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Lumbar Spine (lumbar + spine)
Terms modified by Lumbar Spine Selected AbstractsTreatment of Skeletally Mature Ovariectomized Rhesus Monkeys With PTH(1-84) for 16 Months Increases Bone Formation and Density and Improves Trabecular Architecture and Biomechanical Properties at the Lumbar Spine,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007John Fox PhD Abstract Histomorphometric studies of treatments for osteoporosis in humans are restricted to iliac crest biopsies. We studied the effects of PTH(1-84) treatment at the lumbar spine of skeletally mature ovariectomized rhesus monkeys. PTH increased bone turnover, rapidly normalized BMD, and increased vertebral compressive strength. PTH increased trabecular bone volume primarily by increasing trabecular number by markedly increasing intratrabecular tunneling. Introduction: Histomorphometric studies of the anabolic properties of PTH(1-84) (PTH) and related peptides in human bone are restricted to iliac crest biopsies. The ovariectomized (OVX) monkey is an accepted model of human postmenopausal bone loss and was used to study the effects of PTH treatment at clinically relevant skeletal sites. Materials and Methods: Skeletally mature rhesus monkeys were OVX or sham-operated and, after a bone depletion period of 9 months, treated daily for 16 months with PTH (5, 10, or 25 ,g/kg). Markers of bone formation (serum osteocalcin) and resorption (urine N-telopeptide [NTX]) and lumbar spine BMD were measured throughout the study. Trabecular architecture and vertebral biomechanical properties were quantified at 16 months. Results: PTH treatment induced dose-dependent increases in bone turnover but did not increase serum calcium. Osteocalcin was significantly increased above OVX controls by 1 month. NTX was significantly elevated at 1 month with the highest dose, but not until 12 months with the 5 and 10 ,g/kg doses. Lumbar spine BMD was 5% lower in OVX than in sham animals when treatment was started. All PTH doses increased BMD rapidly, with sham levels restored by 3,7 months with 10 and 25 ,g/kg and by 16 months with 5 ,g/kg. PTH treatment increased trabecular bone volume (BV/TV), primarily by increasing trabecular number, and dose-dependently increased bone formation rate (BFR) solely by increasing mineralizing surface. The largest effects on BV/TV and yield load occurred with the 10 ,g/kg dose. The highest dose reduced trabecular thickness by markedly increasing intratrabecular tunneling. Conclusions: PTH treatment of OVX rhesus monkeys increased bone turnover and increased BV/TV, BMD, and strength at the lumbar spine. All PTH doses were safe, but the 10 ,g/kg dose was generally optimal, possibly because the highest dose resulted in too marked a stimulation of bone remodeling. [source] Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in menJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2010Delnaz Roshandel Abstract The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r2,,,0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMDa) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (,,=,1.83, p,=,.004) and CTX-I (,,=,17.59, p,=,4.74,×,10,4), and lower lumbar spine BMDa (,,=,,0.02, p,=,.026). The minor allele of rs9594759 (C) was associated with lower PINP (,,=,,1.84, p,=,.003) and CTX-I (,,=,,27.02, p,=,6.06,×,10,8) and higher ultrasound BMD at the calcaneus (,,=,0.01, p,=,.037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. © 2010 American Society for Bone and Mineral Research [source] Mutations in the Insulin-Like Factor 3 Receptor Are Associated With Osteoporosis,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008Alberto Ferlin Abstract Introduction: Insulin-like factor 3 (INSL3) is produced primarily by testicular Leydig cells. It acts by binding to its specific G protein,coupled receptor RXFP2 (relaxin family peptide 2) and is involved in testicular descent during fetal development. The physiological role of INSL3 in adults is not known, although substantial INSL3 circulating levels are present. The aim of this study was to verify whether reduced INSL3 activity could cause or contribute to some signs of hypogonadism, such as reduced BMD, currently attributed to testosterone deficiency. Materials and Methods: Extensive clinical, biochemical, and hormonal study, including bone densitometry by DXA, was performed on 25 young men (age, 27,41 yr) with the well-characterized T222P mutation in the RXFP2 gene. Expression analysis of INSL3 and RXFP2 on human bone biopsy and human and mouse osteoblast cell cultures was performed by RT-PCR, quantitative RT-PCR, and immunohistochemistry. Real-time cAMP imaging analysis and proliferation assay under the stimulus of INSL3 was performed on these cells. Lumbar spine and femoral bone of Rxfp2- deficient mice were studied by static and dynamic histomorphometry and ,CT, respectively. Results: Sixteen of 25 (64%) young men with RXFP2 mutations had significantly reduced BMD. No other apparent cause of osteoporosis was evident in these subjects, whose testosterone levels and gonadal function were normal. Expression analyses showed the presence of RXFP2 in human and mouse osteoblasts. Stimulation of these cells with INSL3 produced a dose- and time-dependent increase in cAMP and cell proliferation, confirming the functionality of the RXFP2/INSL3 receptor,ligand complex. Consistent with the human phenotype, bone histomorphometric and ,CT analyses of Rxfp2,/, mice showed decreased bone mass, mineralizing surface, bone formation, and osteoclast surface compared with wildtype littermates. Conclusions: This study suggests for the first time a role for INSL3/RXFP2 signaling in bone metabolism and links RXFP2 gene mutations with human osteoporosis. [source] Early Changes in Biochemical Markers of Bone Formation Predict BMD Response to Teriparatide in Postmenopausal Women With Osteoporosis,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2005Peiqi Chen Abstract The relationship between early changes in biochemical markers of bone turnover and the subsequent BMD response to daily teriparatide therapy in women with postmenopausal osteoporosis was studied. Changes in five biochemical markers, obtained from a subset of women enrolled in the Fracture Prevention Trial, were examined. Early increases in the PICP and the PINP were the best predictors of BMD response to teriparatide in this analysis. Introduction: Early