Disturbance of osteonal bone remodeling and high tensile stresses on the lateral cortex in atypical femoral fracture after long-term treatment with Risedronate and Alfacalcidol for osteoporosis.

An 83 year-old Japanese woman complained of left lateral thigh pain following a low-energy fall 4 months prior to admission. She had been treated for osteoporosis with Risedronate and Alfacalcidol for the previous five years. She was diagnosed with an atypical femoral fracture (AFF) according to the American Society for Bone and Mineral Research (ASBMR) Task Force revised criteria. Radiographs revealed cortical thickening and a transverse radiolucent fracture line in the lateral cortex of the shaft. MRI showed a high intensity signal on the T2WI image 1 cm long in the lateral cortex. The patient had normal levels of bone resorption and formation biomarkers except for low 25(OH) Vitamin D. Double fluorescent labeling was done preoperatively. Due to significant bowing, a corrective osteotomy and intramedullary nailing were performed, and the resected bone wedge was analyzed by bone histomorphometry. Three ground sections of the lateral cortex at the fracture site showed many and large pores, with or without tetracycline labeling. Histomorphometric assessment was done on intracortical pores, classified by a novel criteria, only to assess size of the pores to know prolonged osteoclastic activity and its characteristics of inner surfaces to assess whether bone formation has been occurring or not in labeling period in remodeling cycle, and coalition of multi-pores. Increased size with widespread variation of pores suggested prolonged osteoclastic activity in the reversal/resorptive phase. Bone labeling showed lamellar bone on the endocortical surface. We hypothesize that the case had developed from a regional disturbance of osteonal remodeling in the lateral cortex, in which accumulated microcracks might have initiated a resorption process resulting in resorption cavities, i.e., pores, which became larger due to prolonged activity of secondary osteoclasts. Various sized pores could form lamellar bone, still forming at the time of biopsy, some had formed lamellar bone, but stopped to form before labeling and not to start to form at all, probably due to incomplete coupling. Endocortical lamellar bone might had started to resorbed to smooth off endocortical surface, followed by formation of lamellar bone. The endocortical bone formation was assessed and its formation period is about 2.7 years. A finite element analysis using preoperative CT data revealed high tensile stresses on the lateral aspect of the femur. Histomorphometric results suggest that there might be more pores in the tensile area than the compressive area. These findings may subsequently connect accumulation of microcracks, an increase of size and number of pores and coalition and subsequent fracture in the lateral cortex.

Postharvest Properties of Ultra-Late Maturing Peach Cultivars and Their Attributions to Melting Flesh (M) Locus: Re-evaluation of M Locus in Association With Flesh Texture.

The postharvest properties of two ultra-late maturing peach cultivars, "Tobihaku" (TH) and "Daijumitsuto" (DJ), were investigated. Fruit were harvested at commercial maturity and held at 25°C. TH exhibited the characteristics of normal melting flesh (MF) peach, including rapid fruit softening associated with appropriate level of endogenous ethylene production In contrast, DJ did not soften at all during 3 weeks experimental period even though considerable ethylene production was observed. Fruit of TH and DJ were treated with 5,000 ppm of propylene, an ethylene analog, continuously for 7 days. TH softened rapidly whereas DJ maintained high flesh firmness in spite of an increase in endogenous ethylene production, suggesting that DJ but not TH lacked the ability to be softened in response to endogenous and exogenous ethylene/propylene. DNA-seq analysis showed that tandem endo-polygalacturonase (endoPG) genes located at melting flesh (M) locus, Pp-endoPGM (PGM), and Pp-endoPGF (PGF), were deleted in DJ. The endoPG genes at M locus are known to control flesh texture of peach fruit, and it was suggested that the non-softening property of DJ is due to the lack of endoPG genes. On the other hand, TH possessed an unidentified M haplotype that is involved in determination of MF phenotype. Structural identification of the unknown M haplotype, designated as M 0, through comparison with previously reported M haplotypes revealed distinct differences between PGM on M 0 haplotype (PGM-M0 ) and PGM on other haplotypes (PGM-M1 ). Peach M haplotypes were classified into four main haplotypes: M 0 with PGM-M0 ; M 1 with both PGM-M1 and PGF; M 2 with PGM-M1 ; and M 3 lacking both PGM and PGF. Re-evaluation of M locus in association with MF/non-melting flesh (NMF) phenotypes in more than 400 accessions by using whole genome shotgun sequencing data on database and/or by PCR genotyping demonstrated that M 0 haplotype was the common haplotype in MF accessions, and M 0 and M 1 haplotypes were dominant over M 2 and M 3 haplotypes and co-dominantly determined the MF trait. It was also assumed on the basis of structural comparison of M haplotypes among Prunus species that the ancestral haplotype of M 0 diverged from those of the other haplotypes before the speciation of Prunus persica.

