Understanding of others' knowledge in French and Japanese children: a comparative study with a disambiguation task on 16-38-month-olds.

In order to explain the cultural differences reported in the results of false-belief tasks, we attempted to verify the 'task bias hypothesis' suggested by certain studies (e.g. Tardif et al. (2004). Journal of Child Language, 31, 779-800; Rubio-Fernandez & Geurts (2013). Psychological Science, 24(1), 27-33. doi 10.1177/0956797612447819). At the same time, we aimed to observe the theory of mind (ToM) ability of infants and young children under the age of three in verbal communication. To this end, we propose a new protocol to test young children's ToM ability, with particular attention paid to the linguistic aspect of the task. This original disambiguation task using proper nouns (first names) was tested on a total of 32 children aged between 16 and 38 months, in France and Japan. The results revealed that after the age of 30 months children begin to correctly interpret nouns while simultaneously taking into account their partner's knowledge (50% of the French and 29% of the Japanese children were successful), whereas this remains difficult for younger children (no child under 30 months was successful). The analysis of error types has shown that 'memory bias' was dominant in younger children in particular and 'association bias' was rarely observed across all ages. Given that the results of French and Japanese children did not differ significantly, we assume that this new task design could minimise the influence of cultural difference caused by the characteristics of different languages.

Post-traumatic moderate systemic hypothermia reduces TUNEL positive cells following spinal cord injury in rat.

STUDY DESIGN: A standardized animal model of contusive spinal cord injury (SCI) with incomplete paraplegia was used to test the hypothesis that moderate systemic hypothermia reduces neural cell death. Terminal deoxynucleotidyl transferase [TdT]-mediated deoxyuridine triphosphate [dUTP] nick-end labeling (TUNEL) staining was used as a marker of apoptosis or cell damage. OBJECTIVE: To determine whether or not moderate hypothermia could have a neuroprotective effect in neural cell death following spinal cord injury in rats. SETTING: Kagawa Medical University, Japan. METHODS: Male Sprague-Dawley (SD) rats (n=39) weighing on average 300 g (280-320 g) were used to prepare SCI models. After receiving contusive injury at T11/12, rats were killed at 24 h, 72 h, or 7 days after injury. The spinal cord was removed en bloc and of examined at five segments: 5 and 10 mm rostral to the center of injury, center of injury, and 5 and 10 mm caudal to the center of injury. Rats that received hypothermia (32 degrees C/4 h) were killed at the same time points as those that received normothermia (37 degrees C/3 h). The specimens were stained with hematoxylin and eosin, and subjected to in situ nick-end labeling (TUNEL), a specific method for visualizing cell death in the spinal cord. RESULTS: At 24 h postinjury, TUNEL positive cells (TPC) decreased significantly 10 mm rostral to center of injury in hypothermic animals compared to the normothermia group. At 72 h post-SCI, TPC also decreased significantly at 5 mm rostral, and 5 and 10 mm caudal to the lesion center compared to normothermic animals. At 7 days postinjury, a significant decrease of TPC was observed at the 5 mm rostral and 5 mm caudal sites compared to normothermic animals. CONCLUSION: These results indicate that systemic hypothermia has a neuroprotective effect following SCI by attenuating post-traumatic TPC.

A report of two cases treated with Pauwels' femoral osteotomy for advanced osteoarthritis resulting from a sequela of infectious coxitis in childhood.

Pauwels' femoral valgus osteotomy was performed on two osteoarthritic hips that developed as a sequela of infectious coxitis in the childhood. One of the hips was diagnosed as osteomyelitis of the ipsilateral femur before the operation and was treated with curettage and implantation of antibiotic-impregnated cement beads. The results of both hips were excellent and maintained for 9-11 years.

Embryonic intermediate filament, nestin, expression following traumatic spinal cord injury in adult rats.

