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�������\\������������8��$�Q.�H����� �|i@�-�-�-�-�-�-�-$o0�!3��-�,$��,$,$�-�����.�&�&�&,$^�����(��&,$�-�&�&�&�������ca������$j�&�(!.0Q.�&�3�$��3�&�3��&���7�&S �7!�����-�-�&(���Q.,$,$,$,$���������������������������������������������������������������������3���������\ |:	Submission to: Journal of Spine & Neurosurgery
June 4, 2013

Symptomatic Ossified Ligamentum Flavum Secondary to Hyperparathyroidism
David Dornbos III1,2, Mark Hornyak, MD2

1. Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
2. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA

Corresponding Author:
David Dornbos III, MD
410 W 10th Ave, N1014 Doan Hall
Columbus, OH 43210, USA
Email:  HYPERLINK "mailto:david.dornbos@osumc.edu" david.dornbos@osumc.edu
Phone: 616-915-8560
Fax: 614-293-4281

Key words: ossified ligamentum flavum; hyperparathyroidism; osteoblasts; chronic renal failure




SUMMARY
	Ossification of the ligamentum flavum (OLF) is a relatively rare disease process. It is typically idiopathic, most commonly occurring in the Japanese population.  It has never before been reported as a consequence of hyperparathyroidism.  We report a case of OLF in an African American patient with underlying renal disease and secondary hyperparathyroidism. While a relationship between these two pathologies has not been previously studied, we outline a mechanism by which chronic renal failure and secondary hyperparathyroidism may lead to abnormal bone growth and neurological deficit.   Parathyroid hormone (PTH) has been shown to increase the expression and activity of bone morphogenetic protein (BMP)-2. Osteoblast-like cells at the ossification front of OLF have been previously observed and described as BMP-2 protein positive, supporting a pathologic mechanism in which elevated parathyroid hormone contributes to the development of symptomatic OLF.  Thus, it is important for clinicians to maintain an elevated index of suspicion for OLF in the setting of chronic renal failure and hyperparathyroidism, in an effort to prevent neurological injury. 









INTRODUCTION
	Secondary hyperparathyroidism is a disorder seen within the context of renal failure. Patients exhibit elevated parathyroid hormone (PTH), low calcium, and high phosphorus levels  ADDIN EN.CITE <EndNote><Cite ExcludeYear="1"><Author>Slatopolsky</Author><RecNum>1</RecNum><DisplayText>[1]</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app="EN" db-id="zdedttxdxzadxnevt2h5xe2rfe2rrx0xw90s">1</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Slatopolsky, E.</author><author>Brown, A.</author><author>Dusso, A.</author></authors></contributors><auth-address>Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA.</auth-address><titles><title>Pathogenesis of secondary hyperparathyroidism</title><secondary-title>Kidney Int Suppl</secondary-title><alt-title>Kidney international. Supplement</alt-title></titles><pages>S14-9</pages><volume>73</volume><edition>2000/01/14</edition><keywords><keyword>Animals</keyword><keyword>Calcium/physiology</keyword><keyword>Humans</keyword><keyword>Hyperparathyroidism, Secondary/*etiology</keyword><keyword>Parathyroid Hormone/genetics/secretion</keyword><keyword>Phosphorus/pharmacology</keyword><keyword>Receptors, Calcitriol/analysis</keyword><keyword>Renal Insufficiency/metabolism</keyword><keyword>Vitamin D/metabolism</keyword></keywords><dates><year>1999</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0098-6577 (Print)&#xD;0098-6577 (Linking)</isbn><accession-num>10633458</accession-num><work-type>Research Support, U.S. Gov&apos;t, P.H.S.&#xD;Review</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10633458</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK \l "_ENREF_1" \o "Slatopolsky, 1999 #1" 1]. This disorder commonly results in bone resorption, osteitis fibrosa cystica and calciphylaxis; however, recent studies have also indicated that elevated PTH levels induce bone growth and formation  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_2" \o "Ishida, 1993 #2" 2,  HYPERLINK \l "_ENREF_3" \o "Isogai, 1996 #3" 3]. Most commonly seen in Asian populations, ossification of the ligamentum flavum (OLF) has been reported in other groups as well, including Caucasian, Middle Eastern, and African American. We report a case of symptomatic OLF occurring in a young African American man with secondary hyperparathyroidism, a condition which increases osteoblast activity.  Previous studies have shown increased osteoblast activity at the calcification front of OLF, suggesting a possible relationship between elevated PTH levels and ossification of the ligamentum flavum  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_4" \o "Nakao, 2009 #4" 4-6].  This link should be recognized so further screening and preventative measures may be initiated in patients with known hyperparathyroidism in an effort to reduce the risk of subsequent neurologic sequelae.

CASE REPORT
	History: This 37-year old African American man presented with a two week history of progressive bilateral leg weakness.  The weakness was more pronounced in the right lower extremity and associated with gait disturbance and imbalance.  The patient reported he was able to ambulate but required a walker for assistance. His past medical history was significant for hypertension, although he had no established diagnosis of renal disease or hyperparathyroidism on presentation.  He reported no other neurological or musculoskeletal deficits and denied bowel or bladder symptoms.
	Examination: Upon presentation, the patient exhibited no cervical, thoracic, or lumbar spine tenderness or deformity.  Neurological examination showed normal strength, sensation, and reflexes in bilateral upper extremities. However, examination of the lower extremities revealed weakness of the legs (4/5) with increased tone and hyperactive reflexes throughout. Sensation was diminished to light touch, pin-prick below the nipples, and proprioception was diminished in the toes.  Gait was spastic and grossly ataxic.  He was also found to have urinary retention.
	Imaging: CT scan of the thoracic spine revealed extensive hypertrophy and hyperdensity of the ligamentum flavum extending from T2 to T8, resulting in significant central spinal canal stenosis (Figure 1A).  The maximum stenosis was found at T2-T3, with an AP diameter of 8 mm. An MRI scan of the thoracic spine revealed hypertrophic ligamentum flavum with maximum spinal cord compression at T2-T3 (Figure 1B).  
	Laboratory Investigations:  During his hospitalization, he was found to have renal insufficiency with a creatinine of 1.9 mg/dL. Further evaluation revealed secondary hyperparathyroidism with a PTH level of 318 pg/mL (normal 11 � 67), low total and ionized calcium, high phosphorus, and low calcitriol.
	Treatment: Due to the patient�s clinical condition and imaging findings, surgical decompression was performed. A routine laminectomy was performed via midline approach from T1 to T4.  During laminectomy at the T4 level, normal anatomy and normal epidural tissues were encountered.  When the T2 and T3 laminae were removed, several large pieces of ossified epidural tissue with the consistency of bone were encountered, slightly thicker on the left.  The ossified tissue was not directly attached to the normal bone of the spine, but rather to remnants of normal ligamentum flavum; there was no adhesion to the dura.  Following removal of the ossified tissue, the spinal canal was well decompressed. Per pathology, the ossified remnants were reported to be portions of ligament showing extensive osseous and cartilaginous metaplasia.
	Postoperative Course: The patient remained neurologically unchanged in the early postoperative period, and there were no complications.  He was treated medically with calcium and vitamin D supplementation. His urinary retention resolved within 3 weeks.  His leg strength improved. Two years after surgery, he remains stable, although he continues to have mild spasticity.

DISCUSSION
Hyperparathyroidism
	Secondary hyperparathyroidism is classically seen in the context of chronic renal failure.    Altered vitamin D metabolism and hyperphosphatemia lead to hypocalcemia.  These abnormalities result in hyperplasia of the parathyroid glands and excessive secretion of PTH  ADDIN EN.CITE <EndNote><Cite ExcludeYear="1"><Author>Slatopolsky</Author><Year>1999</Year><RecNum>64</RecNum><DisplayText>[1]</DisplayText><record><rec-number>64</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">64</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Slatopolsky, E.</author><author>Brown, A.</author><author>Dusso, A.</author></authors></contributors><auth-address>Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA.</auth-address><titles><title>Pathogenesis of secondary hyperparathyroidism</title><secondary-title>Kidney Int Suppl</secondary-title><alt-title>Kidney international. Supplement</alt-title></titles><periodical><full-title>Kidney Int Suppl</full-title><abbr-1>Kidney international. Supplement</abbr-1></periodical><alt-periodical><full-title>Kidney Int Suppl</full-title><abbr-1>Kidney international. Supplement</abbr-1></alt-periodical><pages>S14-9</pages><volume>73</volume><edition>2000/01/14</edition><keywords><keyword>Animals</keyword><keyword>Calcium/physiology</keyword><keyword>Humans</keyword><keyword>Hyperparathyroidism, Secondary/*etiology</keyword><keyword>Parathyroid Hormone/genetics/secretion</keyword><keyword>Phosphorus/pharmacology</keyword><keyword>Receptors, Calcitriol/analysis</keyword><keyword>Renal Insufficiency/metabolism</keyword><keyword>Vitamin D/metabolism</keyword></keywords><dates><year>1999</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0098-6577 (Print)&#xD;0098-6577 (Linking)</isbn><accession-num>10633458</accession-num><work-type>Research Support, U.S. Gov&apos;t, P.H.S.&#xD;Review</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10633458</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK \l "_ENREF_1" \o "Slatopolsky, 1999 #1" 1].  Transient PTH elevations are well known to stimulate bone resorption through osteoclast activation, often leading to disorders such as osteitis fibrosa cystica; however, chronic PTH elevations observed in hyperparathyroidism have been shown to stimulate osteoblast-like cells to differentiate into mature osteoblasts, promoting bone formation  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_2" \o "Ishida, 1993 #2" 2,  HYPERLINK \l "_ENREF_3" \o "Isogai, 1996 #3" 3]. This anabolic effect of hyperparathyroidism occurs when PTH triggers an increase in intracellular cyclic-adenosine monophosphate (cAMP) in osteoblasts and chondrocytes.  Following increased production of cAMP, this protein binds the cAMP response element (CRE), which promotes gene transcription of bone morphogenetic protein (BMP)-2  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_4" \o "Nakao, 2009 #4" 4-6]. Via immunohistochemical staining, elevated levels of BMP-2 have been shown to promote differentiation of osteoblasts and chondrocytes, resulting in elevated alkaline phosphatase activity and new bone formation  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_6" \o "Yayama, 2007 #6" 6] (Figure 2).   

