Bone Biopsies (bone + biopsy)

Distribution by Scientific Domains
Medical Sciences92%
Life Sciences7%

Selected Abstracts

A Novel Tetracycline Labeling Schedule for Longitudinal Evaluation of the Short-Term Effects of Anabolic Therapy With a Single Iliac Crest Bone Biopsy: Early Actions of Teriparatide,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2006
Robert Lindsay MD
Abstract We describe a quadruple tetracycline labeling method that allows longitudinal assessment of short-term changes in bone formation in a single biopsy. We show that 1 month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation. Introduction: Iliac crest biopsy, with histomorphometric evaluation, provides important information about cellular activity in bone. However, to obtain longitudinal information, repeat biopsies must be performed. In this study, we show the capability to obtain short-term longitudinal information on bone formation in a single biopsy using a novel, quadruple labeling technique. Materials and Methods: Two tetracycline labels were administered using a standard 3 days on, 12 days off, 3 days on format. Four weeks later, the tetracycline labeling was repeated using the same schedule but with a different tetracycline that can be distinguished from the first by its color under fluorescent light. Iliac crest biopsies were performed 1 week later and prepared undecalcified for histomorphometry. Indices of bone formation 1 month apart were measured and calculated using the two sets of labels. We used this method to investigate the early effects of teriparatide [hPTH(1-34)] treatment on bone formation. The results were compared with those from a group of control subjects who were quadruple-labeled, but did not receive hPTH(1-34). Results: Treatment with hPTH(1-34) dramatically stimulated bone formation on cancellous and endocortical surfaces. This was achieved by both an increase in the linear rate of matrix apposition and extension of the bone-forming surface. New bone was deposited on previously quiescent surfaces (i.e., modeling-based formation), but a proportion of this could occur by encroachment from adjacent resorption cavities. Conclusions: A single transiliac crest bone biopsy, after sequential administration of two sets of tetracycline labels is a useful approach to study the short-term effects of anabolic agents on human bone. One month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation. [source]

Bone Remodeling: Biochemical Markers or Bone Biopsy?

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2006
Pascale M Chavassieux
No abstract is available for this article. [source]

Histomorphometric assessment of bone turnover in uraemic patients: comparison between activation frequency and bone formation rate

HISTOPATHOLOGY, Issue 6 2001
P Ballanti
Histomorphometric assessment of bone turnover in uraemic patients: comparison between activation frequency and bone formation rate Aims:,The histomorphometric assessment of bone formation rate (BFR/BS) in bone biopsies from uraemic patients is of crucial importance in differentiating low from high turnover types of renal osteodystrophy. However, since BFR/BS relies on osteoblasts, activation frequency (Ac.f), encompassing all remodelling phases, has recently been preferred to BFR/BS. This study was carried out to consider whether estimation of Ac.f is superior, in practical terms, to that of BFR/BS in distinguishing between different rates of bone turnover in uraemic patients. Methods and results:,Bone biopsies from 27 patients in predialysis (20 men and seven women; mean age 53 ± 12 years) and 37 in haemodialysis (22 men and 15 women; mean age 53 ± 12 years) were examined. The types of renal osteodystrophy were classified on the basis of morphology. Bone formation rate and Ac.f were evaluated according to standardized procedures. The Ac.f was calculated both as a ratio between BFR/BS and wall thickness (W.Th) and as a reciprocal of erosion, formation and quiescent periods (EP, FP and QP). Patients were affected by renal osteodystrophy with predominant hyperparathyroidism (two predialysis and 16 dialysis), predominant osteomalacia (three predialysis and seven dialysis) or that of advanced (nine predialysis and five dialysis) or mild (seven predialysis and four dialysis) mixed type or adynamic type (six predialysis and five dialysis). Activation frequency, which with either formula requires the measurement of W.Th, i.e. the thickness of bone structural units (BSUs), was not calculated in three dialysis patients with severe hyperparathyroidism and in one predialysis and four dialysis patients with severe osteomalacia, because only incomplete BSUs were found. In dialysis, EP was higher in the adynamic than in the other types of osteodystrophy. During both predialysis and dialysis, FP was higher in osteomalacia than in the other forms of osteodystrophy, and in adynamic osteopathy than in hyperparathyroidism or in advanced and mild mixed osteodystrophy. During predialysis and dialysis, QP was higher in the adynamic than in the other forms of osteodystrophy. Correlations were found between BFR/BS and Ac.f, during predialysis (r=0.97) and dialysis (r=0.95). Conclusions:,The superiority of Ac.f in assessing bone turnover, in comparison to BFR/BS, is conceptual rather than practical. The highest values for FP in osteomalacia and for QP in adynamic bone allow a clearer characterization of these low turnover conditions. [source]

Bone formation following sinus grafting with autogenous bone-derived cells and bovine bone mineral in minipigs: preliminary findings

