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Bone Markers (bone + marker)
Selected AbstractsRecovery From Skeletal Fluorosis (an Enigmatic, American Case),,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2007Etah S Kurland Abstract A 52-year-old man presented with severe neck immobility and radiographic osteosclerosis. Elevated fluoride levels in serum, urine, and iliac crest bone revealed skeletal fluorosis. Nearly a decade of detailed follow-up documented considerable correction of the disorder after removal of the putative source of fluoride (toothpaste). Introduction: Skeletal fluorosis, a crippling bone disorder, is rare in the United States, but affects millions worldwide. There are no data regarding its reversibility. Materials and Methods: A white man presented in 1996 with neck immobility and worsening joint pains of 7-year duration. Radiographs revealed axial osteosclerosis. Bone markers were distinctly elevated. DXA of lumbar spine (LS), femoral neck (FN), and distal one-third radius showed Z scores of +14.3, +6.6, and ,0.6, respectively. Transiliac crest biopsy revealed cancellous volume 4.5 times the reference mean, cortical width 3.2 times the reference mean, osteoid thickness 25 times the reference mean, and wide and diffuse tetracycline uptake documenting osteomalacia. Fluoride (F) was elevated in serum (0.34 and 0.29 mg/liter [reference range: <0.20]), urine (26 mg/liter [reference range: 0.2,1.1 mg/liter]), and iliac crest (1.8% [reference range: <0.1%]). Tap and bottled water were negative for F. Surreptitious ingestion of toothpaste was the most plausible F source. Results: Monitoring for a decade showed that within 3 months of removal of F toothpaste, urine F dropped from 26 to 16 mg/liter (reference range: 0.2,1.1 mg/liter), to 3.9 at 14 months, and was normal (1.2 mg/liter) after 9 years. Serum F normalized within 8 months. Markers corrected by 14 months. Serum creatinine increased gradually from 1.0 (1997) to 1.3 mg/dl (2006; reference range: 0.5,1.4 mg/dl). Radiographs, after 9 years, showed decreased sclerosis of trabeculae and some decrease of sacrospinous ligament ossification. DXA, after 9 years, revealed 23.6% and 15.1% reduction in LS and FN BMD with Z scores of +9.3 and +4.8, respectively. Iliac crest, after 8.5 years, had normal osteoid surface and thickness with distinct double labels. Bone F, after 8.5 years, was 1.15% (reference range, <0.1), which was a 36% reduction (still 10 times the reference value). All arthralgias resolved within 2 years, and he never fractured, but new-onset nephrolithiasis occurred within 9 months and became a chronic problem. Conclusions: With removal of F exposure, skeletal fluorosis is reversible, but likely impacts for decades. Patients should be monitored for impending nephrolithiasis. [source] Growth Hormone Increases Bone Mineral Content in Postmenopausal Osteoporosis: A Randomized Placebo-Controlled TrialJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2003Kerstin Landin-Wilhelmsen Abstract Eighty osteoporotic, postmenopausal women, 50,70 years of age, with ongoing estrogen therapy (HRT), were randomized to recombinant human growth hormone (GH), 1.0 U or 2.5 U/day, subcutaneous, versus placebo. This study was double-blinded and lasted for 18 months. The placebo group then stopped the injections, but both GH groups continued for a total of 3 years with GH and followed for 5 years. Calcium (750 mg) and vitamin D (400 U) were given to all patients. Bone mineral density and bone mineral content were measured with DXA. At 18 months, when the double-blind phase was terminated, total body bone mineral content was highest in the GH 2.5 U group (p = 0.04 vs. placebo). At 3 years, when GH was discontinued, total body and femoral neck bone mineral content had increased in both GH-treated groups (NS between groups). At 4-year follow-up, total body and lumbar spine bone mineral content increased 5% and 14%, respectively, for GH 2.5 U (p = 0.01 and p = 0.0006 vs. placebo). Femoral neck bone mineral density increased 5% and bone mineral content 13% for GH 2.5 U (p = 0.01 vs. GH 1.0 U). At 5-year follow-up, no differences in bone mineral density or bone mineral content were seen between groups. Bone markers showed increased turnover. Three fractures occurred in the GH 1.0 U group. No subjects dropped out. Side effects were rare. In conclusion, bone mineral content increased to 14% with GH treatment on top of HRT and calcium/vitamin D in postmenopausal women with osteoporosis. There seems to be a delayed, extended, and dose-dependent effect of GH on bone. Thus, GH could be used as an anabolic agent in osteoporosis. [source] Tissue reaction to orthodontic tooth movement in different bone turnover conditionsORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 3 2003C. Verna Structured Abstract Authors , Verna C, Melsen B Objectives , To study the tissue reaction to orthodontic load in normal, high, and low bone turnover states. Design , ,Split mouth' design performing orthodontic tooth movement in 52, 6-month-old male rats with: normal (n = 19), high (n = 16), and low bone turnover (n = 17), the latter two being obtained by induction of hyperthyroidism and hypothyroidism, respectively. Performed at the Department of Orthodontics at Aarhus University. Experimental Variable , The upper left first molar was moved for 21 days. Bone markers were administered 7 and 2 days before killing. Histological sections were cut at the coronal and apical levels. Outcome Measure , Alveolar socket area, periodontal ligament width, the relative extension of alveolar wall with erosion surfaces, and the mineralizing surfaces were measured and compared in the three groups. Results , Alveolar socket, periodontal ligament width, and erosion surface were larger on the