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Circulating semaphorin-4D and plexin-B1 levels in postmenopausal women with low bone mass: the 3-month effect of zoledronic acid, denosumab or teriparatide treatment.
Anastasilakis, AD, Polyzos, SA, Makras, P, Gkiomisi, A, Sakellariou, G, Savvidis, M, Papatheodorou, A, Kokkoris, P, Terpos, E
Expert opinion on therapeutic targets. 2015;(3):299-306
Abstract
OBJECTIVE The evaluation of circulating semaphorin-4D (sema4D) and plexin-B1 in postmenopausal women with low bone mass and the effect of antiresorptive or osteoanabolic treatment. METHODS Serum samples were obtained from postmenopausal women with low bone mass at baseline and 3 months after zoledronic acid infusion (n = 30), denosumab injection (n = 30) or teriparatide initiation (n = 28) and from controls matched for age, age at menopause and body mass index (n = 30) at the same time points. MAIN OUTCOME MEASURES Circulating sema4D and plexin-B1. RESULTS Circulating sema4D increased following denosumab (p = 0.026), whereas decreased following teriparatide (p = 0.013). Sema4D/plexin-B1 ratio increased following denosumab (p = 0.004). At baseline, sema4D and plexin-B1 levels were higher in patients pre-treated with bisphosphonates compared to naïve ones (p < 0.001 and p = 0.001, respectively). In bivariate correlations sema4D was inversely correlated with serum carboxyterminal telopeptide of type 1 collagen (rs -0.282, p = 0.002), intact parathyroid hormone (rs -0.388, p < 0.001) and 25(OH)D (rs -0.316, p < 0.001), whereas there was a trend towards correlation with lumbar spine bone mineral density (rs -0.191, p = 0.053). CONCLUSIONS Sema4D levels are independently associated with previous bisphosphonate treatment, intact parathyroid hormone and 25(OH)D levels. Denosumab and teriparatide seem to exert an opposite effect on circulating sema4D levels. Further studies are needed to evaluate whether sema4D mediates the coupling effect that occurs following both antiresorptive and osteoanabolic treatment.
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Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women.
Gambacciani, M, Cappagli, B, Ciaponi, M, Pepe, A, Vacca, F, Genazzani, AR
Maturitas. 2008;(1):2-6
Abstract
OBJECTIVES The aim of the present study was to evaluate the effects of low doses of hormone replacement therapy (HRT) in normal young postmenopausal women. METHODS In an open trial healthy, non-obese postmenopausal women received for 2 years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5 mg norethisterone acetate each pill for 28 days, or 0.5 mg of 17beta-estradiol and 0.25 mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000 mg of calcium per day. Control group consisted of women receiving only 1000 mg of calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green climacteric scale for the first 12 weeks of the study while bleeding profiles, bone mineral density (BMD) and bone turnover were assessed for 24 months. RESULTS LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%, respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women. CONCLUSIONS LD-HRT and Ultra-LD-HRT can alleviate subjective symptoms providing an effective protection against the postmenopausal decrease of BMD.
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Assessment of non-vertebral fracture risk in postmenopausal women.
Roux, C, Briot, K, Horlait, S, Varbanov, A, Watts, NB, Boonen, S
Annals of the rheumatic diseases. 2007;(7):931-5
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Abstract
BACKGROUND Non-vertebral (NV) fractures are responsible for a great amount of morbidity, mortality and cost attributable to osteoporosis. OBJECTIVES To identify risk factors for NV fractures in postmenopausal women with osteoporosis, and to design an assessment tool for prediction of these fractures. METHODS 2546 postmenopausal women with osteoporosis included in the placebo groups of three risedronate controlled trials were included (mean age 72 years, mean femoral T-score -2.5; 60% and 53% of patients with prevalent vertebral and NV fractures, respectively). Over 3 years, 222 NV fractures were observed. Baseline data on 14 risk factors were included in a logistic regression analysis. RESULTS 6 risk factors were associated with NV fracture risk: prevalent NV fracture (p = 0.004), number of prevalent vertebral fractures (p<0.001), femoral T-score (p = 0.031), serum level of 25-hydroxyvitamin D (p<0.001), age (p = 0.012) and height (p = 0.037). An NV risk index was developed by converting the multivariate logistic equation into an additive score. In the group of women with a score > or =2.1, the incidence of NV fracture was 13.2% (95% CI 11.1 to 15.3), 1.5 times higher than that of the general population. CONCLUSIONS The NV risk index is a convenient tool for selection of patients with osteoporosis with a high risk for NV fractures, and may help to choose from available treatments those with a proven efficacy for reduction of NV fracture risk.