CLINICAL ORAL IMPLANTS RESEARCH, Issue 6 2004
Gabor Fuerst
Abstract: Bone formation in a sinus grafted with a cell-free scaffold requires the presence of local progenitor cells that differentiate into osteoblasts. The purpose of this study was to examine the effect of culture expanded autogenous bone-derived cells (ABC) with bovine bone mineral (BBM) on bone formation after single-stage sinus grafting in minipigs. Bone biopsies from the iliac crest were harvested 4 weeks prior to sinus grafting and ABC were culture expanded in vitro. The sinuses of five adult minipigs were grafted. In one sinus of each minipig the space between Schneider's membrane (SM) and the sinus wall was grafted with ABC (325,000 cells per sinus, on average) and BBM. In the other sinus, BBM alone was used. The animals were sacrificed after 12 weeks. One block of each grafted area was prepared by saw cutting and the amount of newly formed bone was analysed by micro-computed tomography (,-CT). The addition of ABC to BBM significantly increased the amount of newly formed bone compared with BBM alone on ,-CT analysis (ABC+BBM: 29.86±6.45% vs. BBM: 22.51±7.28% (P=0.016)). Bone formation was increased near SM (ABC+BBM: 20.7±4.5% vs. BBM: 15.43±3.62% (P=0.009)) and in the middle zone of the grafting material (ABC+BBM: 31.63±7.74% vs. BBM: 22.5±7.91% (P=0.001)), but not near the local host bone (ABC+BBM: 37.23±8.23% vs. BBM: 28.42±12.54% (P=0.15)). These preliminary findings indicate that supplementation of cell-free grafting material with culture expanded ABC can stimulate bone formation in areas with low bone-forming capacity. Résumé La néoformation osseuse dans un sinus grefféà l'aide d'un échafaudage acellulaire requiert la présence de cellules progénitrices locales qui se différencient en ostéoblastes. Le but de cette étude a été d'examiner l'effet de cellules dérivées de l'os autogène (ABC) avec expansion par culture avec un minéral osseux bovin (BBM) sur la formation osseuse après une greffe sinusale en une étape chez le mini-porc. Des biopsies osseuses de la crête iliaque ont été prélevées quatre semaines avant la greffe sinusale et les ABC ont été placées en culture in vitro. Les sinus de cinq mini-porcs adultes ont été greffés. Dans un sinus de chaque mini-porc l'espace entre la membrane de Schneider et la paroi sinusale a été greffé avec les ABC (en moyenne 325 000 cellules/sinus) et BBM. Dans l'autre sinus, BBM seul a été utilisé. Les animaux ont été euthanasiés après douze semaines. Un bloc de chaque aire greffée a été scié et la quantité d'os néoformé a été analysée par tomographie par micro-ordinateur (,-CT). L'addition d'ABC au BBM augmentait significativement la quantité d'os néoformé comparée à l'utilisation du BBM seul lors de l'analyse micro-CT [ABC+BBM : 29,9±6,5% vs BBM : 22,5±7,3% (P=0,016)]. La formation osseuse était augmentée près de la membrane de Schneiderian [ABC+BBM : 20,7±4,5 vs BBM : 15,4±3,6% (P=0,009)] et dans la zone moyenne du matériel greffé [ABC+BBM : 31,6±7,7% vs BBM : 22,5±7,9 (P=0,001)], mais pas dans la région proche de l'hôte (ABC+BBM : 37,2±8,2% vs BBM : 28,4±12,5% (P=0,150). Ces découvertes préliminaires indiquent que l'addition à un matériau acellulaire de ABC en culture d'expansion pouvait stimuler la formation osseuse dans des zones avec des faibles capacités de formation osseuse. Zusammenfassung Knochenformation nach Sinusaugmentation mit autologen Zellen knöchernen Ursprungs und bovinem Knochenmineral in Minipigs: erste Ergebnisse Die Bildung von neuem Knochen im augmentierten Sinus mit einer zellfreien Matrix benötigt lokale Progenitorzellen, welche sich in Osteoblasten differenzieren können. Das Ziel dieser Studie war, den Effekt von in Kultur gezüchteten autologen Zellen knöchernen Ursprungs (ABC) mit bovinem Knochenmineral (BBM) auf die Knochenbildung nach Sinusaugmentation in Minipigs zu untersuchen. Knochenbiopsien vom Beckenkamm wurden 4 Wochen vor der Sinusaugmentation entnommen und die ABC in vitro in einer Kultur vermehrt. Die Kieferhöhlen von 5 ausgewachsenen Minipigs wurden augmentiert. Bei einer Kieferhöhle jedes Minipigs wurde der Raum zwischen der Schneider'schen Membran und der Sinuswand mit ABC (325,000 Zellen pro Sinus in Durchschnitt) und BBM aufgefüllt. In der anderen Kieferhöhle wurde BBM allein verwendet. Die Tiere wurden nach 12 Wochen geopfert. Von jeder augmentierten Region wurde mittels Sägeschnitt ein Block präpariert und die Menge an neu gebildetem Knochen wurde durch Mikro-Computertomographie (,-CT) analysiert. Die Zugabe von ABC zu BBM bewirkte in der ,-CT Analyse eine signifikante Zunahme des neu gebildeten Knochens im Vergleich zu BBM allein (ABC+BBM: 29.86±6.45% gegenüber BBM. 22.51±7.28% (P=0.016)). Die Knochenbildung hatte im Bereich der Schneider'schen Membran (ABC+BBM: 20.7±4.5% gegenüber BBM: 15.43±3.62%(P=0.009)) und in der Mittelzone des Transplantatmaterials (ABC+BBM: 31.63±7.74% gegenüber BBM: 22.5±7.91% (P=0.001)) zugenommen, aber nicht in der Nähe des lokalen Wirtsknochens (ABC+BBM: 37.23±8.23% gegenüber BBM: 28.42±12.54% (P=0.15)). Diese ersten Resultate zeigen, dass der Zusatz von in Kultur gezüchteten ABC zu zellfreien Transplantatmaterialien die Knochenbildung in Regionen mit niedriger Knochenbildungskapazität stimulieren kann. Resumen La formación de nuevo hueso en un seno injertado con una estructura libre de células requiere la presencia de células progenitoras que se diferencien en osteoblastos. El propósito de este estudio fue examinar el efecto de células autógenas derivadas de hueso de cultivo expandido (ABC) con mineral de hueso bovino (BBM) en la formación de hueso tras un injerto del seno en una sola fase en minicerdos. Se tomaron biopsias de hueso de la cresta iliaca 4 semanas antes del injerto del seno y se cultivaron expandidamente las células ABC in vitro. Se injertaron los senos de 5 minicerdos. En un seno de cada minicerdo el espacio entre la membrana de Schneider y la pared del seno se injertó con ABC (325,000 células por seno, de media) y BBM. En el otro seno se uso BBM únicamente. Los animales se sacrificaron tras 12 semanas. Se preparó un bloque de cada área injertada por medio de una sierra y se analizó la cantidad de hueso neoformado por medio de micro tomografía computarizada (,-CT). La adición de ABC a BBM incrementó significativamente la cantidad de hueso neoformado comparado con BBM solo en el análisis de ,-CT [ABC+BBM: 29.86±6.45% vs. BBM: 22.51±7.28% (P=0.016)]. La formación del hueso se incrementó cerca de la membrana de Schneider [ABC+BBM: 20.7±4.5% vs. BBM: 15.43±3.62% (P=0.009)] y en la zona media de del material de injerto [ABC+BBM: 31.63±7.74% vs. BBM: 22.5±7.91% (P=0.001], pero no cerca del hueso huésped local [ABC+BBM: 37.23±8.23% vs. BBM: 28.42±12.54% (P=0.15)]. Estos hallazgos preliminares indican que la suplementación de injertos sin células con ABC de cultivo expandido puede estimular la formación de hueso en áreas con baja capacidad de formación de hueso. [source]

Chronic Recurrent Multifocal Osteomyelitis (CRMO) and Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Syndrome with Associated Neutrophilic Dermatoses: A Report of Seven Cases and Review of the Literature

PEDIATRIC DERMATOLOGY, Issue 5 2009
Brook E. Tlougan M.D.
Classically, patients present with swelling, pain, and impaired mobility of the affected area, with skin lesions developing concurrently or in the future. Bone biopsy reveals inflammatory changes consistent with infectious osteomyelitis, but cultures and histologic staining invariably fail to identify an infectious source. Patients are refractory to antibiotic therapy, but dramatically respond to systemic steroids and may need to be maintained on low-dose steroids to prevent relapse. Numerous authors have suggested that CRMO and synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome lie along the same clinical spectrum. In fact some believe that CRMO is the pediatric presentation of SAPHO. The two syndromes share numerous characteristics, including osteitis, a unifocal or multifocal presentation, hyperostosis, and pustulosis, which all occur in a generally healthy individual. Our seven patients, five of whom were diagnosed with CRMO, and two of whom were diagnosed with SAPHO syndrome further strengthen the idea that CRMO and SAPHO syndrome do indeed lie along the same clinical spectrum. In addition, we include two rare cases of pediatric Sweet's syndrome with evidence of pathergy. [source]

Histomorphometric assessment of bone turnover in uraemic patients: comparison between activation frequency and bone formation rate

