Osteoporosis: Ito M

Engelke K, Adams JE, Armbrecht G, Augat P, Bogado CE, Bouxsein ML, Felsenberg D, Ito M, Prevrhal S, Hans DB, Lewiecki EM. · Institute of Medical Physics, University of Erlangen, Germany; Synarc, Hamburg, Germany. <> · J Clin Densitom. · Pubmed #18442757 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) has developed Official Positions for the clinical use of dual-energy X-ray absorptiometry (DXA) and non-DXA technologies. While only DXA can be used for diagnostic classification according to criteria established by the World Health Organization, DXA and some other technologies may predict fracture risk and be used to monitor skeletal changes over time. ISCD task forces reviewed the evidence for clinical applications of non-DXA techniques and presented reports with recommendations at the 2007 ISCD Position Development Conference. Here we present the ISCD Official Positions for quantitative computed tomography (QCT) and peripheral QCT (pQCT), with supporting medical evidence, rationale, controversy, and suggestions for further study. QCT is available for bone mineral density measurements at the spine, hip, forearm, and tibia. The ISCD Official Positions presented here focus on QCT of the spine and pQCT of the forearm. Measurements at the hip may have clinical relevance, as this is an important fracture site; however, due to limited medical evidence, definitive advice on its use in clinical practice cannot be provided until more data emerge.

Ito M. · Division of Radiology, Nagasaki University Hospital. · Nippon Rinsho. · Pubmed #19432110 No free full text.

Abstract: It is well-known that osteoporosis treatment should be discussed from the view point of bone quality, however, in vivo assessment of bone quality is limited only for bone geometry and trabecular microstructure. Hip structure analysis (HSA) is a program to evaluate geometry and biomechanical property using two-dimensional DXA data of proximal femur. In vivo assessment of trabecular microstructure has been realized by the benefit of recent developments of imaging technique and technology, such as high resolution clinical CT and MR. These imaging techniques are going to be applied to assess risk of fracture and efficacy of anti-osteoporotic agents, although their spatial resolution is lower than real trabecular structure.

Ito M, Chiba K. · Nagasaki University Hospital, Division of Radiology. · Clin Calcium. · Pubmed #18677049 No free full text.

Abstract: Assessment of vertebral fracture based on a thoraco-lumbar spine radiographs is a good tool to evaluate the risk of incident fracture. Presence of vertebral fracture indicates 4 to 7 fold increase of risk of future fracture. However, vertebral fracture are often underdiagnosed. Quantitative (QM) and semi-quantitative (SQ) methods are designed for the assessment of prevalent and incident fracture. The advantages of SQ method are more convenient and reproducible as well as more excellent in the assessment of the risk of future fracture compared to QM. It should be recognized that untrained SQ reader produce a high false negative of grade 1 (mild fracture).

Ito M. · Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #18161150 No free full text.

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Ito M. · Division of Radiology, Nagasaki University Hospital. · Nippon Rinsho. · Pubmed #18161099 No free full text.

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Ito M. · Nagasaki University Hospital, Division of Radiology. · Clin Calcium. · Pubmed #18057661 No free full text.

Abstract: Intermittent administration of parathyroid hormone (PTH) stimulates bone formation, and continuous infusion of PTH stimulates bone resorption. The preclinical and clinical studies showed that PTH improved bone structure such as trabecular connectivity and cortical thickness, as well as increased bone mass. Its contribution to bone strength is produced by the different mechanism from the anti-resorptive agent. Assessment of bone geometry and site-specific bone change using CT will be required to evaluate its efficacy of anabolic agent on bone quality.

Ito M, Anonymous00188. · Nagasaki University Hospital, Division of Radiology. · Clin Calcium. · Pubmed #17607074 No free full text.

Abstract: Among several recent interests in bone quality, two topics will be stated. First, in vivo assessment of bone microstructure has been realized by the benefit of recent developments of imaging technique and technology, which is going to be applied to assess risk of fracture and efficacy of anti-osteoporotic agents. Second, in vitro analyses of nano-structure, including microcrack and cortical porosisty, contribute to assessment of bone material and biomechanical properties.

