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A comparison of the acute effects of calcium and strontium ranelate on the serum marker of bone resorption.
Maresova, KB, Franek, T, Vondracek, T, Stepan, JJ
Clinical chemistry and laboratory medicine. 2011;(2):333-5
Abstract
BACKGROUND To investigate the mechanism by which strontium ranelate (SrR) inhibits the bone resorption, this study compared the effects of SrR and calcium on parathyroid hormone (PTH) and the biochemical marker of bone resorption (serum type 1 collagen cross-linked C-telopeptide, βCTX). METHODS In 10 healthy young subjects, after overnight fasting, 1000 mg of elemental calcium and 2000 mg of SrR containing 600 mg Sr²⁺ were administered consecutively with a 1 week washout period. During the control period no drug was given. Fasting blood samples were drawn at baseline and throughout the next 5-h period. RESULTS After the ingestion of either calcium or SrR, there was a significant increase in serum calcium and strontium concentrations, and a decrease in serum βCTX and intact PTH concentrations as compared to the baseline values (p<0.05). In the fasting subjects, no significant differences in the variable were found as compared to the baseline values. CONCLUSIONS The decrease in PTH and the marker of bone resorption observed after the SrR administration is comparable to the decrease observed after the calcium administration in young adults.
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Infusion of ibandronate once every 3 months effectively decreases bone resorption markers and increases bone mineral density in Chinese postmenopausal osteoporotic women: a 1-year study.
Li, M, Xing, XP, Zhang, ZL, Liu, JL, Zhang, ZL, Liu, DG, Xia, WB, Meng, XW
Journal of bone and mineral metabolism. 2010;(3):299-305
Abstract
The efficacy and safety of intravenous ibandronate were evaluated in postmenopausal osteoporosis women in China. In this multicenter, positive drug-controlled study, 158 postmenopausal osteoporotic women were randomized to receive 2 mg ibandronate given intravenously once every 3 months or 70 mg alendronate given orally once per week. All women also received supplemental calcium (500 mg) and vitamin D (200 IU) daily. One hundred fifty-one patients completed the 1-year study. Ibandronate produced mean increases in bone mineral density (BMD) by 4.27% at the lumbar spine, 3.48% at the femoral neck, and 2.03% at the trochanter. Mean increases in BMD by 4.24% at the lumbar spine, 2.72% at the femoral neck, and 2.99% at the trochanter were observed in the alendronate group. No significant difference was found between the two groups in BMD in all sites measured. Significant decreases in serum c-telopeptide of type I collagen (CTX) and alkaline phosphatase (ALP) were found in the two groups after 1 and 3 months of treatment, respectively; these serum CTX and ALP levels were then maintained at the decreased levels throughout the study period (12 months). No changes of stature were found in the patients of the two groups. Adverse events were similar in the two groups, except more mild muscle pain was observed in the first month after infusion of ibandronate than with oral alendronate (P < 0.001). The results observed in Chinese patients may support the observation that intravenous ibandronate significantly reduced bone resorption and increased BMD with good tolerance in Chinese postmenopausal osteoporotic women. Use of intravenous ibandronate possibly could potentially improve compliance as compared with other oral bisphosphonates because it may avoid the peptic side effects of oral bisphosphonate.
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Antiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using (41)Ca methodology.
Weaver, CM, Martin, BR, Jackson, GS, McCabe, GP, Nolan, JR, McCabe, LD, Barnes, S, Reinwald, S, Boris, ME, Peacock, M
The Journal of clinical endocrinology and metabolism. 2009;(10):3798-805
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Abstract
INTRODUCTION Reduction of ovarian estrogen secretion at menopause increases net bone resorption and leads to bone loss. Isoflavones have been reported to protect bone from estrogen deficiency, but their modest effects on bone resorption have been difficult to measure with traditional analytical methods. METHODS In this randomized-order, crossover, blinded trial in 11 healthy postmenopausal women, we compared four commercial sources of isoflavones from soy cotyledon, soy germ, kudzu, and red clover and a positive control of oral 1 mg estradiol combined with 2.5 mg medroxyprogesterone or 5 mg/d oral risedronate (Actonel) for their antiresorptive effects on bone using novel (41)Ca methodology. RESULTS Risedronate and estrogen plus progesterone decreased net bone resorption measured by urinary (41)Ca by 22 and 24%, respectively (P < 0.0001). Despite serum isoflavone profiles indicating bioavailability of the phytoestrogens, only soy isoflavones from the cotyledon and germ significantly decreased net bone resorption by 9% (P = 0.0002) and 5% (P = 0.03), respectively. Calcium absorption and biochemical markers of bone turnover were not influenced by interventions. CONCLUSIONS Dietary supplements containing genistein-like isoflavones demonstrated a significant but modest ability to suppress net bone resorption in postmenopausal women at the doses supplied in this study over a 50-d intervention period.