Ossified Ligamentum Flavum
	Under normal conditions, the ligamentum flavum is a yellow elastic ligament connecting the spinal laminae from C2 to S1.  It is composed of longitudinally arranged elastic connective tissue fibers. For unknown reasons in ossification of the ligamentum flavum (OLF), the normal architecture is replaced by mature lamellar bone  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_6" \o "Yayama, 2007 #6" 6], representing a form of metaplasia. Idiopathic  OLF is predominantly seen in the Asian population (88.8%)  ADDIN EN.CITE <EndNote><Cite ExcludeYear="1"><Author>Pascal-Moussellard</Author><Year>2005</Year><RecNum>62</RecNum><DisplayText>[7]</DisplayText><record><rec-number>62</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">62</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pascal-Moussellard, H.</author><author>Cabre, P.</author><author>Smadja, D.</author><author>Catonne, Y.</author></authors></contributors><auth-address>Service d&apos;orthopedie Pr. Saillant, CHU Pitie-Salpetriere, Paris, France. hpmous@sasi.fr</auth-address><titles><title>Symptomatic ossification of the ligamentum flavum: a clinical series from the French Antilles</title><secondary-title>Spine (Phila Pa 1976)</secondary-title><alt-title>Spine</alt-title></titles><periodical><full-title>Spine (Phila Pa 1976)</full-title><abbr-1>Spine</abbr-1></periodical><alt-periodical><full-title>Spine (Phila Pa 1976)</full-title><abbr-1>Spine</abbr-1></alt-periodical><pages>E400-5</pages><volume>30</volume><number>14</number><edition>2005/07/19</edition><keywords><keyword>Adult</keyword><keyword>Africa/ethnology</keyword><keyword>Aged</keyword><keyword>Decompression, Surgical</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Ligamentum Flavum/pathology/*radiography/*surgery</keyword><keyword>Magnetic Resonance Imaging</keyword><keyword>Male</keyword><keyword>Martinique/epidemiology</keyword><keyword>Middle Aged</keyword><keyword>*Ossification, Heterotopic/epidemiology/radiography/surgery</keyword><keyword>Paraparesis, Spastic/epidemiology/radiography/surgery</keyword><keyword>Retrospective Studies</keyword><keyword>Tomography, X-Ray Computed</keyword></keywords><dates><year>2005</year><pub-dates><date>Jul 15</date></pub-dates></dates><isbn>1528-1159 (Electronic)&#xD;0362-2436 (Linking)</isbn><accession-num>16025016</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16025016</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK \l "_ENREF_7" \o "Pascal-Moussellard, 2005 #62" 7], primarily Japanese, but has also been seen in Caucasians (8.2%) ADDIN EN.CITE <EndNote><Cite><Author>Xu</Author><Year>2008</Year><RecNum>82</RecNum><DisplayText>[8]</DisplayText><record><rec-number>82</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">82</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Xu, R.</author><author>Sciubba, D. M.</author><author>Gokaslan, Z. L.</author><author>Bydon, A.</author></authors></contributors><auth-address>Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, USA.</auth-address><titles><title>Ossification of the ligamentum flavum in a Caucasian man</title><secondary-title>J Neurosurg Spine</secondary-title><alt-title>Journal of neurosurgery. Spine</alt-title></titles><periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></periodical><alt-periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></alt-periodical><pages>427-37</pages><volume>9</volume><number>5</number><edition>2008/11/04</edition><keywords><keyword>Adult</keyword><keyword>*European Continental Ancestry Group</keyword><keyword>Humans</keyword><keyword>*Ligamentum Flavum</keyword><keyword>Male</keyword><keyword>Ossification of Posterior Longitudinal</keyword><keyword>Ligament/*diagnosis/*ethnology/surgery</keyword><keyword>*Thoracic Vertebrae</keyword></keywords><dates><year>2008</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1547-5654 (Print)&#xD;1547-5646 (Linking)</isbn><accession-num>18976173</accession-num><work-type>Case Reports</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18976173</url></related-urls></urls><electronic-resource-num>10.3171/SPI.2008.9.11.427</electronic-resource-num><language>eng</language></record></Cite></EndNote>[ HYPERLINK \l "_ENREF_8" \o "Xu, 2008 #82" 8], native Africans  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_9" \o "Cabre, 2001 #3" 9], and Middle Eastern populations  ADDIN EN.CITE <EndNote><Cite ExcludeYear="1"><Author>al-Orainy</Author><Year>1998</Year><RecNum>84</RecNum><DisplayText>[10]</DisplayText><record><rec-number>84</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">84</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>al-Orainy, I. A.</author><author>Kolawole, T.</author></authors></contributors><auth-address>Radiology Department # 40, King Khalid University Hospital, Saudi Arabia.</auth-address><titles><title>Ossification of the ligament flavum</title><secondary-title>Eur J Radiol</secondary-title><alt-title>European journal of radiology</alt-title></titles><periodical><full-title>Eur J Radiol</full-title><abbr-1>European journal of radiology</abbr-1></periodical><alt-periodical><full-title>Eur J Radiol</full-title><abbr-1>European journal of radiology</abbr-1></alt-periodical><pages>76-82</pages><volume>29</volume><number>1</number><edition>1999/02/06</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Age Factors</keyword><keyword>Aged</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Infant</keyword><keyword>Ligamentum Flavum/radiography</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Ossification of Posterior Longitudinal</keyword><keyword>Ligament/classification/*epidemiology/radiography</keyword><keyword>Saudi Arabia/epidemiology</keyword><keyword>Sex Factors</keyword><keyword>Spinal Diseases/epidemiology</keyword><keyword>Tomography, X-Ray Computed</keyword></keywords><dates><year>1998</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0720-048X (Print)&#xD;0720-048X (Linking)</isbn><accession-num>9934562</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9934562</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK \l "_ENREF_10" \o "al-Orainy, 1998 #84" 10]. Much less commonly, as seen in this case, it has been described in African Americans  ADDIN EN.CITE <EndNote><Cite ExcludeYear="1"><Author>wiseman</Author><RecNum>12</RecNum><DisplayText>[11]</DisplayText><record><rec-number>12</rec-number><foreign-keys><key app="EN" db-id="pvetx0v9ief0vjede275vta95rz92tdztfae">12</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wiseman, D. B.</author><author>Stokes, J. K.</author><author>Toselli, R. M.</author></authors></contributors><auth-address>Division of Neurosurgery, University of North Carolina, Chapel Hill, 27599, USA.</auth-address><titles><title>Paraparesis in a black man brought on by ossification of the ligamentum flavum: case report and review of the literature</title><secondary-title>J Spinal Disord Tech</secondary-title><alt-title>Journal of spinal disorders &amp; techniques</alt-title></titles><pages>542-5</pages><volume>15</volume><number>6</number><edition>2002/12/07</edition><keywords><keyword>Adult</keyword><keyword>*African Continental Ancestry Group</keyword><keyword>Humans</keyword><keyword>Laminectomy</keyword><keyword>Male</keyword><keyword>Myelography</keyword><keyword>Ossification of Posterior Longitudinal</keyword><keyword>Ligament/*complications/*ethnology/radiography/surgery</keyword><keyword>Paraparesis/*etiology</keyword><keyword>Tomography, X-Ray Computed</keyword></keywords><dates><year>2002</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1536-0652 (Print)&#xD;1536-0652 (Linking)</isbn><accession-num>12468987</accession-num><work-type>Case Reports&#xD;Review</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12468987</url></related-urls></urls><language>eng</language></record></Cite></EndNote>[ HYPERLINK \l "_ENREF_11" \o "Wiseman, 2002 #12" 11]. Additionally, idiopathic OLF tends occur in an older population, typically over 60  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_6" \o "Yayama, 2007 #6" 6].  OLF has previously been described as causing compressive myelopathy, and it typically presents with ataxia, sensory disturbance, or urinary complaints.  This pathology is most commonly seen in the thoracic spine in which the highest degree of stenosis has been observed between T9 and T12  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_6" \o "Yayama, 2007 #6" 6].  Symptoms can present either following long-term chronic cord compression or following a minor acute trauma.
