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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to assess the long-term effects of tibolone 2.5 mg daily (Livial; Organon) on bone mineral density in recently postmenopausal women. An 8-year, open, nonrandomized, prospective study was designed to compare the effects of tibolone 2.5 mg daily (n = 59) with an untreated control group (n = 51). The subjects of this study were 110 recently postmenopausal women (6-36 months since last menstrual period). The main outcome measures were bone mineral density of the spine and femur, measured by dual-energy X-ray absorptiometry, and assessment of biochemical markers of bone metabolism. After 8 years of tibolone use, the mean (+/- SEM) increase in bone mineral density compared with baseline was 4.1% +/- 0.8% (p<0.0001) in the spine and 4.6% +/- 1.8% (p = 0.015) in the femoral neck. Over the same period, bone mineral density in the control group decreased in the spine by -7.5% +/- 1.1%, (p<0.0001) and in the femur by -6.7% +/- 1.2% (p<0.0001). The bone resorption marker, calcium/creatinine ratio, decreased in the tibolone group but not in the control group. Serum bone formation markers decreased (alkaline phosphatase) or stayed approximately the same (osteocalcin) in the tibolone group. Adherence was high, with 58% (34 of 59) of the tibolone group continuing treatment for 8 years. We conclude that tibolone 2.5 mg daily prevents bone loss in the lumbar spine and femoral neck over 8 years and adherence to treatment is high. The greater bone density compared with untreated women would be expected to reduce the risk of bone fractures.
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PMID:Effects of 8 years of treatment with tibolone 2.5 mg daily on postmenopausal bone loss. 1144 64

Biosynthetic bone grafts are considered to contain one or more of three critical components: osteoprogenitor cells, an osteoconductive matrix, and osteoinductive growth factors. The basic requirements of the scaffold material are biocompatibility, mechanical integrity, and osteoconductivity. A major design problem is satisfying these requirements with a single composite. In this study, we hypothesize that one composite that combines bone marrow-derived osteoblasts and a novel mechanical reinforced porous hydroxyapatite with good biocompatibility and osteoconductivity (HA/BMO) can reach these requirements. A novel sintered porous hydroxyapatite (HA) was prepared by the following procedures. The HA slurry was foamed by adding polyoxyethylenelaurylether (PEI) and mixing. The pores were fixed by crosslinking PEI with diepoxy compounds and the HA porous body was sintered at 1200 degrees C for 3 h. The HA sintered porous body had a high porosity (77%), and was completely interconnected. Average pore diameter was 500 microm and the interconnecting path 200 microm in diameter. The compressive (17 MPa) and three-point bending (7 MPa) strengths were high. For in vivo testing, the 2-week subcultured HA/BMO (+) composites were implanted into subcutaneous sites of syngeneic rats until 8 weeks after implantation. These implants were harvested at different time points and prepared for the biochemical analysis of alkaline phosphatase activity (ALP) and bone osteocalcin content (OCN), and histological analysis. ALP and OCN in the HA/BMO group were much higher than those in the HA without BMOs control group 1 week after implantation (p < 0.001). Light microscopy revealed mature bone formation in the HA/BMO composite 4 weeks after implantation. In the SEM study, mineralized collagenous extracellular matrix was noted in HA/BMO composite 2 weeks after implantation with numbers of active osteoblasts. We conclude that the composite of the novel HA and cultured BMOs has osteogenic ability in vivo. These results provide a basis for further studies on the use of this composite as an implant in orthopaedic surgery.
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PMID:In vivo evaluation of a novel porous hydroxyapatite to sustain osteogenesis of transplanted bone marrow-derived osteoblastic cells. 1148 83

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

Inhaled corticosteroids have been used in the treatment of chronic obstructive pulmonary disease (COPD) for many years. However the adverse effects of corticosteroids on bone formation may require special consideration in these patients. This study was undertaken to investigate the effects of long-term inhaled beclomethasone dipropionate treatment on the biochemical markers of bone formation. For this purpose, serum osteocalcin, alkaline phosphatase, free calcium, and inorganic phosphate levels were measured in 65 male COPD patients. Patients in the control group (n = 30) had not taken oral or inhaled corticosteroids for at least 1 year. Only those patients using beclomethasone with metered-dose inhalers were included in the treatment group (n = 35). The mean age of the control group was 61.63 +/- 1.84 (mean +/- SEM). In the treatment group, the mean age was 59.10 +/- 2.29 and patients in this group had taken beclomethasone for an average time of 23.94 +/- 2.72 months (for at least 12 months) at an average concentration of 1,142.0 +/- 79.64 microg/d. The mean serum osteocalcin levels in the control group and treatment group were 7.03 +/- 0.19 ng/mL and 3.74 +/- 0.12 ng/mL, respectively. Comparison of values between groups indicates that serum osteocalcin levels in patients using beclomethasone were significantly lower than that of patients in the control group. Serum alkaline phosphatase levels were 167.96 +/- 1.49 U/L and 168.17 +/- 1.60 U/L for the control and treatment groups, respectively. There was no statistically significant difference among these values (Student's t test; P >.05). The mean values of total serum calcium and inorganic phosphate were not statistically different between the groups (P >.05). These results indicate that long-term inhaled beclomethasone treatment in COPD patients may induce significant changes in osteocalcin levels and require close monitoring for osteoporotic changes.
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PMID:Decreased osteocalcin levels in patients with chronic obstructive pulmonary disease using long-term inhaled beclomethasone dipropionate. 1169 53