reductions in biochemical markers of bone turnover with antiresorptive therapy negatively correlate with subsequent increases in BMD. We undertook this analysis to determine if early changes in biochemical markers with teriparatide therapy predict subsequent increases in BMD. Materials and Methods: In the Fracture Prevention Trial, 1637 postmenopausal women with osteoporosis were randomized to receive daily, self-administered, subcutaneous injections of placebo, teriparatide 20 ,g/day, or teriparatide 40 ,g/day. Serum concentrations of two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and the carboxy-terminal extension peptide of procollagen type 1 [PICP]) and urinary concentrations of two bone resorption markers (free deoxypyridinoline [DPD] and N-terminal telopeptide [NTX]) were assessed in a trial population subset (n = 520) at baseline and at 1, 3, 6, and 12 months. We also assessed serum concentrations of another bone formation marker, the amino-terminal extension peptide of procollagen type 1 (PINP), in a subset of 771 women at baseline and 3 months. Lumbar spine (LS) BMD was measured by DXA at baseline and 18 months. Femoral neck BMD was measured at baseline and 12 months. Results and Conclusion: Baseline bone turnover status correlated positively and significantly with BMD response. The highest correlations occurred for the LS BMD response to teriparatide 20 ,g/day. Among all studied biochemical markers, increases in PICP at 1 month and PINP at 3 months correlated best with increases in LS BMD at 18 months (0.65 and 0.61, respectively; p < 0.05). The relationships between these two biochemical markers and the LS BMD response were stronger than the corresponding relationships for the femoral neck BMD response. Using receiver operator curve analysis, we determined that the increases in PICP at 1 month and PINP at 3 months were the most sensitive and accurate predictors of the LS BMD response. [source] A Detailed Assessment of Alterations in Bone Turnover, Calcium Homeostasis, and Bone Density in Normal PregnancyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2000A. J. Black Abstract The effects of pregnancy on bone turnover and the potential risk of developing an osteoporotic fracture in pregnancy are controversial. Utilizing biochemical markers of bone formation and resorption and dual-energy X-ray absorptiometry (DEXA), bone turnover before, during, and after pregnancy was studied in detail. Ten women (mean age 30 years; range 23,40) were recruited. Prepregnancy data were obtained and then a review was performed at 2-week intervals, once pregnancy was confirmed, until 14 weeks of gestation and thereafter monthly until term. Bone mineral density (BMD) was estimated by DEXA scanning of hip, spine, and forearm preconception and postpartum. In addition, BMD of the forearm at 14 weeks and 28 weeks gestation was obtained. All pregnancies had a successful outcome. Urinary free pyridinium cross-links, free pyridinoline (fPyr) and free deoxypyridinoline (fDPyr), were normal prepregnancy (mean [±SD]) 14.6 nmol/mmol (1.8) and 5.0 nmol/mmol (1.0) creat, respectively. By 14 weeks, they had increased to 20.8 nmol/mmol (4.3) and 6.1 nmol mmol (1.4) (both p < 0.02) and by 28 weeks to 26.3 nmol/mmol (5.6) and 7.4 nmol/mmol (1.6) (both p < 0.01). The ratio of fPyr to fDPyr remained constant. A similar significant increase was observed in N-telopeptide (NTx). Bone formation was assessed by measurement of carboxy-terminal propeptide of type 1 collagen (P1CP) and bone-specific alkaline phosphatase (BSAP). Neither were altered significantly before 28 weeks, but subsequently mean P1CP increased from 110 ,g/liter (23) to 235 ,g/liter (84) at 38 weeks and mean BSAP increased from 11.1 U/liter (5.0) to 28.6 U/liter (11.1) (p < 0.01 for both variables). Lumbar spine (L1,L4) BMD decreased from a prepregnancy mean of 1.075 g/cm (0.115) to 1.054 g/cm2 (0.150) postpartum (p < 0.05). Total hip BMD decreased from a prepregnancy mean of 0.976 g/cm2 (0.089) to 0.941 g/cm2 (0.097) (p < 0.05). Forearm BMD at midradius, one-third distal and ultradistal decreased but did not reach statistical significance. As assessed by these bone markers, in the first 2 trimesters of pregnancy, bone remodeling is uncoupled with a marked increase in bone resorption. A corresponding increase in formation markers is not observed until the third trimester. Spinal BMD exhibits a significant decrease from prepregnancy to the immediate postpartum period with a mean reduction in BMD of 3.5% in 9 months. [source] Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluorideALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002V. Abitbol Background: Previous data have indicated low bone formation as a mechanism of osteoporosis in inflammatory bowel disease. Fluoride can stimulate bone formation. Aim: To assess the effect of fluoride supplementation on lumbar spine bone mineral density in osteoporotic patients with inflammatory bowel disease treated in parallel with calcium and vitamin D. Methods: In this prospective, randomized, double-blind, parallel and placebo-controlled study, 94 patients with inflammatory bowel disease (lumbar spine T score below , 2 standard deviations, normal serum 25OH vitamin D), with a median age of 35 years, were included. Bone mineral density was measured by dual-energy X-ray absorptiometry. Patients were randomized to receive daily either sodium monofluorophosphate (150 mg, n=45) or placebo (n=49) for 1 year, and all received calcium (1 g) and vitamin D (800 IU). The relative change in bone mineral density from 0 to 12 months was tested in each group (fluoride or placebo) and compared between the groups. Results: Lumbar spine bone mineral density increased significantly in both groups after 1 year: 4.8 ± 5.6% (n=29) and 3.2 ± 3.8% (n=31) in the calcium,vitamin D,fluoride and calcium,vitamin D,placebo groups, respectively (P < 0.001 for each group). There was no difference between the groups (P=0.403). Similar results were observed according to corticosteroid intake or disease activity. Conclusions: Calcium and vitamin D seem to increase lumbar spine density in osteoporotic patients with inflammatory bowel disease; fluoride does not provide further benefit. [source] Calcaneal ultrasonometry in patients with Charcot osteoarthropathy and its relationship with densitometry in the lumbar spine and femoral neck and with markers of bone turnoverDIABETIC MEDICINE, Issue 6 