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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic metabolic acidosis may increase alkali mobilization from bone and thus promote the development of osteoporosis. While it is undisputed that overt metabolic acidosis is associated with metabolic bone disease, renal acidification in patients with idiopathic osteoporosis has not been studied systematically. The purpose of this study was to investigate the prevalence of renal acidification defects in patients with 'primary' osteoporosis. Thirty-two women (including 10 premenopausal women) and 16 men who were referred to our department for investigation of osteoporosis were enrolled in this study. Patients with obvious or possible secondary osteoporosis were excluded. None of the patients had overt metabolic acidosis. In random urine samples 12 of the 48 patients had pH levels below 5.5 and were therefore considered to have normal renal acidification. The remaining 36 patients underwent further testing by a short-course oral ammonium chloride load. In this test nine of these 36 patients (7 men and 2 premenopausal women) failed to lower urinary pH below 5.5 despite the induction of systemic metabolic acidosis. In these patients, therefore, the diagnosis of incomplete distal renal tubular acidosis was made (RTA I). Patients with incomplete RTA I had significantly lower spontaneous plasma pH (7.38 +/- 0.0081 vs 7.41 +/- 0.004, mean +/- SEM, p = 0.002), a lower serum bicarbonate concentration (21.9 +/- 0.49 mmol/l vs 23.1 +/- 0.24 mmol/l, p = 0.034), a lower base excess (-2.33 +/- 0.42 mmol/l vs -0.55 +/- 0.21 mmol/l, p = 0.001) and lower Z-scores in bone densitometry (-2.18 +/- 0.27 vs -1.40 +/- 0.15, p = 0.028) than patients with normal renal acidification. In conclusion, a high prevalence of incomplete RTA I (in 44% of the male patients, 20% of the premenopausal female patients and 6% of all female patients) was found in patients with osteoporosis who, without testing, would have been diagnosed as having 'primary' osteoporosis. The mild metabolic acidosis observed in these patients may have contributed to loss of bone mass by a compensatory mobilization of alkali and calcium from bone. Because of possible therapeutic consequences (e.g., administration of alkali salts and high doses of vitamin D) we propose that measurements of urinary pH and, if necessary, ammonium chloride testing should be included in the diagnostic investigation especially of male and of premenopausal female patients with osteoporosis. Since referral bias, although unlikely, cannot be excluded in our study, the prevalence of RTA I in unselected patients with osteoporosis needs to be determined at primary screening institutions.
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PMID:Incomplete renal tubular acidosis in 'primary' osteoporosis. 1119 52

The effect of oral pamidronate on bone mineral density and its adverse effect profile was investigated by a double-masked placebo-controlled study of 122 patients aged 55-75 years with established vertebral osteoporosis. Patients on active therapy received disodium pamidronate 300 mg/day (group A) for 4 weeks every 16 weeks, 150 mg/day (group B) for 4 weeks every 8 weeks or placebo (group C). All patients additionally received 500 mg of calcium and 400 IU vitamin D daily. Dual-energy X-ray absorptiometry measurements of the spine, hip, forearm and total body were performed at baseline and 6-monthly for 2 years using a Hologic QDR 1000 device at two sites. Serum osteocalcin and urinary deoxypyridinoline were measured at the above visits and at 3 months. The percentage change (SEM) in spine bone mineral density (BMD) at 2 years based on intention-to-treat analysis was 4.64 (1.01) in group A, 6.10 (0.87) in group B and 1.13 (1.32) in group C. Analysis of variance showed significant increases in group A and B compared with placebo (p < 0.01). There were also significant rises in femoral neck BMD for group A (p = 0.005), trochanter BMD for groups A and B (p < 0.01) and total-body BMD for groups A and B (p < 0.001). There was a significant reduction in serum osteocalcin and urinary deoxypyridinoline for groups A and B (p < 0.01). There was an excess of gastrointestinal side-effects in the treated groups, particularly group A. We conclude that intermittent pamidronate therapy can prevent bone loss at both the lumbar spine and femoral neck in patients with established vertebral osteoporosis, although due to gastrointestinal side-effects the 300 mg dose in particular does not appear suitable for clinical usage.
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PMID:Intermittent oral disodium pamidronate in established osteoporosis: a 2 year double-masked placebo-controlled study of efficacy and safety. 1079 77