Precursor cells in the ependyma of the lateral ventricles of adult mammalian brain have been reported in brain, and also in the spinal cord. The present study used antibody to the intermediate filament protein (nestin) as an immunohistochemical marker for neural stem cells and precursor cells in a rat model of spinal cord trauma. Male Sprague-Dawley rats (n=25) had a laminectomy at Thll-Thl2, and spinal cord contusion was created by compression with 30 g of force for 10 min. The rats were killed at 24 h, 1 week and 4 weeks after injury, and four levels of the spinal cord were examined: 5 mm and 10 mm, both rostral and caudal region to the injury center. Time- and region-dependent alterations of nestin immunoreactivity were analyzed. Revealed at 24 h post-injury, 5 mm rostral and caudal to the lesions, nestin expression was observed in ependymal cells and around the hemorrhagic and necrotic lesion located in dorsal spinal cord, peaking at 1 week after injury. Moreover, nestin expression was also observed in the white matter of ventral spinal cord, extending into arborizing processes centripetally from the pial surface toward the central canal. At 4 weeks after injury, nestin expression in ependyma decreased 10 mm from the injury site. But nestin expression in white matter increased dramatically with a 100-fold increase in nestin originating from the pial surface, and extension now to all the white matter. The latter was accompanied by glial fibrillary acidic protein positivity into very long arborizing processes, morphologically compatible with radial glia. The findings suggest two possible sources of precursor cells in adult mammalian spinal cord; ependyma of the central canal and subpial astrocytes. Subpial astrocytes may be associated with neural repair and regeneration after spinal cord injury.

Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats.

The aim of this study was to investigate the long-term effect of incadronate on fracture healing of the femoral shaft in rats. Female Sprague-Dawley 8-week-old rats were injected subcutaneously (sc) with either vehicle (V group) or two doses of incadronate (10 microg/kg and 100 microg/kg) three times a week for 2 weeks. Right femoral diaphysis was then fractured and fixed with intramedullary stainless wire. Just after fracture, incadronate treatment was stopped in pretreatment groups (P groups: P-10 and P-100) or continued in continuous treatment groups (C groups: C-10 and C-100). All rats were killed at 25 weeks or 49 weeks after surgery. Fractured femur was evaluated radiologically and mechanically and then stained in Villanueva bone stain and embedded in methyl methacrylate. Undecalcified cross-sections from the fracture area were evaluated microradiologically and histomorphometrically. Radiographic observation showed that the fracture line disappeared in all groups. Cross-sectional area in the C-100 group was the biggest among all groups and in the C-10 group was larger than that in the V group at 25 weeks. Histological and histomorphometric observations showed that the process of fracture healing was delayed under continuous treatment with incadronate as evidenced by the delay of both lamellar cortical shell formation and resolution of original cortex in C groups. Percent linear labeling perimeter, mineral apposition rate (MAR), and bone formation rate (BFR) in C groups significantly decreased compared with the other groups, indicating that the callus remodeling was suppressed under continuous treatment, especially with a high dose. Mechanical study showed that the stiffness and ultimate load of the fractured femur in the C 100 group were the highest among all groups at both 25 weeks and 49 weeks. In conclusion, this study showed that long-term continuous treatment with incadronate delayed the process of fracture healing of femur in rats, especially under high dose but it did not impair the recovery of mechanical integrity of the fracture.

Mechanism of intramedullary high intensity area on T2-weighted magnetic resonance imaging in osteoid osteoma: a possible role of COX-2 expression.

To study the mechanism and pathophysiology of the development of intramedullary high intensity areas on T2-weighted magnetic resonance images (MRI) in cases of osteoid osteoma, we examined the expression of cyclooxygenase-2 (COX-2) in the nidus and surrounding bone tissues. In all six cases showing a marked intramedullary high intensity area adjacent to the nidus before surgery, neoplastic osteoblasts inside the nidus showed strong and diffuse COX-2 immunoreactivity. On the other hand, the osteoblasts rimming the surrounding reactive bone were COX-2 negative. In two cases examined by reverse transcription-polymerase chain reaction (RT-PCR), COX-2 mRNA was detected in abundance in the nidus. Histologically, vascular dilatation together with intramedullary edema was observed in all cases, which was probably reflected as a high intensity area on T2-weighted MRI. From our study, a high level of COX-2 expression in neoplastic osteoblasts in the nidus of osteoid osteomas may cause the secondary changes depicted by MRI.

[Osteoporosis and fracture in rheumatoid arthritis].

Patients with rheumatoid arthritis often have periarticular and generalized osteoporosis. Bone resorption develops through increased productions of cytokines and prostaglandines by synovium and bone. Important risk factors of osteoporosis are functional impairment, postmenopausal state, and corticosteroids usage. Osteoporotic fracture occurs at the spinal body, femoral neck, distal radius, and periprosthetic bone.