2001A. Jirkovská Abstract Aims To assess calcaneal ultrasonometry in Charcot osteoarthropathy (CO) and to compare it with densitometry measured by dual energy X-ray absorptiometry (DEXA) and with bone remodelling markers. Patients and methods A group of 16 diabetic patients in the acute stage of CO with a mean age (± sd) of 51 ± 13 years was compared with 26 sex- and age-matched control subjects. Both calcaneal quantitative ultrasound (QUS) parameter stiffness and bone mineral density (BMD) measured in lumbar spine and femoral neck by DEXA were compared. Collagen type I cross-linked C-telopeptides (ICTP) were used for assessment of bone resorption. Results Patients with acute CO had significantly lower stiffness of the calcaneus in the Charcot and non-Charcot foot (both P < 0.001) and significantly lower femoral neck BMD (P < 0.05) in comparison with the control group. The T-score of stiffness was significantly lower in the Charcot foot compared with the non-Charcot foot (,3.00 ± 1.39 vs. ,2.36 ± 1.12; P < 0.01) and significantly lower than the mean T-score of BMD in the lumbar spine (,0.57 ± 1.28; P < 0.001) and femoral neck (,1.58 ± 1.24; P < 0.05). A significant difference in ICTP (8.49 ± 4.37 vs. 3.92 ± 2.55 ng/ml; P < 0.001) between patients with CO and the control group was found, and a significant correlation was demonstrated between ICTP and the T-score of stiffness (r = ,0.73; P < 0.01). Conclusion The lower calcaneal QUS parameter stiffness in the Charcot foot in comparison with the control group, with the non-Charcot foot and with BMD in the lumbar spine and femoral neck, and its association with increased bone resorption indicate that calcaneal ultrasonometry may be useful in diagnosing the acute stage of CO and in assessing the risk of foot fracture. Diabet. Med. 18, 495,500 (2001) [source] Normative data of bone mineral density in an unselected adult Austrian populationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2003S. Kudlacek Abstract Background There is increasing evidence that correct interpretation of bone mineral density (BMD) measurements by dual energy X-ray absorptiometry (DEXA) requires a population-specific reference range. We therefore collected data on age-related BMD in a random sample of the normal adult Austrian population to establish an appropriate normative database. Methods We measured BMD by DEXA at five different skeletal sites in 1089 subjects, i.e. 654 females and 435 males, aged between 21,76 years, who had been recruited by 17 centres across Austria. Results Age-related bone loss was observed until age 65 years with significant changes at the lumbar spine (r = ,0·23), total hip (r = ,0·07), trochanter (r = ,0·10), femoral neck (r = ,0·30) and Ward's triangle (r = ,0·40) in the women but only at the femoral neck (r = ,0·23) and at Ward's triangle (r = ,0·40) in the men. When we calculated T scores from the BMD data of the young normal adult study population and used the T score set points according to the WHO classification of osteopenia and osteoporosis, we found that, depending on the skeletal site measured, 7·6,27·4% of the women and 16,41% of the men in our study group had low bone mass, whereas 0·6,2·7% of the female and 0·2,1·0% of the male study population were osteoporotic. However, osteoporosis was indicated in 4,9-fold more females and 5,15-fold more males when we based our estimates on the normative data provided by the manufacturers of the DEXA systems. Conclusion Our data underscore the importance of using a population-specific reference range for DEXA measurements to avoid overdiagnosis of osteoporosis. [source] Long-term effects of intravenous high dose methylprednisolone pulses on bone mineral density in patients with multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2005M. Zorzon To determine the effects of high dose methylprednisolone (HDMP) pulses on bone mineral density (BMD) in patients with multiple sclerosis (MS), we studied 25 MS patients who received regular pulses of HDMP as well as pulses of HDMP for relapses, 18 MS patients who received HDMP at the same dose schedule only for relapses, and 61 healthy controls. We measured BMDs at lumbar spine and femoral neck and we assessed biochemical markers of bone metabolism and turnover. The average lifetime dosage of MP was 75.4 (SD 11.9) g in the pulsed HDMP group and 28.6 (SD 18.3) g in the HDMP for relapses group (P < 0.0001). Two MS patients (4.7%) and four controls (6.6%) had osteoporosis (P = NS), whereas 25 patients with MS (58.1%) and 21 controls (34.4%) had osteopenia (P = 0.016). BMDs measured at lumbar spine and femoral neck and biochemical indices of bone metabolism did not differ in MS patients and controls. BMD measures were not associated with lifetime methylprednisolone dosage. In partial correlation analysis, controlling for age, gender and menopausal status there was a significant inverse correlation between BMD at femoral neck and Expanded Disability Status Scale (EDSS) score (r = ,0.31, P =0.05). In conclusion, treatment with repeated HDMP pulses was not associated with osteoporosis in patients with MS who participated in a trial of methylprednisolone. However, osteopenia was observed more frequently in MS patients than healthy controls. Our data are reassuring, as them suggest that repeated pulses of methylprednisolone do not result in substantially increased risk of osteoporosis in MS patients. Moreover, osteopenia was found only in patients treated for relapses, who had a significantly higher EDSS score than patients in the HDMP group, suggesting that decreased mobility may contribute to bone loss more than corticosteroid use. BMD should be monitored in patients with MS, regardless of the use of methylprednisolone. [source] Bone mineral density in familial amyloid polyneuropathy and in other neuromuscular disordersEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2005I. M. Conceição Neuromuscular diseases are a known risk factor for immobilization-induced osteoporosis. The aim of the study was to analyse bone mineral density (BMD) in patients with familial amyloid polyneuropathy (FAP) type I (Val30 Met) and to compare them with a population of patients with other neuromuscular disorders. We studied 24, ambulatory, neuromuscular patients, all men and premenopausal women. We included 12 FAP patients (GI) and 12 patients with other disorders (GII). Clinical data included age, sex, height, weight, alcohol