	While the etiology of OLF has yet to be completely elucidated, multiple theories have attempted to explain the underlying pathogenesis. Likely multifactorial in nature, OLF has been shown to be driven by genetic, mechanical, metabolic, inflammatory, and dietary factors. Longitudinal mechanical stress on the ligamentum flavum, especially along the thoracic region, is believed to promote bone formation in an attempt to provide greater longitudinal strength  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_6" \o "Yayama, 2007 #6" 6]. Due to the elevated prevalence in the Japanese population, genetic studies have revealed a common susceptibility gene, COL6A1  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_12" \o "Kong, 2007 #14" 12]. Further studies have shown Japanese diet and lifestyle, obesity, diabetes mellitus, and other abnormalities in glucose metabolism to be positively correlated with increased risk of OLF  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_13" \o "Mobbs, 2007 #59" 13]. While associations have been seen between hypoparathyroidism and OLF  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_11" \o "Wiseman, 2002 #12" 11,  HYPERLINK \l "_ENREF_14" \o "Li, 2007 #58" 14], no underlying pathologic mechanism has been identified. As previously discussed, an elevated PTH level also has the ability to increase osteoblast differentiation and stimulate BMP-2 transcription, inducing bone formation. Previous studies have identified a significant accumulation of BMP-2 positive cells at the ossification front of OLF  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_6" \o "Yayama, 2007 #6" 6,  HYPERLINK \l "_ENREF_14" \o "Li, 2007 #58" 14], suggesting that these cells are actively forming bone after parathyroid hormone activation. In addition to fibroblasts and chondrocytes at the ossification front, metaplastic mesenchymal cells with osteoblast-like properties have also been observed, suggesting that they also serve a role in bone formation within the ligamentum flavum.  OLF cells contain phenotypic characterizations of both osteoblasts and chondrocytes  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_15" \o "Zhong, 2009 #83" 15].  Further studies have described these cells as hypertrophic chondrocytes with osteoblast-like activity, producing collagen, fibronectin, and osteocalcin with elevated alkaline phosphatase activity  ADDIN EN.CITE  ADDIN EN.CITE.DATA [ HYPERLINK \l "_ENREF_5" \o "Specchia, 2001 #5" 5].  When these OLF cells are stimulated by direct administration of parathyroid hormone, they exhibit increased cAMP and BMP-2 levels, demonstrating characteristic osteoblast-like activity.
	
The elevated PTH levels in hyperparathyroidism may increase the predisposition to development of OLF. Parathyroid hormone has been shown to increase osteoblast differentiation.  It also targets osteoblasts leading to BMP-2 activation.  BMP-2 activation stimulates osteoblasts and chondrocytes to induce bone formation. In a patient with renal failure and subsequent secondary hyperparathyroidism, these elevated hormone levels would be expected to trigger the previously described pathway. With receptive osteoblast-like cells already present at the ligamentum flavum, hyperparathyroidism may promote differentiation and hyperplasia of these cells, leading to new bone formation and ossification of the ligamentum flavum, which may in turn lead to neurologic injury.

CONCLUSION
	While the patient in this case study reveals an association between secondary hyperparathyroidism and ossification of the ligamentum flavum, the question still remains as to whether preventative measures or increased screening would be of benefit for this particular disease process.  In patients with secondary hyperparathyroidism, prevention of OLF could be simply addressed by taking steps to normalize serum PTH levels.  Studies have shown that controlling levels of calcium, phosphorus, and calcitriol decreases the stimulus to the parathyroid gland, subsequently reducing hyperplasia and excessive PTH production. Further prevention of OLF in the setting of hyperparathyroidism could be initiated by decreasing modifiable risk factors, such as obesity, diabetes mellitus, and other glucose metabolism abnormalities. Due to its rare occurrence, routine OLF screening is not likely to be of significant benefit; however, clinicians should be aware of the correlation between hyperparathyroidism and OLF. Attention to complaints, pertinent neurological examination, and follow-up with appropriate imaging studies, could identify OLF sooner in patients with underlying hyperparathyroidism, preventing permanent neurological deficits.  



REFERENCES

 ADDIN EN.REFLIST 1.	Slatopolsky E, Brown A, Dusso A (1999) Pathogenesis of secondary hyperparathyroidism. Kidney Int Suppl 73: S14-9.
2.	Ishida Y, Kawai S (1993) Effects of bone-seeking hormones on DNA synthesis, cyclic AMP level, and alkaline phosphatase activity in cultured cells from human posterior longitudinal ligament of the spine. J Bone Miner Res 8, 1291-300.
3.	Isogai Y, Akatsu T, Ishizuya T, Yamaguchi A, Hori M, et al. (1996) Parathyroid hormone regulates osteoblast differentiation positively or negatively depending on the differentiation stages. J Bone Miner Res 11, 1384-93.
4.	Nakao Y, Koike T, Ohta Y, Manaka T, Imai Y, et al. (2009) Parathyroid hormone enhances bone morphogenetic protein activity by increasing intracellular 3', 5'-cyclic adenosine monophosphate accumulation in osteoblastic MC3T3-E1 cells. Bone 44, 872-7.
5.	Specchia N, Pagnotta A, Gigante A, Logroscino G, Toesca A (2001) Characterization of cultured human ligamentum flavum cells in lumbar spine stenosis. J Orthop Res 19, 294-300.
6.	Yayama T, Uchida K, Kobayashi S, Kokubo Y, Sato R, et al. (2007) Thoracic ossification of the human ligamentum flavum: histopathological and immunohistochemical findings around the ossified lesion. J Neurosurg Spine 7, 184-93.
7.	Pascal-Moussellard H, Cabre P, Smadja D, Catonne Y (2005) Symptomatic ossification of the ligamentum flavum: a clinical series from the French Antilles. Spine (Phila Pa 1976) 30, E400-5.
8.	Xu R, Sciubba DM, Gokaslan ZL, Bydon A (2008) Ossification of the ligamentum flavum in a Caucasian man. J Neurosurg Spine 9, 427-37.
9.	Cabre P, Pascal-Moussellard H, Kaidomar S, Bucki B, Bardin T, et al. (2001) Six cases of cervical ligamentum flavum calcification in Blacks in the French West Indies. Joint Bone Spine 68, 158-65.
10.	al-Orainy IA, Kolawole T (1998) Ossification of the ligament flavum. Eur J Radiol 29, 76-82.
11.	Wiseman DB, Stokes JK, Toselli RM (2002) Paraparesis in a black man brought on by ossification of the ligamentum flavum: case report and review of the literature. J Spinal Disord Tech 15, 542-5.
12.	Kong Q, Ma X, Li F, Guo Z, Qi Q, et al. (2007) COL6A1 polymorphisms associated with ossification of the ligamentum flavum and ossification of the posterior longitudinal ligament. Spine (Phila Pa 1976) 32, 2834-8.
13.	Mobbs RJ, Dvorak M (2007) Ossification of the ligamentum flavum: diet and genetics. J Clin Neurosci 14, 703-5.
14.	Li H, Jiang LS, Dai LY (2007) Hormones and growth factors in the pathogenesis of spinal ligament ossification. Eur Spine J 16, 1075-84.
15.	Zhong ZM, Chen JT (2009) Phenotypic characterization of ligamentum flavum cells from patients with ossification of ligamentum flavum. Yonsei Med J 50, 375-9.













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tt.t5t<t�t�t�t�t�tuMuNu��������������������������潯�����������潤������h�7�aJmHnHuhbVHh�0�aJmHnHuhbVHaJmHnHuh\(�aJmHnHu$h�3�h�0�B*aJmHnHph�uh�3�h�0�aJmHnHuh�3�aJmHnHu@�tVu�u�v�v�v�v�v�v�v�v�v�v�v�v�v���������������gd��gd�7�gd�0����0�^��`�0�gd�0�NuVu^ueuhumuwu�u�u�u�u�u�u{v|v�v�v�v�v�v�v�v�v�v�v�v�v����������������������h}jjh}jUh�3�h��CJaJjh�3�h�:CJUaJh�7�aJmHnHuh�3�h�0�aJmHnHu21�h:p����/ ��=!��"��#��$��%�������sD���y������K�	_ENREF_1�D<EndNote><Cite ExcludeYear="1"><Author>Ishida</Author><RecNum>2</RecNum><DisplayText>[2, 3]</DisplayText><record><rec-number>2</rec-number><foreign-keys><key app="EN" db-id="zdedttxdxzadxnevt2h5xe2rfe2rrx0xw90s">2</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ishida, Y.</author><author>Kawai, S.</author></authors></contributors><auth-address>Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, Japan.</auth-address><titles><title>Effects of bone-seeking hormones on DNA synthesis, cyclic AMP level, and alkaline phosphatase activity in cultured cells from human posterior longitudinal ligament of the spine</title><secondary-title>J Bone Miner Res</secondary-title><alt-title>Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research</alt-title></titles><pages>1291-300</pages><volume>8</volume><number>11</number><edition>1993/11/01</edition><keywords><keyword>Acid Phosphatase/*metabolism</keyword><keyword>Adult</keyword><keyword>Alkaline Phosphatase/drug effects/*metabolism</keyword><keyword>Calcitonin/*pharmacology</keyword><keyword>Cells, Cultured</keyword><keyword>Cyclic AMP/*analysis</keyword><keyword>DNA/*biosynthesis/drug effects</keyword><keyword>Dinoprostone/*pharmacology</keyword><keyword>Humans</keyword><keyword>Middle Aged</keyword><keyword>Ossification of Posterior Longitudinal</keyword><keyword>Ligament/enzymology/*metabolism/pathology</keyword><keyword>Parathyroid Hormone/*pharmacology</keyword></keywords><dates><year>1993</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0884-0431 (Print)&#xD;0884-0431 (Linking)</isbn><accession-num>8266821</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/8266821</url></related-urls></urls><electronic-resource-num>10.1002/jbmr.5650081104</electronic-resource-num><language>eng</language></record></Cite><Cite ExcludeYear="1"><Author>Isogai</Author><RecNum>3</RecNum><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="zdedttxdxzadxnevt2h5xe2rfe2rrx0xw90s">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Isogai, Y.</author><author>Akatsu, T.</author><author>Ishizuya, T.</author><author>Yamaguchi, A.</author><author>Hori, M.</author><author>Takahashi, N.