chest X-rays. The study included grading of the shoulder hyperostosis on the basis of three bilateral standard radiographs, assessing shoulder pain in a standardized way by an interviewer and recording extraskeletal causes of shoulder pain. The prevalence of shoulder hyperostosis was doubled in probands with thoracospinal hyperostosis compared to controls (X2= 5.90, F>0.025, n = 99). Shoulder hyperostosis, irrespective of thoracospinal hyperostosis, predisposed to shoulder pain (40% versus 18%, x2 = 4.06, F>0.05, n = 74). Shoulder hyperostosis in combination with thoracospinal hyperostosis (shoulder DISH) predisposed to shoulder pain to an even greater extent (46% versus 12%, x2 = 6.64, P>0.01, n = 47). We conclude that shoulder hyperostosis is a radiological finding of potential clinical relevanc

Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23 autoantibodies

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 (FGFR1) were identified. He subsequently developed type 1 diabetes mellitus, which raised the possibility of an autoimmune cause for hyperphosphatemic tumoral calcinosis. Luciferase immunoprecipitation systems revealed markedly elevated FGF23 autoantibodies without detectable FGFR1 or Klotho autoantibodies. Using an in vitro FGF23 functional assay, we found that the FGF23 autoantibodies in the patient's plasma blocked downstream signaling via the MAPK/ERK signaling pathway in a dose-dependent manner. Thus, this report describes the first case, to our knowledge, of autoimmune hyperphosphatemic tumoral calcinosis with pathogenic autoantibodies targeting FGF23. Identification of this pathophysiology extends the etiologic spectrum of hyperphosphatemic tumoral calcinosis and suggests that immunomodulatory therapy may be an effective treatment

Thoracic and lumbar vertebral bone mineral density changes in a natural occuring dog model of diffuse idiopathic skeletal hyperostosis

Ankylosing spinal disorders can be associated with alterations in vertebral bone mineral density (BMD). There is however controversy about vertebral BMD in patients wuse idiopathic skeletal hyperostosis (DISH). DISH in Boxer dogs has been considered a natural occurring disease model for DISH in people. The purpose of this study was to compare vertebral BMD between Boxers with and without DISH. Fifty-nine Boxers with (n=30) or without (n=29) DISH that underwent computed tomography were included. Vertebral BMD was calculated for each thoracic and lumbar vertebra by using an earlier reported and validated protocol. For each vertebral body, a region of interest was drawn on the axial computed tomographic images at three separate locations: immediately inferior to the superior end plate, in the middle of the vertebral body, and superior to the inferior end plate. Values from the three axial slices were averaged to give a mean Hounsfield Unit value for each vertebral body. Univariate statistical analysis was performed to identify factors to be included in a multivariate model. The multivariate model including all dogs demonstrated that vertebral DISH status (Coefficient 24.63; 95% CI 16.07 to 33.19; p < 0.001), lumbar vertebrae (Coefficient -17.25; 95% CI -23.42 to -11.09; p < 0.01), and to a lesser extent higher age (Coefficient -0.56; 95% CI -1.07 to -0.05; p = 0.03) were significant predictors for vertebral BMD. When the multivariate model was repeated using only dogs with DISH, vertebral DISH status (Coefficient 20.67; 95% CI, 10.98 to 30.37; p < 0.001) and lumbar anatomical region (Coefficient -38.24; 95% CI, -47.75 to -28.73; p < 0.001) were again predictors for vertebral BMD but age was not. The results of this study indicate that DISH can be associated with decreased vertebral BMD. Further studies are necessary to evaluate the clinical importance and pathophysiology of this finding

Tomb number 2 of the Church of St. Michael in Mornago (Varese, Italy). Anthropological and archaeological study of medieval funeral remains

The current paper aims to present the archaeological and anthropological results of the investigation conducted on a medieval burial which presents several features that recall the Longobard culture. After the archaeological evaluations on the architectural morphology of the tomb and on the grave goods, we proceeded with the anthropological investigations on human and animal bone remains. These analyses allowed us to formulate a hypothesis related to this particular funeral ritual from ancient Longobard tradition. The tomb number 2 of St. Michael church in Mornago represents a rare evidence of inhumation with bird in Northern Italy

Thoracic and Lumbar Vertebral Bone Mineral Density Changes in a Natural Occurring Dog Model of Diffuse Idiopathic Skeletal Hyperostosis

Ankylosing spinal disorders can be associated with alterations in vertebral bone mineral density (BMD). There is however controversy about vertebral BMD in patients wuse idiopathic skeletal hyperostosis (DISH). DISH in Boxer dogs has been considered a natural occurring disease model for DISH in people. The purpose of this study was to compare vertebral BMD between Boxers with and without DISH. Fifty-nine Boxers with (n=30) or without (n=29) DISH that underwent computed tomography were included. Vertebral BMD was calculated for each thoracic and lumbar vertebra by using an earlier reported and validated protocol. For each vertebral body, a region of interest was drawn on the axial computed tomographic images at three separate locations: immediately inferior to the superior end plate, in the middle of the vertebral body, and superior to the inferior end plate. Values from the three axial slices were averaged to give a mean Hounsfield Unit value for each vertebral body. Univariate statistical analysis was performed to identify factors to be included in a multivariate model. The multivariate model including all dogs demonstrated that vertebral DISH status (Coefficient 24.63; 95% CI 16.07 to 33.19; p <0.001), lumbar vertebrae (Coefficient -17.25; 95% CI -23.42 to -11.09; p < 0.01), and to a lesser extent higher age (Coefficient -0.56; 95% CI -1.07 to -0.05; p = 0.03) were significant predictors for vertebral BMD. When the multivariate model was repeated using only dogs with DISH, vertebral DISH status (Coefficient 20.67; 95% CI, 10.98 to 30.37; p < 0.001) and lumbar anatomical region (Coefficient -38.24; 95% CI, -47.75 to -28.73; p < 0.001) were again predictors for vertebral BMD but age was not. The results of this study indicate that DISH can be associated with decreased vertebral BMD. Further studies are necessary to evaluate the clinical importance and pathophysiology of this finding