intake, smoking, calcium intake, physical activity and history of fractures. Serum and urinary calcium, osteocalcin, bone alkaline phosphatase, parathyroid hormone, thyroid stimulating hormone and urinary N-telopeptide cross-linked type 1 collagen were determined in all patients. Bone mineral density of lumbar spine, hip and wrist were determined by dual energy X-ray absorptiometry scan. No statistical differences were found in clinical or analytic data between the two groups, except for body mass index and calciuria, which were lower in GI. In GI, 54.5% were osteoporotic, against 23.1% in GII (P = 0.04). Bone mineral density was lower in GI when compared with GII, and tended to decrease with disease duration. Decreased BMI and the early autonomic involvement in GI probably explain the results. The prevention and early treatment of osteoporosis, in FAP patients should be considered a priority. [source] Physical activity for prevention of osteoporosis in patients with severe haemophilia on long-term prophylaxisHAEMOPHILIA, Issue 3 2010M. KHAWAJI Summary., Physical activity has been considered as an important factor for bone density and as a factor facilitating prevention of osteoporosis. Bone density has been reported to be reduced in haemophilia. To examine the relation between different aspects of physical activity and bone mineral density (BMD) in patients with severe haemophilia on long-term prophylaxis. The study group consisted of 38 patients with severe haemophilia (mean age 30.5 years). All patients received long-term prophylaxis to prevent bleeding. The bone density (BMD g cm,2) of the total body, lumbar spine, total hip, femoral neck and trochanter was measured by dual energy X-ray absorptiometry. Physical activity was assessed using the self-report Modifiable Activity Questionnaire, an instrument which collects information about leisure and occupational activities for the prior 12 months. There was only significant correlation between duration and intensity of vigorous physical activity and bone density at lumber spine L1-L4; for duration (r = 0.429 and P = 0.020) and for intensity (r = 0.430 and P = 0.019); whereas no significant correlation between all aspects of physical activity and bone density at any other measured sites. With adequate long-term prophylaxis, adult patients with haemophilia are maintaining bone mass, whereas the level of physical activity in terms of intensity and duration play a minor role. These results may support the proposition that the responsiveness to mechanical strain is probably more important for bone mass development in children and during adolescence than in adults and underscores the importance of early onset prophylaxis. [source] Low bone mineral density in children and adolescents with inflammatory bowel disease: A population-based study from Western SwedenINFLAMMATORY BOWEL DISEASES, Issue 12 2009Susanne Schmidt MD Abstract Background: Low bone mineral density (BMD) has been recognized as a potential problem in children with inflammatory bowel disease (IBD). The aim of the study was to investigate BMD in Swedish children and adolescents with IBD and to evaluate possible factors affecting BMD. Methods: To evaluate BMD, all patients (n = 144) underwent a dual-energy X-ray absorptiometry (DXA) of the whole body and the spine. BMD values were expressed as Z-scores using normative pediatric data from Lunar (GE Medical Systems). Results: In this population-based study, the lowest BMD values were found in the lumbar spine. The entire IBD group showed significantly lower BMD Z-scores of the lumbar spine (L2,L4) in comparison to healthy references (,0.8 standard deviation [SD], range ,5.9 to 3.7 SD, P < 0.001). Decreased BMD with a Z-score < ,1 SD occurred in 46.7% of the individuals with Crohn's disease (CD) and in 47.0% of those with ulcerative colitis (UC). Low BMD with a Z-score , ,2 SD was present in 26.7% of the patients with CD and in 24.1% of the UC patients. In a multiple regression model with BMD lumbar spine as the depending variable, possible factors associated with lower BMD were male gender, low body mass index (BMI), and treatment with azathioprine. Conclusions: Low BMD is prevalent in Swedish pediatric patients with IBD. Possible risk factors for lower BMD are male gender, low BMI, and treatment with azathioprine, as a probable marker of disease course severity. (Inflamm Bowel Dis 2009) [source] Bone turnover 18 months after a single intravenous dose of zoledronic acidINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2007V. Z. C. Borba Summary Zoledronic acid inhibits bone resorption for up to 12 months. It is not known whether the duration of this antiresorptive effect extends beyond this period of time. The aim of this study was to evaluate the changes in bone turnover at 12 months (T12) and 18 months (T18) after a single injection of 4 mg of zoledronic acid. It is a prospective, longitudinal study, with a follow-up for 18 months. We studied male and female patients (60.5 ± 11.0 years old), with low bone mineral density (BMD) coming from the outpatient clinic in a metabolic bone unit of a tertiary care hospital. All patients received a single intravenous dose of 4 mg of zoledronic acid, bone turnover markers [serum carboxyterminal telopeptide of type I collagen (CTX-I), bone-specific alkaline phosphatase (BSAP)] and BMD [lumbar spine (LS) and total hip (TH)] were measured at baseline, and after 12 months (T12) and 18 months (T18). Median serum CTX-I and BSAP levels were suppressed at T12 in comparison with baseline values: 0.183 to 0.039 ng/ml for CTX-I (p = 0.0002) and 16.95 to 13.96 U/l for BSAP (p = 0.005). At T18, both CTX-I and BSAP continued to be suppressed below baseline at 0.108 ng/ml and 12.23 U/l (p = 0.009 and p = 0.02, vs. T0). Significant increases in BMD at T18 as compared with T12 were observed in patients (median increase 6.1% for LS and 2.0% for TH). Zoledronic acid inhibits bone turnover effectively for 12 months, with evidence for continued suppression and gains in BMD even after 18 months. [source] Biochemical markers of bone turnover and bone mineral density in patients with ,-thalassaemia majorINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2005E. Eren Summary In this study, bone formation markers (bone-specific alkaline phosphatase and osteocalcin) and bone resorption markers (pyridinoline and deoxypyridinoline) were analysed. Bone formation, as evidenced by the levels