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Alendronate and vitamin D2 for prevention of hip fracture in Parkinson's disease: a randomized controlled trial.
Sato, Y, Iwamoto, J, Kanoko, T, Satoh, K
Movement disorders : official journal of the Movement Disorder Society. 2006;(7):924-9
Abstract
Incidence of a fracture, particularly in the hip joint, is high in elderly women with Parkinson's disease (PD), and this is due to the immobilization-induced bone resorption and vitamin D deficiency with reduced bone mineral density (BMD). The objective of this study was to address the possibility that treatment with alendronate and vitamin D2 may reduce the incidence of hip fractures in elderly women with PD. PD patients were randomly assigned to daily treatment with 5 mg alendronate (n = 144) or a placebo combined with 1,000 IU of vitamin D2 (n = 144) and followed for 2 years. Incidence of hip fractures in the two patient groups during the 2-year follow-up period was studied. At baseline, both groups of patients had low BMD with high levels of serum-ionized calcium and urinary deoxypyridinoline (D-Pyr). Hip fractures occurred in 14 patients in the placebo group and 4 in the alendronate group. The relative risk for hip fractures in the alendronate group as compared with the placebo group was 0.29 (95% CI, 0.10-0.85). The number of hip fracture per 1,000 patient-years was 14 and 49 for the alendronate and placebo groups, respectively. In the alendronate group, serum calcium and urinary D-Pyr levels decreased significantly during the follow-up period, while the levels in the placebo group were increased. BMD increased by 3.1% in the alendronate group and decreased by 2.8% in the placebo group (P < 0.01). Treatment with alendronate and vitamin D2 increases BMD in elderly women with PD and leads to the prevention of hip fractures.
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Estrogen, androgen, and the pathogenesis of bone fragility in women and men.
Seeman, E
Current osteoporosis reports. 2004;(3):90-6
Abstract
During growth, estrogen deficiency in females may produce increased bone size as a result of removal of inhibition of periosteal apposition, while failed endosteal apposition produces thin cortices and trabeculae in the smaller bone. In males, androgen deficiency produces reduced periosteal and endosteal apposition, reduced bone size, and cortical and trabecular thickness. At completion of longitudinal growth, advancing age is associated with emergence of a negative bone balance in each basic multicellular unit (BMU) because of reduced bone formation. Bone loss occurs, but slowly because the remodeling rate is slow. In midlife, in females, estrogen deficiency increases remodeling rate, increases the volume of bone resorbed, and decreases the volume of bone formed in each of the numerous BMUs remodeling bone on its endosteal (endocortical, trabecular, intracortical) surfaces so bone loss accelerates. In males, remodeling rate remains slow and is driven largely by reduced bone formation in the BMU. Hypogonadism in 20% to 30% of elderly men contributes to bone loss. In both sexes, calcium malabsorption and secondary hyperparathyroidism may partly be sex-hormone dependent and contributes to cortical bone loss. Concurrent periosteal apposition partly offsets endosteal bone loss, but less so in women than in men. More women than men fracture because their smaller skeleton incurs greater architectural damage and adapts less by periosteal apposition. Sex hormone deficiency during growth and aging is pivotal in the pathogenesis of bone fragility.
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Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation.
Shane, E, Addesso, V, Namerow, PB, McMahon, DJ, Lo, SH, Staron, RB, Zucker, M, Pardi, S, Maybaum, S, Mancini, D
The New England journal of medicine. 2004;(8):767-76
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Abstract
BACKGROUND Osteoporosis is a well-known complication of cardiac transplantation. We conducted a randomized trial comparing alendronate with calcitriol for the prevention of bone loss during the first year after cardiac transplantation. METHODS A total of 149 patients were randomly assigned to receive either alendronate (10 mg per day) or calcitriol (0.5 microg per day) a mean (+/-SD) of 21+/-11 days after transplantation. Estimates of bone loss and the incidence of fractures among untreated patients were obtained from a reference group of 27 prospectively recruited patients who received cardiac transplants within the same period as the intervention groups. RESULTS At one year, the bone mineral density at the lumbar spine had decreased by a mean of 0.7 percent in the alendronate group and 1.6 percent in the calcitriol group (P=0.25 for the test of no difference). The bone mineral density at the femoral neck decreased by a mean of 1.7 percent in the alendronate group and 2.1 percent in the calcitriol group (P=0.69). In the reference group, the mean bone mineral density at the lumbar spine decreased by 3.2 percent (P=0.03 for the comparison with the alendronate group; P=0.15 for the comparison with the calcitriol group), and the mean density at the femoral neck decreased by 6.2 percent (P=0.001 for comparisons with both intervention groups). The incidence of vertebral fractures did not differ significantly among the groups (6.8 percent in the alendronate group, 3.6 percent in the calcitriol group, and 13.6 percent in the reference group). Hypercalciuria developed in 27 percent of the patients in the calcitriol group and 7 percent of those in the alendronate group (P=0.01). CONCLUSIONS The degree of bone loss and the rates of fracture did not differ significantly between the intervention groups. Calcitriol was associated with a higher risk of hypercalciuria. Alendronate-treated patients sustained less bone loss at the spine than those in the reference group, and both intervention groups sustained less bone loss at the hip than the reference group. The requirement for monitoring the serum and urinary calcium levels in calcitriol-treated patients makes alendronate more attractive for the prevention of bone loss early after cardiac transplantation.
