Body fat and cholecalciferol supplementation in elderly homebound individuals.
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Vitamin D deficiency, observed mainly in the geriatric population, is responsible for loss of bone mass and increased risk of bone fractures. Currently, recommended doses of cholecalciferol are advised, but since there are few studies evaluating the factors that influence the serum levels of 25-hydroxyvitamin D (25(OH)D) following supplementation, we analyzed the relationship between the increase in serum 25(OH)D after supplementation and body fat. We studied a group of 42 homebound elderly subjects over 65 years old (31 women) in order to assess whether there is a need for adjustment of the doses of cholecalciferol administered to this group according to their adipose mass. Baseline measurements of 25(OH)D, intact parathyroid hormone and bone remodeling markers (osteocalcin and carboxy-terminal fraction of type 1 collagen) were performed. Percent body fat was measured by dual-energy X-ray absorptiometry. The patients were divided into three groups according to their percent body fat index and were treated with cholecalciferol, 7,000 IU a week, for 12 weeks. The increases in serum levels of 25(OH)D were similar for all groups, averaging 7.46 ng/mL (P < 0.05). It is noteworthy that this increase only shifted these patients from the insufficiency category to hypovitaminosis. Peak levels of 25(OH)D were attained after only 6 weeks of treatment. This study demonstrated that adipose tissue mass does not influence the elevation of 25(OH)D levels following vitamin D supplementation, suggesting that there is no need to adjust vitamin D dose according to body fat in elderly homebound individuals. (+info)
Early changes in biochemical markers of bone turnover predict bone mineral density response to antiresorptive therapy in Korean postmenopausal women with osteoporosis.
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Biochemical markers of bone turnover have been suggested to be useful in monitoring the efficacy of antiresorptive therapy. In this study, we investigated the predictive value of bone turnover markers to determine short-term response in bone mineral density (BMD) and to identify nonresponders in 138 postmenopausal women (mean age 58 years) with osteoporosis given with either hormone thearpy (HT) or alendronate. Urinary type I collagen N-telopeptide (NTx) and serum osteocalcin (OC) at baseline, 3, and 6 months after treatment as well as spine and femoral neck BMD at baseline and 12 months were measured. Significant decreases in both NTx and OC were evident in women on treatment with antiresorptive agents as early as 3 months (p<0.01). Percent change of NTx at 3 months correlated with the percent change of spinal BMD at 12 months of treatment. When bone turnover markers were stratified by tertiles, the average rate of lumbar spine BMD gain increased significantly with increasing tertiles of baseline value (p<0.05) and percent change (p<0.05) of urinary NTx at 3 month of treatment. In terms of BMD response, urinary NTx at 3 months decreased significantly more in BMD responders group than in nonresponders group. Logistic regression analysis demonstrated that percent change of NTx at 3 months is an independent predictor to identify BMD nonresponders, defined as those whose BMD gain remained within the precision error range of dual energy X-ray absorptiometer (DXA). We conclude that biochemical markers of bone turnover, especially percent change in urinary NTx levels, can be used to determine BMD response to antiresorptive therapy in Korean postmenopausal women with osteoporosis. (+info)
Pharmacokinetics of calcitriol and maxacalcitol administered into peritoneal dialysate bags in peritoneal dialysis patients.