In a 12-month randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover. Twenty-eight men with idiopathic osteoporosis aged 27-74 years (mean, 52.4 years) were randomized to receive either nasal SCT (200 IU) or a nasal placebo daily for a period of 1 year. All the men received a daily supplement of 0.5 g of calcium. The men who received SCT had a mean (+/-SEM) increase in BMD of 7.1 +/- 1.7% at the lumbar spine. In contrast, the men who received the placebo had an increase of 2.4 +/- 1.5% (p > 0.05) for the comparison with baseline. The increase in lumbar BMD in the calcitonin group was significantly greater than that in the placebo group (p < 0.05). There were no significant changes in the femoral neck, trochanter, or Ward's triangle relative to both baseline and placebo after 12 months. Treatment with nasal SCT resulted in a significantly pronounced suppression of bone resorption markers (urinary deoxypyridinoline [DPD], type I cross-linked N-telopeptide [NTX], and type I cross-linked C-telopeptide [CTX]) and to a lesser extent in bone formation markers (serum bone-specific alkaline phosphatase [BALP], osteocalcin [OC], serum C-terminal procollagen type I extension peptides [PICP], and serum N-termnal procollagen type I extension peptides [PINP]), whereas the placebo did not. Therapy was tolerated well and there were no treatment-related adverse events. We conclude that intranasal SCT (200 IU daily) is safe and effective in increasing lumbar BMD and reducing bone turnover in men with idiopathic osteoporosis.
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PMID:A randomized trial of nasal spray salmon calcitonin in men with idiopathic osteoporosis: effects on bone mineral density and bone markers. 1187 43

The amount of sodium chloride in the diet of industrialized nations far exceeds physiological requirements. The impact of abundant dietary salt on skeletal health has yet to be established, but is potentially detrimental through increased urinary calcium losses. We examined the effect of increased dietary sodium chloride on urine calcium excretion and bone turnover markers in postmenopausal women and, further, whether potassium citrate attenuates the effects of increased dietary salt. Postmenopausal women (n = 60) were adapted to a low-salt (87 mmol/d sodium) diet for 3 wk, then randomized to a high-salt (225 mmol/d sodium) diet plus potassium citrate (90 mmol/d) or a high-salt diet plus placebo for 4 wk. Urine calcium, urine N-telopeptide, urine cAMP, serum osteocalcin, and fasting serum PTH were measured at the end of the low- and high-salt diets. On the high salt plus placebo diet, urine calcium increased 42 +/- 12 mg/d (mean +/- SEM), but decreased 8 +/- 14 mg/d in the high salt plus potassium citrate group (P = 0.008, potassium citrate vs. placebo, unpaired t test). N-telopeptide increased 6.4 +/- 1.4 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus placebo group and 2.0 +/- 1.7 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus potassium citrate group (P < 0.05, potassium citrate vs. placebo, unpaired t test). Osteocalcin, PTH, and cAMP were not significantly altered. The addition of oral potassium citrate to a high-salt diet prevented the increased excretion of urine calcium and the bone resorption marker caused by a high salt intake. Increased intake of dietary sources of potassium alkaline salts, namely fruit and vegetables, may be beneficial for postmenopausal women at risk for osteoporosis, particularly those consuming a diet generous in sodium chloride.
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PMID:Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet. 1199 33