of serum alkaline phosphatase and osteocalcin, did not appear to be impaired, while bone resorption was grossly increased in all patient groups. The decrease of bone mineral density values was more prominent in the lumbar spine, thus making this site particularly interesting for such studies. The patients had significantly lower femoral neck and lumbar spine bone mineral density when compared with control (all p < 0.001). Our conclusion is that, in spite of the severe bone destruction that occurs in thalassaemia major, the fact that bone formation remains intact calls for a more intensive treatment. [source] Bone mineral density and bone turnover markers in patients receiving a single course of isotretinoin for nodulocystic acneINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2008Nilgun Solak Tekin Associate Professor Background, High-dose isotretinoin has been reported to have adverse effects on bone mineral density (BMD); however, studies evaluating changes in BMD with isotretinoin therapy at different dosages and with varying treatment durations have produced conflicting results. Objective, To investigate the effect of a standard, single course of isotretinoin therapy on BMD and bone turnover markers in patients with nodulocystic acne. Methods, Thirty-six patients (15 male, 21 female) with severe, recalcitrant, nodulocystic acne and 36 healthy controls (16 male, 20 female) were enrolled in the study. Patients received isotretinoin treatment for 4,6 months until a cumulative dose of 120 mg/kg had been achieved. BMD in the lumbar spine and femur was measured at baseline and at the end of therapy by dual-energy X-ray absorptiometry. Serum calcium, phosphate, parathormone, total alkaline phosphatase, osteocalcin, free deoxypyridinoline, and urinary calcium were also measured before and at the end of treatment. Results, No significant differences were found in lumbar spine and femoral BMD between the patient and control groups at the beginning of the study (P > 0.05), and no statistically significant difference was observed between the BMD values in patients at the beginning vs. the end of treatment (P > 0.05). No statistically significant difference in bone turnover markers was found between patients and controls at the beginning of the study (P > 0.05), and no statistically significant changes in bone turnover markers were observed in patients at the beginning vs. the end of treatment (P > 0.05). Conclusion, A single course of isotretinoin therapy has no clinically significant effect on bone metabolism. [source] The frequency of low bone mineral density and its associated risk factors in patients with inflammatory bowel diseasesINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2010Yasser EZZAT Abstract Objective:, To detect the frequency and the predictive factors of low bone mineral density in inflammatory bowel disease (IBD) patients, so as to optimize bone mineral density (BMD) monitoring and treatment for those at risk. Subjects and methods:, Thirty Asian patients were included in this study and were divided into 18 patients with ulcerative colitis (UC), and 12 patients with Crohn's disease (CD). All patients were diagnosed by colonoscopy and histopathological biopsy and were subjected to routine laboratory investigations in addition to 25 hydroxy vitamin D levels as well as serum calcium, phosphorus and alkaline phosphatise. BMD was measured by using dual-energy X-ray absorptiometry (DEXA) scan at lumbar spine and femoral neck; predictive factors for BMD were analyzed by group comparison and step-wise regression analysis. Results:, There was increased frequency of osteoporosis and osteopenia involving the lumbar spine in patients with IBD being more common among CD patients than in the UC group. Positive correlations were found between low BMD measurements and vitamin D levels, body mass index (BMI) (P < 0.001) as well as steroid cumulative dose and duration of therapy (P < 0.001); stepwise regression analysis showed that CD and vitamin D deficiency are predictive factors for both osteoporosis and osteopenia (P = 0.024, P = 0.027, respectively). Conclusion:, Low BMD was found to be more frequent among patients with CD than UC; in addition CD and vitamin D deficiency act as predictive factors for low BMD. We recommend that calcium and vitamin D should be given to all IBD patients; in addition, bisphosphonate administration should be put into consideration. [source] An unusual cause of calf hypertrophy: severe lumbar canal stenosis with S1 nerve root radiculopathyINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 4 2007V. ONG Abstract We report an unusual case of calf hypertrophy in a 62-year-old woman who developed progressive enlargement of the left calf in association with chronic lower back pain. Magnetic resonance imaging (MRI) of the affected calf confirmed enlargement of the soleus muscle. MRI of the lumbar spine showed multilevel degenerative changes. Electromyography revealed neurogenic features consistent with S1 radiculopathy. Our case illustrates that muscular hypertrophy may follow chronic denervation as a consequence of spinal neural compressive disease. The various mechanisms postulated for this distinct condition and therapeutic strategies are outlined. [source] Bone mineral density and perceived menopausal symptoms: factors influencing low back pain in postmenopausal womenJOURNAL OF ADVANCED NURSING, Issue 6 2009Sukhee Ahn Abstract Title.,Bone mineral density and perceived menopausal symptoms: factors influencing low back pain in postmenopausal women. Aim., This paper is a report of a study of the relationships between the factors influencing low back pain in postmenopausal women (i.e. menopausal symptoms, bone mineral density, duration of menopause, hormonal therapy, obesity, inactivity during leisure time, parity, osteoarthritis and drinking coffee). Background., Previous studies have shown that low back pain in postmenopausal women is associated with bone mineral density, menopausal symptoms and lifestyle factors, yet the factors influencing low back pain are not clear and vary with ethnicity. Method., A survey was conducted with postmenopausal women (n = 134) in Korea in 2006. Bone mineral density in the lumbar spine, back pain status, menopausal symptoms and health habits were assessed. Results., Participants' mean age was 59 years. About 70% experienced back pain on more than 1 day during the week prior to the