Skeletal development of mice lacking bone sialoprotein (BSP)--impairment of long bone growth and progressive establishment of high trabecular bone mass.

PubMed

Bouleftour, Wafa; Boudiffa, Maya; Wade-Gueye, Ndeye Marième; Bouët, Guénaëlle; Cardelli, Marco; Laroche, Norbert; Vanden-Bossche, Arnaud; Thomas, Mireille; Bonnelye, Edith; Aubin, Jane E; Vico, Laurence; Lafage-Proust, Marie Hélène; Malaval, Luc

2014-01-01

Adult Ibsp-knockout mice (BSP-/-) display shorter stature, lower bone turnover and higher trabecular bone mass than wild type, the latter resulting from impaired bone resorption. Unexpectedly, BSP knockout also affects reproductive behavior, as female mice do not construct a proper "nest" for their offsprings. Multiple crossing experiments nonetheless indicated that the shorter stature and lower weight of BSP-/- mice, since birth and throughout life, as well as their shorter femur and tibia bones are independent of the genotype of the mothers, and thus reflect genetic inheritance. In BSP-/- newborns, µCT analysis revealed a delay in membranous primary ossification, with wider cranial sutures, as well as thinner femoral cortical bone and lower tissue mineral density, reflected in lower expression of bone formation markers. However, trabecular bone volume and osteoclast parameters of long bones do not differ between genotypes. Three weeks after birth, osteoclast number and surface drop in the mutants, concomitant with trabecular bone accumulation. The growth plates present a thinner hypertrophic zone in newborns with lower whole bone expression of IGF-1 and higher IHH in 6 days old BSP-/- mice. At 3 weeks the proliferating zone is thinner and the hypertrophic zone thicker in BSP-/- than in BSP+/+ mice of either sex, maybe reflecting a combination of lower chondrocyte proliferation and impaired cartilage resorption. Six days old BSP-/- mice display lower osteoblast marker expression but higher MEPE and higher osteopontin(Opn)/Runx2 ratio. Serum Opn is higher in mutants at day 6 and in adults. Thus, lack of BSP alters long bone growth and membranous/cortical primary bone formation and mineralization. Endochondral development is however normal in mutant mice and the accumulation of trabecular bone observed in adults develops progressively in the weeks following birth. Compensatory high Opn may allow normal endochondral development in BSP-/- mice, while impairing primary mineralization.

Disturbances of bone growth and development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ledesma-Medina, J.; Newman, B.; Oh, K.S.

1988-03-01

''What is growth anyway. Can one talk about positive growth in childhood, neutral growth in maturity, and negative growth in old age. Our goal is to help promote normal positive growth in infants and children. To achieve this, we must be cognizant of the morphologic changes of both normal and abnormal bone formation as they are reflected in the radiographic image of the skeleton. The knowledge of the various causes and the pathophysiologic mechanisms of the disturbances of bone growth and development allows us to recognize the early radiographic manifestations. Endocrine and metabolic disorders affect the whole skeleton, but themore » early changes are best seen in the distal ends of the femurs, where growth rate is most rapid. In skeletal infections and in some vascular injuries two-or three-phase bone scintigraphy supercedes radiography early in the course of the disease. MRI has proved to be very helpful in the early detection of avascular bone necrosis, osteomyelitis, and tumor. Some benign bone tumors and many bone dysplasias have distinct and diagnostic radiographic findings that may preclude further studies. In constitutional diseases of bone, including chromosomal aberrations, skeletal surveys of the patient and all family members together with biochemical and cytogenetic studies are essential for both diagnosis and genetic counseling. Our role is to perform the least invasive and most informative diagnostic imaging modalities that corroborate the biochemical and histologic findings to establish the definitive diagnosis. Unrecognized, misdiagnosed, or improperly treated disturbance of bone growth can result in permanent deformity usually associated with disability. 116 references.« less

Anabolic action of parathyroid hormone (PTH) does not compromise bone matrix mineral composition or maturation.

PubMed

Vrahnas, Christina; Pearson, Thomas A; Brunt, Athena R; Forwood, Mark R; Bambery, Keith R; Tobin, Mark J; Martin, T John; Sims, Natalie A

2016-12-01

Intermittent administration of parathyroid hormone (PTH) is used to stimulate bone formation in patients with osteoporosis. A reduction in the degree of matrix mineralisation has been reported during treatment, which may reflect either production of undermineralised matrix or a greater proportion of new matrix within the bone samples assessed. To explore these alternatives, high resolution synchrotron-based Fourier Transform Infrared Microspectroscopy (sFTIRM) coupled with calcein labelling was used in a region of non-remodelling cortical bone to determine bone composition during anabolic PTH treatment compared with region-matched samples from controls. 8week old male C57BL/6 mice were treated with vehicle or 50μg/kg PTH, 5 times/week for 4weeks (n=7-9/group). Histomorphometry confirmed greater trabecular and periosteal bone formation and 3-point bending tests confirmed greater femoral strength in PTH-treated mice. Dual calcein labels were used to match bone regions by time-since-mineralisation (bone age) and composition was measured by sFTIRM in six 15μm 2 regions at increasing depth perpendicular to the most immature bone on the medial periosteal edge; this allowed in situ measurement of progressive changes in bone matrix during its maturation. The sFTIRM method was validated in vehicle-treated bones where the expected progressive increases in mineral:matrix ratio and collagen crosslink type ratio were detected with increasing bone maturity. We also observed a gradual increase in carbonate content that strongly correlated with an increase in longitudinal stretch of the collagen triple helix (amide I:amide II ratio). PTH treatment did not alter the progressive changes in any of these parameters from the periosteal edge through to the more mature bone. These data provide new information about how the bone matrix matures in situ and confirm that bone deposited during PTH treatment undergoes normal collagen maturation and normal mineral accrual. Copyright © 2016 Elsevier Inc. All rights reserved.

Intracranial meningioma causing partial amaurosis in a cat.

PubMed

Goulle, Frédéric; Meige, Frédéric; Durieux, Franck; Malet, Christophe; Toulza, Olivier; Isard, Pierre-François; Peiffer, Robert L; Dulaurent, Thomas

2011-09-01

To describe a case of intracranial meningioma causing visual impairment in a cat, successfully treated by surgery. An adult neutered male domestic cat was referred with a 10-month history of progressive visual impairment and altered behavior. Investigations included physical, ophthalmologic and neurological examinations as well as hematology, serum biochemistry and CT scan of the head. The menace response was absent in the left eye and decreased in the right eye. Electroretinograms were normal on both eyes, as was ophthalmic examination, ruling out an ocular cause and allowing a presumptive diagnosis of partial amaurosis due to a post-retinal lesion. CT scan demonstrated a large sessile extra axial mass along the right parietal bone and thickening of the adjacent bone. Cerebrospinal fluid was not collected because high intracranial pressure represented a risk for brain herniation. A right rostrotentorial craniectomy was performed to remove the tumor. Ten days after surgery, vision was improved, neurological examination was normal and normal behavior was restored. Ten months after surgery, ophthalmological examination showed no visual deficit and CT scan did not reveal any sign of recurrence. Advanced imaging techniques allow veterinarians to detect early cerebral diseases and to provide specific treatment when it is possible. In cases of feline amaurosis due to intracranial meningioma, the vital prognosis is good while the visual prognosis is more uncertain, but recovery of normal vision and normal behavior is possible as demonstrated in the present case. © 2011 American College of Veterinary Ophthalmologists.

Bone regeneration assessment by optical coherence tomography and MicroCT synchrotron radiation

NASA Astrophysics Data System (ADS)

Negrutiu, Meda L.; Sinescu, Cosmin; Canjau, Silvana; Manescu, Adrian; Topalá, Florin I.; Hoinoiu, Bogdan; Romînu, Mihai; Márcáuteanu, Corina; Duma, Virgil; Bradu, Adrian; Podoleanu, Adrian G.

2013-06-01

Bone grafting is a commonly performed surgical procedure to augment bone regeneration in a variety of orthopaedic and maxillofacial procedures, with autologous bone being considered as the "gold standard" bone-grafting material, as it combines all properties required in a bone-graft material: osteoinduction (bone morphogenetic proteins - BMPs - and other growth factors), osteogenesis (osteoprogenitor cells) and osteoconduction (scaffold). The problematic elements of bone regenerative materials are represented by their quality control methods, the adjustment of the initial bone regenerative material, the monitoring (noninvasive, if possible) during their osteoconduction and osteointegration period and biomedical evaluation of the new regenerated bone. One of the research directions was the interface investigation of the regenerative bone materials and their behavior at different time periods on the normal femoral rat bone. 12 rat femurs were used for this investigation. In each ones a 1 mm diameter hole were drilled and a bone grafting material was inserted in the artificial defect. The femurs were removed after one, three and six months. The defects repaired by bone grafting material were evaluated by optical coherence tomography working in Time Domain Mode at 1300 nm. Three dimensional reconstructions of the interfaces were generated. The validations of the results were evaluated by microCT. Synchrotron Radiation allows achieving high spatial resolution images to be generated with high signal-to-noise ratio. In addition, Synchrotron Radiation allows acquisition of volumes at different energies and volume subtraction to enhance contrast. Evaluation of the bone grafting material/bone interface with noninvasive methods such as optical coherence tomography could act as a valuable procedure that can be use in the future in the usual clinical techniques. The results were confirmed by microCT. Optical coherence tomography can be performed in vivo and can provide a qualitative and quantitative evaluation of the bone augmentation procedure.

Hardness of the subchondral bone of the patella in the normal state, in chondromalacia, and in osteoarthrosis.

PubMed

Björkström, S; Goldie, I F

1982-06-01

The hardness of bone is its property of withstanding the impact of a penetrating agent. It has been found that articular degenerative changes in, for example, the tibia (knee) are combined with a decrease in the hardness of the subchondral bone. In this investigation the hardness of subchondral bone in chondromalacia and osteoarthrosis of the patella has been analysed and compared with normal subchondral bone. Using an indentation method originally described by Brinell the hardness of the subchondral bone was evaluated in 7 normal patellae, in 20 with chondromalacia and in 33 with osteoarthrosis. A microscopic and microradiographic study of the subchondral bone was carried out simultaneously. Hardness was lowest in the normal material. The mean hardness value beneath the degenerated cartilage differed only slightly from that of the normal material, but the variation of values was increased. The hardness in bone in the chondromalacia area was lower than the hardness in bone covered by surrounding normal cartilage. The mean hardness value in bone beneath normal parts of cartilage in specimens with chondromalacia was higher than the mean hardness value of the normal material. In the microscopic and microradiographic examination it became evident that there was a relationship between trabecular structure and subchondral bone hardness; high values: coarse and solid structure; low values: slender and less regular structure.

Occurrence and pattern of long bone fractures in growing dogs with normal and osteopenic bones.

PubMed

Kumar, K; Mogha, I V; Aithal, H P; Kinjavdekar, P; Singh, G R; Pawde, A M; Kushwaha, R B

2007-11-01

A retrospective study was undertaken to record the occurrence and pattern of long bone fractures, and the efficacy of Intramedullary (IM) Steinmann pin fixing in growing dogs. All the records of growing dogs during a 10-year-period were screened to record the cause of trauma, the age and sex of the animal, the bone involved, the type and location of the fracture, the status of fixation, alignment, maintenance of fixation and fracture healing. The results were analysed and comparisons were made between growing dogs with normal and osteopenic bones. Among the 310 cases of fractures recorded, the bones were osteopenic in 91 cases (29%). Minor trauma was the principal cause of fracture in dogs with osteopenia (25%), and indigenous breeds were most commonly affected (38%). Fractures in dogs with osteopenic bones were most commonly recorded in the age group of 2-4 months (53%), whereas fractures in normal dogs were almost equally distributed between 2 and 8 months of age. Male dogs were affected significantly more often in both groups. In osteopenic bones, most fractures were recorded in the femur (56%), and they were distributed equally along the length of the bone. Whereas in normal bones, fractures were almost equally distributed in radius/ulna, femur and tibia, and were more often recorded at the middle and distal third of long bones. Oblique fractures were most common in both groups; however, comminuted fractures were more frequent in normal bones, whereas incomplete fractures were more common in osteopenic bones. Ninety-nine fracture cases treated with IM pinning (66 normal, 33 osteopenic) were evaluated for the status of fracture reduction and healing. In a majority of the cases (61%) with osteopenic bones, the diameter of the pin was relatively smaller than the diameter of the medullary cavity (<70-75%), whereas in 68% of the cases in normal bones the pin diameter was optimum. The status of fracture fixing was satisfactory to good in significantly more osteonormal (59%) than osteopenic dogs (42%). Fracture healing, however, was satisfactory in significantly more cases with osteopenic than normal bones. The appearance of callus was relatively early and the amount of bridging callus was relatively large in greater number of osteopenic bone fractures. Mal-union and non-union were recorded more often in osteopenic cases than in normal cases. However, the incidence of bone shortening and osteomyelitis was significantly higher in normal bones than in osteopenic bones.

Does osteoporosis reduce the primary tilting stability of cementless acetabular cups?

PubMed

von Schulze Pellengahr, Christoph; von Engelhardt, Lars V; Wegener, Bernd; Müller, Peter E; Fottner, Andreas; Weber, Patrick; Ackermann, Ole; Lahner, Matthias; Teske, Wolfram

2015-04-21

Cementless hip cups need sufficient primary tilting stability to achieve osseointegration. The aim of the study was to assess differences of the primary implant stability in osteoporotic bone and in bone with normal bone density. To assess the influence of different cup designs, two types of threaded and two types of press-fit cups were tested. The maximum tilting moment for two different cementless threaded cups and two different cementless press-fit cups was determined in macerated human hip acetabuli with reduced (n=20) and normal bone density (n=20), determined using Q-CT. The tilting moments for each cup were determined five times in the group with reduced bone density and five times in the group with normal bone density, and the respective average values were calculated. The mean maximum extrusion force of the threaded cup Zintra was 5670.5 N (max. tilting moment 141.8 Nm) in bone with normal density and.5748.3 N (max. tilting moment 143.7 Nm) in osteoporotic bone. For the Hofer Imhof (HI) threaded cup it was 7681.5 N (192.0 Nm) in bone with normal density and 6828.9 N (max. tilting moment 170.7 Nm) in the group with osteoporotic bone. The mean maximum extrusion force of the macro-textured press-fit cup Metallsockel CL was 3824.6 N (max. tilting moment 95.6 Nm) in bone with normal and 2246.2 N (max. tilting moment 56.2 Nm) in osteoporotic bone. For the Monoblock it was 1303.8 N (max. tilting moment 32.6 Nm) in normal and 1317 N (max. tilting moment 32.9 Nm) in osteoporotic bone. There was no significance. A reduction of the maximum tilting moment in osteoporotic bone of the ESKA press-fit cup Metallsockel CL was noticed. Results on macerated bone specimens showed no statistically significant reduction of the maximum tilting moment in specimens with osteoporotic bone density compared to normal bone, neither for threaded nor for the press-fit cups. With the limitation that the results were obtained using macerated bone, we could not detect any restrictions for the clinical indication of the examined cementless cups in osteoporotic bone.

Differences in Bone Quality between High versus Low Turnover Renal Osteodystrophy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Porter, Daniel S.; Pienkowski, David; Faugere, Marie-Claude

2012-01-01

Abnormal bone turnover is common in chronic kidney disease (CKD), but its effects on bone quality remain unclear. This study sought to quantify the relationship between abnormal bone turnover and bone quality. Iliac crest bone biopsies were obtained from CKD-5 patients on dialysis with low (n=18) or high (n=17) turnover, and from volunteers (n=12) with normal turnover and normal kidney function. Histomorphometric methods were used to quantify the microstructural parameters; Fourier transform infrared spectroscopy and nanoindentation were used to quantify the material and mechanical properties in bone. Reduced mineral-to-matrix ratio, mineral crystal size, stiffness and hardness were observed in bonemore » with high turnover compared to bone with normal or low turnover. Decreased cancellous bone volume and trabecular thickness were seen in bone with low turnover compared to bone with normal or high turnover. Bone quality, as defined by its microstructural, material, and mechanical properties, is related to bone turnover. These data suggest that turnover related alterations in bone quality may contribute to the known diminished mechanical competence of bone in CKD patients, albeit from different mechanisms for bone with high (material abnormality) vs. low (microstructural alteration) turnover. The present findings suggest that improved treatments for renal osteodystrophy should seek to avoid low or high bone turnover and aim for turnover rates as close to normal as possible.« less

Bone growth and bone development in the presence of implants or after induced leg-lengthening studied using the Oxford Scanning Proton Microprobe

NASA Astrophysics Data System (ADS)

Pålsgård, Eva; Johansson, Carina; Li, Gang; Grime, Geoff W.; Triffitt, J. T.

1997-07-01

To respond to varying environmental demands the bone tissue in the body is under continual reconstruction throughout life. It is known that metallic elements are important for maintaining normal bone structure, but their roles are not well understood. More information about the effects of metal excess or deficiency is needed to help in the development of metallic bone implants and to improve the treatment of bone fractures and defects. The Oxford Scanning Proton Microprobe (SPM) is being applied in two studies involving metal ions in bone: (1) bone regrowth and bonding to titanium bone implants may be influenced by diffusion of Ti ions into the bone. We are using microPIXE to determine the metal ion content of bone developing in contact with implants of pure Nb, Ti and Ti alloys. (2) Bone lengthening as a surgical procedure is induced by fracturing the bone and allowing it to heal with a small gap between the fractured ends created by the use of external fixators. The gap can be slowly increased during the healing process to stimulate the production of new bone. The enzymes and other constituents of the developing bone need certain metals for their function. Using experimental animals we have studied the concentrations of the metals and whether a deficiency of trace metals limits the optimum rate of bone lengthening.

How B cells influence bone biology in health and disease.

PubMed

Horowitz, Mark C; Fretz, Jackie A; Lorenzo, Joseph A

2010-09-01

It is now well established that important regulatory interactions occur between the cells in the hematopoietic, immune and skeletal systems (osteoimmunology). B lymphocytes (B cells) are responsible for the generation and production of antibodies or immunoglobulins in the body. Together with T cells these lymphocytes comprise the adaptive immune system, which allows an individual to develop specific responses to an infection and retain memory of that infection, allowing for a faster and more robust response if that same infection occurs again. In addition to this immune function, B cells have a close and multifaceted relationship with bone cells. B cells differentiate from hematopoietic stem cells (HSCs) in supportive niches found on endosteal bone surfaces. Cells in the osteoblast lineage support HSC and B cell differentiation in these niches. B cell differentiation is regulated, at least in part, by a series of transcription factors that function in a temporal manner. While these transcription factors are required for B cell differentiation, their loss causes profound changes in the bone phenotype. This is due, in part, to the close relationship between macrophage/osteoclast and B cell differentiation. Cross talk between B cells and bone cells is reciprocal with defects in the RANKL-RANK, OPG signaling axis resulting in altered bone phenotypes. While the role of B cells during normal bone remodeling appears minimal, activated B cells play an important role in many inflammatory diseases with associated bony changes. This review examines the relationship between B cells and bone cells and how that relationship affects the skeleton and hematopoiesis during health and disease. Copyright 2010 Elsevier Inc. All rights reserved.

A model for hematopoietic death in man from irradiation of bone marrow during radioimmunotherapy.

PubMed

Scott, B R; Dillehay, L E

1990-11-01

There are numerous institutions worldwide performing clinical trials of radioimmunotherapy (RIT) for cancer. For RIT, an exponentially decaying radionuclide is attached by using a chelating agent to a specific monoclonal or polyclonal tumour antibody (e.g. antiferritin IgG). The major limitation to RIT is toxicity to normal tissue in organs other than the one containing the tumour (e.g. bone marrow). The focus of this manuscript is on modelling the risk (or probability) of hematopoietic death in man for exponentially decaying patterns of high-energy beta irradiation (e.g. 90Y) of bone marrow by radioimmunoglobulin injected into the blood. The analytical solutions presented are only applicable to protocols for which significant uptake of radioactivity by the bone marrow does not occur, and only for high energy beta emitters. However, the generic equation used to obtain the analytical solutions is applicable to any continuous pattern of high energy beta irradiation. A model called the "normalized dose model" was used to generate calculated values for the LD50 as a function of the effective half-time for the radioimmunoglobulin in the blood. A less complicated empirical model was used to describe the calculated values. This model is presumed to be valid for effective half-times in blood of up to about 20 days. For longer effective half-times, the LD50 can be estimated using the normalized-dose model presented. In this manuscript, we also provide a modified Weibull model that allows estimation of the risk of hematopoietic death for single or multiple injections (in one cycle) of radioimmunoglobulin, for patients with normal susceptibility to irradiation and for patients with heightened susceptibility. With the modified Weibull model, the risk of hematopoietic death depends on the level of medical treatment provided to mitigate radiation injuries.

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultheiss, Timothy E.; Wong, Jeffrey; Liu, An

2007-03-15

Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribsmore » and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk.« less

Quantification of Cyclic Ground Reaction Force Histories During Daily Activity in Humans

NASA Technical Reports Server (NTRS)

Breit, G. A.; Whalen, R. T.; Wade, Charles E. (Technical Monitor)

1994-01-01

Theoretical models and experimental studies of bone remodeling suggest that bone density and structure are influenced by local cyclic skeletal tissue stress and strain histories. Estimation of long-term loading histories in humans is usually achieved by assessment of physical activity level by questionnaires, logbooks, and pedometers, since the majority of lower limb cyclic loading occurs during walking and running. These methods provide some indication of the mechanical loading history, but fail to consider the true magnitude of the lower limb skeletal forces generated by various daily activities. These techniques cannot account for individual gait characteristics, gait speed, and unpredictable high loading events that may influence bone mass significantly. We have developed portable instrumentation to measure and record the vertical component of the ground reaction force (GRFz) during normal daily activity. This equipment allows long-term quantitative monitoring of musculoskeletal loads, which in conjunction with bone mineral density assessments, promises to elucidate the relationship between skeletal stresses and bone remodeling.

Bone mineral density in anorexia nervosa: Only weight and menses recovery?

PubMed

Jáuregui-Lobera, Ignacio; Bolaños-Ríos, Patricia; Sabaté, Juan

2016-11-01

The study objectives were to analyze the presence of reduced bone mass in a sample of patients with anorexia nervosa (AN) and amenorrhea, to assess Bone Mineral Density (BMD) recovery after having a normal weight is reached and regular menses are resumed, and to predict BMD after a treatment period considering different variables (baseline BMD, baseline and final body mass index (BMI), treatment duration). 35 patients with AN (mean age 20.57±5.77) were studied at treatment start (T 0 ) and after they had recovered their normal weight and regular menses (T 1 ) in order to measure their BMD using quantitative computed tomography (QCT) of the lumbar spine (L2-L4). At T 0 , 2.86% of patients had normal BMD, while a reduced bone mass consistent with osteopenia or with osteoporosis was found in 22.86% and 74.28% of patients respectively. At T 1 , the percentages were 20%, 20%, and 60% respectively. No significant differences were seen in L2-L3 and mean BMD (L2-L4). A significant difference was however found for L4 (p<0.05). A positive relationship was seen between final body mass index (BMI) and final BMD in patients with T 0 -T 1 >11 months, but not when the time period was ≤11 months. This follow-up study of changes not only in BMD but also in BMI and recovery of menses has clinical relevance from the viewpoint of the day-by-day treatment process. Use of QCT makes the study more relevant because this is a more advanced technique that allows for differentiating trabecular and cortical bone. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Automated bone age assessment of older children using the radius

NASA Astrophysics Data System (ADS)

Tsao, Sinchai; Gertych, Arkadiusz; Zhang, Aifeng; Liu, Brent J.; Huang, Han K.

2008-03-01

The Digital Hand Atlas in Assessment of Skeletal Development is a large-scale Computer Aided Diagnosis (CAD) project for automating the process of grading Skeletal Development of children from 0-18 years of age. It includes a complete collection of 1,400 normal hand X-rays of children between the ages of 0-18 years of age. Bone Age Assessment is used as an index of skeletal development for detection of growth pathologies that can be related to endocrine, malnutrition and other disease types. Previous work at the Image Processing and Informatics Lab (IPILab) allowed the bone age CAD algorithm to accurately assess bone age of children from 1 to 16 (male) or 14 (female) years of age using the Phalanges as well as the Carpal Bones. At the older ages (16(male) or 14(female) -19 years of age) the Phalanges as well as the Carpal Bones are fully developed and do not provide well-defined features for accurate bone age assessment. Therefore integration of the Radius Bone as a region of interest (ROI) is greatly needed and will significantly improve the ability to accurately assess the bone age of older children. Preliminary studies show that an integrated Bone Age CAD that utilizes the Phalanges, Carpal Bones and Radius forms a robust method for automatic bone age assessment throughout the entire age range (1-19 years of age).

[Orbital decompression in Grave's ophtalmopathy].

PubMed

Longueville, E

2010-01-01

Graves disease orbitopathy is a complex progressive inflammatory disease. Medical treatment remains in all cases the proposed treatment of choice. Surgical treatment by bone decompression can be considered as an emergency mainly in cases of optic neuropathy or ocular hypertension not being controlled medically or in post-traumatic exophthalmos stage. Emergency bone decompression eliminates compression or stretching of the optic nerve allowing visual recovery. The uncontrolled ocular hypertension will benefit from decompression. The normalization of intraocular pressure may be obtained by this surgery or if needed by the use of postoperative antiglaucoma drops or even filtration surgery. In all operated cases, the IOP was normalized with an average decrease of 7.71 mmHg and a cessation of eye drops in 3/7 cases. Regarding sequelae, our therapeutic strategy involves consecutively surgery of the orbit, extraocular muscles and eyelids. The orbital expansion gives excellent results on the cosmetic level and facilitates the implementation of subsequent actions.

On foundations of discrete element analysis of contact in diarthrodial joints.

PubMed

Volokh, K Y; Chao, E Y S; Armand, M

2007-06-01

Information about the stress distribution on contact surfaces of adjacent bones is indispensable for analysis of arthritis, bone fracture and remodeling. Numerical solution of the contact problem based on the classical approaches of solid mechanics is sophisticated and time-consuming. However, the solution can be essentially simplified on the following physical grounds. The bone contact surfaces are covered with a layer of articular cartilage, which is a soft tissue as compared to the hard bone. The latter allows ignoring the bone compliance in analysis of the contact problem, i.e. rigid bones are considered to interact through a compliant cartilage. Moreover, cartilage shear stresses and strains can be ignored because of the negligible friction between contacting cartilage layers. Thus, the cartilage can be approximated by a set of unilateral compressive springs normal to the bone surface. The forces in the springs can be computed from the equilibrium equations iteratively accounting for the changing contact area. This is the essence of the discrete element analysis (DEA). Despite the success in applications of DEA to various bone contact problems, its classical formulation required experimental validation because the springs approximating the cartilage were assumed linear while the real articular cartilage exhibited non-linear mechanical response in reported tests. Recent experimental results of Ateshian and his co-workers allow for revisiting the classical DEA formulation and establishing the limits of its applicability. In the present work, it is shown that the linear spring model is remarkably valid within a wide range of large deformations of the cartilage. It is also shown how to extend the classical DEA to the case of strong nonlinearity if necessary.

Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone.

PubMed

Whitson, Heather E; Lobaugh, Bruce; Lyles, Kenneth W

2006-10-01

Bisphosphonate therapy is a common and effective treatment for Paget's disease of bone, osteoporosis, hypercalcemia of malignancy and cancer metastatic to bone. Clinically significant hypocalcemia has not been reported in patients with Paget's disease of bone and normal parathyroid function treated with an aminobisphosphonate. We treated a 52-year-old woman with polyostotic Paget's disease of bone (serum alkaline phosphatase level-1971 IU/L [normal 31-110 IU/L]), who had not previously received bisphosphonates, with daily oral 30 mg risedronate, oral 1000 mg elemental calcium and oral 400 IU cholecalciferol. After 10 days of treatment, she developed severe hypocalcemia (5.4 mg/dL [normal 8.7-10.2 mg/dL]), requiring hospitalization and support with 5 days of intravenous calcium gluconate. On the day risedronate treatment began, her PTH was low normal at 14 pg/mL (normal 12-72 pg/mL), consistent with a relatively suppressed PTH axis due to high bone turnover. Her vitamin D level was within normal limits (serum 25(OH)D 19 ng/mL [normal 8-38 ng/mL]), although possibly not optimally repleted. We hypothesize that this case represents an example of hungry bone syndrome in a patient with extensive Paget's disease of bone who received risedronate, causing acute suppression of bone resorption while elevated bone formation rates continued. In the year following her recovery, the patient was successfully treated with slowly titrated anti-resorptive therapy (subcutaneous calcitonin followed by titrated doses of risedronate), and is now clinically well. Physicians should be aware of the potential for hypocalcemia when patients with polyostotic Paget's disease and markedly elevated indicators of bone remodeling are initiated on powerful anti-resorptive therapy.

High fat diet promotes achievement of peak bone mass in young rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna

Highlights: • High fat diet helps in achieving peak bone mass at younger age. • Shifting from high fat to normal diet normalizes obese parameters. • Bone parameters are sustained even after withdrawal of high fat diet. - Abstract: The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fatmore » mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.« less

Antibiotic penetration into bone in relation to the immediate management of open fractures: a review.

PubMed

Hughes, S P

1992-01-01

Bone is a vascular structure, which is capable of responding to changes in the systemic circulation. Antibiotics carried within the systemic circulation reach the capillaries in bone, and depending on molecular size, pass through the capillary walls to enter the fluid space. Following an open fracture, contamination with pathogenic organisms can occur both at the moment of injury, but also in the hospital, which is a particular problem in grade III fractures in which extensive soft tissue damage can occur in combination with an exposed wound. Antibiotics administered intravenously can be measured in bone by both bioassay and radioactive isotope techniques and are shown to reach bone in effective concentrations. It is apparent that short-course high-dose antibiotic therapy is appropriate for open fractures, and need not be continued as long as the normal fracture-healing process continues. However if infection in bone develops, further surgery is important to remove new dead tissue to allow adequate antibiotic penetration into bone. Thus antibiotics are useful when combined with effective surgical management, but do not on their own offer the only answer to management of the patient.

Multi analytical technique study of human bones from an archaeological discovery.

PubMed

Lachowicz, J I; Palomba, S; Meloni, P; Carboni, M; Sanna, G; Floris, R; Pusceddu, V; Sarigu, M

2017-03-01

In 1953, during the building restoration of San Michele church (Bono, Sardinia, 16th-19th Century), a high number of disarticulated skeletons were recovered. From a group of 412 hip bones, two of these, affected by several pathological lesions, were analysed. The two coxal bones can be referred to the same individual, an adult man. A multi-analytical study, started with the purpose of investigating the bone pathology, was extended to characterize the mineral components of a large representative set of bones from the same ossuary, all attributed to adult men who lived in the region four-two centuries ago. A quantitative ICP-AES analysis for Ca, Fe, Mg, Mn, Na, Pb and Zn was executed, and a chemometric investigation on the results was performed. This approach gave evidence of the effects of diagenesis, allowed some hypothesis of the incidence of the known dietary habits on bone composition, and completely differentiated the pathological bones from those of a normal population on the basis of the mineral composition. Moreover, porosity, crystallinity and FT-IR analysis were conducted on both non- and pathological sample. Copyright © 2016 Elsevier GmbH. All rights reserved.

3D Printed Pediatric Temporal Bone: A Novel Training Model.

PubMed

Longfield, Evan A; Brickman, Todd M; Jeyakumar, Anita

2015-06-01

Temporal bone dissection is a fundamental element of otologic training. Cadaveric temporal bones (CTB) are the gold standard surgical training model; however, many institutions do not have ready access to them and their cost can be significant: $300 to $500. Furthermore, pediatric cadaveric temporal bones are not readily available. Our objective is to develop a pediatric temporal bone model. Temporal bone model. Tertiary Children's Hospital. Pediatric patient model. We describe the novel use of a 3D printer for the generation of a plaster training model from a pediatric high- resolution CT temporal bone scan of a normal pediatric temporal bone. Three models were produced and were evaluated. The models utilized multiple colors (white for bone, yellow for the facial nerve) and were of high quality. Two models were drilled as a proof of concept and found to be an acceptable facsimile of the patient's anatomy, rendering all necessary surgical landmarks accurately. The only negative comments pertaining to the 3D printed temporal bone as a training model were the lack of variation in hardness between cortical and cancellous bone, noting a tactile variation from cadaveric temporal bones. Our novel pediatric 3D temporal bone training model is a viable, low-cost training option for previously inaccessible pediatric temporal bone training. Our hope is that, as 3D printers become commonplace, these models could be rapidly reproduced, allowing for trainees to print models of patients before performing surgery on the living patient.

The short-term effects of cisplatin chemotherapy on bone turnover.

PubMed

Young, D R; Virolainen, P; Inoue, N; Frassica, F J; Chao, E Y

1997-11-01

Cisplatin is an effective agent in the treatment of osteosarcoma of bone but little is known of its effects on normal bone turnover. Twenty-four dogs divided into three study groups were used to study the effect of cisplatin on normal bone turnover at the distant site of surgery. Group 1 served as the control group, group 2 received four cycles of cisplatin every 3 weeks before the surgery, and group 3 received four cycles postoperatively. The bone turnover rate was evaluated by measuring levels of systemic bone markers, osteocalcin, alkaline phospohatase, urine pyridinoline cross-links, and by determination histomorphometric indices. Histomorphological analysis showed poor correlation on bone formation with systemic bone markers at distant sites of surgery. Histomorphometrically normal bone turnover was affected by administration of cisplatin, but the effect was temporary, late, and less significant than what occurred at the surgical site. Our data showed that significant effects of cisplatin are observed at the site of active cellular induction and proliferation, such as implant-host interface, and less effects are seen at the sites of normal bone turnover.

Reduced vertebral bone density in hypercalciuric nephrolithiasis

NASA Technical Reports Server (NTRS)

Pietschmann, F.; Breslau, N. A.; Pak, C. Y.

1992-01-01

Dual-energy x-ray absorptiometry and single-photon absorptiometry were used to determine bone density at the lumbar spine and radial shaft in 62 patients with absorptive hypercalciuria, 27 patients with fasting hypercalciuria, and 31 nonhypercalciuric stone formers. Lumbar bone density was significantly lower in patients with absorptive (-10%) as well as in those with fasting hypercalciuria (-12%), with 74 and 92% of patients displaying values below the normal mean, whereas only 48% of the nonhypercalciuric stone formers had bone density values below the normal mean. In contrast, radial bone density was similar in all three groups of renal stone formers investigated. The comparison of urinary chemistry in patients with absorptive hypercalciuria and low normal bone density compared to those with high normal bone density showed a significantly increased 24 h urinary calcium excretion on random diet and a trend toward a higher 24 h urinary uric acid excretion and a higher body mass index in patients with low normal bone density. Moreover, among the patients with absorptive hypercalciuria we found a statistically significant correlation between the spinal bone density and the 24 h sodium and sulfate excretion and the urinary pH. These results gave evidence for an additional role of environmental factors (sodium and animal proteins) in the pathogenesis of bone loss in absorptive hypercalciuria. In conclusion, our data suggest an osteopenia of trabecular-rich bone tissues in patients with fasting and absorptive hypercalciurias.

Manipulation of immune system via immortal bone marrow stem cells.

PubMed

Ruedl, Christiane; Khameneh, Hanif Javanmard; Karjalainen, Klaus

2008-09-01

Extensive amplification of hematopoietic stem cells (HSCs) and their multipotent primitive progenitors (MPPs) in culture would greatly benefit not only clinical transplantation but also provide a potential tool to manipulate all cellular lineages derived from these cells for gene therapy and experimental purposes. Here, we demonstrate that mouse bone marrow cultures containing cells engineered to over-express NUP98-HOXB4 fusion protein support self-renewal of physiologically normal HSC and MPP for several weeks leading practically to their unlimited expansion. This allows time consuming and cumulative in vitro experimental manipulations without sacrificing their ability to differentiate in vivo or in vitro to any hematopoietic lineage.

Functional Adaptation of the Calcaneus in Historical Foot Binding.