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Comparison of the effects of calcium loading with calcium citrate or calcium carbonate on bone turnover in postmenopausal women.
Kenny, AM, Prestwood, KM, Biskup, B, Robbins, B, Zayas, E, Kleppinger, A, Burleson, JA, Raisz, LG
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2004;(4):290-4
Abstract
Calcium supplementation is known to increase bone mineral density and decrease fractures, but the relative efficacy of different forms of calcium supplementation is not established. We compared the effects of calcium carbonate and calcium citrate on markers of bone resorption in older postmenopausal women in an open-labeled crossover study. Forty women were randomized to receive 1000 mg/day of either calcium citrate or calcium carbonate for 12 weeks, followed by a 2-week washout without calcium supplements and 12 weeks treatment with the alternate calcium supplement. All women received vitamin D (900 IU/day). Thirty-four women (25 Caucasian, nine Hispanic) completed the study. No significant differences in the decrease in parathyroid hormone (PTH) or bone specific alkaline phosphatase or the increase in urinary calcium/creatinine were detected between the two treatments. However, calcium citrate supplementation decreased the collagen cross-link resorption markers, urinary N-telopeptide (-30%), C-telopeptide (-31%), free deoxypyridinoline (19%) and serum N-telopeptide (-8%), compared to no significant change following calcium carbonate supplementation (+2%, +3%, +2% and +2%, respectively; P<0.05). Calcium citrate decreased markers of bone resorption significantly more than calcium carbonate in postmenopausal women, although no differences in their effects in calcium excretion or PTH were detected.
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Mechanism of action of bisphosphonates.
Reszka, AA, Rodan, GA
Current osteoporosis reports. 2003;(2):45-52
Abstract
In recent years, substantial progress has been made in understanding the mechanism for bisphosphonate suppression of bone turnover. Bisphosphonates can now be distinguished based on their molecular and cellular mechanisms of action. Simple bisphosphonates such as clodronate and etidronate inhibit bone resorption through induction of osteoclast apoptosis. Clodronate, and perhaps etidronate, triggers apoptosis by generating a toxic analog of adenosine triphosphate, which then targets the mitochondria, the energy center within the cell. For nitrogen-containing bisphosphonates, the direct intracellular target is the enzyme farnesyl diphosphate synthase in the cholesterol biosynthetic pathway. Its inhibition suppresses a process called protein geranylgeranylation, which is essential for the basic cellular processes required for osteoclastic bone resorption. Although nitrogen-containing bisphosphonates can induce osteoclast apoptosis, this is not necessary for their inhibition of bone resorption.
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Effects of a low-dose and ultra-low-dose combined oral contraceptive use on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study.
Nappi, C, Di Spiezio Sardo, A, Acunzo, G, Bifulco, G, Tommaselli, GA, Guida, M, Di Carlo, C
Contraception. 2003;(5):355-9
Abstract
In this prospective, controlled, randomized study, we compared the effect of a low-dose 21-day combined oral contraceptive (COC) containing 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GTD) (Group A; n = 19) with an ultra-low-dose 24-day COC containing 15 microg EE and 60 microg GTD (Group B; n = 18) on bone turnover and bone mineral density (BMD) in young, fertile women. Nineteen healthy fertile women were used as untreated controls (Group C). At 3, 6, 9 and 12 months of the study serum osteocalcin (BGP), urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) were measured in all subjects. At baseline and after 12 months BMD was determined at lumbar spine by dual-energy X-ray absorptiometry in all patients. In both Groups A and B, urinary levels of PYD and D-PYD at 6, 9 and 12 months, were significantly reduced in comparison with basal values and with control subjects (p < 0.05). No significant differences in urinary PYD and D-PYD levels were observed between Groups A and B during the entire period of treatment. At 12 months, no statistically significant difference in spinal BMD values was detected between the three groups and in comparison with basal values. The present study suggests that the two COCs could exert a similar positive effect on bone turnover in young postadolescent women, without any significant and appreciable modification of BMD.
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Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate.
Eastell, R, Barton, I, Hannon, RA, Chines, A, Garnero, P, Delmas, PD
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2003;(6):1051-6
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Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures. Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p < 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p < 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.