The effects of teriparatide on acceleration of bone healing following atypical femoral fracture: comparison between daily and weekly administration.

We compared the effectiveness of promoting bone healing between two teriparatide preparations for atypical femoral fracture (AFF). A total of 45 AFFs were included in this study, and we compared the duration of bone union. Teriparatide administered by daily injection enhanced bone union more than weekly administration in complete AFFs. INTRODUCTION: The efficacy of teriparatide for atypical femoral fracture (AFF) has been recently reported. Although two different teriparatide preparations can be used to treat osteoporosis in Japan, daily or weekly injection, all previous reports on the effectiveness of teriparatide for AFF only examined daily injection formulations. Therefore, we compared the promotion of bone healing between the two teriparatide preparations for AFF. METHODS: A total of 45 consecutive AFFs in 43 Japanese patients were included in this study. They received either a daily 20-µg teriparatide injection (daily group; n = 32) or a once-a-week 56.5-µg teriparatide injection (weekly group; n = 13). We compared the clinical background and duration of bone union between these two groups. RESULTS: When all patents were included, the fracture healing time was not significantly different between the two groups. Only patients with complete AFFs had significantly fewer daily bisphosphonate or denosumab injections than the weekly group (P < 0.05). The fracture healing time in the daily group (6.1 ± 4.1 months) was significantly shorter than that in the weekly group (10.1 ± 4.2 months) (P < 0.05). Even if the influence of bisphosphonate or denosumab usage was excluded, a similar significant difference was observed in the fracture healing time (P < 0.05). There was no significant difference between the two groups among patients with incomplete AFFs. CONCLUSIONS: Daily teriparatide injections enhance bone union more than weekly injections in complete AFF patients.

TRPV1, ASICs and P2X2/3 expressed in bone cells simultaneously regulate bone metabolic markers in ovariectomized mice.

OBJECTIVES: Nociceptors are expressed at peripheral terminals of neurons. Recent studies have shown that TRPV1, a nociceptor, is expressed in bone tissue and regulates bone metabolism. We have demonstrated that a TRPV1 antagonist improved pain-like behavior in ovariectomized (OVX) mice. The aim of this study was to determine whether nociceptors, including TRPV1, acid-sensing ion channel (ASIC) and P2X2/3 are expressed in bone cells, and to examine the effects of nociceptor antagonists on bone metabolism. METHODS: The expression of nociceptors in femoral bone tissue and cultured bone marrow cells in OVX and sham-operated mice were examined. The effects of nociceptor antagonists on the up-regulated expression of bone metabolic markers, Runx2, Osterix, osteocalcin and RANKL, were also examined. RESULTS: TRPV1, ASIC 2 and 3, and P2X2 and 3, were expressed in bone tissue and bone marrow cells, and the expression levels of ASIC1 and 2, and P2X2 were significantly increased in OVX mice in comparison with those in sham mice. Treatment with nociceptor antagonists significantly inhibited the expression of bone metabolic markers in OVX mice. CONCLUSION: An array of nociceptors, TRPV1, ASICs and P2X2/3, could simultaneously regulate not only increases in skeletal pain but also bone turnover in OVX mice.

Reconstructed animation from four-phase grip MRI of the wrist with ulnar-sided pain.

In order to visualize dynamic variations related to ulnar-sided wrist pain, animation was reconstructed from T2* coronal-sectioned magnetic resonance imaging in each of the four phases of grip motion for nine wrists in patients with ulnar pain. Eight of the nine wrists showed a positive ulnar variance of less than 2 mm. Ulnocarpal impaction and triangular fibrocartilage complex injury were assessed on the basis of animation and arthroscopy, respectively. Animation revealed ulnocarpal impaction in four wrists. In one of the four wrists, the torn portion of the articular disc was impinged between the ulnar head and ulnar proximal side of the lunate. In another wrist, the ulnar head impacted the lunate directly through the defect in the articular disc that had previously been excised. An ulnar shortening osteotomy successfully relieved ulnar wrist pain in all four cases with both ulnocarpal impaction and Palmer's Class II triangular fibrocartilage complex tears. This method demonstrated impairment of the articular disc and longitudinal instability of the distal radioulnar joint simultaneously and should be of value in investigating dynamic pathophysiology causing ulnar wrist pain.

Arthrography in thumb polydactyly with bifurcation at the interphalangeal or metacarpophalangeal joints provides practical information at surgery.

