Hiroyoshi Ogasa

Effects of Basic Fibroblast Growth Factor on the Repair of Large Osteochondral Defects of Articular Cartilage in Rabbits: Dose–Response Effects and Long-Term Outcomes

Articular cartilage possesses a limited capacity for self-renewal. The regenerated tissue often resembles fibrocartilage-like tissue rather than hyaline cartilage, and degeneration of the articular surface eventually occurs. The purpose of this study was to investigate the effect of basic fibroblast growth factor (bFGF) on the healing of full-thickness articular cartilage defects. bFGF (0, 10, 50, 100, 250, 500, or 1000 ng) was mixed with collagen gel and implanted into full-thickness articular cartilage defects drilled into rabbit knees. The repaired tissue was examined grossly and histologically, and was evaluated with the use of a grading scale at 4, 12, 24, and 50 weeks. At 4 weeks, treatment with 100 ng of bFGF had greatly stimulated cartilage repair both grossly and histologically in comparison with untreated defects (those filled with plain collagen gel). The average total scores on the histological grading scale were significantly better for the defects treated with bFGF than for the untreated defects. These improvements were evident as long as 50 weeks postoperatively, although slight deterioration was noted in the repaired cartilage. Immunohistochemical staining for type II collagen showed that this cartilage-specific collagen was diffusely distributed in the repaired tissue at 50 weeks. These findings suggest that bFGF may be a practical and important candidate for use in cartilage repair.

Effects of basic fibroblast growth factor on osteoblast-related gene expression in the process of medullary bone formation induced in rat femur

Abstract. The effects of basic fibroblast growth factor (bFGF) on osteogenic differentiation in-vivo were investigated using a rat bone marrow ablation model. bFGF was infused directly into rat femora for 6 days after bone marrow ablation. The contralateral femur was infused with vehicle only and used as control. Bone formation was induced in the rat femoral cavity, and the gene expression of osteoblast markers was examined. Treatment with bFGF at 50 and 100 ng/day significantly enhanced the mRNA levels of osteopontin compared with the levels in the control leg, with increases of 25% and 24%, respectively. In contrast, bFGF infusion at 50 ng/day provoked a significant (nearly 20%) inhibition of expression for type I collagen. Infusion of bFGF at a higher dose exhibited an inhibitory tendency for bFGF action on gene expression. There were no significant changes in alkaline phosphatase and osteocalcin mRNA levels in response to any dose of bFGF. The findings presented here suggest that bFGF modulates osteogenic differentiation in-vivo and may play an important role in the process of bone remodeling.

Continuous infusion of PTH1–34 delayed fracture healing in mice

Hyperparathyroidism, which is increased parathyroid hormone (PTH) levels in the blood, could cause delayed or non-union of bone fractures. But, no study has yet demonstrated the effects of excess continuous PTH exposure, such as that seen in hyperparathyroidism, for fracture healing. Continuous human PTH1–34 (teriparatide) infusion using an osmotic pump was performed for stabilized tibial fractures in eight-week-old male mice to determine the relative bone healing process compared with saline treatment. Radiographs and micro-computed tomography showed delayed but increased calcified callus formation in the continuous PTH1–34 infusion group compared with the controls. Histology and quantitative histomorphometry confirmed that continuous PTH1–34 treatment significantly increased the bone callus area at a later time point after fracture, since delayed endochondral ossification occurred. Gene expression analyses showed that PTH1–34 resulted in sustained Col2a1 and reduced Col10a1 expression, consistent with delayed maturation of the cartilage tissue during fracture healing. In contrast, continuous PTH1–34 infusion stimulated the expression of both Bglap and Acp5 through the healing process, in accordance with bone callus formation and remodeling. Mechanical testing showed that continuously administered PTH1–34 increased the maximum load on Day 21 compared with control mice. We concluded that continuous PTH1–34 infusion resulted in a delayed fracture healing process due to delayed callus cell maturation but ultimately increased biomechanical properties.