treated than on the control side in the three groups. The normal and hypothyroid groups showed a wider periodontal ligament at the bucco-distal site at the coronal level, while the hyperthyroid group showed a widening which was not spatially oriented. The normal and hyperthyroid groups showed higher erosion at the corono-mesial site. The mineralizing surfaces were larger on the treated than on the control side in the normal and hypothyroid groups, but not in the hyperthyroid group. Conclusion , In the hyperthyroid group, the widening of the periodontal ligament was not spatially oriented and the increased erosion was not accompanied by increased formation, as observed in the normal and hypothyroid groups. [source] Effects of 10 years of growth hormone (GH) replacement therapy in adult GH-deficient menCLINICAL ENDOCRINOLOGY, Issue 3 2005Lucia I. Arwert Summary Objective, GH-deficient adults have changes in body composition, bone mineral density (BMD) and lipid profile that can be altered by GH substitution. However, long-term data on GH substitution (up to 10 years of follow-up) are limited. Design, The effects of 10 years of GH replacement therapy on BMD, body composition, bone parameters, serum lipids and glucose metabolism were studied. Patients, Twenty-three childhood-onset GH-deficient men (mean age at baseline 28·6 years) were studied during 10 years of GH substitution therapy. A group of 19 age-matched healthy men served as a control group for BMD measurements at baseline and after 10 years. Results, BMD of the lumbar spine increased during the 10 years of GH therapy. Bone markers and BMD in the hip increased during the first 5 years of GH therapy, but were not different from baseline after 10 years. BMD changes over time in the lumbar spine and femoral neck were significantly different in the patients compared to the controls. After 10 years the difference between the groups had decreased, but BMD was still higher in the controls than in the patients. Lipid profile had improved after 10 years of GH therapy, but body mass index (BMI), waist,hip ratio (WHR), fasting glucose and glycosylated haemoglobin (HbA1c) had increased compared to baseline. Conclusions, This long-term follow-up study found that 10 years of GH substitution in GH-deficient men causes sustained improvements in BMD in the lumbar spine and lipid profile but not in body composition. [source] Bioactive and Degradable Composite Microparticulates for the Tissue Cell Population and Osteogenic DevelopmentADVANCED ENGINEERING MATERIALS, Issue 10 2009Hye-Sun Yu Bioactive and degradable composite microspheres (bioactive glass,synthetic biopolymer) were produced to deliver tissue cells and to aid their osteogenic development targeted for hard tissues. Cellular population (left, SEM cell image at day 3) and osteoblastic differentiation (right, immunofluorescence staining with bone marker at day 14) on the microspheres was evident, suggesting the composite microspheres provided effective 3D substrate conditions for hard tissue regeneration. [source] Association of a single nucleotide polymorphism in the steroid and xenobiotic receptor (SXR) gene (IVS1-579A/G) with bone mineral densityGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2 2007Tomohiko Urano Vitamin K2 plays an important role in the bone metabolism. The steroid and xenobiotic receptor (SXR) as a nuclear receptor activated by vitamin K2 as well as rifampicin could increase bone markers such as alkaline phosphatase in human osteoblastic cells. Thus, the SXR could mediate vitamin K2 signaling pathway in bone cells. Therefore, we analyzed expression of the SXR mRNA in human primary osteoblasts and chondrocytes. We also studied association of a single nucleotide polymorphism (SNP) in the SXR gene with bone mineral density (BMD). Expression levels of the SXR mRNA were analyzed during the culture course of human primary osteoblasts and chondrocytes. Association of a SNP in the SXR gene in intron 1 (IVS1-579A>G) with BMD was examined in 294 healthy postmenopausal Japanese women. The SXR mRNA increased at day 5 and then decreased at day 10 in human primary osteoblasts. Its mRNA gradually increased in human primary chondrocytes until day 10. As an association study of a SNP in the SXR gene (IVS1-579A/G), the subjects without the A allele (GG; n = 47) had significantly higher total BMD than the subjects bearing at least one A allele (AA + AG; n = 247) (Z score ± SD; 0.635 ± 1.031 versus 0.268 ± 1.061; P = 0.0298). The SXR mRNA was expressed and regulated in primary human osteoblasts and chondrocytes. A genetic variation at the SXR gene locus is associated with BMD, suggesting an involvement of the SXR gene in human bone metabolism. [source] Bone turnover markers and prediction of fracture: A prospective follow-up study of 1040 elderly women for a mean of 9 yearsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2010Kaisa K Ivaska Abstract Osteoporosis is characterized by compromised bone mass and strength, predisposing to an increased risk of fracture. Increased bone metabolism has been suggested to be a risk factor for fracture. The aim of this study was to evaluate whether baseline bone turnover markers are associated with long-term incidence of fracture in a population-based sample of 1040 women who were 75 years old (Malmö OPRA study). Seven bone markers (S-TRACP5b, S-CTX-I, S-OC[1,49], S-TotalOC, S-cOC, S-boneALP, and urinary osteocalcin) were measured at baseline and 1-year follow-up visit. During the mean follow-up of 9.0 years (range 7.4,10.9), 363 women sustained at least one fracture of any type, including 116 hip fractures and 103 clinical vertebral fractures. High S-TRACP5b and S-CTX-I levels were associated with increased risk of any fracture with hazard ratios [HRs (95% confidence interval)] of 