We carried out arthrography in 19 thumbs of 18 patients in whom duplication was observed at the interphalangeal (Wassel type II) or metacarpophalangeal (Wassel type IV) joints on radiographs. The average age at surgery was 12.3 months and average duration of post-surgical follow-up was 21.3 months. Based on the arthrographic findings, the types of cartilaginous connections were subdivided into five groups. In group 1, there was a cartilaginous connection at the base of duplicated phalanges. In group 2, there was a cartilaginous connection of the radial digit between the distal and proximal phalanges, or between the proximal phalanx and metacarpal. In group 3, the phalanges separated at a common joint without any cartilaginous connection. In group 4, the radial digit demonstrated fibrous attachment to the capsule without any joint formation. In group 5, each joint was completely separated without any cartilaginous connection. These arthrographic findings could not be detected on radiographs. Different surgical procedures were carried out according to the form of cartilaginous connection.

Improvement in pinch function after surgical treatment for thumb in the plane of the hand.

Thumb in the plane of the hand (TPH) is a congenital deformity in which the nail plane of the radial-most digit is parallel to that of other digits, but structurally the digit retains the characteristics of a thumb. Four hands from four patients were retrospectively diagnosed as having TPH, with the underlying congenital conditions being symbrachydactyly, cleft hand and constriction band syndrome. Thumb web-plasty was carried out in all hands; one required additional rotation osteotomy of the metacarpal. Postoperative hand function was markedly improved and pinch function was possible in all cases. In most cases of TPH, the thumb has the potential to act in opposition, indicating that a thumb web-plasty is worth considering as an initial procedure.

Diffusion-weighted magnetic resonance imaging of the ulnar nerve in cubital tunnel syndrome.

Diffusion-weighted images based on magnetic resonance reveal the microstructure of tissues by monitoring the random movement of water molecules. In this study, we investigated whether this new technique could visualize pathologic lesions on ulnar nerve in cubital tunnel. Six elbows in six healthy males without any symptoms and eleven elbows in ten patients with cubital tunnel syndrome underwent on diffusion-weighted MRI. No signal from the ulnar nerve was detected in normal subjects. Diffusion-weighted MRI revealed positive signals from the ulnar nerve in all of the eleven elbows with cubital tunnel syndrome. In contrast, conventional T2W-MRI revealed high signal intensity in eight elbows and low signal intensity in three elbows. Three elbows with low signal MRI showed normal nerve conduction velocity of the ulnar nerve. Diffusion-weighted MRI appears to be an attractive technique for diagnosis of cubital tunnel syndrome in its early stages which show normal electrophysiological and conventional MRI studies.

Effect of triangular ligament tears on distal radioulnar joint instability and evaluation of three clinical tests: a biomechanical study.

Using 11 fresh/frozen cadaver specimens, instability of the distal radioulnar joint (DRUJ) during passive wrist motion was measured by motion analysis and three clinical tests (ulno-carpal stress test, piano-key test, and DRUJ ballottement test) were performed. Release of the triangular ligament from the palmar approach was performed to simulate instability of the DRUJ. Displacement of the distal radius against the ulnar head was measured at various degrees of forearm rotation. Release of the triangular ligament at the ulnar fovea and around the base of the ulnar styloid process caused various degrees of DRUJ instability during passive wrist motion. After complete triangular ligament release, only the DRUJ ballottement test demonstrated a statistically significant degree of accuracy in the evaluation of distal radioulnar joint instability.

Corrective osteotomy for volar instability of the distal radioulnar Joint associated with radial shaft malunion.

Volar instability of the distal radioulnar joint is an uncommon wrist disorder. We report three cases of recurrent volar instability of the distal radioulnar joint secondary to fracture of the radial shaft. In all cases, X-rays showed a volar apex deformity of the radial shaft. Opening wedge osteotomy and iliac bone grafting was performed on the distal diaphysis of the radius instead of on the radial shaft, in order to adjust the distal radioulnar joint more easily. Pre-operative dislocations and painful clunks disappeared in all three patients. However, slight instability of the distal radioulnar joint remained in all cases. Osteoarthritis of the distal radioulnar joint was noted in one patient 31 months after the operation. All of the patients were satisfied with the results and did not desire further operations.