Ito M. · Nagasaki University Hospital, Division of Radiology. · Clin Calcium. · Pubmed #17142935 No free full text.

Abstract: Quantitative computed tomography (QCT) provides three-dimensional bone mineral density (BMD) of trabecular and cortical components separately, as well as macroscopic bone configuration. High resolution CT (HRCT) measures bone geometry more precisely than conventional CT, which enables to assess the effects of anti-osteoporotic agents. HRCT is also able to analyze in vivo trabecular microstructure. CT has an advantage to demonstrate the trabecular microstructure in axial skeleton such as vertebra or hip, which can be expected to contribute to evaluate the effects of anti-osteoporotic agents.

Ito M, Minami A. · Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #16972677 No free full text.

Abstract: Most of osteoporotic spinal fractures can be successfully treated with conservative treatment. In some patients, however, conservative treatment is not effective and progressive vertebral collapse with neurological problems at thoraco-lumbar spine may occur. In this chapter, surgical indication and timing in patients with osteoporotic vertebral collapse are described. Surgical options including vertebroplasty, kyphoplasty, anterior reconstruction, posterior reconstruction, and combined anterior and posterior surgery are also described. The readers can understand both advantages and disadvantages of each surgical procedure. In senile patients, preoperative general conditions including comorbid medical problems should be taken into account to determine surgical treatments. Rigid and long spinal fusion using metal implants may lead to spinal fractures at adjacent vertebral bodies to the fused segments.

Ito M. · Nagasaki University Hospital, Division of Radiology. · Clin Calcium. · Pubmed #16951468 No free full text.

Abstract: It is generally known that approximately 70 percent of bone strength is explained by bone mineral density, and the remaining 30 percent by "bone quality". Especially, in the monitoring of treatment, bone mineral density cannot fully explain the efficacy upon the risk of fracture. "Bone quality" has two aspects: structure property and material property. They are both influenced by bone turnover and have a relation to bone strength. From the viewpoint of diagnosis of osteoporosis, the factors of bone quality that can be clinically evaluated, are bone biomarkers as indices of bone remodeling, and structure property including bone geometry and trabecular microstructure. This article discusses the evaluation of bone quality and its clinical significance.

Miyamoto K, Ito M, Segawa H. · Department of Molecular Nutrition, Institution of Health Biosciences, The University of Tokushima Graduate School. · Clin Calcium. · Pubmed #15876740 No free full text.

Abstract: The hormones currently believe to influence inorganic phosphate (Pi) metabolism are parathyroid hormone (PTH) and the active metabolite to vitamin D. A new class of phosphate-regulating factors, collectively known as the phosphatonins have been shown to be associated with the hypophosphatemic diseases. The reabsorption of Pi in the kidney is a major determinant of the plasma Pi level. Reabsorption is largely regulated by the type II a sodium-dependent Pi cotransporter (NPT2a) that is expressed in renal proximal tubular cells. Phosphatonins cause Pi wasting by controlling the amount of NPT2a on the apical surface of the proximal tubular cell. A recent finding indicates that mutations in NPT2a can contribute to nephrolithiasis and osteoporosis in humans and suggests that changes in NPT2a levels may also cause other human disease. We discuss the roles of phosphatonins and NPT2a in bone formation.

Ito M. · Division of Radiology, Nagasaki University Hospital. · Clin Calcium. · Pubmed #15577170 No free full text.

Abstract: Bone quality including "structural property" and "material property" , which is strongly affected by bone remodeling and has an influence on bone biomechanical property. Structural property means macroscopical geometry, bone size, trabecular microstructure, cortical thickness and cortical porosity. Material property means mineralization, crystal size, collagen and microdamage. Although most of them are analyzed in vitro, in the future, noninvasive assessment of bone quality may help to guide therapy of osteoporosis.