1.16 (1.04,1.29) and 1.13 (1.01,1.27) per SD increase, respectively. They also were associated with increased risk of clinical vertebral fracture with HRs of 1.22 (1.01,1.48) and 1.32 (1.05,1.67), respectively. Markers were not associated with risk for hip fracture. Results were similar when we used resorption markers, including urinary osteocalcin, measured at the 1-year visit or an average of the two measurements. The HRs were highest for any fracture in the beginning of the follow-up period, 2.5 years from baseline. For vertebral fractures, the association was more pronounced and lasted for a longer period of time, at least for 5 years. In conclusion, elevated levels of S-TRACP5b, S-CTX-I, and urinary osteocalcin are associated with increased fracture risk for up to a decade in elderly women. © 2010 American Society for Bone and Mineral Research [source] Effect of Fracture on Bone Turnover Markers: A Longitudinal Study Comparing Marker Levels Before and After Injury in 113 Elderly Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2007Kaisa K Ivaska PhD Abstract In this longitudinal, prospective, and population-based study (n = 1044), seven BTMs were assessed before and after trauma in 113 elderly women (85 with fractures). Markers were not altered in the immediate postfracture period but were clearly elevated during fracture repair. Recent fracture should thus be taken into account when markers are used in clinical practice. Introduction: Fracture may influence the levels of bone turnover markers (BTM) and have implications for their use in clinical practice. In this longitudinal, prospective, and population-based study, we assessed prefracture levels of BTMs and compared them with postfracture levels of the same individuals immediately after fracture and during fracture repair. This is the first study in which the effect of fracture on bone markers has been evaluated with prefracture samples available. Materials and Methods: Serum and urine were collected at the emergency unit from 85 women (77.9 ± 1.8 yr) who sustained a fracture after low-energy trauma and 28 controls (77.8 ± 2.0 yr) with similar trauma but no fracture. All were participants of the Malmö OPRA study (n = 1044), and pretrauma samples were collected 1.05 ± 0.85 yr before. Bone turnover was assessed by seven different BTMs reflecting different stages of bone metabolism {C-terminal cross-linked telopeptides of type I collagen [S-CTX], S-TRACP5b, N-terminal propeptides of type I collagen [S-PINP], serum osteocalcin (S-OC[1,49] and S-TotalOC), urinary deoxypyridinoline [U-DPD], and urinary osteocalcin [U-OC]}. Results: BTMs sampled within a few hours after fracture were not altered from preinjury levels. Both bone formation and bone resorption markers were, however, significantly increased 4 mo after fracture. The elevation was most pronounced after hip fracture. Bone turnover remained elevated up to 12 mo after fracture. Conclusions: We believe this study extends our knowledge on the skeletal postfracture metabolic processes. In addition, it may provide a basis for future means to monitor pharmacological intervention promoting fracture healing. [source] Effect of Teriparatide {rhPTH(1-34)} on BMD When Given to Postmenopausal Women Receiving Hormone Replacement TherapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2006Louis G Ste-Marie Abstract The effects of teriparatide when given in combination with HRT were studied in postmenopausal women with low bone mass or osteoporosis. The data provide evidence that the adverse event profile for combination therapy with teriparatide + HRT together is consistent with that expected for each treatment alone and that the BMD response is greater than for HRT alone. Introduction: Teriparatide {rhPTH(1-34)}, given as a once-daily injection, activates new bone formation in patients with osteoporosis. Hormone replacement therapy (HRT) prevents osteoporosis by reducing bone resorption and formation. Combination therapy with these two compounds, in small clinical trials, increased BMD and reduced vertebral fracture burden. The purpose of this study was to determine whether teriparatide provided additional effect on BMD when given in combination with HRT. Materials and Methods: A randomized, double-blind, placebo-controlled study was conducted in postmenopausal women with either low bone mass or osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n = 125) or teriparatide 40 ,g/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median treatment exposure of 13.8 months. Approximately one-half of the patients in each group were pretreated with HRT for at least 12 months before randomization. Patients received 1000 mg calcium and 400,1200 IU of vitamin D daily as oral supplementation. BMD was measured by DXA. Results: Compared with HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one-third distal radius was lower, in the combination therapy but not in the HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared with HRT. A similar profile of BMD and bone markers was evident in both randomized patients as well as in subgroups of patients not pretreated or pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg cramps were more frequently reported in the TPTD40 + HRT group. Conclusions: Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent, provides additional increases in BMD beyond that provided by HRT alone. The adverse effects of teriparatide when added to HRT were similar to the adverse effects described for teriparatide administered alone. Whether teriparatide was initiated at the same time as HRT or after at least 1 year on HRT, the incremental increases over HRT alone were similar. [source] Parathyroid Hormone-Related Protein Induced Coupled Increases in Bone Formation and Resorption Markers