Concentration of bisphosphonate (incadronate) in callus area and its effects on fracture healing in rats.

The aim of the present study was to investigate effects of incadronate on early stages of fracture healing and to detect its concentration in callus area (Ca.Ar). Rats were injected three times per week with either two doses of incadronate (10 microg/kg and 100 microg/kg) or vehicle for 2 weeks. Femora were then fractured and fixed and animals were divided into pretreatment (P-10 and P-100) and continuous treatment (C-10 and C-100) groups. Incadronate treatment was stopped in P-10 and P-100 groups but continued in C-10 and C-100 groups. Animals were killed at 2 weeks and 4 weeks after fracture. Results showed significantly large callus, compared with the control, only in C-100 group at 4 weeks but not at 2 weeks. Both linear labeled surface (LS) and eroded surface (ES) decreased significantly in C-10 and C-100 groups at 2 weeks and 4 weeks. Osteoclast number (N.Oc) decreased significantly in C-10 and C-100 groups at 2 weeks but increased slightly at 4 weeks. However, there was no significant difference in the above parameters in P-10 and P-100 groups at 4 weeks. Apoptotic osteoclasts were observed only in the C-100 group at 4 weeks. A time-course decrease in incadronate concentration was detected in P-10 and P-100 groups whereas an increase was observed in C-10 and C-100 groups. These findings suggest that larger callus under incadronate treatment may result from the inhibition of bone resorption, histological characteristics of callus may be correlated with incadronate concentration, and metabolism of incadronate in bone may be related to the rate of bone turnover.

Intraarticular osteoid osteoma associated with synovitis: a possible role of cyclooxygenase-2 expression by osteoblasts in the nidus.

To clarify the condition of development of synovitis associated with intraarticular osteoid osteoma (OO), expressions of cyclooxygenase-2 (COX-2) protein and its messenger ribonucleic acid were investigated both in the nidus and the synovial tissue using immunohistochemical and reverse transcription-polymerase chain reaction analyses. Diffuse and strong COX-2 immunoreactivity was found in osteoblast-like tumor cells in the nidus of all six cases of OO (three of six cases were intraarticular OO associated with synovitis) and one case of osteoblastoma associated with synovitis. Expression of COX-2 messenger ribonucleic acid was demonstrated in one case of OO associated with synovitis, and was higher in the nidus than that in the inflamed synovial tissue. However, there were no significant difference between the nidus and synovium in the expression of cytosolic phospholipase A2, one of the enzymes involved in arachidonic acid metabolism, and inflammatory cytokines such as interleukin-1beta and tumor necrosis factor alpha. Finally, as there was only one case in which the examinations of gene expression were performed, no definitive overall conclusions could be reached; rather it is suggested that COX-2 expressed primarily by osteoblasts in the nidus of intraarticular OO may play a role in activating the pathway of arachidonic acid metabolism, resulting in synovitis of the involved joint.

Factors influencing joint-preserving operations in the treatment of the late stages of osteoarthritis of the hip.

Between November 1983 and December 1992, 136 hips (119 patients) with coxarthritis were operated on using joint-preserving techniques based on the rationale of Pauwels' osteotomy. The criterion for selection was a patient in whom the height of the joint space in the weight-bearing area of the hip was less than 1 mm. The mean age at operation was 48 years and the mean follow-up 109 months (60 to 171). Hips were categorised using Bombelli's classification of osteoarthritis, into atrophic and non-atrophic types. The endpoint was defined as that at which the height of the joint space became less than 1 mm again. The Kaplan-Meier curve showed that the rate of survival of the non-atrophic group was significantly better than that of the atrophic group. Cox's proportional hazard model indicated that the factors influencing the results of joint-preserving operations included Bombelli's classification, postoperative incongruence of the joint and the height of the joint space.

IL-4, but not vitamin D(3), induces monoblastic cell line UG3 to differentiate into multinucleated giant cells on osteoclast lineage.