Ito M. · Department of Radiology, Nagasaki University School of Medicine. · Nippon Rinsho. · Pubmed #15035138 No free full text.

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Ito M. · Department of Radiology, Nagasaki University School of Medicine. · Nippon Rinsho. · Pubmed #11979910 No free full text.

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Ito M, Nishida A, Uetani M, Hayashi K. · Department of Radiology, Nagasaki University, 1--7-1 Sakamoto, Nagasaki, Japan. · Semin Musculoskelet Radiol. · Pubmed #11500152 No free full text.

Abstract: The characteristic of osteoporosis in the Japanese population is different from that in the Caucasian population. The different incidence of vertebral and hip fracture may be related to both genetic and lifestyle factors. In the aspect of genetics, approximately 77% of the Japanese have the bb genotype of the vitamin D receptor gene, which is considered to be associated with higher bone mass and lower bone turnover than the Bb genotype. The incidence of vertebral fracture is significantly lower in the younger birth cohorts in both genders. However, the total number of hip fractures rapidly grows as the elderly population increases in Japan. It may be explained by some epidemiological studies that the traditional Japanese lifestyle may prevent hip fractures in the Japanese elderly. The knowledge of the differences of osteoporosis between Caucasian and Japanese people must contribute to the prevention of osteoporosis and its complications.

Miki T, Nakatsuka K, Naka H, Masaki H, Imanishi Y, Ito M, Inaba M, Morii H, Nishizawa Y. · Department of Geriatric Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, Japan. · J Bone Miner Metab. · Pubmed #15490267 No free full text.

Abstract: In order to evaluate the efficacy and safety of intermittent subcutaneous administration of 1-34 N-terminal peptide of human parathyroid hormone (hPTH 1-34), 100 units of hPTH 1-34 was subcutaneously injected once a week for 1 year in ten patients with primary osteoporsis (one male and nine females) with no qualitative abnormality of the bone according to the results of iliac crest biopsy performed previously, followed by a second biopsy after the end of the 1-year administration. Written consent of the patients for participation in the study was obtained. The mean lumbar bone mineral density (LBMD) definitely increased, by 1.8%, 3.4%, and 4.6% after 12, 24, and 48 weeks of hPTH administration, in accordance with previous clinical studies. Histomorphometric analysis after double-tetracycline labeling was completed in six patients (one male and five females) after the exclusion of those who dropped out because of adverse events unrelated to the test drug, or refusal of continuation. Examination of thin hard-tissue sections revealed no qualitative abnormalities of bone tissue or bone marrow cavity, such as osteomalacia, woven bone, or osteitis fibrosa, precluding the contribution of qualitatively abnormal tissue elements to any changes of LBMD in response to hPTH 1-34 administration. Histomorphometric measurement in the second biopsy revealed a tendency for an increase of bone volume, a significant increase of osteoid surface, and a tendency for an increase in other parameters of bone formation, compared with values obtained in the preadministration biopsy. Indices of two-dimensional microstructure obtained by microfocus computed tomography (CT) and results of node-strut analysis indicated improvement of trabecular continuity. In five patients in whom three-dimensional reconstruction images were analyzed, there were significant increases of bone volume and trabecular thickness, and a significant decrease in the trabecular bone pattern factor, a parameter related to the continuity, suggesting an improvement of the three-dimensional trabcular microstructure. Intermittent weekly subcutaneous injections of hPTH (1-34) for 48 weeks increased trabecular bone volume and improved microstructure, without causing the appearance of abnormal bone elements in primary osteoporosis.

