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Bisphosphonates ( BPs) are bone resorption inhibitors, which are increasingly used in the treatment of bone metabolic diseases in women of childbearing age. It is unclear whether the use of BPs in women of childbearing age will affect the health of their offspring. This article retrieved 66 reports in the past 40 years by searching on the databases of Pubmed, Embase, Ovid, Medline and so on. A number of reports found that BPs may be responsible for shortening gestational age, increasing spontaneous abortion, and decreasing neonatal birth weight. Three women's offsprings were found to have abnormal blood calcium after birth. Cases of skeletal malformations include two bilateral talipes equinus, one Apert's syndrome and one rickets. However, there have been many reports of no reproductive abnormalities or abnormal blood calcium level. Occasionally, children breast-fed by women who had received BPs have had a transient hypocalcemia. There is currently insufficient evidence to confirm that BPs can cause significant reproductive malformations during pregnancy or pre-pregnancy. However, due to the long-term presence of BPs in the bones, women of childbearing age who have a need for pregnancy should choose to use these drugs with caution.
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<p><b>BACKGROUND</b>Genetic factors are important in the pathogenesis of osteoporosis, but less is known about the genetic determinants of osteoporosis treatment. We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase (FDPS) in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China.</p><p><b>METHODS</b>The study group comprised 639 postmenopausal women aged (62.2 ± 7.0) years with osteoporosis or osteopenia who had been randomly assigned to low dose group (70 mg/2 w) or standard dose group (70 mg/w) of alendronate in this 1-year study. We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul. Before and after treatment, serum levels of calcium, phosphate, alkaline phosphatase (ALP), cross linked C-telopeptide of type I collagen (β-CTX) were detected. Bone mineral density (BMD) at lumbar spine and proximal femur was measured. The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD, bone turnover biomarkers after the treatment.</p><p><b>RESULTS</b>The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck, and patients with CC genotype had significantly higher baseline femoral neck BMD ((733.6 ± 84.1) mg/cm(2)) than those with AC genotypes ((703.0 ± 86.9) mg/cm(2)) and AA genotypes ((649.8 ± 62.4) mg/cm(2)) (P < 0.01). No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS. The percentage change of serum ALP level was significantly lower in patients with CC genotype (-22.9%) than that in those with AC genotype (-24.1%) and AA genotype (-29.8%) of FDPS after 12 months of alendronate treatment (P < 0.05). Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype.</p><p><b>CONCLUSIONS</b>FDPS gene was probably a candidate gene to predict femoral neck BMD at baseline. FDPS gene alleles could predict change percentage of ALP after treatment of alendronate, but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.</p>
Subject(s)
Female , Humans , Middle Aged , Alendronate , Therapeutic Uses , Asian People , Bone Density Conservation Agents , Therapeutic Uses , Geranyltranstransferase , Genetics , Osteoporosis, Postmenopausal , Drug Therapy , Genetics , Polymorphism, GeneticABSTRACT
Objective To study the effects of 1,25-(OH)_2-vitamin D_3[1,25-(OH)_2D_3] on proliferation,differentiation, and secretion of osteoprotegerin and RANK ligand (RANKL)in cultured marrow mesenchymal cells of rhesus monkey (RhBMSCs). Methods Three different concentrations of 1,25-(OH)_2D_3 (10~(-12) ,10~(-10), and 10~(-8)mol/L)were added to the cultured RhBMSCs in vitro. MTT was used to observe cell proliferation and ELISA technique was used to measure the concentration of alkaline phosphatase (ALP), osteocalcin, osteoprotegerin, and RANKL. Mineralization nodus was identified via alizarin red staining. Results Under different concentration of 1,25-(OH)_2D_3, RhBMSCs proliferation were promoted within 7 days but were suppressed beyond 7 days. No significant dose-dependent manner was found. Differentiation of RhBMSCs into osteoblast was promoted by 1,25-(OH)_2D_3. The levels of ALP and osteocalcin in groups with various concentrations of 1,25-(OH)_2D_3 were higher than those of control group [ALP(ng/ml) ,7 d:31.40±1.25,26.50±0.50,28.47± 0.25 vs 13.48±0.26;10 d:33.37±0.68,35.30±1.57,33.27±0.67 vs 17.14±0.55;13 d:35.37±0.12,30.47± 0. 25 , 30. 27±1.25 vs 16.55 ± 1.13 ; osteocalcin (ng/ml), 7 d:4.47±0. 29,4.00 ±0. 60,3.73±0.78 vs 1.63± 0.55;10 d:5.63±0.57,5.17±0.15,4.30±0. 10 vs 2.17±0. 15;13 d:7.03±0.15,5.53±0.25,5.27±0.31 vs 2.23±0. 55 ; all P < 0. 05], but no typical mineralization nodus was found in either group. Secretions of osteoprotegerin and RANKL from RhBMSCs were stimulated by 1,25-(OH)_2D_3 [osteoprotegerin (pg/ml), 7 d: 72.57±0.67,68.00±1.75,64.23±0.87 vs 30. 13±1.72; 10 d:62.03±1.62,51.80±1.30,28.93±0.95 vs 18.13±1.40;13 d:65.13±0.71,62.43±2.11,44.93+1.63 vs 36.70±0.95 ;RANKL(pg/ml) ,7 d:74.33+0.61, 82.37±2.15,85.23±0.45 vs 70.83±1.71 ;10 d:83.30±0.46,86.70±0.56,88.23±0.91 vs 74.20±1.83;13 d: 81.70±1.81,81.07±0.95,84.70±1.41 vs 72.73±0.97 ;all P<0.05]. The secretion of RANKL was increased at first and then decreased, whereas the secretion of osteoprotegerin had the opposite tendency. The secretions of RANKL and osteoprotegerin were both in a dose-dependent manner. Conclusions 1,25-(OH)_2D_3 promotes differentiation of RhBMSCs into osteoblasts,resulting in increased secretions of osteoprotegerin and RANKL