</author><author>Suda, T.</author></authors></contributors><auth-address>Laboratory for Bone Metabolism, Asahi Chemical Industry Co., Ltd., Shizuoka-ken, Japan.</auth-address><titles><title>Parathyroid hormone regulates osteoblast differentiation positively or negatively depending on the differentiation stages</title><secondary-title>J Bone Miner Res</secondary-title><alt-title>Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research</alt-title></titles><pages>1384-93</pages><volume>11</volume><number>10</number><edition>1996/10/01</edition><keywords><keyword>Alkaline Phosphatase/genetics/metabolism</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Blotting, Northern</keyword><keyword>Bone Marrow Cells</keyword><keyword>Bucladesine/pharmacology</keyword><keyword>Cell Count</keyword><keyword>Cell Differentiation/drug effects</keyword><keyword>Cells, Cultured</keyword><keyword>Colony-Forming Units Assay</keyword><keyword>DNA/metabolism</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Forskolin/pharmacology</keyword><keyword>Humans</keyword><keyword>Hydroxyproline/metabolism</keyword><keyword>Mice</keyword><keyword>Osteoblasts/cytology/*drug effects/enzymology</keyword><keyword>Osteocalcin/metabolism</keyword><keyword>RNA, Messenger/metabolism</keyword><keyword>Staining and Labeling</keyword><keyword>Teriparatide/*pharmacology</keyword><keyword>Tetradecanoylphorbol Acetate/toxicity</keyword></keywords><dates><year>1996</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0884-0431 (Print)&#xD;0884-0431 (Linking)</isbn><accession-num>8889836</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/8889836</url></related-urls></urls><electronic-resource-num>10.1002/jbmr.5650111003</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_2sD���y������K�	_ENREF_3�D<EndNote><Cite ExcludeYear="1"><Author>Nakao</Author><RecNum>4</RecNum><DisplayText>[4-6]</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="zdedttxdxzadxnevt2h5xe2rfe2rrx0xw90s">4</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nakao, Y.</author><author>Koike, T.</author><author>Ohta, Y.</author><author>Manaka, T.</author><author>Imai, Y.</author><author>Takaoka, K.</author></authors></contributors><auth-address>Department of Orthopaedic Surgery, Osaka City University Medical School, Osaka, Japan.</auth-address><titles><title>Parathyroid hormone enhances bone morphogenetic protein activity by increasing intracellular 3&apos;, 5&apos;-cyclic adenosine monophosphate accumulation in osteoblastic MC3T3-E1 cells</title><secondary-title>Bone</secondary-title><alt-title>Bone</alt-title></titles><pages>872-7</pages><volume>44</volume><number>5</number><edition>2009/05/16</edition><keywords><keyword>Alkaline Phosphatase/genetics</keyword><keyword>Animals</keyword><keyword>Bone Morphogenetic Proteins/pharmacology</keyword><keyword>Cell Line</keyword><keyword>Core Binding Factor Alpha 1 Subunit/genetics</keyword><keyword>Cyclic AMP/*metabolism</keyword><keyword>Mice</keyword><keyword>Osteoblasts/*drug effects/*metabolism</keyword><keyword>Osteocalcin/genetics</keyword><keyword>Parathyroid Hormone/*pharmacology</keyword><keyword>Recombinant Proteins/pharmacology</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Signal Transduction/drug effects</keyword><keyword>Smad6 Protein/genetics</keyword><keyword>Transforming Growth Factor beta/pharmacology</keyword></keywords><dates><year>2009</year><pub-dates><date>May</date></pub-dates></dates><isbn>1873-2763 (Electronic)&#xD;1873-2763 (Linking)</isbn><accession-num>19442611</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19442611</url></related-urls></urls><electronic-resource-num>10.1016/j.bone.2009.01.370</electronic-resource-num><language>eng</language></record></Cite><Cite ExcludeYear="1"><Author>Specchia</Author><RecNum>5</RecNum><record><rec-number>5</rec-number><foreign-keys><key app="EN" db-id="zdedttxdxzadxnevt2h5xe2rfe2rrx0xw90s">5</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Specchia, N.</author><author>Pagnotta, A.</author><author>Gigante, A.</author><author>Logroscino, G.</author><author>Toesca, A.</author></authors></contributors><auth-address>Department of Orthopedics, Istituto di Patologia dell&apos; Apparato Locomotore, University of Ancona, Italy. specchia@popcsi.unian.it</auth-address><titles><title>Characterization of cultured human ligamentum flavum cells in lumbar spine stenosis</title><secondary-title>J Orthop Res</secondary-title><alt-title>Journal of orthopaedic research : official publication of the Orthopaedic Research Society</alt-title></titles><pages>294-300</pages><volume>19</volume><number>2</number><edition>2001/05/12</edition><keywords><keyword>Alkaline Phosphatase/metabolism</keyword><keyword>Bone Matrix/metabolism</keyword><keyword>Cells, Cultured</keyword><keyword>Collagen/metabolism</keyword><keyword>Cyclic AMP/metabolism</keyword><keyword>Fibronectins/metabolism</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>Ligamentum Flavum/drug effects/metabolism/*pathology</keyword><keyword>Lumbosacral Region</keyword><keyword>Middle Aged</keyword><keyword>Osteoblasts/cytology/drug effects/metabolism</keyword><keyword>Osteonectin/metabolism</keyword><keyword>Parathyroid Hormone/pharmacology</keyword><keyword>Reference Values</keyword><keyword>S100 Proteins/metabolism</keyword><keyword>Spinal Fractures/metabolism/pathology</keyword><keyword>Spinal Stenosis/metabolism/*pathology</keyword></keywords><dates><year>2001</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0736-0266 (Print)&#xD;0736-0266 (Linking)</isbn><accession-num>11347704</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11347704</url></related-urls></urls><electronic-resource-num>10.1016/S0736-0266(00)00026-7</electronic-resource-num><language>eng</language></record></Cite><Cite ExcludeYear="1"><Author>Yayama</Author><RecNum>6</RecNum><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="zdedttxdxzadxnevt2h5xe2rfe2rrx0xw90s">6</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yayama, T.</author><author>Uchida, K.</author><author>Kobayashi, S.</author><author>Kokubo, Y.</author><author>Sato, R.</author><author>Nakajima, H.</author><author>Takamura, T.</author><author>Bangirana, A.</author><author>Itoh, H.</author><author>Baba, H.</author></authors></contributors><auth-address>Departments of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medical Sciences, Fukui, Japan. yayama@fmsrsa.fukui-med.ac.jp</auth-address><titles><title>Thoracic ossification of the human ligamentum flavum: histopathological and immunohistochemical findings around the ossified lesion</title><secondary-title>J Neurosurg Spine</secondary-title><alt-title>Journal of neurosurgery. Spine</alt-title></titles><pages>184-93</pages><volume>7</volume><number>2</number><edition>2007/08/11</edition><keywords><keyword>Aged</keyword><keyword>Bone Morphogenetic Protein 2</keyword><keyword>Bone Morphogenetic Proteins/metabolism</keyword><keyword>Chondrocytes/metabolism</keyword><keyword>Collagen Type I/metabolism</keyword><keyword>Collagen Type II/metabolism</keyword><keyword>Decompression, Surgical</keyword><keyword>Disease Progression</keyword><keyword>Elastic Tissue/pathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>*Ligamentum Flavum/radiography/surgery</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Nervous System Diseases/etiology</keyword><keyword>Ossification, Heterotopic/complications/*metabolism/*pathology/radiography</keyword><keyword>*Thoracic Vertebrae</keyword><keyword>Tissue Distribution</keyword><keyword>Tomography, X-Ray Computed</keyword><keyword>Transforming Growth Factor beta/metabolism</keyword><keyword>Vascular Endothelial Growth Factor A/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1547-5654 (Print)&#xD;1547-5646 (Linking)</isbn><accession-num>17688058</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17688058</url></related-urls></urls><electronic-resource-num>10.3171/SPI-07/08/184</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_4sD���y������K�	_ENREF_16D<EndNote><Cite ExcludeYear="1"><Author>Ishida</Author><Year>1993</Year><RecNum>8</RecNum><DisplayText>[2, 3]</DisplayText><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ishida, Y.</author><author>Kawai, S.</author></authors></contributors><auth-address>Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, Japan.</auth-address><titles><title>Effects of bone-seeking hormones on DNA synthesis, cyclic AMP level, and alkaline phosphatase activity in cultured cells from human posterior longitudinal ligament of the spine</title><secondary-title>J Bone Miner Res</secondary-title><alt-title>Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research</alt-title></titles><periodical><full-title>J Bone Miner Res</full-title><abbr-1>Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research</abbr-1></periodical><alt-periodical><full-title>J Bone Miner Res</full-title><abbr-1>Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research</abbr-1></alt-periodical><pages>1291-300</pages><volume>8</volume><number>11</number><edition>1993/11/01</edition><keywords><keyword>Acid Phosphatase/*metabolism</keyword><keyword>Adult</keyword><keyword>Alkaline Phosphatase/drug effects/*metabolism</keyword><keyword>Calcitonin/*pharmacology</keyword><keyword>Cells, Cultured</keyword><keyword>Cyclic AMP/*analysis</keyword><keyword>DNA/*biosynthesis/drug effects</keyword><keyword>Dinoprostone/*pharmacology</keyword><keyword>Humans</keyword><keyword>Middle Aged</keyword><keyword>Ossification of Posterior Longitudinal</keyword><keyword>Ligament/enzymology/*metabolism/pathology</keyword><keyword>Parathyroid Hormone/*pharmacology</keyword></keywords><dates><year>1993</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0884-0431 (Print)&#xD;0884-0431 (Linking)</isbn><accession-num>8266821</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/8266821</url></related-urls></urls><electronic-resource-num>10.1002/jbmr.5650081104</electronic-resource-num><language>eng</language></record></Cite><Cite ExcludeYear="1"><Author>Isogai</Author><Year>1996</Year><RecNum>11</RecNum><record><rec-number>11</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">11</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Isogai, Y.