HISTOPATHOLOGY, Issue 6 2001
P Ballanti
Histomorphometric assessment of bone turnover in uraemic patients: comparison between activation frequency and bone formation rate Aims:,The histomorphometric assessment of bone formation rate (BFR/BS) in bone biopsies from uraemic patients is of crucial importance in differentiating low from high turnover types of renal osteodystrophy. However, since BFR/BS relies on osteoblasts, activation frequency (Ac.f), encompassing all remodelling phases, has recently been preferred to BFR/BS. This study was carried out to consider whether estimation of Ac.f is superior, in practical terms, to that of BFR/BS in distinguishing between different rates of bone turnover in uraemic patients. Methods and results:,Bone biopsies from 27 patients in predialysis (20 men and seven women; mean age 53 ± 12 years) and 37 in haemodialysis (22 men and 15 women; mean age 53 ± 12 years) were examined. The types of renal osteodystrophy were classified on the basis of morphology. Bone formation rate and Ac.f were evaluated according to standardized procedures. The Ac.f was calculated both as a ratio between BFR/BS and wall thickness (W.Th) and as a reciprocal of erosion, formation and quiescent periods (EP, FP and QP). Patients were affected by renal osteodystrophy with predominant hyperparathyroidism (two predialysis and 16 dialysis), predominant osteomalacia (three predialysis and seven dialysis) or that of advanced (nine predialysis and five dialysis) or mild (seven predialysis and four dialysis) mixed type or adynamic type (six predialysis and five dialysis). Activation frequency, which with either formula requires the measurement of W.Th, i.e. the thickness of bone structural units (BSUs), was not calculated in three dialysis patients with severe hyperparathyroidism and in one predialysis and four dialysis patients with severe osteomalacia, because only incomplete BSUs were found. In dialysis, EP was higher in the adynamic than in the other types of osteodystrophy. During both predialysis and dialysis, FP was higher in osteomalacia than in the other forms of osteodystrophy, and in adynamic osteopathy than in hyperparathyroidism or in advanced and mild mixed osteodystrophy. During predialysis and dialysis, QP was higher in the adynamic than in the other forms of osteodystrophy. Correlations were found between BFR/BS and Ac.f, during predialysis (r=0.97) and dialysis (r=0.95). Conclusions:,The superiority of Ac.f in assessing bone turnover, in comparison to BFR/BS, is conceptual rather than practical. The highest values for FP in osteomalacia and for QP in adynamic bone allow a clearer characterization of these low turnover conditions. [source]

Bone material quality in transiliac bone biopsies of postmenopausal osteoporotic women after 3 years of strontium ranelate treatment

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2010
Paul Roschger
Abstract Strontium ranelate (SrR) is a relatively new treatment for osteoporosis. In this study we investigated its potential impact on human bone material quality in transiliac bone biopsies from postmenopausal osteoporotic women treated 3 years with calcium and vitamin D plus either 2,g SrR per day or placebo. Bone mineralization density distribution (BMDD), strontium (Sr) concentration, collagen cross-link ratio, and indentation modulus were analyzed by quantitative backscattered electron imaging, electron-induced X-ray fluorescence analysis, synchrotron radiation induced micro X-ray fluorescence elemental mapping, Fourier transform infrared imaging, and nanoindentation, respectively. The BMDD of SrR-treated patients was shifted to higher atomic numbers (Zmean +1.5%, p,<,.05 versus placebo). We observed Sr being preferentially incorporated in bone packets formed during SrR treatment up to 6% atom fraction [Sr/(Sr,+,Ca)] depending on the SrR serum levels of the individuals (correlation r,=,0.84, p,=,.018). Collagen cross-link ratio was preserved in SR-treated bone. The indentation modulus was significantly decreased in younger versus older bone packets for both placebo- (,20.5%, p,<,.0001) and SrR-treated individuals (,24.3%, p,<,.001), whereas no differences were found between the treatment groups. In conclusion, our findings indicate that after SrR treatment, Sr is heterogeneously distributed in bone and preferentially present in bone packets formed during treatment. The effect of SrR on BMDD seems to be due mainly to the uptake of Sr and not to changes in bone calcium content. Taken together, these data provide evidence that the investigated bone quality determinants at tissue level were preserved in postmenopausal osteoporotic women after 3-year treatment with 2,g SrR per day plus calcium and vitamin D. © 2010 American Society for Bone and Mineral Research [source]

Bone mineralization defects and vitamin D deficiency: Histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675,patients

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2010
Matthias Priemel
Abstract Parathyroid hormone (PTH) is only one measurable index of skeletal health, and we reasoned that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25-Hydroxyvitamin D [25(OH)D] level. A cohort from the northern European population with its known high prevalence of vitamin D deficiency therefore would be ideal to answer the latter question. We examined 675 iliac crest biopsies from male and female individuals, excluding all patients who showed any signs of secondary bone diseases at autopsy. Structural histomorphometric parameters, including osteoid indices, were quantified using the Osteomeasure System according to ASBMR standards, and serum 25(OH)D levels were measured for all patients. Statistical analysis was performed by Student's t test. The histologic results demonstrate an unexpected high prevalence of mineralization defects, that is, a pathologic increase in osteoid. Indeed, 36.15% of the analyzed patients presented with an osteoid surface per bone surface (OS/BS) of more than 20%. Based on the most conservative threshold that defines osteomalacia at the histomorphometric level with a pathologic increase in osteoid volume per bone volume (OV/BV) greater than 2% manifest mineralization defects were present in 25.63% of the patients. The latter were found independent of bone volume per trabecular volume (BV/TV) throughout all ages and affected both sexes equally. While we could not establish a minimum 25(OH)D level that was inevitably associated with mineralization defects, we did not find pathologic accumulation of osteoid in any patient with circulating 25(OH)D above 75,nmol/L. Our data demonstrate that pathologic mineralization defects of bone occur in patients with a serum 25(OH)D below 75,nmol/L and strongly argue that in conjunction with a sufficient calcium intake, the dose of vitamin D supplementation should ensure that circulating levels of 25(OH)D reach this minimum threshold (75,nmol/L or 30,ng/mL) to maintain skeletal health. © 2010 American Society for Bone and Mineral Research [source]

Perspective: Quantifying Osteoblast and Osteocyte Apoptosis: Challenges and Rewards,,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2007
Robert L Jilka
Abstract Since the initial demonstration of the phenomenon in murine and human bone sections ,10 yr ago, appreciation of the biologic significance of osteoblast apoptosis has contributed greatly not only to understanding the regulation of osteoblast number during physiologic bone remodeling, but also the pathogenesis of metabolic bone diseases and the pharmacology of some of the drugs used for their treatment. It is now appreciated that all major regulators of bone metabolism including bone morphogenetic proteins (BMPs), Wnts, other growth factors and cytokines, integrins, estrogens, androgens, glucocorticoids, PTH and PTH-related protein (PTHrP), immobilization, and the oxidative stress associated with aging contribute to the regulation of osteoblast and osteocyte life span by modulating apoptosis. Moreover, osteocyte apoptosis has emerged as an important regulator of remodeling on the bone surface and a critical determinant of bone strength, independently of bone mass. The detection of apoptotic osteoblasts in bone sections remains challenging because apoptosis represents only a tiny fraction of the life span of osteoblasts, not unlike a 6-mo -long terminal illness in the life of a 75-yr -old human. Importantly, the phenomenon is 50 times less common in human bone biopsies because human osteoblasts live longer and are fewer in number. Be that as it may, well-controlled assays of apoptosis can yield accurate and reproducible estimates of the prevalence of the event, particularly in rodents where there is an abundance of osteoblasts for inspection. In this perspective, we focus on the biological significance of the phenomenon for understanding basic bone biology and the pathogenesis and treatment of metabolic bone diseases and discuss limitations of existing techniques for quantifying osteoblast apoptosis in human biopsies and their methodologic pitfalls. [source]