Shiraishi A, Miyabe S, Nakano T, Umakoshi Y, Ito M, Mihara M. · Product Research Department, Chugai Pharmaceutical Co, Ltd,, 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan. · BMC Musculoskelet Disord. · Pubmed #19527501 links to  free full text

Abstract: BACKGROUND: We conducted the present study to investigate the therapeutic effects of a combination treatment of alfacalcidol (ALF) and risedronate (RIS) on the bone mechanical properties of bone and calcium (Ca) metabolism using an ovariectomized (OVX) rat model of osteoporosis. METHODS: Female Wistar rats were OVX- or sham-operated at 40 weeks of age. Twelve weeks post-surgery, rats were randomized into seven groups: 1) sham + vehicle, 2) OVX + vehicle, 3) OVX + ALF 0.025 microg/kg/day, 4) OVX + ALF 0.05 microg, 5) OVX + RIS 0.3 mg, 6) OVX + RIS 3.0 mg, 7) OVX + ALF 0.025 microg + RIS 0.3 mg. Each drug was administered orally five times a week for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral midshaft. In the lumbar vertebra, structural and material analyses were performed using micro-computed tomography (micro-CT) and microbeam X-ray diffraction (micro-XRD), respectively. Biochemical markers in serum and urine were also determined. RESULTS: (1) With respect to improvement in the mechanical strength of the lumbar spine and the femoral midshaft, the combination treatment of ALF and RIS at their sub-therapeutic doses was more effective than each administered as a monotherapy; (2) In the suppression of bone resorption and the amelioration of microstructural parameters, the effects of ALF and RIS were considered to be independent and additive; (3) The improvement of material properties, such as microstructural parameters and the biological apatite (Bap) c-axis orientation, contributed to the reinforcement of spinal strength; and (4) The combination treatment of ALF and RIS normalized urinary Ca excretion, suggesting that this treatment ameliorated the changes in Ca metabolism. CONCLUSION: These results demonstrate that the combination treatment of ALF and RIS at their sub-therapeutic doses can improve the mechanical properties of the spine as well as the femur and ameliorate changes in Ca metabolism in an animal model of osteoporosis, suggesting that the combination treatment of ALF and RIS has a therapeutic advantage over each monotherapy for the treatment of osteoporosis.

Asaba Y, Ito M, Fumoto T, Watanabe K, Fukuhara R, Takeshita S, Nimura Y, Ishida J, Fukamizu A, Ikeda K. · Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan. · J Bone Miner Res. · Pubmed #18847324 No free full text.

Abstract: Hypertension and osteoporosis are two major age-related disorders; however, the underlying molecular mechanism for this comorbidity is not known. The renin-angiotensin system (RAS) plays a central role in the control of blood pressure and has been an important target of antihypertensive drugs. Using a chimeric RAS model of transgenic THM (Tsukuba hypertensive mouse) expressing both the human renin and human angiotensinogen genes, we showed in this study that activation of RAS induces high turnover osteoporosis with accelerated bone resorption. Transgenic mice that express only the human renin gene were normotensive and yet exhibited a low bone mass, suggesting that osteoporosis occurs independently of the development of hypertension per se. Ex vivo cultures showed that angiotensin II (AngII) acted on osteoblasts and not directly on osteoclast precursor cells and increased osteoclastogenesis-supporting cytokines, RANKL and vascular endothelial growth factor (VEGF), thereby stimulating the formation of osteoclasts. Knockdown of AT2 receptor inhibited the AngII activity, whereas silencing of the AT1 receptor paradoxically enhanced it, suggesting a functional interaction between the two AngII receptors on the osteoblastic cell surface. Finally, treatment of THM mice with an ACE inhibitor, enalapril, improved osteoporosis and hypertension, whereas treatment with losartan, an angiotensin receptor blockers specific for AT1, resulted in exacerbation of the low bone mass phenotype. Thus, blocking the synthesis of AngII may be an effective treatment of osteoporosis and hypertension, especially for those afflicted with both conditions.

Takahata M, Ito M, Abe Y, Abumi K, Minami A. · Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan. · Bone. · Pubmed #18835375 No free full text.