survey and 35% suffered back pain daily. Women with back pain reported more severe menopausal symptoms than those without back pain. Based on bone mineral density scores, 26·9% of the women were considered to be at risk of osteoporosis. However, there was no association between back pain status and fracture risk status. Based on a multiple logistic regression model, menopausal symptoms, drinking coffee and inactivity during leisure time were statistically significant influencing factors for low back pain in this sample. Conclusion., The prevalence of low back pain in postmenopausal women should be recognized in association with menopausal symptoms and health habits. Further research is needed to develop interventions for the management of low back pain in postmenopausal women. [source] Clinical Characteristics of Flexed Posture in Elderly WomenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2003Lara Balzini PT Objectives: To investigate the relationships between the severity of flexed posture (FP), skeletal fragility, and functional status level in elderly women. Design: Cross-sectional study. Setting: Geriatric rehabilitation research hospital. Participants: Sixty elderly women (aged 70,93) with FP referred to a geriatric rehabilitation department for chronic back pain without apparent comorbid conditions. Measurements: Multidimensional clinical assessment included the severity of FP (standing occiput-to-wall distance) demographic (age) and anthropometric (height, weight) data, clinical profile (number of falls, pain assessment, Mini-Mental State Examination, Comorbidity Severity Index, Geriatric Depression Scale, Multidimensional Fatigue Inventory), measures of skeletal fragility (number of vertebral fractures by spine radiograph, bone mineral density (BMD), and T-score of lumbar spine and proximal femur), muscular impairment assessment (muscle strength and length), motor performance (Short Physical Performance Battery, Performance Oriented Mobility Assessment, instrumented gait analysis), and evaluation of disability (Barthel Index, Nottingham Extended Activities of Daily Living Index). Results: The severity of FP was classified as mild in 11, moderate in 28, and severe in 21 patients. Although there were no differences between FP groups on the skeletal fragility measurements, the moderate and severe FP groups were significantly different from the mild FP group for greater pain at the level of the cervical and lumbar spine. The severe FP group was also significantly different from the mild but not the moderate FP group in the following categories: clinical profile (greater depression, reduced motivation), muscle impairment (weaker spine extensor, ankle plantarflexor, and dorsiflexor muscles; shorter pectoralis and hip flexor muscles), the motor function performance-based tests (lower scores in the balance and gait subsets of the Performance Oriented Mobility Assessment), the instrumented gait analysis (slower and wider base of support), and disability (lower score on the Nottingham Extended Activities of Daily Living Index). The total number of vertebral fractures was not associated with differences in severity of FP, demographic and anthropometric characteristics, clinical profile, muscular function, performance-based and instrumental measures of motor function, and disability, but it was associated with reduced proximal femur and lumbar spine BMD. Conclusion: The severity of FP in elderly female patients (without apparent comorbid conditions) is related to the severity of vertebral pain, emotional status, muscular impairments, and motor function but not to osteoporosis, and FP has a measurable effect on disability. In contrast, the presence of vertebral fractures in patients with FP is associated with lower BMD but not patients' clinical and functional status. Therefore, FP, back pain, and mobility problems can occur without osteoporosis. Older women with FP and vertebral pain may be candidates for rehabilitation interventions that address muscular impairments, posture, and behavior modification. Randomized controlled trials are needed to support these conclusions. [source] Real-time ultrasound-guided spinal anesthesia in patients with a challenging spinal anatomy: two case reportsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010K. J. CHIN Spinal anesthesia may be challenging in patients with poorly palpable surface landmarks or abnormal spinal anatomy. Pre-procedural ultrasound imaging of the lumbar spine can help by providing additional anatomical information, thus permitting a more accurate estimation of the appropriate needle insertion site and trajectory. However, actual needle insertion in the pre-puncture ultrasound- assisted technique remains a ,blind' procedure. We describe two patients with an abnormal spinal anatomy in whom ultrasound-assisted spinal anesthesia was unsuccessful. Successful dural puncture was subsequently achieved using a technique of real-time ultrasound- guided spinal anesthesia. This may be a useful option in patients in whom landmark-guided and ultrasound-assisted techniques have failed. [source] Fibre type composition of the human psoas major muscle with regard to the level of its originJOURNAL OF ANATOMY, Issue 6 2009Juraj Arbanas Abstract The aim of our study was to explore the fibre type composition of the human psoas major muscle at different levels of its origin, from the first lumbar to the fourth lumbar vertebra, and to compare the muscle fibre size and distribution of different fibre types between levels with respect to its complex postural and dynamic function. Muscle samples were collected from 15 young males (younger than 35 years). Serial transverse sections (5 ,m) of the samples were cut by cryomicrotome. Type I, IIA and IIX muscle fibres were typed using myosin heavy chain identification. The serial sections were analysed using a light microscope with a magnitude of 100×. The differences between measurements were evaluated using a repeated-measures anova and Scheffé test for post-hoc analysis. Our study showed that the human psoas major muscle was composed of type I, IIA and IIX muscle fibres. It had a predominance of type IIA muscle fibres, whereas type I muscle fibres had the largest cross-sectional area. Type IIX muscle fibres were present as a far smaller percentage and had the smallest cross-sectional area. Moreover, the fibre type composition of the psoas major muscle was different