Identification of a novel COL2A1 mutation (c.1744G>A) in a Japanese family: a case report.

INTRODUCTION: Mutations in the gene encoding the type II collagen gene (COL2A1) have been found to affect the entire skeletal system. Recently, inheritable skeletal dysplasia caused by novel COL2A1 mutations has been linked to an inherited disease of the hip joint that neither involves the entire skeletal system nor is characterized by the presence of concomitant disorders, such as spinal or ocular abnormalities. CASE PRESENTATION: A 27-year-old Japanese woman previously diagnosed with avasucular necrosis (AVN) of the femoral head on the basis of radiological findings was referred to the study site for surgical management of a painful hip joint. She had no history of disease but suffered from bilateral hip joint lesions. Analysis of her pedigree revealed that bilateral hip joint lesions affected more than three generations of her family. Based on these findings, haplotype analysis of her and her family members was performed by examining select candidate genes from the critical interval for epiphyseal dysplasia of the femoral head on 12q13 and sequencing the promoter and exonic regions of COL2A1. CONCLUSION: A novel COL2A1 mutation (c.1744G>A) was identified within one Japanese family.

Rotational acetabular osteotomy with resection of the capital drop and double floor for advanced osteoarthritis of the hip.

Rotational acetabular osteotomy (RAO) is an established joint preservation technique for early stage osteoarthritis (OA). To extend the application of RAO for advanced OA with significant osteophyte formation, we added intraarticular procedures including removal of the double floor and the capital drop to create medialisation and better coverage of the femoral head.
The procedures were performed for seven joints with advanced OA. The average age of patients at surgery was 39 years. The follow-up periods ranged from five to 23 years. The capital drop was resected in five joints and both the capital drop and the double floor were removed in the other two joints.
The Japanese Orthopaedic Association Hip Score improved from 53 points before surgery to 69 at the latest follow-up. The range of flexion was decreased. The centre-edge angle, Sharp angle and acetabular head index were significantly improved. The femoral head was medialised 5 mm by surgery. Three joints (43%) showed progression of osteoarthritis. One joint (14%) needed replacement at seven years after RAO. Resection of the capital drop and curtain osteophyte with RAO improved joint congruity and medialisation of the femoral head, but decreased the range of motion of the joint due to increased bony coverage. Progression of degeneration of the joint is not preventable. We abandoned these procedures for advanced osteoarthritis of the hip joint especially in older patients who were suitable for replacement arthroplasty.

Total hip arthroplasty with an HPF stem: the radiological findings around the cementless anatomical-shape stem for developmental dysplasia of the hip.

BACKGROUND: We developed the HPF stem to suit the Japanese femoral bone marrow canal in developmental dysplasia of the hip. This anatomical-shape cementless stem improves canal occupation by the lateral and anterior flares. We report the clinical performance of the stem and details of the change in the X-rays, especially of the femoral side. MATERIALS AND METHODS: We investigated 53 joints of total hip arthroplasty using the stem in 48 cases. The follow-up period was 8 years on average. We checked the Harris hip score (HHS) for clinical assessment. Existence of postoperative thigh pain was also investigated. For radiological assessment, the direction of stem insertion and initial fixation mode immediately after surgery were estimated. At the latest follow-up, we estimated the radiological findings of bone atrophy, spot welds, radiolucent zone, osteolysis, and sinking of the stem over 2 mm. Biological fixation was classified into four types: bone ingrowth, ingrowth suspected, suboptimum, and unstable fixation. RESULTS: HHS was improved from 44 points before surgery to 92 points at the final follow-up. Light thigh pain appeared temporarily in three joints after surgery. Press-fit was achieved in femurs including total fit in 12 femurs, proximal fit in 4, middle fit in 25, and distal fit in 2. First degree stress shielding was seen in 25 femurs and second degree in 28. Forty-eight joints showed bone-ingrowth fixation, and five joints were ingrowth-suspected. DISCUSSION: The clinical performance was excellent. Total or proximal fit was seen in only 30%. In these joints, cortical hypertrophy at the middle part of the stem and slight proximal bone atrophy appeared frequently, suggesting the stress transmission to the stem middle or distal portion, and there is a limit to the stress shielding evasion by the anatomical-shape stem.