A highly potent 26,27-Hexafluoro-1a,25-dihydroxyvitamin D3 on calcification in SV40-transformed human fetal osteoblastic cells.

26,27-hexafluoro-1a,25-dihydroxyvitamin D3 (F6-D3) has been reported to be 5-10 times more potent than 1a,25-dihydroxyvitamin D3[1,25(OH)2D3] in biological systems in vivo and in vitro. However, the effect of F6-D3 on bone formation has yet to be clarified. In the present study, we investigated the effect of F6-D3 on SV40-transfected human fetal osteoblastic cells (SV-HFO) and found it to be about 100 times greater than that of 1,25(OH)2D3 in stimulating calcification. F6-D3 was also about 100 times more effective than 1,25(OH)2D3 in enhancing the expression of mRNA for alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In the presence of 10?8 M F6-D3 and 10?6 M 1,25(OH)2D3, the calcification began on day 9 and increased up to day 19. Expression of mRNA for ALP and OCN reached a maximum on day 4 and thereafter declined. On the other hand, when osteoblastic cells were incubated with a low level of [1b-3H]-F6-D3- or [1b-3H]-1,25(OH)2D3, each radioactive peak could not be detected. However, on the incubation of osteoblastic cells and radioactive substrate in the presence of ketoconazole, a selective inhibitor of CYP24, a clear peak for each substrate was detected. This suggested that F6-D3 as well as 1,25(OH)2D3 is metabolized by CYP24. Osteoblastic cells were incubated with 10?8 M[1b-3H]-F6-D3 or 10?8 M[1b-3H]-1,25(OH)2D3 for 4, 9, and 14 days. A small peak of 1,25(OH)2D3 was observed and thereafter its level decreased. In addition, two unknown peaks increased when the culture period was extended. In the case of F6-D3, peaks of F6-D3 and 26,27-hexafluoro-23-oxo-1a,25(OH)2D3(23-oxo-F6) were clearly detected, the latter being about 4 times higher than the former. Both peaks was retained up to day 14. The amount of unlabeled F6-D3 and 23-oxo-F6 calculated from the specific radioactivity in the cells may be similar to the amount of 1,25(OH)2D3 and its metabolites. The strong activity of F6-D3 in stimulating calcification may be due to the fact that F6-D3 is much more potent than 1,25(OH)2D3 in enhancing the expression of mRNA for ALP, OCN, and OPN and that the amount of F6-D3 and 23-oxo-F6 accumulated in the cells is much greater than that of 1,25(OH)2D3 and its metabolite.

Phase-independent inhibition by retinoic acid of mineralization correlated with loss of tetranectin expression in a human osteoblastic cell line.

We have recently reported that retinoic acid inhibits dexamethasone-induced alkaline phosphatase activity and mineralization in human osteoblastic cell line SV-HFO. In this study, we show that this inhibitory effect on alkaline phosphatase activity depends on the stage of cell differentiation; however, expression of tetranectin, which is a recently reported bone matrix protein, was completely inhibited by treatment with retinoic acid, irrespective of the stage of cell differentiation. Similarly, mineral deposit formation in SV-HFO cells was phase-independently inhibited by retinoic acid. To our knowledge, this is the first report that retinoic acid downregulates the tetranectin expression in human osteoblastic cells independent of the stage of cell differentiation, and is correlated with inhibition of mineralization.

Hormonal regulation of tissue-specific ectopic expression of an Arabidopsis endoplasmic reticulum-type omega-3 fatty acid desaturase (FAD3) gene.

A common feature of the membrane lipids of higher plants is a large content of polyunsaturated fatty acids, which typically consist of dienoic and trienoic fatty acids. Two types of omega-3 fatty acid desaturase. which are present in the plastids and in the endoplasmic reticulum (ER), respectively, are responsible for the conversion of dienoic to trienoic fatty acids. To establish a system for investigating the tissue-specific, and hor-mone-regulated expression of the ER-type desaturase gene (FAD3), transgenic plants of Arabidopsis thaliana (L.) Heynh. containing the firefly luciferase gene (LUC) fused to the FAD3 promoter (FAD3::LUC) were constructed. At different times during plant development, FAD3::LUC was actively expressed at two major sites, the vegetative shoot meristem and the floral organs. Transgenic plants with LUC fused to the promoter of FAD7 (FAD7::LUC) which encodes plastid-type desaturase, were also constructed. FAD3::LUC and FAD7::LUC were expressed in the same organs during reproductive growth, but not during vegetative growth. In plants exposed to both auxin and cytokinin, FAD3::LUC expression was ectopically induced in the root tissues. However, this induction by auxin and cytokinin was inhibited when abscisic acid was also present. FAD3::LUC expression could be induced in the roots by auxin and cytokinin if the hormones were applied during vegetative growth, but not if they were applied during germination or reproductive growth. Analysis of the fatty acid composition in the roots of Arabidopsis fad mutant and wild-type plants confirmed that the response of FAD3::LUC expression to various hormones reflected the response of endogenous FAD3 gene expression. These results suggest that the expression of ER-type desaturase is regulated through synergistic and antagonistic hormonal interactions, and that such hormonal regulation and the tissue specificity of the expression of this gene are further modified in accordance with the growth phase in plant development.