</author><author>Akatsu, T.</author><author>Ishizuya, T.</author><author>Yamaguchi, A.</author><author>Hori, M.</author><author>Takahashi, N.</author><author>Suda, T.</author></authors></contributors><auth-address>Laboratory for Bone Metabolism, Asahi Chemical Industry Co., Ltd., Shizuoka-ken, Japan.</auth-address><titles><title>Parathyroid hormone regulates osteoblast differentiation positively or negatively depending on the differentiation stages</title><secondary-title>J Bone Miner Res</secondary-title><alt-title>Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research</alt-title></titles><periodical><full-title>J Bone Miner Res</full-title><abbr-1>Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research</abbr-1></periodical><alt-periodical><full-title>J Bone Miner Res</full-title><abbr-1>Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research</abbr-1></alt-periodical><pages>1384-93</pages><volume>11</volume><number>10</number><edition>1996/10/01</edition><keywords><keyword>Alkaline Phosphatase/genetics/metabolism</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Blotting, Northern</keyword><keyword>Bone Marrow Cells</keyword><keyword>Bucladesine/pharmacology</keyword><keyword>Cell Count</keyword><keyword>Cell Differentiation/drug effects</keyword><keyword>Cells, Cultured</keyword><keyword>Colony-Forming Units Assay</keyword><keyword>DNA/metabolism</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Forskolin/pharmacology</keyword><keyword>Humans</keyword><keyword>Hydroxyproline/metabolism</keyword><keyword>Mice</keyword><keyword>Osteoblasts/cytology/*drug effects/enzymology</keyword><keyword>Osteocalcin/metabolism</keyword><keyword>RNA, Messenger/metabolism</keyword><keyword>Staining and Labeling</keyword><keyword>Teriparatide/*pharmacology</keyword><keyword>Tetradecanoylphorbol Acetate/toxicity</keyword></keywords><dates><year>1996</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0884-0431 (Print)&#xD;0884-0431 (Linking)</isbn><accession-num>8889836</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/8889836</url></related-urls></urls><electronic-resource-num>10.1002/jbmr.5650111003</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_2sD���y������K�	_ENREF_3D<EndNote><Cite ExcludeYear="1"><Author>Nakao</Author><Year>2009</Year><RecNum>60</RecNum><DisplayText>[4-6]</DisplayText><record><rec-number>60</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">60</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nakao, Y.</author><author>Koike, T.</author><author>Ohta, Y.</author><author>Manaka, T.</author><author>Imai, Y.</author><author>Takaoka, K.</author></authors></contributors><auth-address>Department of Orthopaedic Surgery, Osaka City University Medical School, Osaka, Japan.</auth-address><titles><title>Parathyroid hormone enhances bone morphogenetic protein activity by increasing intracellular 3&apos;, 5&apos;-cyclic adenosine monophosphate accumulation in osteoblastic MC3T3-E1 cells</title><secondary-title>Bone</secondary-title><alt-title>Bone</alt-title></titles><periodical><full-title>Bone</full-title><abbr-1>Bone</abbr-1></periodical><alt-periodical><full-title>Bone</full-title><abbr-1>Bone</abbr-1></alt-periodical><pages>872-7</pages><volume>44</volume><number>5</number><edition>2009/05/16</edition><keywords><keyword>Alkaline Phosphatase/genetics</keyword><keyword>Animals</keyword><keyword>Bone Morphogenetic Proteins/pharmacology</keyword><keyword>Cell Line</keyword><keyword>Core Binding Factor Alpha 1 Subunit/genetics</keyword><keyword>Cyclic AMP/*metabolism</keyword><keyword>Mice</keyword><keyword>Osteoblasts/*drug effects/*metabolism</keyword><keyword>Osteocalcin/genetics</keyword><keyword>Parathyroid Hormone/*pharmacology</keyword><keyword>Recombinant Proteins/pharmacology</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Signal Transduction/drug effects</keyword><keyword>Smad6 Protein/genetics</keyword><keyword>Transforming Growth Factor beta/pharmacology</keyword></keywords><dates><year>2009</year><pub-dates><date>May</date></pub-dates></dates><isbn>1873-2763 (Electronic)&#xD;1873-2763 (Linking)</isbn><accession-num>19442611</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19442611</url></related-urls></urls><electronic-resource-num>10.1016/j.bone.2009.01.370</electronic-resource-num><language>eng</language></record></Cite><Cite ExcludeYear="1"><Author>Specchia</Author><Year>2001</Year><RecNum>65</RecNum><record><rec-number>65</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">65</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Specchia, N.</author><author>Pagnotta, A.</author><author>Gigante, A.</author><author>Logroscino, G.</author><author>Toesca, A.</author></authors></contributors><auth-address>Department of Orthopedics, Istituto di Patologia dell&apos; Apparato Locomotore, University of Ancona, Italy. specchia@popcsi.unian.it</auth-address><titles><title>Characterization of cultured human ligamentum flavum cells in lumbar spine stenosis</title><secondary-title>J Orthop Res</secondary-title><alt-title>Journal of orthopaedic research : official publication of the Orthopaedic Research Society</alt-title></titles><periodical><full-title>J Orthop Res</full-title><abbr-1>Journal of orthopaedic research : official publication of the Orthopaedic Research Society</abbr-1></periodical><alt-periodical><full-title>J Orthop Res</full-title><abbr-1>Journal of orthopaedic research : official publication of the Orthopaedic Research Society</abbr-1></alt-periodical><pages>294-300</pages><volume>19</volume><number>2</number><edition>2001/05/12</edition><keywords><keyword>Alkaline Phosphatase/metabolism</keyword><keyword>Bone Matrix/metabolism</keyword><keyword>Cells, Cultured</keyword><keyword>Collagen/metabolism</keyword><keyword>Cyclic AMP/metabolism</keyword><keyword>Fibronectins/metabolism</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>Ligamentum Flavum/drug effects/metabolism/*pathology</keyword><keyword>Lumbosacral Region</keyword><keyword>Middle Aged</keyword><keyword>Osteoblasts/cytology/drug effects/metabolism</keyword><keyword>Osteonectin/metabolism</keyword><keyword>Parathyroid Hormone/pharmacology</keyword><keyword>Reference Values</keyword><keyword>S100 Proteins/metabolism</keyword><keyword>Spinal Fractures/metabolism/pathology</keyword><keyword>Spinal Stenosis/metabolism/*pathology</keyword></keywords><dates><year>2001</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0736-0266 (Print)&#xD;0736-0266 (Linking)</isbn><accession-num>11347704</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11347704</url></related-urls></urls><electronic-resource-num>10.1016/S0736-0266(00)00026-7</electronic-resource-num><language>eng</language></record></Cite><Cite ExcludeYear="1"><Author>Yayama</Author><Year>2007</Year><RecNum>74</RecNum><record><rec-number>74</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">74</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yayama, T.</author><author>Uchida, K.</author><author>Kobayashi, S.</author><author>Kokubo, Y.</author><author>Sato, R.</author><author>Nakajima, H.</author><author>Takamura, T.</author><author>Bangirana, A.</author><author>Itoh, H.</author><author>Baba, H.</author></authors></contributors><auth-address>Departments of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medical Sciences, Fukui, Japan. yayama@fmsrsa.fukui-med.ac.jp</auth-address><titles><title>Thoracic ossification of the human ligamentum flavum: histopathological and immunohistochemical findings around the ossified lesion</title><secondary-title>J Neurosurg Spine</secondary-title><alt-title>Journal of neurosurgery. Spine</alt-title></titles><periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></periodical><alt-periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></alt-periodical><pages>184-93</pages><volume>7</volume><number>2</number><edition>2007/08/11</edition><keywords><keyword>Aged</keyword><keyword>Bone Morphogenetic Protein 2</keyword><keyword>Bone Morphogenetic Proteins/metabolism</keyword><keyword>Chondrocytes/metabolism</keyword><keyword>Collagen Type I/metabolism</keyword><keyword>Collagen Type II/metabolism</keyword><keyword>Decompression, Surgical</keyword><keyword>Disease Progression</keyword><keyword>Elastic Tissue/pathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>*Ligamentum Flavum/radiography/surgery</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Nervous System Diseases/etiology</keyword><keyword>Ossification, Heterotopic/complications/*metabolism/*pathology/radiography</keyword><keyword>*Thoracic Vertebrae</keyword><keyword>Tissue Distribution</keyword><keyword>Tomography, X-Ray Computed</keyword><keyword>Transforming Growth Factor beta/metabolism</keyword><keyword>Vascular Endothelial Growth Factor A/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1547-5654 (Print)&#xD;1547-5646 (Linking)</isbn><accession-num>17688058</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17688058</url></related-urls></urls><electronic-resource-num>10.3171/SPI-07/08/184</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_4JD<EndNote><Cite ExcludeYear="1"><Author>Yayama</Author><Year>2007</Year><RecNum>74</RecNum><DisplayText>[6]</DisplayText><record><rec-number>74</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">74</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yayama, T.</author><author>Uchida, K.</author><author>Kobayashi, S.</author><author>Kokubo, Y.</author><author>Sato, R.</author><author>Nakajima, H.</author><author>Takamura, T.</author><author>Bangirana, A.</author><author>Itoh, H.</author><author>Baba, H.