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OBJECTIVES: It is well known that injection of calcitriol (CT) or maxacalcitol (OCT) is very effective in hemodialysis patients with secondary hyperparathyroidism (2HPT). However, it is difficult to use these drugs with peritoneal dialysis (PD) patients with 2HPT because these drugs must be injected two or three times per week. The objective of the present study was to evaluate the stability of physiological activities of CT and OCT in PD bags and to determine the CT or OCT dosage for intraperitoneal (IP) administration. MATERIALS AND METHODS: We added CT 1.5 microg or OCT 10 microg to Dianeal PD-2 (approximate pH = 5.0, calcium = 0.87 mmol/L; Baxter,Tokyo, Japan), Midpeliq 250 (approximate pH = 7.0, Ca = 1.0 mmol/L;Terumo Corporation, Tokyo, Japan), and Peritoliq 250 (approximate pH = 5.5, Ca = 1.0 mmol/L; Terumo Corp.). Dialysis solutions were collected from the PD bags at 0, 1, 4, 8, 12, 24, 48, and 72 hours after addition of CT and OCT. The activities of CT and OCT in the dialysis effluent were measured by radioimmunoassay. The levels of serum and effluent OCT after a single IP administration of 10 microg OCT were examined in 4 PO patients with advanced 2HPT. RESULTS: Although the levels of CT and OCT in PD bags made of polyvinyl resins decreased by 70% - 75% immediately after injection, levels in PD bags made of polypropylene resins decreased only slightly. The concentration of CT mixed into the acidic solution in glass containers was stable; the decreased concentration of CT in the PD solution might be due to adsorption onto polyvinyl resins. The maximum serum concentration after IP administration of 10 microg OCT was 750 pg/mL after 5 minutes, and remained at 500 pg/mL at 60 minutes. These results show good peritoneal transport of OCT but not rapid disappearance, unlike intravenous administration. CONCLUSIONS: If peritoneal administration of vitamin D derivatives is contemplated, it is important to select the composition of PD bag resins, type of vitamin D analog, and time lag to use when deciding the dosage of injectable vitamin D preparations, such as OCT or CT, for IP administration to PD patients. It appears that IP administration in overnight dwells might be useful for PD patients as a complementary vitamin D preparation. (+info)
Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment.
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BACKGROUND: After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL), a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment. METHODS: Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis. RESULTS: ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone. CONCLUSION: In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option. (+info)
Additive growth inhibitory effects of ibandronate and antiestrogens in estrogen receptor-positive breast cancer cell lines.
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INTRODUCTION: Bisphosphonates are inhibitors of osteoclast-mediated tumor-stimulated osteolysis, and they have become standard therapy for the management of bone metastases from breast cancer. These drugs can also directly induce growth inhibition and apoptosis of osteotropic cancer cells, including estrogen receptor-positive (ER+) breast cancer cells. METHODS: We examined the anti-proliferative properties of ibandronate on two ER+ breast cancer cell lines (MCF-7 and IBEP-2), and on one ER negative (ER-) cell line (MDA-MB-231). Experiments were performed in steroid-free medium to assess ER regulation and the effect of ibandronate in combination with estrogen or antiestrogens. RESULTS: Ibandronate inhibited cancer cell growth in a dose- and time-dependent manner (approximate IC50: 10(-4) M for MCF-7 and IBEP-2 cells; 3 x 10(-4) M for MDA-MB-231 cells), partly through apoptosis induction. It completely abolished the mitogenic effect induced by 17beta-estradiol in ER+ breast cancer cells, but affected neither ER regulation nor estrogen-induced progesterone receptor expression, as documented in MCF-7 cells. Moreover, ibandronate enhanced the growth inhibitory action of partial (4-hydroxytamoxifen) and pure (ICI 182,780, now called fluvestrant or Faslodex) antiestrogens in estrogen-sensitive breast cancer cells. Combination analysis identified additive interactions between ibandronate and ER antagonists. CONCLUSION: These data constitute the first in vitro evidence for additive effects between ibandronate and antiestrogens, supporting their combined use for the treatment of bone metastases from breast cancer. (+info)
Quality of life and pain in premenopausal women with major depressive disorder: the POWER Study.