Comparison of once-weekly teriparatide and alendronate against new osteoporotic vertebral fractures at week 12.

The objective of the present multicenter randomized study was to compare weekly teriparatide with alendronate in their inhibition of vertebral collapse, effects on delayed union, pain relief, and improvement of quality of life (QOL) in women with new osteoporotic vertebral fractures within 1 week after onset of the fracture. Patients were randomly allocated to the teriparatide and alendronate groups. Vertebral collapse, low back pain assessed by a visual analog scale, and QOL assessed by EuroQol 5 dimension at weeks 1, 2, 4, 8, and 12 after the start of the treatment were compared between the groups. Lumbar bone mineral density (BMD) at baseline and week 12 and the rate of delayed union at week 12 were also compared. Each group consisted of 48 subjects. Vertebral collapse progressed over time in both groups, with no significant difference between the groups. Pain on rising up from lying position, turning over in bed, and resting in the lying position improved over time in both groups, with no significant difference between the groups. There were no significant differences in increase in BMD and delayed union. QOL in the teriparatide group showed significant improvement in comparison with that in the alendronate group at week 12. The weekly formulation of teriparatide showed comparable inhibition of vertebral collapse, increase in BMD, promotion of bone union, and improvement of pain and significant improvement of QOL at week 12 in comparison with alendronate in patients with a new osteoporotic vertebral fracture within 1 week after onset of the fracture. The weekly formulation of teriparatide may have improved components of QOL other than pain at week 12.

Prediction of fracture lines of the calcaneus using a three-dimensional finite element model.

The various lines of calcaneal fractures indicate their complex nature and make their treatment challenging. There is still much debate regarding the position and direction of these fracture lines, even for the primary fracture line. The computed tomography-based finite element model is known to provide accurate predictions of fracture loads and virtual fracture locations for the femur and distal radius. This study aimed to establish how to predict the calcaneus fracture lines using the computed tomography-based finite element model for patients with contralateral calcaneal fractures and to investigate whether the predicted lines were similar to those of the fractured calcaneus. The calcanei of five men and two women aged 44-77 years (average age, 60 years) with contralateral calcaneal fractures were analyzed. To assess the precision of the predicted fracture lines of the contralateral calcanei, they were compared with the fracture locations found by three-dimensional models of the calcanei. The fracture lines of the finite element model simulated the actual fracture lines and diagnosed joint depression types of fractures (five cases) and tongue types (two cases), but only under certain conditions for each case. This trial simulated calcaneal fractures using a patient-specific computed tomography-based nonlinear finite element model. Therefore, we suggest that it is possible to reproduce calcaneal fractures using the finite element model. It was possible to predict with precision the actual calcaneal fracture for each patient and to reproduce fracture conditions. Therefore, this method is valuable because it can provide an understanding of the pathomechanism of calcaneal fractures. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:483-489, 2019.

Study of Atypical Femoral Fracture Cases Coupled in a Multicenter Study.

UNLABELLED: There are several causes of atypical femoral fractures (AFF) in elderly Japanese patients, including longterm bisphosphonate (BP) use or bowed femoral shaft stress fractures, but the available sample size for examining AFF etiology in a single institution is limited. The purpose of this study was to categorize the characteristics of AFF by analyzing the data compiled on patients treated at our hospital and at affiliated institutes. This multicenter, retrospective, observational study included 34 AFF cases (bilateral AFF 10) in one male and 23 female patients (age range 30-90 years, mean age 73.0 years). Evaluation measures included the presence/absence of BP use, duration of BP use, history of other drug use, presence/absence of comorbidities, fracture site, presence/absence of femoral lateral bowing, bone biopsy parameters, and time to bone union. Nineteen patients were prescribed BP for osteoporosis (duration range 4-10 years, mean duration 6.1 years). Subtrochanteric and femoral shaft fractures were seen in 16 and 18 cases, respectively (complete fractures 22, incomplete fractures 12). Femoral lateral bowing (n = 16) occurred with femoral shaft fractures. Mean time to bone union was 9.0 months (complete fractures 11.3 months, incomplete fractures 3.7 months). AFF could be substantially caused by three factors: BP use, drugs other than BP/comorbidity, and femoral lateral bowing. Twenty four patients were classified as having BP-related-type (n = 2), drug/comorbidity-type (n = 3), lateral bowing-type (n = 2), or mixed-type (n = 17) AFF. AFF etiology cannot be explained by a single cause; thus, a multifactorial etiology, including poor bone quality due to mutual interactions and mechanical stress, seems to be responsible for the occurrence of AFF. LEVEL OF EVIDENCE: Ⅳ diagnostic.