Abstract: Bone grafting is commonly used to treat skeletal disorders associated with a large bone defect or unstable joint. Spinal arthrodesis surgery, which is the most common application of bone graft, is performed in the elderly and anti-resorptive therapy is sometimes started postoperatively in patients with bone fragility due to osteoporosis, despite insufficient knowledge about the effects of these drugs on bone graft healing. Therefore, we studied the effect of bisphosphonates (BP) and selective estrogen receptor modulators (SERM) on bone graft healing in an ovariectomized rat spinal arthrodesis model. Female Sprague-Dawley rats (n=100) were ovariectomized or sham-operated, and randomized into four groups: Sham (sham-operated+vehicle), Ovx (ovariectomy+vehicle), Ovx-Rlx (ovariectomy+raloxifene, 1 mg/kg/day), and Ovx-Aln (ovariectomy+alendronate, 0.01 mg/kg/day). Four weeks after ovariectomy, lumbar spinal arthrodesis surgery was performed using an autologous bone graft. Animals were killed 2, 4, and 8 weeks after surgery, and fusion assessment, three-dimensional micro-computed tomography, histomorphometry, mRNA expression analysis, and serum bone metabolic marker analysis were performed. The results indicated that neither BP nor SERM significantly altered the fusion rate, but the bone graft healing process was differentially affected. BP inhibited endochondral ossification and graft bone resorption, but induced the growth of a larger, denser fusion mass compared to Ovx by strongly suppressing osteoclastic activity. SERM mildly suppressed bone remodeling, but did not significantly inhibit the ossification process, leading to a fusion mass comparable with that of Sham animals. These findings suggested that spinal fusion surgery outcome is not likely to be altered by BP or SERM treatment started immediately after spinal arthrodesis surgery; however, to avoid adverse effects of BP on bone graft healing, BP treatment should be delayed during the immediate postoperative period.

Mori H, Tanaka M, Kayasuga R, Masuda T, Ochi Y, Yamada H, Kishikawa K, Ito M, Nakamura T. · Pharmacological Research Laboratories, Ono Pharmaceutical Co., Ltd., Osaka, Japan. · Bone. · Pubmed #18718565 No free full text.

Abstract: This study examined the effect of the highly potent nitrogen-containing bisphosphonate, minodronic acid (ONO-5920/YM529), on bone mineral density (BMD), bone turnover, bone microarchitecture and bone strength in ovariectomized (OVX) cynomolgus monkeys. Skeletally mature female cynomolgus monkeys, aged 9-17 years, were ovariectomized or sham-operated. Minodronic acid was administered orally once a day in doses of 0, 0.015, and 0.15 mg/kg from the day after surgery for 17 months. Bone resorption markers (urinary N-terminal cross-linking telopeptide of type I collagen and deoxypyridinoline), bone formation markers (serum osteocalcin and bone alkaline phosphatase) and lumbar vertebral BMD were measured at baseline and at 4, 8, 12 and 16 months after surgery. Treatment with minodronic acid dose-dependently inhibited OVX-induced increase in bone turnover markers and decrease in lumbar vertebral BMD, and minodronic acid at 0.15 mg/kg completely prevented these changes. At 17 months after surgery, minodronic acid also suppressed bone resorption (Oc.S/BS and N.Oc/BS) and bone formation (OS/BS, MS/BS, MAR, BFR/BS, and BFR/BV) in the lumbar vertebral bodies and tibia. In the mechanical tests, ultimate load on lumbar vertebral bodies and femoral neck of the OVX-control animals were significantly reduced compared to the sham animals. Minodronic acid prevented these reductions in bone strength at 0.15 mg/kg. There was significant correlation between BMD and bone strength, suggesting that the increase in bone strength was associated with the increase in BMD produced by minodronic acid. In micro-CT analysis of the lumbar vertebral bodies, minodronic acid improved trabecular architecture, converting rod structures into plate structures, and preventing the increase in trabecular disconnectivity at 0.15 mg/kg. In conclusion, similar to patients with postmenopausal osteoporosis, reduction in bone strength of lumbar vertebral bodies and femoral neck was clearly demonstrated in OVX cynomolgus monkeys. Minodronic acid prevented these reductions at a once-daily oral administration. Also, minodronic acid prevented OVX-induced changes in bone turnover, bone mass and bone microarchitecture. Long-term minodronic acid treatment was well tolerated and no adverse effects could be detected. These results suggest that minodronic acid may be a clinically useful drug for osteoporosis.