</author></authors></contributors><auth-address>Departments of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medical Sciences, Fukui, Japan. yayama@fmsrsa.fukui-med.ac.jp</auth-address><titles><title>Thoracic ossification of the human ligamentum flavum: histopathological and immunohistochemical findings around the ossified lesion</title><secondary-title>J Neurosurg Spine</secondary-title><alt-title>Journal of neurosurgery. Spine</alt-title></titles><periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></periodical><alt-periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></alt-periodical><pages>184-93</pages><volume>7</volume><number>2</number><edition>2007/08/11</edition><keywords><keyword>Aged</keyword><keyword>Bone Morphogenetic Protein 2</keyword><keyword>Bone Morphogenetic Proteins/metabolism</keyword><keyword>Chondrocytes/metabolism</keyword><keyword>Collagen Type I/metabolism</keyword><keyword>Collagen Type II/metabolism</keyword><keyword>Decompression, Surgical</keyword><keyword>Disease Progression</keyword><keyword>Elastic Tissue/pathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>*Ligamentum Flavum/radiography/surgery</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Nervous System Diseases/etiology</keyword><keyword>Ossification, Heterotopic/complications/*metabolism/*pathology/radiography</keyword><keyword>*Thoracic Vertebrae</keyword><keyword>Tissue Distribution</keyword><keyword>Tomography, X-Ray Computed</keyword><keyword>Transforming Growth Factor beta/metabolism</keyword><keyword>Vascular Endothelial Growth Factor A/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1547-5654 (Print)&#xD;1547-5646 (Linking)</isbn><accession-num>17688058</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17688058</url></related-urls></urls><electronic-resource-num>10.3171/SPI-07/08/184</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_6JD<EndNote><Cite ExcludeYear="1"><Author>Yayama</Author><Year>2007</Year><RecNum>74</RecNum><DisplayText>[6]</DisplayText><record><rec-number>74</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">74</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yayama, T.</author><author>Uchida, K.</author><author>Kobayashi, S.</author><author>Kokubo, Y.</author><author>Sato, R.</author><author>Nakajima, H.</author><author>Takamura, T.</author><author>Bangirana, A.</author><author>Itoh, H.</author><author>Baba, H.</author></authors></contributors><auth-address>Departments of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medical Sciences, Fukui, Japan. yayama@fmsrsa.fukui-med.ac.jp</auth-address><titles><title>Thoracic ossification of the human ligamentum flavum: histopathological and immunohistochemical findings around the ossified lesion</title><secondary-title>J Neurosurg Spine</secondary-title><alt-title>Journal of neurosurgery. Spine</alt-title></titles><periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></periodical><alt-periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></alt-periodical><pages>184-93</pages><volume>7</volume><number>2</number><edition>2007/08/11</edition><keywords><keyword>Aged</keyword><keyword>Bone Morphogenetic Protein 2</keyword><keyword>Bone Morphogenetic Proteins/metabolism</keyword><keyword>Chondrocytes/metabolism</keyword><keyword>Collagen Type I/metabolism</keyword><keyword>Collagen Type II/metabolism</keyword><keyword>Decompression, Surgical</keyword><keyword>Disease Progression</keyword><keyword>Elastic Tissue/pathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>*Ligamentum Flavum/radiography/surgery</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Nervous System Diseases/etiology</keyword><keyword>Ossification, Heterotopic/complications/*metabolism/*pathology/radiography</keyword><keyword>*Thoracic Vertebrae</keyword><keyword>Tissue Distribution</keyword><keyword>Tomography, X-Ray Computed</keyword><keyword>Transforming Growth Factor beta/metabolism</keyword><keyword>Vascular Endothelial Growth Factor A/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1547-5654 (Print)&#xD;1547-5646 (Linking)</isbn><accession-num>17688058</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17688058</url></related-urls></urls><electronic-resource-num>10.3171/SPI-07/08/184</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_6sD���y������K�	_ENREF_7sD���y������K�	_ENREF_8�D<EndNote><Cite ExcludeYear="1"><Author>Cabre</Author><Year>2001</Year><RecNum>3</RecNum><DisplayText>[9]</DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cabre, P.</author><author>Pascal-Moussellard, H.</author><author>Kaidomar, S.</author><author>Bucki, B.</author><author>Bardin, T.</author><author>Smadja, D.</author><author>Arfi, S.</author></authors></contributors><auth-address>Service de neurologie, h pital Pierre-Zobda-Quitmann, CHRU Fort de France, Martinique. Pcabre@outremer.com</auth-address><titles><title>Six cases of cervical ligamentum flavum calcification in Blacks in the French West Indies</title><secondary-title>Joint Bone Spine</secondary-title><alt-title>Joint, bone, spine : revue du rhumatisme</alt-title></titles><periodical><full-title>Joint Bone Spine</full-title><abbr-1>Joint, bone, spine : revue du rhumatisme</abbr-1></periodical><alt-periodical><full-title>Joint Bone Spine</full-title><abbr-1>Joint, bone, spine : revue du rhumatisme</abbr-1></alt-periodical><pages>158-65</pages><volume>68</volume><number>2</number><edition>2001/04/28</edition><keywords><keyword>African Continental Ancestry Group</keyword><keyword>Aged</keyword><keyword>Calcinosis/*ethnology/*pathology</keyword><keyword>Cervical Vertebrae</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Ligamentum Flavum/*pathology</keyword><keyword>Magnetic Resonance Imaging</keyword><keyword>Male</keyword><keyword>Microscopy, Electron</keyword><keyword>Middle Aged</keyword><keyword>Retrospective Studies</keyword><keyword>Spinal Cord Compression/ethnology/pathology</keyword><keyword>West Indies</keyword></keywords><dates><year>2001</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1297-319X (Print)&#xD;1297-319X (Linking)</isbn><accession-num>11324932</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11324932</url></related-urls></urls><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_9uD���y������K�
_ENREF_10uD���y������K�
_ENREF_11J
D<EndNote><Cite ExcludeYear="1"><Author>Yayama</Author><RecNum>6</RecNum><DisplayText>[6]</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="pvetx0v9ief0vjede275vta95rz92tdztfae">6</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yayama, T.</author><author>Uchida, K.</author><author>Kobayashi, S.</author><author>Kokubo, Y.</author><author>Sato, R.</author><author>Nakajima, H.</author><author>Takamura, T.</author><author>Bangirana, A.</author><author>Itoh, H.</author><author>Baba, H.</author></authors></contributors><auth-address>Departments of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medical Sciences, Fukui, Japan. yayama@fmsrsa.fukui-med.ac.jp</auth-address><titles><title>Thoracic ossification of the human ligamentum flavum: histopathological and immunohistochemical findings around the ossified lesion</title><secondary-title>J Neurosurg Spine</secondary-title><alt-title>Journal of neurosurgery. Spine</alt-title></titles><pages>184-93</pages><volume>7</volume><number>2</number><edition>2007/08/11</edition><keywords><keyword>Aged</keyword><keyword>Bone Morphogenetic Protein 2</keyword><keyword>Bone Morphogenetic Proteins/metabolism</keyword><keyword>Chondrocytes/metabolism</keyword><keyword>Collagen Type I/metabolism</keyword><keyword>Collagen Type II/metabolism</keyword><keyword>Decompression, Surgical</keyword><keyword>Disease Progression</keyword><keyword>Elastic Tissue/pathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>*Ligamentum Flavum/radiography/surgery</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Nervous System Diseases/etiology</keyword><keyword>Ossification, Heterotopic/complications/*metabolism/*pathology/radiography</keyword><keyword>*Thoracic Vertebrae</keyword><keyword>Tissue Distribution</keyword><keyword>Tomography, X-Ray Computed</keyword><keyword>Transforming Growth Factor beta/metabolism</keyword><keyword>Vascular Endothelial Growth Factor A/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1547-5654 (Print)&#xD;1547-5646 (Linking)</isbn><accession-num>17688058</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17688058</url></related-urls></urls><electronic-resource-num>10.3171/SPI-07/08/184</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_6J
D<EndNote><Cite ExcludeYear="1"><Author>Yayama</Author><RecNum>6</RecNum><DisplayText>[6]</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="pvetx0v9ief0vjede275vta95rz92tdztfae">6</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yayama, T.</author><author>Uchida, K.</author><author>Kobayashi, S.</author><author>Kokubo, Y.</author><author>Sato, R.</author><author>Nakajima, H.</author><author>Takamura, T.</author><author>Bangirana, A.</author><author>Itoh, H.</author><author>Baba, H.</author></authors></contributors><auth-address>Departments of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medical Sciences, Fukui, Japan. yayama@fmsrsa.fukui-med.ac.jp</auth-address><titles><title>Thoracic ossification of the human ligamentum flavum: histopathological and immunohistochemical findings around the ossified lesion</title><secondary-title>J Neurosurg Spine</secondary-title><alt-title>Journal of neurosurgery. Spine</alt-title></titles><pages>184-93</pages><volume>7</volume><number>2</number><edition>2007/08/11</edition><keywords><keyword>Aged</keyword><keyword>Bone Morphogenetic Protein 2</keyword><keyword>Bone Morphogenetic Proteins/metabolism</keyword><keyword>Chondrocytes/metabolism</keyword><keyword>Collagen Type I/metabolism</keyword><keyword>Collagen Type II/metabolism</keyword><keyword>Decompression, Surgical</keyword><keyword>Disease Progression</keyword><keyword>Elastic Tissue/pathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>*Ligamentum Flavum/radiography/surgery</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Nervous System Diseases/etiology</keyword><keyword>Ossification, Heterotopic/complications/*metabolism/*pathology/radiography</keyword><keyword>*Thoracic Vertebrae</keyword><keyword>Tissue Distribution</keyword><keyword>Tomography, X-Ray Computed</keyword><keyword>Transforming Growth Factor beta/metabolism</keyword><keyword>Vascular Endothelial Growth Factor A/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1547-5654 (Print)&#xD;1547-5646 (Linking)</isbn><accession-num>17688058</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17688058</url></related-urls></urls><electronic-resource-num>10.3171/SPI-07/08/184</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_6JD<EndNote><Cite ExcludeYear="1"><Author>Yayama</Author><Year>2007</Year><RecNum>74</RecNum><DisplayText>[6]</DisplayText><record><rec-number>74</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">74</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yayama, T.