between levels of its origin starting from the first lumbar to the fourth lumbar vertebra. We conclude that the fibre type composition of the psoas major muscle indicated its dynamic and postural functions, which supports the fact that it is the main flexor of the hip joint (dynamic function) and stabilizer of the lumbar spine, sacroiliac and hip joints (postural function). The cranial part of the psoas major muscle has a primarily postural role, whereas the caudal part of the muscle has a dynamic role. [source] The intrinsic shape of the human lumbar spine in the supine, standing and sitting postures: characterization using an active shape modelJOURNAL OF ANATOMY, Issue 2 2009Judith R. Meakin Abstract The shape of the lumbar spine in the sagittal plane varies between individuals and as a result of postural changes but it is not known how the shape in different postures is related. Sagittal images of the lumbar spines of 24 male volunteers were acquired using a positional magnetic resonance scanner. The subjects were imaged lying supine, standing and sitting. An active shape model was used to characterize shape in terms of independent modes of variation. Two modes were identified that described the total (mode 1) and distribution (mode 2) of the curvature. The spinal shape was found to be intercorrelated between the three postures for both modes, suggesting that the lumbar spine has an element of shape that is partially maintained despite postural alterations. Mode 1 values indicated that the spine was straightest when standing and curviest when sitting. Mode 2 values indicated that the distribution in the curvature was most even when sitting and least even when lying supine. Systematic differences in the behaviour of the spine, when changing posture, were found that suggest that the shape of the spine may affect its biomechanics. [source] Three-dimensional sonographic evaluation of the fetal lumbar spinal canalJOURNAL OF ANATOMY, Issue 5 2002Thomas Wallny Abstract In a prospective cross-sectional ultrasound study the size of the fetal lumbar spinal canal was evaluated to determine reference values for the lumbar part of the vertebral canal. One hundred and sixty-seven pregnant women undergoing routine obstetric ultrasound were studied between 16 and 41 weeks of gestation. Exclusion criteria consisted of structural fetal anomalies or growth restriction. Area and volume of the vertebral canal at L1, L3 and L5 were calculated by three-dimensional (3D) ultrasound. Length of the lumbar spine was also determined. The size of the spinal canal and spinal length correlated well with gestational age. No gestational-age-dependent differences in area and volume measurements between upper and lower lumbar spine were found. The results provide an in vivo assessment of the spinal canal by 3D ultrasound over the entire gestation period. [source] Association with replication between estrogen-related receptor , (ESRR,) Polymorphisms and bone phenotypes in women of European ancestryJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2010Latifa Elfassihi Abstract Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen-related receptor , (ESRR,) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRR, sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual-energy X-ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20,kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRR, in the determination of bone density in women. © 2010 American Society for Bone and Mineral Research [source] Parathyroid hormone (PTH),induced bone gain is blunted in SOST overexpressing and deficient miceJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2010Ina Kramer Abstract Intermittent parathyroid hormone (PTH) treatment is a potent bone anabolic principle that suppresses expression of the bone formation inhibitor Sost. We addressed the relevance of Sost suppression for PTH-induced bone anabolism in vivo using mice with altered Sost gene dosage. Six-month-old Sost overexpressing and 2-month-old Sost deficient male mice and their wild-type littermates were subjected to daily injections of 100,µg/kg PTH(1,34) or vehicle for a 2-month period. A follow-up study was performed in Sost deficient mice using 40 and 80,µg/kg PTH(1,34). Animals were sacrificed 4 hours after the final PTH administration and Sost expression in long bone diaphyses was determined by qPCR. Bone changes were analyzed in vivo in the distal femur metaphysis by pQCT and ex vivo in the tibia and lumbar spine by DXA. Detailed ex vivo analyses of the femur were performed by pQCT, µCT, and histomorphometry. Overexpression of Sost resulted in osteopenia and Sost deletion in high bone mass. As shown before, PTH suppressed Sost in wild-type mice. PTH treatment induced substantial increases in bone mineral density, content, and cortical thickness and in aging wild-type mice also led to cancellous bone gain owing to amplified bone formation rates. PTH-induced bone gain was blunted at all doses and skeletal sites in Sost overexpressing and deficient mice owing to attenuated bone formation rates, whereas bone resorption was not different from that in PTH-treated wild-type controls. These data suggest that suppression of the bone formation inhibitor Sost by intermittent PTH treatment contributes to PTH bone anabolism. © 2010 American Society for Bone and Mineral Research [source] Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2010David L Kendler Abstract Patients treated with bisphosphonates for osteoporosis may discontinue or require a switch to other therapies. Denosumab binds to RANKL and is a potent inhibitor of bone resorption that has been shown to increase bone mineral density (BMD) and decrease fracture risk in postmenopausal women with osteoporosis. This was a multicenter, international, randomized, double-blind, double-dummy study in 504 postmenopausal women,,,55 years of age with a BMD T- score of ,2.0 or less and ,4.0 or more who had been receiving alendronate therapy for at least 6 months. Subjects received open-label branded alendronate 70,mg once weekly for 1 month and then were randomly assigned to either continued weekly alendronate therapy or subcutaneous denosumab 60,mg every 6 months and were followed for 12 months. Changes in BMD and biochemical markers of bone turnover were evaluated. In subjects transitioning to denosumab, total hip BMD increased by 1.90% at month 12 compared with a 1.05% increase in subjects