PubMed

Reznikov, Natalie; Phillips, Carina; Cooke, Martyn; Garbout, Amin; Ahmed, Farah; Stevens, Molly M

2017-09-01

The normal structure of human feet is optimized for shock dampening during walking and running. Foot binding was a historical practice in China aimed at restricting the growth of female feet for aesthetic reasons. In a bound foot the shock-dampening function normally facilitated by the foot arches is withdrawn, resulting in the foot functioning as a rigid extension of the lower leg. An interesting question inspiring this study regards the nature of adaptation of the heel bone to this nonphysiological function using the parameters of cancellous bone anisotropy and 3D fabric topology and a novel intertrabecular angle (ITA) analysis. We found that the trabecular microarchitecture of the normal heel bone, but not of the bound foot, adapts to function by increased anisotropy and preferred orientation of trabeculae. The anisotropic texture in the normal heel bone consistently follows the physiological stress trajectories. However, in the bound foot heel bone the characteristic anisotropy pattern fails to develop, reflecting the lack of a normal biomechanical input. Moreover, the basic topological blueprint of cancellous bone investigated by the ITA method is nearly invariant in both normal and bound foot. These findings suggest that the anisotropic cancellous bone texture is an acquired characteristic that reflects recurrent loading conditions; conversely, an inadequate biomechanical input precludes the formation of anisotropic texture. This opens a long-sought-after possibility to reconstruct bone function from its form. The conserved topological parameters characterize the generic 3D fabric of cancellous bone, which is to a large extent independent of its adaptation to recurrent loading and perhaps determines the mechanical competence of trabecular bone regardless of its functional adaptation. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Experiment K305: Quantitative analysis of selected bone parameters. Supplement 2: Bone elongation rate and bone mass in metaphysis of long bones

NASA Technical Reports Server (NTRS)

Jee, W. S. S.; Kimmel, D. B.; Smith, C.; Dell, R. B.

1981-01-01

The proximal humeral metaphysis of rats from time periods recovery plus zero days (R+0), recovery plus six days (R+6), and recovery plus twenty nine days (R+29) was analyzed. The volume of calcified cartilage and bone in flight and synchronous controls was reduced in groups R+0 and R+6, but was normal in group R+29. The number of functional bone cells (osteoblasts and osteoclasts) was decreased in proportion to the amount of bone in the early groups, and was normal in the last group. The fatty marrow volume was increased only in flight animals of groups R+0 and R+6, but was normal in the R+29 group. Accumulation of excess fatty marrow was seen only in flight animals. The decreased amount of bone and calcified cartilage is believed to be the result of a temporarily slowed or arrested production of calcified cartilage as a substrate for bone formation. This would have resulted from slowed bone elongation during flight and synchronous control conditions. Bone elongation returned to normal by twenty nine days after return.

Assessment of Mechanical Performance of Bone Architecture Using Rapid Prototyping Models

NASA Astrophysics Data System (ADS)

Saparin, Peter; Woesz, Alexander; Thomsen, Jasper S.; Fratzl, Peter

2008-06-01

The aim of this on-going research project is to assess the influence of bone microarchitecture on the mechanical performance of trabecular bone. A testing chain consist-ing of three steps was established: 1) micro computed tomography (μCT) imaging of human trabecular bone; 2) building of models of the bone from a light-sensitive polymer using Rapid Prototyping (RP); 3) mechanical testing of the models in a material testing machine. A direct resampling procedure was developed to convert μCT data into the format of the RP machine. Standardized parameters for production and testing of the plastic models were established by use of regular cellular structures. Next, normal, osteoporotic, and extreme osteoporotic vertebral trabecular bone architectures were re-produced by RP and compression tested. We found that normal architecture of vertebral trabecular bone exhibit behaviour characteristic of a cellular structure. In normal bone the fracture occurs at much higher strain values that in osteoporotic bone. After the fracture a normal trabecular architecture is able to carry much higher loads than an osteoporotic architecture. However, no statistically significant differences were found in maximal stress during uniaxial compression of the central part of normal, osteoporotic, and extreme osteoporotic vertebral trabecular bone. This supports the hypothesis that osteoporotic trabecular bone can compensate for a loss of trabeculae by thickening the remaining trabeculae in the loading direction (compensatory hypertrophy). The developed approach could be used for mechanical evaluation of structural data acquired non-invasively and assessment of changes in performance of bone architecture.

The gut microbiota regulates bone mass in mice

PubMed Central

Sjögren, Klara; Engdahl, Cecilia; Henning, Petra; Lerner, Ulf H; Tremaroli, Valentina; Lagerquist, Marie K; Bäckhed, Fredrik; Ohlsson, Claes

2012-01-01

The gut microbiota modulates host metabolism and development of immune status. Here we show that the gut microbiota is also a major regulator of bone mass in mice. Germ-free (GF) mice exhibit increased bone mass associated with reduced number of osteoclasts per bone surface compared with conventionally raised (CONV-R) mice. Colonization of GF mice with a normal gut microbiota normalizes bone mass. Furthermore, GF mice have decreased frequency of CD4+ T cells and CD11b+/GR 1 osteoclast precursor cells in bone marrow, which could be normalized by colonization. GF mice exhibited reduced expression of inflammatory cytokines in bone and bone marrow compared with CONV-R mice. In summary, the gut microbiota regulates bone mass in mice, and we provide evidence for a mechanism involving altered immune status in bone and thereby affected osteoclast-mediated bone resorption. Further studies are required to evaluate the gut microbiota as a novel therapeutic target for osteoporosis. © 2012 American Society for Bone and Mineral Research. PMID:22407806

Dimensional, Geometrical, and Physical Constraints in Skull Growth.

PubMed

Weickenmeier, Johannes; Fischer, Cedric; Carter, Dennis; Kuhl, Ellen; Goriely, Alain

2017-06-16

After birth, the skull grows and remodels in close synchrony with the brain to allow for an increase in intracranial volume. Increase in skull area is provided primarily by bone accretion at the sutures. Additional remodeling, to allow for a change in curvatures, occurs by resorption on the inner surface of the bone plates and accretion on their outer surfaces. When a suture fuses too early, normal skull growth is disrupted, leading to a deformed final skull shape. The leading theory assumes that the main stimulus for skull growth is provided by mechanical stresses. Based on these ideas, we first discuss the dimensional, geometrical, and kinematic synchrony between brain, skull, and suture growth. Second, we present two mechanical models for skull growth that account for growth at the sutures and explain the various observed dysmorphologies. These models demonstrate the particular role of physical and geometrical constraints taking place in skull growth.

Dimensional, Geometrical, and Physical Constraints in Skull Growth

NASA Astrophysics Data System (ADS)

Weickenmeier, Johannes; Fischer, Cedric; Carter, Dennis; Kuhl, Ellen; Goriely, Alain

2017-06-01

After birth, the skull grows and remodels in close synchrony with the brain to allow for an increase in intracranial volume. Increase in skull area is provided primarily by bone accretion at the sutures. Additional remodeling, to allow for a change in curvatures, occurs by resorption on the inner surface of the bone plates and accretion on their outer surfaces. When a suture fuses too early, normal skull growth is disrupted, leading to a deformed final skull shape. The leading theory assumes that the main stimulus for skull growth is provided by mechanical stresses. Based on these ideas, we first discuss the dimensional, geometrical, and kinematic synchrony between brain, skull, and suture growth. Second, we present two mechanical models for skull growth that account for growth at the sutures and explain the various observed dysmorphologies. These models demonstrate the particular role of physical and geometrical constraints taking place in skull growth.

Molecular Interaction of Bone Marrow Adipose Tissue with Energy Metabolism.

PubMed

Suchacki, Karla J; Cawthorn, William P

2018-01-01

The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT. Though still dwarfed by research into white and brown adipose tissues, BMAT is now recognised as endocrine organ and is attracting increasing attention from biomedical researchers around the globe. We are beginning to learn the importance of BMAT both within and beyond the bone, allowing us to better appreciate the role of BMAT in normal physiology and disease.

Functional Adaptation of the Calcaneus in Historical Foot Binding

PubMed Central

Reznikov, Natalie; Phillips, Carina; Cooke, Martyn; Garbout, Amin; Ahmed, Farah

2017-01-01

ABSTRACT The normal structure of human feet is optimized for shock dampening during walking and running. Foot binding was a historical practice in China aimed at restricting the growth of female feet for aesthetic reasons. In a bound foot the shock‐dampening function normally facilitated by the foot arches is withdrawn, resulting in the foot functioning as a rigid extension of the lower leg. An interesting question inspiring this study regards the nature of adaptation of the heel bone to this nonphysiological function using the parameters of cancellous bone anisotropy and 3D fabric topology and a novel intertrabecular angle (ITA) analysis. We found that the trabecular microarchitecture of the normal heel bone, but not of the bound foot, adapts to function by increased anisotropy and preferred orientation of trabeculae. The anisotropic texture in the normal heel bone consistently follows the physiological stress trajectories. However, in the bound foot heel bone the characteristic anisotropy pattern fails to develop, reflecting the lack of a normal biomechanical input. Moreover, the basic topological blueprint of cancellous bone investigated by the ITA method is nearly invariant in both normal and bound foot. These findings suggest that the anisotropic cancellous bone texture is an acquired characteristic that reflects recurrent loading conditions; conversely, an inadequate biomechanical input precludes the formation of anisotropic texture. This opens a long‐sought‐after possibility to reconstruct bone function from its form. The conserved topological parameters characterize the generic 3D fabric of cancellous bone, which is to a large extent independent of its adaptation to recurrent loading and perhaps determines the mechanical competence of trabecular bone regardless of its functional adaptation. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. PMID:28561380

From Milk to Bones, Moving Calcium Through the Body: Calcium Kinetics During Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott; Bloomberg, Jacob; Lee, Angie (Technical Monitor)

2002-01-01

Did you know that when astronauts are in space, their height increases about two inches? This happens because the weightlessness of space allows the spine, usually compressed in Earth's gravity, to expand. While this change is relatively harmless, other more serious things can happen with extended stays in weightlessness, notably bone loss. From previous experiments, scientists have observed that astronauts lose bone mass at a rate of about one percent per month during flight. Scientists know that bone is a dynamic tissue - continually being made and repaired by specialized bone cells throughout life. Certain cells produce new bone, while other cells are responsible for removing and replacing old bone. Research on the mechanisms of bone metabolism and the effects of space flight on its formation and repair are part of the exciting studies that will be performed during STS-107. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. Ninety-nine percent of calcium in the body is stored in the skeleton. However, calcium may be released, or resorbed, from bone to provide for other tissues when you are not eating. To better understand how and why weightlessness induces bone loss, astronauts will participate in a study of calcium kinetics - that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Survival and endogenous colony formation in irradiated mice grafted with normal or infectious mononucleosis bone marrow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louwagie, A. C.; Verwilghen, R. L.

1973-07-01

Mice were exposed to 850 or 975 rad of whole-body radiation; three hr later mice were given normal human bone marrow, infectious mononucleosis bone marrow, or cells from malignant blood diseases. The surviving mice were killed at day 9 and the spleen nodules were counted. Some mice were also given antihuman antilymphocytic serum (ALS). In mice exposed to 975 rad, the highest survival was observed in mice grafted with infectious mononucleosis bone marrow, while none of the animals grafted with cells from malignant blood diseases survived 9 days. In mice exposed to 850 rad, grafting of normal or infectious mononucleosismore » bone marrow markedly decreased the survival. Endogenous spleen colonies were induced in all animals grafted with normal or infectious mononucleosis bone marrow. (HLW)« less

Methods and application of bone densitometry in clinical diagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wahner, H.W.; Riggs, B.L.

1986-01-01

With the awareness of osteoporosis as a major health problem for an aging population, there is great interest in early recognition and treatment of abnormal bone loss. Effective prevention of bone loss has to occur prior to the occurrence of irreparable damage. Standard radiographic procedures are not sensitive enough for the task. Therefore, a number of alternative procedures to estimate bone loss have been developed over the years, ranging from efforts to quantitate information obtained from radiographic images to sophisticated procedures such as neutron activation analysis or procedures based on the Compton scatter phenomenon. Only two procedures, photon absorptiometry andmore » computed tomography (CT), have emerged as applicable for routine clinical use. In photon absorptiometry the entire bone mineral (cortical and trabecular bone) of a specific skeletal site is measured. CT allows measuring of bone mineral of trabecular or cortical bone alone. Normally, bone mass reaches a maximum in the third decade and then continuously declines. This age-related bone loss is greater in women in whom an accelerated rate of loss occurs at the menopause. When bone density reaches a critical fracture threshold, skeletal fractures occur (spine, hip, and distal long bones). The age at which this critical fracture threshold is reached depends on the maximal bone mass achieved in early adulthood and the rate of loss with increasing age. With the exception of NaF, present-day therapeutic efforts only retard or prevent bone loss but do not significantly add bone mineral to the skeleton. Recognition of high-risk groups and early treatment are therefore required. 79 references.« less

Growth of erythroid burst-forming units (BFU-E) in cultures of canine bone marrow and peripheral blood cells: effect of serum from irradiated dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kreja, L.; Baltschukat, K.; Nothdurft, W.

1988-08-01

Erythroid burst-forming units (BFU-E) from canine bone marrow and peripheral blood could be grown in methylcellulose in the presence of an appropriate batch of fetal calf serum (FCS), transferrin, and erythropoietin (Epo). However, improved colony formation (size and number of bursts) was obtained when serum from total body irradiated dogs was present in the culture. This serum, obtained from dogs at day 9 after total body irradiation with a dose of 3.9 Gy, reduced markedly the Epo requirement of BFU-E. Furthermore, it allowed the omission of FCS from the culture medium if cholesterol and bovine serum albumin (BSA) were usedmore » as FCS substitutes. BFU-E concentrations were found to be rather different in the peripheral blood and in bone marrow samples from different sites (i.e., iliac crest, sternum, and humerus) of normal beagles. The studies further show that canine bone marrow BFU-E can be cryopreserved in liquid nitrogen.« less

Bone compositional study during healing of subcritical calvarial defects in rats by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ahmed, Rafay; Wing Lun Law, Alan; Cheung, Tsz Wing; Lau, Condon

2017-07-01

Subcritical calvarial defects are important to study bone regeneration during healing. In this study 1mm calvarial defects were created using trephine in the parietal bones of Sprague-Dawley rats (n=7) that served as in vivo defects. Subjects were sacrificed after 7 days and the additional defects were created on the harvested skull with the same method to serve as control defects. Raman spectroscopy is established to investigate mineral/matrix ratio, carbonate/phosphate ratio and crystallinity of three different surfaces; in vivo defects, control defects and normal surface. Results show 21% and 23% decrease in mineral/matrix after 7 days of healing from surface to in vivo and control to in vivo defects, respectively. Carbonate to phosphate ratio was found to be increased by 39% while crystallinity decreased by 26% in both surface to in vivo and control to in vivo defects. This model allows to study the regenerated bone without mechanically perturbing healing surface.

Therapies for Musculoskeletal Disease: Can we Treat Two Birds with One Stone?

PubMed Central

Girgis, Christian M.; Mokbel, Nancy; DiGirolamo, Douglas J.

2014-01-01

Musculoskeletal diseases are highly prevalent with staggering annual health care costs across the globe. The combined wasting of muscle (sarcopenia) and bone (osteoporosis)— both in normal aging and pathologic states—can lead to vastly compounded risk for fracture in patients. Until now, our therapeutic approach to the prevention of such fractures has focused solely on bone, but our increasing understanding of the interconnected biology of muscle and bone has begun to shift our treatment paradigm for musculoskeletal disease. Targeting pathways that centrally regulate both bone and muscle (eg, GH/IGF-1, sex steroids, etc.) and newly emerging pathways that might facilitate communication between these 2 tissues (eg, activin/myostatin) might allow a greater therapeutic benefit and/or previously unanticipated means by which to treat these frail patients and prevent fracture. In this review, we will discuss a number of therapies currently under development that aim to treat musculoskeletal disease in precisely such a holistic fashion. PMID:24633910

Low Bone Density

MedlinePlus

... Bone Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone ... to people with normal bone density. Detecting Low Bone Density A bone density test will determine whether ...

Applicability of strain measurements on a contra angle handpiece for the determination of alveolar bone quality during dental implant surgery.

PubMed

Krafft, Tim; Winter, Werner; Wichmann, Manfred; Karl, Matthias

2012-07-01

Alveolar bone quality is considered to be an important prognostic factor in dental implant stability. Although numerous methods have been described, no technique allows for reliable diagnostics. The purpose of this study was to determine if strain measurements on the shaft of a contra angle handpiece during implant bed preparation could be used for the determination of bone quality. Experiments in polyurethane foam and human cadaver bone were conducted to investigate whether strain measurements could be correlated with other diagnostic parameters, such as the surgeon's tactile sensation during drilling, implant insertion torque, implant stability, elastic modulus of bone and bone quality as assessed radiographically. Tests were also performed to determine if strain measurements could be used to distinguish various types of bone. As axial feed and contact pressure during the drilling process could not be standardized under simulated clinical conditions, substantial deviations in the time needed to complete the drilling occurred. Under controlled circumstances using polyurethane foam, this problem could be addressed by a normalization procedure, but great variations occurred in human cadaver bone. As bone quality could not be reliably determined, especially when a cortical layer was present, strain measurements on a contra angle handpiece appears to be inappropriate for this purpose. Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

NASA Technical Reports Server (NTRS)

Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

1998-01-01

The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

Bone apatite composition of necrotic trabecular bone in the femoral head of immature piglets.

PubMed

Aruwajoye, Olumide O; Kim, Harry K W; Aswath, Pranesh B

2015-04-01

Ischemic osteonecrosis of the femoral head (IOFH) can lead to excessive resorption of the trabecular bone and collapse of the femoral head as a structure. A well-known mineral component to trabecular bone is hydroxyapatite, which can be present in many forms due to ionic substitution, thus altering chemical composition. Unfortunately, very little is known about the chemical changes to bone apatite following IOFH. We hypothesized that the apatite composition changes in necrotic bone possibly contribute to increased osteoclast resorption and structural collapse of the femoral head. The purpose of this study was to assess the macroscopic and local phosphate composition of actively resorbed necrotic trabecular bone to isolate differences between areas of increased osteoclast resorption and normal bone formation. A piglet model of IOFH was used. Scanning electron microscopy (SEM), histology, X-ray absorbance near edge structure (XANES), and Raman spectroscopy were performed on femoral heads to characterize normal and necrotic trabecular bone. Backscattered SEM, micro-computed tomography and histology showed deformity and active resorption of necrotic bone compared to normal. XANES and Raman spectroscopy obtained from actively resorbed necrotic bone and normal bone showed increased carbonate-to-phosphate content in the necrotic bone. The changes in the apatite composition due to carbonate substitution may play a role in the increased resorption of necrotic bone due to its increase in solubility. Indeed, a better understanding of the apatite composition of necrotic bone could shed light on osteoclast activity and potentially improve therapeutic treatments that target excessive resorption of bone.

[Biphasic ceramic wedge and plate fixation with locked adjustable screws for open wedge tibial osteotomy].

PubMed

Lavallé, F; Pascal-Mousselard, H; Rouvillain, J L; Ribeyre, D; Delattre, O; Catonné, Y

2004-10-01

The aim of this radiological study was to evaluate the use of a biphasic ceramic wedge combined with plate fixation with locked adjustable screws for open wedge tibial osteotomy. Twenty-six consecutive patients (27 knees) underwent surgery between December 1999 and March 2002 to establish a normal lower-limb axis. The series included 6 women and 20 men, mean age 50 years (16 right knees and 11 left knees). Partial weight-bearing with crutches was allowed on day 1. A standard radiological assessment was performed on day 1, 90, and 360 (plain AP and lateral stance films of the knee). A pangonogram was performed before surgery and at day 360. Presence of a lateral metaphyseal space, development of peripheral cortical bridges, and osteointegration of the bone substitute-bone interface were evaluated used to assess bone healing. The medial tibial angle between the line tangent to the tibial plateau and the anatomic axis of the tibia (beta) was evaluated to assess preservation of postoperative correction. The HKA angle was determined. Three patients were lost to follow-up and 23 patients (24 knees) were retained for analysis. At last follow-up, presence of peripheral cortical bridges and complete filling of the lateral metaphyseal space demonstrated bone healing in all patients. Good quality osteointegration was achieved since 21 knees did not present an interface between the bone substitute and native bone (homogeneous transition zone). The beta angle was unchanged for 23 knees. A normal axis was observed in patients (16 knees) postoperatively. Use of a biphasic ceramic wedge in combination with plate fixation with locked adjustable screws is a reliable option for open wedge tibial osteotomy. The bone substitute fills the gap well. Tolerance and integration are optimal. Bone healing is achieved. Plate fixation with protected weight bearing appears to be a solid assembly, maintaining these corrections.

Toward Patient Specific Long Lasting Metallic Implants for Mandibular Segmental Defects

NASA Astrophysics Data System (ADS)

Shayesteh Moghaddam, Narges

Mandibular defects may result from tumor resection, trauma, or inflammation. The goals of mandibular reconstruction surgeries are to restore mandible function and aesthetics. To this end, surgeons use a combination of bone grafts and metallic implants. These implants have drastically different mechanical properties than the surrounding bone. As a result, the stress distribution in the mandible changes after surgery. The long-term abnormal stress/strain distribution may lead to either graft failure due to bone resorption as a result of stress shielding, or hardware failure due to stress concentrations. During the healing period of six to nine months it is important that complete immobilization, bringing mandibular micro-motion down to the level of 200-500 mum during chewing, is achieved. After this period it is desired that bone undergo normal stress for long-term success of the treatment. Although current high stiffness fixation hardware accomplishes this immobilization during the healing period, the hardware continues to alter the normal stress-strain trajectory seen during chewing once the engrafted bone heals. Over the long-term, the immobilized and stress-shielded engrafted bone tends to resorb. On the other hand, hardware fracturing or/and screw loosening is observed as the stress is concentrated at certain locations on the hardware. Equally as important is the permanent loss of chewing power due to the altered stress-strain relationships. The first stage of this research is to study the problems encountered following a mandibular segmental defect reconstructive surgery. To this end, we constructed a finite element model of a healthy mandible, which includes cortical and cancellous bone, teeth (enamel and dentin components), and the periodontal ligament. Using this model, we studied a healthy adult mandible under maximum molar bite force for stress, strain, displacement, and reaction force distribution. For mandibular segmental defect reconstruction the current standard of care consists of the use of Surgical Grade 5 titanium also known as Ti-6Al-4V hardware and either a single or double fibula barrel vascularized bone graft. We expanded our model to simulate the effects of this surgery. The expanded model includes both single and double barrel fibular bone graft repair of a right M1-M3 containing section of the mandible, Ti-6Al-4V fixation hardware and screws. We found that the stiffness mismatch between the fixation hardware and the bone causes stress shielding on the host mandible and the bone graft, and stress concentration at the fixation hardware and screws. The simulations results show that while a double-barrel graft is preferred, in the long-term it does not create the optimal outcome due to the abnormal stress pattern. To improve the long-term outcome with metallic implants it is essential to recreate the normal stress pattern. To achieve this outcome we investigated the use of porous nitinol as a substitute for the currently used titanium hardware. While NiTi already has a lower stiffness than titanium, it is possible to add porosity to further reduce the stiffness to be closer to that of cortical bone. The ultimate goal is to create fixation hardware that has sufficient stiffness for immobilization while recreating the normal stress pattern in the bone. Using a finite element model of devices fabricated from Surgical Grade 5 titanium and NiTi, we have found that stiffness-tuned NiTi hardware with conventional geometries should result in recreation of normal stress-strain trajectories and better treatment outcome. Finally, to further improve the outcome, we suggest the use of a two-stage mechanism Bone Bandaid which supports both the immobilization/healing and regenerative phases of mandibular segmental defect treatment. This device is made of two materials. The stiff Ti-6Al-4V portion provides the support during the healing period and is disengaged afterwards. The second material is a NiTi wire-frame to facilitate normal stress distribution after the initial healing period. The titanium part of this fixation hardware is released following radiological verification that the surgical osteotomies have healed. The release procedure is performed under local anesthetic via a microsurgical tool. With the titanium fixation hardware no longer functional, the NiTi webbing would act as a superstructure, like a skin, to the underlying grafted cortical bone. This device facilitates stress transduction through the normal stress-strain trajectories, allows restoration of power, drives cortical bone remodeling and strengthening, provides long-term strength, and a good bone bed for dental implants. If bone chips are used, instead of single or double bone graft, the webbing is more likely to support the bone chips while they are being incorporated with the mandible. We have performed computer simulation to investigate the two stages of the operation of the device. Our FEA results indicate that the Bone Bandaid supports both the immobilization needed during healing and the distribution of stress through the engrafted bone once it has healed. (Abstract shortened by ProQuest.).

Fixation of a split fracture of the lateral tibial plateau with a locking screw plate instead of cannulated screws would allow early weight bearing: a computational exploration.

PubMed

Carrera, Ion; Gelber, Pablo Eduardo; Chary, Gaetan; González-Ballester, Miguel A; Monllau, Juan Carlos; Noailly, Jerome

2016-10-01

To assess, with finite element (FE) calculations, whether immediate weight bearing would be possible after surgical stabilization either with cannulated screws or with a locking plate in a split fracture of the lateral tibial plateau (LTP). A split fracture of the LTP was recreated in a FE model of a human tibia. A three-dimensional FE model geometry of a human femur-tibia system was obtained from the VAKHUM project database, and was built from CT images from a subject with normal bone morphologies and normal alignment. The mesh of the tibia was reconverted into a geometry of NURBS surfaces. A split fracture of the lateral tibial plateau was reproduced by using geometrical data from patient radiographs. A locking screw plate (LP) and a cannulated screw (CS) systems were modelled to virtually reduce the fracture and 80 kg static body-weight was simulated. While the simulated body-weight led to clinically acceptable interfragmentary motion, possible traumatic bone shear stresses were predicted nearby the cannulated screws. With a maximum estimation of about 1.7 MPa maximum bone shear stresses, the Polyax system might ensure more reasonable safety margins. Split fractures of the LTP fixed either with locking screw plate or cannulated screws showed no clinically relevant IFM in a FE model. The locking screw plate showed higher mechanical stability than cannulated screw fixation. The locking screw plate might also allow full or at least partial weight bearing under static posture at time zero.

Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass

NASA Technical Reports Server (NTRS)

Elefteriou, Florent; Takeda, Shu; Liu, Xiuyun; Armstrong, Dawna; Karsenty, Gerard

2003-01-01

Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

[Toward an anthropometric diagnosis of osteopenia and a biochemical diagnosis of osteoporoses].

PubMed

Cointry, Gustavo R; Capozza, Ricardo F; Ferretti, Jose L; Frost, Harold M

2003-01-01

The current (metabolic) conception of bone-weakening diseases regards bone strength as determined by a systemically-controlled "mineralized mass" which grows until it reaches a peak and then is lost at individually-specific rates. This concept disregards bone biomechanics. Skeletons are structures, it reaches of which depends on the stiffness and the spatial distribution rather than the volume of the calcified material. Rather than allowing a systemic regulation of their "mass" as a way to optimize their strength, bones autocontrol their stiffness by orienting bone formation and destruction as locally determined by the directional sensing, by osteocytes, of the strains caused by mechanical usage (gravity, muscle contractions). Bone mass and strength are just side products of that control. Endocrine-metabolic systems modulate non-directionally the work of bone cells as required for achieving a mineral equilibrium, despite the biomechanical controls, and can determine osteopenias and osteoporoses. Osteoporoses are not "intense osteopenias" (as per the current WHO's conception) but "osteopenic bone fragilities" (as recently stated by the NIH). The diagnosis of osteopenia is an anthropometric problem that can be solved densitometrically; but that of bone fragility is a biomechanical matter that requires evaluation of bone material's stiffness and distribution by other means ("resistometry"). For therapeutic purposes, osteopenias and osteoporoses should be also evaluated according to the relationship between bone mass or strength and muscle mass or strength in order to distinguish between "mechanical" (disuse) and "metabolic" etiologies (intrinsic bone lesion, or systemic disequilibrium), in which the bone/muscle proportionality tends to remain normal or to deteriorate, respectively.

Evidence for a Role for Nanoporosity and Pyridinoline Content in Human Mild Osteogenesis Imperfecta.

PubMed

Paschalis, Eleftherios P; Gamsjaeger, Sonja; Fratzl-Zelman, Nadja; Roschger, Paul; Masic, Admir; Brozek, Wolfgang; Hassler, Norbert; Glorieux, Francis H; Rauch, Frank; Klaushofer, Klaus; Fratzl, Peter

2016-05-01

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous connective tissue disorder characterized by bone fragility that arises from decreased bone mass and abnormalities in bone material quality. OI type I represents the milder form of the disease and according to the original Sillence classification is characterized by minimal skeletal deformities and near-normal stature. Raman microspectroscopy is a vibrational spectroscopic technique that allows the determination of bone material properties in bone biopsy blocks with a spatial resolution of ∼1 µm, as a function of tissue age. In the present study, we used Raman microspectroscopy to evaluate bone material quality in transiliac bone biopsies from children with a mild form of OI, either attributable to collagen haploinsufficiency OI type I (OI-Quant; n = 11) or aberrant collagen structure (OI-Qual; n = 5), as a function of tissue age, and compared it against the previously published values established in a cohort of biopsies from healthy children (n = 54, ages 1 to 23 years). The results indicated significant differences in bone material compositional characteristics between OI-Quant patients and healthy controls, whereas fewer were evident in the OI-Qual patients. Differences in both subgroups of OI compared with healthy children were evident for nanoporosity, mineral maturity/crystallinity as determined by maxima of the v1 PO4 Raman band, and pyridinoline (albeit in different direction) content. These alterations in bone material compositional properties most likely contribute to the bone fragility characterizing this disease. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Conformational Changes in the Carpus During Finger Traps Distraction

PubMed Central

Leventhal, Evan L.; Moore, Douglas C.; Akelman, Edward; Wolfe, Scott W.; Crisco, Joseph J.

2010-01-01

Introduction Wrist distraction is a common treatment maneuver used clinically for the reduction of distal radial fractures and mid-carpal dislocations. Wrist distraction is also required during wrist arthroscopy to access the radiocarpal joint and has been used as a test for scapholunate ligament injury. However, the effect of a distraction load on the normal wrist has not been well studied. The purpose of this study was to measure the 3-D conformational changes of the carpal bones in the normal wrist as a result of a static distractive load. Methods The dominant wrists of 14 healthy volunteers were scanned using computed tomography at rest and during application of 98N of distraction. Load was applied using finger traps and volunteers were encouraged to relax their forearm muscles and to allow distraction of the wrist. The motions of the bones in the wrist were tracked between the unloaded and loaded trial using markerless bone registration. The average displacement vector of each bone was calculated relative to the radius as well as the interbone distances for 20 bone-bone interactions. Joint separation was estimated at the radiocarpal, midcarpal and carpal-metacarpal joints in the direction of loading using the radius, lunate, capitate and 3rd metacarpal. Results With loading, the distance between the radius and 3rd metacarpal increased an average of 3.3±3.1mm in the direction of loading. This separation was primarily located in the axial direction at the radiocarpal (1.0±1.0mm) and midcarpal (2.0±1.7mm) joints. There were minimal changes in the transverse direction within the distal row, although the proximal row narrowed by 0.98±0.7mm. Distraction between the radius and scaphoid (2.5±2.2mm) was 2.4 times greater than between the radius and lunate (1.0±1.0mm). Conclusions Carpal distraction has a significant effect on the conformation of the carpus, especially at the radiocarpal and midcarpal joints. In the normal wrist, external traction causes twice as much distraction at the lunocapitate joint than at the radiolunate joint. PMID:20141894

Conformational changes in the carpus during finger trap distraction.

PubMed

Leventhal, Evan L; Moore, Douglas C; Akelman, Edward; Wolfe, Scott W; Crisco, Joseph J

2010-02-01

Wrist distraction is a common treatment maneuver used clinically for the reduction of distal radial fractures and midcarpal dislocations. Wrist distraction is also required during wrist arthroscopy to access the radiocarpal joint and has been used as a test for scapholunate ligament injury. However, the effect of a distraction load on the normal wrist has not been well studied. The purpose of this study was to measure the three-dimensional conformational changes of the carpal bones in the normal wrist as a result of a static distractive load. Using computed tomography, the dominant wrists of 14 healthy volunteers were scanned at rest and during application of 98 N of distraction. Load was applied using finger traps, and volunteers were encouraged to relax their forearm muscles and to allow distraction of the wrist. The motions of the bones in the wrist were tracked between the unloaded and loaded trial using markerless bone registration. The average displacement vector of each bone relative to the radius was calculated, as were the interbone distances for 20 bone-bone interactions. Joint separation was estimated at the radiocarpal, midcarpal, and carpometacarpal joints in the direction of loading using the radius, lunate, capitate, and third metacarpal. With loading, the distance between the radius and third metacarpal increased an average of 3.3 mm +/- 3.1 in the direction of loading. This separation was primarily in the axial direction at the radiocarpal (1.0 mm +/- 1.0) and midcarpal (2.0 mm +/- 1.7) joints. There were minimal changes in the transverse direction within the distal row, although the proximal row narrowed by 0.98 mm +/- 0.7. Distraction between the radius and scaphoid (2.5 mm +/- 2.2) was 2.4 times greater than that between the radius and lunate (1.0 mm +/- 1.0). Carpal distraction has a significant (p < .01) effect on the conformation of the carpus, especially at the radiocarpal and midcarpal joints. In the normal wrist, external traction causes twice as much distraction at the lunocapitate joint than at the radiolunate joint. Copyright 2010. Published by Elsevier Inc.

Comparative assessment of bone pose estimation using Point Cluster Technique and OpenSim.

PubMed

Lathrop, Rebecca L; Chaudhari, Ajit M W; Siston, Robert A

2011-11-01

Estimating the position of the bones from optical motion capture data is a challenge associated with human movement analysis. Bone pose estimation techniques such as the Point Cluster Technique (PCT) and simulations of movement through software packages such as OpenSim are used to minimize soft tissue artifact and estimate skeletal position; however, using different methods for analysis may produce differing kinematic results which could lead to differences in clinical interpretation such as a misclassification of normal or pathological gait. This study evaluated the differences present in knee joint kinematics as a result of calculating joint angles using various techniques. We calculated knee joint kinematics from experimental gait data using the standard PCT, the least squares approach in OpenSim applied to experimental marker data, and the least squares approach in OpenSim applied to the results of the PCT algorithm. Maximum and resultant RMS differences in knee angles were calculated between all techniques. We observed differences in flexion/extension, varus/valgus, and internal/external rotation angles between all approaches. The largest differences were between the PCT results and all results calculated using OpenSim. The RMS differences averaged nearly 5° for flexion/extension angles with maximum differences exceeding 15°. Average RMS differences were relatively small (< 1.08°) between results calculated within OpenSim, suggesting that the choice of marker weighting is not critical to the results of the least squares inverse kinematics calculations. The largest difference between techniques appeared to be a constant offset between the PCT and all OpenSim results, which may be due to differences in the definition of anatomical reference frames, scaling of musculoskeletal models, and/or placement of virtual markers within OpenSim. Different methods for data analysis can produce largely different kinematic results, which could lead to the misclassification of normal or pathological gait. Improved techniques to allow non-uniform scaling of generic models to more accurately reflect subject-specific bone geometries and anatomical reference frames may reduce differences between bone pose estimation techniques and allow for comparison across gait analysis platforms.

[Effects of recombinant human alpha-2b and gamma interferons on bone marrow megakaryocyte progenitors (CFU-Meg) from patients with chronic myelocytic leukemia].

PubMed

Tanabe, Y; Dan, K; Kuriya, S; Nomura, T

1989-10-01

The effects of recombinant human interferon (IFN) alpha-2b and gamma on the bone marrow megakaryocyte progenitors (CFU-Meg) were compared between eight patients in the chronic phase of Ph1-positive chronic myelocytic leukemia (CML) and five hematologically normal patients. CFU-Meg was assayed in plasma clot culture added with phytohemagglutinin-stimulated leukocyte-conditioned medium as a source of colony stimulating activity. The average count of CFU-Meg colonies formed from the bone marrow of CML patients was 5.5 times that of normal controls. Spontaneous CFU-Meg colonies were grown in seven of eight CML patients, but in none of five controls. Colony formation by CFU-Meg in CML as well as normal bone marrow was suppressed by the two preparations of IFN in a dose dependent fashion. Their suppressive influence on colonies from CFU-Meg was comparable between CML and normal bone marrow at lower concentrations, but was less marked for CML than normal bone marrow at higher concentrations. The formation of CFU-Meg colonies from CML bone marrow was more severely suppressed by IFN-gamma than IFN-alpha-2b. Depletion of either T lymphocytes or adherent cells from the CML bone marrow cells diminished the suppressive effects of IFN-gamma, but had no influence on the effects of IFN-alpha-2b.