Production of ergothioneine by Methylobacterium species.

Metabolomic analysis revealed that Methylobacterium cells accumulate a large amount of ergothioneine (EGT), which is a sulfur-containing, non-proteinogenic, antioxidative amino acid derived from histidine. EGT biosynthesis and its role in methylotrophy and physiology for plant surface-symbiotic Methylobacterium species were investigated in this study. Almost all Methylobacterium type strains can synthesize EGT. We selected one of the most productive strains (M. aquaticum strain 22A isolated from a moss), and investigated the feasibility of fermentative EGT production through optimization of the culture condition. Methanol as a carbon source served as the best substrate for production. The productivity reached up to 1000 µg/100 ml culture (1200 µg/g wet weight cells, 6.3 mg/g dry weight) in 38 days. Next, we identified the genes (egtBD) responsible for EGT synthesis, and generated a deletion mutant defective in EGT production. Compared to the wild type, the mutant showed better growth on methanol and on the plant surface as well as severe susceptibility to heat treatment and irradiation of ultraviolet (UV) and sunlight. These results suggested that EGT is not involved in methylotrophy, but is involved in their phyllospheric lifestyle fitness of the genus in natural conditions.

Weekly Teriparatide for Delayed Unions of Atypical Subtrochanteric Femur Fractures.

INTRODUCTION: The occurrence of atypical femur fractures (AFFs) in patients on prolonged bisphosphonate treatment has been gaining medical attention, but the use of pharmacotherapy for these fractures has not been explored in detail. The authors describe a case of AFFs successfully treated with once-weekly administration of 56.5 µg teriparatide (TPTD). CASE PRESENTATION: The patient was a 74-year-old female patient who had been taking alendronate for approximately 6 years and who suffered with a fall while walking. X-rays revealed a subtrochanteric right femur fracture. The contralateral femur showed cortical thickening and a transverse radiolucent fracture line. Based on these specific features, the patient was diagnosed with AFF. The patient underwent osteosynthesis with intramedullary nailing for the right fracture. Alendronate treatment was discontinued. Low-intensity pulsed ultrasonography therapy did not affect the healing of the fracture with delayed union, even after 3 months of application. Prophylactic osteosynthesis was performed for the subtrochanteric left femur. Bone tissue collected from the left fracture site during surgery showed severe suppression of bone turnover. Union of bilateral femurs was achieved after 3 months of a once-weekly administration of TPTD. CONCLUSION: Once-weekly TPTD treatment is shown to be beneficial for improving the healing of AFFs showing delayed union.

Dialyzability of the antiepileptic drug zonisamide in patients undergoing hemodialysis.

PURPOSE: The influence of hemodialysis on plasma zonisamide (ZNS) concentration has not been clarified. In this study, the dialyzability of ZNS during hemodialysis was investigated in four ZNS-treated women with systemic lupus erythematosus complicated by seizures. METHODS: The total and unbound plasma concentrations of ZNS were measured before and after hemodialysis. The concentration of ZNS in the spent dialysate also was determined. RESULTS: The reduction in plasma ZNS concentration after a 4.5-h hemodialysis was 52.0 +/- 7.6%, and the dialyzer (BLF-16GW) clearance of ZNS was 55.1 +/- 7.0 ml/min. Dosage was gradually increased up to 200 to 500 mg/day, and the seizures were controlled satisfactorily. CONCLUSIONS: The plasma concentration of ZNS was reduced by approximately 50% during one session of dialysis. For patients undergoing daytime hemodialysis sessions every 2 or 3 days, the usual dosage of ZNS (4-8 mg/kg/day) may be prescribed once a day in the evening. If seizures occur after hemodialysis, a supplemental daily dose may be prescribed in the morning.