continuing on alendronate (p,<,.0001). Significantly greater BMD gains with denosumab compared with alendronate also were achieved at 12 months at the lumbar spine, femoral neck, and 1/3 radius (all p,<,.0125). Median serum CTX levels remained near baseline in the alendronate group and were significantly decreased versus alendronate (p,<,.0001) at all time points with denosumab. Adverse events and serious adverse events were balanced between groups. No clinical hypocalcemic adverse events were reported. Transition to denosumab produced greater increases in BMD at all measured skeletal sites and a greater reduction in bone turnover than did continued alendronate with a similar safety profile in both groups. Copyright © 2010 American Society for Bone and Mineral Research [source] Bone Health in Children and Adolescents After Renal Transplantation,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2009Helena Valta MD Abstract The basis for lifelong bone health is established in childhood and adolescence. Whereas pediatric renal transplant (RTx) patients are at risk for impaired bone mass gain and fractures, scarce data on this subject are available. We performed a cross-sectional and longitudinal study of bone health in a national cohort of 106 pediatric RTx patients (median age, 12.6 yr; median follow-up, 5.1 yr after RTx). The patients underwent clinical evaluation, DXA for BMD, and spinal imaging for vertebral fractures. In longitudinal analysis, the median lumbar spine BMD Z-score was lowest (median, ,1.0) at 1 yr postoperatively but increased to a peak value of ,0.2 at 5 yr. In boys, the lumbar spine BMD Z-score increased also during puberty but decreased in girls. In cross-sectional analysis, the lumbar spine, hip, and whole body BMD Z-scores were < ,2 SD in 4%, 6%, and 6% of the patients, respectively. Sixteen percent had sustained peripheral fractures, and 8% had vertebral fractures. Female sex and age >15 yr (OR, 56.26; 95% CI, 5.17,611.82; p = 0.0007) as well as high plasma PTH levels (OR, 4.03; 95% CI, 1.37,11.85; p = 0.009) were significant predictors for low BMD. Three-year cumulative glucocorticoid dose, outside the immediate post-RTx years, was not associated with BMD parameters. The observed BMD results were satisfactory. However, the high (8%) prevalence of vertebral fractures warrants careful evaluation of bone health in these patients. [source] Simplified System for Absolute Fracture Risk Assessment: Clinical Validation in Canadian Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2009William D Leslie Abstract Absolute 10-yr fracture risk based on multiple factors is the preferred method for risk assessment. A simplified risk assessment system from sex, age, DXA, and two clinical risk factors (CRFs),prior fracture and systemic corticosteroid (CS) use-has been used in Canada since 2005. This study was undertaken to evaluate this system in the Canadian female population. A total of 16,205 women ,50 yr of age at the time of baseline BMD (1998,2002) were identified in a database containing all clinical DXA test results for the Province of Manitoba, Canada. Basal 10-yr fracture risk from age and minimum T-score (lumbar spine, femur neck, trochanter, total hip) was categorized as low (<10%), moderate (10,20%), or high (>20%). Health service records since 1987 were assessed for prior fracture codes (N = 5224), recent major CS use (N = 616), and fracture codes after BMD testing (mean, 3.1 yr of follow-up) for the hip, vertebrae, forearm, or humerus (designated osteoporotic, N = 757). Fracture risk predicted from age and minimum T-score alone showed a significant gradient in observed fracture rates (low 5.1 [95% CI, 4.1,6.4], moderate 11.5 [95% CI, 10.1,13.0], high 25.4 [95% CI, 23.2,27.9] per 1000 person-years; p -for-trend <0.0001). There was an incremental increase in incident fracture rates from a prior fracture (13.9 [95% CI, 11.3,16.4] per 1000 person-years) or major CS use (11.2 [95% CI, 4.1,18.2] per 1000 person-years). This simplified fracture risk assessment system provides an assessment of fracture risk that is consistent with observed fracture rates. [source] Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2009Jacques P Brown Abstract Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double-blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score , ,2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one-third radius; p , 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab- and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments. [source] A Haplotype-Based Analysis of the LRP5 Gene in Relation to Osteoporosis Phenotypes in Spanish Postmenopausal Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2008Lídia Agueda Abstract LRP5 encodes the low-density lipoprotein receptor-related protein 5, a transmembrane protein involved in Wnt signaling. LRP5 is an important regulator of osteoblast growth and differentiation, affecting bone mass in vertebrates. Whether common variations in LRP5 are associated with normal BMD variation or osteoporotic phenotypes is of great relevance. We used a haplotype-based approach to search for common disease-associated variants in LRP5 in a cohort of 964 Spanish postmenopausal women. Twenty-four SNPs were selected, covering the LRP5 region, including the missense changes p.V667M and p.A1330V. The SNPs were genotyped and evaluated for association with BMD at the lumbar spine (LS) or femoral neck (FN) and with osteoporotic fracture, at single SNP and haplotype levels, by regression methods. Association with LS BMD was found for SNP 1, rs312009, located in the 5,-flanking region (p = 0.011, recessive model). SNP 6, rs2508836, in intron 1, was also associated with BMD, both at LS (p = 0.025, additive model) and FN (p = 0.031, recessive model). Two polymorphisms were associated with fracture: SNP 11, rs729635, in intron 1, and SNP 15, rs643892, in intron 5 (p = 0.007 additive model and p = 0.019 recessive model, respectively). Haplotype analyses did not provide additional information, except for haplotype "GC" of the block located at the 3,end of the gene. This haplotype spans intron 22 and the 3, untranslated region and was associated with FN BMD (p = 0.029, one copy of the haplotype versus none). In silico analyses showed that SNP 1 (rs312009) lies in a putative RUNX2 binding site. Electro-mobility shift assays confirmed RUNX2 binding to this site. [source] | ||||||||||||||||||||||||||||||||||