Space flight and bone formation.

PubMed

Doty, St B

2004-12-01

Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

Space flight and bone formation

NASA Technical Reports Server (NTRS)

Doty, St B.

2004-01-01

Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

Trabecular bone adaptation to low-magnitude high-frequency loading in microgravity.

PubMed

Torcasio, Antonia; Jähn, Katharina; Van Guyse, Maarten; Spaepen, Pieter; Tami, Andrea E; Vander Sloten, Jos; Stoddart, Martin J; van Lenthe, G Harry

2014-01-01

Exposure to microgravity causes loss of lower body bone mass in some astronauts. Low-magnitude high-frequency loading can stimulate bone formation on earth. Here we hypothesized that low-magnitude high-frequency loading will also stimulate bone formation under microgravity conditions. Two groups of six bovine cancellous bone explants were cultured at microgravity on a Russian Foton-M3 spacecraft and were either loaded dynamically using a sinusoidal curve or experienced only a static load. Comparable reference groups were investigated at normal gravity. Bone structure was assessed by histology, and mechanical competence was quantified using μCT and FE modelling; bone remodelling was assessed by fluorescent labelling and secreted bone turnover markers. Statistical analyses on morphometric parameters and apparent stiffness did not reveal significant differences between the treatment groups. The release of bone formation marker from the groups cultured at normal gravity increased significantly from the first to the second week of the experiment by 90.4% and 82.5% in response to static and dynamic loading, respectively. Bone resorption markers decreased significantly for the groups cultured at microgravity by 7.5% and 8.0% in response to static and dynamic loading, respectively. We found low strain magnitudes to drive bone turnover when applied at high frequency, and this to be valid at normal as well as at microgravity. In conclusion, we found the effect of mechanical loading on trabecular bone to be regulated mainly by an increase of bone formation at normal gravity and by a decrease in bone resorption at microgravity. Additional studies with extended experimental time and increased samples number appear necessary for a further understanding of the anabolic potential of dynamic loading on bone quality and mechanical competence.

What Is Breast in the Bone?

PubMed

Shemanko, Carrie S; Cong, Yingying; Forsyth, Amanda

2016-10-22

The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women. Breast cancer spreads to the bone in approximately 70% of cases with advanced breast cancer. Despite treatment, new bone metastases will still occur in 30%-50% of patients. Only 20% of patients with bone metastases survive five years after the diagnosis of bone metastasis. The breast cancer cells in the bone microenvironment release soluble factors that engage osteoclasts and/or osteoblasts and result in bone breakdown. The breakdown of the bone matrix, in turn, enhances the proliferation of the cancer cells, creating a vicious cycle. Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins. Interestingly, prolactin has the potential to affect multiple proteins that are involved in both breast development and likely bone metastasis, as well. Prolactin has normal bone homeostatic roles and, combined with the natural "recycling" of proteins in different tissues that can be used for breast development and function, or in bone function, increases the impact of prolactin signaling in breast cancer bone metastases. Thus, this review will focus on the role of prolactin in breast development, bone homeostasis and in breast cancer to bone metastases, covering the molecular aspects of the vicious cycle.

Fetal nasal bone length in the second trimester: comparison between population groups from different ethnic origins.

PubMed

Papasozomenou, Panayiota; Athanasiadis, Apostolos P; Zafrakas, Menelaos; Panteris, Eleftherios; Loufopoulos, Aristoteles; Assimakopoulos, Efstratios; Tarlatzis, Basil C

2016-03-01

To compare normal ranges of ultrasonographically measured fetal nasal bone length in the second trimester between different ethnic groups. A prospective, non-interventional study in order to establish normal ranges of fetal nasal bone length in the second trimester in a Greek population was conducted in 1220 singleton fetuses between 18 completed weeks and 23 weeks and 6 days of gestation. A literature search followed in order to identify similar studies in different population groups. Fetal nasal bone length mean values and percentiles from different population groups were compared. Analysis of measurements in the Greek population showed a linear association, i.e., increasing nasal bone length with increasing gestational age from 5.73 mm at 18 weeks to 7.63 mm at 23 weeks. Eleven studies establishing normal ranges of fetal nasal bone length in the second trimester were identified. Comparison of fetal nasal bone length mean values between the 12 population groups showed statistically significant differences (P<0.0001). Normal ranges of fetal nasal bone length in the second trimester vary significantly between different ethnic groups. Hence, distinct ethnic nomograms of fetal nasal bone length in the second trimester should be used in a given population rather than an international model.

The golden ratio of nasal width to nasal bone length.

PubMed

Goynumer, G; Yayla, M; Durukan, B; Wetherilt, L

2011-01-01

To calculate the ratio of fetal nasal width over nasal bone length at 14-39 weeks' gestation in Caucasian women. Fetal nasal bone length and nasal width at 14-39 weeks' gestation were measured in 532 normal fetuses. The mean and standard deviations of fetal nasal bone length, nasal width and their ratio to one another were calculated in normal fetuses according to the gestational age to establish normal values. A positive and linear correlation was detected between the nasal bone length and the gestational week, as between the nasal width and the gestational week. No linear growth pattern was found between the gestational week and the ratio of nasal width to nasal bone length, nearly equal to phi, throughout gestation. The ratio of nasal width to nasal bone length, approximately equal to phi, can be calculated at 14-38 weeks' gestation. This might be useful in evaluating fetal abnormalities.

High fat diet promotes achievement of peak bone mass in young rats.

PubMed

Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna; Pote, Satish T; Mittal, Monika; Chattopadhyay, Naibedya; Wani, Mohan R; Bhat, Manoj Kumar

2014-12-05

The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fat mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.

Onlay bone augmentation on mouse calvarial bone using a hydroxyapatite/collagen composite material with total blood or platelet-rich plasma.

PubMed

Ohba, Seigo; Sumita, Yoshinori; Umebayashi, Mayumi; Yoshimura, Hitoshi; Yoshida, Hisato; Matsuda, Shinpei; Kimura, Hideki; Asahina, Izumi; Sano, Kazuo

2016-01-01

The aim of this study was to assess newly formed onlay bone on mouse calvarial bone using a new artificial bone material, a hydroxyapatite/collagen composite, with total blood or platelet-rich plasma. The hydroxyapatite/collagen composite material with normal saline, total blood or platelet-rich plasma was transplanted on mouse calvarial bone. The mice were sacrificed and the specimens were harvested four weeks after surgery. The newly formed bone area was measured on hematoxylin and eosin stained specimens using Image J software. The hydroxyapatite/collagen composite materials with total blood or platelet-rich plasma induced a significantly greater amount of newly formed bone than that with normal saline. Moreover, bone marrow was observed four weeks after surgery in the transplanted materials with total blood or platelet-rich plasma but not with normal saline. However, there were no significant differences in the amount of newly formed bone between materials used with total blood versus platelet-rich plasma. The hydroxyapatite/collagen composite material was valid for onlay bone augmentation and this material should be soaked in total blood or platelet-rich plasma prior to transplantation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detection and evaluation of normal and malignant cells using laser-induced fluorescence spectroscopy.

PubMed

Khosroshahi, Mohamad E; Rahmani, Mahya

2012-01-01

The aim of this research is to study the normalized fluorescence spectra (intensity variations and area under the fluorescence signal), relative quantum yield, extinction coefficient and intracellular properties of normal and malignant human bone cells. Using Laser-Induced Fluorescence Spectroscopy (LIFS) upon excitation of 405 nm, the comparison of emission spectra of bone cells revealed that fluorescence intensity and the area under the spectra of malignant bone cells was less than that of normal. In addition, the area ratio and shape factor were changed. We obtained two emission bands in spectra of normal cells centered at about 486 and 575 nm and for malignant cells about 482 and 586 nm respectively, which are most likely attributed to NADH and riboflavins. Using fluorescein sodium emission spectrum, the relative quantum yield of bone cells is numerically determined.

Sclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing

NASA Astrophysics Data System (ADS)

Spatz, J. M.; Ellman, R.; Cloutier, A. M.; Louis, L.; van Vliet, M.; Dwyer, D.; Stolina, M.; Ke, H. Z.; Bouxsein, M. L.

2017-02-01

Whereas much is known regarding the musculoskeletal responses to full unloading, little is known about the physiological effects and response to pharmacological agents in partial unloading (e.g. Moon and Mars) environments. To address this, we used a previously developed ground-based model of partial weight-bearing (PWB) that allows chronic exposure to reduced weight-bearing in mice to determine the effects of murine sclerostin antibody (SclAbII) on bone microstructure and strength across different levels of mechanical unloading. We hypothesize that treatment with SclAbII would improve bone mass, microarchitecture and strength in all loading conditions, but that there would be a greater skeletal response in the normally loaded mice than in partially unloaded mice suggesting the importance of combined countermeasures for exploration-class long duration spaceflight missions. Eleven-week-old female mice were assigned to one of four loading groups: normal weight-bearing controls (CON) or weight-bearing at 20% (PWB20), 40% (PWB40) or 70% (PWB70) of normal. Mice in each group received either SclAbII (25 mg/kg) or vehicle (VEH) via twice weekly subcutaneous injection for 3 weeks. In partially-unloaded VEH-treated groups, leg BMD decreased -5 to -10% in a load-dependent manner. SclAbII treatment completely inhibited bone deterioration due to PWB, with bone properties in SclAbII-treated groups being equal to or greater than those of CON, VEH-treated mice. SclAbII treatment increased leg BMD from +14 to +18% in the PWB groups and 30 ± 3% in CON (p < 0.0001 for all). Trabecular bone volume, assessed by μCT at the distal femur, was lower in all partially unloaded VEH-treated groups vs. CON-VEH (p < 0.05), and was 2-3 fold higher in SclAbII-treated groups (p < 0.001). Midshaft femoral strength was also significantly higher in SclAbII vs. VEH-groups in all-loading conditions. These results suggest that greater weight bearing leads to greater benefits of SclAbII on bone mass, particularly in the trabecular compartment. Altogether, these results demonstrate the efficacy of sclerostin antibody therapy in preventing astronaut bone loss during terrestrial solar system exploration.

Sclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing.

PubMed

Spatz, J M; Ellman, R; Cloutier, A M; Louis, L; van Vliet, M; Dwyer, D; Stolina, M; Ke, H Z; Bouxsein, M L

2017-02-01

Whereas much is known regarding the musculoskeletal responses to full unloading, little is known about the physiological effects and response to pharmacological agents in partial unloading (e.g. Moon and Mars) environments. To address this, we used a previously developed ground-based model of partial weight-bearing (PWB) that allows chronic exposure to reduced weight-bearing in mice to determine the effects of murine sclerostin antibody (SclAbII) on bone microstructure and strength across different levels of mechanical unloading. We hypothesize that treatment with SclAbII would improve bone mass, microarchitecture and strength in all loading conditions, but that there would be a greater skeletal response in the normally loaded mice than in partially unloaded mice suggesting the importance of combined countermeasures for exploration-class long duration spaceflight missions. Eleven-week-old female mice were assigned to one of four loading groups: normal weight-bearing controls (CON) or weight-bearing at 20% (PWB20), 40% (PWB40) or 70% (PWB70) of normal. Mice in each group received either SclAbII (25mg/kg) or vehicle (VEH) via twice weekly subcutaneous injection for 3 weeks. In partially-unloaded VEH-treated groups, leg BMD decreased -5 to -10% in a load-dependent manner. SclAbII treatment completely inhibited bone deterioration due to PWB, with bone properties in SclAbII-treated groups being equal to or greater than those of CON, VEH-treated mice. SclAbII treatment increased leg BMD from +14 to +18% in the PWB groups and 30 ± 3% in CON (p< 0.0001 for all). Trabecular bone volume, assessed by μCT at the distal femur, was lower in all partially unloaded VEH-treated groups vs. CON-VEH (p< 0.05), and was 2-3 fold higher in SclAbII-treated groups (p< 0.001). Midshaft femoral strength was also significantly higher in SclAbII vs. VEH-groups in all-loading conditions. These results suggest that greater weight bearing leads to greater benefits of SclAbII on bone mass, particularly in the trabecular compartment. Altogether, these results demonstrate the efficacy of sclerostin antibody therapy in preventing astronaut bone loss during terrestrial solar system exploration. Copyright © 2017 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Microsatellite Analysis for Identification of Individuals Using Bone from the Extinct Steller's Sea Cow (Hydrodamalis gigas).

PubMed

Warner, Jeffery F; Harpole, Michael G; Crerar, Lorelei D

2017-01-01

Microsatellite DNA can provide more detailed population genetic information than mitochondrial DNA which is normally used to research ancient bone. The methods detailed in this chapter can be utilized for any type of bone. However, for this example, four microsatellite loci were isolated from Steller's sea cow (Hydrodamalis gigas) using published primers for manatee and dugong microsatellites. The primers DduC05 (Broderick et al., Mol Ecol Notes 6:1275-1277, 2007), Tmakb60, TmaSC5 (Pause et al., Mol Ecol Notes 6: 1073-1076, 2007), and TmaE11 (Garcia-Rodriguez et al., Mol Ecol 12:2161-2163, 2000) all successfully amplified microsatellites from H. gigas. The DNA samples were from bone collected on Bering or St. Lawrence Islands. DNA was analyzed using primers with the fluorescent label FAM-6. Sequenced alleles were then used to indicate a difference in the number of repeats and thus a difference in individuals. This is the first time that H. gigas microsatellite loci have been isolated. These techniques for ancient bone microsatellite analysis allow an estimate of population size for a newly discovered St. Lawrence Island sea cow population.

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

PubMed Central

Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

2015-01-01

Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain.

PubMed

Pacheco-Costa, Rafael; Davis, Hannah M; Sorenson, Chad; Hon, Mary C; Hassan, Iraj; Reginato, Rejane D; Allen, Matthew R; Bellido, Teresita; Plotkin, Lilian I

2015-12-01

Connexin 43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43(ΔCT/fl)) were studied. Cx43(ΔCT/fl) mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43(fl/fl) controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43(ΔCT) is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43(ΔCT) mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43(ΔCT) were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. Copyright © 2015 Elsevier Inc. All rights reserved.

An improved instrument for the in vivo detection of lead in bone.

PubMed Central

Gordon, C L; Chettle, D R; Webber, C E

1993-01-01

An improved instrument for the fluorescence excitation measurement of concentrations of lead in bone has been developed. This is based on a large area high purity germanium detector and a point source of 109Cd. The source is positioned in a tungsten shield at the centre of the detector face such that 88keV photons cannot enter the detector directly. In vivo measurements are calibrated with plaster of Paris phantoms. Occupationally non-exposed men show a minimum detectable concentration of about 6 micrograms/g bone mineral. Measurements of tibia lead concentrations in 30 non-occupationally exposed men between the ages of 23 and 73 showed an annual increment of 0.46 microgram/g bone mineral/year. The mean deviation from the regression of tibia lead upon age was 3.5 micrograms/g bone mineral. Tibia lead concentration in one subject with a history of exposure to lead was 69.6 (SD 3.5) micrograms/g bone mineral. The improved precision of the point source large detector system means that greater confidence can be placed on the results of in vivo measurements of lead concentration. This will allow studies of the natural history of non-occupational lead accumulation in normal subjects and should permit investigations of the efficacy of therapeutic interventions in subjects poisoned with lead. PMID:8343425

High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats

PubMed Central

Kasai, Shunji; Ito, Akemi; Shindo, Kaori; Toyoshi, Tohru; Bando, Masahiro

2015-01-01

Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. PMID:26147575

Biaxial Normal Strength Behavior in the Axial-Transverse Plane for Human Trabecular Bone—Effects of Bone Volume Fraction, Microarchitecture, and Anisotropy

PubMed Central

Sanyal, Arnav; Keaveny, Tony M.

2013-01-01

The biaxial failure behavior of the human trabecular bone, which has potential relevance both for fall and gait loading conditions, is not well understood, particularly for low-density bone, which can display considerable mechanical anisotropy. Addressing this issue, we investigated the biaxial normal strength behavior and the underlying failure mechanisms for human trabecular bone displaying a wide range of bone volume fraction (0.06–0.34) and elastic anisotropy. Micro-computer tomography (CT)-based nonlinear finite element analysis was used to simulate biaxial failure in 15 specimens (5 mm cubes), spanning the complete biaxial normal stress failure space in the axial-transverse plane. The specimens, treated as approximately transversely isotropic, were loaded in the principal material orientation. We found that the biaxial stress yield surface was well characterized by the superposition of two ellipses—one each for yield failure in the longitudinal and transverse loading directions—and the size, shape, and orientation of which depended on bone volume fraction and elastic anisotropy. However, when normalized by the uniaxial tensile and compressive strengths in the longitudinal and transverse directions, all of which depended on bone volume fraction, microarchitecture, and mechanical anisotropy, the resulting normalized biaxial strength behavior was well described by a single pair of (longitudinal and transverse) ellipses, with little interspecimen variation. Taken together, these results indicate that the role of bone volume fraction, microarchitecture, and mechanical anisotropy is mostly accounted for in determining the uniaxial strength behavior and the effect of these parameters on the axial-transverse biaxial normal strength behavior per se is minor. PMID:24121715

Normal bone and soft tissue distribution of fluorine-18-sodium fluoride and artifacts on 18F-NaF PET/CT bone scan: a pictorial review.

PubMed

Sarikaya, Ismet; Elgazzar, Abdelhamid H; Sarikaya, Ali; Alfeeli, Mahmoud

2017-10-01

Fluorine-18-sodium fluoride (F-NaF) PET/CT is a relatively new and high-resolution bone imaging modality. Since the use of F-NaF PET/CT has been increasing, it is important to accurately assess the images and be aware of normal distribution and major artifacts. In this pictorial review article, we will describe the normal uptake patterns of F-NaF in the bone tissues, particularly in complex structures, as well as its physiologic soft tissue distribution and certain artifacts seen on F-NaF PET/CT images.

Gene Expression in Bone

NASA Astrophysics Data System (ADS)

D'Ambrogio, A.

Skeletal system has two main functions, to provide mechanical integrity for both locomotion and protection and to play an important role in mineral homeostasis. There is extensive evidence showing loss of bone mass during long-term Space-Flights. The loss is due to a break in the equilibrium between the activity of osteoblasts (the cells that forms bone) and the activity of osteoclasts (the cells that resorbs bone). Surprisingly, there is scanty information about the possible altered gene expression occurring in cells that form bone in microgravity.(Just 69 articles result from a "gene expression in microgravity" MedLine query.) Gene-chip or microarray technology allows to screen thousands of genes at the same time: the use of this technology on samples coming from cells exposed to microgravity could provide us with many important informations. For example, the identification of the molecules or structures which are the first sensors of the mechanical stress derived from lack of gravity, could help in understanding which is the first event leading to bone loss due to long-term exposure to microgravity. Consequently, this structure could become a target for a custom-designed drug. It is evident that bone mass loss, observed during long-time stay in Space, represents an accelerated model of what happens in aging osteoporosis. Therefore, the discovery and design of drugs able to interfere with the bone-loss process, could help also in preventing negative physiological processes normally observed on Earth. Considering the aims stated above, my research is designed to:

[Atraumatic bone expansion: Interest of piezo-surgery, conicals expanders and immediate implantation combination].

PubMed

Iraqui, O; Lakhssassi, N; Berrada, S; Merzouk, N

2016-06-01

The durability of dental implants depends on the presence of a 1mm coating bone sheath all around the fixture. Therefore, bone resorption represents a challenge for the practitioner. Bone expansion is a surgical technique that allows the management of horizontal bone atrophy. Cortical bone splitting allows for an enlargement of the residual crest by displacement of the vestibular bone flap. The immediate placement of implants secures the widening and allows for a 97% survival rate. However, bone expansion is hard to undertake in sites with high bone density. Furthermore, the use of traditional instruments increases patient's stress and the risk for an interruptive fracture during bone displacement. Non-traumatic bone expansion is one solution to this problem. The combination of piezo-surgery and conical expanders allows for a secured displacement of the selected bone flap as well as an immediate implant placement, avoiding the risk of slipping, overheating, or fracture, all within an undeniable operative comfort. Non-traumatic bone expansion is a reliable, reproducible, conservative, and economical in time and cost procedure. We describe our atraumatic bone expension and immediate implant placement technique in high bone density sites and illustrate it by a clinical case. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Bone growth and turnover in progesterone receptor knockout mice.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda

2008-05-01

The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bonesmore » of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.« less

Tibial changes in experimental disuse osteoporosis in the monkey

NASA Technical Reports Server (NTRS)

Young, D. R.; Niklowitz, W. J.; Steele, C. R.

1983-01-01

The mechanical properties and structural changes in the monkey tibia with disuse osteoporosis and during subsequent recovery are investigated. Bone mending stiffness is evaluated in relation to microscopic changes in cortical bone and Norland bone mineral analysis. Restraint in the semireclined position is found to produce regional losses of bone most obviously in the anterior-proximal tibiae. After six months of restraint, the greatest losses of bone mineral in the proximal tibiae range from 23 percent to 31 percent; the largest changes in bone stiffness range from 36 percent to 40 percent. Approximately eight and one-half months of recovery are required to restore the normal bending properties. Even after 15 months of recovery, however, the bone mineral content does not necessarily return to normal levels. Histologically, resorption cavities in cortical bone are seen within one month of restraint; by two and one-half months of restraint there are large resorption cavities subperiosteally, endosteally, and intracortically. After 15 months of recovery, the cortex consists mainly of first-generation haversian systems. After 40 months, the cortex appears normal, with numerous secondary and tertiary generations of haversian systems.

Clec11a/osteolectin is an osteogenic growth factor that promotes the maintenance of the adult skeleton

PubMed Central

Yue, Rui; Shen, Bo; Morrison, Sean J

2016-01-01

Bone marrow stromal cells maintain the adult skeleton by forming osteoblasts throughout life that regenerate bone and repair fractures. We discovered that subsets of these stromal cells, osteoblasts, osteocytes, and hypertrophic chondrocytes secrete a C-type lectin domain protein, Clec11a, which promotes osteogenesis. Clec11a-deficient mice appeared developmentally normal and had normal hematopoiesis but reduced limb and vertebral bone. Clec11a-deficient mice exhibited accelerated bone loss during aging, reduced bone strength, and delayed fracture healing. Bone marrow stromal cells from Clec11a-deficient mice showed impaired osteogenic differentiation, but normal adipogenic and chondrogenic differentiation. Recombinant Clec11a promoted osteogenesis by stromal cells in culture and increased bone mass in osteoporotic mice in vivo. Recombinant human Clec11a promoted osteogenesis by human bone marrow stromal cells in culture and in vivo. Clec11a thus maintains the adult skeleton by promoting the differentiation of mesenchymal progenitors into mature osteoblasts. In light of this, we propose to call this factor Osteolectin. DOI: http://dx.doi.org/10.7554/eLife.18782.001 PMID:27976999

Mice with cancer-induced bone pain show a marked decline in day/night activity.

PubMed

Majuta, Lisa A; Guedon, Jean-Marc G; Mitchell, Stefanie A T; Kuskowski, Michael A; Mantyh, Patrick W

2017-09-01

Cancer-induced bone pain (CIBP) is the most common type of pain with cancer. In humans, this pain can be difficult to control and highly disabling. A major problem with CIBP in humans is that it increases on weight-bearing and/or movement of a tumor-bearing bone limiting the activity and functional status of the patient. Currently, there is less data concerning whether similar negative changes in activity occur in rodent models of CIBP. To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Osteosarcoma cells were injected and confined to 1 femur of the adult male mouse. Every 7 days, spontaneous horizontal and vertical activities were assessed over a 20-hour day and night period using automated activity boxes. Mechanical hypersensitivity of the hind paw skin was assessed using von Frey testing. As the tumor cells grew within the femur, there was a significant decline in horizontal and vertical activity during the times of the day/night when the mice are normally most active. Mice also developed significant hypersensitivity in the skin of the hind paw in the tumor-bearing limb. Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status.

Normalization of cortical bone density in children and adolescents with hyperthyroidism treated with antithyroid medication.

PubMed

Numbenjapon, N; Costin, G; Pitukcheewanont, P

2012-09-01

We assessed bone size and bone density (BD) measurements using computed tomography (CT) in children and adolescents with hyperthyroidism treated with antithyroid medication. We found that cortical BD appeared to improve at 1 year and normalize at 2 years in all tested patients. Our previous study demonstrated that cortical BD in children and adolescents with untreated hyperthyroidism was significantly decreased as compared to age-, sex- and ethnicity-matched healthy controls. The present report evaluated whether attainment of euthyroidism by medical antithyroid treatment was able to improve or normalize cortical BD in these patients. Anthropometrics and three-dimensional CT bone measurements including cross-sectional area (CSA), cortical bone area (CBA) and cortical BD at midshaft of the femur (cortical bone), and CSA and BD of L(1) to L(3) vertebrae (cancellous bone) in 15 children and adolescents after 1- and 2-year treatments with antithyroid medication were reviewed and compared to their pretreatment results. All patients were euthyroid at 1 and 2 years after medical antithyroid treatment. After adjusting for age, height, weight and Tanner stage, a significant increase in cortical BD in all patients (15/15) was found after 1 year of treatment (P < 0.001). Normalization of cortical BD was demonstrated in all tested patients (10/15) after 2 years. There were no significant changes in the other cancellous or cortical bone parameters. Cortical BD was improved at 1 year and normalized at 2 years in hyperthyroid patients rendered euthyroid with antithyroid medication.

Eldecalcitol normalizes bone turnover markers regardless of their pre-treatment levels.

PubMed

Shiraki, Masataka; Saito, Hitoshi; Matsumoto, Toshio

2012-09-01

Three-year treatment with eldecalcitol has been shown to improve lumbar and total hip bone mineral density (BMD), decrease bone turnover markers, and lower the incidences of vertebral and wrist fractures in patients with osteoporosis more than with treatment with alfacalcidol under vitamin D repletion. The purpose of this study was to determine whether there was a risk of eldecalcitol causing severely suppressed bone turnover in osteoporosis patients with low pre-treatment levels of bone turnover markers. Post-hoc analysis was conducted on the data from a 3-year, randomized, double-blind, active-comparator, clinical trial of eldecalcitol versus alfacalcidol under vitamin D repletion conducted in Japan. Enrolled patients with baseline measurements of bone turnover markers were stratified into tertiles according to their pre-treatment levels of serum bone-specific alkaline phosphatase, serum procollagen type I N-terminal propeptide, or urinary collagen-N-telopeptide. Eldecalcitol treatment rapidly reduced bone turnover markers, and kept them within the normal range. However, in the patients whose baseline values for bone turnover were low, eldecalcitol treatment did not further reduce bone turnover markers during the 3-year treatment period. Further long-term observation may be required to reach the conclusion. CLINICALTRIALS.GOV NUMBER: NCT00144456. Eldecalcitol normalizes, but does not overly suppress, bone turnover regardless of baseline levels of bone turnover markers. Thus, it is unlikely that eldecalcitol treatment will increase the risk of severely suppressed bone turnover and therefore deterioration of bone quality, at least for a treatment duration of 3 years.

Distribution Characteristics of Air-Bone Gaps – Evidence of Bias in Manual Audiometry

PubMed Central

Margolis, Robert H.; Wilson, Richard H.; Popelka, Gerald R.; Eikelboom, Robert H.; Swanepoel, De Wet; Saly, George L.

2015-01-01

Objective Five databases were mined to examine distributions of air-bone gaps obtained by automated and manual audiometry. Differences in distribution characteristics were examined for evidence of influences unrelated to the audibility of test signals. Design The databases provided air- and bone-conduction thresholds that permitted examination of air-bone gap distributions that were free of ceiling and floor effects. Cases with conductive hearing loss were eliminated based on air-bone gaps, tympanometry, and otoscopy, when available. The analysis is based on 2,378,921 threshold determinations from 721,831 subjects from five databases. Results Automated audiometry produced air-bone gaps that were normally distributed suggesting that air- and bone-conduction thresholds are normally distributed. Manual audiometry produced air-bone gaps that were not normally distributed and show evidence of biasing effects of assumptions of expected results. In one database, the form of the distributions showed evidence of inclusion of conductive hearing losses. Conclusions Thresholds obtained by manual audiometry show tester bias effects from assumptions of the patient’s hearing loss characteristics. Tester bias artificially reduces the variance of bone-conduction thresholds and the resulting air-bone gaps. Because the automated method is free of bias from assumptions of expected results, these distributions are hypothesized to reflect the true variability of air- and bone-conduction thresholds and the resulting air-bone gaps. PMID:26627469

Bone mineral density level by dual energy X-ray absorptiometry in rheumatoid arthritis.

PubMed

Makhdoom, Asadullah; Rahopoto, Muhammad Qasim; Awan, Shazia; Tahir, Syed Muhammad; Memon, Shazia; Siddiqui, Khaleeque Ahmed

2017-01-01

To observe the level of bone mineral density by Dual Energy X-ray Absorptiometry in rheumatoid arthritis patients. The observational study was conducted at Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan, from January 2011 to December 2014. Bone mineral density was measured from the femoral neck, ward's triangle and lumbar spine, in patients 25-55 years of age, who were diagnosed with rheumatoid arthritis. All the cases were assessed for bone mineral density from appendicular as well as axial skeleton. Data was collected through a designed proforma and analysis was performed using SPSS 21. Of the 229 rheumatoid arthritis patients, 33(14.4%) were males. Five (15.1%) males had normal bone density, 14(42.4%) had osteopenia and 14(42.4%) had osteoporosis. Of the 196(85.5%) females, 45(29.9%) had normal bone density, 72 (37.7%) had osteopenia and 79(40.30%) had osteoporosis. Of the 123(53.7%) patients aged 30-50 years, 38(30.9%) had normal bone density, 59(48.0%) had osteopenia, and 26(21.1%) had osteoporosis. Of the 106(46.3%) patients over 50 years, 12(11.3%) had normal bone density, 27 (25.5%) had osteopenia and 67(63.2%) had osteoporosis. Osteoporosis and osteopenia were most common among rheumatoid arthritis patients. Assessment of bone mineral density by Dual Energy X-ray Absorptiometry can lead to quick relief in the clinical symptoms with timely therapy.

Gross, histologic, and computed tomographic characterization of nonpathological intrascleral cartilage and bone in the domestic goat (Capra aegagrus hircus).

PubMed

Tusler, Charlotte A; Good, Kathryn L; Maggs, David J; Zwingenberger, Allison L; Reilly, Christopher M

2017-05-01

To characterize grossly, histologically, and via computed tomography (CT) the appearance of intrascleral cartilage, bone, or both in domestic goats with otherwise normal eyes and to correlate this with age, sex, and breed. Sixty-eight domestic goats (89 eyes). Forty-nine formalin-fixed globes from 38 goats underwent high-resolution CT, and gross and light microscopic examination. An additional 40 eyes from 30 goats underwent light microscopy only. Age, breed, and sex of affected goats were retrieved from medical records. Considering all methods of evaluation collectively, cartilage was detected in 42% of eyes (44% of goats) and bone in 11% of eyes (12% of goats); bone was never seen without cartilage. Goats in which bone, cartilage, or both were detected ranged from 0.25 to 13 (median = 3.5) years of age, represented 11 of 12 breeds of the study population, and had a male:female ratio of 11:19. Bone was detected in the eyes of significantly more males (n = 8) than females (n = 2). No sex predilection was noted for cartilage alone. Histology revealed intrascleral chondrocyte-like cells, hyaline cartilage, and islands of lamellar bone. Some regions of bone had central, adipose-rich, marrow-like cavities. CT localized mineralized tissue as adjacent to or partially surrounding the optic nerve head. This is the first report of intrascleral bone or cartilage in a normal goat and of intrascleral bone in an otherwise normal mammal. The high prevalence of intrascleral cartilage and bone in this study suggests that this finding is normal and likely represents an adaptation in goats. © 2016 American College of Veterinary Ophthalmologists.

Growth, body composition, and bone density following pediatric liver transplantation.

PubMed

Sheikh, Amin; Cundy, Tim; Evans, Helen Maria

2018-04-24

Patients transplanted for cholestatic liver disease are often significantly fat-soluble vitamin deficient and malnourished pretransplant, with significant corticosteroid exposure post-transplant, with increasing evidence of obesity and metabolic syndrome post-LT. Our study aimed to assess growth, body composition, and BMD in patients post-pediatric LT. Body composition and bone densitometry scans were performed on 21 patients. Pre- and post-transplant anthropometric data were analyzed. Bone health was assessed using serum ALP, calcium, phosphate, and procollagen-1-N-peptide levels. Median ages at transplant and at this assessment were 2.7 and 10.6 years, respectively. Physiological markers of bone health, median z-scores for total body, and lumbar spine aBMD were normal. Bone area was normal for height and BMAD at L3 was normal for age, indicating, respectively, normal cortical and trabecular bone accrual. Median z-scores for weight, height, and BMI were 0.6, -0.9, 1.8 and 0.6, 0.1, 0.8 pre- and post-transplant, respectively. Total body fat percentages measured on 21 body composition scans revealed 2 underweight, 7 normal, 6 overweight, and 6 obese. Bone mass is preserved following pediatric LT with good catch-up height. About 52% of patients were either overweight/obese post-transplant, potentially placing them at an increased risk of metabolic syndrome and its sequelae in later life. BMI alone is a poor indicator of nutritional status post-transplant. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Regional responsiveness of the tibia to intermittent administration of parathyroid hormone as affected by skeletal unloading

NASA Technical Reports Server (NTRS)

Halloran, B. P.; Bikle, D. D.; Harris, J.; Tanner, S.; Curren, T.; Morey-Holton, E.

1997-01-01

To determine whether the acute inhibition of bone formation and deficit in bone mineral induced by skeletal unloading can be prevented, we studied the effects of intermittent parathyroid hormone (PTH) administration (8 micrograms/100 g/day) on growing rats submitted to 8 days of skeletal unloading. Loss of weight bearing decreased periosteal bone formation by 34 and 51% at the tibiofibular junction and tibial midshaft, respectively, and reduced the normal gain in tibial mass by 35%. Treatment with PTH of normally loaded and unloaded animals increased mRNA for osteocalcin (+58 and +148%, respectively), cancellous bone volume in the proximal tibia (+41 and +42%, respectively), and bone formation at the tibiofibular junction (+27 and +27%, respectively). Formation was also stimulated at the midshaft in unloaded (+47%, p < 0.05), but not loaded animals (-3%, NS). Although cancellous bone volume was preserved in PTH-treated, unloaded animals, PTH did not restore periosteal bone formation to normal nor prevent the deficit in overall tibial mass induced by unloading. We conclude that the effects of PTH on bone formation are region specific and load dependent. PTH can prevent the decrease in cancellous bone volume and reduce the decrement in cortical bone formation induced by loss of weight bearing.

Fractal analysis of bone structure with applications to osteoporosis and microgravity effects

NASA Astrophysics Data System (ADS)

Acharya, Raj S.; LeBlanc, Adrian; Shackelford, Linda; Swarnakar, Vivek; Krishnamurthy, Ram; Hausman, E.; Lin, Chin-Shoou

1995-05-01

We characterize the trabecular structure with the aid of fractal dimension. We use alternating sequential filters (ASF) to generate a nonlinear pyramid for fractal dimension computations. We do not make any assumptions of the statistical distributions of the underlying fractal bone structure. The only assumption of our scheme is the rudimentary definition of self-similarity. This allows us the freedom of not being constrained by statistical estimation schemes. With mathematical simulations, we have shown that the ASF methods outperform other existing methods for fractal dimension estimation. We have shown that the fractal dimension remains the same when computed with both the x-ray images and the MRI images of the patella. We have shown that the fractal dimension of osteoporotic subjects is lower than that of the normal subjects. In animal models, we have shown that the fractal dimension of osteoporotic rats was lower than that of the normal rats. In a 17 week bedrest study, we have shown that the subject's prebedrest fractal dimension is higher than that of the postbedrest fractal dimension.