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Tibolone and osteoporosis.
Lazovic, G, Radivojevic, U, Milosevic, V, Lazovic, A, Jeremic, K, Glisic, A
Archives of gynecology and obstetrics. 2007;(6):577-81
Abstract
BACKGROUND We conducted a 5-year prospective, observational, controlled study to assess the effects of tibolone 1.25 mg/day on bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis. METHODS The subjects were 420 women, an average of 66.4 years old, who had been postmenopausal between 8 and 19 years when enrolled in the study. Of the 420 women enrolled, 346 agreed to take tibolone for 5 years. The 74 who refused tibolone took only calcium/vitamin D supplements and served as the control group. BMD was measured in the lumbar spine and total hip region at baseline and annually by dual-energy X-ray absorptiometry (DXA). RESULTS At the first two follow-up visits, women taking tibolone had a significant increase in BMD at the spine (P < 0.001) and at the hip (P < 0.001) when compared to baseline values and when compared to BMD values for the control group, which decreased from baseline. In the final 3 years of the study, BMD values (spine and hip) continued to decrease in the control group and also tended to decrease in the tibolone group, but at the end of the fifth year, mean BMD in the tibolone group was still higher than BMD before the start of tibolone treatment (P < 0.05). Calculations showed that if women taking tibolone continued to lose BMD at the same rate as during the final 3 years of the study, after 11 years of tibolone treatment the average patient would have the same BMD as she had when treatment started. CONCLUSION This 5-year observational study provides evidence that tibolone is effective in increasing BMD in postmenopausal women with osteopenia and osteoporosis during the first 2 years of treatment, but because BMD starts to decline in the third year, it is vital that postmenopausal women start treatment with tibolone as early as possible, so that bone mineral density levels are kept high as long as possible.
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[Effect of soybean intake on bone mineral density and bone turnover markers in postmenopausal women].
Son, GS
Taehan Kanho Hakhoe chi. 2006;(6):933-41
Abstract
OBJECTIVE The purpose of this study was to evaluate the effects of soybean intake on bone mineral density and bone turnover markers in postmenopausal rural Korean women. METHOD This study was carried out during nine months from Oct. 25 2004 to Aug. 31 2005. The subjects of this study were female patients over 50 living in rural areas diagnosed with osteoporosis. There were 18 women in the experimental group and 20 in the control group. In this study, the experimental group received 100 mg of isoflavone (soybean) and calcium 1,500 mg for nine months while the control group received 1,500 mg of calcium only. RESULTS After the soybean intake, the change of bone mineral density between the experimental group and control group was statistically significant. However, the bone turnover markers of osteocalcin and deoxypyridinoline between the experimental group and control group were not significantly different statistically. In the Pearson Correlation between bone mineral density and bone turnover markers, the osteocalcin and deoxypyridinoline of the experimental group had a positive correlation, and osteocalcin and DPD/osteocalcin ratio had a negative correlation. In the control group, osteocalcin and DPD/osteocalcin ratio had a negative correlation. CONCLUSIONS This result showed that soybean intake changed bone mineral density in postmenopausal woman.
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Exercise maintains bone density at spine and hip EFOPS: a 3-year longitudinal study in early postmenopausal women.