Long-term use of high-dose corticosteroids often results in bone loss, which may lead to osteoporosis-related fractures. This was a multicenter, double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy (prednisone > or = 7.5 mg/day or equivalent) for 6 or more months were randomized to receive placebo, risedronate 2.5 mg/day, or risedronate 5 mg/day for 12 months. All patients received calcium 1 g and vitamin D 400 IU daily. The primary endpoint was lumbar spine bone mineral density (BMD) at month 12. Additional measurements included BMD at the femoral neck and trochanter and the incidence of vertebral fractures. Overall, there were statistically significant treatment effects on BMD at 12 months at the lumbar spine (p < 0.001), femoral neck (p = 0.004), and trochanter (p = 0.010). Risedronate 5 mg increased BMD at 12 months by a mean (SEM) of 2.9% (0.49%) at the lumbar spine, 1.8% (0.46%) at the femoral neck, and 2.4% (0.54%) at the trochanter, whereas BMD was maintained only in the control group. Although not powered to show fracture efficacy, we observed a reduction in the incidence of vertebral fractures of 70% in the combined risedronate treatment groups, relative to placebo (p = 0.042). Risedronate was well tolerated, had a good safety profile, and was not associated with gastrointestinal adverse events. We conclude that risedronate increases BMD and potentially reduces the incidence of vertebral fractures in patients with corticosteroid-induced osteoporosis.
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PMID:Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study. 1084 Nov 69

Osteoporosis in men poses a unique therapeutic challenge. Clinical studies have focused largely on the more prevalent problem of post-menopausal osteoporosis, with few gender-specific studies exploring treatment options in men. Idiopathic osteoporosis in middle-aged men presents an additional dilemma, because in the majority of patients it is a low bone turnover state for which there are currently no available anabolic agents. We conducted an 18-month randomized, double blind, placebo-controlled trial of 23 men with idiopathic osteoporosis, 30-68 yr old (mean age +/- SEM, 50 +/- 1.9 yr). All patients received 1,500 mg calcium and 400 IU vitamin D daily. Ten patients were randomized to receive 400 IU PTH-(1-34), and 13 patients received vehicle, administered by daily sc injection. Serum and urinary biochemistries, including markers of bone turnover were measured every 3 months. Bone densitometry of the lumbar spine, hip, and radius was performed every 6 months. PTH-(1-34) was associated with a marked 13.5% increase in bone mass at the lumbar spine, whereas that in the control group did not change (P < 0.001). The mean lumbar spine T-score improved from -3.5 +/- 0.2 to 2.4 +/- 0.4. Femoral neck bone mineral density in the PTH-treated group increased 2.9% (P < 0.05). The 1/3 site of the distal radius showed no change from baseline in the PTH-treated group. There were no significant changes in serum calcium concentration, 24-h urinary calcium excretion, or 1,25-dihydroxyvitamin D in either group. All markers of bone turnover increased in the PTH-treated patients, with the greatest changes in serum osteocalcin and urinary N-telopeptide (230% and 375% above baseline by 12 months, respectively; P < 0.001). Free pyridinoline and markers of bone formation that showed little correlation with each other at baseline, became highly correlated in the PTH-treated group (r = 0.1; P = 0.29 at baseline; to r = 0.7; P < 0.0001 at 18 months), a pattern absent in the control patients. The best predictor of the lumbar spine response to PTH at 18 months was the combination of pyridinoline at baseline and osteocalcin at 3 months (70% of the variance). PTH is a potent stimulator of skeletal dynamics in men with idiopathic, low turnover osteoporosis; is associated with substantial increases in lumbar spine and hip bone density; and may prove to be an efficacious anabolic agent in men with this disorder.
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PMID:Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. 1099 88