Fractal analysis of bone structure with applications to osteoporosis and microgravity effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acharya, R.S.; Swarnarkar, V.; Krishnamurthy, R.

1995-12-31

The authors characterize the trabecular structure with the aid of fractal dimension. The authors use Alternating Sequential filters to generate a nonlinear pyramid for fractal dimension computations. The authors do not make any assumptions of the statistical distributions of the underlying fractal bone structure. The only assumption of the scheme is the rudimentary definition of self similarity. This allows them the freedom of not being constrained by statistical estimation schemes. With mathematical simulations, the authors have shown that the ASF methods outperform other existing methods for fractal dimension estimation. They have shown that the fractal dimension remains the same whenmore » computed with both the X-Ray images and the MRI images of the patella. They have shown that the fractal dimension of osteoporotic subjects is lower than that of the normal subjects. In animal models, the authors have shown that the fractal dimension of osteoporotic rats was lower than that of the normal rats. In a 17 week bedrest study, they have shown that the subject`s prebedrest fractal dimension is higher than that of the postbedrest fractal dimension.« less

What We Should Know Before Using Tissue Engineering Techniques to Repair Injured Tendons: A Developmental Biology Perspective

PubMed Central

Liu, Chia-Feng; Aschbacher-Smith, Lindsey; Barthelery, Nicolas J.; Dyment, Nathaniel; Butler, David

2011-01-01

Tendons connect muscles to bones, and serve as the transmitters of force that allow all the movements of the body. Tenocytes are the basic cellular units of tendons, and produce the collagens that form the hierarchical fiber system of the tendon. Tendon injuries are common, and difficult to repair, particularly in the case of the insertion of tendon into bone. Successful attempts at cell-based repair therapies will require an understanding of the normal development of tendon tissues, including their differentiated regions such as the fibrous mid-section and fibrocartilaginous insertion site. Many genes are known to be involved in the formation of tendon. However, their functional roles in tendon development have not been fully characterized. Tissue engineers have attempted to generate functional tendon tissue in vitro. However, a lack of knowledge of normal tendon development has hampered these efforts. Here we review studies focusing on the developmental mechanisms of tendon development, and discuss the potential applications of a molecular understanding of tendon development to the treatment of tendon injuries. PMID:21314435

Four weeks of training in a sledge jump system improved the jump pattern to almost natural reactive jumps.

PubMed

Kramer, Andreas; Ritzmann, Ramona; Gruber, Markus; Gollhofer, Albert

2012-01-01

In spite of extensive training regimens during long-term space missions with existing training devices, astronauts suffer from muscle and bone loss. It has been suggested that reactive jumps inducing high forces in the muscles-consequently exposing the bones to high strains-help to counteract these degradations. In a previous study, a new sledge jump system (SJS) was found to allow fairly natural reactive jumps. The aim of the present study was to evaluate if training in the SJS would further reduce the differences between jumps in the SJS and normal jumps, particularly with respect to ground reaction forces (GRF) and rate of force development (RFD). Sixteen participants in a training group (TG) and 16 in a control group (CON) were tested before and after the TGs four-week hopping training in the SJS. During the tests, kinetic, kinematic and electromyographic data were compared between hops on the ground and in the SJS. After the training period, the GRF, the RFD and the leg stiffness in the SJS significantly increased for the TG (but not for CON) by 10, 35 and 38%, respectively. The kinematic and electromyographic data showed no significant changes. A short training regimen in the SJS reduced the differences between jumps in the SJS and normal jumps. Considering that a natural movement that exposes the muscles and thus also the bones to high loads is regarded as important for the preservation of muscle and bone, the SJS seems to be a promising countermeasure.

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

PubMed Central

Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

2012-01-01

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

Does bone measurement on the radius indicate skeletal status. Concise communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazess, R.B.; Peppler, W.W.; Chesney, R.W.

1984-03-01

Single-photon (I-125) absorptiometry was used to measure bone mineral content (BMC) of the distal third of the radius, and dual-photon absorptiometry (Gd-153) was used to measure total-body bone mineral (TBBM), as well as the BMC of major skeletal regions. Measurements were done in normal females, normal males, osteoporotic females, osteoporotic males, and renal patients. The BMC of the radius predicted TBBM well in normal subjects, but was less satisfactory in the patient groups. The spinal BMC was predicted with even lower accuracy from radius measurement. The error in predicting areal density (bone mass per unit projected skeletal area) of themore » lumbar and thoracic spine from the radius BMC divided by its width was smaller, but the regressions differed significantly among normals, osteoporotics, and renal patients. There was a preferential spinal osteopenia in the osteoporotic group and in about half of the renal patients. Bone measurements on the radius can indicate overall skeletal status in normal subjects and to a lesser degree in patients, but these radius measurements are inaccurate, even on the average, as an indicator of spinal state.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagemaker, G.; Visser, T.P.; van Bekkum, D.W.

alpha-Thalassemic heterozygous (Hbath/+) mice were used to investigate the possible selective advantage of transplanted normal (+/+) hemopoietic cells. Without conditioning by total-body irradiation (TBI), infusion of large numbers of normal bone marrow cells failed to correct the thalassemic peripheral blood phenotype. Since the recipients' stem cells are normal with respect to number and differentiation capacity, it was thought that the transplanted stem cells were not able to lodge, or that they were not stimulated to proliferate. Therefore, a nonlethal dose of TBI was given to temporarily reduce endogenous stem cell numbers and hemopoiesis. TBI doses of 2 or 3 Gymore » followed by infusion of normal bone marrow cells proved to be effective in replacing the thalassemic red cells by normal red cells, whereas a dose of 1 Gy was ineffective. It is concluded that cure of thalassemia by bone marrow transplantation does not necessarily require eradication of thalassemic stem cells. Consequently, the objectives of conditioning regimens for bone marrow transplantation of thalassemic patients (and possibly other nonmalignant hemopoietic disorders) should be reconsidered.« less

The C-terminal fragment of parathyroid hormone-related peptide promotes bone formation in diabetic mice with low-turnover osteopaenia

PubMed Central

Lozano, D; Fernández-de-Castro, L; Portal-Núñez, S; López-Herradón, A; Dapía, S; Gómez-Barrena, E; Esbrit, P

2011-01-01

BACKGROUND AND PURPOSE Current data suggest that parathyroid hormone (PTH)-related peptide (PTHrP) domains other than the N-terminal PTH-like domain contribute to its role as an endogenous bone anabolic factor. PTHrP-107-139 inhibits bone resorption, a fact which has precluded an unequivocal demonstration of its possible anabolic action in vivo. We thus sought to characterize the osteogenic effects of this peptide using a mouse model of diabetic low-turnover osteopaenia. EXPERIMENTAL APPROACH PTHrP-107-139 was administered to streptozotocin-induced diabetic mice, with or without bone marrow ablation, for 13 days. Osteopaenia was confirmed by dual-energy X-ray absorptiometry and microcomputed tomography analysis. Histological analysis was performed on paraffin-embedded bone tissue sections by haematoxylin/eosin and Masson's staining, and tartrate-resistent acid phosphatase immunohistochemistry. Mouse bone marrow stromal cells and osteoblastic MC3T3-E1 cells were cultured in normal and/or high glucose (HG) medium. Osteogenic and adipogenic markers were assessed by real-time PCR, and PTHrP and the PTH1 receptor protein expression by Western blot analysis. KEY RESULTS PTHrP-107-139 reversed the alterations in bone structure and osteoblast function, and also promoted bone healing after marrow ablation without affecting the number of osteoclast-like cells in diabetic mice. This peptide also reversed the high-glucose-induced changes in osteogenic differentiation in both bone marrow stromal cells and the more differentiated MC3T3-E1 cells. CONCLUSIONS AND IMPLICATIONS These findings demonstrate that PTHrP-107-139 promotes bone formation in diabetic mice. This mouse model and in vitro cell cultures allowed us to identify various anabolic effects of this peptide in this scenario. PMID:21175568

Osteopathia striata with cranial sclerosis: clinical, radiological, and bone histological findings in an adolescent girl.

PubMed

Ward, L M; Rauch, F; Travers, R; Roy, M; Montes, J; Chabot, G; Glorieux, F H

2004-08-15

Osteopathia striata with cranial sclerosis (OS-CS) is a rare skeletal dysplasia characterized by linear striations of the long bones, osteosclerosis of the cranium, and extra-skeletal anomalies. We provide a comprehensive description of the skeletal phenotype in a French-Canadian girl with a moderate to severe form of sporadic OS-CS. Multiple medical problems, including anal stenosis and the Pierre-Robin sequence, were evident in the first few years of life. At 14 years, she was fully mobile, with normal intellect and stature. She suffered chronic lower extremity pain in the absence of fractures, as well as severe headaches, unilateral facial paralysis, and bilateral mixed hearing loss. Biochemical indices of bone and mineral metabolism were within normal limits. Bone densitometry showed increased areal bone mineral density in the skull, trunk, and pelvis, but not in the upper and lower extremities. An iliac bone biopsy specimen revealed an increased amount of trabecular bone. Trabeculae were abnormally thick, but there was no evidence of disturbed bone remodeling. In a cranial bone specimen, multiple layers of periosteal bone were found that covered a compact cortical compartment containing tightly packed haversian canals. Bone lamellation was normal in both the iliac and skull samples. Osteoclast differentiation studies showed that peripheral blood osteoclast precursors from this patient formed functional osteoclasts in vitro. Thus, studies of bone metabolism did not explain why bone mass is increased in most skeletal areas of this patient. Cranial histology points to exuberant periosteal bone formation as a potential cause of the cranial sclerosis.

Air and Bone Conduction Frequency-specific Auditory Brainstem Response in Children with Agenesis of the External Auditory Canal

PubMed Central

Sleifer, Pricila; Didoné, Dayane Domeneghini; Keppeler, Ísis Bicca; Bueno, Claudine Devicari; Riesgo, Rudimar dos Santos

2017-01-01

Introduction  The tone-evoked auditory brainstem responses (tone-ABR) enable the differential diagnosis in the evaluation of children until 12 months of age, including those with external and/or middle ear malformations. The use of auditory stimuli with frequency specificity by air and bone conduction allows characterization of hearing profile. Objective  The objective of our study was to compare the results obtained in tone-ABR by air and bone conduction in children until 12 months, with agenesis of the external auditory canal. Method  The study was cross-sectional, observational, individual, and contemporary. We conducted the research with tone-ABR by air and bone conduction in the frequencies of 500 Hz and 2000 Hz in 32 children, 23 boys, from one to 12 months old, with agenesis of the external auditory canal. Results  The tone-ABR thresholds were significantly elevated for air conduction in the frequencies of 500 Hz and 2000 Hz, while the thresholds of bone conduction had normal values in both ears. We found no statistically significant difference between genders and ears for most of the comparisons. Conclusion  The thresholds obtained by bone conduction did not alter the thresholds in children with conductive hearing loss. However, the conductive hearing loss alter all thresholds by air conduction. The tone-ABR by bone conduction is an important tool for assessing cochlear integrity in children with agenesis of the external auditory canal under 12 months. PMID:29018492

Multiple congenital brachymetatarsia. A one-stage combined shortening and lengthening procedure without iliac bone graft.

PubMed

Kim, J S; Baek, G H; Chung, M S; Yoon, P W

2004-09-01

We performed nine metatarsal and three proximal phalangeal lengthenings in five patients with congenital brachymetatarsia of the first and one or two other metatarsal bones, by a one-stage combined shortening and lengthening procedure using intercalcary autogenous bone grafts from adjacent shortened metatarsal bones. Instead of the isolated lengthening of the first and the other metatarsal bones, we shortened the adjacent normal metatarsal and used the excised bone to lengthen the short toes, except for the great toe, to restore the normal parabola. One skin incision was used. All the operations were performed bilaterally and the patients were followed up for a mean period of 69.5 months (29 to 107). They all regained a nearly normal parabola and were satisfied with the cosmetic results. Our technique is straightforward and produces good cosmetic results. Satisfactory, bony union is achieved, morbidity is low, and no additional surgery is required for the removal of metal implants.

Bone marrow invasion in multiple myeloma and metastatic disease.

PubMed

Vilanova, J C; Luna, A

2016-04-01

Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Biomechanical properties of the mandible, as assessed by bending test, in rats fed a low-quality protein.

PubMed

Bozzini, Carlos E; Champin, Graciela M; Alippi, Rosa M; Bozzini, Clarisa

2013-04-01

The present study describes the effects of feeding growing rats with diets containing increasing concentrations of wheat gluten (a low quality protein, G) on both the morphometrical and the biomechanical properties of the mandible. Female rats were fed one of six diets containing different concentrations (5-30%) of G between the 30th and 90th days of life. Control rats were fed a diet containing 20% casein (C), which allows a normal growth and development of the bone. Mandibular growth was estimated directly on excised and cleaned bones by taking measurements between anatomical points. Mechanical properties of the right hemimandibles were determined by using a three-point bending mechanical test to obtain a load/deformation curve and estimate the structural properties of the bone. Bone material properties were calculated from structural and geometric properties. The left hemimandibles were ashed and the ash weight obtained. Calcium content was determined by atomic energy absorption. Results were summarised as means±SEM. Comparisons between parameters were performed by ANOVA and post-test. None of the G-fed groups could achieve a normal growth performance as compared to the C-fed control group. Like body size, age-related increments in mandibular weight, length, height and area (index of mandibular size) were negatively affected by the G diets, as was the posterior part of the bone (posterior to molar III). The cross-sectional geometry of the mandible (cross-sectional area and rectangular moment of inertia) as well as its structural properties (yielding load, fracture load, and stiffness) were also severely affected by the G diets. However, material properties (Young's modulus and maximum elastic stress) and calcium concentration in ashes and the degree of mineralisation were unaffected. The differences in strength and stiffness between treated and control rats seemed to be the result of an induced loss of gain in bone growth and mass, in the absence of changes in the quality of the bone mineralised material. Copyright © 2012 Elsevier Ltd. All rights reserved.

Flexible intramedullary nailing for the treatment of unicameral bone cysts in long bones.

PubMed

Roposch, A; Saraph, V; Linhart, W E

2000-10-01

Unicameral bone cyst is characterized by its tenacity and risk of recurrence. Pathological fracture is common and is often the presenting symptom. The objective of the present study was to evaluate the results of flexible intramedullary nailing for the treatment of a unicameral bone cyst with or without a pathological fracture. Flexible intramedullary nailing for the treatment of a unicameral bone cyst was performed in thirty-two patients. Thirty of these patients presented with a pathological fracture; twenty-four were managed immediately with intramedullary nailing, and the other six had been managed conservatively at other clinics before they were referred to our department. The remaining two cysts were detected incidentally. The cyst was located in the humerus in twenty-one patients, in the femur in nine, and in the radius in two. The mean age of the patients at the time of surgery was 9.8 years, and the mean duration of follow-up was 53.7 months. Radiographic evaluation was performed according to the criteria of Capanna et al., and the cyst was classified as completely healed, healed with residual radiolucency (osteolysis), recurred, or having no response. The healing period ranged from three to 105 months. Fourteen cysts healed completely, and sixteen healed with residual radiolucent areas visible on radiographs. There was recurrence of two cysts that had healed with residual radiolucency. All of the cysts in the present study responded to treatment. A change of nails was necessary in nine patients, as the nails had become too short after bone growth. No major complications were observed. Flexible intramedullary nailing provides early stability, which allows early mobilization and thus obviates the need for a plaster cast and decreases the prevalence of the most common complication: a pathological fracture. This method of treatment also allows for an early return to normal activity.

Bone age maturity assessment using hand-held device

NASA Astrophysics Data System (ADS)

Ratib, Osman M.; Gilsanz, Vicente; Liu, Xiaodong; Boechat, M. I.

2004-04-01

Purpose: Assessment of bone maturity is traditionally performed through visual comparison of hand and wrist radiograph with existing reference images in textbooks. Our goal was to develop a digital index based on idealized hand Xray images that can be incorporated in a hand held computer and used for visual assessment of bone age for patients. Material and methods: Due to the large variability in bone maturation in normals, we generated a set of "ideal" images obtained by computer combinations of images from our normal reference data sets. Software for hand-held PDA devices was developed for easy navigation through the set of images and visual selection of matching images. A formula based on our statistical analysis provides the standard deviation from normal based on the chronological age of the patient. The accuracy of the program was compared to traditional interpretation by two radiologists in a double blind reading of 200 normal Caucasian children (100 boys, 100 girls). Results: Strong correlations were present between chronological age and bone age (r > 0.9) with no statistical difference between the digital and traditional assessment methods. Determinations of carpal bone maturity in adolescents was slightly more accurate using the digital system. The users did praise the convenience and effectiveness of the digital Palm Index in clinical practice. Conclusion: An idealized digital Palm Bone Age Index provides a convenient and effective alternative to conventional atlases for the assessment of skeletal maturity.

[Microsurgical transplantation of bone tumors of uncertain prognosis in athymic nude mice].

PubMed

Duprez, A; Féry, A; Sommelet, J

1986-01-01

Eight cases of human bone or soft tissue tumours were transplanted to nude mice. After such transplants to nude mice which are immunologically deficient, the malignant tumors developed like benign tumours, but maintaining malignant cytological characteristics. The transplants of normal human tissues or of benign tumours decreased in size or remained stable. The technique allowed a change of an original diagnosis of osteosarcoma to a final diagnosis of chondrosarcoma. It made it possible to diagnose a benign osteoblastoma, the diagnosis of which was doubtful before the transplant between osteosarcoma and chondroblastoma. It was possible to diagnose the malignancy of a haemangiopericytoma of muscle. Two aggressive tumours--a non-ossifying fibroma and a giant-cell tumour--were rated as benign after transplantation. This technique also allowed a more precise diagnosis of the grade of one chondrosarcoma and one osteosarcoma. Finally, transplantation also made it possible to test the efficacy of chemotherapy. In a patient so treated, the extreme cell proliferation after transplantation to the nude mouse led to a change in the drugs administered.

Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases

PubMed Central

Hardaway, Aimalie L.; Herroon, Mackenzie K.; Rajagurubandara, Erandi

2014-01-01

Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease. PMID:24398857

[Osteoporosis treatment in patients with hyperthyroidism].

PubMed

Saito, Jun; Nishikawa, Tetsuo

2009-05-01

Childhood thyroid hormone (T3) is essential for the normal development of endochondral and intramembranous bone and plays an important role in the linear growth and maintenance of bone mass. In adult, T3 stimulates osteoclastic bone resorption mediated primarily by TR alpha and local conversion by deiodinase D2 may play a role in local activation. TSH seems to be an inhibitor of bone resorption and formation. In thyrotoxicosis patients with Graves' disease, there is increased bone remodelling, characterized by an imbalance between bone resorption and formation, which results in a decrease of bone mineral density (BMD) and an increased risk for osteoporotic fracture. Antithyroid treatment is able to reduce dramatically the bone resorption and to normalize BMD reduction. But previous hyperthyroidism is independently associated with an increased risk for fracture. Although further studies relating to the mechanism for possible impaired bone strength in these patients will be needed, bisphosphonates may be beneficial treatment for prevention of bone fractures in patients with severe risk for fractures, such as post-menopausal women.

Analysis of bone protein and mineral composition in bone disease using synchrotron infrared microspectroscopy

NASA Astrophysics Data System (ADS)

Miller, Lisa M.; Hamerman, David; Chance, Mark R.; Carlson, Cathy S.

1999-10-01

Infrared (IR) microspectroscopy is an analytical technique that is highly sensitive to the chemical components in bone. The brightness of a synchrotron source permits the examination of individual regions of bone in situ at a spatial resolution superior to that of a conventional infrared source. At Beamlines U10B and U2B at the National Synchrotron Light Source, we are examining the role of bone chemical composition in bone disease. In osteoarthritis (OA), it has been demonstrated that the bone underlying the joint cartilage (subchondral bone) becomes thickened prior to cartilage breakdown. Using synchrotron infrared microspectroscopy, we have examined the chemical composition of the subchondral bone in histologically normal and OA monkeys. Results demonstrate that the subchondral bone of OA monkeys is significantly more mineralized than the normal bone, primarily due to an increase in carbonate concentration in the OA bone. High resolution analysis indicates that differences in carbonate content are uniform throughout the subchondral bone region, suggesting that high subchondral bone carbonate may be a marker for OA. Conversely, increases in phosphate content are more pronounced in the region near the marrow space, suggesting that, as the subchondral bone thickens, the bone also becomes more mineralized. Osteoporosis is a disease characterized by a reduction in bone mass and a skeleton that is more susceptible to fracture. To date, it is unclear whether bone remodeled after the onset of osteoporosis differs in chemical composition from older bone. Using fluorescence-assisted infrared microspectroscopy, we are comparing the composition of monkey bone remodeled at various time points after the onset of osteoporosis (induced by ovariectomy). We find that the chemical composition of bone remodeled one year after ovariectomy and one year prior to necropsy is similar to normal bone. On the other hand, bone remodeled two years after ovariectomy is less mature, indicated by lower mineral/protein ratios and higher acid phosphate content. This immature bone may also be a symptom of slower bone formation rates related to estrogen deficiency.

The orthotropic elastic properties of fibrolamellar bone tissue in juvenile white-tailed deer femora

PubMed Central

Barrera, John W.; Le Cabec, Adeline; Barak, Meir M.

2017-01-01

Fibrolamellar bone is a transient primary bone tissue found in fast growing juvenile mammals, several species of birds and large dinosaurs. Despite the fact that this bone tissue is prevalent in many species, the vast majority of bone structural and mechanical studies are focused on humans osteonal bone tissue. Previous research revealed the orthotropic structure of fibrolamellar bone, but only a handful of experiments investigated its elastic properties, mostly in the axial direction. Here we have performed for the first time an extensive biomechanical study to determine the elastic properties of fibrolamellar bone in all three orthogonal directions. We have tested 30 fibrolamellar bone cubes (2×2×2mm) from the femora of five juvenile white-tailed deer (Odocoileus virginianus) in compression. Each bone cube was compressed iteratively, within its elastic region, in the axial, transverse and radial directions and bone stiffness (Young’s modulus) was recorded. Next, the cubes were kept for seven days at 4°C and then compressed again to test whether bone stiffness had significantly deteriorated. Our results demonstrated that bone tissue in the deer femora has orthotropic elastic behavior where the highest stiffness was in the axial direction followed by the transverse and the radial directions respectively (21.6±3.3 GPa, 17.6±3.0 GPa and 14.9±1.9 GPa respectively). Our results also revealed a slight non-significant decrease in bone stiffness after seven days. Finally, our sample size allowed us to establish that population variance was much bigger in the axial direction compared to the radial direction which potentially reflects bone adaptation to the large diversity in loading activity between individuals in the loading direction (axial) compared to the normal (radial) direction. This study confirms that the well mechanically-studied human transverse-isotropic osteonal bone is just one possible functional adaptation of bone tissue and that other vertebrate species use an orthotropic bone tissue structure which is more suitable for their mechanical requirements. PMID:27231028

Runx2- and histone deacetylase 3-mediated repression is relieved in differentiating human osteoblast cells to allow high bone sialoprotein expression.

PubMed

Lamour, Virginie; Detry, Cédric; Sanchez, Christelle; Henrotin, Yves; Castronovo, Vincent; Bellahcène, Akeila

2007-12-14

Bone sialoprotein (BSP) is a bone matrix glycoprotein whose expression coincides with terminal osteoblastic differentiation and the onset of mineralization. In this study we show that BSP expression is considerably increased in confluent Saos-2 human osteosarcoma cells and in differentiating normal human osteoblasts, concomitantly with the decrease of Runx2, a key transcription factor controlling bone formation. Therefore, we investigated the role of Runx2 in the regulation of BSP expression in Saos-2 cells. Using a mobility shift assay, we demonstrated that Runx2 binds to the BSP promoter only in preconfluent cells. Histone deacetylase 3 (HDAC3) has been recently shown to act as a Runx2 co-repressor. Chromatin immunoprecipitation assays demonstrated that both Runx2 and HDAC3 are detectable at the BSP promoter in preconfluent Saos-2 cells but not when they are confluent and overexpress BSP. Consistently, nuclear Runx2 protein level is down-regulated, whereas Saos-2 cells became increasingly confluent. Finally, the suppression of HDAC3, Runx2, or both by RNA interference induced the expression of BSP at both mRNA and protein levels in Saos-2 cells. Our data demonstrate that Runx2 and HDAC3 repress BSP gene expression and that this repression is suspended upon osteoblastic cell differentiation. Both the nuclear disappearance of Runx2 and the non-recruitment of HDAC3 represent new means to relieve Runx2-mediated suppression of BSP expression, thus allowing the acquisition of a fully differentiated and mineralization-competent phenotype by osteoblast cells.

Mice with cancer-induced bone pain show a marked decline in day/night activity

PubMed Central

Majuta, Lisa A.; Guedon, Jean-Marc G.; Mitchell, Stefanie A.T.; Kuskowski, Michael A.; Mantyh, Patrick W.

2017-01-01

Abstract Introduction: Cancer-induced bone pain (CIBP) is the most common type of pain with cancer. In humans, this pain can be difficult to control and highly disabling. A major problem with CIBP in humans is that it increases on weight-bearing and/or movement of a tumor-bearing bone limiting the activity and functional status of the patient. Currently, there is less data concerning whether similar negative changes in activity occur in rodent models of CIBP. Objectives: To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Methods: Osteosarcoma cells were injected and confined to 1 femur of the adult male mouse. Every 7 days, spontaneous horizontal and vertical activities were assessed over a 20-hour day and night period using automated activity boxes. Mechanical hypersensitivity of the hind paw skin was assessed using von Frey testing. Results: As the tumor cells grew within the femur, there was a significant decline in horizontal and vertical activity during the times of the day/night when the mice are normally most active. Mice also developed significant hypersensitivity in the skin of the hind paw in the tumor-bearing limb. Conclusion: Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status. PMID:29392229

Alteration of mineral crystallinity and collagen cross-linking of bones in osteopetrotic toothless (tl/tl) rats and their improvement after treatment with colony stimulating factor-1

NASA Technical Reports Server (NTRS)

Wojtowicz, A.; Dziedzic-Goclawska, A.; Kaminski, A.; Stachowicz, W.; Wojtowicz, K.; Marks, S. C. Jr; Yamauchi, M.

1997-01-01

A common feature of various types of mammalian osteopetroses is a marked increase in bone mass accompanied by spontaneous bone fractures. The toothless (tl/tl) rat osteopetrotic mutation is characterized by drastically reduced bone resorption due to a profound deficiency of osteoclasts and their precursors. An altered bone morphology has also been observed. The mutants cannot be cured by bone marrow transplantation, but skeletal defects are greatly reduced after treatment with colony stimulating factor 1 (CSF-1). The objectives of this study were to characterize mineral and collagen matrices in cancellous and compact bone isolated from long bones of 6-week-old normal littermates, tl/tl osteopetrotic mutants and mutants (tl/tl) treated with CSF-1. There were no differences in bone mineral content, but a significant decrease in the crystallinity of mineral evaluated by the method based on electron paramagnetic resonance spectrometry was observed in all bones of tl/tl mutants as compared to that of controls. Within the collagen matrix, slight decreases in the labile cross-links, but significant increases in the content of the stable cross-links, pyridinoline, and deoxypyridinoline, were observed in both cancellous and compact bone of osteopetrotic mutants. In tl/tl mutants treated with human recombinant CSF-1, the normalization of the crystallinity of bone mineral as well as collagen cross-links was found. Our results indicate that remodeling of bone matrix in tl/tl mutants is highly suppressed, but that after treatment with CSF-1, this activity recovers significantly. Taken together, these data provide further support for the hypothesis that CSF-1 is an essential factor for normal osteoclast differentiation and bone remodelling.

An atlas of radiological interpretation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calder, J.F.; Chessell, G.

1988-01-01

This book is concerned with pathologic entities and their impact on the skeleton. The book is divided into nine chapters. After a discussion of normal anatomic features, the authors discuss trauma, avascular necrosis and osteochondritis, bone infections, diseases of the joints, bone tumors, reticuloses and hemopoietic disorders, endocrine and metabolic bone diseases, and congenital abnormalities. A line drawing accompanies every radiograph to contrast the pathologic findings with the normal anatomic features.

High calcium to phosphorus ratio impairs growth and bone mineralization in Pekin ducklings.

PubMed

Zhu, Y W; Wen, J; Jiang, X X; Wang, W C; Yang, L

2018-04-01

Two experiments were conducted to investigate the effect of high dietary calcium (Ca) level on growth performance, Ca and phosphorus (P) metabolism, and nutrient utilization in ducklings subjected to normal and low P levels in diets. A completely randomized design was used with a factorial arrangement of 2 total dietary P levels [normal-P (0.60%) and low-P (0.45%) groups] × 4 dietary Ca levels [low-Ca (0.55%), normal-Ca (0.75%), medium-Ca (0.95%) and high-Ca (1.15%) groups)]. Compared to normal-P group, low-P group had lower (P < 0.05) final body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI) and reduced (P < 0.05) serum Ca and P levels, bone Ca, P, and ash content, and bone mineral density in ducklings during the starter period. Under the low-P group, birds from high-Ca group had lower (P < 0.05) final BW, ADG, ADFI, bone ash content, bone mineral density, and the utilization of energy, Ca, and P than those from low-Ca, normal-Ca, and medium-Ca groups. Our results indicate that high-Ca diet induced greater growth suppression and bone mineralization loss in ducklings fed a low-P diet. The aggravated negative effect of high dietary Ca level with a low P level might be related to the elevated serum alkaline phosphatase activity and the reduced utilization of energy, Ca, and P.

The Application of Bone Marrow Transplantation to the Treatment of Genetic Diseases

NASA Astrophysics Data System (ADS)

Parkman, Robertson

1986-06-01

Genetic diseases can be treated by transplantation of either normal allogeneic bone marrow or, potentially, autologous bone marrow into which the normal gene has been inserted in vitro (gene therapy). Histocompatible allogeneic bone marrow transplantation is used for the treatment of genetic diseases whose clinical expression is restricted to lymphoid or hematopoietic cells. The therapeutic role of bone marrow transplantation in the treatment of generalized genetic diseases, especially those affecting the central nervous system, is under investigation. The response of a generalized genetic disease to allogeneic bone marrow transplantation may be predicted by experiments in vitro. Gene therapy can be used only when the gene responsible for the disease has been characterized. Success of gene therapy for a specific genetic disease may be predicted by its clinical response to allogeneic bone marrow transplantation.

Assessment of bone turnover markers and bone mineral density in normal short boys.

PubMed

Gayretli Aydin, Zeynep Gökçe; Bideci, Aysun; Emeksiz, Hamdi C; Çelik, Nurullah; Döğer, Esra; Bukan, Neslihan; Yildiz, Ummügülsüm; Camurdan, Orhun M; Cinaz, Peyami

2015-11-01

To investigate whether there is a change in bone turnover-related biochemical markers and bone mineral density of children with constitutional delay of growth and puberty (CDGP) in the prepubertal period. We measured serum calcium, phosphorus, alkaline phosphatase, parathormone, 25-OH vitamin D, osteocalcin, osteoprotogerin and urinary deoxypyridinoline levels (D-pyd), and bone mineral density (BMD) in 31 prepubertal boys with CDGP. These children were compared with 22 prepubertal boys with familial short stature (FSS) and 27 normal prepubertal boys. Urinary D-pyd was significantly high in CDGP group as compared to control group (p=0.010). Volumetric BMD did not significantly differ between CDGP, FSS, and control groups (p=0.450). Volumetric BMD and urinary D-pyd levels of FSS and control groups were similar. Mean or median levels of calcium, phosphorus, alkaline phosphatase, parathormone, and osteoprotegerin did not significantly differ between CDGP, FSS, and control groups. Our data suggest that prepubertal boys with CDPG have normal bone turnover. However, their significantly higher urinary D-pyd levels relative to those of FSS and control groups might be an indicator of later development of osteoporosis. Therefore, long-term follow-up studies monitoring bone mineral status of prepubertal boys with CDPG from prepuberty to adulthood are needed to better understand bone metabolism of these patients.

The anatomy of Nikyo (Aikido's second teaching).

PubMed

Eckert, J W; Lee, T K

1993-12-01

Nikyo is the second teaching of Aikido (ni-two, kyo-teaching, in Japanese). It is a joint-lock technique that results in extreme pain. It allows one to control an opponent by destroying his will to continue fighting. Nikyo is accomplished by flexing and adducting an opponent's wrist producing an instantaneous sharp pain that causes him to fall to his knees involuntarily to alleviate the pressure. The exact etiology of the pain elicited by this technique has been obscure to many practitioners. The usual explanations have been nerve compression, joint capsular stretch, tendon/muscle strain, or partial ligamentous disruption. Studies of a cadaver's wrist have shown that Nikyo forcibly compresses the pisiform bone against the ulna, two bones that do not normally articulate. The intense pain thereby produced results from stimulation of the periosteal nerves in these bony surfaces.

Growth hormone and bone health.

PubMed

Bex, Marie; Bouillon, Roger

2003-01-01

Growth hormone (GH) and insulin-like growth factor-I have major effects on growth plate chondrocytes and all bone cells. Untreated childhood-onset GH deficiency (GHD) markedly impairs linear growth as well as three-dimensional bone size. Adult peak bone mass is therefore about 50% that of adults with normal height. This is mainly an effect on bone volume, whereas true bone mineral density (BMD; g/cm(3)) is virtually normal, as demonstrated in a large cohort of untreated Russian adults with childhood-onset GHD. The prevalence of fractures in these untreated childhood-onset GHD adults was, however, markedly and significantly increased in comparison with normal Russian adults. This clearly indicates that bone mass and bone size matter more than true bone density. Adequate treatment with GH can largely correct bone size and in several studies also bone mass, but it usually requires more than 5 years of continuous treatment. Adult-onset GHD decreases bone turnover and results in a mild deficit, generally between -0.5 and -1.0 z-score, in bone mineral content and BMD of the lumbar spine, radius and femoral neck. Cross-sectional surveys and the KIMS data suggest an increased incidence of fractures. GH replacement therapy increases bone turnover. The three controlled studies with follow-up periods of 18 and 24 months demonstrated a modest increase in BMD of the lumbar spine and femoral neck in male adults with adult-onset GHD, whereas no significant changes in BMD were observed in women. GHD, whether childhood- or adult-onset, impairs bone mass and strength. Appropriate substitution therapy can largely correct these deficiencies if given over a prolonged period. GH therapy for other bone disorders not associated with primary GHD needs further study but may well be beneficial because of its positive effects on the bone remodelling cycle. Copyright 2003 S. Karger AG, Basel

Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I

NASA Technical Reports Server (NTRS)

Kostenuik, P. J.; Harris, J.; Halloran, B. P.; Turner, R. T.; Morey-Holton, E. R.; Bikle, D. D.

1999-01-01

Skeletal unloading decreases bone formation and osteoblast number in vivo and decreases the number and proliferation of bone marrow osteoprogenitor (BMOp) cells in vitro. We tested the ability of parathyroid hormone (PTH) to stimulate BMOp cells in vivo by treating Sprague Dawley rats (n = 32) with intermittent PTH(1-34) (1 h/day at 8 microg/100 g of body weight), or with vehicle via osmotic minipumps during 7 days of normal weight bearing or hind limb unloading. Marrow cells were flushed from the femur and cultured at the same initial density for up to 21 days. PTH treatment of normally loaded rats caused a 2.5-fold increase in the number of BMOp cells, with similar increases in alkaline phosphatase (ALP) activity and mineralization, compared with cultures from vehicle-treated rats. PTH treatment of hind limb unloaded rats failed to stimulate BMOp cell number, ALP activity, or mineralization. Hind limb unloading had no significant effect on PTH receptor mRNA or protein levels in the tibia. Direct in vitro PTH challenge of BMOp cells isolated from normally loaded bone failed to stimulate their proliferation and inhibited their differentiation, suggesting that the in vivo anabolic effect of intermittent PTH on BMOp cells was mediated indirectly by a PTH-induced factor. We hypothesize that this factor is insulin-like growth factor-I (IGF-I), which stimulated the in vitro proliferation and differentiation of BMOp cells isolated from normally loaded bone, but not from unloaded bone. These results suggest that IGF-I mediates the ability of PTH to stimulate BMOp cell proliferation in normally loaded bone, and that BMOp cells in unloaded bone are resistant to the anabolic effect of intermittent PTH therapy due to their resistance to IGF-I.

