Neoadjuvant teriparatide therapy targeting the osteoporotic spine: influence of administration period from the perspective of bone histomorphometry.

OBJECTIVE: Teriparatide (TPTD) is a potent promoter of early-stage osteogenesis and may be a useful adjuvant therapy to reduce complications related to bone fragility in spinal surgery patients with osteoporosis. However, effective neoadjuvant TPTD therapy regimens remain poorly understood. This study aimed to examine the effect of preoperative TPTD administration on cancellous bone with bone histomorphometry and to clarify the timing of preoperative TPTD administration for patients with spinal fusion and osteoporosis. METHODS: In this longitudinal multicenter study, 57 patients with spinal fusion and osteoporosis, who consented to undergo iliac biopsy, were allocated to the following treatment groups: neoadjuvant TPTD therapy group (n = 42) and no neoadjuvant therapy (NTC) group (n = 15). Patients in the TPTD group were categorized into subgroups on the basis of duration of preoperative TPTD administration, as follows: 1 month (n = 9), 2 months (n = 8), 3 months (n = 9), 4 months (n = 7), and 6 months (n = 9). All patient samples were preoperatively double labeled with tetracycline, and iliac biopsies were performed during spinal fusion surgery. Histomorphometric analyses were performed on nondecalcified, thin-sliced specimens. Specimens were classified on the basis of TPTD administration duration and subsequently compared with those of the NTC group. Postoperative complications and Oswestry Disability Index scores were evaluated at 1 and 2 years after surgery. RESULTS: There were no demographic differences between groups. Mineralizing surface/bone surface, a key parameter of dynamic bone formation, started to increase after 1 month of TPTD administration; this increase became significant after 3 months of administration and peaked at 4 months, with a 6-fold increase relative to that of the NTC group. The patients who received preoperative TPTD for 3 months or more had superior clinical results in terms of the osteoporotic complication rate and Oswestry Disability Index scores, except for bisphosphonate-pretreated patients. CONCLUSIONS: When considering neoadjuvant TPTD therapy, the authors recommend at least 3 months of preoperative administration to provide a more substantial anabolic effect from the early postoperative stage.

Experimental arthritis and Porphyromonas gingivalis administration synergistically decrease bone regeneration in femoral cortical defects.

Porphyromonas gingivalis infection can lead to periodontitis and dysbiosis, which are known risk factors for rheumatoid arthritis (RA). We investigated whether P. gingivalis administration affected bone regeneration in mice with or without arthritis. We administered P. gingivalis to male DBA/1 J mice that were or were not sensitised to type II collagen-induced arthritis (CIA). All mice underwent drilling of bilateral femurs. We histologically evaluated new bone regeneration (bone volume of the defect [BVd]/tissue volume of the defect [TVd]) using micro-computed tomography (micro-CT), osteoclast number/bone area, and active osteoblast surface/bone surface (Ob.S/BS). We measured serum cytokine levels and bone mineral density of the proximal tibia using micro-CT. CIA resulted in significantly reduced bone regeneration (BVd/TVd) at all time-points, whereas P. gingivalis administration showed similar effects at 2 weeks postoperatively. CIA resulted in higher osteoclast number/bone area and lower Ob.S/BS at 2 and 3 weeks postoperatively, respectively. However, P. gingivalis administration resulted in lower Ob.S/BS only at 2 weeks postoperatively. During later-stage bone regeneration, CIA and P. gingivalis administration synergistically decreased BVd/TVd, increased serum tumour necrosis factor-α, and resulted in the lowest bone mineral density. Therefore, RA and dysbiosis could be risk factors for prolonged fracture healing.

The polyphenol (-)-epigallocatechin-3-gallate prevents apoA-IIowa amyloidosis in vitro and protects human embryonic kidney 293 cells against amyloid cytotoxicity.

INTRODUCTION: Apolipoprotein A-I (apoA-I) amyloidosis is either a non-hereditary form with deposits of wild-type apoA-I proteins in atherosclerotic plaques or a hereditary form with progressive accumulation of mutant apoA-I proteins in different tissues. Several small polyphenolic molecules reportedly inhibited formation of fibrillar assemblies of some amyloidogenic proteins and their cytotoxicity, but small molecules that inhibit apoA-I fibril formation have never been reported. METHODS: Our methods included a thioflavin-T-binding assay, atomic force microscopy and dot blot and cell-based assays. RESULTS: We showed that (-)-epigallocatechin-3-gallate (EGCG), a tea-derived flavanol, inhibited in vitro fibril formation and disaggregated fibrils preformed by the N-terminal 1-83 fragments of wild-type (WT) apoA-I and the G26R point mutation of apoA-I (apoA-IIowa). We eliminated a common structure recognized by the anti-amyloid antibody OC by incubating apoA-IIowa with EGCG or treating apoA-IIowa fibrils with EGCG, which supported the above observation. In addition, EGCG rescued human embryonic kidney 293 cells from cytotoxicity and attenuated production of reactive oxygen species, which were induced by apoA-IIowa fibrils. CONCLUSIONS: Our results support the concept that EGCG inhibits amyloid fibril formation of various amyloidogenic proteins. Thus, EGCG may be a candidate for providing a structure to develop de novo inhibitors for amyloidosis treatment.