Vitamin D supplementation, when given with calcium, has been shown to increase bone mineral density (BMD) and reduce the incidence of hip fracture in elderly subjects. Despite its widespread use, the benefits of vitamin D supplementation in younger women and as a single agent are less clear. We performed a randomized co-twin, placebo-controlled, double-blind trial over 2 years to measure the effect of vitamin D3 supplementation on bone density and bone metabolism in young postmenopausal women. Seventy-nine monozygotic (MZ) twin pairs (mean age, 58.7 years; range, 47-70 years) were recruited. For each twin pair, one was randomized to 800 IU cholecalciferol/day for 2 years and the other was randomized to placebo. BMD was measured at the spine and hip and heel ultrasound at baseline, 12, 18, and 24 months. Samples were collected at 0, 3, and 6 months to measure serum calcium, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary deoxypyridinoline (DPD). In total, 64 pairs completed the study. No differences in baseline characteristics were seen between the groups. At 6 months, the treatment group had an increase in serum vitamin D [mean +/- SEM intrapair difference, 14.1+/-2.4 microg/liter (p < 0.001)]. There were no significant differences in other serum measurements or bone markers at 3 months or 6 months. At 24 months, no significant treatment effect was seen on BMD or calcaneal ultrasound change within pairs. Subanalysis of treatment response by vitamin D receptor (VDR) genotype revealed no significant difference in effect on BMD variables with treatment. On the basis of these results, vitamin D supplementation, on its own, cannot be recommended routinely as an osteoporosis prevention for healthy postmenopausal women with normal vitamin D levels under the age of 70 years.
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PMID:A randomized controlled trial of vitamin D supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs. 1109 10

Vitamin D deficiency may lead to loss of type II muscle fibres, and thereby to atrophy of proximal muscles with an increased risk of falling and bone fractures. The aim of the study was to determine if six months of vitamin D treatment (0.5 microg alphacalcidol) could positively influence values for muscle strength and functional mobility in vitamin D-deficient older women. Twenty-seven women entered the study which took place at a teaching hospital outpatient department. Ten vitamin D-deficient (serum 25(OH)D3 <20 nmol/L) older (>70 years) women and 13 age-matched female subjects with normal vitamin D levels (serum 25(OH)D3 >30 nmol/L) completed the study. Preand post-treatment data were obtained for isometric knee extensor strength, handgrip strength and functional mobility (walking distance over 2 minutes and the timed i'Up & Go" test). Six months of treatment with alphacalcidol led to significant improvements (compared to the controls) in values of isometric knee extensor strength (left leg: 14.6% +/- 5.7%. p=0.03; right leg: 11.5% +/- 5.0%, p=0.02) (mean +/- SEM). The achievements in the timed "Up & Go" test and 2-minute walking test did not improve in the alphacalcidol group compared to the controls after 6 months. However, within the vitamin D-deficient group, 6 months of alphacalcidol treatment led to a significant increase in the walking distance over 2 minutes (increase from 137.6 +/- 12.6 to 151.3 +/- 11.2 meters, p=0.03). The controls, with normal vitamin D levels, did not exhibit improvements in performance of any of the tests over a period of 6 months. Summarized, alphacalcidol seems to improve muscle strength and walking distance over 2 minutes in vitamin D-deficient older women.
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PMID:Muscle strength, functional mobility and vitamin D in older women. 1121 49