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BACKGROUND: Most of the literatures only reported that there is a great difference between diabetics who have a high 24-hour urinary albumin excretion rate and those without renal damage, but there is no obvious difference between cases of microalbuminuria and those without renal damage.OBJECTIVE: To probe into the relationship between diabetic nephropathy and osteoporosis.DESIGN: A case-control study.SETTING: Department of Endocrinology, West China Hospital of Sichuan University.PARTICIPANTS: According to the diagnostic standard set by the American Diabetes Association in 1997 (fasting blood glucose ≥ 7 mmol/L,postprandial blood glucose ≥ 11.1 mmol/L), 96 diabetic patients were selected, including 56 males ＜ 60 years old and 40 females who had not entered the menopausal period, excluding the influence of age and osteoporosis caused by menopause. The average age of the subjects was (48.7±10.5)years, their duration were from one month to twenty-one years with the aver age of (7.85±2.56) years, and their general information had no significant differences.METHODS: According to the urine albumine excretion rate and renal function, the patients were divided into four groups: normal albuminuria group (n=48), microalbuminuria group (n=28), macroalbuminuria group (n=15), renal failure group (n=5). The bone mineral densities of lumbar spines (L2-4), femoral neck, Ward's triangle and trochanter were detected with Dual energy X-ray absorptiometry, and then the fasting blood glucose,2-hour postprandial blood glucose, glycosylated hemoglobin A, alkaline phosphatase, calcium, phosphorus, blood urea nitrogen, creatinine and urine albumine excretion rate were compared between the patients with and without osteoporosis.MAIN OUTCOME MEASURES: The fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin A, alkaline phosphatase, calcium, phosphorus, blood urea nitrogen, creatinine and urine albumine excretion rate, as well as the bone mineral density, were observed in all the patients.RESULTS: The L2-3 bone mineral density in the macroalbuminuria group was significantly different from that in the microalbuminuria group (P ＜ 0.05). The proximal femur bone mineral density in the microalbuminuria group was significantly different from that in the normal albuminuria group (P ＜ 0.05). The bone mineral densities of proximal femur and lumbar spine in the renal failure group were significantly decreased as compared with those in the other groups (P ＜ 0.01). The disease course,glycosylated hemoglobin A, alkaline phosphatase and body mass index were significantly different between the patients with and without osteoporosis (P ＜ 0.05).CONCLUSION: The incidence rate of osteoporosis is increased with the aggravation of nephropathy, and diabetic nephropathy may be closely correlated with the decrease of bone mineral density and the occurrence of osteoporosis.
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Objective To investigate the relationship between the TRAb-producing cell precursors and different clinical stages of Graves' disease.Methods Peripheral lymphocytes were infected with Epstein-Barr virus,a kind of lymphocyte precursor stimulator,and were stimulated to produce TRAb.Results Of the total wells containing Ig-producing B cell precursors,there were 34.6% and 29.1% from 2 untreated patients,30% from 1 relapsing patient and only 1.3% and 3.8% from 2 healthy controls that secreted TRAb,respectively.As for the wells containing B cell precursors from 2 remission patients with undetectable TRAb in circulation,the percentage (10.7%) of TRAb-containing wells from one was higher than that from the other (5.3%).And the latter had similar percentage of TRAb-positive wells with the controls.The isotype of TRAb in supernatants of our EBV-transformed B lymphocytes was predominantly IgM.Conclusion The frequencies of TRAb-specific precursors were different at three distinct clinical stages of the disease.
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Objective To investigate the heritability of Graves′ disease (GD) and to discuss its clinical significance. Methods The heritability of GD was calculated using Falconer′s formula and by investigating the GD numbers of 1968 first relatives of 526 established GD patients. Results The heritability of GD was 45%, appearantlymuchlowerthanthoseofprevious reports in China. Conclusion The onset of GD is affected by both inheritant and environmental factors, the latter seems to be predominant over the former.