Effects Of a One-Month Treatment With PTH(1,34) on Bone Formation on Cancellous, Endocortical, and Periosteal Surfaces of the Human Ilium,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2007
Robert Lindsay MD
Abstract Using bone histomorphometry, we found that a 1-month treatment with PTH(1,34) [hPTH(1,34)] stimulated new bone formation on cancellous, endocortical, and periosteal bone surfaces. Enhanced bone formation was associated with an increase in osteoblast apoptosis. Introduction: The precise mechanisms by which hPTH(1,34) increases bone mass and improves bone structure are unclear. Using bone histomorphometry, we studied the early effects of treating postmenopausal women with osteoporosis with hPTH(1,34). Materials and Methods: Tetracycline-labeled iliac crest bone biopsies were obtained from 27 postmenopausal women with osteoporosis who were treated for 1 month with hPTH(1,34), 50 ,g daily subcutaneously. The results were compared with tetracycline-labeled biopsies from a representative control group of 13 postmenopausal women with osteoporosis. Results: The bone formation rate on the cancellous and endocortical surfaces was higher in hPTH(1,34),treated women than in control women by factors of 4.5 and 5.0, respectively. We also showed a 4-fold increase in bone formation rate on the periosteal surface, suggesting that hPTH(1,34) has the potential to increase bone diameter in humans. On the cancellous and endocortical surfaces, the increased bone formation rate was primarily caused by stimulation of formation in ongoing remodeling units, with a modest amount of increased formation on previously quiescent surfaces. hPTH(1,34),stimulated bone formation was associated with an increase in osteoblast apoptosis, which may reflect enhanced turnover of the osteoblast population and may contribute to the anabolic action of hPTH(1,34). Conclusions: These findings provide new insight into the cellular basis by which hPTH(1,34) improves cancellous and cortical bone architecture and geometry in patients with osteoporosis. [source]

Comparison Insight Bone Measurements by Histomorphometry and ,CT,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005
Daniel Chappard MD
Abstract Morphometric analysis of 70 bone biopsies was done in parallel by ,CT and histomorphometry. ,CT provided higher results for trabecular thickness and separation because of the 3D shape of these anatomical objects. Introduction: Bone histomorphometry is used to explore the various metabolic bone diseases. The technique is done on microscopic 2D sections, and several methods have been proposed to extrapolate 2D measurements to the 3D dimension. X-ray ,CT is a recently developed imaging tool to appreciate 3D architecture. Recently the use of 2D histomorphometric measurements have been shown to provide discordant results compared with 3D values obtained directly. Material and Methods: Seventy human bone biopsies were removed from patients presenting with metabolic bone diseases. Complete bone biopsies were examined by ,CT. Bone volume (BV/TV), Tb.Th, and Tb.Sp were measured on the 3D models. Tb.Th and Tb.Sp were measured by a method based on the sphere algorithm. In addition, six images were resliced and transferred to an image analyzer: bone volume and trabecular characteristics were measured after thresholding of the images. Bone cores were embedded undecalcified; histological sections were prepared and measured by routine histomorphometric methods providing another set of values for bone volume and trabecular characteristics. Comparison between the different methods was done by using regression analysis, Bland-Altman, Passing-Bablock, and Mountain plots. Results: Correlations between all parameters were highly significant, but ,CT overestimated bone volume. The osteoid volume had no influence in this series. Overestimation may have been caused by a double threshold used in ,CT, giving trabecular boundaries less well defined than on histological sections. Correlations between Tb.Th and Tb.Sp values obtained by 3D or 2D measurements were lower, and 3D analysis always overestimated thickness by ,50%. These increases could be attributed to the 3D shape of the object because the number of nodes and the size of the marrow cavities were correlated with 3D values. Conclusion: In clinical practice, ,CT seems to be an interesting method providing reliable morphometric results in less time than conventional histomorphometry. The correlation coefficient is not sufficient to study the agreement between techniques in histomorphometry. The architectural descriptors are influenced by the algorithms used in 3D. [source]

Differential Effects of Teriparatide and Alendronate on Bone Remodeling in Postmenopausal Women Assessed by Histomorphometric Parameters,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005
Monique Arlot MD
Abstract An 18-month randomized double-blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once-daily teriparatide 20 ,g with alendronate 10 mg on bone histomorphometry. Biopsies were obtained from 42 patients. Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment. Introduction: Alendronate and teriparatide increased BMD, assessed by DXA, by different mechanisms of action, supported by changes in biochemical markers of bone turnover. The purpose of this cross-sectional study was to explore the differential effects of these two osteoporosis treatments at the bone tissue level by examining bone histomorphometric parameters of bone turnover after either 6 or 18 months of treatment. Materials and Methods: Patients were a cohort from a randomized parallel double-blind study conducted to compare the effects of once-daily teriparatide 20 ,g and alendronate 10 mg in postmenopausal women with osteoporosis. Transiliac crest bone biopsies were obtained after tetracycline double labeling from 42 patients treated for 6 months (n = 23) or 18 months (n = 14); 5 additional patients were biopsied from contralateral sides at 6 and 18 months. Biopsy specimens adequate for quantitative analysis were analyzed by 2D histomorphometry from 17 patients at 6 months (teriparatide, n = 8; alendronate, n = 9) and 15 patients at 18 months (teriparatide, n = 8; alendronate, n = 7). Data were analyzed by two-sample tests. Results: Histomorphometric indices of bone formation were significantly and markedly greater in the teriparatide group than in the alendronate group at 6 and 18 months, whereas indices of bone resorption were only significantly greater in the teriparatide group than in the alendronate group at 6 months. Bone formation and activation frequency were significantly lower at 18 months compared with 6 months in the teriparatide group, returning to levels comparable with untreated postmenopausal women. In the teriparatide group, the peak in histomorphometric bone formation indices coincided with peak levels for N-terminal propeptide of type I collagen, a biochemical marker of bone formation. The degree of mineralization was lower at 18 months than at 6 months with treatment in both groups but was not different between groups. Conclusions: These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide. [source]

SAPHO syndrome masquerading as metastatic bone disease

JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 5 2005
NH Theumann
Summary A 46-year-old woman who had had a right mastectomy for breast carcinoma a month before underwent bone scintigraphy. The examination revealed multiple pelvic, vertebral and sternal hot spots suggestive of bone metastases. Standard X-rays and CT confirmed the presence of bony lesions but they were not typical of bone metastases. As the radiographic appearance was reminiscent of SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis), bone biopsies were performed. Histology showed fibrosis and hyperostosis but no tumour cells. On further questioning, the patient revealed she had had palmar pustulosis and sacroiliitis some years earlier. The purpose of the case report is to show that accurate diagnosis of SAPHO syndrome requires careful clinical and radiological examinations. [source]