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BACKGROUND: Whereas it is established that organic pain may induce depression, it is unclear whether pain is more common in healthy subjects with depression. We assessed the prevalence of pain in premenopausal women with major depression (MDD). Subjects were 21- to 45-year-old premenopausal women with MDD (N = 70; age: 35.4 +/- 6.6; mean +/- SD) and healthy matched controls (N = 36; age 35.4 +/- 6.4) participating in a study of bone turnover, the P.O.W.E.R. (Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression) Study. METHODS: Patients received a clinical assessment by a pain specialist, which included the administration of two standardized forms for pain, the Brief Pain Inventory - Short Form, and the Initial Pain Assessment Tool, and two scales of everyday stressors, the Hassles and Uplifts Scales. In addition, a quality-of-life instrument, the SF-36, was used. The diagnosis of MDD was established by a semi-structured interview, according to the DSM-IV criteria. Substance P (SP) and calcitonin-gene-related-peptide (CGRP), neuropeptides which are known mediators of pain, were measured every hour for 24 h in a subgroup of patients (N = 17) and controls (N = 14). RESULTS: Approximately one-half of the women with depression reported pain of mild intensity. Pain intensity was significantly correlated with the severity of depression (r2 = 0.076; P = 0.04) and tended to be correlated with the severity of anxiety, (r2 = 0.065; P = 0.07), and the number of depressive episodes (r2 = 0.072; P = 0.09). Women with MDD complained of fatigue, insomnia, and memory problems and experienced everyday negative stressors more frequently than controls. Quality of life was decreased in women with depression, as indicated by lower scores in the emotional and social well-being domains of the SF-36. SP (P < 0.0003) and CGRP (P < 0.0001) were higher in depressed subjects. CONCLUSION: Women with depression experienced pain more frequently than controls, had a lower quality of life, and complained more of daily stressors. Assessment of pain may be important in the clinical evaluation of women with MDD. SP and CGRP may be useful biological markers in women with MDD. (+info)
Ghrelin against alendronate-induced gastric damage in rats.
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Alendronate sodium, a primary amino bisphosphonate, is widely used in the treatment of various diseases that are associated with bone resorption, such as postmenopausal osteoporosis and Paget's disease of bone. Although the adverse effects of biphosphonates on the gastrointestinal system have been demonstrated in experimental and clinical studies, the exact mechanisms underlying this damage are not clear yet. Ghrelin, a 28 amino acid peptide produced predominantly by the stomach, was shown to exert a potent protective action on the stomach of rats exposed to ethanol or stress. Our objective was to evaluate the possible anti-oxidant and anti-inflammatory effects of ghrelin against alendronate-induced gastric damage. Wistar albino rats were administered alendronate (20 mg/kg) by gavage for 4 days, along with either ghrelin (10 ng/kg per day) or saline given i.p. After decapitation, stomach tissues were removed for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and tissue collagen content, while the extent of tissue damage was analyzed microscopically. Formation of reactive oxygen species was determined by chemiluminesence using a luminol probe in fresh gastric tissues. Serum tumor necrosis factor (TNF-alpha) and lactate dehydrogenase levels were assessed in trunk blood. Oral administration of alendronate-induced significant gastric damage, accompanied by increased MPO activity, collagen content, MDA and luminol levels (P < 0.01-P < 0.001), while tissue GSH was decreased (P < 0.01). On the other hand, ghrelin treatment reversed these alterations (P < 0.05-P < 0.001) as well as elevating serum TNF-alpha levels significantly (P < 0.001). The findings of the present study suggest that alendronate induces oxidative gastric damage by a local irritant effect, and ghrelin ameliorates this damage by its possible antioxidant and anti-inflammatory properties. (+info)
c-Fos protein as a target of anti-osteoclastogenic action of vitamin D, and synthesis of new analogs.
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Although active vitamin D drugs have been used for the treatment of osteoporosis, how the vitamin D receptor (VDR) regulates bone cell function remains largely unknown. Using osteoprotegerin-deficient mice, which exhibit severe osteoporosis due to excessive receptor activator of NF-kappaB ligand/receptor activator of NF-kappaB (RANKL/RANK) stimulation, we show herein that oral treatment of these mice with 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] inhibited bone resorption and prevented bone loss, suggesting that VDR counters RANKL/RANK signaling. In M-CSF-dependent osteoclast precursor cells isolated from mouse bone marrow, 1alpha,25(OH)2D3 potently and dose-dependently inhibited their differentiation into multinucleate osteoclasts induced by RANKL. Among signaling molecules downstream of RANK, 1alpha,25(OH)2D3 inhibited the induction of c-Fos protein after RANKL stimulation, and retroviral expression of c-Fos protein abrogated the suppressive effect of 1alpha,25(OH)2D3 on osteoclast development. By screening vitamin D analogs based on their c-Fos-suppressing activity, we identified a new analog, named DD281, that inhibited bone resorption and prevented bone loss in ovariectomized mice, more potently than 1alpha,25(OH)2D3, with similar levels of calcium absorption. Thus, c-Fos protein is an important target of the skeletal action of VDR-based drugs, and DD281 is a bone-selective analog that may be useful for the treatment of bone diseases with excessive osteoclastic activity. (+info)