Maternal Perinatal Diet Induces Developmental Programming of Bone Architecture

PubMed Central

Devlin, MJ; Grasemann, C; Cloutier, AM; Louis, L; Alm, C; Palmert, MR; Bouxsein, ML

2013-01-01

Maternal high fat diet can alter offspring metabolism via perinatal developmental programming. This study tests the hypothesis that maternal high fat diet also induces perinatal programming of offspring bone mass and strength. We compared skeletal acquisition in pups from C57Bl/6J mice fed high fat or normal diet from preconception through lactation. Three-week-old male and female pups from high fat (HF-N) and normal mothers (N-N) were weaned onto normal diet. Outcomes at 14 and 26 wks of age included body mass, body composition, whole body bone mineral content via pDXA, femoral cortical and trabecular architecture via μCT, and glucose tolerance. Female HF-N had normal body mass and glucose tolerance, with lower %body fat but higher serum leptin at 14 wks vs. N-N (p<0.05 for both). Whole body bone mineral content was 12% lower at 14 wks and 5% lower at 26 wks, but trabecular bone volume fraction was 20% higher at 14 wks in female HF-N vs. N-N (p<0.05 for all). Male HF-N had normal body mass and mildly impaired glucose tolerance, with lower %body fat at 14 wks and lower serum leptin at 26 wks vs. N-N (p<0.05 for both). Serum insulin was higher at 14 wks and lower at 26 wks in HF-N vs. N-N (p<0.05). Trabecular BV/TV was 34% higher and cortical bone area was 6% higher at 14 wks vs. N-N (p<0.05 for both). These data suggest maternal high fat diet has complex effects on offspring bone, supporting the hypothesis that maternal diet alters postnatal skeletal homeostasis. PMID:23503967

Osteoarthritis

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... cartilage, which normally absorbs stress and covers the bones, so they can move smoothly. The cartilage of ... the cartilage becomes completely worn down and the bone rubs on bone. Bony spurs usually develop around ...

Bisphosphonates for prevention of postmenopausal osteoporosis.

PubMed

Ravn, Pernille

2002-02-01

Our studies showed that 5 mg alendronate per day was the lowest, most effective dose that persistently prevented bone loss in recently postmenopausal women with normal bone mass. The effect on bone mass and biochemical markers was found comparable to that of commonly recommended regimens of postmenopausal HRT, and 5 mg alendronate per day is suggested as a new option for prevention of postmenopausal osteoporosis. HRT must, however, still be considered the first choice for this indication because of additional beneficial effects on other organ systems. The effect of alendronate was unaffected by bone or fat mass status, but increased with increasing postmenopausal age. The implications were that alendronate stabilized bone mass to a comparable extent in women at particular risk of osteoporosis because of thin body habitus or low bone mass and in healthy postmenopausal women with normal bone mass. Calcium supplementation was insufficient to prevent bone loss and did not add an effect on bone metabolism when combined with alendronate treatment in recently postmenopausal women. The gastrointestinal risk and adverse event profile of 5 mg alendronate per day was comparable to that of placebo, and this dose of alendronate appeared safe for long-term use. Bone loss resumed at a normal postmenopausal rate promptly after withdrawal of alendronate in early postmenopausal women consistent with a substantial underlying natural bone loss during early menopause. Oral ibandronate increased bone mass at all skeletal regions in elderly postmenopausal women with low bone mass, and 2.5 mg ibandronate per day was the lowest dose with this effect. The results are indicative of ibandronate as an option for secondary prevention of postmenopausal osteoporosis, but longer-term phase III trials should be performed before ibandronate can be recommended for this indication. The study showed that 2.5 mg ibandronate per day was efficient for prevention of bone loss and increment in bone mass in a population of women at particular risk of osteoporosis because of low bone mass. There were no differences between 2.5 mg ibandronate per day and placebo in terms of side effects, including complaints from the gastrointestinal tract, and ibandronate appeared safe for longer-term use in this dosing. Bone loss resumed at a normal postmenopausal rate when treatment was withdrawn. The response in bone mass and biochemical markers indicated that 2.5 mg ibandronate per day is equivalent to 10 mg alendronate per day in postmenopausal women. Our studies of two recently developed biochemical markers, urine CTX and serum total OC, showed that bone turnover was lowest in the premenopausal period, where these biochemical markers furthermore revealed a negative association with bone mass. It indicated that increased bone turnover contributes to a small premenopausal bone loss and resulting lowered bone mass. In consistence, a small premenopausal bone loss was observed in some regions of the hip. The biochemical markers increased at the time of menopause, consistent with initiation of the postmenopausal bone loss, and became gradually more negatively associated with bone mass as time past the menopause increased. The biochemical markers were furthermore higher in postmenopausal women with low bone mass, consistent with the characterization of postmenopausal osteoporosis as a condition with increased bone turnover. Our results consistently indicated a central role of increased bone turnover for development of low bone mass and osteoporosis. It is, however, also important to stress that the associations between biochemical markers and bone mass were too weak to allow for a valid individual estimation of bone mass based on biochemical markers. In contrast, the biochemical markers were shown as valid tools for monitoring and prediction of treatment effect of bisphosphonates. CTX, NTX, and total OC revealed the best performance characteristics in this respect. Six months after start of treatment, the level of suppression of these biochemical markers of bone resorption and formation accurately reflected the size of the 1-2 year response in bone mass in groups of women treated with bisphosphonate. This was a clear advance over bone densitometry, which has a precision error in the area of the anticipated yearly bone mass response during bisphosphonate therapy. The relationship was consistent during treatment with alendronate or ibandronate and in younger or elderly postmenopausal women. In individual patients, cut-off values of an about 40% decrease in urine CTX or NTX and an about 20% decrease in total OC validly predicted long-term prevention of bone loss. The sensitivity of prediction was high, but the specificity low. This implicated that the biochemical markers could be used as an exact method to detect "responders" to therapy, whereas "non-responders" to bisphosphonate treatment should be detected with bone densitometry in patients who do not reveal a decrease below the cut-off value in the biochemical marker during treatment. However, before such approach can be generally recommended the cut-off values of the biochemical markers should be validated in future clinical trials of bisphosphonate. Postmenopausal osteoporosis develops slowly over many years and mainly becomes a significant individual and socio-economic health problem 1-3 decades after the menopause. Prevention of postmenopausal osteoporosis by bisphosphonates is therefore likely to imply a treatment regimen of at least a decade, as presently recommended for HRT (Consensus Development Statement 1997). However, future cost-effectiveness studies should reveal when bisphosphonate treatment should ideally be initiated. Our studies showed that the bisphosphonates were effective over the range from general recommendation (recently postmenopausal women with normal bone mass) to a reservation for women at particular risk of osteoporosis (elderly women, thin women, or women with osteopenia). Presently available biochemical markers could be used for groupwise and individual monitoring and prediction of treatment response. Most presently available biochemical markers, however, have the drawback of a low specificity. Recent studies of CTX measured in serum are promising, and indicate that this new biochemical marker might have overcome these drawbacks due to a pronounced response to treatment and a low long-term biological variation (Christgau et al. 1998b, Rosen et al. 1998, and 2000).

Mapping bone interstitial fluid movement: Displacement of ferritin tracer during histological processing

PubMed Central

Ciani, Cesare; Doty, Stephen B.; Fritton, Susannah P.

2014-01-01

Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin “halos.” Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2–3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6–15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin “halos,” with some processing methods allowing more redistribution of the ferritin tracer than others. Based on these results and the fact that “halo” labeling has not been found with any other tracer, as we seek to further delineate the movement of interstitial fluid and the role it plays in bone mechanotransduction, we believe that ferritin “halo” labeling should not be used to demonstrate physiological bone interstitial fluid flow. PMID:15964255

Mapping bone interstitial fluid movement: displacement of ferritin tracer during histological processing.

PubMed

Ciani, Cesare; Doty, Stephen B; Fritton, Susannah P

2005-09-01

Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin "halos." Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2-3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6-15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin "halos," with some processing methods allowing more redistribution of the ferritin tracer than others. Based on these results and the fact that "halo" labeling has not been found with any other tracer, as we seek to further delineate the movement of interstitial fluid and the role it plays in bone mechanotransduction, we believe that ferritin "halo" labeling should not be used to demonstrate physiological bone interstitial fluid flow.

Healthy Bones Matter

MedlinePlus

... Health Topics Kids Pages Healthy Bones Matter Healthy Bones Matter What you know about your bones Bones support your body and allow you to ... where you “deposit” and “withdraw” bone tissue. How bones grow Think of your bones as a “bank” ...

The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects

NASA Technical Reports Server (NTRS)

Zerwekh, J. E.; Ruml, L. A.; Gottschalk, F.; Pak, C. Y.; Blomqvist, C. G. (Principal Investigator)

1998-01-01

This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation. Thus, under the conditions of this study, the human skeleton appears to respond to unloading by a rapid and sustained increase in bone resorption and a more subtle decrease in bone formation.

Bone metabolism in galactosemia.

PubMed

Panis, B; Forget, P Ph; van Kroonenburgh, M J P G; Vermeer, C; Menheere, P P; Nieman, F H; Rubio-Gozalbo, M E

2004-10-01

Classical galactosemia is an autosomal recessively inherited disorder of galactose metabolism. Treatment consists of life-long dietary restriction of galactose. Despite treatment, long-term complications occur such as a decreased bone mineral density (BMD). A decreased BMD might be the result of either dietary deficiencies secondary to the galactose-restricted diet or unknown intrinsic factors. In this study, 40 children with classical galactosemia (13 males and 27 females, aged 3-17 years) on dietary treatment were included to gain insight in the bone metabolism of galactosemics. We found weight and height Z scores significantly decreased in galactosemics. Mean areal BMD Z scores of lumbar spine and of femoral neck as measured by Dual energy X-ray Absorptiometry (DXA) were -0.6 (P < 0.001) and -0.3 (P = 0.066), respectively. Mean volumetric BMD of the femoral neck was significant lower in galactosemics (P < 0.001). The recommended dietary allowances (RDA) for calcium, magnesium, zinc, vitamin D, and protein were met in all patients. Mean serum levels of calcium, phosphate, magnesium, zinc, 1,25-dihydroxy vitamin D (1,25OHD), parathormone (PTH), 17-beta estradiol, bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were normal. Serum levels of IGF-1 Z score, carboxylated osteocalcin (cOC), N-terminal telopeptide (NTX), and C-terminal telopeptide (CTX) were significantly lower in galactosemics than in control subjects. The different bone markers were strongly correlated. The low levels of IGF-1 Z score, formation marker cOC, and resorption markers NTX and CTX suggest a decreased bone metabolism in galactosemics.

Rib Bone Graft Adjusted to Fit the Facial Asymmetry: A Frame Structure Graft.

PubMed

Lee, Yoon Ho; Choi, Jong Hwan; Hwang, Kun; Choi, Jun Ho

2015-10-01

The authors introduce the concept of a "frame structure graft" in which a harvested rib bone was adjusted to fit facial asymmetry. On the costochondral junction of the sixth or seventh rib, a 5 cm incision was made. Through a subperiosteal dissection, the rib bone was harvested. Using a reciprocating saw, the harvested rib was scored on its anterior surface as well as its posterior surface with a partial depth at different intervals. The harvested rib bone was placed on the skin surface of the unaffected side of the face and a curvature was created exactly matching that of the unaffected side by bending the bone using a greenstick fracture. Thereafter, the graft was adjusted to conceal the asymmetry of the deficient side. The adjusted "frame structure" was transferred to the defect through the incisions on the affected side, and the "frame structure" graft was placed on the mandible or zygoma. The graft fixation was done externally with at least 2 Kirschner wires (K-wires). From January 2005 to August 2013, a total of 30 patients (13 men, 17 women, mean age 25.6 years) received a frame structure graft. All 30 patients achieved good healing at the operation site without complications. Donor-site morbidity as pneumothorax from the rib bone harvest was not found. Merits of this frame structure graft, the authors think, are that this method could allow a similar curvature to the normal side. In addition, the procedure itself is easy.

[Characteristics of bone tissue of rats after flight aboard biosputnik Kosmos-1129].

PubMed

Rogacheva, I V; Stupakov, G P; Volozhin, A I; Pavlova, M N; Poliakov, A N

1984-01-01

Bones of rats flown for 19 days onboard Cosmos-1129 were examined. The examination included bone mass, density, mineral composition, reconstruction parameters, and elemental composition at R + 1, R + 6, and R + 29. After flight the rats developed osteoporosis in the spongy structures of tubular bones and a smaller thickness of the cortical layer of the diaphysis; they showed no mineralization of the microstructures, a slight decrease of the Ca concentration, and a normal content of P. At R + 6 these changes progressively developed and at R + 29 they returned to normal.

Relationships of muscle strength and bone mineral density in ambulatory children with cerebral palsy.

PubMed

Chen, C-L; Lin, K-C; Wu, C-Y; Ke, J-Y; Wang, C-J; Chen, C-Y

2012-02-01

This work explores the relationships of muscle strength and areal bone mineral density (aBMD) in ambulatory children with cerebral palsy (CP). The knee extensor strength, but not motor function, was related to aBMD. Thus, muscle strength, especially antigravity muscle strength, was more associated with aBMD in these children than motor function. Muscle strength is related to bone density in normal children. However, no studies have examined these relationships in ambulatory children with CP. This work explores the relationships of muscle strength and aBMD in ambulatory children with CP. Forty-eight ambulatory children with spastic CP, aged 5-15 years, were classified into two groups based on Gross Motor Function Classification System levels: I (n = 28) and II (n = 20). Another 31 normal development (ND) children were recruited as the comparison group for the aBMD. Children with CP underwent assessments of growth, lumbar and distal femur aBMD, Gross Motor Function Measure-66 (GMFM-66), and muscle strength of knee extensor and flexor by isokinetic dynamometer. The distal femur aBMD, but not lumbar aBMD, was lower in children with CP than in ND children (p < 0.05). Children with level I had greater knee flexor strength and GMFM-66 scores than those with level II (p < 0.001). However, the knee extensor strength and distal femur and lumbar aBMD did not differ between two groups. Regression analysis revealed the weight and knee extensor strength, but not GMFM-66 scores, were related positively to the distal femur and lumbar aBMD (adjusted r (2) = 0.56-0.65, p < 0.001). These results suggest the muscle strength, especially antigravity muscle strength, were more associated with the bone density of ambulatory children with CP than motor function. The data may allow clinicians for early identifying the ambulatory CP children of potential low bone density.

Image analysis for dental bone quality assessment using CBCT imaging

NASA Astrophysics Data System (ADS)

Suprijanto; Epsilawati, L.; Hajarini, M. S.; Juliastuti, E.; Susanti, H.

2016-03-01

Cone beam computerized tomography (CBCT) is one of X-ray imaging modalities that are applied in dentistry. Its modality can visualize the oral region in 3D and in a high resolution. CBCT jaw image has potential information for the assessment of bone quality that often used for pre-operative implant planning. We propose comparison method based on normalized histogram (NH) on the region of inter-dental septum and premolar teeth. Furthermore, the NH characteristic from normal and abnormal bone condition are compared and analyzed. Four test parameters are proposed, i.e. the difference between teeth and bone average intensity (s), the ratio between bone and teeth average intensity (n) of NH, the difference between teeth and bone peak value (Δp) of NH, and the ratio between teeth and bone of NH range (r). The results showed that n, s, and Δp have potential to be the classification parameters of dental calcium density.

Three-phase bone scan in osteomyelitis and other musculoskeletal disorders.

PubMed

Sutter, C W; Shelton, D K

1996-10-01

The three-phase bone scan is very sensitive and is the study of choice in the evaluation of patients with suspected osteomyelitis and normal radiographs. If the underlying bone pathology, such as a healing fracture or degenerative disease, is detected on radiographs of the bone, the indium-111-labeled autologous leukocyte scan is the most cost-effective second study. When fracture of the long bones is clinically suspected but radiographs are normal and a delay in definitive diagnosis is acceptable, it is practical and economical to take follow-up films in 10 to 14 days. In cases requiring prompt diagnosis or when follow-up radiographic films are not diagnostic, the three-phase bone scan is the most cost-effective study. The three-phase bone scan is also used in the evaluation of occupational and sports injuries, including shin splints, stress and occult fractures, enthesiopathies and reflex sympathetic dystrophy.

Growth, sexual and bone development in a boy with bilateral anorchia under testosterone treatment guided by the development of his monozygotic twin.

PubMed

Vandewalle, Sara; Van Caenegem, Eva; Craen, Margarita; Taes, Youri; Kaufman, Jean-Marc; T'Sjoen, Guy

2018-03-28

Sex steroids are essential for sexual maturation, linear growth and bone development. However, there is no consensus on the optimal timing, dosage and dosage interval of testosterone therapy to induce pubertal development and achieve a normal adult height and bone mass in children with hypogonadism. A monozygotic monochorial male twin pair, of which one boy was diagnosed with anorchia at birth due to testicular regression syndrome was followed from the age of 3 until the age of 18 years. Low dose testosterone substitution (testosterone esters 25 mg/2 weeks) was initiated in the affected twin based on the start of pubertal development in the healthy twin and then gradually increased accordingly. Both boys were followed until age 18 and were compared as regards to linear growth, sexual maturation, bone maturation and bone development. Before puberty induction both boys had a similar weight and height. During puberty, a slightly faster weight and height gain was observed in the affected twin. Both boys ended up however, with a similar and normal (near) adult height and weight and experienced a normal development of secondary sex characteristics. At the age of 17 and 18 years, bone mineral density, body composition and volumetric bone parameters at the forearm and calf were evaluated in both boys. The affected boy had a higher lean mass and muscle cross-sectional area. The bone mineral density at the lumbar spine and whole body was similar. Trabecular and cortical volumetric bone parameters were comparable. At one cortical site (proximal radius), however, the affected twin had a smaller periosteal and endosteal circumference with a thicker cortex. In conclusion, a low dose testosterone substitution in bilateral anorchia led to a normal onset of pubertal development and (near) adult height. Furthermore, there was no difference in bone mineral density at the age of 17 and 18 years.

PET/MRI of metabolic activity in osteoarthritis: A feasibility study.

PubMed

Kogan, Feliks; Fan, Audrey P; McWalter, Emily J; Oei, Edwin H G; Quon, Andrew; Gold, Garry E

2017-06-01

To evaluate positron emission tomography / magnetic resonance imaging (PET/MRI) knee imaging to detect and characterize osseous metabolic abnormalities and correlate PET radiotracer uptake with osseous abnormalities and cartilage degeneration observed on MRI. Both knees of 22 subjects with knee pain or injury were scanned at one timepoint, without gadolinium, on a hybrid 3.0T PET-MRI system following injection of 18 F-fluoride or 18 F-fluorodeoxyglucose (FDG). A musculoskeletal radiologist identified volumes of interest (VOIs) around bone abnormalities on MR images and scored bone marrow lesions (BMLs) and osteophytes using a MOAKS scoring system. Cartilage appearance adjacent to bone abnormalities was graded with MRI-modified Outerbridge classifications. On PET standardized uptake values (SUV) maps, VOIs with SUV greater than 5 times the SUV in normal-appearing bone were identified as high-uptake VOI (VOI High ). Differences in 18 F-fluoride uptake between bone abnormalities, BML, and osteophyte grades and adjacent cartilage grades on MRI were identified using Mann-Whitney U-tests. SUV max in all subchondral bone lesions (BML, osteophytes, sclerosis) was significantly higher than that of normal-appearing bone on MRI (P < 0.001 for all). Of the 172 high-uptake regions on 18 F-fluoride PET, 63 (37%) corresponded to normal-appearing subchondral bone on MRI. Furthermore, many small grade 1 osteophytes (40 of 82 [49%]), often described as the earliest signs of osteoarthritis (OA), did not show high uptake. Lastly, PET SUV max in subchondral bone adjacent to grade 0 cartilage was significantly lower compared to that of grades 1-2 (P < 0.05) and grades 3-4 cartilage (P < 0.001). PET/MRI can simultaneously assess multiple early metabolic and morphologic markers of knee OA across multiple tissues in the joint. Our findings suggest that PET/MR may detect metabolic abnormalities in subchondral bone, which appear normal on MRI. 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;45:1736-1745. © 2016 International Society for Magnetic Resonance in Medicine.

Deterioration of Cortical Bone Microarchitecture: Critical Component of Renal Osteodystrophy Evaluation.

PubMed

Sharma, Ashish K; Toussaint, Nigel D; Masterson, Rosemary; Holt, Stephen G; Rajapakse, Chamith S; Ebeling, Peter R; Mohanty, Sindhu T; Baldock, Paul; Elder, Grahame J

2018-05-23

Cortical bone is a significant determinant of bone strength and its deterioration contributes to bone fragility. Thin cortices and increased cortical porosity have been noted in patients with chronic kidney disease (CKD), but the "Turnover Mineralization Volume" classification of renal osteodystrophy does not emphasize cortical bone as a key parameter. We aimed to assess trabecular and cortical bone microarchitecture by histomorphometry and micro-CT in patients with CKD G5 and 5D (dialysis). Transiliac bone biopsies were performed in 14 patients undergoing kidney transplantation (n = 12) and parathyroidectomy (n = 2). Structural parameters were analysed by histomorphometry and micro-CT including trabecular bone volume, thickness (TbTh), number (TbN) and separation and cortical thickness (CtTh) and porosity (CtPo). Indices of bone remodelling and mineralisation were obtained and relationships to bone biomarkers examined. Associations were determined by Spearman's or Pearson's rank correlation coefficients. By micro-CT, trabecular parameters were within normal ranges in most patients, but all patients showed very low CtTh (127 ± 44 µm) and high CtPo (60.3 ± 22.5%). CtPo was inversely related to TbN (r = -0.56; p = 0.03) by micro-CT and to TbTh (r = -0.60; p = 0.024) by histomorphometry and correlated to parathyroid hormone values (r = 0.62; p = 0.021). By histomorphometry, bone turnover was high in 50%, low in 21% and normal in 29%, while 36% showed abnormal patterns of mineralization. Significant positive associations were observed between osteoblast surface, osteoclast surface, mineralization surface and bone turnover markers. Deterioration of cortical -microarchitecture despite predominantly normal trabecular parameters reinforces the importance of comprehensive cortical evaluation in patients with CKD. © 2018 S. Karger AG, Basel.

Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finkelstein, J.S.; Klibanski, A.; Neer, R.M.

To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), whilemore » trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.« less

[Regional blood flow and bone uptake of methylene-diphosphonate-technetium-99m].

PubMed

Vattimo, A; Martini, G; Pisani, M

1983-05-30

Sudeck's atrophy of the foot is an acute, patchy osteoporosis that, on bone scan, shows an increase in both bone blood flow and local bone uptake of bone-seeking radionuclides. The purpose of this study was to evaluate the relationship between bone uptake of 99mTc-MDP and local bone blood flow. In some patients with Sudeck's atrophy of one foot we measured local bone blood flow and bone uptake of 99mTc-MDP. External counting of radioactivity, with a count-rate of 1 second was performed for 60 minutes after i.v. injection of a known dose of 99mTc-MDP in some patients with Sudeck's atrophy of the foot. The regions of interest (ROI) were selected on the basis of a bone scan performed 24 hours earlier. We assumed that the data recorded during the first seconds (7-10) reflect local blood flow and the data at 60 minutes reflect the bone uptake. The ratio between the local blood flow in the involved and healthy foot was higher than the local bone uptake ratio. The ratio between bone uptake and local bone blood flow was higher in the normal foot than in the affected one. These results suggest that the bone avidity for bone-seeking radionuclides is lower in Sudeck's atrophy than in normal bone.

Increased osteoblastic activity and expression of receptor activator of NF-kappaB ligand in nonuremic nephrotic syndrome.

PubMed

Freundlich, Michael; Alonzo, Evelyn; Bellorin-Font, Ezequiel; Weisinger, Jose R

2005-07-01

Patients with nephrotic syndrome (NS), even with normal GFR, often display altered mineral homeostasis and abnormal bone histology. However, the latter, mostly osteomalacia and increased bone resorption, cannot be readily explained by the prevalent concentrations of parathyroid hormone and vitamin D metabolites. The transmembrane receptor activator of NF-kappaB ligand (RANKL) of osteoblasts is essential for osteoclast formation and differentiation. Osteoblasts activity and the expression of RANKL were tested in cultures of normal human osteoblasts with sera obtained from patients with NS and normal GFR (129 +/- 26 ml/min per 1.73 m2) during relapse and remission of their NS. Osteoblasts that were cultured in vitro with sera during relapse displayed elevated concentrations of alkaline phosphatase (AP) and increased expression of RANKL. By contrast, during remission, AP concentrations were significantly lower (P < 0.05) and RANKL expression notably attenuated or absent. AP correlated with the proteinuria (r = 0.5, P < 0.05) and was not significantly affected by the therapeutic administration of corticosteroids. Whereas parathyroid hormone levels were normal (35 +/- 21 pg/ml), the serum markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) were lower during relapse compared with remission. Thus, sera from patients with NS and normal GFR stimulate the activity of osteoblasts and upregulate their expression of RANKL. These alterations, more prominent during clinically active NS, are transient and reversible upon remission. These disturbances of bone biology may play an important pathogenic role in the abnormal bone histology observed in patients with NS even before a decline in GFR occurs.

Phenomenon of formation of giant fat-containing cells in human bone marrow cultures induced by human serum factor: normal and leukemic patterns.

PubMed

Svet-Moldavskaya, I A; Zinzar, S N; Svet-Moldavsky, G J; Arlin, Z; Vergara, C; Koziner, B; Clarkson, B D; Holland, J F

1983-08-01

Normal human sera induce the formation of fat-containing cells (FCC) in human bone marrow cultures. A nearly complete monolayer of FCC is formed after 7-14 days of cultivation with 20% human sera in the medium. FCC-inducing activity (FCCIA) is nondialyzable through 14,900-dalton cutoff membrane and is stable at 56 degrees C for 30 min. Abundant FCCIA was found in 83% of normal human sera but in only 20% of sera from untreated patients with different hemopoietic disorders and in 32% of treated leukemic patients. It is suggested that FCCIA may be involved in regulation of the bone marrow microenvironment an that it varies in normal individuals and in patients with different diseases.

Unbiased estimation of the calcaneus volume using the Cavalieri principle on computed tomography images.

PubMed

Acer, N; Bayar, B; Basaloglu, H; Oner, E; Bayar, K; Sankur, S

2008-11-20

The size and shape of tarsal bones are especially relevant when considering some orthopedic diseases such as clubfoot. For this reason, the measurements of the tarsal bones have been the subject of many studies, none of which has used stereological methods to estimate the volume. In the present stereological study, we estimated the volume of calcaneal bone of normal feet and dry bones. We used a combination of the Cavalieri principle and computer tomographic scans taken from eight males and nine dry calcanei to estimate the volumes of calcaneal bones. The mean volume of dry calcaneal bones was estimated, producing mean results using the point-counting method and Archimedes principle being 49.11+/-10.7 or 48.22+/-11.92 cm(3), respectively. A positive correlation was found between anthropometric measurements and the volume of calcaneal bones. The findings of the present study using the stereological methods could provide data for the evaluation of normal and pathological volumes of calcaneal bones.

Transient chondrogenic phase in the intramembranous pathway during normal skeletal development.

PubMed

Nah, H D; Pacifici, M; Gerstenfeld, L C; Adams, S L; Kirsch, T

2000-03-01

Calvarial and facial bones form by intramembranous ossification, in which bone cells arise directly from mesenchyme without an intermediate cartilage anlage. However, a number of studies have reported the emergence of chondrocytes from in vitro calvarial cell or organ cultures and the expression of type II collagen, a cartilage-characteristic marker, in developing calvarial bones. Based on these findings we hypothesized that a covert chondrogenic phase may be an integral part of the normal intramembranous pathway. To test this hypothesis, we analyzed the temporal and spatial expression patterns of cartilage characteristic genes in normal membranous bones from chick embryos at various developmental stages (days 12, 15 and 19). Northern and RNAse protection analyses revealed that embryonic frontal bones expressed not only the type I collagen gene but also a subset of cartilage characteristic genes, types IIA and XI collagen and aggrecan, thus resembling a phenotype of prechondrogenic-condensing mesenchyme. The expression of cartilage-characteristic genes decreased with the progression of bone maturation. Immunohistochemical analyses of developing embryonic chick heads indicated that type II collagen and aggrecan were produced by alkaline phosphatase activity positive cells engaged in early stages of osteogenic differentiation, such as cells in preosteogenic-condensing mesenchyme, the cambium layer of periosteum, the advancing osteogenic front, and osteoid bone. Type IIB and X collagen messenger RNAs (mRNA), markers for mature chondrocytes, were also detected at low levels in calvarial bone but not until late embryonic stages (day 19), indicating that some calvarial cells may undergo overt chondrogenesis. On the basis of our findings, we propose that the normal intramembranous pathway in chicks includes a previously unrecognized transient chondrogenic phase similar to prechondrogenic mesenchyme, and that the cells in this phase retain chondrogenic potential that can be expressed in specific in vitro and in vivo microenvironments.

Influence of Body Weight on Bone Mass, Architecture, and Turnover

PubMed Central

Iwaniec, Urszula T.; Turner, Russell T.

2016-01-01

Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. While the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size. PMID:27352896

Femoral press-fit fixation in ACL reconstruction using bone-patellar tendon-bone autograft: results at 15 years follow-up.

PubMed

Widuchowski, Wojciech; Widuchowska, Malgorzata; Koczy, Bogdan; Dragan, Szymon; Czamara, Andrzej; Tomaszewski, Wieslaw; Widuchowski, Jerzy

2012-06-27

If anterior cruciate ligament (ACL) reconstruction is to be performed, decision regarding graft choice and its fixation remains one of the most controversial. Multiple techniques for ACL reconstruction are available. To avoid disadvantages related to fixation devices, a hardware-free, press-fit ACL reconstruction technique was developed. The aim of this study was to evaluate clinical outcome and osteoarthritis progression in long term after ACL reconstruction with central third patellar-tendon autograft fixed to femur by press-fit technique. Fifty two patients met inclusion/excusion criteria for this study. The patients were assessed preoperatively and at 15 years after surgery with International Knee Documentation Committee Knee Ligament Evaluation Form, Lysholm knee score, Tegner activity scale and radiographs. Good overall clinical outcomes and self-reported assessments were documented, and remained good at 15 years. The mean Lysholm and Tegner scores improved from 59.7 ± 18.5 and 4.2 ± 1.0 preoperatively to 86.4 ± 5.6 (p = 0.004) and 6.9 ± 1.4 (p = 0.005) respectively at follow-up. The IKDC subjective score improved from 60.1 ± 9.2 to 80.2 ± 8.1 (p = 0.003). According to IKDC objective score, 75% of patients had normal or nearly normal knee joints at follow-up. Grade 0 or 1 results were seen in 85% of patients on laxity testing. Degenerative changes were found in 67% of patients. There was no correlation between arthritic changes and stability of knee and subjective evaluation (p > 0.05). ACL reconstruction with patellar tendon autograft fixed to femur with press-fit technique allows to achieve good self-reported assessments and clinical ligament evaluation up to 15 years. Advantages of the bone-patellar-tendon-bone (BPTB) press-fit fixation include unlimited bone-to-bone healing, cost effectiveness, avoidance of disadvantages associated with hardware, and ease for revision surgery. BPTB femoral press-fit fixation technique can be safely applied in clinical practice and enables patients to return to preinjury activities including high-risk sports.

Electron Micrographs of Quail Limb Bones formed in microgravity

NASA Technical Reports Server (NTRS)

2003-01-01

Electron micrographs of quail limb bones that formed under the influence of microgravity show decreased mineralization compared to bones formed in normal gravity. The letters B and C indicate bone and cartilage sides of the sample, respectively, with the arrows marking the junction between bone and cartilage cells. The asterisks indicate where mineralization begins. The bone that developed during spaceflight (top) shows less mineral compared to the control sample (bottom); the control sample clearly shows mineral deposits (dark spots) that are absent in the flight sample. Quail eggs are small and develop quickly, making them ideal for space experiments. In late 2001, the Avian Development Facility (ADF) made its first flight and carried eggs used in two investigations, development and function of the irner-ear balance system in normal and altered gravity environments, and skeletal development in embryonic quail.

Measurement of the normalized broadband ultrasound attenuation in trabecular bone by using a bidirectional transverse transmission technique

NASA Astrophysics Data System (ADS)

Lee, Kang Il

2015-01-01

A new method for measuring the normalized broadband ultrasound attenuation (nBUA) in trabecular bone by using a bidirectional transverse transmission technique was proposed and validated with measurements obtained by using the conventional transverse transmission technique. There was no significant difference between the nBUA measurements obtained for 14 bovine femoral trabecular bone samples by using the bidirectional and the conventional transverse transmission techniques. The nBUA measured by using the two transverse transmission techniques showed strong positive correlations of r = 0.87 to 0.88 with the apparent bone density, consistent with the behavior in human trabecular bone invitro. We expect that the new method can be usefully applied for improved accuracy and precision in clinical measurements.

Biomechanical testing of isolated bones: holographic study

NASA Astrophysics Data System (ADS)

Silvennoinen, Raimo; Nygren, Kaarlo; Karna, Markku

1992-08-01

Holographic nondestructive testing (HNDT) is used to investigate the complex structures of bones of various shapes and sizes subjected to forces. Three antlered deer skulls of different species were investigated and significant species-specific differences were observed. The HNDT method was also used to verify the advanced healing of an osteosynthetized sheep jawbone. Radioulnar bones of a normal and an orphaned moose calf were subjected to a bending test. The undernourished calf showed torsio displacement combined with the bending of the bone, which was not seen in the normal calf. The effects of the masticatory forces on the moose skull surface were studied by simulating masseter muscle contractions with jawbones in occlusion. The fringe patterns showed fast-moving bone surfaces on the naso- maxillo-lacrimal region.

Design of a Model of Forearm Bone Fractures for Educational Purposes

ERIC Educational Resources Information Center

Jastaniah, Saddig; Hamdan, Abdulrahman; Alhadrami, Abdullah; Almatrafi, Talal; Arif, Ahmed; Almalki, Hassan

2016-01-01

This work explores a new approach to demonstrate possible forearm fractures in humans as an educating means for student radiographers. The Design of abnormal bones are not normally available as phantoms; the manufacturer usually produces normal human musculoskeletal models for educational purposes. Hence fractures and abnormalities are usually…

The Use of Backscattered Electron Imaging and Transmission Electron Microscopy to Assess Bone Architecture and Mineral Loci: Effect of Intermittent Slow-Release Sodium Fluoride Therapy

NASA Astrophysics Data System (ADS)

Zerwekh, Joseph E.; Bellotto, Dennis; Prostak, Kenneth S.; Hagler, Herbert K.; Pak, Charles Y. C.

1996-04-01

Backscattered electron imaging (BEI) and transmission electron microscopy (TEM) were used to examine the effects of treatment with intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate on bone architecture and crystallinity. Examination was performed in nondecalcified biopsies obtained from patients following up to four years of therapy (placebo or SRNaF) and compared to pretreatment biopsies from each patient, as well as to bone from young, normal subjects. BEI images disclosed increased areas of recent bone formation following fluoride administration. There was no evidence of a mineralization defect in any biopsy and both cortical and trabecular architecture remained normal. TEM analysis demonstrated intrafibrillar platelike crystals and extrafibrillar needlelike crystals for both the pre- and post-treatment biopsies as well as for the bone from young normal subjects. There was no evidence of increased crystal size or of an increase in extrafibrillar mineral deposition. These observations suggest that intermittent SRNaF and continuous calcium therapy exerts an anabolic action on the skeleton not accompanied by a mineralization defect or an alteration of bone mineral deposition. The use of BEI and TEM holds promise for the study of the pathophysiology and treatment of metabolic bone diseases.

Interdependence of skeletal sclerosis and elevated circulating levels of 1,25-dihydroxyvitamin D in osteopetrotic (op and tl) rats.