Trabecular bone volume fraction mapping by low-resolution MRI

MAGNETIC RESONANCE IN MEDICINE, Issue 1 2001
M.A. Fernández-Seara
Abstract Trabecular bone volume fraction (TBVF) is highly associated with the mechanical competence of trabecular bone. TBVF is ordinarily measured by histomorphometry from bone biopsies or, noninvasively, by means of high-resolution microcomputed tomography and, more recently, by micro-MRI. The latter methods require spatial resolution sufficient to resolve trabeculae, along with segmentation techniques that allow unambiguous assignment of the signal to bone or bone marrow. In this article it is shown that TBVF can be measured under low-resolution conditions by exploiting the attenuation of the MR signal resulting from fractional occupancy of the imaging voxel by bone and bone marrow, provided that a reference signal is available from a marrow volume devoid of trabeculation. The method requires accurate measurement of apparent proton density, which entails correction for various sources of error. Key among these are the spatial nonuniformity in the RF field amplitude and effects of the slice profile, which are determined by B1 field mapping and numerical integration of the Bloch equations, respectively. By contrast, errors from variations in bone marrow composition (hematopoietic vs. fatty) between trabecular and reference site are predicted to be small and usually negligible. The method was evaluated in phantoms and in vivo in the distal radius and found to be accurate to 1% in marrow volume fraction. Finally, in a group of 12 patients of varying skeletal status, TBVF in the calcaneus was found to strongly correlate with integral bone mineral density of the lumbar vertebrae (r2 = 0.83, p < 0.0001). The method may fail in large imaging objects such as the human trunk at high magnetic field where standing wave and RF penetration effects cause intensity variations that cannot be corrected. Magn Reson Med 46:103,113, 2001. © 2001 Wiley-Liss, Inc. [source]

Novel and recurrent germline LEMD3 mutations causing Buschke,Ollendorff syndrome and osteopoikilosis but not isolated melorheostosis

CLINICAL GENETICS, Issue 6 2009
Y Zhang
Mutations in the LEMD3 gene were recently incriminated in Buschke,Ollendorff syndrome (BOS) and osteopoikilosis, with or without melorheostosis. The relationship of this gene with isolated sporadic melorheostosis is less clear. We investigated LEMD3 in a two-generation BOS family showing an extremely variable expression of the disease, in a sporadic patient with skin features of BOS, and in an additional subject with isolated melorheostosis. We identified two different mutations, both resulting in a premature stop codon, in the two cases of BOS. The mutation (c.2564G>A) reported in the familial case is novel, while that observed in the sporadic case (c.1963C>T) has been previously reported in an American woman with osteopoikilosis and melorheostosis who had a family history of isolated osteopoikilosis. The search for mutations in DNA extracted from the peripheral blood, as well as skin and bone biopsies of the patient with melorheostosis failed to identify any pathogenic change. Our results further expand the LEMD3 mutation repertoire, corroborate the extreme interfamilial and intrafamilial clinical variability of LEMD3 mutations, and underline the lack of a clear phenotype,genotype correlation in BOS. The present study supports the general conclusion that LEMD3 mutations do not contribute to isolated sporadic melorheostosis. The genetic or epigenetic influences that are responsible for the development of melorheostosis require further investigation. [source]

Back-scattered electron imaging and elemental microanalysis of retrieved bone tissue following maxillary sinus floor augmentation with calcium sulphate

CLINICAL ORAL IMPLANTS RESEARCH, Issue 8 2008
Nicola Slater
Abstract Objectives: To investigate the presence and composition of residual bone graft substitute material in bone biopsies from the maxillary sinus of human subjects, following augmentation with calcium sulphate (CaS). Material and methods: Bone cores were harvested from the maxillary sinus of patients who had undergone a sinus lift procedure using CaS G170 granules 4 months after the initial surgery. Samples from seven patients, which contained residual biomaterial particles, were examined by field emission scanning electron microscopy and energy dispersive X-ray spectroscopy was used to determine the composition of the remaining bone graft substitute material. Results: Residual graft material occurred in isolated areas surrounded by bone and consisted of individual particles up to 1 mm in length and smaller spherical granules. On the basis of 187 separate point analyses, the residual material was divided into three categories (A, B and C) consisting of: A, mainly CaS (S/P atomic% ratio ,2.41); B, a heterogeneous mixture of CaS and calcium phosphate (S/P=0.11,2.4) and C, mainly calcium phosphate (S/P,0.11; C), which had a mean Ca : P ratio of 1.63±0.2, consistent with Ca-deficient hydroxyapatite. Linescans and elemental maps showed that type C material was present in areas which appeared dense and surrounded, or were adjacent to, more granular CaS-containing material, and also occurred as spherical particles. The latter could be disintegrating calcium phosphate in the final stages of the resorption process. Conclusions: CaS resorption in the human maxillary sinus is accompanied by CaP precipitation which may contribute to its biocompatibility and rapid replacement by bone. [source]

Does platelet-rich plasma promote remodeling of autologous bone grafts used for augmentation of the maxillary sinus floor?