Mice with a targeted deletion of the tetranectin gene exhibit a spinal deformity.

Tetranectin is a plasminogen-binding, homotrimeric protein belonging to the C-type lectin family of proteins. Tetranectin has been suggested to play a role in tissue remodeling, due to its ability to stimulate plasminogen activation and its expression in developing tissues such as developing bone and muscle. To test the functional role of tetranectin directly, we have generated mice with a targeted disruption of the gene. We report that the tetranectin-deficient mice exhibit kyphosis, a type of spinal deformity characterized by an increased curvature of the thoracic spine. The kyphotic angles were measured on radiographs. In 6-month-old normal mice (n = 27), the thoracic angle was 73 degrees +/- 2 degrees, while in tetranectin-deficient 6-month-old mice (n = 35), it was 93 degrees +/- 2 degrees (P < 0.0001). In approximately one-third of the mutant mice, X-ray analysis revealed structural changes in the morphology of the vertebrae. Histological analysis of the spines of these mice revealed an apparently asymmetric development of the growth plate and of the intervertebral disks of the vertebrae. In the most advanced cases, the growth plates appeared disorganized and irregular, with the disk material protruding through the growth plate. Tetranectin-null mice had a normal peak bone mass density and were not more susceptible to ovariectomy-induced osteoporosis than were their littermates as determined by dual-emission X-ray absorptiometry scanning. These results demonstrate that tetranectin plays a role in tissue growth and remodeling. The tetranectin-deficient mouse is the first mouse model that resembles common human kyphotic disorders, which affect up to 8% of the population.

Horse-related injuries in a thoroughbred stabling area in Japan.

To investigate the demographic details and patterns of injuries related to horse handling, we reviewed 637 horse-related injuries in 581 stable- or stud-workers in a representative area of thoroughbred stabling in Japan. We found that (1) injuries occurred most frequently in a group of a relatively young workers, with a seasonal variation; (2) the principal mechanism of injury was kicks, which accounted for 39.2% of all injuries, including 11 serious and one lethal visceral injuries; (3) the upper half of the body was more frequently involved than the lower half; and (4) the peripheral bones (hand and foot) and the ribs accounted for more than half of 148 fractures. These findings are distinct from those in horse-riding injuries reported in the literature and emphasize the importance in developing preventive strategies specifically for workers in horse stables.

Tetranectin in slow intra- and extrafusal chicken muscle fibers.

Tetranectin is a C-type lectin that occurs in the mammalian musculoskeletal system. In the present report we describe the first studies on an avian tetranectin. A full-length chicken tetranectin cDNA was isolated. Comparison of the deduced amino acid sequence of chicken tetranectin with mouse and human tetranectin showed an identity of 67 and 68%, respectively. Northern blot analysis demonstrated broad expression of chicken tetranectin mRNA, which was first detected on embryonic day 4. Tetranectin protein was detected in chicken serum and egg yolk. Since muscle is one of few tissues in which tetranectin protein is retained, we examined the distribution of tetranectin in various muscle types in chicken. Myofibers strongly positive for tetranectin were observed in several muscles including m. tibialis ant. and m. sartorius (from embryonic day 10 to adult). Using antibodies to fast and slow myosin heavy chains (MHC) and double immunostaining techniques, we found that tetranectin was restricted to slow (type I) muscle fibers. Similarly only slow intrafusal fibers accumulated tetranectin. The pattern of immunostaining in chickens differs markedly from that seen in mouse muscles, indicating that tetranectin performs a role in muscle that is not associated with a hitherto recognized muscle type or function.