Ding H, Koinuma N, Stevenson M, Ito M, Monma Y. · Department of Health Administration and Policy, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. · J Bone Miner Metab. · Pubmed #18095061 No free full text.

Abstract: We constructed a mathematical model for assessing the cost-effectiveness of providing BMD (bone mineral density) scans to Japanese women aged 55 years and over and treating, with risedronate, those that are shown to be osteoporotic. Fracture rates, cost data, utility values, and the increased risks of fractures associated with T-score and vertebral fracture history were taken from published literature. We estimated the cost of fractures avoided due to risedronate treatment, allowing the net changes in cost, incorporating both intervention and fracture costs to be calculated. The QALYs (quality adjusted life years) gained through treatment were calculated enabling cost per QALY ratios to be presented. Further analyses were undertaken assuming treatment was reserved for older women and/or those who had sustained a vertebral fracture in the previous 2 years. Cost per QALY values were inversely related to absolute risk of fracture. Assuming a cost per QALY value threshold of US dollars 100,000, we concluded that providing BMD scans to women aged 70 years and over who had sustained a vertebral fracture in the previous 2 years and treating those that were osteoporotic was cost-effective. However, providing BMD scans for women without a vertebral fracture in the previous 2 years was not cost-effective, even in women aged 85 years and older.

Abe Y, Takahata M, Ito M, Irie K, Abumi K, Minami A. · Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Sapporo, Japan. · Bone. · Pubmed #17707711 No free full text.

Abstract: Bone grafting is commonly used to treat skeletal disorders associated with large bone defect or unstable joint. It can take several months, however, to achieve a solid union and bony fusion sometimes delays or fails especially in osteoporosis patients. Therefore, we used a rat spinal arthrodesis model to examine whether intermittent administration of human PTH(1-34) accelerates bone graft healing. Eighty-two male Sprague-Dawley rats underwent posterolateral spinal arthrodesis surgery using autologous bone grafts. Animals were given daily subcutaneous injections of hPTH(1-34) (40 microg/kg/day PTH group) or 0.9% saline vehicle (control group) from immediately after surgery till death. Five rats each were killed 2, 4, 7, and 14 days after the surgery, and mRNA expression analysis was performed on harvested grafted bone. Seven rats each were killed 14, 28, and 42 days after the surgery, and the lumbar spine, which contained the grafted spinal segment, was subjected to fusion assessment, microstructural analysis using three-dimensional micro-computed tomography, and histologic examination. Serum bone metabolism markers were analyzed. The results indicated that PTH administration decreased the time required for graft bone healing and provided a structurally superior fusion mass in the rat spinal arthrodesis model. PTH administration increased the fusion rate on day 14 (14% in the control group and 57% in the PTH group), accelerated grafted bone resorption, and produced a larger and denser fusion mass compared to control. mRNA expression of both osteoblast- and osteoclast-related genes was upregulated by PTH treatment, and serum bone formation and resorption marker levels were higher in the PTH group than in the control group. Histologically calculated mineral apposition rate, mineralized surface and osteoclast surface were also higher in the PTH group than in the control group. These findings suggest that intermittent administration of PTH(1-34) enhanced bone turn over dominantly on bone formation at the graft site, leading to the acceleration of the spinal fusion. Based on the results of this study, intermittent injection of hPTH(1-34) might be an efficient adjuvant intervention in spinal arthrodesis surgery and all other skeletal reconstruction surgeries requiring bone grafts.

Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, Ito M, Takeshita S, Ikeda K. · Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522, Japan. · Cell Metab. · Pubmed #17550781 No free full text.