CLINICAL ORAL IMPLANTS RESEARCH, Issue 3 2005
Gerry M. Raghoebar
Abstract: The aim of this study was to evaluate the effect of platelet-rich plasma (PRP) on remodeling of autologous bone grafts used for augmentation of the floor of the maxillary sinus. In five edentulous patients suffering from insufficient retention of their upper denture related to a severely resorbed maxilla, the floor of both maxillary sinus was augmented with an autologous bone graft from the iliac crest. Randomly, PRP was added to the bone graft used to augment the floor of the left or right sinus (split-mouth design). Three months after the reconstruction, bone biopsies were taken with a trephine from the planned implant sites (N=30). Subsequently, three implants were placed in the left and right posterior maxilla. Microradiograms were made of all biopsies (N=30), whereafter the biopsies were processed for light microscopic examination. In addition, clinical parameters were scored. Wound healing was uneventful, clinically no difference was observed between the side treated with PRP or not. Also microradiographical and histomorphological examination of the biopsies revealed no statistical difference between the PRP- and non-PRP side. One implant placed in the PRP side of the graft was lost during the healing phase. Implant-retained overdentures were fabricated 6 months after implantation. All patients functioned well (follow-up 20.2±4.3 months). In this study, no beneficial effect of PRP on wound healing and bone remodeling was observed. It is posed that PRP has no additional value in promoting healing of grafted non-critical size defects. Résumé Le but de cette étude a été d'évaluer l'effet du plasma riche en plaquettes sur le remodelage de greffons osseux autogènes utilisés pour l'épaississement du plancher sinusal. Chez cinq patients édentés souffrant d'une rétention insuffisante de leur prothèse supérieure en relation avec un maxillaire sévèrement résorbé, les planchers sinusaux des deux maxillaires ont étéépaissis avec un greffon d'os autogène provenant de la crête iliaque. Au hasard, du plasma riche en plaquettes (PRP) a été ajouté au greffon osseux utilisé pour épaissir le plancher du sinus gauche ou droit (modèle de bouche divisée). Trois mois après la reconstruction, des biopsies osseuses ont été obtenues avec un trépan des sites planifiés pour placer des implants (N=30). Ensuite, trois implants ont été placés dans les parties maxillaires gauches et droites. Des microradiogrammes des 30 biopsies ont été effectuées, ces dernières ont ensuite été utilisées pour l'examen au microscope optique. De plus, des paramètres cliniques ont été enregistrés. La guérison a été parfaite, cliniquement aucune différence n'a été observée entre les sites traités avec PRP ou sans. L'examen microradiographique et histomorphologique des biopsies n'a révélé aucune différence significative entre les sites PRP et non-PRP. Un implant placé dans le site PRP du greffon a été perdu durant la phase de guérison. Des prothèses retenues sur implants ont été fabriquées six mois après l'insertion des implants. Tous les patients ont une mise en fonction excellente après un suivi de 20±4,3 mois. Dans cette étude, aucun effet bénéfique additionnel du PRP sur la guérison et le remodelage osseux n'a été observé. Le PRP n'aurait aucune valeur supplémentaire à promouvoir la guérison dans ce type d'opération. Zusammenfassung Das Ziel dieser Studie war, den Einfluss von plättchenreichem Plasma auf die Remodellierung von autologen Knochentransplantaten, welche für die Augmentation des Sinusbodens vom Sinus maxillaris verwendet wurden, auszuwerten. Bei 5 zahnlosen Patienten, welche aufgrund einer stark resorbierten Maxilla über einen ungenügenden Halt der Oberkieferprothese klagten, wurde der Sinus maxillaris mit autologem Knochen vom Beckenkamm augmentiert. Zufällig wurde dem Knochen, der zur Augmentation des rechten oder linken Sinusbodens verwendet wurde, plättchenreiches Plasma (PRP) hinzugefügt (unterschiedlich behandelte Seiten). Drei Monate nach der Augmentation wurden mittels Hohlfräsen Biopsien an den geplanten Implantatlokalisationen entnommen (N=30). Danach wurden je drei Implantate in die rechte und linke posteriore Maxilla eingesetzt. Von allen Biopsien wurde Mikroröntgenbilder angefertigt (N=30), danach wurden die Biopsien für die lichtmikroskopische Untersuchung aufgearbeitet. Zusätzlich wurden klinische Parameter aufgenommen. Die Wundheilung war unauffällig. Klinisch konnten keine Unterschiede zwischen den mit und ohne PRP behandelten Seiten beobachtet werden. Ebenso ergab die mikroradiographische und histomorphometrische Untersuchung der Biopsien keine statistisch signifikanten zwischen der PRP und nicht-PRP Seite. Ein Implantat, welches in eine PRP Seite eingesetzt worden war, ging während der Einheilphase verloren. Die implantatgetragenen Hybridprothesen wurden 6 Monate nach Implantation angefertigt. Alle Patienten funktionierten problemlos (Beobachtungszeit bis 20.2±4.3 Monate). In dieser Studie konnte kein positiver Einfluss des PRP auf die Wundheilung und die Knochenremodellierung beobachtet werden. Es wird vermutet, dass PRP keinen zusätzlichen Effekt bei der Förderung der Heilung von Transplantaten in Defekten mit nicht-kritischer Grösse hat. Resumen La intención de este estudio fue evaluar el efecto del plasma rico en plaquetas en el remodelado de injertos de hueso autólogo usado para aumento del suelo del seno maxilar. Se aumentó el suelo de ambos senos maxilares con injertos de hueso autólogo de la cresta iliaca en 5 pacientes edéntulos que padecían de insuficiente retención de su dentadura superior relacionada con un maxilar severamente reabsorbido. Aleatoriamente, se añadió plasma rico en plaquetas (PRP) al injerto óseo usado para aumentar el suelo del seno derecho o izquierdo (diseño de boca partida). Tres meses tras la reconstrucción, se tomaron biopsias de hueso con un trépano de los lugares de implantes planificados (N=30). Subsecuentemente se colocaron tres implantes en el maxilar posterior derecho e izquierdo. Se hicieron microrradiogramas de todas las biopsias (N=30), posteriormente las biopsias se procesaron para microscopía óptica. Además se tomaron parámetros clínicos. La cicatrización de la herida tuvo lugar sin incidentes. Clínicamente no se observó diferencia alguna entre el lado tratado con PRP o no. Tampoco el examen microrradiográfico e histomorfológico de las biopsias revelaron diferencias estadísticamente significativas entre los lados con o sin PRP. Un implante colocado en el lado del PRP se perdió durante la cicatrización. Las dentaduras implantorretenidas se fabricaron a los seis meses de la implantación. Todos los pacientes funcionaron bien (seguimiento de 20.2±4.3 meses). En este estudio no se observó ningún efecto beneficioso del PRP sobre la cicatrización y sobre el remodelado óseo. Se plantea que el PRP no tiene ningún valor adicional en promover la cicatrización de defectos no críticos injertados. [source]

Fate of monocortical bone blocks grafted in the human maxilla: a histological and histomorphometric study