Comparison of cardiovascular parameters between patients with ossification of posterior longitudinal ligament and patients with cervical spondylotic myelopathy.

SUMMARY OF BACKGROUND DATA: Ossification of the posterior longitudinal ligament (OPLL) is an ectopic bone formation in the ligament tissue of the spine, causing myelopathy as a result of chronic pressure on the spinal cord and nerve roots. It has been further categorized into 4 types, that is, segmental, continuous, mixed types, and the other types; however, differences in the detail of the progression in the ossification and natural history of the disease among these types have not been clarified. OBJECTIVE: To find out the systemic feature, which has relevance to the disease state of OPLL. METHODS: To characterize these types, we conducted an investigation of cardiovascular factors [blood pressure, blood loss during or after surgery, bleeding time, coagulation factors (prothrombin test, activated partial thromboplastin time)] among OPLL, cervical spondylotic myelopathy (CSM), and subtypes of OPLL (continuous, mixed, segmental, and the other types). STUDY DESIGN: Retrospective case series. RESULTS: These parameters of patients with cervical spondylotic myelopathy were used as a control (CSM patients). Although there was no significant difference in bleeding time and coagulation factors, blood loss after surgery of OPLL patients was significantly higher than that of CSM patients (P<0.01). Furthermore, blood loss of patients with continuous type of ossification was significantly higher (P<0.05) than that of patients with segmental type of ossification, which was nearly equal to that of CSM patients. Blood loss of patients with mixed type of ossification showed the value of the middle of segmental and continuous types.

A functional RNAi screen for Runx2-regulated genes associated with ectopic bone formation in human spinal ligaments.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic ossification in the spinal ligaments, which enlarges with time and compresses the spinal cord, resulting in serious neurological symptoms. We previously reported that Runx2 expression was enhanced in spinal ligament cells from OPLL patients (OPLL cells). To clarify genes regulated by Runx2, Runx2 expression was first enhanced by culturing primary OPLL cells in osteogenic medium (OS induction) and then inhibited by siRNAs targeted to Runx2. DNA microarray demonstrated that in addition to chondrogenic factors such as connective tissue growth factor and cartilage oligomeric matrix protein, angiopoietin-1 was also significantly increased by OS induction and decreased by siRNAs for Runx2 in OPLL cells, suggesting that these genes are regulated by Runx2. However, these changes were not observed in non-OPLL control cells (from cervical spondylotic myelopathy patients). Furthermore, Runx2 was not decreased by siRNAs for angiopoietin-1. OS induction and RNAi inhibition of angiopoietin-1 expression was also observed in osteoblasts. Both siRNAs for Runx2 and angiopoietin-1 completely inhibited aggrecan-1 expression. These results suggest that angiopoietin-1 is downstream of Runx2 in both OPLL primary cells and osteoblasts. Angiopoietin-1 may play an important role in ectopic ossification.

Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments.

To reveal the involvement of extracellular nucleotides in the ossification process in ossification of the posterior longitudinal ligament of the spine (OPLL), the mRNA expression profiles of P2 purinoceptors, mechanical stress-induced ATP release, and ATP-stimulated expression of osteogenic genes were analyzed in ligament cells derived from the spinal ligament of OPLL patients (OPLL cells) and non-OPLL cells derived from the spinal ligaments of cervical spondylotic myelopathy patients as a control. The extracellular ATP concentrations of OPLL cells in static culture were significantly higher than those of non-OPLL cells, and this difference was diminished in the presence of ARL67156, an ecto-nuclease inhibitor. Cyclic stretch markedly increased the extracellular ATP concentrations of both cell types to almost the same level. P2Y1 purinoceptor subtypes were intensively expressed in OPLL cells, but only weakly expressed in non-OPLL cells. Not only ATP addition but also cyclic stretch raised the mRNA levels of alkaline phosphatase and osteopontin in OPLL cells, which were blocked by MRS2179, a selective P2Y1 antagonist. These increases in the expression of osteogenic genes were not observed in non-OPLL cells. These results suggest an important role of P2Y1 and extracellular ATP in the progression of OPLL stimulated by mechanical stress.