The formation of multinucleated giant cells (MGCs) from monocytes/macrophages is controlled by various cytokines, the roles of which are not fully understood. Both interleukin (IL)-4 and 1alpha,25(OH)(2) vitamin D(3) (D(3)) are known to induce MGC formation from monocytes/macrophages. D(3) is also known as a stimulator of osteoclast formation in the presence of stroma cells, and IL-4 as an inhibitor. Previously, we showed that IL-4-induced MGCs from monocytes/macrophages expressed tartrate resistant acid phosphatase (TRAP) activity and hydroxyapatite-resorptive activity in the presence of M-CSF without stroma cells. In this study, we examined the effects of D(3) and/or IL-4 on MGC formation and the characteristics of these MGCs using a monoblastic cell line (UG3), to elucidate the involvement of these factors in osteoclast development without stroma cells. D(3)-induced MGCs showed none of the markers of osteoclasts, such as TRAP activity, calcitonin receptor (cal-R) expression, hydroxyapatite-resorptive activity, and bone-resorptive activity. A low concentration of D(3) synergistically stimulated IL-4-induced TRAP-positive MGC formation, whereas a high concentration of D(3) inhibited it. When IL-4 was added on day 7 of the 2-week culture with D(3), TRAP positivity reached maximum. On the other hand, delayed addition of D(3) on day 7 of culture did not increase the TRAP positivity. Although the fusion rate increased during the first week of the 2-week culture in the presence of D(3), it increased further in the second week following the addition of IL-4 on day 7. Furthermore, IL-4-induced, or IL-4- and D(3)-induced MGCs differentiated into functional osteoclasts with bone-resorptive activity following coculture with osteoblastic cells, whereas D(3)-induced MGCs did not acquire bone-resorptive activity even after coculture with osteoblastic cells in the presence of D(3). These findings suggest that IL-4 initiates osteoclast development of UG3 cells, although stroma cells were necessary for development of functional osteoclasts. On the other hand, D(3) had only a "supportive" effect on this differentiation. IL-4 and direct contact with stroma cells may regulate different stages in the multistep process of osteoclastogenesis of UG3 cells.

Effect of an intermittent weekly dose of human parathyroid hormone (1-34) on osteoporosis: a randomized double-masked prospective study using three dose levels.

To test the effect of amino-terminal peptide 1-34 of human parathyroid hormone (hPTH (1-34)) as a possible bone anabolic agent in the treatment of osteoporosis, weekly subcutaneous injection of 50 units (L group), 100 units (M group) or 200 units (H group) of hPTH (1-34) was started in 220 patients with osteoporosis at 71 institutions randomly divided into three groups in a double-masked system. Lumbar spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) increased by 0.6%, 3.6% and 8.1% after 48 weeks in groups L, M and H respectively, responses in groups M and H being significantly higher than in L (p<0.05, Mann-Whitney U-test). Since the coefficient of variation for lumbar spine measurement stayed at 1-2.5%, increases of 3.6% and 8.1% appeared significant. Metacarpal BMD and cortical thickness measured by radiogrammetry did not change significantly. Serum calcium decreased in each group and serum phosphorus decreased in groups M and H. Urinary calcium/creatinine decreased at the 12th week in group H and at the 24th and 48th weeks in groups M and L. Serum 25(OH) vitamin D and 1,25(OH)(2) vitamin D decreased in each group at the 48th week (p<0.05). Serum bone-type alkaline phosphatase was increased at the fourth week in groups H and M and decreased at the 48th week in group H. Urinary hydroxyproline, pyridinoline and deoxypyridinoline declined significantly in each group. Backache improved in 30-40% of each group. No serious adverse effects were found during the test period. Intermittent weekly injection of hPTH (1-34) increased lumbar BMD in osteoporosis, suggesting usefulness in the treatment of osteoporosis.

Effect of bisphosphonate (incadronate) on fracture healing of long bones in rats.