for 7 Years in a Patient With Malignant Islet Cell Tumors,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2002Ph.D., Yasuhiro Takeuchi M.D. Abstract Parathyroid hormone-related protein (PTHrP) and PTH share the common PTH/PTHrP receptor. Although an elevated level of circulating PTHrP in patients with malignancies causes hypercalcemia as does PTH, chronic and systemic effects of PTHrP on bone metabolism in humans are not well understood because tumor-burden patients showing hypercalcemia usually have a poor prognosis. We investigated bone and calcium metabolism in a patient with malignant islet cell tumors showing hypercalcemia due to the elevated plasma PTHrP level for 7 years. Hypercalcemia and hypercalciuria continued throughout the clinical course in spite of frequent infusions of bisphosphonates. Bone resorption markers and a bone formation marker were consistently elevated as seen in primary hyperparathyroidism, a disease caused by an autonomous hypersecretion of PTH. Based on biochemical measurements including bone markers and serum 1,25-dihydroxyvitamin D, the clinical features of this case essentially are the same as those of primary hyperparathyroidism except for the elevated level of plasma PTHrP with suppressed intact PTH level. Therefore, it is suggested that chronic and systemic effects of PTHrP on bone as well as calcium metabolism are indistinguishable from those of PTH in human. [source] Cross-Sectional Evaluation of Bone Metabolism in Men,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2001P. Szulc Abstract There are relatively few data concerning age-related changes of bone turnover in men. The aim of the study was to evaluate age-related changes of the levels of serum and urinary biochemical markers of bone metabolism in a large cohort of 934 men aged 19,85 years and to investigate their association with bone mineral density (BMD). Bone formation was evaluated using serum levels of osteocalcin (OC), bone alkaline phosphatase (BAP), and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by measurement of urinary excretion of ,-isomerized C-terminal telopeptide of collagen type I (,-CTX) of free deoxypyridinoline (fDpyr) and total Dpyr (tDPyr) and of the serum level of ,-CTX. Levels of biochemical bone markers were very high in young men and decreased rapidly until the age of 40 years and then more slowly until 60 years of age. After the age of 60 years, markers of bone formation remained stable while resorption markers showed a moderate and variable increase with aging. Serum and urinary ,-CTX levels were elevated only in about 5% of elderly men. The age-related increase of urinary excretion of tDpyr and of its free and peptide-bound fractions was related to the presence of elevated levels in a subgroup of about 15% of elderly men. Before 60 years of age, levels of biochemical bone markers were not correlated with BMD, whereas after 60 years of age, they were correlated negatively with BMD. After adjustment for age and body weight, BMD in men with the highest levels of biochemical bone markers (i.e., in the upper quartile) was 1.8,12.5% (i.e., 0.25,0.89 SD) lower than in men with levels of biochemical bone markers in the lowest quartile. In conclusion, bone turnover in men is high in young adults and decreases to reach a nadir at 55,60 years of age. After the age of 60 years, bone resorption markers,but not bone formation markers,increase in some men and are associated with lower BMD, suggesting that this imbalance is responsible for increasing bone loss in elderly men. [source] Growth Hormone Induces Bone Morphogenetic Proteins and Bone-Related Proteins in the Developing Rat PeriodontiumJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2001Huika Li Abstract The hypothesis that growth hormone (GH) up-regulates the expression of enzymes, matrix proteins, and differentiation markers involved in mineralization of tooth and bone matrices was tested by the treatment of Lewis dwarf rats with GH over 5 days. The molar teeth and associated alveolar bone were processed for immunohistochemical demonstration of bone morphogenetic proteins 2 and 4 (BMP-2 and -4), bone morphogenetic protein type IA receptor (BMPR-IA), bone alkaline phosphatase (ALP), osteocalcin (OC), osteopontin (OPN), bone sialoprotein (BSP), and E11 protein (E11). The cementoblasts, osteoblasts, and periodontal ligament (PDL) cells responded to GH by expressing BMP-2 and -4, BMPR-IA, ALP, OC, and OPN and increasing the numbers of these cells. No changes were found in patterns of expression of the late differentiation markers BSP and E11 in response to GH. Thus, GH evokes expression of bone markers of early differentiation in cementoblasts, PDL cells, and osteoblasts of the periodontium. We propose that the induction of BMP-2 and -4 and their receptor by GH compliments the role of GH-induced insulin-like growth factor 1 (IGF-1) in promoting bone and tooth root formation. [source] Effects of a New Selective Estrogen Receptor Modulator (MDL 103,323) on Cancellous and Cortical Bone in Ovariectomized Ewes: A Biochemical, Histomorphometric, and Densitometric StudyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2001Pascale Chavassieux Abstract The aims of this study performed in ewes were: (1) to confirm in this animal model the effects on bone of ovariectomy (OVX) alone or associated with Lentaron (L), a potent peripheral aromatase inhibitor, used to amplify the effects of OVX and (2) to evaluate the effects of a new selective estrogen receptor modulator (SERM; MDL 103,323) on bone remodeling. Thirty-nine old ewes were divided into five groups: sham (n = 7); OVX (n = 8); OVX + L (n = 8); OVX + L + MDL; 0.1 mg/kg per day (n = 8); and OVX + L + MDL 1 mg/kg per day (n = 8). The animals were treated for 6 months. Biochemical markers of bone turnover (urinary excretion of type 1 collagen C-telopeptide [CTX], serum osteocalcin [OC], and bone alkaline phosphatase [BAP]) were measured each month. Bone biopsy specimens were taken at the beginning and after death at the end of the experiment. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) on the lumbar spine and femur. OVX induced a significant increase in biochemical markers. This effect was the highest after 3 months for CTX (+156% vs. sham) and after 4 months for OC and BAP (+74% and +53% vs. sham, respectively). L tended to amplify the effect of OVX on OC and BAP. OVX induced significant increases in the porosity, eroded, and osteoid surfaces in cortical bone but no effect was observed in cancellous bone. MDL treatment reduced the bone turnover as assessed by bone markers, which returned to sham levels as well as histomorphometry both in cortical and in cancellous bone. Cancellous osteoid thickness decreased by 27% (p < 0.05), mineralizing perimeter by 81% (p < 0.05), and activation frequency by 84% (p < 0.02) versus OVX + L. Femoral and spinal BMD were increased by MDL and tended to return to the sham values. The effects of OVX on bone turnover were different on cortical and cancellous bone. These effects on cortical bone were reflected by changes in biochemical markers. MDL markedly reduces bone turnover and increases BMD suggesting that this new agent may prevent postmenopausal bone loss. [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] Alveolar ridge augmentation using implants coated with recombinant human growth/differentiation factor-5: histologic observationsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2010Giuseppe Polimeni Polimeni G, Wikesjö UME, Susin C, Qahash M, Shanaman RH, Prasad HS, Rohrer MD, Hall J. Alveolar ridge augmentation using implants coated with recombinant human growth/differentiation factor-5: histologic observations. J Clin Periodontol 2010; 37: 759-768 doi: 10.1111/j.1600-051X.2010.01579.x. Abstract Objectives: In vitro and in vivo preclinical studies suggest that growth/differentiation factor-5 (GDF-5) may induce local bone formation. The objective of this study was to evaluate the potential of recombinant human GDF-5 (rhGDF-5) coated onto an oral implant with a purpose-designed titanium porous oxide surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge. Materials and Methods: Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with 30 or 60 ,g rhGDF-5, and six animals received implants coated with 120 ,g rhGDF-5 or left uncoated (control). Treatments were alternated between jaw quadrants. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7, and 8 post-surgery when they were euthanized for histologic evaluation. Results: The clinical examination showed no noteworthy differences between implants coated with rhGDF-5. The cover screw and implant body were visible/palpable through the alveolar mucosa for both rhGDF-5-coated and control implants. There was a small increase in induced bone height for implants coated with rhGDF-5 compared with the control, induced bone height averaging (±SD) 1.6±0.6 mm for implants coated with 120 ,g rhGDF-5 versus 1.2±0.5, 1.2±0.6, and 0.6±0.2 mm for implants coated with 60 ,g rhGDF-5, 30 ,g rhGDF-5, or left uncoated, respectively (p<0.05). Bone formation was predominant at the lingual aspect of the implants. Narrow yellow and orange fluorescent markers throughout the newly formed bone indicate relatively slow new bone formation within 3,4 weeks. Implants coated with rhGDF-5 displayed limited peri-implant bone remodelling in the resident bone; the 120 ,g dose exhibiting more advanced remodelling than the 60 and 30 ,g doses. All treatment groups exhibited clinically relevant osseointegration. Conclusions: rhGDF-5-coated oral implants display a dose-dependent osteoinductive and/or osteoconductive effect, bone formation apparently benefiting from local factors. Application of rhGDF-5 appears to be safe as it is associated with limited, if any, adverse effects. [source] Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observationsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2010Cristiano Susin Susin C, Qahash M, Polimeni G, Lu PH, Prasad HS, Rohrer MD, Hall J, Wikesjö UME. Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observations. J Clin Periodontol 2010; 37: 574,581. doi: 10.1111/j.1600-051X.2010.01554.x. Abstract Background: Pre-clinical studies have shown that recombinant human bone morphogenetic protein-2 (rhBMP-2) coated onto purpose-designed titanium porous-oxide surface implants induces clinically relevant bone formation and osseointegration. The objective of this study was to examine the potential of rhBMP-7, also known as recombinant human osteogenic protein-1 (rhOP-1), coated onto titanium porous-oxide surface implants to support vertical alveolar ridge augmentation and implant osseointegration. Materials and Methods: Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in six young adult Hound Labrador mongrel dogs. The animals received implants coated with rhBMP-7 at 1.5 or 3.0 mg/ml randomized to contra-lateral jaw quadrants. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at 3, 4, 7, and 8 weeks post-surgery when they were euthanized for histological evaluation. Results: Without striking differences between treatments, the implant sites exhibited a swelling that gradually regressed to become hard to palpation disguising the implant contours. The histological evaluation showed robust bone formation; the newly formed bone assuming characteristics of the contiguous resident bone, bone formation (height and area) averaging 4.1±1.0 versus 3.6±1.7 mm and 3.6±1.9 versus 3.1±1.8 mm2; and bone density 56%versus 50% for implants coated with rhBMP-7 at 1.5 and 3.0 mg/ml, respectively. Both treatments exhibited clinically relevant osseointegration, the corresponding bone,implant contact values averaging 51% and 47%. Notable peri-implant resident bone remodelling was observed for implants coated with rhBMP-7 at 3.0 mg/ml. Conclusions: rhBMP-7 coated onto titanium porous-oxide surface implants induces clinically relevant local bone formation including osseointegration and vertical augmentation of the alveolar ridge, the higher concentration/dose associated with some local side effects. [source] Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior maxilla (Type IV bone) in non-human primatesJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2008Ulf M. E. Wikesjö Abstract Background: Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce local bone formation including osseointegration. The objective of this study was to evaluate local bone formation and osseointegration at such implants placed into Type IV bone. Material and Methods: rhBMP-2-coated implants were installed into the edentulated posterior maxilla in eight young adult Cynomolgus monkeys: four animals each received three TPO implants adsorbed with rhBMP-2 (2.0 mg/ml) and four animals each received three TPO implants adsorbed with rhBMP-2 (0.2 mg/ml). Contra-lateral jaw quadrants received three TPO implants without rhBMP-2 (control). Treatments were alternated between left and right jaw quadrants. Mucosal flaps were advanced and sutured to submerge the implants. The animals received fluorescent bone markers at weeks 2, 3, 4, and at week 16 when they were euthanized for histologic analysis. Results: Clinical healing was uneventful. Extensive local bone formation was observed in animals receiving implants adsorbed with rhBMP-2 (2.0 mg/ml). The newly formed bone exhibited a specific pinpoint bone,implant contact pattern regardless of rhBMP-2 concentration resulting in significant osseointegration; rhBMP-2 (2.0 mg/ml): 43% and rhBMP-2 (0.2 mg/ml): 37%. Control implants exhibited a thin layer of bone covering a relatively larger portion of the implant threads. Thus, TPO control implants bone exhibited significantly greater bone,implant contact (,75%; p<0.05). There were no statistically significant differences between rhBMP-2-coated and control implants relative to any other parameter including peri-implant and intra-thread bone density. Conclusion: rhBMP-2-coated TPO implants enhanced/accelerated local bone formation in Type IV bone in a dose-dependent fashion in non-human primates resulting in significant osseointegration. rhBMP-2-induced de novo bone formation did not reach the level of osseointegration observed in native resident bone within the 16-week interval. [source] Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: histologic observationsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2008Ulf M. E. Wikesjö Abstract Background: Studies using ectopic rodent, orthotopic canine, and non-human primate models show that bone morphogenetic proteins (BMPs) coated onto titanium surfaces induce local bone formation. The objective of this study was to examine the ability of recombinant human BMP-2 (rhBMP-2) coated onto a titanium porous oxide implant surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge. Material and Methods: Bilateral, critical-size, 5 mm, supra-alveolar, peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml, and six animals received implants coated with rhBMP-2 at 3.0 mg/ml or uncoated control. Treatments were randomized between jaw quadrants. The mucoperiosteal flaps were advanced, adapted and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7 and 8 post-surgery when they were euthanized for histologic evaluation. Results: Jaw quadrants receiving implants coated with rhBMP-2 exhibited gradually regressing swelling that became hard to palpate disguising the contours of the implants. The histologic evaluation showed robust bone formation reaching or exceeding the implant platform. The newly formed bone exhibited characteristics of the adjoining resident Type II bone including cortex formation for sites receiving implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml. Sites receiving implants coated with rhBMP-2 at 3.0 mg/ml exhibited more immature trabecular bone formation, seroma formation and peri-implant bone remodelling resulting in undesirable implant displacement. Control implants exhibited minimal, if any, bone formation. Thus, implants coated with rhBMP-2 at 0.75, 1.5 and 3.0 mg/ml exhibited significant bone formation (height and area) compared with the sham-surgery control averaging (±SD) 4.4±0.4, 4.2±0.7 and 4.2±1.2 versus 0.8±0.3 mm; and 5.0±2.2, 5.6±2.2 and 7.4±3.5 versus 0.7±0.3 mm2, respectively (p<0.01). All the treatment groups exhibited clinically relevant osseointegration. Conclusions: rhBMP-2 coated onto titanium porous oxide implant surfaces induced clinically relevant local bone formation including vertical augmentation of the alveolar ridge and osseointegration. Higher concentrations/doses were associated with untoward effects. [source] The critical-size supraalveolar peri-implant defect model: characteristics and useJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2006Ulf M. E. Wikesjö Abstract Objective: Novel implant technologies and reconstructive therapies for alveolar augmentation require pre-clinical evaluation to estimate their biologic potential, efficacy, and safety before clinical application. The objective of this report is to present characteristics and use of the critical-size, supraalveolar, peri-implant defect model. Methods: Bilateral extraction of the mandibular premolars was performed in 12 Hound Labrador mongrel dogs following horizontal surgical cut-down of the alveolar ridge approximating 6 mm. Each jaw quadrant received three custom-produced TiUniteÔ, ,4.0 × 10 mm threaded implants placed into osteotomies prepared into the extraction sites of the third and fourth premolars. The implants exhibited a reference notch 5 mm from the implant platform to facilitate surgical placement leaving 5 mm of the implant in a supraalveolar position, and to serve as a reference point in the radiographic, histologic and histometric analysis. The implants were submerged under the mucoperiosteal flaps for primary intention healing. Fluorescent bone markers were administered at weeks 3 and 4 post-surgery, and pre-euthanasia. The animals were euthanized following an 8-week healing interval when block biopsies were collected for analysis. Results: Healing was generally uneventful. The radiographic and histometric evaluations demonstrate the limited osteogenic potential of this defect model. Whereas lingual peri-implant sites exhibited a mean (±SE) bone gain of 0.4±0.1 mm, resorption of the buccal crestal plate resulted in a mean bone loss of 0.4±0.2 mm for an overall osteogenic potential following sham-surgery averaging 0.0±0.1 mm. Overall bone density and bone,implant contact in the contiguous resident bone averaged 79.1±1.1% and 76.9±2.3%, respectively. Conclusion: The results suggest that the critical-size, supraalveolar, peri-implant defect model appears a rigorous tool in the evaluation of candidate technologies for alveolar reconstruction and osseointegration of endosseous oral implants. Limited innate osteogenic potential allows critical evaluation of osteogenic, osteoconductive, or osteoinductive technologies in a challenging clinical setting. [source] Bone mineral content and bone metabolism in young adults with severe periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2001Nina Von Wowern Abstract Objectives: To clarify in young adults with severe periodontitis (1) whether the bone mineral content (BMC) or density (BMD) in the mandible/other skeletal sites and the systemic bone metabolism differed from normal and (2) whether mandibular/forearm BMC did change during the 5 to 10-year follow-up. Material and Methods: 24 young otherwise normal patients with verified severe periodontitis were included, of which 20 attended the follow-up visit. Mandibular/forearm BMC was measured at both visits by dual-photon absorptiometry, supplemented with femoral neck/lumbar spine BMD measurements at follow-up visit by dual-energy X-ray absorptiometry. Serum alkaline phosphatase/ionized calcium, urinary excretion of pyridinoline/deoxy-pyridinoline were analysed at the follow-up visit. A conventional periodontal examination was performed at both visits. Results: Mandibular BMC was significantly below normal mean BMC at both visits. The mandibular Z-scores were ,2.00 in 33.3% (8/24). BMC/BMD in the remaining sites and the values for bone markers did not differ from normal. Mandibular/forearm BMC was stable while a significant aggravation of alveolar bone loss occurred during the trial without change of probing depth. Conclusions: Severe periodontitis in young adults seems to be a local disorder associated with relatively low BMC in the jaws without systemic alterations of BMC/BMD and bone metabolism. Zusammenfassung Zielsetzung: Abklärung ob bei jungen Erwachsenen mit schwerer Parodontitis (1) der Mineralgehalt und die Dichte des Knochens im Unterkiefer bzw. anderen Teilen des Skeletts sowie deer Knochenstoffwechsel sich von normalen Verhältnissen unterscheiden und (2) ob sich der Mineralgehalt des Unterkiefer- bzw. des Unterarmknochens während eines Beobachtungszeitraums von 5 bis 10 Jahren verändern. Material und Methoden: 24 allgemein gesunde Patienten mit schwerer Parodontitis nahmen an der Studie teil von denen 20 an der Nachuntersuchung teilnahme. Der Mineralgehalt des Unterkiefer- bzw. Unterarmknochens wurde bei beiden Untersuchungen mittels Dual-Photonen-Absorptiometrie bestimmt. Zusätzlich wurden bei der Nachuntersuchung die Knochendichte des Obserschenkelhalses und der Lendenwirbel mittels Dual-Energie-Röntgen-Absorptiometrie erfaßt. Die Serumkonzentrationen alkalischer Phosphatase sowie der Kalzium-Ionen und die Ausscheidung von Pyridinolin sowie Desoxypyridinolin im Urin wurden bei der Nachuntersuchung analysiert. Zu jedem Untersuchungstermin fand eine klinische Untersuchung der parodontalen Verhältnisse statt. Ergebnisse: Der Mineralgehalt des Unterkieferknochens lag zu beiden Untersuchungsterminen unter den mittleren Normalwerten. Die Z-Werte des Unterkiefers lagen in 8 von 24 Fällen (33.3%) ,2.00. Der Mineralgehalt und die Dichte des Knochens der übrigen Regionen und die Werte der Knochenmarker unterschieden sich nicht von den Normalwerten. Der Mineralgehalt des Unterkiefer- und Unterarmknochens verhielt sich während des Untersuchungszeitraumes stabil, während es zu einer deutlichen Verschlimmerung des alveolären Knochenabbaus ohne Veränderung der Sondierungstiefen kam. Schlußfolgerungen: Bei schwerer Parodontitis bei jungen Erwachsenen scheint es sich um eine lokale Störung mit relativ geringem Mineralgehalt der Kieferknochen zu handeln ohne systemische Veränderungen von Mineralgehalt und Dichte des Knochens bzw. des Knochenstoffwechsels. Résumé Le but de cette étude était de connaître chez les jeunes adultes souffrant de parodontite sévère (1) si le contenu en minéraux osseux (BMC) ou la densité (BMD) dans des sites mandibulaires ou du squelette et le métabolisme osseux systémique étaient différents par rapport à ceux de personnes normales et (2) si le BMC de la mandibule ou de l'avant-bras changeait durant une période de suivi de 5 à 10 années. 