Risk Factors Associated With Short-term Clinical Results After Total Hip Arthroplasty for Patients With Rheumatoid Arthritis

Clinical outcomes of total hip arthroplasty for rheumatoid arthritis are reportedly worse than those of total hip arthroplasty for osteoarthritis of the hip. The authors examined pre- and postoperative factors associated with the modified Harris hip score (mHHS). Fifty-one joints of 48 rheumatoid arthritis patients who underwent total hip arthroplasty were studied retrospectively. The authors examined the correlation between preoperative rheumatoid arthritis disease activity (Disease Activity Score in 28 joints-C-reactive protein and C-reactive protein) and mHHS at 1 year after total hip arthroplasty. Furthermore, pre- and postoperative mHHS values were compared between patients with other affected joints and patients with no affected joints in the lower limbs. The mean mHHS improved to 73.5 points postoperatively from 36.4 points preoperatively. Preoperative Disease Activity Score in 28 joints-C-reactive protein and C-reactive protein values were negatively correlated with pre- and postoperative mHHS values. Preoperative mHHS was not significantly different between the affected and not affected groups; however, postoperative mHHS was significantly lower in the affected group than in the not affected group. Total hip arthroplasty showed good clinical results for rheumatoid arthritis at short-term follow-up. However, pre- and postoperative mHHS values were influenced by preoperative rheumatoid arthritis disease activity. Moreover, the presence of additional affected joints in the lower limbs preoperatively resulted in a lower postoperative mHHS. Unlike patients with osteoarthritis, patients with rheumatoid arthritis often have multiple affected joints, which may contribute to a lower mHHS. Comprehensive treatment, including surgery for the other affected joints in the lower limbs, may improve a patients postoperative mHHS. [Orthopedics. 2018; 41(6):e772-e776.].

Morning Stiffness in Rheumatoid Arthritis: Investigating its Relationship with Disease Activity as Assessed by Power Doppler Ultrasonography and Composite Scores

Abstract Objective: This study investigated potential associations of morning stiffness (MS) with rheumatoid arthritis (RA) disease activity and ultrasonography (US). Methods: We conducted a cross-sectional analysis of 100 consecutive patients with RA divided into MS-positive group (n = 38) and MS-negative group (n = 62). US findings, disease activity score in 28 joints (DAS28) and Clinical Disease Activity Index (CDAI) were compared. Results: DAS28, CDAI and the number of power Doppler (PD) signal-positive joints were significantly higher in the MS-positive group (p < 0.01). The number of patients who did not achieve the DAS28 or CDAI remission criteria was significantly higher in the MS-positive group (p < 0.01). When cut-off points were applied, MS duration of ≥10 min was associated with PD signal-positive joints, with a sensitivity of 47.5% and a specificity of 92.3% (area under curve = 0.7087, chi-square test: p < 0.0001). Conclusion: This study showed that in patients with MS duration of ≥10 min, there was a high probability of PD-positive joints in the hand.

Non-union of Osteoporotic Vertebral Fracture

麻痺のない骨粗鬆症性椎体骨折の椎体骨癒合不全例について検討した．対象は3ヶ月以上経過観察可能であった椎体癒合不全例10例11椎体で，男性1例，女性9例で，平均年齢76歳である．X 線前後，側面像に加えて仰臥位側面像を追加し，椎体内 vacumn が存在し椎体幅が増大したものを椎体癒合不全と定義した．治療は軟性または半硬性コルセットを厳密に装着し仰臥位での臥床の禁止を徹底指示した．検討項目として椎体高位，癒合不全の出現時期，椎体圧潰率，骨癒合の有無を検討し，疼痛は VAS で評価した．罹患椎体高位は L1椎体が5例と多かった．初診時から追跡可能であった5例では癒合不全の出現時期は平均3ヶ月であった．圧潰率は初診時52％，癒合不全時32％，最終26％であった．骨癒合の有無は骨癒合ありが6椎体55％に認めたが，完全癒合は2椎体18％であった．疼痛を VAS で評価すると癒合不全診断時平均8.6が最終2.6と低下していたが疼痛残存例が多かった．

Study of Operative Treatment for Osgood-Schlatter's Disease

In 15 cases of Osgood-Schlatters disease, namely total of 18 knees, the excision of bone fragments and plasty of tibial tuberosity were carried out and the results of the these operations were studied.Pain in 16 out of 18 knees (89%) was gone permanently, and the remaining two knees (11%) had signs of slight pain with exercising.All cases returned to sports in early stage. An average period of starting sports after operation was 1.6 monthes.When the isolated fragment is recognized and simptoms continue with conservative treatment, and if they wish to resume sports activity again, an operative treatment is recommended.