This study was designed to test whether bisphosphonates disturb the process of fracture healing. Female Sprague-Dawley rats were injected with either two doses of bisphosphonate (incadronate) (10 microg/kg and 100 microg/kg) or vehicle three times a week for 2 weeks. Right femora were then fractured and fixed with intramedullary wires. Incadronate treatment was stopped in pretreatment groups (P-10 and P-100 groups), while the treatment was continued in continuous treatment groups (C-10 and C-100 groups). Animals were sacrificed at 6 and 16 weeks after surgery. Soft X-ray of all fractured femora was taken. After mechanical testing, fractured femora were stained in Villanueva bone stain and embedded in methyl methacrylate. Cross-sections near fracture line were analyzed by microradiography and histomorphometry. Radiographic study showed that bony callus was present in all the fractures and incadronate treatment led to a larger callus, especially in C-100 group at both 6 and 16 weeks. Histologic study showed that the process of fracture healing in pretreatment groups was delayed at 6 weeks, but reached control level thereafter and showed same characteristics as in control at 16 weeks. Woven bony callus could still be seen in continuous treatment groups at 16 weeks. Mechanical study indicated that the ultimate load of C-100 group was slightly higher than the other treatment groups and control. The results suggest that pretreatment with incadronate did not affect fracture healing at 16 weeks after fracture. However, continuous incadronate treatment could lead to larger callus, but it delayed remodeling process during fracture healing, especially with high-dose treatment.

Middle-term results of anatomic medullary locking total hip arthroplasty.

We report the results of cementless, anatomic, medullary locking hip prosthesis application in our first consecutive series. We used the so-called Asian size of prosthesis with proportionally smaller stem sizes in both diameter and length. Forty-seven stems and sockets were analyzed with a mean follow-up of 69 months. The mean Merle d'Aubigné hip scores were 8 points preoperatively and 16 points at the final follow-up. Radiologically, the stems showed excellent stability without loosening. Stress shielding around the stems did occur in most cases but did not progress. Preoperative bone quality influenced the extent of stress shielding evaluated at the final follow-up: higher stress shielding was noted in poorer quality bones at the time of operation. There were problems with the sockets. The shallow socket and impingement at the protruded rim seemed to cause a high incidence of dislocation (13%). Massive polyethylene wear occurred in 5 sockets. These sockets were 48 and 46 mm in diameter with 26 mm heads. In conclusion, the stems of the anatomic medullary locking hip prostheses used in Japan showed satisfactory stability even in poor quality bones, but there were problems with the polyethylene liners. Our solution was to use larger sockets with 22 mm heads.

Preadministration of incadronate disodium can prevent bone loss in rat proximal tibial metaphysis when induced by hindlimb immobilization by bandage.

The purpose of this study is to determine whether short-term preadministration of bisphosphonates prevents bone loss in rat proximal tibial metaphysis when induced by hindlimb immobilization by bandage. Six-month-old female Sprague Dawley rats were injected with incadronate disodium (YM-175, 10 micrograms/kg) or vehicle, three times per week for 2 weeks (YM or V groups). Then, the left hindlimb was fixed to the abdomen with a bandage (V-B, YM-B groups), or only the abdomen was bandaged as control (V-SHM, YM-SHM groups), for 4 weeks. The animals were subsequently killed and left proximal tibiae were processed undecalcified for quantitative histomorphometric evaluation. Immobilization-induced cancellous bone loss resulted not only from increased percent eroded surface area but also from decreased percent labeling surface and bone formation rate in V-B compared with V-SHM animals. In contrast, preadministration of YM-175 decreased percent eroded surface significantly and prevented the loss of cancellous bone mass in YM-B compared with V-B animals. Cancellous bone mass was neither increased nor decreased by preadministration of YM-175 in YM-SHM animals. Our results suggest that preadministration of bisphosphonates is effective in prevention of bone loss at the tibial metaphysis when induced by hindlimb immobilization in rats.

IL-13 as well as IL-4 induces monocytes/macrophages and a monoblastic cell line (UG3) to differentiate into multinucleated giant cells in the presence of M-CSF.

The formation of multinucleated giant cells (MGCs) from monocytes/macrophages is controlled by various cytokines whose crucial roles are not fully understood. In this study, we found that interleukin (IL)-13 as well as IL-4 induced peripheral blood monocytes (PBMs) and monoblastic cell line, UG3, to differentiate into MGCs in the presence of macrophage colony-stimulating factor (M-CSF), while IL-2, IL-7 or IL-10 did not. The presence of M-CSF was essential to this MGC formation, because IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF) could not replace M-CSF. IL-4 and IL-13 have been known to inhibit the formation of osteoclast-like cells in the presence of stroma cells or osteoblastic cells. But in our system without stroma cells, IL-4 or IL-13 induced some of characteristics of osteoclasts such as tartrate-resistant acid phosphatase (TRAP) activity, vitronectin receptor (vit-R) expression and resorptive activity for hydroxyapatite, but not the expression of receptors for parathyroid hormone or calcitonin. These results suggest possible involvement of IL-4 and IL-13 in MGCs and osteoclasts development, and UG3 may be useful to further investigate the roles of IL-4 and IL-13 in the formation and physiology of MGCs, and the relationship between these MGCs and osteoclasts.

