Bone and mineral最新文献

To determine the potential adverse effects, if any, of long-term fluoride ingestion in humans, samples were collected from 25 adult females taking daily doses of fluoride (mean, 23 mg elemental F) for the treatment of osteoporosis and from 38 osteoporotic female controls. Patients in the fluoride group had been receiving therapy for approximately 18 months with a mean duration of 4.2 years and had serum fluoride values of at least 10 μmol/l. Laboratory analyses for fluoride were conducted on plasma, urine and drinking water samples collected from each panelist. Blood was also collected for blood chemistry analyses and plasma lymphocytes were examined for the frequency of sister chromatid exchange (SCE). Plasma and urine fluoride levels were significantly different between the two groups, while water fluoride was not. The SCE frequency, a measurement of potential genotoxicity, did not differ between the two groups. Of the blood chemistry parameters measured, albumin, alkaline phosphatase, sodium, chloride, the albumin/globulin (A/G) ratio, indirect bilirubin, lactate dehydrogenase (LDH), and γ-glutamyl transferase (GGT) were found to be significantly different between the two groups (P ≤ 0.05). However, none of the mean group values were outside stated normal ranges for any of these parameters. We conclude that the risk of developing adverse systemic effects from the ingestion of fluoride, at dosages and for a duration comparable with that of our panel, is minimal.

The bisphosphonate, 1-hydroxyethylidene-1,1-bisphosphonate (HEBP), was examined for its effect on calcium phosphate precipitation in pH 7.4, 22°C suspensions of 7∶2∶1 phosphatidylcholine (PC):dicetylphosphate (DCP):cholesterol (Choi) and 7∶1∶1 PCphosphatidylserine (PS).Chol liposomes. HEBP (0.5–50 μmol/l) in the suspending medium had little, if any, effect on precipitation that formed inside phosphate-rich (50 mmol/l) aqueous interiors of liposomes as a result of ionophore (X-537A) driven 2.25 mmol/l Ca²⁺ influxes from the medium. On the other hand, HEBP had a significant negative impact on the subsequent spread of the precipitate into the surrounding medium when the latter was made metastable with 1.5 mmol/l total inorganic phosphate (PO₄). The inhibitory effect of HEBP was more strongly felt in the 7PC∶1PS∶1Chol liposomal suspensions, with only 1 μmol/l HEBP needed to effectively block extraliposomal precipitation compared to 7.5 μmol/l for 7PC∶2DCP∶1Chol suspensions. Direct encapsulation of HEBP (1–1000 μmol/l) together with PO₄ in the aqueous cores of 7PC∶2DCP∶Cho1 liposomes reduced somewhat (~ 30%) intraliposomal yields and delayed but did not block extraliposomal precipitate development. These results provide a possible physicochemical explanation for the suppression of matrix vesicle initiated mineralization in ectopically-induced osteoid tissue of HEBP treated mice [1]. In particular, the liposome results suggest that membrane phosphatidylserine interactions with mineral may enhance HEBP's effectiveness in vivo.

Sex steroid hormones are known to have gender-dependent effects on bone and cartilage in vivo and in vitro. To investigate whether this is a general property of steroids, or is specific to the sex steroid hormones, we examined whether the effects on bone of l,25-(OH)₂D₃ and 24,25(OH)₂D₃, the two active metabolites of vitamin D, are also gender-dependent. One-month-old male and female rats were treated for 1 month with various doses of 1,25-(OH)₂D₃, 24,25-(OH)₂D₃, or a combination of both metabolites. The direct effects of both metabolites on the skeleton of the treated animals were similar in male and female rats. 24,25-(OH)₂D₃ alone or in combination with l,25-(OH)₂D₃ increased bone calcium and phosphorus, while l,25-(OH)₂D₃ slightly decreased bone mineral content. 24,25-(OH)₂D₃ also enhanced the differentiation of cartilage in the growth plate, increasing the size of the hypertrophic zone. In addition, an increased metaphyseal bone volume was observed following 24,25-(OH)₂D₃ treatment in rats of both sexes, but not with l,25-(OH)₂D₃. Vitamin D metabolites affected the weight gain of the experimental animals in a gender-dependent manner; l,25-(OH)₂D₃ increased weight gain of male rats and 24,25-(OH)₂D₃ decreased weight gain of female rats. In addition, l,25-(OH)₂D₃ increased bone weight and ash weight in male animals. These gender-dependent effects of vitamin D metabolites may occur indirectly via effects of sex steroid hormones, the latter being a sex-related effect.

In the present study we assessed the effects of ipriflavone in the prevention of increased bone turnover and the rapid bone loss that follows medical induced hypogonadism caused by the administration of a gonadotropin hormone-releasing hormone agonist (GnRH-A). In a double blind, placebo-controlled study, ipriflavone (600 mg/day, tdd (three divided doses)) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with 3.75 mg leuproreline acetate every 30 days, for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma bone GLA protein levels showed a substantial (P < 0.01) increase, while spine bone density and total body bone density significantly (P < 0.01) decreased after 3 and 6 months of GnRH-A administration. Conversely, in ipriflavone treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medical induced hypogonadism. Thus, ipriflavone administration can be of value in the prevention of osteopenia in women treated with GnRH-A.

We investigated the role of protein kinase C (PKC) in osteoblast function using a set of putative PKC modulating factors and an in situ peptide substrate-based kinase assay in different types of osteoblastic cells. Primary calvarial rat osteoblastic cells (ROB) and ROS 17/2.8 osteosarcoma cells showed an equally high PKC activity when a maximal dose of PKC-activating phorbol ester was applied. The osteosarcoma cell line UMR 106-01 showed only 5–10% of this maximal PKC activity. All 3 cell types responded to 10 U/ml thrombin with a 2-fold stimulation of PKC activity. However, no distinct direct effects of parathyroid hormone (bPTH (1–34)) or transforming growth factor-β₂ (TGF-β₂) were found in either of the cell types. The thrombin-induced stimulation of PKC was associated with an increase in the PTH-mediated cAMP response of ROB. Down-regulation of PKC-activity was found when ROB were treated for 24 h with phorbol ester and, interestingly, also after a 24 h treatment with bPTH (1–34) and TGF-β₂. We conclude that differences in PKC activity exist among osteoblastic cell types, which may be related to their different proliferative activity. Direct PKC activation may lead to modulation of the cAMP signaling pathway. Down-regulation of PKC activity by bPTH (1–34) and TGF-β₂ provides an interesting possible mechanism for the long-term regulation of signal transduction.