Abstract: Bone remodeling is performed by osteoclasts and osteoblasts at the bone surface. Inside of bone is a network of numerous osteocytes, whose specific function has remained an enigma. Here we describe a transgenic mouse model in which inducible and specific ablation of osteocytes is achieved in vivo through targeted expression of diphtheria toxin (DT) receptor. Following a single injection of DT, approximately 70%-80% of the osteocytes, but apparently no osteoblasts, were killed. Osteocyte-ablated mice exhibited fragile bone with intracortical porosity and microfractures, osteoblastic dysfunction, and trabecular bone loss with microstructural deterioration and adipose tissue proliferation in the marrow space, all of which are hallmarks of the aging skeleton. Strikingly, these "osteocyte-less" mice were resistant to unloading-induced bone loss, providing evidence for the role of osteocytes in mechanotransduction. Thus, osteocytes represent an attractive target for the development of diagnostics and therapeutics for bone diseases, such as osteoporosis.

Hiramatsu K, Asaba Y, Takeshita S, Nimura Y, Tatsumi S, Katagiri N, Niida S, Nakajima T, Tanaka S, Ito M, Karsenty G, Ikeda K. · Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology (NCGG), 36-3 Gengo, Morioka, Obu, Aichi 474-8522, Japan. · Endocrinology. · Pubmed #17363454 links to  free full text

Abstract: We previously identified gamma-glutamyltransferase (GGT) by expression cloning as a factor inducing osteoclast formation in vitro. To examine its pathogenic role in vivo, we generated transgenic mice that overexpressed GGT in a tissue-specific manner utilizing the Cre-loxP recombination system. Systemic as well as local production of GGT accelerated osteoclast development and bone resorption in vivo by increasing the sensitivity of bone marrow macrophages to receptor activator of nuclear factor-kappaB ligand, an essential cytokine for osteoclastogenesis. Mutated GGT devoid of enzyme activity was as potent as the wild-type molecule in inducing osteoclast formation, suggesting that GGT acts not as an enzyme but as a cytokine. Recombinant GGT protein increased receptor activator of nuclear factor-kappaB ligand expression in marrow stromal cells and also stimulated osteoclastogenesis from bone marrow macrophages at lower concentrations. Thus, GGT is implicated as being involved in diseases characterized by accelerated osteoclast development and bone destruction and provides a new target for therapeutic intervention.

Toyone T, Toyone T, Tanaka T, Wada Y, Kamikawa K, Ito M, Kimura K, Yamasita T, Matsushita S, Shiboi R, Kato D, Kaneyama R, Otsuka M. · Department of Orthopaedic Surgery, Teikyo University School of Medicine Ichihara Hospital, 3426-3 Anesaki, Ichihara-city, Chiba 299-0111, Japan. · Spine (Phila Pa 1976). · Pubmed #17139228 No free full text.

Abstract: STUDY DESIGN: Prospective consecutive series. OBJECTIVE: To analyze supine and standing radiographs and the association of back pain using subjective pain criteria. SUMMARY OF BACKGROUND DATA: It has been considered that there is little correlation between the degree of collapse of the vertebral body and the level of pain. In previous studies, however, measurements have only been based on supine radiographs. Although there were 2 authors who reported the results of supine lateral and standing lateral radiographs in patients with thoracolumbar vertebral fractures, as far as we know, there has not been any detailed report concerning the correlation between radiologic findings using supine and standing lateral radiographs and back pain. METHODS: We examined 100 consecutively treated patients, prospectively. Back pain and the supine and standing radiographs were assessed 1 month after injury. Changes in vertebral wedging rate (WR) from supine to standing position (Delta WR) was reported by the following equation: Delta WR = WR(standing)-WR(supine). RESULTS: The median age of the cohort was 75 years (range, 60-89 years). The median VAS of back pain at supine position, at standing position, and when standing erect was 13, 33, and 41, respectively. The median wedging rate on the supine and standing radiographs were 28% and 37%, respectively (P < 0.001). There was a significant correlation between Delta WR and back pain when standing erect (r = 0.79, P < 0.001). CONCLUSION: Changes in vertebral wedging rate between supine and standing position and its association with back pain may give a clue to the pathogenesis of pain from osteoporotic thoracolumbar vertebral compression fractures.