Engelke, K, Kemmler, W, Lauber, D, Beeskow, C, Pintag, R, Kalender, WA
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2006;(1):133-42
Abstract
It is an important aim in the prevention of osteoporosis to stop or decelerate bone loss during the early postmenopausal years. Here we report on results of the 3-year EFOPS exercise trial in osteopenic women. The exercise strategy emphasized low-volume high-resistance strength training and high-impact aerobics. Forty-eight fully compliant women (55.1+/-3.3 years) with no medication or illness affecting bone metabolism participated in the exercise group (EG); 30 women (55.5+/-3.0 years) served as non-training controls (CG). At baseline there were no significant between-group differences with respect to physical fitness, bone mineral density, pain and nutritional status. The training consisted of two group training and two home training sessions per week. The study participants of both groups were individually supplemented with calcium and vitamin D (cholecalciferol). Bone mineral density (BMD) was measured by DXA at the lumbar spine, proximal femur and distal forearm and by QCT at the lumbar spine. Speed of sound and broadband ultrasound attenuation were determined at the calcaneus by quantitative ultrasound (QUS). Pain frequency and intensity at different skeletal sites were assessed via questionnaire. After 38 months, the following within-group changes were measured: DXA lumbar spine, EG: 0.8% n.s.; CG: -3.3% P<0.001; QCT trabecular ROI, EG: 1.1% n.s; CG: -7.7% P<0.001; QCT cortical ROI, EG: 5.3% P<0.001; CG: -2.6% P<0.001; DXA total hip: EG: -0.2% n.s; CG -1.9%, P<0.001; DXA distal forearm, EG: -2.8% P<0.001; CG: -3.8% P<0.001; BUA, EG: -0.3% n.s; CG -5.4% P<0.001; SOS, EG: 0.3% n.s; CG -1.0% P<0.001. At year 3 between-group differences relative to the exercise group were: DXA lumbar spine: 4.1% P<0.001; QCT trabecular ROI: 8.8% P<0.001; QCT cortical ROI: 7.9% P<0.001; DXA total hip: 2.1%, P<0.001; DXA distal forearm: 1.0% n.s.; BUA: 5.8% P<0.05; SOS: 1.3% P<0.001. Pain frequency and intensity in the spine significantly decreased in the exercise group and increased in the control group, while no between-group differences were detected in the main joints. In summary, over a period of 3 years our low-volume/high-intensity exercise program was successful to maintain bone mineral density at the spine, hip and calcaneus, but not at the forearm.
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Clinical significance of alendronate in postmenopausal type 2 diabetes mellitus.
Ikeda, T, Manabe, H, Iwata, K
Diabetes & metabolism. 2004;(4):355-8
Abstract
OBJECTIVES To examine early changes in biochemical markers of bone turnover and bone mineral density (BMD) in a clinical trial of anti-resorptive agent alendronate versus alfacalcidol in postmenopausal women with type 2 diabetes mellitus. METHODS 12 subjects (mean age; 73.1 +/- 6.3 yrs, duration of diabetes; 13.2 +/- 3.7 yrs) were administered alendronate sodium (5 mg/day) and 12 subjects (mean age; 70.7 +/- 7.8 yrs, duration of diabetes; 12.8 +/- 2.0 yrs) were administered alfacalcidol (0.5 microg/day) for 12 months. Urinary N-telopeptide cross-linked collagen type I (NTx), one of biochemical markers, and radial bone mineral density (BMD) were measured as a marker of bone turnover. RESULTS After 12 months, urinary NTx did not change in women with alfacalcidol treatment, however urinary NTx significantly decreased after alendronate treatment. The BMD significantly decreased by 3.33% (p<0.05) in women with alfacalcidol treatment, while the BMD did not decrease in women with alendronate treatment. CONCLUSION Alendronate that produces reduction in urinary NTx and inhibition of decrease in BMD may have a clinical significance to reduce the risk of bone fracture in postmenopausal type 2 diabetic women.
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[Intensive vitamin D supplementation in the treatment of osteoporosis].
Stefíková, K, Chylová, K, Krivosíková, Z, Spustová, V, Dzúrik, R
Vnitrni lekarstvi. 2004;(4):286-90
Abstract
Vitamin D deficiency is not possible to correct with the nutritional vitamin D doses in postmenopausal women with decreased bone mineral density. The aim of study was to evaluated the effectivity and safety of 15,000 IU/week vitamin D administrated in 52 postmenopausal women with osteopenia or osteoporosis. Patients were divided into two groups. Treated group was supplemented by calcium 0.5 g/d and 25-hydroxycholecalciferol 15,000 IU/week and control group was supplemented by calcium and placebo for two months. Plasma calcium concentration did not change in the vitamin D treated group while it decreased (p < 0.001) in the control group. Neither calciuria nor fractional excretion of calcium changed during the treatment period. Plasma inorganic phosphate concentration did not change in any group, but urinary inorganic phosphate excretion increased in the vitamin D treated group (p < 0.001). The starting 25-hydroxycholecalciferol plasma concentrations were almost at the deficiency range in both groups. The 25-hydroxycholecalciferol plasma concentration increased substantially (p < 0.001) in the treated group, but it remained at the starting level in control group during the treatment period. Similar plasma concentration increase (p < 0.001) was apparent also in 1.25-dihydroxycholecalciferol. Plasma intact parathormone concentration did not change in the vitamin D treated patients, while it increased (p < 0.01) in the control group. None of the vitamin D treated women suffered from hypercalcemia and mild hypercalciuria was observed in one patient. In conclusion, the study presents an evidence on the effectiveness and safety of 15,000 IU/week 25-hydroxycholecalciferol dosage schedule.