PubMed

Popoff, S N; Osier, L K; Zerwekh, J E; Marks, S C

1994-01-01

Osteopetrosis describes a heterogeneous group of inherited, metabolic bone disorders characterized by reduced bone resorption which coexists with elevated circulating levels of 1,25-dihydroxyvitamin D [1,25(OH)2D]. To determine whether or not skeletal sclerosis and high concentrations of 1,25(OH)2D are interdependent, this study used two distinct, nonallelic osteopetrotic mutations in the rat, osteopetrosis (op) and toothless (tl). The op rat is a mutation in which skeletal sclerosis can be cured (mutant) or induced (normal) following the transfer of normal or mutant osteoclast progenitors, respectively. Although these procedures are ineffective in rats of tl stock, infusions of pharmacological doses of macrophage colony-stimulating factor (CSF-1) can stimulate bone resorption and eliminate most of the excess skeletal matrix in tl mutants. This study examined the effects of cure/induction in neonatal mutant/normal rats of op stock and CSF-1 infusions in mutant rats of tl stock on skeletal (bone resorption) and serum [1,25(OH)2D] parameters as a function of time after treatment. Osteopetrotic mutants transplanted (cured) with normal spleen cells demonstrated cellular changes in osteoclast phenotype within 2-3 days followed by histologic and radiographic evidence for increased bone resorption that culminated in a normal appearance of the skeleton by 4 weeks. The markedly elevated serum levels of 1,25(OH)2D observed in untreated mutants fell significantly in transplanted mutants by the end of the first week and were similar to those in normal littermates at 3 and 4 weeks. Normal littermates transplanted (induced) with mutant spleen cells showed a progressive increase in skeletal sclerosis paralleled by significant increases in circulating levels of 1,25(OH)2D.(ABSTRACT TRUNCATED AT 250 WORDS)

Do vegetarians have a normal bone mass?

PubMed

New, Susan A

2004-09-01

Public health strategies targeting the prevention of poor bone health on a population-wide basis are urgently required, with particular emphasis being placed on modifiable factors such as nutrition. The aim of this review was to assess the impact of a vegetarian diet on indices of skeletal integrity to address specifically whether vegetarians have a normal bone mass. Analysis of existing literature, through a combination of observational, clinical and intervention studies were assessed in relation to bone health for the following: lacto-ovo-vegetarian and vegan diets versus omnivorous, predominantly meat diets, consumption of animal versus vegetable protein, and fruit and vegetable consumption. Mechanisms of action for a dietary "component" effect were examined and other potential dietary differences between vegetarians and non-vegetarians were also explored. Key findings included: (i) no differences in bone health indices between lacto-ovo-vegetarians and omnivores; (ii) conflicting data for protein effects on bone with high protein consumption (particularly without supporting calcium/alkali intakes) and low protein intake (particularly with respect to vegan diets) being detrimental to the skeleton; (iii) growing support for a beneficial effect of fruit and vegetable intake on bone, with mechanisms of action currently remaining unclarified. The impact of a "vegetarian" diet on bone health is a hugely complex area since: 1) components of the diet (such as calcium, protein, alkali, vitamin K, phytoestrogens) may be varied; 2) key lifestyle factors which are important to bone (such as physical activity) may be different; 3) the tools available for assessing consumption of food are relatively weak. However, from data available and given the limitations stipulated above, "vegetarians" do certainly appear to have "normal" bone mass. What remains our challenge is to determine what components of a vegetarian diet are of particular benefit to bone, at what levels and under which mechanisms.

A unified theory of bone healing and nonunion: BHN theory.

PubMed

Elliott, D S; Newman, K J H; Forward, D P; Hahn, D M; Ollivere, B; Kojima, K; Handley, R; Rossiter, N D; Wixted, J J; Smith, R M; Moran, C G

2016-07-01

This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This 'bone-healing unit' produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff's law, Perren's strain theory and Frost's concept of the "mechanostat". In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture - healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. Cite this article: Bone Joint J 2016;98-B:884-91. ©2016 The British Editorial Society of Bone & Joint Surgery.

Biotechnology

NASA Image and Video Library

2002-07-31

This diagram shows the normal pathways of calcium movement in the body and indicates changes (green arrows) seen during preliminary space flight experiments. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. To better understand how and why weightlessness induces bone loss, astronauts have participated in a study of calcium kinetics -- that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Subsequent somatic axis and bone tissue metabolism responses to a low-zinc diet with or without phytase inclusion in broiler chickens.

PubMed

Muszyński, Siemowit; Tomaszewska, Ewa; Kwiecień, Małgorzata; Dobrowolski, Piotr; Tomczyk-Warunek, Agnieszka

2018-01-01

Zinc is required for normal bone development and cartilage formation. The purpose of this study was to assess the effect of with adding organic Zn (alone or phytase inclusion) at the reduced dose to growing male Ross 308 chickens on somatic axis and bone tissue metabolism. 200 one-day old broilers were divided into the negative control group fed diet without Zn or phytase inclusion, positive control group receiving Zn in the 100% of daily recommended dose from ZnO, and two experimental groups fed diet introduced Zn in 25% of daily recommendation as a glycine chelate (Zn-Gly) with or without phytase inclusion (500 FTU·kg-1). Supplemental organic Zn increased bone Zn and Mg content, serum IGF-1, growth hormone and leptin concentration. Additional phytase inclusion increased body weight gain, blood plasma Ca, Fe, Zn and osteocalcin concentration and tibia ash percentage when compared to the Zn-deprived control. Bone geometry, yield and ultimate strengths were enhanced in both organic Zn supplemented groups, and the overall mechanical strength parameters of bone were better in these groups than in the positive control group supplemented with standard dose of inorganic Zn. Also marked improvements in the thickness of articular and the growth plate cartilages as well as real bone volume and thickness of metaphyseal trabeculae were achieved in all broilers fed Zn-supplemented diet irrespective of phytase inclusion, however, the highest cancellous bone mass and the best trabecular structure were noted after ZnO supplementation. In concludion, although dietary organic Zn given to growing broilers in 25% of daily recommended dose improved general bone properties and mechanical strength, the obtained results do not allow to unambiguously state that organic Zn supplementation at this level, even after phytase inclusion, is sufficient for proper bone development.

Subsequent somatic axis and bone tissue metabolism responses to a low-zinc diet with or without phytase inclusion in broiler chickens

PubMed Central

Tomaszewska, Ewa; Kwiecień, Małgorzata; Dobrowolski, Piotr; Tomczyk-Warunek, Agnieszka

2018-01-01

Zinc is required for normal bone development and cartilage formation. The purpose of this study was to assess the effect of with adding organic Zn (alone or phytase inclusion) at the reduced dose to growing male Ross 308 chickens on somatic axis and bone tissue metabolism. 200 one-day old broilers were divided into the negative control group fed diet without Zn or phytase inclusion, positive control group receiving Zn in the 100% of daily recommended dose from ZnO, and two experimental groups fed diet introduced Zn in 25% of daily recommendation as a glycine chelate (Zn-Gly) with or without phytase inclusion (500 FTU·kg-1). Supplemental organic Zn increased bone Zn and Mg content, serum IGF-1, growth hormone and leptin concentration. Additional phytase inclusion increased body weight gain, blood plasma Ca, Fe, Zn and osteocalcin concentration and tibia ash percentage when compared to the Zn-deprived control. Bone geometry, yield and ultimate strengths were enhanced in both organic Zn supplemented groups, and the overall mechanical strength parameters of bone were better in these groups than in the positive control group supplemented with standard dose of inorganic Zn. Also marked improvements in the thickness of articular and the growth plate cartilages as well as real bone volume and thickness of metaphyseal trabeculae were achieved in all broilers fed Zn-supplemented diet irrespective of phytase inclusion, however, the highest cancellous bone mass and the best trabecular structure were noted after ZnO supplementation. In concludion, although dietary organic Zn given to growing broilers in 25% of daily recommended dose improved general bone properties and mechanical strength, the obtained results do not allow to unambiguously state that organic Zn supplementation at this level, even after phytase inclusion, is sufficient for proper bone development. PMID:29373588

[High prevalence of osteoporosis in asymptomatic postmenopausal Mapuche women].

PubMed

Ponce, Lucía; Larenas, Gladys; Riedemann, Pablo

2002-12-01

Genetic and environmental factors are responsible for variations in the frequency of osteoporosis. Prevalence of osteoporosis in Mapuche women (native Chileans) is unknown. To assess the prevalence and risk factors for osteoporosis in Mapuche women. A random sample of 95 asymptomatic postmenopausal Mapuche females, stratified by age, was studied. Women with diseases or medications that could interfere with calcium metabolism were excluded. Spine and femoral neck bone mass density was determined using a Lunar DPX Alpha densitometer. Seventeen percent of women had normal bone mineral density in both spine and femoral neck. In the spine, 25.3% had a normal bone mineral density, 17.9% had osteopenia and 56.8% had osteoporosis. In the femoral neck, 34.7% had a normal bone mineral density, 57.9% had osteopenia, and 7.4% had osteoporosis. There was a positive correlation between bone mineral density and body mass index. Women with more than one hour per day of physical activity, had a significantly lower proportion of osteopenia or osteoporosis. No association between bone mineral density and parity or calcium intake, was observed. There is a high prevalence of osteopenia and osteoporosis among Mapuche women. Osteoporosis was associated with low body mass index.

Tenofovir alafenamide (TAF) treatment of HBV, what are the unanswered questions?

PubMed

Viganò, Mauro; Loglio, Alessandro; Grossi, Glenda; Lampertico, Pietro

2018-02-01

Tenofovir disoproxil fumarate (TDF), an ester prodrug of tenofovir (TFV), is one of the recommended drugs for chronic hepatitis B (CHB) patients. However, reduced kidney function and loss of bone mineral density have been reported in some CHB patients treated with TDF. Consequent to these safety issues, tenofovir alafenamide (TAF) [Vemlidy®], a phosphonate prodrug of TFV, was developed for the treatment of CHB patients. Areas covered: The favourable pharmacological profile of TAF allows a marked reduction in dosage (25 mg/day) thus reducing systemic exposure to tenofovir and improving the bone and renal safety, keeping however the same virological efficacy, compared to TDF 300 mg/day. In two ongoing 96-week phase III trials in mainly treatment-naive HBeAg-positive or -negative patients, TAF showed similar viral suppression but was associated with significantly higher alanine aminotransferase normalization rates and more favourable renal and bone safety compared to TDF. In a 48-week TAF switch study enrolling patients treated with TDF for 96 weeks, glomerular, tubular and bone safety parameters rapidly improved while virological suppression was maintained. Expert commentary: Waiting long-term large scale clinical practice studies aimed to confirm these advantages, TAF represents an helpful treatment option for both naïve and TDF-exposed CHB patients.

Rictor is required for optimal bone accrual in response to anti-sclerostin therapy in the mouse.

PubMed

Sun, Weiwei; Shi, Yu; Lee, Wen-Chih; Lee, Seung-Yon; Long, Fanxin

2016-04-01

Wnt signaling has emerged as a major target pathway for the development of novel bone anabolic therapies. Neutralizing antibodies against the secreted Wnt antagonist sclerostin (Scl-Ab) increase bone mass in both animal models and humans. Because we have previously shown that Rictor-dependent mTORC2 activity contributes to Wnt signaling, we test here whether Rictor is required for Scl-Ab to promote bone anabolism. Mice with Rictor deleted in the early embryonic limb mesenchyme (Prx1-Cre;Rictor(f/f), hereafter RiCKO) were subjected to Scl-Ab treatment for 5weeks starting at 4months of age. In vivo micro-computed tomography (μCT) analyses before the treatment showed that the RiCKO mice displayed normal trabecular, but less cortical bone mass than the littermate controls. After 5weeks of treatment, Scl-Ab dose-dependently increased trabecular and cortical bone mass in both control and RiCKO mice, but the increase was significantly blunted in the latter. Dynamic histomorphometry revealed that the RiCKO mice formed less bone than the control in response to Scl-Ab. In addition, the RiCKO mice possessed fewer osteoclasts than normal under the basal condition and exhibited lesser suppression in osteoclast number by Scl-Ab. Consistent with the fewer osteoclasts in vivo, bone marrow stromal cells (BMSC) from the RiCKO mice expressed less Rankl but normal levels of Opg or M-CSF, and were less effective than the control cells in supporting osteoclastogenesis in vitro. The reliance of Rankl on Rictor appeared to be independent of Wnt-β-catenin or Wnt-mTORC2 signaling as Wnt3a had no effect on Rankl expression by BMSC from either control or RICKO mice. Overall, Rictor in the limb mesenchymal lineage is required for the normal response to the anti-sclerostin therapy in both bone formation and resorption. Copyright © 2016 Elsevier Inc. All rights reserved.

Dwarfism in Alaskan malamutes: a disease resembling metaphyseal dysplasia in human beings.

PubMed Central

Sande, R. D.; Alexander, J. E.; Spencer, G. R.; Padgett, G. A.; Davis, W. C.

1982-01-01

In a study of 300 Alaskan Malamutes, dwarfism was shown to be an autosomal recessive inherited disease with complete penetrance that resulted in disturbed endochondral bone formation. Osseous growth disturbance was manifest at the metaphyses of tubular bones. Clinical and radiographic changes were very similar to those of rickets, although appositional bone formation rates were normal. Serum calcium, phosphorus, and alkaline phosphatase were within normal limits. Urinary excretion of calcium, phosphate, and amino acids were normal. Excess matrix was formed in the zone of cartilage cell proliferation, and the matrix persisted in the growth plate. Normal stresses resulted in microfractures in the metaphyses with subsequent interference of vascular penetration into the zone of degenerated cartilage cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7065114

Characterization of microgravity effects on bone structure and strength using fractal analysis

NASA Technical Reports Server (NTRS)

Acharya, Raj S.; Shackelford, Linda

1995-01-01

The effect of micro-gravity on the musculoskeletal system has been well studied. Significant changes in bone and muscle have been shown after long term space flight. Similar changes have been demonstrated due to bed rest. Bone demineralization is particularly profound in weight bearing bones. Much of the current techniques to monitor bone condition use bone mass measurements. However, bone mass measurements are not reliable to distinguish Osteoporotic and Normal subjects. It has been shown that the overlap between normals and osteoporosis is found for all of the bone mass measurement technologies: single and dual photon absorptiometry, quantitative computed tomography and direct measurement of bone area/volume on biopsy as well as radiogrammetry. A similar discordance is noted in the fact that it has not been regularly possible to find the expected correlation between severity of osteoporosis and degree of bone loss. Structural parameters such as trabecular connectivity have been proposed as features for assessing bone conditions. In this report, we use fractal analysis to characterize bone structure. We show that the fractal dimension computed with MRI images and X-Ray images of the patella are the same. Preliminary experimental results show that the fractal dimension computed from MRI images of vertebrae of human subjects before bedrest is higher than during bedrest.

In vivo competitive studies between normal and common gamma chain-defective bone marrow cells: implications for gene therapy.

PubMed

Otsu, M; Sugamura, K; Candotti, F

2000-09-20

Corrective gene transfer into hematopoietic stem cells (HSCs) is being investigated as therapy for X-linked severe combined immunodeficiency (XSCID) and it is hoped that selective advantage of gene-corrected HSCs will help in achieving full immune reconstitution after treatment. Lines of evidence from the results of allogeneic bone marrow transplantation in patients with XSCID support this hypothesis that, however, has not been rigorously tested in an experimental system. We studied the competition kinetics between normal and XSCID bone marrow (BM) cells using a murine bone marrow transplantation (BMT) model. For easy chimerism determination, we used genetic marking with retrovirus-mediated expression of the enhanced green fluorescent protein (EGFP). We found that XSCID BM cells were able to compete with normal BM cells for engraftment of myeloid lineages in a dose-dependent manner, whereas we observed selective repopulation of T, B, and NK cells deriving from normal BM cells. This was true despite the evidence of competitive engraftment of XSCID lineage marker-negative/c-Kit-positive (Lin-/c-Kit+) cells in the bone marrow of treated animals. From these results we extrapolate that genetic correction of XSCID HSCs will result in selective advantage of gene-corrected lymphoid lineages with consequent restoration of lymphocyte populations and high probability of clinical benefit.

Three-dimensional ultrasonography measurement of fetal nasal bone length during the midtrimester in Taiwanese women.

PubMed

Yang, Pei-Yin; Wu, Joung-Liang; Yeh, Guang-Perng; Tsung-Che Hsieh, Charles

2012-09-01

To evaluate the normal range of the fetal nasal bone length (NBL) in Taiwanese women using three-dimensional (3D) ultrasound, and compare the NBL of normal fetuses with Down syndrome to determine its significance in screening for trisomy 21. A total of 102 consecutive fetuses and another 7 fetuses with trisomy 21, determined by karyotyping at 15-22 weeks' gestation, were evaluated with 3D ultrasound before amniocentesis at Changhua Christian Hospital between November 2003 and April 2004. The normal range for NBL in the second trimester in the Taiwanese population was investigated, and a linear relationship with gestational age was noted. The NBL increased with advancing gestational age (NBL in cm=0.0264×gestational age in weeks -0.042 (R(2)=0.2416). The median of the biparietal diameter/nasal bone length ratio had a stable value which tended to change minimally between 15 and 22 weeks of gestation. Chromosomally normal fetuses had statistically longer nasal bones than fetuses with Down syndrome (p=0.014). We present a reference range for 3D ultrasound measurement of the fetal NBL. A short nasal bone at 15 to 22 weeks is associated with a high risk of trisomy 21. Copyright © 2012. Published by Elsevier B.V.

Comparison of titanium elastic intramedullary nailing versus injection of bone marrow in treatment of simple bone cysts in children: a retrospective study.

PubMed

Li, Wenchao; Xu, Ruijiang; Du, Minghua; Chen, Hui

2016-08-15

Simple bone cysts are common benign lytic bone lesions in children. The main goals of treatment for bone cysts are to prevent pathological fractures, support the healing process, and prevent recurrence. This retrospective study compared fixation with titanium elastic intramedullary nailing (TEN) versus aspiration and injection of autogenous bone marrow (ABM) for the treatment of simple bone cysts in children. Forty-six patients (mean follow-up, 62 months; range, 34-71 months) who presented with bone cysts (30 in the humerus, 16 in the femur) from January 2006 to December 2012 were retrospectively evaluated. Patients were treated with either TEN or ABM injection. Radiographs were evaluated according to previously established criteria. Clinical evaluations of pain, infection, additional fractures, and range of motion were performed. After treatment, all patients were pain-free and had normal range of motion in adjacent joints. In the ABM group, 14 (60.9 %) bone cysts completely healed, six (26.1 %) healed with small residuals after two injections, and three (13.0 %) recurred. In the TEN group, 16 (69.6 %) bone cysts completely healed, four (17.4 %) healed with small residuals, and three (13.0 %) recurred. There were no significant differences in radiographic outcomes between groups at the final follow-up (P > 0.05). Three patients developed skin irritation as a result of the nail ends. Additional fractures occurred in four patients who underwent ABM injection and in two patients who underwent TEN. No significant associations were found between pathological fractures and cyst activity, location, or treatment outcomes in the patients studied. Both TEN and ABM injection are safe and effective treatment for bone cysts. ABM injection promotes osteogenic differentiation of bone marrow stromal cells; multiple injections can reduce the likelihood of recurrence. TEN stabilizes the affected bone and thus allows early limb mobilization. It also reduces pressure in the capsule wall by continuous decompression to promote cyst healing. ABM injections can be used to treat cyst recurrence after previous TEN, with favorable results.

Quantitative computed tomography and cranial burr holes: a model to evaluate the quality of cranial reconstruction in humans.

PubMed

Worm, Paulo Valdeci; Ferreira, Nelson Pires; Ferreira, Marcelo Paglioli; Kraemer, Jorge Luiz; Lenhardt, Rene; Alves, Ronnie Peterson Marcondes; Wunderlich, Ricardo Castilho; Collares, Marcus Vinicius Martins

2012-05-01

Current methods to evaluate the biologic development of bone grafts in human beings do not quantify results accurately. Cranial burr holes are standardized critical bone defects, and the differences between bone powder and bone grafts have been determined in numerous experimental studies. This study evaluated quantitative computed tomography (QCT) as a method to objectively measure cranial bone density after cranial reconstruction with autografts. In each of 8 patients, 2 of 4 surgical burr holes were reconstructed with autogenous wet bone powder collected during skull trephination, and the other 2 holes, with a circular cortical bone fragment removed from the inner table of the cranial bone flap. After 12 months, the reconstructed areas and a sample of normal bone were studied using three-dimensional QCT; bone density was measured in Hounsfield units (HU). Mean (SD) bone density was 1535.89 (141) HU for normal bone (P < 0.0001), 964 (176) HU for bone fragments, and 453 (241) HU for bone powder (P < 0.001). As expected, the density of the bone fragment graft was consistently greater than that of bone powder. Results confirm the accuracy and reproducibility of QCT, already demonstrated for bone in other locations, and suggest that it is an adequate tool to evaluate cranial reconstructions. The combination of QCT and cranial burr holes is an excellent model to accurately measure the quality of new bone in cranial reconstructions and also seems to be an appropriate choice of experimental model to clinically test any cranial bone or bone substitute reconstruction.

Lack of biochemical hypogonadism in elderly Arab males with low bone mineral density disease.

PubMed

Al Attia, Haider M; Jaysundaram, Krishnasamy; Saraj, Fouad

2010-01-01

The aim of the study is to study the relationship between androgen levels and bone mineral density (BMD) in elderly Arab males. Forty-five elderly Arab males underwent Dual X-ray absorptiometry for measurement of BMD. The outcomes were defined as per WHO description. Assays for testosterone (T), gonadotropins (LH and FSH) and estradiol (E2), in the serum were carried out. The ratio of T/LH was used as a surrogate for the cFT assay. We excluded patients receiving hormonal ablation for prostatic neoplasm and patients with chronic liver or renal disease and patients receiving corticosteroids. Twelve were osteoporotic (26.5%); 22 osteopenic (49%); and 11(24.5%) had normal outcome. Osteoporotic patients were significantly older (78.17 +/- 7.59 years) than the osteopenic (70.14 +/- 5.92, P

Maternal perinatal diet induces developmental programming of bone architecture.

PubMed

Devlin, M J; Grasemann, C; Cloutier, A M; Louis, L; Alm, C; Palmert, M R; Bouxsein, M L

2013-04-01

Maternal high-fat (HF) diet can alter offspring metabolism via perinatal developmental programming. This study tests the hypothesis that maternal HF diet also induces perinatal programming of offspring bone mass and strength. We compared skeletal acquisition in pups from C57Bl/6J mice fed HF or normal diet from preconception through lactation. Three-week-old male and female pups from HF (HF-N) and normal mothers (N-N) were weaned onto normal diet. Outcomes at 14 and 26 weeks of age included body mass, body composition, whole-body bone mineral content (WBBMC) via peripheral dual-energy X-ray absorptiometry, femoral cortical and trabecular architecture via microcomputed tomography, and glucose tolerance. Female HF-N had normal body mass and glucose tolerance, with lower body fat (%) but higher serum leptin at 14 weeks vs. N-N (P<0.05 for both). WBBMC was 12% lower at 14 weeks and 5% lower at 26 weeks, but trabecular bone volume fraction was 20% higher at 14 weeks in female HF-N vs. N-N (P<0.05 for all). Male HF-N had normal body mass and mildly impaired glucose tolerance, with lower body fat (%) at 14 weeks and lower serum leptin at 26 weeks vs. N-N (P<0.05 for both). Serum insulin was higher at 14 weeks and lower at 26 weeks in HF-N vs. N-N (P<0.05). Trabecular BV/TV was 34% higher and cortical bone area was 6% higher at 14 weeks vs. N-N (P<0.05 for both). These data suggest that maternal HF diet has complex effects on offspring bone, supporting the hypothesis that maternal diet alters postnatal skeletal homeostasis.

Kit W-sh Mutation Prevents Cancellous Bone Loss during Calcium Deprivation.

PubMed

Lotinun, Sutada; Suwanwela, Jaijam; Poolthong, Suchit; Baron, Roland

2018-01-01

Calcium is essential for normal bone growth and development. Inadequate calcium intake increases the risk of osteoporosis and fractures. Kit ligand/c-Kit signaling plays an important role in regulating bone homeostasis. Mice with c-Kit mutations are osteopenic. The present study aimed to investigate whether impairment of or reduction in c-Kit signaling affects bone turnover during calcium deprivation. Three-week-old male WBB6F1/J-Kit W /Kit W-v /J (W/W v ) mice with c-Kit point mutation, Kit W-sh /HNihrJaeBsmJ (W sh /W sh ) mice with an inversion mutation in the regulatory elements upstream of the c-Kit promoter region, and their wild-type controls (WT) were fed either a normal (0.6% calcium) or a low calcium diet (0.02% calcium) for 3 weeks. μCT analysis indicated that both mutants fed normal calcium diet had significantly decreased cortical thickness and cancellous bone volume compared to WT. The low calcium diet resulted in a comparable reduction in cortical bone volume and cortical thickness in the W/W v and W sh /W sh mice, and their corresponding controls. As expected, the low calcium diet induced cancellous bone loss in the W/W v mice. In contrast, W sh /W sh cancellous bone did not respond to this diet. This c-Kit mutation prevented cancellous bone loss by antagonizing the low calcium diet-induced increase in osteoblast and osteoclast numbers in the W sh /W sh mice. Gene expression profiling showed that calcium deficiency increased Osx, Ocn, Alp, type I collagen, c-Fms, M-CSF, and RANKL/OPG mRNA expression in controls; however, the W sh mutation suppressed these effects. Our findings indicate that although calcium restriction increased bone turnover, leading to osteopenia, the decreased c-Kit expression levels in the W sh /W sh mice prevented the low calcium diet-induced increase in cancellous bone turnover and bone loss but not the cortical bone loss.

Measurement of Bone Growth in Osteopetrosis

PubMed Central

Sanger, V. L.; Frederickson, T. N.; Morrill, C. C.

1964-01-01

Day-old chicks were injected with 0.2 ml. of a suspension of lymphomatosis virus which was known to cause osteopetrosis in a high percentage of susceptible birds. A comparable number of uninoculated chicks were kept for controls. Alizarin red S was administered for the purpose of marking the bones in order to measure the rate of growth of normal bone and the osteopetrotic bone. The dye was given at 27, 41 and 55 days of age. In this experiment it was found that a layer of normal bone was formed on the surface of the tibia at a rate of 0.25 mm. per week but in the largest osteopetrotic lesion that was found in any chicken spongy bone was formed at a rate greater than 1 mm. per week. Alizarin red S was irritating to tissue and was toxic when given intravenously. ImagesFig. 1.Fig. 2. PMID:17649533

Cortical bone thickening in Type A posterior atlas arch defects: experimental report.

PubMed

Sanchis-Gimeno, Juan A; Llido, Susanna; Guede, David; Martinez-Soriano, Francisco; Ramon Caeiro, Jose; Blanco-Perez, Esther

2017-03-01

To date, no information about the cortical bone microstructural properties in atlas vertebrae with posterior arch defects has been reported. To test if there is an increased cortical bone thickening in atlases with Type A posterior atlas arch defects in an experimental model. Micro-computed tomography (CT) study on cadaveric atlas vertebrae. We analyzed the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry vertebrae with a Type A atlas arch defect and normal control vertebrae. The micro-CT study revealed significant differences in cortical bone thickness (p=.005), cortical volume (p=.003), and medullary volume (p=.009) values between the normal and the Type A vertebrae. Type A congenital atlas arch defects present a cortical bone thickening that may play a protective role against atlas fractures. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum tumour necrosis factor alpha in osteopenic and osteoporotic postmenopausal females: A cross-sectional study in Pakistan.

PubMed

Murad, Rafat; Shezad, Zahra; Ahmed, Saara; Ashraf, Mussarat; Qadir, Murad; Rehman, Rehana

2018-03-01

To compare biochemical parameters serum tumour necrosis factor alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D in postmenopausal women. This cross-sectional study was carried out from June 2015 to July 2016 at Jinnah Medical and Dental College, Karachi, and comprised postmenopausal women. Bone mineral density done by dual energy X-ray absorptiometryscan categorised subjects by World Health Organisation classification into normal (T score > -1) osteopenic (T score between -1 and -2.5) and osteoporotic (T score < -2.5). Biochemical parameters like tumour necrosis alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D were measured by solid phase enzyme amplified sensitivity immunoassay method. SPSS 16 was used to analyse the data. Of the 146 women, 34(23%) were normal, 93(67%) were osteopenic and 19(13%) were osteoporotic. There was significant difference in mean body mass index, serum tumour necrosis factor alpha and calcium in all the three groups (p<0.01). Significant mean difference was observed in serum calcium levels between normal and osteopenic, and between normal and osteoporotic group (p<0.05 each) without any significant mean difference between osteopenic and osteoporotic groups (p>0.05). A significant difference was observed for mean tumour necrosis factor alpha values between normal and osteoporotic groups (p<0.05). Tumour necrosis factor alpha showed negative correlation with bone mineral density in osteopenic and osteoporotic groups (p>0.05). Increased bone turnover in postmenopausal osteopenic women can be predicted by increased serum cytokine.

Substitutions of aspartic acid for glycine-220 and of arginine for glycine-664 in the triple helix of the pro alpha 1(I) chain of type I procollagen produce lethal osteogenesis imperfecta and disrupt the ability of collagen fibrils to incorporate crystalline hydroxyapatite.

PubMed Central

Culbert, A A; Lowe, M P; Atkinson, M; Byers, P H; Wallis, G A; Kadler, K E

1995-01-01

We identified two infants with lethal (type II) osteogenesis imperfecta (OI) who were heterozygous for mutations in the COL1A1 gene that resulted in substitutions of aspartic acid for glycine at position 220 and arginine for glycine at position 664 in the product of one COL1A1 allele in each individual. In normal age- and site-matched bone, approximately 70% (by number) of the collagen fibrils were encrusted with plate-like crystallites of hydroxyapatite. In contrast, approximately 5% (by number) of the collagen fibrils in the probands' bone contained crystallites. In contrast with normal bone, the c-axes of hydroxyapatite crystallites were sometimes poorly aligned with the long axis of fibrils obtained from OI bone. Chemical analysis showed that the OI samples contained normal amounts of calcium. The probands' bone samples contained type I collagen, overmodified type I collagen and elevated levels of type III and V collagens. On the basis of biochemical and morphological data, the fibrils in the OI samples were co-polymers of normal and mutant collagen. The results are consistent with a model of fibril mineralization in which the presence of abnormal type I collagen prevents normal collagen in the same fibril from incorporating hydroxyapatite crystallites. Images Figure 1 Figure 2 Figure 3 PMID:7487936

Bone remodelling around HA-coated acetabular cups

PubMed Central

Nielsen, P. T.; Søballe, K.

2006-01-01

This study was designed to investigate bone remodelling around the cup in cementless THA. Previous studies indicate an advantage of better sealing of the bone-prosthesis interface by HA/TCP coating of implants, inhibiting polyethylene-induced osteolysis. One hundred patients gave informed consent to participate in a controlled randomized study between porous coated Trilogy versus Trilogy Calcicoat (HA/TCP coated). The cup was inserted in press-fit fixation. The femoral component was a cementless porous coated titanium alloy stem (Bi-Metric), with a modular 28-mm CrCo head. The Harris Hip Score (HHS) and bone mineral density (BMD) determined by DEXA scanning were used to study the effect. Measurements revealed no difference between the two groups after 3 years either in the clinical outcome or in terms of periprosthetic bone density. Patients with a body mass index above normal regained more bone mineral than patients with normal weight. This finding supports the assumption that load is beneficial to bone remodelling. PMID:16761153

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

PubMed

McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

2008-02-01

Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

Anorexia Nervosa and Bone

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2014-01-01

Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure and reduced bone strength, all of which contribute to increased fracture risk., Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising addition concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen-progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiologic estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN. PMID:24898127

Increasing dietary protein requirements in elderly people for optimal muscle and bone health.

PubMed

Gaffney-Stomberg, Erin; Insogna, Karl L; Rodriguez, Nancy R; Kerstetter, Jane E

2009-06-01

Osteoporosis and sarcopenia are degenerative diseases frequently associated with aging. The loss of bone and muscle results in significant morbidity, so preventing or attenuating osteoporosis and sarcopenia is an important public health goal. Dietary protein is crucial for development of bone and muscle, and recent evidence suggests that increasing dietary protein above the current Recommended Dietary Allowance (RDA) may help maintain bone and muscle mass in older individuals. Several epidemiological and clinical studies point to a salutary effect of protein intakes above the current RDA (0.8 g/kg per day) for adults aged 19 and older. There is evidence that the anabolic response of muscle to dietary protein is attenuated in elderly people, and as a result, the amount of protein needed to achieve anabolism is greater. Dietary protein also increases circulating insulin-like growth factor, which has anabolic effects on muscle and bone. Furthermore, increasing dietary protein increases calcium absorption, which could be anabolic for bone. Available evidence supports a beneficial effect of short-term protein intakes up to 1.6 to 1.8 g/kg per day, although long-term studies are needed to show safety and efficacy. Future studies should employ functional measures indicative of protein adequacy, as well as measures of muscle protein synthesis and maintenance of muscle and bone tissue, to determine the optimal level of dietary protein. Given the available data, increasing the RDA for older individuals to 1.0 to 1.2 g/kg per day would maintain normal calcium metabolism and nitrogen balance without affecting renal function and may represent a compromise while longer-term protein supplement trials are pending.

Partial Reductions in Mechanical Loading Yield Proportional Changes in Bone Density, Bone Architecture, and Muscle Mass

PubMed Central

Ellman, Rachel; Spatz, Jordan; Cloutier, Alison; Palme, Rupert; Christiansen, Blaine A; Bouxsein, Mary L

2014-01-01

Although the musculoskeletal system is known to be sensitive to changes in its mechanical environment, the relationship between functional adaptation and below-normal mechanical stimuli is not well defined. We investigated bone and muscle adaptation to a range of reduced loading using the partial weight suspension (PWS) system, in which a two-point harness is used to offload a tunable amount of body weight while maintaining quadrupedal locomotion. Skeletally mature female C57Bl/6 mice were exposed to partial weight bearing at 20%, 40%, 70%, or 100% of body weight for 21 days. A hindlimb unloaded (HLU) group was included for comparison in addition to age-matched controls in normal housing. Gait kinematics was measured across the full range of weight bearing, and some minor alterations in gait from PWS were identified. With PWS, bone and muscle changes were generally proportional to the degree of unloading. Specifically, total body and hindlimb bone mineral density, calf muscle mass, trabecular bone volume of the distal femur, and cortical area of the femur midshaft were all linearly related to the degree of unloading. Even a load reduction to 70% of normal weight bearing was associated with significant bone deterioration and muscle atrophy. Weight bearing at 20% did not lead to better bone outcomes than HLU despite less muscle atrophy and presumably greater mechanical stimulus, requiring further investigation. These data confirm that the PWS model is highly effective in applying controllable, reduced, long-term loading that produces predictable, discrete adaptive changes in muscle and bone of the hindlimb. PMID:23165526

Extended flow cytometry characterization of normal bone marrow progenitor cells by simultaneous detection of aldehyde dehydrogenase and early hematopoietic antigens: implication for erythroid differentiation studies

PubMed Central

Mirabelli, Peppino; Di Noto, Rosa; Lo Pardo, Catia; Morabito, Paolo; Abate, Giovanna; Gorrese, Marisa; Raia, Maddalena; Pascariello, Caterina; Scalia, Giulia; Gemei, Marica; Mariotti, Elisabetta; Del Vecchio, Luigi

2008-01-01

Background Aldehyde dehydrogenase (ALDH) is a cytosolic enzyme highly expressed in hematopoietic precursors from cord blood and granulocyte-colony stimulating factor mobilized peripheral blood, as well as in bone marrow from patients with acute myeloblastic leukemia. As regards human normal bone marrow, detailed characterization of ALDH+ cells has been addressed by one single study (Gentry et al, 2007). The goal of our work was to provide new information about the dissection of normal bone marrow progenitor cells based upon the simultaneous detection by flow cytometry of ALDH and early hematopoietic antigens, with particular attention to the expression of ALDH on erythroid precursors. To this aim, we used three kinds of approach: i) multidimensional analytical flow cytometry, detecting ALDH and early hematopoietic antigens in normal bone marrow; ii) fluorescence activated cell sorting of distinct subpopulations of progenitor cells, followed by in vitro induction of erythroid differentiation; iii) detection of ALDH+ cellular subsets in bone marrow from pure red cell aplasia patients. Results In normal bone marrow, we identified three populations of cells, namely ALDH+CD34+, ALDH-CD34+ and ALDH+CD34- (median percentages were 0.52, 0.53 and 0.57, respectively). As compared to ALDH-CD34+ cells, ALDH+CD34+ cells expressed the phenotypic profile of primitive hematopoietic progenitor cells, with brighter expression of CD117 and CD133, accompanied by lower display of CD38 and CD45RA. Of interest, ALDH+CD34- population disclosed a straightforward erythroid commitment, on the basis of three orders of evidences. First of all, ALDH+CD34- cells showed a CD71bright, CD105+, CD45- phenotype. Secondly, induction of differentiation experiments evidenced a clear-cut expression of glycophorin A (CD235a). Finally, ALDH+CD34- precursors were not detectable in patients with pure red cell aplasia (PRCA). Conclusion Our study, comparing surface antigen expression of ALDH+/CD34+, ALDH-/CD34+ and ALDH+/CD34- progenitor cell subsets in human bone marrow, clearly indicated that ALDH+CD34- cells are mainly committed towards erythropoiesis. To the best of our knowledge this finding is new and could be useful for basic studies about normal erythropoietic differentiation as well as for enabling the employment of ALDH as a red cell marker in polychromatic flow cytometry characterization of bone marrow from patients with aplastic anemia and myelodysplasia. PMID:18510759

Gluteal muscle attachment during proximal femoral reconstruction in a canine model.