</author><author>Uchida, K.</author><author>Kobayashi, S.</author><author>Kokubo, Y.</author><author>Sato, R.</author><author>Nakajima, H.</author><author>Takamura, T.</author><author>Bangirana, A.</author><author>Itoh, H.</author><author>Baba, H.</author></authors></contributors><auth-address>Departments of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medical Sciences, Fukui, Japan. yayama@fmsrsa.fukui-med.ac.jp</auth-address><titles><title>Thoracic ossification of the human ligamentum flavum: histopathological and immunohistochemical findings around the ossified lesion</title><secondary-title>J Neurosurg Spine</secondary-title><alt-title>Journal of neurosurgery. Spine</alt-title></titles><periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></periodical><alt-periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></alt-periodical><pages>184-93</pages><volume>7</volume><number>2</number><edition>2007/08/11</edition><keywords><keyword>Aged</keyword><keyword>Bone Morphogenetic Protein 2</keyword><keyword>Bone Morphogenetic Proteins/metabolism</keyword><keyword>Chondrocytes/metabolism</keyword><keyword>Collagen Type I/metabolism</keyword><keyword>Collagen Type II/metabolism</keyword><keyword>Decompression, Surgical</keyword><keyword>Disease Progression</keyword><keyword>Elastic Tissue/pathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>*Ligamentum Flavum/radiography/surgery</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Nervous System Diseases/etiology</keyword><keyword>Ossification, Heterotopic/complications/*metabolism/*pathology/radiography</keyword><keyword>*Thoracic Vertebrae</keyword><keyword>Tissue Distribution</keyword><keyword>Tomography, X-Ray Computed</keyword><keyword>Transforming Growth Factor beta/metabolism</keyword><keyword>Vascular Endothelial Growth Factor A/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1547-5654 (Print)&#xD;1547-5646 (Linking)</isbn><accession-num>17688058</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17688058</url></related-urls></urls><electronic-resource-num>10.3171/SPI-07/08/184</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_6
D<EndNote><Cite ExcludeYear="1"><Author>Kong</Author><Year>2007</Year><RecNum>14</RecNum><DisplayText>[12]</DisplayText><record><rec-number>14</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">14</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kong, Q.</author><author>Ma, X.</author><author>Li, F.</author><author>Guo, Z.</author><author>Qi, Q.</author><author>Li, W.</author><author>Yuan, H.</author><author>Wang, Z.</author><author>Chen, Z.</author></authors></contributors><auth-address>Department of Orthopaedic Surgery, Peking University Third Hospital, Beijing, China.</auth-address><titles><title>COL6A1 polymorphisms associated with ossification of the ligamentum flavum and ossification of the posterior longitudinal ligament</title><secondary-title>Spine (Phila Pa 1976)</secondary-title><alt-title>Spine</alt-title></titles><periodical><full-title>Spine (Phila Pa 1976)</full-title><abbr-1>Spine</abbr-1></periodical><alt-periodical><full-title>Spine (Phila Pa 1976)</full-title><abbr-1>Spine</abbr-1></alt-periodical><pages>2834-8</pages><volume>32</volume><number>25</number><edition>2008/02/05</edition><keywords><keyword>Aged</keyword><keyword>Asian Continental Ancestry Group/genetics</keyword><keyword>Case-Control Studies</keyword><keyword>China</keyword><keyword>Collagen Type VI/*genetics</keyword><keyword>Female</keyword><keyword>Gene Frequency</keyword><keyword>Genetic Predisposition to Disease</keyword><keyword>Haplotypes</keyword><keyword>Humans</keyword><keyword>Introns</keyword><keyword>Ligamentum Flavum/*pathology</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Odds Ratio</keyword><keyword>Ossification of Posterior Longitudinal Ligament/*genetics/pathology</keyword><keyword>Ossification, Heterotopic/*genetics/pathology</keyword><keyword>*Polymorphism, Single Nucleotide</keyword><keyword>*Promoter Regions, Genetic</keyword><keyword>Risk Assessment</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2007</year><pub-dates><date>Dec 1</date></pub-dates></dates><isbn>1528-1159 (Electronic)&#xD;0362-2436 (Linking)</isbn><accession-num>18246005</accession-num><work-type>Multicenter Study&#xD;Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18246005</url></related-urls></urls><electronic-resource-num>10.1097/BRS.0b013e31815b761c</electronic-resource-num><language>eng</language></record></Cite></EndNote>uD���y������K�
_ENREF_12jD<EndNote><Cite ExcludeYear="1"><Author>Mobbs</Author><Year>2007</Year><RecNum>59</RecNum><DisplayText>[13]</DisplayText><record><rec-number>59</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">59</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mobbs, R. J.</author><author>Dvorak, M.</author></authors></contributors><auth-address>Prince of Wales Hospital, Peripheral Nerve Research Foundation, 3 Wansey Road, Randwick, New South Wales 2031, Australia. ralphmobbs@hotmail.com</auth-address><titles><title>Ossification of the ligamentum flavum: diet and genetics</title><secondary-title>J Clin Neurosci</secondary-title><alt-title>Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia</alt-title></titles><periodical><full-title>J Clin Neurosci</full-title><abbr-1>Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia</abbr-1></periodical><alt-periodical><full-title>J Clin Neurosci</full-title><abbr-1>Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia</abbr-1></alt-periodical><pages>703-5</pages><volume>14</volume><number>7</number><edition>2007/04/27</edition><keywords><keyword>Diet/*adverse effects</keyword><keyword>*Food Habits</keyword><keyword>Humans</keyword><keyword>Life Style</keyword><keyword>Ligamentum Flavum/*pathology</keyword><keyword>Magnetic Resonance Imaging</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Ossification, Heterotopic/*etiology/*genetics</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2007</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0967-5868 (Print)&#xD;0967-5868 (Linking)</isbn><accession-num>17459710</accession-num><work-type>Case Reports</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17459710</url></related-urls></urls><electronic-resource-num>10.1016/j.jocn.2006.01.010</electronic-resource-num><language>eng</language></record></Cite></EndNote>uD���y������K�
_ENREF_13.D<EndNote><Cite ExcludeYear="1"><Author>Wiseman</Author><Year>2002</Year><RecNum>66</RecNum><DisplayText>[11, 14]</DisplayText><record><rec-number>66</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">66</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wiseman, D. B.</author><author>Stokes, J. K.</author><author>Toselli, R. M.</author></authors></contributors><auth-address>Division of Neurosurgery, University of North Carolina, Chapel Hill, 27599, USA.</auth-address><titles><title>Paraparesis in a black man brought on by ossification of the ligamentum flavum: case report and review of the literature</title><secondary-title>J Spinal Disord Tech</secondary-title><alt-title>Journal of spinal disorders &amp; techniques</alt-title></titles><periodical><full-title>J Spinal Disord Tech</full-title><abbr-1>Journal of spinal disorders &amp; techniques</abbr-1></periodical><alt-periodical><full-title>J Spinal Disord Tech</full-title><abbr-1>Journal of spinal disorders &amp; techniques</abbr-1></alt-periodical><pages>542-5</pages><volume>15</volume><number>6</number><edition>2002/12/07</edition><keywords><keyword>Adult</keyword><keyword>*African Continental Ancestry Group</keyword><keyword>Humans</keyword><keyword>Laminectomy</keyword><keyword>Male</keyword><keyword>Myelography</keyword><keyword>Ossification of Posterior Longitudinal</keyword><keyword>Ligament/*complications/*ethnology/radiography/surgery</keyword><keyword>Paraparesis/*etiology</keyword><keyword>Tomography, X-Ray Computed</keyword></keywords><dates><year>2002</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1536-0652 (Print)&#xD;1536-0652 (Linking)</isbn><accession-num>12468987</accession-num><work-type>Case Reports&#xD;Review</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12468987</url></related-urls></urls><language>eng</language></record></Cite><Cite ExcludeYear="1"><Author>Li</Author><Year>2007</Year><RecNum>58</RecNum><record><rec-number>58</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">58</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Li, H.</author><author>Jiang, L. S.</author><author>Dai, L. Y.</author></authors></contributors><auth-address>Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.</auth-address><titles><title>Hormones and growth factors in the pathogenesis of spinal ligament ossification</title><secondary-title>Eur Spine J</secondary-title><alt-title>European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society</alt-title></titles><periodical><full-title>Eur Spine J</full-title><abbr-1>European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society</abbr-1></periodical><alt-periodical><full-title>Eur Spine J</full-title><abbr-1>European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society</abbr-1></alt-periodical><pages>1075-84</pages><volume>16</volume><number>8</number><edition>2007/04/12</edition><keywords><keyword>Hormones/*physiology</keyword><keyword>Humans</keyword><keyword>Intercellular Signaling Peptides and Proteins/*physiology</keyword><keyword>Ligaments/pathology/physiopathology</keyword><keyword>Ossification, Heterotopic/*etiology/pathology/physiopathology</keyword><keyword>Spinal Diseases/*etiology/pathology/physiopathology</keyword><keyword>Spine/pathology/physiopathology</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0940-6719 (Print)&#xD;0940-6719 (Linking)</isbn><accession-num>17426989</accession-num><work-type>Review</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17426989</url></related-urls></urls><custom2>2200765</custom2><electronic-resource-num>10.1007/s00586-007-0356-4</electronic-resource-num><language>eng</language></record></Cite></EndNote>uD���y������K�
_ENREF_11uD���y������K�
_ENREF_14�D<EndNote><Cite ExcludeYear="1"><Author>Yayama</Author><Year>2007</Year><RecNum>74</RecNum><DisplayText>[6, 14]</DisplayText><record><rec-number>74</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">74</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yayama, T.</author><author>Uchida, K.</author><author>Kobayashi, S.</author><author>Kokubo, Y.</author><author>Sato, R.</author><author>Nakajima, H.</author><author>Takamura, T.</author><author>Bangirana, A.</author><author>Itoh, H.</author><author>Baba, H.</author></authors></contributors><auth-address>Departments of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medical Sciences, Fukui, Japan. yayama@fmsrsa.fukui-med.ac.jp</auth-address><titles><title>Thoracic ossification of the human ligamentum flavum: histopathological and immunohistochemical findings around the ossified lesion</title><secondary-title>J Neurosurg Spine</secondary-title><alt-title>Journal of neurosurgery. Spine</alt-title></titles><periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></periodical><alt-periodical><full-title>J Neurosurg Spine</full-title><abbr-1>Journal of neurosurgery. Spine</abbr-1></alt-periodical><pages>184-93</pages><volume>7</volume><number>2</number><edition>2007/08/11</edition><keywords><keyword>Aged</keyword><keyword>Bone Morphogenetic Protein 2</keyword><keyword>Bone Morphogenetic Proteins/metabolism</keyword><keyword>Chondrocytes/metabolism</keyword><keyword>Collagen Type I/metabolism</keyword><keyword>Collagen Type II/metabolism</keyword><keyword>Decompression, Surgical</keyword><keyword>Disease Progression</keyword><keyword>Elastic Tissue/pathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>*Ligamentum Flavum/radiography/surgery</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Nervous System Diseases/etiology</keyword><keyword>Ossification, Heterotopic/complications/*metabolism/*pathology/radiography</keyword><keyword>*Thoracic Vertebrae</keyword><keyword>Tissue Distribution</keyword><keyword>Tomography, X-Ray Computed</keyword><keyword>Transforming Growth Factor beta/metabolism</keyword><keyword>Vascular Endothelial Growth Factor A/metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1547-5654 (Print)&#xD;1547-5646 (Linking)</isbn><accession-num>17688058</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17688058</url></related-urls></urls><electronic-resource-num>10.3171/SPI-07/08/184</electronic-resource-num><language>eng</language></record></Cite><Cite ExcludeYear="1"><Author>Li</Author><Year>2007</Year><RecNum>58</RecNum><record><rec-number>58</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">58</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Li, H.</author><author>Jiang, L. S.</author><author>Dai, L. Y.</author></authors></contributors><auth-address>Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.</auth-address><titles><title>Hormones and growth factors in the pathogenesis of spinal ligament ossification</title><secondary-title>Eur Spine J</secondary-title><alt-title>European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society</alt-title></titles><periodical><full-title>Eur Spine J</full-title><abbr-1>European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society</abbr-1></periodical><alt-periodical><full-title>Eur Spine J</full-title><abbr-1>European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society</abbr-1></alt-periodical><pages>1075-84</pages><volume>16</volume><number>8</number><edition>2007/04/12</edition><keywords><keyword>Hormones/*physiology</keyword><keyword>Humans</keyword><keyword>Intercellular Signaling Peptides and Proteins/*physiology</keyword><keyword>Ligaments/pathology/physiopathology</keyword><keyword>Ossification, Heterotopic/*etiology/pathology/physiopathology</keyword><keyword>Spinal Diseases/*etiology/pathology/physiopathology</keyword><keyword>Spine/pathology/physiopathology</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0940-6719 (Print)&#xD;0940-6719 (Linking)</isbn><accession-num>17426989</accession-num><work-type>Review</work-type><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17426989</url></related-urls></urls><custom2>2200765</custom2><electronic-resource-num>10.1007/s00586-007-0356-4</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_6uD���y������K�
_ENREF_14�D<EndNote><Cite ExcludeYear="1"><Author>Zhong</Author><Year>2009</Year><RecNum>83</RecNum><DisplayText>[15]</DisplayText><record><rec-number>83</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">83</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhong, Z. M.</author><author>Chen, J. T.</author></authors></contributors><auth-address>Department of Orthopedic and Spinal Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China.</auth-address><titles><title>Phenotypic characterization of ligamentum flavum cells from patients with ossification of ligamentum flavum</title><secondary-title>Yonsei Med J</secondary-title><alt-title>Yonsei medical journal</alt-title></titles><periodical><full-title>Yonsei Med J</full-title><abbr-1>Yonsei medical journal</abbr-1></periodical><alt-periodical><full-title>Yonsei Med J</full-title><abbr-1>Yonsei medical journal</abbr-1></alt-periodical><pages>375-9</pages><volume>50</volume><number>3</number><edition>2009/07/02</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Cells, Cultured</keyword><keyword>Collagen Type I/genetics/metabolism</keyword><keyword>Collagen Type II/genetics/metabolism</keyword><keyword>Collagen Type VI/genetics/metabolism</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Ligamentum Flavum/metabolism/*pathology</keyword><keyword>Male</keyword><keyword>Microscopy, Fluorescence</keyword><keyword>Middle Aged</keyword><keyword>Ossification, Heterotopic/metabolism/*pathology</keyword><keyword>Osteocalcin/genetics/metabolism</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Young Adult</keyword></keywords><dates><year>2009</year><pub-dates><date>Jun 30</date></pub-dates></dates><isbn>1976-2437 (Electronic)&#xD;0513-5796 (Linking)</isbn><accession-num>19568599</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19568599</url></related-urls></urls><custom2>2703760</custom2><electronic-resource-num>10.3349/ymj.2009.50.3.375</electronic-resource-num><language>eng</language></record></Cite></EndNote>uD���y������K�
_ENREF_15J
D<EndNote><Cite ExcludeYear="1"><Author>Specchia</Author><Year>2001</Year><RecNum>65</RecNum><DisplayText>[5]</DisplayText><record><rec-number>65</rec-number><foreign-keys><key app="EN" db-id="w955ttexyawsa1eezt35d2zr9pwexzwdsxrz">65</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Specchia, N.</author><author>Pagnotta, A.</author><author>Gigante, A.</author><author>Logroscino, G.</author><author>Toesca, A.</author></authors></contributors><auth-address>Department of Orthopedics, Istituto di Patologia dell&apos; Apparato Locomotore, University of Ancona, Italy. specchia@popcsi.unian.it</auth-address><titles><title>Characterization of cultured human ligamentum flavum cells in lumbar spine stenosis</title><secondary-title>J Orthop Res</secondary-title><alt-title>Journal of orthopaedic research : official publication of the Orthopaedic Research Society</alt-title></titles><periodical><full-title>J Orthop Res</full-title><abbr-1>Journal of orthopaedic research : official publication of the Orthopaedic Research Society</abbr-1></periodical><alt-periodical><full-title>J Orthop Res</full-title><abbr-1>Journal of orthopaedic research : official publication of the Orthopaedic Research Society</abbr-1></alt-periodical><pages>294-300</pages><volume>19</volume><number>2</number><edition>2001/05/12</edition><keywords><keyword>Alkaline Phosphatase/metabolism</keyword><keyword>Bone Matrix/metabolism</keyword><keyword>Cells, Cultured</keyword><keyword>Collagen/metabolism</keyword><keyword>Cyclic AMP/metabolism</keyword><keyword>Fibronectins/metabolism</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>Ligamentum Flavum/drug effects/metabolism/*pathology</keyword><keyword>Lumbosacral Region</keyword><keyword>Middle Aged</keyword><keyword>Osteoblasts/cytology/drug effects/metabolism</keyword><keyword>Osteonectin/metabolism</keyword><keyword>Parathyroid Hormone/pharmacology</keyword><keyword>Reference Values</keyword><keyword>S100 Proteins/metabolism</keyword><keyword>Spinal Fractures/metabolism/pathology</keyword><keyword>Spinal Stenosis/metabolism/*pathology</keyword></keywords><dates><year>2001</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0736-0266 (Print)&#xD;0736-0266 (Linking)</isbn><accession-num>11347704</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11347704</url></related-urls></urls><electronic-resource-num>10.1016/S0736-0266(00)00026-7</electronic-resource-num><language>eng</language></record></Cite></EndNote>sD���y������K�	_ENREF_5b���������666666666vvvvvvvvv666666>666666666666666666666666666�6666666666�666666666666hH66666666666666666666666666666666666666666666666666666666666666666�62���� 0@P`p������2(�� 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p��8X�V~PJ_HmH	nH	sH	tH	@`�@8w4NormalCJ_HaJmH	sH	tH	DA`�DDefault Paragraph FontRi�R�Table Normal�4�
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