Evaluation of the efficacy of incision and drainage versus hainosankyuto treatment for perianal abscess in infants: a multicenter study.

PURPOSE: We retrospectively compared the short-term outcomes between incision and drainage (ID) and hainosankyuto (TJ-122, Tsumura & Co, Tokyo, Japan) treatment for perianal abscess (PA) in infants. METHODS: We retrospectively examined 48 consecutive patients (median age 129 days; range 19-330 days) who presented with PA over a 3 year period. Group 1 comprised 26 patients who were treated with ID at presentation, and Group 2 comprised 22 patients who were treated with oral TJ-122 at presentation; oral treatment was continued until the disappearance of purulent discharge and resolution of induration at the abscess site. RESULTS: PAs were identified in all 48 patients at presentation. The median duration of follow-up was 26 months (range 13-40 months). At presentation, there were no differences in the gender, age, birth weight, duration of symptoms, skin erosion or prevalence of diarrhea between the two groups. Purulent discharge resolved within a median period of 26 days (range 7-42 days) in Group 2, but persisted for 40 days (range 4-196 days) in Group 1. The induration resolved within a median period of 39 days (range 7-91 days) in Group 2, but persisted for 70 days (range 4-308 days) in Group 1 (p = 0.04). CONCLUSIONS: TJ-122 treatment was more beneficial than ID in treating PA in infants.

Comparative study of skin phototoxicity with three drugs by an in vivo mouse model.

Photosafety evaluation is becoming important during the drug development process in pharmaceutical companies. Both in vitro and in vivo test systems have been developed for the evaluation of phototoxic potential of chemicals. In the present study, we conducted an in vivo phototoxicity test using BALB/c mice. The mice were treated with sparfloxacin, lomefloxacin, or a quinoline derivative orally followed by the irradiation of simulated sunlight, and resulting phototoxic reactions of the ears were assessed. Sparfloxacin and lomefloxacin, but not the quinoline derivative, are well known to cause photoirritation in humans. All three drugs exhibited positive reaction in the 3T3 neutral red uptake phototoxicity test (3T3 NRU PT). In the in vivo test, sparfloxacin and lomefloxacin exhibited positive skin reaction in mice, but the quinoline derivative did not. The results of in vivo phototoxicity test in the mice coincided with phototoxic potential of these drugs in humans. The exposure levels of sparfloxacin or lomefloxacin at the minimum effective dose that exhibited phototoxic reaction in the mice were comparable with those in humans treated with the recommended therapeutic dose.

Successful surgical treatment of angiosarcoma of the spine: a case report.

STUDY DESIGN: Case report. OBJECTIVES: To report primary angiosarcoma of the T8 vertebra, which was successfully managed with en bloc spondylectomy and postoperative chemotherapy. SUMMARY OF BACKGROUND DATA: To the best of our knowledge, the present case is the first documented example of successful treatment of angiosarcoma of the spine. METHODS: Angiosarcoma of the eighth thoracic vertebra was diagnosed in a 48-year-old man with impending neurologic deficit. Imaging findings revealed a nonspecific high-grade lesion. A total spondylectomy of T8 by en bloc resection was performed. The defect of the vertebral body was reconstructed with a apatite-wollastonite glass ceramic prosthesis; moreover, the T6-T10 vertebrae were instrumented by the pedicle screw, hook and rod system. The histologic diagnosis of the excised specimen was high-grade angiosarcoma. Postoperative chemotherapy was implemented to prevent local recurrence and distant metastasis. RESULTS: No sign of local recurrence or metastasis was evident 5 years after surgery. CONCLUSION: This case is the first documented example of successful treatment of angiosarcoma of the thoracic spine. Radiologic findings were nonspecific; consequently, correct diagnosis was established by pathologic examination. Immediate, aggressive operative treatment and postoperative adjuvant chemotherapy afforded a satisfactory outcome.