24 patients normaux mais souffrant de parodontite sévère ont été inclus dans cette investigation mais seul 20 ont poursuivi l'étude. Le BMC de la mandibule et de l'avant-bras ont été mesurés aux 2 sites par absorptiométrie par photon double, avec également des mesures BMD au niveau du fémur et de la colonne vertébrale lors de la visite de suivi par absorptiométrie par RX àénergie double. Le calcium ionisé par phosphatase alcaline sérique et l'excrétion urinaire de pyridinoline/deoxypyridinoline ont été analysés lors de l'examen de suivi. Un examen parodontal conventionnel a été effectué aux 2 visites. Le BMC mandibulaire était significativement inférieur au BMC moyen normal lors des deux visites. Les scores Z mandibulaires étaient ,2.00 dans 33.3% (8/24) des cas. BMC/BMD dans les sites restants et les valeurs des marqueurs osseux ne différaient pas des normaux. BMC mandibulaire/avant-bras était stable tandis qu'une aggravation significative de la perte osseuse alvéolaire se produisait durant l'étude sans changement de la profondeur au sondage. La parodontite sévère chez les jeunes adultes semble être un désordre local associéà un BMC relativement bas dans les mâchoires sans altération systémique de BMC/BMD ni du métabolisme osseux. [source] Zoledronic acid for the treatment of osteopenia in pediatric Crohn's diseasePEDIATRICS INTERNATIONAL, Issue 5 2010Anne Marie Sbrocchi Abstract Background:, Pediatric patients with Crohn's disease often have low bone mass (osteopenia) for age. No randomized, placebo-controlled trials using zoledronic acid have ever been performed in this population. The objective of this study was to assess the efficacy of zoledronic acid in children with Crohn's disease and osteopenia. Methods:, A double-blind, randomized, placebo-controlled design was used. Thirteen adolescents received either a single intravenous dose of zoledronic acid (0.066 mg/kg, max 4 mg, n= 7) or saline placebo (n= 6). The primary outcome was change in lumbar spine bone mineral density (LSBMD) z-score at 6 months. Secondary outcomes included bone markers and adverse events. Results:, At 6 months, the change in LSBMD z-score was significantly higher in the zoledronic acid group compared to placebo (0.7 vs 0.1, P < 0.001). Volumetrically adjusted LSBMD z-score also significantly increased in the treated group. This significant difference persisted until 12 months. With zoledronic acid, urinary C-telopeptide excretion decreased by 50% at 6 months and remained suppressed at 12 months (P= 0.02), but no changes were observed with placebo. Both groups had similar adverse events which included transient fever, arthralgias, and nausea (3/7 treated, 2/6 placebo, P= NS). Conclusions:, In this study, zoledronic acid demonstrated a significant increase in LSBMD at 6 and 12 months following a well-tolerated infusion. [source] Prophylactic Bisphosphonate Treatment Prevents Bone Fractures After Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2007M. Bodingbauer A randomized controlled prospective open-label single center trial was performed. At the time of transplantation patients were randomly assigned to one of two treatment arms: The study group of 47 patients received zoledronic acid (ZOL, 8 infusions at 4 mg during the first 12 months after LT), calcium (1000 mg/d) and vitamin D (800 IE/d). The control group consisted of 49 patients who received calcium and vitamin D at same doses (CON). The incidence of bone fractures or death was predefined as the primary endpoint. Secondary endpoints included bone mineral density (BMD), serum biochemical markers of bone metabolism, parameters of trabecular bone histomorphometry and mineralization density distribution (BMDD). Patients were followed up for 24 months. Analysis was performed on an intention-to-treat basis. The primary endpoint fracture or death was reached in 26% of patients in the ZOL group and 46% in the CON group (p = 0.047, log rank test). Densitometry results were different between the groups at the femoral neck at 6 months after LT (mean+/-SD BMD ZOL: 0.80 ± 0.19 g/cm2 vs. CON: 0.73 ± 0.14 g/cm2, p = 0.036). Mixed linear models of biochemical bone markers showed less increase of osteocalcin in the ZOL group and histomorphometry and BMDD indicated a reduction in bone turnover. Prophylactic treatment with the bisphosphonate zoledronic acid reduces bone turnover and fractures after liver transplantation. [source] The use of molecular markers of bone turnover in the management of patients with metastatic bone diseaseCLINICAL ENDOCRINOLOGY, Issue 6 2008Markus J. Seibel Summary Biochemical markers of bone turnover are widely used in clinical practice. These indices have been shown to be associated with the occurrence, prognosis and therapeutic response of malignant bone lesions. For example, markers of bone resorption are often elevated in patients with established bone metastases and while this may point to a role of these markers in the diagnostic workup of cancer patients, the available evidence does not permit any final conclusions as to the accuracy and validity of the presently used markers in the early diagnosis of bone metastases. Many bone turnover markers appear to respond to antiresorptive and antineoplastic therapies, and recent evidence from prospective trials suggests that the aim of bisphosphonate therapy should be to normalize rates of bone remodelling to optimize therapeutic and prognostic outcomes. However, it remains unknown whether the use of bone markers in the routine clinical setting has any defined beneficial effects on overall outcome in cancer patients. Clearly, bone turnover markers have insufficient diagnostic or prognostic value to be used in isolation; however, the combination of these markers with other diagnostic techniques may improve clinical assessment of patients with bone-seeking cancers. This article reviews the available evidence (as of August 2007) on the clinical use of bone turnover markers in the management of patients with metastatic bone disease. [source] | ||||||||||