BACKGROUND: Interactions between the receptor activator of the NF-kappaB ligand (RANKL) and its receptor, RANK, are important in the terminal differentiation and activation of osteoclasts. In the current investigation, we examine the feasibility of using genetically modified mesenchymal stem cells (MSCs), C3H10T1/2 cells as a platform for the sustained systemic delivery of therapeutic proteins into the circulation in an osteoporosis model, and investigate retroviral-mediated gene therapy of RANK-Fc as a means of ameliorating ovariectomy (OVX)-induced bone resorption. METHODS: C3H10T1/2 cells were transduced with a MSCV-based retroviral vector containing cDNA of a fusion protein combining the extracellular domain of murine RANK with the human immunoglobulin constant domain (MSCV-RANK-Fc-eGFP). Young adult female mice were subjected to OVX or sham surgery, followed by treatment with transduced cells or PBS 4 weeks later. The expression of RANK-Fc by these cells was assessed, both in vitro and in vivo. Total bone mineral density (BMD) was measured and GFP expression was examined. RESULTS: Transduced cells produced biologically active RANK-Fc in vitro and in vivo. Mice that were subjected to OVX followed by treatment with cells transduced with MSCV-RANK-Fc-eGFP 4 weeks later contained no significant but higher total BMD than either the control vector or PBS-treated mice after 8 weeks. Higher GFP expression was attained in the liver, spleen, and intra-abdominal fat of mice treated with MSCV-RANK-Fc-eGFP. CONCLUSION: The data collectively indicate that C3H10T1/2 cells are effectively transduced with a MSCV-based retrovirus, and are capable of secreting biologically active RANK-Fc in vitro and in vivo. Moreover, gene therapy facilitating the sustained delivery of RANK-Fc may be an effective method to reverse OVX-induced osteoporosis.
Animals ; Bone Density ; Bone Resorption ; DNA, Complementary ; Female ; Genetic Therapy ; Humans ; Immunoglobulins ; Intra-Abdominal Fat ; Liver ; Mesenchymal Stromal Cells ; Mice* ; NF-kappa B ; Osteoclasts ; Osteoporosis* ; Ovariectomy* ; Retroviridae* ; Spleen ; Young Adult ; Zidovudine

No abstract available.
Calcium* ; Receptors, Calcium-Sensing*

No abstract available.

No abstract available.
Leptin* ; Metabolism*

Osteoporosis, now defined as a disease characterized by a low bone mass and a microarchitectural deterioration of bone tissue leading to an enhanced bone fragility and fracture risk, is a major public health problem, affecting 200 million individuals worldwide. Optimal treatment and prevention of osteoporosis require modification of risk factors, particularly smoking cessation, adequate physical activity, and attention to diet, in addition to pharmacologic intervention. A number of pharmacologic options are now available to health care providers. The estrogens and raloxifene both prevent bone loss in postmenopausal women, and the estrogens probably also decrease the risk of first fracture. There is a good evidence that raloxifene prevents further fractures in postmenopausal women who already have had fractures and some evidence that estrogen does as well. Bisphosphonate alendronate prevents bone loss and reduces fractures in healthy and osteoporotic postmenopausal women, and in osteoporotic men as well. Risedronate is more potent and has fewer upper gastrointestinal side effects than alendronate, and reduces the incidence of fractures in osteoporotic women. An intermittent use of potent bisphosphonate zoledronate also increases bone mineral density and may become an alternative in the prevention and treatment of osteoporosis. Calcitonin increases bone mineral density in early postmenopausal women and men with idiopathic osteoporosis, and also reduces the risk of new fractures in osteoporotic women. All of the agents discussed above prevent bone resorption, whereas teriparatide increases bone formation and is effective in the treatment of osteoporotic women and men. Bisphosphonates are also effective in the treatment of secondary osteoporosis associated with the use of glucocorticoids to treat inflammation or prevent rejection after transplantation. New avenues for targeting osteoporosis will emerge as our knowledge of the regulatory mechanisms of bone remodelling increases, although issues of tissue specificity may remain to be solved.
Alendronate ; Bone and Bones ; Bone Density ; Bone Resorption ; Calcitonin ; Diet ; Diphosphonates ; Estrogens ; Female ; Glucocorticoids ; Health Personnel ; Humans ; Incidence ; Inflammation ; Male ; Motor Activity ; Organ Specificity ; Osteogenesis ; Osteoporosis ; Osteoporosis, Postmenopausal* ; Public Health ; Raloxifene Hydrochloride ; Risedronate Sodium ; Risk Factors ; Smoking Cessation ; Teriparatide

