PTH, via the PTH/PTH-related protein receptor type 1 that couples to both protein kinase A (PKA) and protein kinase C (PKC) pathways, and the canonical Wnt-beta-catenin signaling pathway play important roles in bone formation. In the present study we have examined the interaction between the PTH and Wnt signaling pathways in mouse osteoblastic MC3T3-E1 cells. PTH dose- and time-dependently increased the concentrations of beta-catenin. The PKA activator, forskolin, and the PKC activator, phorbol 12-myristate-13-acetate, as well as the PTH analog, [Nle(8,18),Tyr(34)]human PTH-(3-34)amide, all increased beta-catenin levels. Both H-89, a specific PKA inhibitor, and PKC inhibitors, staurosporine and calphostin C, antagonized PTH stimulation of beta-catenin levels. TGF-beta as well as transfection of the TGF-beta-signaling molecule, Smad3, enhanced beta-catenin levels, and this was antagonized by transfection of a dominant-negative Smad3. The transcriptional activity of transfected dominant-active beta-catenin was enhanced by PTH, an effect that was antagonized by cotransfection of a dominant-negative Smad3. PTH as well as LiCl(2), which mimics the effects of the Wnt-beta-catenin pathway, rescued the dexamethasone- and etoposide-induced apoptosis of osteoblastic cells. In conclusion, the data demonstrate that PTH stimulates osteoblast beta-catenin levels via Smad3, and that both PKA and PKC pathways are involved. The canonical Wnt-beta-catenin pathway is likely to be involved in the antiapoptotic actions of PTH by acting through Smad3 in osteoblasts.

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The LD-100 system is a useful bone densitometry device and the database of age-related changes in TBD, CoTh, and EMTb established in this study will provide fundamental data for future studies related to bone status.

The present study revealed that body composition is related to vertebral fracture risk in GC-treated patients. Lower % fat can be included in the determination of vertebral fractures in postmenopausal GC-treated patients. The influence of body composition on vertebral fracture risk may be different between the pre- and postmenopausal state in GC patients.

Abstract. Controversy still exists about whether vitamin D status is related to the severity of primary hyperparathyroidism (pHPT), although vitamin D insufficiency is frequent in pHPT. The present study was therefore performed to examine the relationships between vitamin D status and various parameters in 30 postmenopausal pHPT patients. BMD values were measured by dual-energy x-ray absorptiometry at the lumbar spine (L 2-4 ), femoral neck (FN) and distal one third of the radius (Rad 1/3). Serum levels of 25 hydroxy-vitamn D 3 [25(OH)D] and 1,25-dihydroxy vitamin D 3 [1,25(OH) 2 D 3 ] were 15.8 ± 3.5 µg/l and 69.3 ± 33.3 ng/l in pHPT patients, respectively. Serum levels of calcium and PTH seemed to be negatively correlated to serum 25(OH)D levels, although the differences were not significant. However, when subjects with the highest serum PTH levels (PTH>1000 pg/ml) were excluded from the analysis, the correlation was significant between serum 25(OH)D levels and PTH, indicating that vitamin D status affects the severity of pHPT when severe cases were excluded. In addition, serum levels of 1,25(OH) 2 D 3 were significantly and negatively correlated to serum 25(OH)D levels. On the other hand, serum levels of 25(OH)D were significantly and positively correlated to BMD (Z-score) at the lumbar spine, but not at the radius and femoral neck; however, serum 25(OH)D levels were not correlated to the levels of any bone metabolic indices measured. Moreover, serum levels of 25(OH)D were not related to urinary calcium and the tubular reabsorption rate of phosphorus, and they were similar in groups with and without renal stones. In conclusion, vitamin D status seemed to be related to the severity of disease in postmenopausal patients with pHPT. In particular, the relationship between serum 25(OH)D level and BMD at the lumbar spine was predominant. Primary hyperparathyroidism (pHPT) is a relatively common endocrine disorder that causes secondary osteoporosis. Patients with pHPT have reduced BMD, especially at the cortical bone [6,7]. Several studies suggested that pHPT was associated with an increased risk of vertebral and forearm fractures, and a subsequent decrease of fracture risk after parathyroidectomy [8][9][10][11][12], although our recent cross-sectional study sug- gested that the threshold of BMD for vertebral fractures was lower, especially at radial bone in female pHPT patients [13]. As for bone geometry, our previous study using peripheral quantitative computed tomography in female pHPT patients suggested that an excess of endogenous PTH stimulated periosteal bone formation, which might partly compensate for a decrease in bone strength induced by low BMD [14].As for vitamin D insufficiency, several studies indicated that vitamin D insufficiency is related to the severity of pHPT [15][16][17][18]. Rao et al. [16] reported that suboptimal vitamin D nutrition stimulates parathyroid adenoma growth, although other reports did not confirm this [17,19,20]. Several reports suggested that vitamin D receptor polymorphisms a...