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Compliance of osteoporotic patients with different treatment regimens.
Segal, E, Tamir, A, Ish-Shalom, S
The Israel Medical Association journal : IMAJ. 2003;(12):859-62
Abstract
BACKGROUND The treatment of osteoporosis among postmenopausal women represents a major public health challenge since long-term therapy is needed to prevent fractures and chronic disability. OBJECTIVES To assess compliance with osteoporosis drug therapy among Israeli postmenopausal women treated with either a bisphosphonate (alendronate) or a selective estrogen receptor modulator (raloxifene); to identify factors affecting compliance among these patients; and to compare adherence to the treatment in these two groups. METHODS Our study included 178 consecutive patients aged 67.41 +/- 8.52 years who were treated for osteoporosis with alendronate or raloxifene in the Metabolic Bone Diseases Unit. All the patients received supplementation with calcium carbonate 1,500 mg and 600 IU vitamin D daily. Compliance was assessed at a clinic visit 6 months after starting therapy. RESULTS The dropout rate was 23% (41 patients): 20 patients (31%) in the raloxifene group and 21 (18%) in the alendronate group (P = 0.0041). The main reasons for dropout were side effects and/or noncompliance, 16 and 24 patients (39% and 58.53%) respectively. The most frequent side effect was abdominal pain in 9 patients (42.8%) who discontinued alendronate use. The reasons for non-compliance were a fear of side effects and high drug price in 6 (30%) and 4 (20%) patients respectively in the raloxifene group, and inconvenience caused by medication use in 3 patients (14.3%) in the alendronate group. Logistic regression analysis of factors that may influence compliance included age, previous fractures, family history of osteoporosis, bone density T-score less than -2.5, and presence and number of concomitant diseases. Age was the only statistically significant parameter in this model: 67.8 +/- 8.8 in non-compliant versus 64.11 +/- 7.4 in compliant patients (P = 0.029). CONCLUSION At least 20% of the patients discontinued chronic treatment for osteoporosis during the initial 6 months of therapy. The main reasons were gastrointestinal side effects in the alendronate group and fear of side effects and high drug price in the raloxifene group. Older age was the only statistically significant factor influencing compliance.
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Effect of estrogen replacement therapy on parathyroid hormone secretion in elderly postmenopausal women.
Vincent, A, Riggs, BL, Atkinson, EJ, Oberg, AL, Khosla, S
Menopause (New York, N.Y.). 2003;(2):165-71
Abstract
OBJECTIVE Women undergo two phases of involutional bone loss that have opposing effects on parathyroid hormone (PTH) secretion. During the early phase, the loss of the direct restraining effect of estrogen on bone resorption causes an outflow of skeletal calcium into the extracellular fluid. This causes a compensatory decrease in PTH secretion. In the late phase, loss of extraskeletal effects of estrogen (on intestinal and renal calcium handling) leads to increases in whole body losses of calcium and a compensatory increase in PTH secretion. Moreover, long-term estrogen replacement therapy (ERT) suppresses both basal and stimulated PTH secretion in these women. Whereas the effects of estrogen on PTH secretion have been assumed to be due to its extraskeletal actions, estrogen may also have direct effects on the parathyroid glands. The goal of the present study was to test for these possible direct effects of estrogen on PTH secretion. DESIGN Basal and ethylenediaminetetraacetic acid (EDTA)-stimulated PTH secretion was assessed in 10 elderly postmenopausal women (mean age, 76.4 years) before and after acute (3 days) estrogen replacement with transdermal estradiol, 0.1 mg/day. In addition, similar studies were performed in 10 age-matched women (mean age, 74.5 years) who had been on long-term ERT. These women were studied before and after 3 days of estrogen withdrawal. RESULTS Estrogen treatment or withdrawal had no significant effect on either basal or stimulated PTH secretion. CONCLUSIONS These data provide evidence that, in elderly postmenopausal women, estrogen does not have significant direct effects on PTH secretion and point to the importance of the actions of estrogen on intestinal and renal calcium handling as the major mechanisms for its effects on modulating calcium homeostasis and, indirectly, PTH secretion.