No abstract available.
Hyperparathyroidism, Primary ; Parathyroid Neoplasms

PURPOSES: To evaluate the effect of hormone replacement therapy(HRT) on serum insulin-like growth factors(IGFs) levels and to investigate if changes in serum IGFs reflect changes in BMD after HRT in postmenopausal women. MATERIAL & METHODS: IGF-I and IGF-II were measured by radioimmunoassay after Bio-spin P-10 seperation in sera obtained every 3 months from postmenopausal women who was taking premarin alone (premarin group; n=17) or premarin-medroxyprogesterone acetate(MPA group; n=42) for 1 year. Also, bone mineral density(BMD) were determined before and 1 year after HRT by dual energy X-ray absorptiometry(DEXA). All statistics were performed by Paired t-test, student's t-test, repeated measures ANOVA test, Pearson's coefficient. RESULTS: HRT increased BMD of the lumbar spine and proximal femur in both premarin group and MPA group, but any difference in degreee of increase in BMD was not noted between premarin group and MPA group. Compared with pretreatment levels, serum IGF-I levels decreased at 3, 6 and 12 months after therapy only in latter group whereas serum IGF-II levels increased at 6 and 12 months after HRT in both groups. Changes in serum IGF-I and IGF-II levels during therapy did not show any difference by the bone response to HRT. Changes in serum IGF-II levels after HRT did not correlated with the 1 year changes in BMD at any skeletal sites studied, but changes in serum IGF-I levels from pretreatment to 6 months after HRT was negatively correlated with change in BMD of Ward's triangle. CONCLUSION: HRT influences serum IGF levels in postmenopausal women and changes in serum IGF-I levels may predict the changes in BMD of Ward's triangle after HRT.
Bone Density* ; Estrogens, Conjugated (USP) ; Female ; Femur ; Hormone Replacement Therapy* ; Humans ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Postmenopause ; Radioimmunoassay ; Spine

Binocular diplopia after catarat surgery is a rare phenomenon, and it happens by variable mechanisms including extraocular muscle injury during bridle suture placement and myotoxicity of local anesthetics. We experienced three cases of binocular diplopia following successful cataract surgery in patients who had no history of strabismus, amblyopia and neurologic or systemic disease which might be related to mobility disorder. We report these cases and previous literature is reviewed.
Amblyopia ; Anesthetics, Local ; Cataract* ; Diplopia ; Humans ; Strabismus ; Sutures ; Telescopes*

No Abstract Available.
Knee* ; Synovitis, Pigmented Villonodular*

In this unprecedented era of the overwhelming volume of medical data, machine learning can be a promising tool that may shed light on an individualized approach and a better understanding of the disease in the field of osteoporosis research, similar to that in other research fields. This review aimed to provide an overview of the latest studies using machine learning to address issues, mainly focusing on osteoporosis and fractures. Machine learning models for diagnosing and classifying osteoporosis and detecting fractures from images have shown promising performance. Fracture risk prediction is another promising field of research, and studies are being conducted using various data sources. However, these approaches may be biased due to the nature of the techniques or the quality of the data. Therefore, more studies based on the proposed guidelines are needed to improve the technical feasibility and generalizability of artificial intelligence algorithms.