Fractures due to osteoporosis are one of the major complications after heart transplantation, occurring mostly during the first 6 months after the graft, with an incidence ranging from 18% to 50% for vertebral fractures. Bone mineral density (BMD) decreases dramatically following the graft, at trabecular sites as well as cortical sites. This is explained by the relatively high doses of glucocorticoids used during the months following the graft, and by a long-term increase of bone turnover which is probably due to cyclosporine. There is some evidence for a beneficial effect on BMD of antiresorptive treatments after heart transplantation. The aim of this study was to assess prospectively the effect on BMD of a 3-year treatment of quarterly infusions of 60 mg of pamidronate, combined with 1 g calcium and 1000 U vitamin D per day, in osteoporotic heart transplant recipients, and that of a treatment with calcium and vitamin D in heart transplant recipients with no osteoporosis. BMD of the lumbar spine and the femoral neck was measured by dual-energy X-ray absorptiometry in all patients every 6 months for 2 years and after 3 years. Seventeen patients, (1 woman, 16 men) aged 46+/-4 years (mean +/- SEM) received only calcium and vitamin D. A significant decrease in BMD was observed after 6 months following the graft, at the lumbar spine (- 6.6%) as well as at the femoral neck (-7.8%). After 2 years, BMD tended to recover at the lumbar spine, whereas the loss persisted after 3 years at the femoral neck. Eleven patients (1 woman and 10 men) aged 46+/-4 years (mean +/- SEM) started treatment with pamidronate on average 6 months after the graft, because they had osteoporosis of the lumbar spine and/or femoral neck (BMD T-score below -2.5 SD). Over the whole treatment period, a continuous increase in BMD at the lumbar spine was noticed, reaching 18.3% after 3 years (14.3% compared with the BMD at the time of the graft). BMD at the femoral neck was lowered in the first year by -3.4%, but recovered totally after 3 years of treatment. In conclusion, a 3-year study of treatment with pamidronate given every 3 months to patients with existing osteoporosis led to a significant increase in lumbar spine BMD and prevented loss at the femoral neck. However, since some of these patients were treated up to 14 months after the transplant, they may already have passed through the phase of most rapid bone loss. In patients who were not osteoporotic at baseline, treatment with calcium and vitamin D alone was not able to prevent the rapid bone loss that occurs immediately after transplantation.
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PMID:Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study. 1234 30

Tumour-induced hypercalcaemia (TIH) is a frequent complication of advanced cancer but has been rarely reported in patients with malignant melanoma, and its pathogenesis remains unexplored. We studied eight patients with TIH and melanoma. We determined the incidence and pathogenesis of this complication and the effects of bisphosphonate therapy. The incidence of TIH in 751 patients with melanoma was 1.1%. All patients had liver and bone metastases at the time of hypercalcaemia. All patients had osteolytic lesions, most often multiple. The median survival was 30 days (range 4-136 days). After rehydration, the mean (+/- SEM) corrected calcium was 3.42 +/- 0.17 mmol/l. Parathyroid hormone levels were adequately suppressed and vitamin D concentrations were normal. Serum osteocalcin, a marker of bone formation, was low, except in the two patients with renal insufficiency, whereas fasting urinary calcium and hydroxyproline were increased, indicating inhibition of bone formation and stimulation of bone resorption. Increased parathyroid hormone-related protein secretion was noted in only one patient. Three of four patients became normocalcaemic after bisphosphonate therapy for a median duration of 2 weeks. In conclusion, hypercalcaemia is a rare complication of melanoma. It occurs in the context of far advanced disease and is essentially due to aggressive lytic bone metastases with an uncoupling in bone turnover. Bisphosphonates can offer short-term palliation.
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PMID:Hypercalcaemia of melanoma: incidence, pathogenesis and therapy with bisphosphonates. 1159 84