PubMed

Pluhar, G Elizabeth; Manley, Paul A; Heiner, John P; Vanderby, Ray; Markel, Mark D

2007-02-01

In this 18 month in vivo canine study we compared three methods of attaching the gluteal muscles to the proximal femur during hip reconstruction with an allograft-prosthesis composite (APC). All three methods are commonly practiced in human hip revision surgery and data on their effectiveness in dogs is directly relevant to human treatment. The methods compared were host gluteal tendon sutured to allograft tendon, host greater trochanter apposed to allograft using a cable grip system, and host cortical bone shells around the allograft secured with cerclage wires. For each method, we assessed changes in allograft-host bone fusion, weight bearing, gluteal muscle mass, and structural properties through qualitative radiography, gait analysis, histology, and biomechanical testing. Hip reconstruction using the WRAP method resulted in the greatest limb use with complete resolution of gluteal muscle atrophy 18 months after surgery. This method yielded a stronger, more stable hip joint that allowed for more normal limb function. These hips had the more rapid rate of bony union at the host bone-allograft junction and little resorption of the graft. The increased limb use and resultant larger gluteal muscle mass conferred to the WRAP hip composites the greatest tensile strength and stiffness when tested 18 months after reconstruction. There was a large amount of new bone formation on the periosteal surface where the WRAP reconstructions had an overlay of live bone that resulted in a more rapid union and increased cortical width at the level of the osteotomy. New bone also penetrated into the allograft a greater distance from the osteotomy in the WRAP group.

[Fractography of the long tubular bones of the lower extremities in trauma by blunt objects].

PubMed

Kriukov, V N; Bakhmet'ev, V I

1991-01-01

New data on micromorphological signs of fracture of long tubular bones in normal distribution and transformation of deforming forces are presented. Fractographic signs of bone for each destructive stage, signs of repeated trauma are singled out. Interrelationship between bone microstructure and conditions of its destruction is stated.

Abnormal bone formation induced by implantation of osteosarcoma-derived bone-inducing substance in the X-linked hypophosphatemic mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshikawa, H.; Masuhara, K.; Takaoka, K.

1985-01-01

The X-linked hypophosphatemic mouse (Hyp) has been proposed as a model for the human familial hypophosphatemia (the most common form of vitamin D-resistant rickets). An osteosarcoma-derived bone-inducing substance was subcutaneously implanted into the Hyp mouse. The implant was consistently replaced by cartilage tissue at 2 weeks after implantation. The cartilage matrix seemed to be normal, according to the histological examination, and 35sulphur (TVS) uptake was also normal. Up to 4 weeks after implantation the cartilage matrix was completely replaced by unmineralized bone matrix and hematopoietic bone marrow. Osteoid tissue arising from the implantation of bone inducing substance in the Hypmore » mouse showed no radiologic or histologic sign of calcification. These findings suggest that the abnormalities of endochondral ossification in the Hyp mouse might be characterized by the failure of mineralization in cartilage and bone matrix. Analysis of the effects of bone-inducing substance on the Hyp mouse may help to give greater insight into the mechanism and treatment of human familial hypophosphatemia.« less

Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways*

PubMed Central

Quint, Patrick; Ruan, Ming; Pederson, Larry; Kassem, Moustapha; Westendorf, Jennifer J.; Khosla, Sundeep; Oursler, Merry Jo

2013-01-01

Normal bone turnover requires tight coupling of bone resorption and bone formation to preserve bone quantity and structure. With aging and during several pathological conditions, this coupling breaks down, leading to either net bone loss or excess bone formation. To preserve or restore normal bone metabolism, it is crucial to determine the mechanisms by which osteoclasts and osteoblast precursors interact and contribute to coupling. We showed that osteoclasts produce the chemokine sphingosine 1-phosphate (S1P), which stimulates osteoblast migration. Thus, osteoclast-derived S1P may recruit osteoblasts to sites of bone resorption as an initial step in replacing lost bone. In this study we investigated the mechanisms by which S1P stimulates mesenchymal (skeletal) cell chemotaxis. S1P treatment of mesenchymal (skeletal) cells activated RhoA GTPase, but this small G protein did not contribute to migration. Rather, two S1P receptors, S1PR1 and S1PR2, coordinately promoted migration through activation of the JAK/STAT3 and FAK/PI3K/AKT signaling pathways, respectively. These data demonstrate that the chemokine S1P couples bone formation to bone resorption through activation of kinase signaling pathways. PMID:23300082

Bone histomorphometry in de novo renal transplant recipients indicates a further decline in bone resorption 1 year posttransplantation.

PubMed

Evenepoel, Pieter; Behets, Geert J; Viaene, Liesbeth; D'Haese, Patrick C

2017-02-01

Renal transplantation is believed to have a major impact on bone health. The present prospective observational bone biopsy study aimed to define the natural history of bone histomorphometry parameters in contemporaneous de novo renal transplant recipients. Paired bone biopsies were performed at the time of transplantation and at one-year posttransplantation in an unselected cohort of 36 patients referred for deceased kidney replacement. Parameters of mineral metabolism and circulating bone turnover markers were monitored as well. Static parameters of bone formation and especially bone resorption being already low-normal in the majority of patients at the time of renal transplantation, further declined during the first posttransplant year. However, interindividual variation was substantial, and significance was reached only for bone resorption parameters. Bone mineralization and trabecular bone volume were within the normal range at the time of transplantation (83.3% and 91.7% of graft recipients, respectively) and showed little change one-year posttransplantation. Changes in osteoclast number were paralleled by changes in circulating tartrate-resistant acid phosphatase 5b levels. Finally, cumulative glucocorticoid dose, but not the posttransplantation parathyroid hormone level, associated with trabecular bone loss. Thus, the impact of renal transplantation on bone histomorphometry is limited with only bone resorption, being already low at the time of transplantation, showing a further decline. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Increased concentrations of bone sialoprotein in joint fluid after knee injury.

PubMed Central

Lohmander, L S; Saxne, T; Heinegård, D

1996-01-01

OBJECTIVE: To detect evidence for localised changes in bone matrix metabolism after joint trauma and in post-traumatic osteoarthritis by quantification of bone sialoprotein in joint fluid and serum after knee injury in a cross sectional study. METHODS: Samples of knee joint fluid and serum were obtained from volunteers with normal knees (n = 19), patients with rupture of the anterior cruciate ligament isolated or combined with tear of a meniscus (n = 114), and patients with isolated meniscus lesions (n = 80). Concentrations of bone sialoprotein were determined by ELISA. Concentrations of other markers of joint tissue metabolism in these samples were determined in previous investigations. RESULTS: The median concentrations of bone sialoprotein in joint fluid from healthy volunteers was 122 ng ml-1 (range 41 to 183). Concentrations of bone sialoprotein were increased in both injury groups compared with the reference group (median for cruciate ligament injury 146 ng ml-1, range 72 to 339; median for meniscus injury 166 ng ml-1, range 75 to 376). After injury, bone sialoprotein increased quickly and remained increased for six months. Bone sialoprotein in joint fluid was increased only in samples from joints with normal or nearly normal (fibrillated) cartilage, and was within reference range in joints with radiographic signs of osteoarthritis. Bone sialoprotein concentrations in joints with cruciate ligament injury were positively correlated with levels of aggrecan and cartilage oligomeric matrix protein fragments, and with levels of stromelysin-1 and tissue inhibitor of metalloproteinase-1. The ratios between the concentrations of bone sialoprotein in joint fluid and serum were > 1 in the majority of the cruciate ligament injury cases. CONCLUSIONS: The release of significant amounts of bone sialoprotein into joint fluid in connection with acute joint trauma may be associated with injury to, and active remodelling of, the cartilage-bone interface and subchondral bone. The findings are consistent with dramatic shifts in cartilage, bone, and synovial metabolism following joint injury. Bone sialoprotein concentrations in synovial fluid may be a useful marker of subchondral injury and remodelling following joint injury. PMID:8882132

SU-E-T-619: Planning 131I Thyroid Treatments for Patients Requiring Hemodialysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stroud, D

Purpose: Treatment of 131I thyroid cancer patients who also require regular hemodialysis (HD) treatments requires consideration of the administered activity and the HD schedule. In this work the red bone marrow is considered the dose limiting organ and the treatment plan optimized the HD schedule with the amount of radioactivity administered. Methods: The ‘Safe’ dose was considered to be 2 Gy (200 rad) to the red bone marrow.1 131Iodine doses of 50 mCi to 100 mCi were modeled and found to require a range of HD schedules. In order to achieve the safe dose to the red marrow, more aggressivemore » HD schedules are required. 100 mCi required an aggressive HD treatment of every 24 hours for at least one week to achieve the ‘safe’ dose and an exposure appropriate for release from the hospital. A more normal schedule of HD beginning at 18 hours then every 48 hours allowed for up to 60 mCi administered dose allowed for a safe dose and expected release after less than one week.2In addition room was equipped with video cameras cameras for monitoring the patient and their vital signs from an adjacent room during HD. In this way the dialysis nurses were able to monitor the patient closely from an adjoining room. Results: Two HD patients were administered adjusted doses of about 50 mCi. The medical and nursing staff were exposed to no more than 4 mR for the entire treatment. The residual Iodine in the patient appeared to be normal after 4 to 6 days when the patient was released. Conclusion: With careful treatment planning 131Iodine treatments can be performed safely for patients needing HD and treatments appear to be as effective as those for patients with normal renal function.« less

TU-A-12A-08: Computing Longitudinal Material Changes in Bone Metastases Using Dual Energy Computed Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidtlein, CR; Hwang, S; Veeraraghavan, H

Purpose: This study demonstrates a methodology for tracking changes in metastatic bone disease using trajectories in material basis space in serial dual energy computed tomography (DECT) studies. Methods: This study includes patients with bone metastases from breast cancer that had clinical surveillance CT scans using a General Electric CT750HD in dual energy mode. A radiologist defined regions-of-interested (ROI) for bone metastasis, normal bone, and marrow across the serial DECT scans. Our approach employs a Radon transform to forward-projection the basis images, namely, water and iodine, into sinogram space. This data is then repartitioned into fat/bone and effective density/Z image pairsmore » using assumed energy spectrums for the x-ray energies. This approach both helps remove negative material densities and avoids adding spectrum-hardening artifacts. These new basis data sets were then reconstructed via filtered back-projection to create new material basis pair images. The trajectories of these pairs were then plotted in the new basis space providing a means to both visualize and quantitatively measure changes in the material properties of the tumors. Results: ROI containing radiologist defined metastatic bone disease showed well-defined trajectories in both fat/bone and effective density/Z space. ROI that contained radiologist defined normal bone and marrow did not exhibit any discernible trajectories and were stable from scan to scan. Conclusions: The preliminary results show that changes in material composition and effective density/Z image pairs were seen primarily in metastasis and not in normal tissue. This study indicates that by using routine clinical DECT it may be possible to monitor therapy response of bone metastases because healing or worsening bone metastases change material composition of bone. Additional studies are needed to further validate these results and to test for their correlation with outcome.« less

Bone microstructure in men assessed by HR-pQCT: Associations with risk factors and differences between men with normal, low, and osteoporosis-range areal BMD.

PubMed

Okazaki, Narihiro; Burghardt, Andrew J; Chiba, Ko; Schafer, Anne L; Majumdar, Sharmila

2016-12-01

The primary objective of this study was to analyze the relationships between bone microstructure and strength, and male osteoporosis risk factors including age, body mass index, serum 25-hydroxyvitamin D level, and testosterone level. A secondary objective was to compare microstructural and strength parameters between men with normal, low, and osteoporosis-range areal bone mineral density (aBMD). Seventy-eight healthy male volunteers (mean age 62.4 ± 7.8 years, range 50-84 years) were recruited. The participants underwent dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultra-distal radius and tibia. From the HR-pQCT images, volumetric bone mineral density (BMD) and cortical and trabecular bone microstructure were evaluated, and bone strength and cortical load fraction (Ct.LF) were estimated using micro-finite element analysis (μFEA). Age was more strongly correlated with bone microstructure than other risk factors. Age had significant positive correlations with cortical porosity at both ultra-distal radius and tibia ( r  = 0.36, p  = 0.001, and r  = 0.47, p  < 0.001, respectively). At the tibia, age was negatively correlated with cortical BMD, whereas it was positively correlated with trabecular BMD. In μFEA, age was negatively correlated with Ct.LF, although not with bone strength. Compared with men with normal aBMD, men with low or osteoporosis-range aBMD had significantly poor trabecular bone microstructure and lower bone strength at the both sites, while there was no significant difference in cortical bone. Cortical bone microstructure was negatively affected by aging, and there was a suggestion that the influence of aging may be particularly important at the weight-bearing sites.

Bone marrow adipocytes: a neglected target tissue for growth hormone.

PubMed

Gevers, Evelien F; Loveridge, Nigel; Robinson, Iain C A F

2002-10-01

Bone marrow (BM) contains numerous adipocytes. These share a common precursor with osteoblasts and chondrocytes, but their function is unknown. It is unclear what regulates the differentiation of these three different cell types, though their subsequent metabolic activity is under hormonal regulation. GH and estrogen stimulate bone growth and mineralization, by direct effects on chondrocytes and osteoblasts. GH also stimulates lipolysis in subcutaneous and visceral adipocytes. However, adipocytes in BM have largely been ignored as potential targets for GH or estrogen action. We have addressed this by measuring BM adipocyte number, perimeter and area as well as bone area and osteoblast activity in GH-deficient dwarf (dw/dw), normal, or ovariectomized (Ovx) rats, with or without GH, IGF-1, PTH, or estrogen treatment or high fat feeding. Marrow adipocyte numbers were increased 5-fold (P < 0.001) in dw/dw rats, and cell size was also increased by 20%. These values returned toward normal in dw/dw rats given GH but not when given IGF-1. Cancellous bone area and osteoblast number were significantly (P < 0.005) lower in dw/dw rats, though alkaline phosphatase (ALP) activity in individual osteoblasts was unchanged. GH treatment increased % osteoblast covered bone surface without affecting individual cell ALP activity. Ovariectomy in normal or dw/dw rats had no affect on marrow adipocyte number nor size, although estrogen treatment in ovariectomized (Ovx) normal rats did increase adipocyte number. Ovx decreased tibial cancellous bone area in normal rats (64%; P < 0.05) and decreased osteoblast ALP-activity (P < 0.01) but did not affect the percentage of osteoblast-covered bone surface. Estrogen replacement reversed these changes. While treatment with PTH by continuous sc infusion decreased cancellous bone (P < 0.05) and high fat feeding increased the size of BM adipocytes (P < 0.01), they did not affect BM adipocyte number. These results suggest that GH has a specific action on BM adipocytes that is not simply due to altered bone or fat metabolism. We conclude that the marrow adipocyte lineage is an important and specific target for GH action. The inverse relationship between adipocyte number and osteoblast covered bone surface, together with the well-known effects of GH on epiphysial chondrocytes leads us to propose that GH plays two important roles on cells of all three lineages. During differentiation, it regulates the numbers of each cell type that are maintained from the common precursor lineage. Subsequently it has cell-specific effects on the metabolic activities of the differentiated cells. In the case of marrow adipocytes, GH-dependent lipolysis could provide an important hormonally regulated local high energy source in bone.

Diagram of Calcium Movement in the Human Body

NASA Technical Reports Server (NTRS)

2002-01-01

This diagram shows the normal pathways of calcium movement in the body and indicates changes (green arrows) seen during preliminary space flight experiments. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. To better understand how and why weightlessness induces bone loss, astronauts have participated in a study of calcium kinetics -- that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Handling of induced hypercalcaemia in hyperthyroidism

PubMed Central

Lim, P.; Jacob, E.; Khoo, O. T.

1969-01-01

The mean serum calcium of 13 hyperthyroid patients was found to be significantly higher than that of controls matched for sex and age, though none of the patients' values were outside the normal range. Nevertheless, these patients responded very promptly to hypercalcaemia (induced by an intravenous calcium load), and their serum calcium returned to normal much more rapidly compared with the matched controls. There was also increased retention of intravenous calcium load, possibly owing to increased calcitonin production. Calcium infusion may be useful in treating bone diseases in which increased bone resorption exceeds bone accretion. PMID:5354875

Content and distribution of noncollagenous matrix proteins in bone and cementum: relationship to speed of formation and collagen packing density.

PubMed

Nanci, A

1999-06-30

The organic matrix of collagen-based calcified tissues consists of a supporting collagen meshwork and various noncollagenous matrix proteins (NCPs). Together, they contribute to determining the structure and biomechanical properties of the tissue. Their respective organization and interrelation can advantageously be examined by immunocytochemistry, an approach which allows correlation of composition with structure. The aim of this article is to review postembedding immuno- and lectin-gold-labeling data on the characterization of the noncollagenous compartment in rat and human bone and cementum, and on its relationship to collagen. The two major NCPs, bone sialoprotein and osteopontin, generally codistribute and accumulate in cement lines and in the spaces among the mineralized collagen fibrils. However, there are variations in their distribution and density of labeling throughout the tissue. Indeed, bone and cementum can form in environments that are either poor or enriched in NCPs. The amount of NCPs generally correlates with bone and cementum types and with speed of formation of the tissue and packing density of collagen fibrils. Taken together, the data suggest that production of both collagenous and noncollagenous constituents can be "modulated" during formation of collagen-based calcified tissues. It is concluded that, in addition to structural and compositional parameters, tissue dynamics must be taken into consideration in order to understand the significance of the apparent accumulation of NCPs at some sites and to determine the mechanisms of normal and pathological calcified tissue formation. Copyright 1999 Academic Press.

EVALUATION OF CALCIUM 47 IN NORMAL MAN AND ITS USE IN THE EVALUATION OF BONE HEALING FOLLOWING RADIATION THERAPY IN METASTATIC DESEASE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brady, L.W.; Croll, M.N.; Stanton, L.

1962-02-01

It was concluded that radioactlve Ca/sup 47/ is an isotope suitable for the study of calcium metabolism in the body. It is easily traced by external counting technics. Local uptake measurements as well as ratios over various areas of the skeleton can be determined, thus yielding useful diagnostic information. It is a safe agent for use. It is possible to differentiate normal bone from areas of diseased bone using it. It is not useful for scintiscanning. It is grossly applicable in the evaluation of effects of radiation therapy to local metastatic lesions in bone. These observations support the fact thatmore » bone- seeking isotopes may well be useful as diagnostic agents for the evaluation of subradiographic metastases. (auth)« less

Role of Corticosteroids in Bone Loss During Space Flight

NASA Technical Reports Server (NTRS)

Wronski, Thomas J.; Halloran, Bernard P.; Miller, Scott C.

1998-01-01

The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

The skeletal consequences of thyrotoxicosis.

PubMed

Nicholls, Jonathan J; Brassill, Mary Jane; Williams, Graham R; Bassett, J H Duncan

2012-06-01

Euthyroid status is essential for normal skeletal development and the maintenance of adult bone structure and strength. Established thyrotoxicosis has long been recognised as a cause of high bone turnover osteoporosis and fracture but more recent studies have suggested that subclinical hyperthyroidism and long-term suppressive doses of thyroxine (T4) may also result in decreased bone mineral density (BMD) and an increased risk of fragility fracture, particularly in postmenopausal women. Furthermore, large population studies of euthyroid individuals have demonstrated that a hypothalamic-pituitary-thyroid axis set point at the upper end of the normal reference range is associated with reduced BMD and increased fracture susceptibility. Despite these findings, the cellular and molecular mechanisms of thyroid hormone action in bone remain controversial and incompletely understood. In this review, we discuss the role of thyroid hormones in bone and the skeletal consequences of hyperthyroidism.

Recent developments in metabolic bone diseases: a gnathic perspective.

PubMed

Raubenheimer, Erich J; Noffke, Claudia E; Hendrik, Hilde D

2014-12-01

Metabolic bone diseases often are asymptomatic and progress sub clinically. Many patients present at a late stage with catastrophic skeletal and extra skeletal complications. In this article, we provide an overview of normal bone remodeling and a synopsis of recent developments in the following conditions: osteoporosis, rickets/osteomalacia, endocrine-induced bone disease, chronic kidney disease-mineral bone disorder and Paget's disease of bone. Our discussion will emphasize the clinical and microscopic manifestations of these diseases in the jaws.

Vitamin D: the light side of sunshine.

PubMed

Mason, R S; Sequeira, V B; Gordon-Thomson, C

2011-09-01

Under normal circumstances, vitamin D is mainly obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D (25OHD), the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of ingested calcium (and phosphate). This assists in building bone at younger ages and ensures that despite obligatory urinary losses, bone does not need to be resorbed to maintain blood calcium concentrations. Vitamin D compounds appear to have direct effects to improve bone and muscle function, and there is good, although not entirely consistent, evidence that supplemental vitamin D and calcium together reduce falls and fractures in older individuals. On the basis of calcium control and musculoskeletal function, target levels for 25OHD in blood are at least 50-60 nmol/l and there may be a case for higher targets of 75-80 nmol/l. There are vitamin D receptors in most nucleated cells and some evidence, although not consistent, that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality and increase insulin responsiveness. Vitamin D levels are maintained better in the presence of adequate calcium intakes, more exercise and less obesity. Genetic variation may have an effect on vitamin D blood levels and response to treatment with vitamin D.

Alternative cells for regeneration.

PubMed

Slack, Jonathan M W

2012-04-17

Normally, in fish fin regeneration, bone regenerates from bone. But what happens when there is no bone? Singh et al. (2012) show in this issue of Developmental Cell that the bony rays still regenerate from an alternative cell source. Copyright © 2012 Elsevier Inc. All rights reserved.

9 CFR 95.13 - Bone meal for use as fertilizer or as feed for domestic animals; requirements for entry.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bone meal for use as fertilizer or as...), AND HAY AND STRAW, OFFERED FOR ENTRY INTO THE UNITED STATES § 95.13 Bone meal for use as fertilizer or... bone meal, which, in the normal process of manufacture, has been prepared by heating bone under a...

9 CFR 95.13 - Bone meal for use as fertilizer or as feed for domestic animals; requirements for entry.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Bone meal for use as fertilizer or as...), AND HAY AND STRAW, OFFERED FOR ENTRY INTO THE UNITED STATES § 95.13 Bone meal for use as fertilizer or... bone meal, which, in the normal process of manufacture, has been prepared by heating bone under a...

9 CFR 95.13 - Bone meal for use as fertilizer or as feed for domestic animals; requirements for entry.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Bone meal for use as fertilizer or as...), AND HAY AND STRAW, OFFERED FOR ENTRY INTO THE UNITED STATES § 95.13 Bone meal for use as fertilizer or... bone meal, which, in the normal process of manufacture, has been prepared by heating bone under a...

9 CFR 95.13 - Bone meal for use as fertilizer or as feed for domestic animals; requirements for entry.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Bone meal for use as fertilizer or as...), AND HAY AND STRAW, OFFERED FOR ENTRY INTO THE UNITED STATES § 95.13 Bone meal for use as fertilizer or... bone meal, which, in the normal process of manufacture, has been prepared by heating bone under a...

9 CFR 95.13 - Bone meal for use as fertilizer or as feed for domestic animals; requirements for entry.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Bone meal for use as fertilizer or as...), AND HAY AND STRAW, OFFERED FOR ENTRY INTO THE UNITED STATES § 95.13 Bone meal for use as fertilizer or... bone meal, which, in the normal process of manufacture, has been prepared by heating bone under a...

Outcomes of bone density measurements in coeliac disease.

PubMed

Bolland, Mark J; Grey, Andrew; Rowbotham, David S

2016-01-29

Some guidelines recommend that patients with newly diagnosed coeliac disease undergo bone density scanning. We assessed the bone density results in a cohort of patients with coeliac disease. We searched bone density reports over two 5-year periods in all patients from Auckland District Health Board (2008-12) and in patients under 65 years from Counties Manukau District Health Board (2009-13) for the term 'coeliac.' Reports for 137 adults listed coeliac disease as an indication for bone densitometry. The average age was 47 years, body mass index (BMI) 25 kg/m(2), and 77% were female. The median time between coeliac disease diagnosis and bone densitometry was 261 days. The average bone density Z-score was slightly lower than expected (Z-score -0.3 to 0.4) at the lumbar spine, total hip and femoral neck, but 88-93% of Z-scores at each site lay within the normal range. Low bone density was strongly related to BMI: the proportions with Z-score <-2 for BMI <20, 20-25, 25-30, and >30 kg/m(2) were 28%, 15%, 6% and 0% respectively. Average bone density was normal, suggesting that bone density measurement is not indicated routinely in coeliac disease, but could be considered on a case-by-case basis for individuals with strong risk factors for fracture.

Clinical investigation and mechanism of air-bone gaps in large vestibular aqueduct syndrome.

PubMed

Merchant, Saumil N; Nakajima, Hideko H; Halpin, Christopher; Nadol, Joseph B; Lee, Daniel J; Innis, William P; Curtin, Hugh; Rosowski, John J

2007-07-01

Patients with large vestibular aqueduct syndrome (LVAS) often demonstrate an air-bone gap at the low frequencies on audiometric testing. The mechanism causing such a gap has not been well elucidated. We investigated middle ear sound transmission in patients with LVAS, and present a hypothesis to explain the air-bone gap. Observations were made on 8 ears from 5 individuals with LVAS. The diagnosis of LVAS was made by computed tomography in all cases. Investigations included standard audiometry and measurements of umbo velocity by laser Doppler vibrometry (LDV) in all cases, as well as tympanometry, acoustic reflex testing, vestibular evoked myogenic potential (VEMP) testing, distortion product otoacoustic emission (DPOAE) testing, and middle ear exploration in some ears. One ear with LVAS had anacusis. The other 7 ears demonstrated air-bone gaps at the low frequencies, with mean gaps of 51 dB at 250 Hz, 31 dB at 500 Hz, and 12 dB at 1,000 Hz. In these 7 ears with air-bone gaps, LDV showed the umbo velocity to be normal or high normal in all 7; tympanometry was normal in all 6 ears tested; acoustic reflexes were present in 3 of the 4 ears tested; VEMP responses were present in all 3 ears tested; DPOAEs were present in 1 of the 2 ears tested, and exploratory tympanotomy in 1 case showed a normal middle ear. The above data suggest that an air-bone gap in LVAS is not due to disease in the middle ear. The data are consistent with the hypothesis that a large vestibular aqueduct introduces a third mobile window into the inner ear, which can produce an air-bone gap by 1) shunting air-conducted sound away from the cochlea, thus elevating air conduction thresholds, and 2) increasing the difference in impedance between the scala vestibuli side and the scala tympani side of the cochlear partition during bone conduction testing, thus improving thresholds for bone-conducted sound. We conclude that LVAS can present with an air-bone gap that can mimic middle ear disease. Diagnostic testing using acoustic reflexes, VEMPs, DPOAEs, and LDV can help to identify a non-middle ear source for such a gap, thereby avoiding negative middle ear exploration. A large vestibular aqueduct may act as a third mobile window in the inner ear, resulting in an air-bone gap at low frequencies.

The osteoporotic vertebral structure is well adapted to the loads of daily life, but not to infrequent "error" loads.

PubMed

Homminga, J; Van-Rietbergen, B; Lochmüller, E M; Weinans, H; Eckstein, F; Huiskes, R

2004-03-01

Osteoporotic vertebral fractures typically have a gradual onset, frequently remain clinically undetected, and do not seem to be related to traumatic events. The osteoporotic vertebrae may therefore be expected to display a less "optimal" bone architecture, leading to an uneven load distribution over the bone material. We evaluated the trabecular load distribution in an osteoporotic and a healthy vertebra under normal daily loading by combining three recent innovations: high resolution computed tomography (microCT) of entire bones, microfinite element analyses (microFEA), and parallel supercomputers. Much to our surprise, the number of highly loaded trabeculae was not higher in the osteoporotic vertebra than in the healthy one under normal daily loads (8% and 9%, respectively). The osteoporotic trabeculae were more oriented in the longitudinal direction, compensating for effects of bone loss and ensuring adequate stiffness for normal daily loading. The increased orientation did, however, make the osteoporotic structure less resistant against collateral "error" loads. In this case, the number of overloaded trabeculae in the osteoporotic vertebra was higher than in the healthy one (13% and 4%, respectively). These results strengthen the paradigm of a strong relationship between bone morphology and external loads applied during normal daily life. They also indicate that vertebral fractures result from actions like forward flexion or lifting, loads that may not be "daily" but are normally not traumatic either. If future clinical imaging techniques would enable such high-resolution images to be obtained in vivo, the combination of microCT and microFEA would produce a powerful tool to diagnose osteoporosis.

Influence of mandibular morphology on the hyoid bone in atypical deglutition: a correlational study.

PubMed

Machado, Almiro J; Crespo, Agrício N

2011-11-01

evaluate the possible correlation with the radiographic position of the hyoid bone and mandibular angle in lateral radiographs of children with atypical deglutition. This was an observational study using cephalometric analysis of lateral teleradiographs for the distances of H-MP (hyoid to mandibular plane). Spearman's correlation analysis was performed with MA (mandibular angle) in two groups: the experimental group with atypical deglutition and the control group normal deglutition. Both groups included subjects in mixed dentition stage. there was a significant moderate negative correlation between MA (mandibular angle) and hyoid bone (H-MP) in the normal group (R = -0.406, p = 0.021). However, there was no significant correlation between the MA and H-MP (R = 0.029, p = 0.83) in the group with atypical deglutition. there is a moderate negative correlation between the position of the hyoid bone and mandibular angle in the group of normal swallowing and there is no correlation between variables H-MP and MA in the group of atypical swallowing.

Inhibition of particulate debris-induced osteolysis by alendronate in a rat model.

PubMed

Thadani, Peter J; Waxman, Bryan; Sladek, Eduard; Barmada, Riad; Gonzalez, Mark H

2002-01-01

A rat model was used to study the efficacy of alendronate therapy in inhibition of particle-induced periprosthetic osteolysis. A prosthesis was simulated by inserting a cylindrical polymethylmethacrylate plug into the distal femur of 24 rats allowing the plug to communicate with the joint space. Intra-articular injections of irregularly-shaped ultra-high molecular weight polyethylene particles of 20-200 pm in diameter were administered at 2-week intervals. The rats were randomized into two groups (n=12 each). Group A rats received twice weekly subcutaneous injections of alendronate sodium while group B rats received injections of saline vehicle only. At 10 weeks all rats were sacrificed. The distal femurs were harvested and axial sections were prepared for histologic analysis. Each section was graded on a scale of 1-4, quantifying the degree of osteolysis surrounding the polymethylmethacrylate plug. Microscopic examination showed a significant (P<.0001) difference in the amount of periprosthetic bone. Femurs from group A treated with alendronate demonstrated mostly normal or near-normal periprosthetic trabeculations, whereas femurs from group B treated with saline showed extensive bone resorption. There was no qualitative difference in the inflammatory cellular response between the groups. This study established the ability of alendronate to inhibit the osteoclastic-mediated osteolysis around joint implants.

Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults

ERIC Educational Resources Information Center

Cobb, Kensi M.; Stuart, Andrew

2016-01-01

Purpose The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults. Method Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level…

FES-Rowing versus Zoledronic Acid to Improve Bone Health in SCI

DTIC Science & Technology

2013-10-01

bone density (total hip and femoral neck) according to the World Health Organization (WHO) definitions of normal (T-score >-1), osteopenia (T-score...0.694 ± 0.22 0.759 ± 0.19 0.748 ± 0.21 0.982 ± 0.08 Osteoporosis status • Normal • Osteopenia • Osteoporosis/BMD lower than expected for age

[Diet, nutrition and bone health].

PubMed

Miggiano, G A D; Gagliardi, L

2005-01-01

Nutrition is an important "modifiable" factor in the development and maintenance of bone mass and in the prevention of osteoporosis. The improvement of calcium intake in prepuberal age translates to gain in bone mass and, with genetic factor, to achievement of Peak Bone Mass (PBM), the higher level of bone mass reached at the completion of physiological growth. Individuals with higher PBM achieved in early adulthood will be at lower risk for developing osteoporosis later in life. Achieved the PBM, it is important maintain the bone mass gained and reduce the loss. This is possible adopting a correct behaviour eating associated to regular physical activity and correct life style. The diet is nutritionally balanced with caloric intake adequate to requirement of individual. This is moderate in protein (1 g/kg/die), normal in fat and the carbohydrates provide 55-60% of the caloric intake. A moderate intake of proteins is associated with normal calcium metabolism and presumably does'nt alter bone turnover. An adequate intake of alkali-rich foods may help promote a favorable effect of dietary protein on the skeleton. Lactose intolerance may determinate calcium malabsorption or may decrease calcium intake by elimination of milk and dairy products. Omega3 fatty acids may "down-regulate" pro-inflammatory cytokines and protect against bone loss by decreasing osteoclast activation and bone reabsorption. The diet is characterized by food containing high amount of calcium, potassium, magnesium and low amount of sodium. If it is impossible to reach the requirement with only diet, it is need the supplement of calcium and vitamin D. Other vitamins (Vit. A, C, E, K) and mineral (phosphorus, fluoride, iron, zinc, copper and boron) are required for normal bone metabolism, thus it is need adequate intake of these dietary components. It is advisable reduce ethanol, caffeine, fibers, phytic and ossalic acid intake. The efficacy of phytoestrogens is actually under investigation. Some drugs may interfere with calcium and other nutrients and produce an unfavourable effect on bone health.

Yellow-bellied Marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation

PubMed Central

Wojda, Samantha J.; McGee-Lawrence, Meghan E.; Gridley, Richard A.; Auger, Janene; Black, Hal L.; Donahue, Seth W.

2012-01-01

Reduced skeletal loading typically results in decreased bone strength and increased fracture risk for humans and many other animals. Previous studies have shown bears are able to prevent bone loss during the disuse that occurs during hibernation. Studies with smaller hibernators, which arouse intermittently during hibernation, show that they may lose bone at the microstructural level. These small hibernators, like bats and squirrels, do not utilize intracortical remodeling. However, slightly larger mammals like marmots do. In this study we examined the effects of hibernation on bone structural, mineral, and mechanical properties in yellow-bellied marmots (Marmota flaviventris). This was done by comparing cortical bone properties in femurs and trabecular bone properties in tibias from marmots killed before hibernation (fall) and after hibernation (spring). Age data were not available for this study; however, based on femur length the post-hibernation marmots were larger than the pre-hibernation marmots. Thus, cross-sectional properties were normalized by allometric functions of bone length for comparisons between pre- and post-hibernation. Cortical thickness and normalized cortical area were higher in post-hibernation samples; no other normalized cross-sectional properties were different. No cortical bone microstructural loss was evident in osteocyte lacunar measurements, intracortical porosity, or intracortical remodeling cavity density. Osteocyte lacunar area, porosity, and density were surprisingly lower in post-hibernation samples. Trabecular bone volume fraction was not different between pre- and post-hibernation. Measures of both trabecular and cortical bone mineral content were higher in post-hibernation samples. Three-point bending failure load, failure energy, elastic energy, ultimate stress, and yield stress were all higher in post-hibernation samples. These results support the idea that, like bears, marmots are able to prevent disuse osteoporosis during hibernation, thus preventing increased fracture risk and promoting survival of the extreme environmental conditions that occur in hibernation. PMID:22037004

Yellow-bellied marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation.