CLINICAL ORAL IMPLANTS RESEARCH, Issue 6 2003
Ilara R. Zerbo
Abstract: Local bone defects in the anterior maxilla are commonly grafted with monocortical blocks of autologous bone in order to restore the defect site prior to the placement of dental implants. Increasing evidence suggests that osteocytes are involved in the control of bone remodelling and thus may be important for optimalisation of bone structure around implants, and thus for implant osseointegration. However, it is not well known whether osteocytes will survive when bone blocks are grafted into defects. We grafted 19 patients with monocortical bone blocks derived from the symphysis, to the defect site in the maxillary alveolar process. The bone grafts were left to heal for times varying from 2.5 to 7 months. During implant installation, bone biopsies were removed using a trephine burr, and processed for hard tissue histology. Bone histology and histomorphometry were then carried out in order to gain insight into the density, viability and remodelling of the graft. Clinically, all the bone grafts were successful, with no implant failures, and little resorption was seen. Histologically, bone volume expressed as percentage of tissue volume at the implant site varied from 27% to 57% with an overall average of 41%. Bone fields with empty osteocyte lacunae were observed and measured. The amount of this so-called nonvital bone (NVB) varied between 1% and 34% of the total tissue volume. The amount of NVB decreased significantly with the time of healing. The data suggest that the majority of the osteocytes of the monocortical bone do not survive grafting. The results indicate that the NVB is progressively remodelled into new vital bone 7 months after grafting. Résumé Les lésions osseuses locales dans le maxillaire antérieur sont souvent greffées avec des blocs monocorticaux d'os autogène afin de restaurer le site avant le placement d'implants. Il semble de plus en plus évident que les ostéocytes sont induits dans le contrôle du remodelage osseux et pourraient donc être importants pour optimiser la structure osseuse autour des implants et donc l'ostéoïntégration implantaire. Cependant le taux de survie des ostéocytes lorsque les blocs osseux sont greffés dans les lésions n'est pas suffisament connu. Dix-neuf patients ont été greffés avec des blocs osseux monocorticaux provenant de la symphyse dans le site de la lésion au niveau des alvéoles maxillaires. Les greffons osseux sont restés in situ durant des périodes de 2,5 à 7 mois. Pendant l'insertion des implants des biopsies osseuses ont été prélevées avec un trépan et analysées par histologie. L'histologie osseuse et l'histomorphométrie ont été effectuées afin d'analyser la densité, la viabilité et le remodelage osseux. Cliniquement tous les greffons osseux ont été effectués avec succès sans aucun échec implantaire et peu de résorption. Histologiquement, le volume osseux exprimé en tant que pourcentage du volume tissulaire au site implantaire variait de 27 à 57 % avec une moyenne totale de 41 %. Les champs osseux avec une lacune d'ostéocytes vides ont été observés et mesurés. La quantité d'os non-vivant variait de 1 à 34 % du volume tissulaire total. La quantité d'os non-vivant diminuait significativement avec le temps de guérison. Ces données suggèrent que la majorité des ostéocytes de l'os monocortical ne survivent pas au greffage. Les résultats indiquent que l'os non-vivant est progressivement remodelé en nouvel os vivant en sept mois après le greffage. Zusammenfassung Das Schicksal von monokortikalen Knochenblöcken, welche in die menschliche Maxilla transplantiert werden: eine histologische und histomorphometrische Studie Lokale Knochendefekte in der anterioren Maxilla werden normalerweise mit monokortikalen Blöcken aus autologem Knochen aufgebaut, um den Defekt vor der Eingliederung von dentalen Implantaten aufzufüllen. Aufgrund zunehmender Evidenz wird vermutet, dass Osteozyten an der Kontrolle der Knochenremodellierung beteiligt und daher wichtig für die Optimierung der Knochenstrukturen um Implantate und für die Osseointegration der Implantate sind. Es ist jedoch nicht ausreichend bekannt, ob Osteozyten überleben, wenn Knochenblöcke in Defekte transplantiert werden. Bei 19 Patienten wurden monokortikale Knochenblöcke von der Symphyse in den Defektbereich des Alveolarfortsatzes im Oberkiefer transplantiert. Die Knochentransplantate heilten in einer Zeit zwischen 2.5 und 7 Monaten ein. Während der Implantation wurden mit einer Hohlfräse Knochenbiopsien entnommen und für die Hartgewebshistologie aufgearbeitet. Der Knochen wurde histologisch und histomorphometrisch untersucht, um Einsicht in die Dichte, Vitalität und Remodellierung des Transplantats zu erlangen. Klinisch waren alle Knochentransplantate erfolgreich eingeheilt. Es konnten keine Implantatmisserfolge gesehen werden und es traten nur geringe Resorptionen auf. Histologisch variierte das Knochenvolumen, ausgedrückt als Prozentsatz Gewebevolumen an der Implantatstelle, von 27% bis 57% mit einem Durchschnitt von 41%. Knochenfelder mit leeren Osteozytenlakunen konnten beobachtet und ausgemessen werden. Die Menge dieses sogenannten nicht-vitalen Knochens variierte zwischen 1% und 34% des totalen Gewebevolumens. Die Menge des nicht-vitalen Knochens nahm signifikant mit der Länge der Einheilzeit ab. Die Daten lassen vermuten, dass die Mehrzahl der Osteozyten des monokortikalen Knochens die Transplantation nicht überleben. Die Resultate zeigen, dass der nicht-vitale Knochen innert 7 Monaten nach der Transplantation progressiv in neuen vitalen Knochen umgebaut wird. Resumen Los defectos óseos locales en el maxilar anterior se injertan comúnmente con bloques monocorticales de hueso autólogo en orden a restaurar el lugar del defecto antes de la colocación de implantes dentales. Una creciente evidencia sugiere que los osteocitos están involucrados en el control del remodelado óseo y de este modo ser importantes para la optimalización de la estructura ósea alrededor de los implantes y así para la osteointegración de los implantes. Sin embargo, no se conoce bien si los osteocitos sobrevivirán cuando los bloques óseos sean injertados en los defectos. Hemos injertado a 19 pacientes con bloques de hueso monocortical derivados de la sínfisis al lugar del defecto en el proceso alveolar maxilar. Los injertos óseos se dejaron cicatrizar por un periodo de tiempo que varió entre 2.5 a 7 meses. Durante la implantación se tomaron biopsias óseas usando una fresa de trépano y se procesaron para histología de tejidos duros. Se llevaron a cabo entonces histología ósea e histomorfometría en orden a hacerse una idea acerca de la densidad, viabilidad y remodelado del injerto. Clínicamente, todos los injertos óseos tuvieron éxito sin fracasos de implantes y se observó poca reabsorción ósea. Histológicamente, el volumen óseo expresado como porcentaje de volumen tisular en el lugar del implante varió del 27% al 57% con una media general del 41%. Se observaron y midieron campos óseos con lagunas óseas vacías. La cantidad de hueso no vital disminuyó significativamente durante el tiempo de cicatrización. [source]

High concentrations of bioactive glass material (BioGran®) vs. autogenous bone for sinus floor elevation

CLINICAL ORAL IMPLANTS RESEARCH, Issue 4 2002
Histomorphometrical observations on three split mouth clinical cases
Abstract: In this study, high concentrations of bioactive glass (BG) particles were compared with autogenous bone in their capacity to augment maxillary bone when grafted in the human sinus floor using a split mouth design. Three female patients with severe maxillary atrophy underwent bilateral sinus floor elevation and bone grafting using 80,100% BG particles (300,355 ,m in size) mixed with 20% to 0% iliac crest bone particles at one (experimental) side, and 100% iliac crest derived bone particles at the other (control) side. A total of 22 bone biopsies was taken at the time of fixture installation; that is, at 4, 6 and 15 months after grafting, and processed for histology and histomorphometry. At the control (autogenous bone) sides, trabecular bone amounted to 39% of the biopsy volume in the graft (site) at 4 months, almost 41% at 6 months, and 42% at 15 months. This bone contained viable osteocytes and was mostly of mature, lamellar type. At the experimental (BG particles) sides, the graft consisted of 27% of mostly woven (and some lamellar) bone at 4 months, 36% (woven and lamellar) bone at 6 months, and 39% (mainly lamellar) bone at 15 months. The grafted BG particles started to excavate at 4 months and their centers gradually filled with bone tissue. As a consequence, the volume of BG particles in the biopsy decreased from 29% at 4 months to 15% at 6 months and 8% at 15 months. The BG particles appeared to resorb within 1,2 years by dissolution rather than by osteoclastic activity. Parameters for bone turnover (% osteoid surface, % resorption surface) indicated that bone remodeling was very active at both experimental and control sides, during more than 6 months. These results suggest that mixtures of mainly (80,90%) BG particles and some (10,20%) autogenous bone are effective for bone regeneration in the augmented sinus offer 6 months healing time, while about 12 months healing time is needed for 100% BG particles. [source]

Diabetic foot osteomyelitis: a progress report on diagnosis and a systematic review of treatment,