Osteoporosis is a major complication of organ transplantation. Little is known about the risk of developing osteoporosis in bone marrow transplant (BMT) recipients. We studied early and late changes in bone mineral density (BMD), as well as biochemical markers of bone remodeling, in patients at the time of allogeneic BMT (alloBMT) and up to 13 years thereafter. In a cross-sectional study, 102 patients (40 women, 62 men, mean age +/- SEM, 38.9 +/- 1.6 years) were segregated into a first group (A, n = 48) and evaluated before or during the first weeks (mean +/- SD 0.3 +/- 0.1 month, range -0.5 to 3 months) following alloBMT, and a second group (B, n = 54) studied 60.1 +/- 5.6 months (range 6-156 months) following alloBMT. Lumbar spine (LS) BMD was similar in groups A and B and was within normal limits. In contrast, femoral neck (FN) Z- and T-scores were significantly decreased in group B compared with group A (-0.68 +/- 0.14 vs -0.03 +/- 0.14 SD and -0.84 +/- 0.14 vs -0.22 +/- 0.14 SD, respectively; p < or = 0.002). Osteopenia (T-score between -1 and -2.5 SD) was present in 35% of group A and 43% of group B patients (NS). Osteoporosis (T-score < -2.5 SD) was detected in 7% of group B patients, but in none of those in group A (p = 0.05). In a longitudinal study, 56 subjects were evaluated at the time of alloBMT, and 33 and 23 were studied 6 or 12 months later, respectively (13 women, 20 men, 37.5 +/- 1.6 years). All were treated with supplements of calcium and vitamin D. Amenorrheic women received hormone replacement therapy (HRT). Three-monthly pamidronate infusions were given to 15 men and 10 non-amenorrheic women who were osteopenic/osteoporotic or had elevated baseline bone turnover markers. Mean baseline LS and FN Z- and T-scores were within normal range. Six months after BMT, FN BMD decreased by 4.2 +/- 0.7% (p < 0.001), and whole body BMD and bone mineral content by 1.5 +/- 0.4% and 3.1 +/- 0.6%, respectively (p < or = 0.0001). Twelve months after the graft, there was no further significant bone loss and only FN BMD decrease remained significantly different compared with baseline (-5.6 +/- 1.1%, p < or = 0.0001). These results indicate that the risk of decreased BMD is higher for the femoral neck than the lumbar spine and whole body levels in patients with allogeneic bone marrow transplantation, and that bone loss occurs mainly during the first 6 months after the graft.
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PMID:Allogeneic bone marrow transplantation is associated with a preferential femoral neck bone loss. 1171 93

Bone disease is a frequently reported complication in primary biliary cirrhosis (PBC), but its pathogenesis is poorly understood. Calcium malabsorption has been considered as an important contributing factor. Ursodeoxycholic acid (UDCA) is the treatment of choice in PBC, improving survival, but its effect on calcium absorption is unknown. In this study, we have measured fractional calcium absorption, using a single isotope method, in a group of female PBC patients (median age: 60 years, range: 46-78 years) and age-matched female controls (median age: 58 years, range: 36-74). Bone mineral density (BMD) in PBC patients was significantly lower than age-matched controls (g/cm(2) +/- SEM; lumbar spine: controls 1.139+/-0.028, PBC patients 1.004+/-0.026, p = 0.0028; femoral neck: controls 0.944+/-0.034, PBC patients 0.819+/-0.023, p = 0.0032). Twenty two PBC patients, who were not vitamin D-deficient, were off and on UDCA for approximately 1 month and approximately 8 weeks, respectively. Fractional calcium absorption in PBC patients prior to UDCA treatment (mean +/- SEM, 33.8+/-2.6%) was significantly lower than controls (52.0+/-2.4%, p<0.001). Following UDCA therapy, fractional calcium absorption increased significantly (Off UDCA: 33.1+/-2.6%, On UDCA: 36.6+/-2.5%, p<0.0058). Osteocalcin levels were significantly raised in the PBC group (mean +/- SEM, ng/ml, 41.4+/-2.02) compared to controls (31.1+/-2.64, p = 0.002). There were no differences in parathyroid hormone (PTH) or 25-hydroxyvitamin D levels between these two groups or following UDCA therapy. In conclusion, we found that PBC patients display low spinal and femoral neck BMD, reduced fractional calcium absorption, and elevated plasma osteocalcin. The calcium malabsorption is corrected partially by UDCA therapy. Long-term studies are required to determine whether this effect can be sustained, and whether a sustained increase in fractional calcium absorption can translate into a favorable change in bone strength in patients with PBC.
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PMID:Ursodeoxycholic acid enhances fractional calcium absorption in primary biliary cirrhosis. 1218 28


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