To investigate the effects of 12 months of GH treatment on cortical and trabecular bone content of IGFs, iliac crest bone biopsies were obtained from 25 patients with GH deficiency (9 women and 16 men; ages, 21-61 yr; mean, 46 yr) who were randomized to sc injections with GH (2 IU/m(2).d) or placebo for 12 months. Levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-5, osteocalcin, OPG, RANKL, and total protein were determined in extracts obtained after EDTA and guanidine hydrochloride extraction. Calcium was determined after HCl hydrolysis. Comparing changes during GH or placebo treatment, significant increases were observed during GH substitution for cortical and trabecular bone content of IGF-I [mean difference vs. placebo (mean +/- SEM), 97 +/- 30 and 72 +/- 38%] and OPG (mean difference vs. placebo, 109 +/- 59 and 51 +/- 19%). Also, a significant decline was found for cortical osteocalcin (mean difference vs. placebo, -49 +/- 22%) during GH treatment. In conclusion, our results indicate that long-term GH treatment increases the accumulation of IGF-I and OPG in cortical and trabecular bone in patients with GH deficiency, and this may in turn lead to an increase in bone mass and improved skeletal biomechanical competence.
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PMID:Effects of 12 months of GH treatment on cortical and trabecular bone content of IGFs and OPG in adults with acquired GH deficiency: a double-blind, randomized, placebo-controlled study. 1205 Feb 46

Adult hypopituitary patients with growth hormone deficiency (GHD) show a significant decrease in bone mass and an increased fracture rate. Replacement therapy with GH increases bone turnover. Most of the long-term data on bone mineral content (BMC) and bone mineral density (BMD) have been acquired in open, noncontrolled trials involving limited numbers of patients. To determine whether long-term GH therapy is beneficial for bone despite the increased bone turnover, 100 patients (59 men and 41 women), aged 25-65 years (mean, 49.7 years) with adult-onset GHD were randomized to treatment with GH (40 men and 28 women; mean dose, 0.18 IU/kg per week) or to a nontreated control group (19 men and 13 women) for 24 months. Despite a similar increase in parameters of bone turnover (osteocalcin [OC], procollagen type I carboxy-terminal propeptide [PICP], and pyridinolines ([PYD]) in male and female GH-treated patients compared with controls, the effects on BMC and BMD as evaluated by dual-energy X-ray absorptiometry were gender specific. A significant increase in spine BMC and BMD and total hip BMD and a decrease in BMD at the ultradistal radius over time was observed in male GH-treated patients compared with the evolution in controls (mean +/- SEM change at 24 months: +6.8 +/- 1.1% and p = 0.009, +5.1 +/- 0.8% and p = 0.005, +3.5 +/- 0.7% and p = 0.02, and -2.6 +/- 0.8% and p = 0.008, respectively). No significant treatment effects were observed in female patients. Despite the increase in the total remodeling space induced by GH treatment, prolonged GH therapy in adult-onset GHD has a positive effect on bone balance, maintaining bone mass in women, and even increasing it in men over a 2 year-period.
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PMID:The effects of growth hormone replacement therapy on bone metabolism in adult-onset growth hormone deficiency: a 2-year open randomized controlled multicenter trial. 1205 64

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

The aim of this study was to examine whether the presence of apolipoprotein E epsilon4 (ApoE epsilon4) is associated with a lower bone mineral density (BMD), lower quantitative ultrasound (QUS) measurements, higher bone turnover and fracture risk, and whether these relations are modified by gender and age. A total of 1406 elderly men and women (> or =65 years) of the Longitudinal Aging Study Amsterdam (LASA) participated in this study. In all participants, QUS measurements were assessed, as well as serum osteocalcin (OC) and urine deoxypyridinolin (DPD/Cr urine). Follow-up of fractures was done each three months. In a subsample ( n = 604), total body bone mineral content (BMC) and BMD of the hip and lumbar spine were measured. In addition, prevalent vertebral deformities were identified on radiographs. In women, the presence of ApoE epsilon4 was associated with significantly lower femoral neck BMD (g/cm(2); mean +/- SEM; epsilon4+, 0.64 +/- 0.01 vs. epsilon4-, 0.67 +/- 0.01; p = 0.04), lower trochanter BMD (g/cm(2); mean +/- SEM; epsilon4+, 0.58 +/- 0.01 vs. epsilon4-, 0.61 +/- 0.01; p = 0.01) and lower total body BMC (g; mean +/- SEM; epsilon4+, 1787 +/- 40.0 vs. epsilon4-, 1863 +/- 23.8; p = 0.04). Women with ApoE epsilon4 also had a higher risk of severe vertebral deformities (OR=2.78; 95%CI: 1.21-6.34). In men, the associations between ApoE status and both hip BMD and QUS depended on age. Only among the younger men (65-69 years) was the presence of ApoE epsilon4 associated with lower BMD values. Bone markers and fractures were not associated with ApoE epsilon4 in either women, or men. In conclusion, this large community-based study confirms the importance of ApoE epsilon4 as a possible genetic risk factor related to BMD and vertebral deformities and demonstrates that its effect is gender related, and depends on age in men only.
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PMID:Effects of gender and age on the association of apolipoprotein E epsilon4 with bone mineral density, bone turnover and the risk of fractures in older people. 1219 33


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