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2008
A. R. Berendt
Abstract The International Working Group on the Diabetic Foot appointed an expert panel to provide evidence-based guidance on the management of osteomyelitis in the diabetic foot. Initially, the panel formulated a consensus scheme for the diagnosis of diabetic foot osteomyelitis (DFO) for research purposes, and undertook a systematic review of the evidence relating to treatment. The consensus diagnostic scheme was based on expert opinion; the systematic review was based on a search for reports of the effectiveness of treatment for DFO published prior to December 2006. The panel reached consensus on a proposed scheme that assesses the probability of DFO, based on clinical findings and the results of imaging and laboratory investigations. The literature review identified 1168 papers, 19 of which fulfilled criteria for detailed data extraction. No significant differences in outcome were associated with any particular treatment strategy. There was no evidence that surgical debridement of the infected bone is routinely necessary. Culture and sensitivity of isolates from bone biopsy may assist in selecting properly targeted antibiotic regimens, but empirical regimens should include agents active against staphylococci, administered either intravenously or orally (with a highly bioavailable agent). There are no data to support the superiority of any particular route of delivery of systemic antibiotics or to inform the optimal duration of antibiotic therapy. No available evidence supports the use of any adjunctive therapies, such as hyperbaric oxygen, granulocyte-colony stimulating factor or larvae. We have proposed a scheme for diagnosing DFO for research purposes. Data to inform treatment choices in DFO are limited, and further research is urgently needed. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Mutations in the Insulin-Like Factor 3 Receptor Are Associated With Osteoporosis,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008
Alberto 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]

A Novel Tetracycline Labeling Schedule for Longitudinal Evaluation of the Short-Term Effects of Anabolic Therapy With a Single Iliac Crest Bone Biopsy: Early Actions of Teriparatide,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2006
Robert Lindsay MD
Abstract We describe a quadruple tetracycline labeling method that allows longitudinal assessment of short-term changes in bone formation in a single biopsy. We show that 1 month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation. Introduction: Iliac crest biopsy, with histomorphometric evaluation, provides important information about cellular activity in bone. However, to obtain longitudinal information, repeat biopsies must be performed. In this study, we show the capability to obtain short-term longitudinal information on bone formation in a single biopsy using a novel, quadruple labeling technique. Materials and Methods: Two tetracycline labels were administered using a standard 3 days on, 12 days off, 3 days on format. Four weeks later, the tetracycline labeling was repeated using the same schedule but with a different tetracycline that can be distinguished from the first by its color under fluorescent light. Iliac crest biopsies were performed 1 week later and prepared undecalcified for histomorphometry. Indices of bone formation 1 month apart were measured and calculated using the two sets of labels. We used this method to investigate the early effects of teriparatide [hPTH(1-34)] treatment on bone formation. The results were compared with those from a group of control subjects who were quadruple-labeled, but did not receive hPTH(1-34). Results: Treatment with hPTH(1-34) dramatically stimulated bone formation on cancellous and endocortical surfaces. This was achieved by both an increase in the linear rate of matrix apposition and extension of the bone-forming surface. New bone was deposited on previously quiescent surfaces (i.e., modeling-based formation), but a proportion of this could occur by encroachment from adjacent resorption cavities. Conclusions: A single transiliac crest bone biopsy, after sequential administration of two sets of tetracycline labels is a useful approach to study the short-term effects of anabolic agents on human bone. One month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation. [source]

Cytokines, Osteoprotegerin, and RANKL In Vitro and Histomorphometric Indices of Bone Turnover in Patients With Different Bone Diseases,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2003
Heide Siggelkow
Abstract Cytokines are supposed to play an essential role in the regulation of the bone metabolic unit. However, information on cytokine production of primary human osteoblasts from patients with metabolic bone disease is scarce, and few attempts have been made to correlate such data to histomorphometric parameters of individual patients. We investigated 11 patients with metabolic bone disease referred to our outpatient department for bone biopsy and analyzed interleukin (IL)-1, IL-6, and TNF-, protein release and gene expression in primary osteoblast cultures. Compared with four controls, five patients showed normal cytokine protein release, whereas six patients showed much higher levels of interleukin-6 (26-fold) and TNF-, (84-fold). All three cytokines were strongly correlated concerning gene expression and/or protein levels (r = 0.72,0.96). Histomorphometric analysis of the bone samples showed that eroded surface (ES/BS) as a parameter of bone resorption was significantly associated with TNF-,. In addition, RANKL gene expression was positively associated with ES/BS and osteoclast surface (Oc.S/BS). Finally, the formation parameters osteoid volume and osteoid surface were negatively associated with TNF-,. In conclusion, in an in vitro-ex vivo model of bone cells obtained from a group of 11 patients with different forms of metabolic bone disease, cytokine release in conditioned medium was significantly associated with bone resorption and bone formation, as quantified by histomorphometry. TNF-, seemed to be the more important cytokine; its effect on bone resorption could be mediated by RANKL. [source]

Percutaneous coaxial trephine bone biopsy

JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 4 2007
DC Cameron
First page of article [source]

PTHrP-independent hypercalcemia with increased proinflammatory cytokines and bone resorption in two children with CD19-negative precursor B acute lymphoblastic leukemia

PEDIATRIC BLOOD & CANCER, Issue 7 2007
Hidetaka Niizuma MD
Abstract Hypercalcemia in childhood acute lymphoblastic leukemia (ALL) is rare and occasionally associated with parathyroid hormone-related protein (PTHrP). However, the pathogenesis of PTHrP-independent hypercalcemia remains unclear. We report two children with precursor B ALL who had marked hypercalcemia (15.8 and 16.6 mg/dl, respectively) and disseminated osteolysis. Serum tumor necrosis factor-, (TNF-,) and IL-6 were markedly elevated, whereas 1,25(OH)2 vitamin D3, intact PTH and PTHrP were decreased or undetected. Analysis of urinary deoxypyridinoline (DPY) or bone biopsy of the osteolytic lesion showed an increased bone resorption, and administration of bisphosphonate improved the hypercalcemia. Patients had ALL with immunophenotype positive for CD10, CD34, and HLA-DR but negative for CD19 and obtained remission with chemotherapy. These findings suggest that increased osteoclastic bone resorption via stimulation with TNF-, and IL-6 may be mechanism causing PTHrP-independent hypercalcemia in some patients with precursor B ALL lacking CD19 expression. Pediatr Blood Cancer 2007;49:990,993. © 2006 Wiley-Liss, Inc. [source]

Anatomical considerations of the deep peroneal nerve for biopsy of the proximal fibula in Thais

CLINICAL ANATOMY, Issue 2 2009
S. Chompoopong
Abstract The present research aims to study the anatomical relationship between the deep peroneal nerve and the neighboring structures in the proximal fibula of Thais, with special regard to define the boundaries of a "safe" area when performing a biopsy of the proximal fibula. The proximal parts of 118 legs of 59 formalin-embalmed adult cadavers (31 males, 28 females) were investigated. The distance from the apex of the fibular head to the point of origin of the deep peroneal nerve, the distance from the most lateral prominence of the fibular head to the anterior intermuscular septum, and the angle between the deep peroneal nerve and the fibula axis were measured. The results showed that the mean distances from the apex of the fibular head to the point of origin of the deep peroneal nerve was 28.4 ± 4.8 mm and from the most lateral prominence of the fibular head to the anterior intermuscular septum was 14.9 ± 2.0 mm. The mean angle between the deep peroneal nerve and the fibular axis was 28.1° ± 7.2°. In conclusion, these findings suggest that a "safe" area for bone biopsy in the proximal fibula of Thais is palpable anterior to the fibular head and downward laterally, not lower than 28 mm or 8% of the fibular length and from the most lateral prominence transverse medially not further than 14 mm. The inferior boundary of this area is an oblique line of the deep peroneal nerve about 28° from the fibular axis. Clin. Anat. 22:256,260, 2009. © 2008 Wiley-Liss, Inc. [source]