[Treatment of severe osteoporosis for internal medicine].

Some physicians of internal medicine recognize what is called severe osteoporosis is the bed-ridden condition because of severe pain and spinal deformity due to compression fractures. And also hip fracture makes a bed-ridden. In the end stage of osteoporosis, as effects of drugs to increase bone mineral density are limited, prevention of bed-ridden is needed a team-treatment not only by physician or orthopedic doctor but also by rehabilitation doctor and psychologist.

The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading.

The ADAMs (a disintegrin and metalloprotease) family of proteins is involved in a variety of cellular interactions, including cell adhesion and ecto- domain shedding. Here we show that ADAM 12 binds to cell surface syndecans. Three forms of recombinant ADAM 12 were used in these experiments: the cys-teine-rich domain made in Escherichia coli (rADAM 12-cys), the disintegrin-like and cysteine-rich domain made in insect cells (rADAM 12-DC), and full-length human ADAM 12-S tagged with green fluorescent protein made in mammalian cells (rADAM 12-GFP). Mesenchymal cells specifically and in a dose-dependent manner attach to ADAM 12 via members of the syndecan family. After binding to syndecans, mesenchymal cells spread and form focal adhesions and actin stress fibers. Integrin beta1 was responsible for cell spreading because function-blocking monoclonal antibodies completely inhibited cell spreading, and chondroblasts lacking beta1 integrin attached but did not spread. These data suggest that mesenchymal cells use syndecans as the initial receptor for the ADAM 12 cysteine-rich domain-mediated cell adhesion, and then the beta1 integrin to induce cell spreading. Interestingly, carcinoma cells attached but did not spread on ADAM 12. However, spreading could be efficiently induced by the addition of either 1 mM Mn(2+) or the beta1 integrin-activating monoclonal antibody 12G10, suggesting that in these carcinoma cells, the ADAM 12-syndecan complex fails to modulate the function of beta1 integrin.

Characterization of a zebra mutant of rice with increased susceptibility to light stress.

The rice zebra mutant TCM248 is a single recessive mutant. This mutant develops transverse-striped leaves with green and white sectors under alternate light/dark growth conditions. Mutants that were grown under a higher light intensity during the light period showed a more intense striped phenotype. The white tissues contained abnormal chloroplasts with few internal membrane structures, while the green tissues in the mutants contained normal chloroplasts. The white tissue contained only trace amounts of Chls and carotenoids, and mRNA accumulation of nuclear genes encoding chloroplast proteins (rbcS, cab) was strongly suppressed compared to that in the wild type plants. A series of growth condition shift experiments demonstrated that the mutant displayed the striped phenotype only if it was exposed to the alternate light/dark growth conditions during a limited stage of early leaf development. These data suggest that the zebra gene is involved in the acquisition of photoprotective capacity of the plants and that this gene functions at an early stage of chloroplast differentiation.

Possible involvement of protein phosphorylation in the wound-responsive expression of Arabidopsis plastid omega-3 fatty acid desaturase gene.

The plastid omega-3 fatty acid desaturase (FAD7) catalyzes the conversion of linoleic acid to linolenic acid. Wounding enhances the expression of the FAD7 gene in leaves and induces its expression in stems and roots. The wound-induced expression of the FAD7 promoter was investigated in transgenic tobacco plants carrying the -825 Arabidopsis FAD7 promoter::beta-glucuronidase (GUS) fusion gene. The protein kinase inhibitor, staurosporine, and the protein phosphatase inhibitor, calyculin A, suppressed the wound induction of the FAD7 gene in stems. A tobacco mitogen-activated protein kinase (WIPK) was rapidly activated upon wounding not only in leaves but also in stems and roots, indicating that WIPK probably mediates the wound signals in most vegetative organs. The FAD7 promoter::GUS fusion gene was introduced into the transgenic tobacco plants in which the wipk gene was expressed constitutively at a high level or into the transgenic plants in which the wipk gene was suppressed possibly due to the transgene-induced gene silencing. The wound-induced expression of the FAD7 gene in stems was enhanced in the former transgenic tobacco plants and suppressed in the latter plants. These results suggest that the wound activation of the FAD7 promoter depends on both protein phosphorylation and dephosphorylation events especially in stems, and also that WIPK is involved in such signaling cascades.