Osteoclasts are present in gp130-deficient mice.

Interleukin (IL)-6, IL-11, leukemia inhibitory factor, and oncostatin M similarly induce osteoclast formation in cocultures of osteoblastic cells and bone marrow cells. These cytokines share a common signal transducer, gp130, which forms a receptor complex with the specific receptor for each cytokine. To investigate the role of gp130 in osteoclast development, we examined bone tissues in gp130-deficient and wild-type newborn mice of the ICR background. Soft x-ray radiographs and microfocus x-ray computed tomographs revealed that bone marrow cavities were present in tibiae and radii of both wild-type and gp130-deficient mice. Microfocus x-ray computed tomography and histological examination demonstrated a decrease in the amount of trabeculae at the metaphysial region in tibiae and radii of the gp130-deficient mice compared with the wild-type mice. The number ofosteoclasts in gp130-deficient mice was about double that in the wild-type mice. There were no apparent differences in the distributions of alkaline phosphatase-positive osteoblasts and the osteoid surface on the trabecular bone at the metaphysial region between the wild-type and gp130-deficient mice. The volume of mineralized trabecular bones was also decreased at mandibulae, accompanied by the increased number of osteoclasts in gp130-deficient mice compared with the wild-type and heterozygous mice. These results suggest that the formation of osteoclasts is not solely dependent on gp130 signaling, at least during fetal development. The osteoclastic bone resorption in gp130-deficient mice may be caused by the functional redundancy of bone-resorbing hormones and cytokines other than those of the IL-6 family.

Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes: a possible mechanism of pathological neovascularization in arthritis.

Prolonged incubation with interleukin-1 beta (IL-1) induced the release of large amounts of NO and subsequently inhibited DNA synthesis and the biosynthesis and accumulation of proteoglycans in cultured rabbit articular chondrocytes (RAC). IL-1 also inhibited DNA synthesis in bovine aortic endothelial cells (BAE). On the other hand, DNA synthesis in BAE cocultured with RAC was not inhibited by prolonged incubation with IL-1. Moreover, conditioned media from RAC incubated for a long period with IL-1 stimulated DNA synthesis in BAE alone. This growth stimulatory activity was mainly due to the release of basic fibroblast growth factor, a heparin-binding growth factor, into RAC culture. Gelatin zymography of the RAC culture medium revealed that IL-1 increased the production of matrix metalloproteinase-2 (MMP-2) and MMP-9. NG-Monomethyl-L-arginine, an inhibitor of NO synthesis, inhibited all of these actions of IL-1. These results indicate that NO from RAC treated with IL-1 stimulates MMPs, which, in turn, degrade the extracellular matrix produced by RAC, resulting in the release of large amounts of basic fibroblast growth factor stored in the matrix, which then stimulates adjacent BAE proliferation. Thus, NO produced from RAC treated with IL-1 may modulate angiogenesis in the synovium of arthritic patients.

A histomorphometric study on effects of single and concurrent intermittent administration of human PTH (1-34) and bisphosphonate cimadronate on tibial metaphysis in ovariectomized rats.

This study compared the single administration of hPTH(1-34), bisphosphonate cimadronate (YM-175), and concurrent therapy of these two for restoration of lost bone mass in ovariectomized (OVX) rats. Animals were untreated for 4 weeks after surgery, and then injected s.c. with vehicle (OVX+V), hPTH(1-34) (30 micrograms/kg) (OVX+P), YM-175 (5 micrograms/kg) (OVX+Y), or a combination of these two (OVX+P+Y), 3 days a week, for 8 weeks, and sacrificed. Their proximal tibia were processed undecalcified for quantitative bone histomorphometry. Although OVX+Y showed a reduction of bone turnover compared to OVX+V, it failed to restore lost bone mass in OVX rats. In contrast, OVX+P exhibited a stimulation of bone formation and restored cancellous osteopenia due to OVX. OVX+P+Y also resulted a recovery of osteopenia, however, stimulation of bone formation by PTH was suppressed by YM-175.