PubMed

Wojda, Samantha J; McGee-Lawrence, Meghan E; Gridley, Richard A; Auger, Janene; Black, Hal L; Donahue, Seth W

2012-01-01

Reduced skeletal loading typically results in decreased bone strength and increased fracture risk for humans and many other animals. Previous studies have shown bears are able to prevent bone loss during the disuse that occurs during hibernation. Studies with smaller hibernators, which arouse intermittently during hibernation, show that they may lose bone at the microstructural level. These small hibernators, like bats and squirrels, do not utilize intracortical remodeling. However, slightly larger mammals like marmots do. In this study we examined the effects of hibernation on bone structural, mineral, and mechanical properties in yellow-bellied marmots (Marmota flaviventris). This was done by comparing cortical bone properties in femurs and trabecular bone properties in tibias from marmots killed before hibernation (fall) and after hibernation (spring). Age data were not available for this study; however, based on femur length the post-hibernation marmots were larger than the pre-hibernation marmots. Thus, cross-sectional properties were normalized by allometric functions of bone length for comparisons between pre- and post-hibernation. Cortical thickness and normalized cortical area were higher in post-hibernation samples; no other normalized cross-sectional properties were different. No cortical bone microstructural loss was evident in osteocyte lacunar measurements, intracortical porosity, or intracortical remodeling cavity density. Osteocyte lacunar area, porosity, and density were surprisingly lower in post-hibernation samples. Trabecular bone volume fraction was not different between pre- and post-hibernation. Measures of both trabecular and cortical bone mineral content were higher in post-hibernation samples. Three-point bending failure load, failure energy, elastic energy, ultimate stress, and yield stress were all higher in post-hibernation samples. These results support the idea that, like bears, marmots are able to prevent disuse osteoporosis during hibernation, thus preventing increased fracture risk and promoting survival of the extreme environmental conditions that occur in hibernation. Copyright © 2011 Elsevier Inc. All rights reserved.

CALCIUM-47 IN THE STUDY OF BONE PHYSIOLOGY AND PATHOLOGY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guerin, R.A.

1962-06-01

The use of Ca/sup 45/, Ca/sup 47/, Ga/sup 67/, and Sr/sup 85/ in the study of Ca metabolism of bone in human subjects is discussed. Ca/sup 47/ is considered to be most suitable because of its short half-life ( approximates 5 days) and high specific activity (10 mc/mg for Ca/sup 47/ Cl/sub 2/). Studies were conducted in 28 patients injected intravenously with Ca/sup 47/; uptake in various bones was followed by external scintillometry for periods up to 11 days later. In healthy subjects the distribution of activity was symmetrical, with highest uptake in sternum and manubrium and lower uptake inmore » cranium (particularly the occipital region), clavicle, and iliac crest. Epiphyses of the long bones showed less avidity for Ca/sup 47/, that in tibia being highest. Sternum fixed 2 to 21/2 more Ca/sup 47/ than the upper tibial epiphysis. This indicates that in the normal adult more Ca is taken up by spongy than compact bone. The Ca/sup 47/ content of bone increased rapidly, reaching a plateau by the 5th or 6th day in most bones and by the 10th day in some, such as clavicle. Studies in pathologic cases showed the very high, but transient, uptake by callus in fractures and and uptake in Paget's disease of bone that was 3 times normal. Higher than normal uptake was also noted in bone lesions in lymphogranulomatosis, where osteogenesis compensating for increased bone destruction could be detected. Pathologic states could also be detected by following the disappearance of Ca/sup 47/ from plasma, it being delayed by hypercalcemia associated with multiple cancer metastases in bone or accelerated by hypocalcemia, such as in Paget's disease. The rate of urinary excretion of radioactivity was also of diagnostic value. (H.H.D.)« less

Synergy of bone marrow transplantation and curcumin ensue protective effects at early onset of diabetes in mice.

PubMed

Arivazhagan, Arivarasan; Krishna, Soni; Yadav, Shivangi; Shah, Harshit Rajesh; Kumar, Pravir; Ambasta, Rashmi Kumar

2015-07-01

The aim of this study was to investigate the early onset effects of diabetes on pro-angiogenic signaling pathway, total number of bone marrow cells, organs (pancreas and kidney) damage and the reversal effect of diabetes by combinatorial treatment of curcumin and bone marrow transplantation in streptozotocin (STZ) induced diabetic mice. In the present study, Streptozotocin induced diabetic mice were transplanted with bone marrow cells (2 × 10(6) ) followed by the administration of curcumin (80 mg/kg bodyweight). Effect of diabetes on the different organs was studied by H&E, Western blotting and immunofluorescence using vascular endothelial growth factor (VEGF), platelet/endothelial cell adhesion molecule (PECAM), insulin, Caspase-9 and Caspase-3 antibodies. The effect of diabetes results in the reduction of the total cell number and viability of the bone marrow cells, organ degeneration and lower VEGF/PECAM expression. However, transplantation with normal bone marrow cells significantly reduced the blood glucose levels (above normal range) and initiated the organ regeneration via the VEGF/PECAM mediated manner. Curcumin treatment further reduced the blood glucose level (near normal); and accelerated the organ regeneration, enhanced VEGF/PECAM expression and decreased caspase expression level in the organs. Curcumin also had a protective role against the glucotoxicity test performed on the bone marrow cells. This study suggests that bone marrow transplantation and curcumin administration is an effective treatment in reversing the early onset effects of diabetes via the VEGF/PECAM signaling pathway. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

A fundamental study of cryoablation on normal bone: diagnostic imaging and histopathology.

PubMed

Yoshimoto, Yuta; Azuma, Kazuo; Miya, Atsushi; Makino, Eiichi; Nakamoto, Hidekazu; Abe, Nobutaka; Kaburagi, Masashi; Ueda, Hisaki; Kuroda, Kohei; Tsuka, Takeshi; Sugiyama, Akihiko; Imagawa, Tomohiro; Murahata, Yusuke; Itoh, Norihiko; Osaki, Tomohiro; Shimizu, Tadashi; Okamoto, Yoshiharu

2014-10-01

Cryoablation is a minimally invasive cancer treatment. In this study, the effects of cryoablation on normal rabbit bone were evaluated using imaging and histopathological examinations. Cryoablation was performed using a Cryo-Hit (Galil Medical, Yokneam, Israel). Under anesthesia, one cryoablation needle was inserted at the center of the femur (day 0). To create an ice ball (2 x 3 cm), two 10-min freeze cycles were performed, separated by a 5-min thaw cycle. During cryoablation, changes in the bone and regional tissue were monitored using magnetic resonance imaging (MRI). MRI scans, computed tomography (CT) scans, and collections from the femur (for histopathological evaluation) were performed on days 7, 14, 28, and 56. In terms of the all rabbits' general conditions, we did not observe lameness, decreased appetite, or any other side effects during the experimental periods. Histopathological evaluations of the femur were performed using hematoxylin and eosin staining. MRI indicated inflammation around the ice ball on day 7. Subsequently, the area of inflammation gradually decreased from days 14 to 56. In the histopathological examination, necrosis of bone marrow cells and endosteum were observed from days 7 to 56. No regeneration of bone marrow cells was observed during the experimental period. On the other hand, cryoablation did not influence osteoblasts. Furthermore, there was no pathologic fracture during the experimental period. Our results suggest that cryoablation does not induce severe adverse effects on normal bone, and therefore has potential as a therapeutic option for bone tumors, including metastatic tumors to bone. Copyright © 2014 Elsevier Inc. All rights reserved.

PET Index of Bone Glucose Metabolism (PIBGM) Classification of PET/CT Data for Fever of Unknown Origin Diagnosis

PubMed Central

Yang, Jian; Liu, Xinxin; Ai, Danni; Fan, Jingfan; Zheng, Youjing; Li, Fang; Huo, Li; Wang, Yongtian

2015-01-01

Objectives Fever of unknown origin (FUO) remains a challenge in clinical practice. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is helpful in diagnosing the etiology of FUO. This paper aims to develop a completely automatic classification method based on PET/CT data for the computer-assisted diagnosis of FUO. Methods We retrospectively analyzed the FDG PET/CT scan of 175 FUO patients, 79 males and 96 females. The final diagnosis of all FUO patients was achieved through pathology or clinical evaluation, including 108 normal patients and 67 FUO patients. CT anatomic information was used to acquire bone functional information from PET images. The skeletal system of FUO patients was classified by analyzing the standardized uptake value (SUV) and the PET index of bone glucose metabolism (PIBGM). The SUV distributions in the bone marrow and the bone cortex were also studied in detail. Results The SUV and PIBGM of the bone marrow only slightly differed between the FUO patients and normal people, whereas the SUV of whole bone structures and the PIBGM of the bone cortex significantly differed between the normal people and FUO patients. The method detected 43 patients from 67 FUO patients, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 64.18%, 95%, 93.48%, 72.73%, and 83.33%, respectively. Conclusion The experimental results demonstrate that the study can achieve automatic classification of FUO patients by the proposed novel biomarker of PIBGM, which has the potential to be utilized in clinical practice. PMID:26076139

Influence of weight and body fat distribution on bone density in postmenopausal women.

PubMed

Murillo-Uribe, A; Carranza-Lira, S; Martínez-Trejo, N; Santos-González, J

2000-01-01

To determine whether obesity or body fat distribution induces a greater modification on bone remodeling biochemistry (BRB) and bone density in postmenopausal women. One hundred and thirteen postmenopausal patients were studied. They were initially divided according to body mass index (BMI), and afterwards by waist-hip ratio (WHR) as well as combinations of the two factors. Hormone measurements and assessments of BRB were also done. Dual-emission X-ray absorptiometry from the lumbar column and hip was performed with Lunar DPXL equipment, and the standard deviation in relation to young adult (T) and age-matched subjects (Z) was calculated. Statistical analysis was done by the Mann-Whitney U test. The relation of BMI and WHR with the variables was calculated by simple regression analysis. When divided according to BMI, there was greater bone density in the femoral neck in those with normal weight. After dividing according to WHR, the Z scores had a trend to a lesser decrease in those with upper level body fat distribution. Divided according to BMI and WHR, obese patients with upper-level body fat distribution had greater bone density in the lumbar column than those with normal weight and lower-level body fat distribution. With the same WHR, those with normal weight had greater bone density than those who were obese. A beneficial effect of upper-level body fat distribution on bone density was found. It is greater than that from obesity alone, and obesity and upper-level body fat distribution have an additive effect on bone density.

Chondrocyte burst promotes space for mineral expansion.

PubMed

Hara, Emilio Satoshi; Okada, Masahiro; Nagaoka, Noriyuki; Hattori, Takako; Iida, Letycia Mary; Kuboki, Takuo; Nakano, Takayoshi; Matsumoto, Takuya

2018-01-22

Analysis of tissue development from multidisciplinary approaches can result in more integrative biological findings, and can eventually allow the development of more effective bioengineering methods. In this study, we analyzed the initial steps of mineral formation during secondary ossification of mouse femur based on biological and bioengineering approaches. We first found that some chondrocytes burst near the mineralized area. External factors that could trigger chondrocyte burst were then investigated. Chondrocyte burst was shown to be modulated by mechanical and osmotic pressure. A hypotonic solution, as well as mechanical stress, significantly induced chondrocyte burst. We further hypothesized that chondrocyte burst could be associated with space-making for mineral expansion. In fact, ex vivo culture of femur epiphysis in hypotonic conditions, or under mechanical pressure, enhanced mineral formation, compared to normal culture conditions. Additionally, the effect of mechanical pressure on bone formation in vivo was investigated by immobilization of mouse lower limbs to decrease the body pressure onto the joints. The results showed that limb immobilization suppressed bone formation. Together, these results suggest chondrocyte burst as a novel fate of chondrocytes, and that manipulation of chondrocyte burst with external mechano-chemical stimuli could be an additional approach for cartilage and bone tissue engineering.

Bone scintigraphy in the investigation of occult lameness in the dog.

PubMed

Schwarz, T; Johnson, V S; Voute, L; Sullivan, M

2004-05-01

99mTechnetium methylene diphosphonate (99mTc-MDP) scintigraphy was performed in 14 dogs of different breeds after clinical lameness examination, radiography and synovial fluid analysis failed to localise lameness to a specific area of pain. The scintigraphic protocol included an intravenous injection of 17 MBq 99mTc-MDP/kg bodyweight and vascular, soft tissue and bone phase scans in standardised positions with a low-energy all-purpose collimator. Confirmation of diagnosis was achieved in nine dogs by arthroscopy, repeated lesion-orientated radiography, computed tomography and response to treatment. In seven cases, bone phase scans showed single elbow uptakes, in two cases unilateral limb uptake, and in one case each a single shoulder and tibia uptake; in three cases there was no increased uptake. Vascular and soft tissue phase images did not reveal additional information. Diagnosis of humeral condyle fissures, a fragmented medial coronoid process, panosteitis and arthropathy was possible in nine cases. Skeletal pathology was ruled out in three normal scintigrams. In two dogs with unilateral uptake of multiple joints, no diagnostic benefit was gained from scintigraphy. The highly sensitive and relatively specific uptake allowed localisation and characterisation or exclusion of skeletal lesions in most dogs.

MANAGEMENT OF BILATERAL FEMORAL NECK FRACTURE IN A NONAGENARIAN PATIENT--CASE REPORT.

PubMed

Popescu, D; Trandabaţ, C; Puha, B; Veliceasa, B; Alexa, O

2016-01-01

Simultaneous bilateral femoral neck fracture is rare injury. Cases with this type of fracture have been reported in the literature since the 1950s, following the introduction of electroconvulsive therapy which generates violent hip muscle contractions. In young patients' simultaneous bilateral femoral neck fracture results from high energy trauma (car accident or fall from height) in a normal bone. Pathological changes in bone structure occurring in chronic kidney disease, vitamin D deficiency, osteomalacia, osteoporosis, metabolic imbalances and administration of corticosteroids explain the occurrence of this particular type of fracture following low-energy trauma. We present the case of a 90-year-old female patient who suffered a simple fall from her own height resulting in a Garden IV bilateral femoral neck fracture. Our therapeutic option in this patient was bilateral uncemented bipolar hemiarthroplasty in a single session using a single tray of sterile surgical instruments and two sterile drapes. Postoperative outcome was very good, allowing the initiation of functional recovery on the first postoperative day. Uncemented hemiarthroplasty proved to be a good choice in such a patient in the associated diseases may trigger the risk of cardiovascular disturbances specific to bone cement implantation syndrome.

Chondroblastoma of the patella with aneurysmal bone cyst.

PubMed

Tan, Honglue; Yan, Mengning; Yue, Bing; Zeng, Yiming; Wang, You

2014-01-01

Chondroblastoma of the patella is rare. Aneurysmal bone cysts, which develop from a prior lesion such as a chondroblastoma, are seldom seen in the patella. The authors report a case of a 36-year-old man who presented with 2 years of right knee pain without calor, erythema, pain on palpation, or abnormal range of motion. Radiological studies suggested aneurysmal bone cyst. The lesion was excised with curettage and the residual cavity filled with autogenous bone graft. Histopathology revealed chondroblastoma associated with a secondary aneurysmal bone cyst. In the follow-up period, the patient demonstrated normal joint activities with no pain. Normal configuration of the patella and bone union were shown on plain radiographs. The authors present a review of the literature of all cases of patellar chondroblastoma with aneurysmal bone cyst. This case is the 14th report of aneurysmal bone cyst arising in a chondroblastoma of the patella. According to the literature, computed tomography and magnetic resonance imaging are useful in the study of these lesions. The pathologic diagnosis is based on the presence of chondroblastoma and aneurysmal bone cyst. Treatment of this lesion includes patellectomy, curettage alone, and curettage with bone grafting. Despite the risk of recurrence of this lesion in the patella, the authors first recommend curettage followed by filling the cavity with bone graft. To protect the anterior tension of the patella intraoperatively, the bone window should be made at the medial edge of the patella to perform the curettage and bone grafting.

Bone aluminium in haemodialysed patients and in rats injected with aluminium chloride: relationship to impaired bone mineralisation.

PubMed Central

Ellis, H A; McCarthy, J H; Herrington, J

1979-01-01

Iliac bone aluminium was determined by neutron activation analysis in 34 patients with chronic renal failure and in eight control subjects. In 17 patients treated by haemodialysis there was a significant increase in the amount of aluminium (mean +/- SE = 152 +/- 30 ppm bone ash). In eight patients treated by haemodialysis and subsequent renal transplantation, bone aluminium was still significantly increased (92 +/- 4.5 ppm bone ash) but was less than in the haemodialysed patients. In some patients aluminium persisted in bone for many years after successful renal transplantation. There was no relationship between hyperparathyroidism and bone aluminium. Although no statistically significant relationship was found between the mineralisation status of bone and bone aluminium, patients dialysed for the longest periods tended to be those with the highest levels of aluminium, osteomalacia, and dialysis encephalopathy. In 20 rats given daily intraperitoneal injections of aluminium chloride for periods of up to three months, there was accumulation of aluminium in bone (163 +/- 9 ppm ash) to levels comparable to those obtained in the dialysis patients, and after about eight weeks osteomalacia developed. The increased bone aluminium and osteomalacia persisted after injections had been stopped for up to 49 days, although endochondral ossification was restored to normal. As a working hypothesis it is suggested that aluminium retained in the bone of the dialysis patients and the experimental animals interferes with normal mineralisation. Images Fig. 5 Fig. 6 PMID:389958

Ultrasonography of the distal limbs in Nellore and Girolando calves 8 to 12 months of age

PubMed Central

2014-01-01

Background Ultrasonography can be used anywhere and allows rapid, noninvasive differentiation of soft tissue structures of the musculoskeletal system. The objectives of this study were to describe the ultrasonographic appearance of the structures of the metacarpo-/metatarsophalangeal and the interphalangeal joints, the appearance of the growth plates of the distal metacarpus/metatarsus and of the proximal phalanx and to measure the cross-sectional dimensions of the DDFT and SDFT in Nellore and Girolando calves eight to 12 months of age. Results In the longitudinal dorsal view the common digital extensor tendon and the digital extensor tendon were depicted as echogenic parallel fiber bundles located directly under the skin. The joint spaces appeared as anechoic interruptions of the hyperechogenic bone surfaces. The normal amount of synovial fluid could not be depicted. The growth plates were seen as anechoic interruptions of the bone surface proximal and distal to the fetlock joint space. In transverse sonograms of the distal palmar/plantar regions, the flexor tendons and branchs of the suspensory ligament were imaged as echogenic structures. The lumen of the digital flexor tendon sheath could not be imaged in these normal cattle. The thin digital distal annular ligament and the reversal of positions of the DDFT and SDFT could be appreciated. No significant differences were found between the cross-sectional measurements of the DDFT and the SDFT from Nellore and Girolando in any age, thoracic/pelvic limbs, right/left sides and lateral/medial digits. Conclusions The results of this study establish important ultrasonographic reference data of the normal structures of the distal limbs and the normal dimensions of the flexor tendons in Nellore and Girolando calves for use in clinical practice. PMID:24774582

Bone structure studies with holographic interferometric nondestructive testing and x-ray methods

NASA Astrophysics Data System (ADS)

Silvennoinen, Raimo; Nygren, Kaarlo; Rouvinen, Juha; Petrova, Valentina V.

1994-02-01

Changes in the biomechanics and in the molecular texture and structure of isolated radioulnar bones of subadult European moose (Alces alces L.) collected in various environmentally polluted areas of Finland were investigated by means of holographic interferometric non- destructive testing (HNDT), radiological, morphometrical, and x-ray diffraction methods. By means of small caudal-cranial bending forces, the surface movements of the lower end (distal epiphysis) of the radial bone were recorded with the HNDT method. To study bone molecular texture and structure changes under external compressing forces, the samples for x-ray diffraction analysis were taken from the upper end of the ulnar bone (olecranon tip). Results showed that the bones obtained from the Harjavalta area and those of North Karelian moose showing malnutrition and healing femoral fractures produced different HNDT pictures compared with the four normally developed North Karelian moose. In the x-ray diffraction, the Harjavalta samples showed changes in molecular texture and structure compared with the samples from the apparently normal North Karelian animals.

CELLS INVOLVED IN THE IMMUNE RESPONSE

PubMed Central

Abdou, Nabih I.; Richter, Maxwell

1969-01-01

Rabbits were made immunologically tolerant to either human serum albumin or bovine gamma globulin by the neonatal administration of antigen. At 10 wk of age, they were challenged with the tolerogenic antigen and found to be non-responsive. However, these tolerant rabbits could respond with humoral antibody formation directed toward the tolerogenic antigen if they were treated with normal, allogeneic bone marrow or bone marrow obtained from a rabbit made tolerant toward a different antigen. They were incapable of responding if they were given bone marrow obtained from a rabbit previously made tolerant to the tolerogenic antigen. Irradiated rabbits were unable to respond if treated with tolerant bone marrow, but could respond well if given normal bone marrow. Since it has previously been demonstrated that the antibody-forming cell, in an irradiated recipient of allogeneic bone marrow, is of recipient and not donor origin, the data presented strongly indicate that the unresponsive cell in the immunologically tolerant rabbit is the antigen-reactive cell. PMID:4183777

Predicting Bone Mechanical Properties of Cancellous Bone from DXA, MRI, and Fractal Dimensional Measurements

NASA Technical Reports Server (NTRS)

Harrigan, Timothy P.; Ambrose, Catherine G.; Hogan, Harry A.; Shackleford, Linda; Webster, Laurie; LeBlanc, Adrian; Lin, Chen; Evans, Harlan

1997-01-01

This project was aimed at making predictions of bone mechanical properties from non-invasive DXA and MRI measurements. Given the bone mechanical properties, stress calculations can be made to compare normal bone stresses to the stresses developed in exercise countermeasures against bone loss during space flight. These calculations in turn will be used to assess whether mechanical factors can explain bone loss in space. In this study we assessed the use of T2(sup *) MRI imaging, DXA, and fractal dimensional analysis to predict strength and stiffness in cancellous bone.

Excessive Vitamin E Intake Does Not Cause Bone Loss in Male or Ovariectomized Female Mice Fed Normal or High-Fat Diets.

PubMed

Ikegami, Hiroko; Kawawa, Rie; Ichi, Ikuyo; Ishikawa, Tomoko; Koike, Taisuke; Aoki, Yoshinori; Fujiwara, Yoko

2017-10-01

Background: Animal studies on the effects of vitamin E on bone health have yielded conflicting and inconclusive results, and to our knowledge, no studies have addressed the effect of vitamin E on bone in animals consuming a high-fat diet (HFD). Objective: This study aimed to evaluate the effect of excessive vitamin E on bone metabolism in normal male mice and ovariectomized female mice fed a normal diet (ND) or HFD. Methods: In the first 2 experiments, 7-wk-old male mice were fed an ND (16% energy from fat) containing 75 (control), 0 (vitamin E-free), or 1000 (high vitamin E) mg vitamin E/kg (experiment 1) or an HFD (46% energy from fat) containing 0, 200, 500, or 1000 mg vitamin E/kg (experiment 2) for 18 wk. In the third experiment, 7-wk-old sham-operated or ovariectomized female mice were fed the ND (75 mg vitamin E/kg) or HFD containing 0 or 1000 mg vitamin E/kg for 8 wk. At the end of the feeding period, blood and femurs were collected to measure bone turnover markers and analyze histology and microcomputed tomography. Results: In experiments 1 and 2, vitamin E intake had no effect on plasma alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activity, or bone formation, resorption, or volume in femurs in mice fed the ND or HFDs. In experiment 3, bone volume was significantly reduced (85%) in ovariectomized mice compared with that in sham-operated mice ( P < 0.05), but it did not differ among mice fed the 3 diets. Plasma ALP and TRAP activities and bone formation and resorption in femur were similar among ovariectomized mice fed the HFD containing 0 or 1000 mg vitamin E/kg. Conclusions: The results suggest that excess vitamin E intake does not cause bone loss in normal male mice or in ovariectomized or sham-operated female mice, regardless of dietary fat content. © 2017 American Society for Nutrition.

Crystallographic orientation of the c-axis of biological apatite as a new index of the quality of subchondral bone in knee joint osteoarthritis.

PubMed

Lee, Jee-Wook; Kobayashi, Akio; Nakano, Takayoshi

2017-05-01

The aim of the present study was to investigate the preferred orientation of biological apatite (BAp) as a new index of the quality of subchondral bone (SB) in knee joint osteoarthritis (OA). Ten OA and five normal knee joints were obtained. Thickness, quantity and bone mineral density (BMD) of SB were analyzed at the medial condyle of the femur in dry conditions by peripheral quantitative computed tomography. In addition, the preferred crystallographic orientation of the c-axis of BAp was evaluated as bone quality parameter using a microbeam X-ray diffractometer technique. BMD and thickness of SB were significantly increased in OA specimens compared to normal knee specimens (P < 0.01), and the preferred orientation of the c-axis of BAp along the normal direction of SB surface was significantly higher in OA specimens (P < 0.01), reflecting the change in stress of concentration in the pathological portion without cartilage. SB sclerosis in OA results in both proliferation of bone tissues and enhanced degree of preferential alignment of the c-axis of BAp. Our findings could have major implications for the diagnosis of clinical studies, including pathologic elucidation in OA.

Survival and characteristics of murine leukaemic and normal stem cells after hyperthermia: a murine model for human bone marrow purging.

PubMed

Gidáli, J; Szamosvölgyi, S; Fehér, I; Kovács, P

1990-01-01

The effect of hyperthermia in vitro on the survival and leukaemogenic effectiveness of WEHI 3-B cells and on the survival and transplantation efficiency of bone marrow cells was compared in a murine model system. Normal murine clonogenic haemopoietic cells (day 9 CFU-S and CFU-GM) proved to be significantly less sensitive to 42.5 degrees C hyperthermia (Do values: 54.3 and 41.1 min, respectively) than leukaemic clonogenic cells (CFU-L) derived from suspension culture or from bone marrow of leukaemic mice (Do: 17.8 min). Exposure for 120 min to 42.5 degrees C reduced the surviving fraction of CFU-L to 0.002 and that of CFU-S to 0.2. If comparable graft sizes were transplanted from normal or heat exposed bone marrow, 60-day survival of supralethally irradiated mice was similar. Surviving WEHI 3-B cells were capable of inducing leukaemia in vivo. The two log difference in the surviving fraction of CFU-L and CFU-S after 120 min exposure to 42.5 degrees C suggests that hyperthermia ex vivo may be a suitable purging method for autologous bone marrow transplantation.

Design and analysis of a novel mechanical loading machine for dynamic in vivo axial loading

NASA Astrophysics Data System (ADS)

Macione, James; Nesbitt, Sterling; Pandit, Vaibhav; Kotha, Shiva

2012-02-01

This paper describes the construction of a loading machine for performing in vivo, dynamic mechanical loading of the rodent forearm. The loading machine utilizes a unique type of electromagnetic actuator with no mechanically resistive components (servotube), allowing highly accurate loads to be created. A regression analysis of the force created by the actuator with respect to the input voltage demonstrates high linear correlation (R2 = 1). When the linear correlation is used to create dynamic loading waveforms in the frequency (0.5-10 Hz) and load (1-50 N) range used for in vivo loading, less than 1% normalized root mean square error (NRMSE) is computed. Larger NRMSE is found at increased frequencies, with 5%-8% occurring at 40 Hz, and reasons are discussed. Amplifiers (strain gauge, linear voltage displacement transducer (LVDT), and load cell) are constructed, calibrated, and integrated, to allow well-resolved dynamic measurements to be recorded at each program cycle. Each of the amplifiers uses an active filter with cutoff frequency at the maximum in vivo loading frequencies (50 Hz) so that electronic noise generated by the servo drive and actuator are reduced. The LVDT and load cell amplifiers allow evaluation of stress-strain relationships to determine if in vivo bone damage is occurring. The strain gauge amplifier allows dynamic force to strain calibrations to occur for animals of different sex, age, and strain. Unique features are integrated into the loading system, including a weightless mode, which allows the limbs of anesthetized animals to be quickly positioned and removed. Although the device is constructed for in vivo axial bone loading, it can be used within constraints, as a general measurement instrument in a laboratory setting.

Design and analysis of a novel mechanical loading machine for dynamic in vivo axial loading.

PubMed

Macione, James; Nesbitt, Sterling; Pandit, Vaibhav; Kotha, Shiva

2012-02-01

This paper describes the construction of a loading machine for performing in vivo, dynamic mechanical loading of the rodent forearm. The loading machine utilizes a unique type of electromagnetic actuator with no mechanically resistive components (servotube), allowing highly accurate loads to be created. A regression analysis of the force created by the actuator with respect to the input voltage demonstrates high linear correlation (R(2) = 1). When the linear correlation is used to create dynamic loading waveforms in the frequency (0.5-10 Hz) and load (1-50 N) range used for in vivo loading, less than 1% normalized root mean square error (NRMSE) is computed. Larger NRMSE is found at increased frequencies, with 5%-8% occurring at 40 Hz, and reasons are discussed. Amplifiers (strain gauge, linear voltage displacement transducer (LVDT), and load cell) are constructed, calibrated, and integrated, to allow well-resolved dynamic measurements to be recorded at each program cycle. Each of the amplifiers uses an active filter with cutoff frequency at the maximum in vivo loading frequencies (50 Hz) so that electronic noise generated by the servo drive and actuator are reduced. The LVDT and load cell amplifiers allow evaluation of stress-strain relationships to determine if in vivo bone damage is occurring. The strain gauge amplifier allows dynamic force to strain calibrations to occur for animals of different sex, age, and strain. Unique features are integrated into the loading system, including a weightless mode, which allows the limbs of anesthetized animals to be quickly positioned and removed. Although the device is constructed for in vivo axial bone loading, it can be used within constraints, as a general measurement instrument in a laboratory setting.

Percutaneous osteoplasty with a bone marrow nail for fractures of long bones: experimental study.

PubMed

Nakata, Kouhei; Kawai, Nobuyuki; Sato, Morio; Cao, Guang; Sahara, Shinya; Tanihata, Hirohiko; Takasaka, Isao; Minamiguchi, Hiroyuki; Nakai, Tomoki

2010-09-01

To develop percutaneous osteoplasty with the use of a bone marrow nail for fixation of long-bone fractures, and to evaluate its feasibility and safety in vivo and in vitro. Six long bones in three healthy swine were used in the in vivo study. Acrylic cement was injected through an 11-gauge bone biopsy needle and a catheter into a covered metallic stent placed within the long bone, creating a bone marrow nail. In the in vitro study, we determined the bending, tug, and compression strengths of the acrylic cement nails 9 cm long and 8 mm in diameter (N = 10). The bending strength of the artificially fractured bones (N = 6) restored with the bone marrow nail and cement augmentation was then compared with that of normal long bones (N = 6). Percutaneous osteoplasty with a bone marrow nail was successfully achieved within 1 hour for all swine. After osteoplasty, all swine regained the ability to run until they were euthanized. Blood tests and pathologic findings showed no adverse effects. The mean bending, tug, and compression strengths of the nail were 91.4 N/mm(2) (range, 75.0-114.1 N/mm(2)), 20.9 N/mm(2) (range, 6.6-30.4 N/mm(2)), and 103.0 N/mm(2) (range, 96.3-110.0 N/mm(2)), respectively. The bending strength ratio of artificially fractured bones restored with bone marrow nail and cement augmentation to normal long bone was 0.32. Percutaneous osteoplasty with use of a bone marrow nail and cement augmentation appears to have potential in treating fractures of non-weight-bearing long bones. Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.

Impact of endocrine hyperfunction and phosphate wasting on bone in McCune-Albright syndrome.

PubMed

Lala, R; Matarazzo, P; Andreo, M; Defilippi, C; de Sanctis, C

2002-01-01

Skin dysplasia, as café-au-lait spots, bone fibrous dysplasia and peripheral endocrinopathies are the main clinical features of McCune-Albright syndrome (MAS). This illness is due to activating mutations of the Gsalpha protein and is spread with a mosaic pattern in affected tissues that consist of intermixed areas of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic pituitary control, is the hallmark of the endocrine syndromes: precocious puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In addition, phosphate wasting as hyperphosphaturia is often present. The impact of hormonal hypersecretion and phosphate loss on the bones of patients with MAS is poorly understood both in normal and fibrous bone tissue. As hypercortisolism and hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone hypersecretion stimulate bone growth and mineralization, and phosphate wasting reduces bone mineral content. All these actions can be exerted at varying times and degrees in a single patient on lesional and non-lesional bones. Sonographic evidence of multiple diffused hyperechogenic spots in the testes of patients with MAS do not seem to be related to alterations in calcium-phosphate metabolism but rather to zonal dysplasia/hyperplasia of testicular tissue.

Total bone calcium in normal women: effect of age and menopause status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallagher, J.C.; Goldgar, D.; Moy, A.

1987-12-01

Bone density in different regions of the skeleton was measured in 392 normal women aged 20-80 years by dual photon absorpiometry. In premenopausal women, aged 25-50 years, multiple regression analysis of regional bone density on age, height, and weight showed a small significant decrease in total bone density (less than 0.01) but no significant change in other regions of the skeleton. In postmenopausal women there were highly significant decreases in all regions of the skeleton (p less than 0.001), and bone density in these areas decreased as a logarithmic function of years since menopause. Based on multiple regression analyses, themore » decrease in spine density and total bone calcium was 2.5-3.0 times greater in the 25 years after menopause than the 25 years before menopause. The largest change, however, occurred in the first five years after menopause. During this time the estimated annual change in spine density and total bone calcium was about 10 times greater than that in the premenopausal period. These results demonstrate the important effect of the menopause in determining bone mass in later life.« less

Single- and dual-photon absorptiometry in osteoporosis and osteomalacia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wahner, H.W.

Single- and dual-photon absorptiometric methods have been used in the past to identify populations at risk for bone loss, to define the osteoporotic syndrome in terms of bone mass, and to evaluate treatment regimens to prevent bone loss. Technical improvements have made these procedures available for the nontraumatic measurement of bone mineral in the management of the individual patient suspected of having osteoporosis or other bone loss. This requires a different approach to data interpretation because decisions have to be made on the basis of a single measurement. Osteoporosis and osteomalacia cannot be distinguished by bone mineral measurements because bothmore » are characterized by a decrease in content of bone mineral. Bone mineral measurements can be used to assess the risk of fracture and, with it, the severity of bone loss. This allows treatment decisions to be made. Repeated measurements made under well-defined conditions allow estimation of long-term rate of bone loss and monitoring of treatment effect. 38 references.« less

Curative bone marrow transplantation in erythropoietic protoporphyria after reversal of severe cholestasis.

PubMed

Wahlin, Staffan; Aschan, Johan; Björnstedt, Mikael; Broomé, Ulrika; Harper, Pauline

2007-01-01

We report the case of a middle-age patient presenting with severe progressive protoporphyric cholestasis. To halt further progression of liver disease, medical treatment was given aimed at different mechanisms possibly causing cholestasis in erythropoietic protoporphyria. Within eighty days, liver biochemistry completely normalized and liver histology markedly improved. Bone marrow transplantation was performed to prevent relapse of cholestatic liver disease by correcting the main site of protoporphyrin overproduction. Thirty-three months after cholestatic presentation and ten months after bone marrow transplantation, liver and porphyrin biochemistry remains normal. The patient is in excellent condition and photosensitivity is absent. The theoretical role of each treatment used to successfully reverse cholestasis and the role of bone marrow transplantation in erythropoietic protoporphyria are discussed. Medical treatment can resolve hepatic abnormalities in protoporphyric cholestasis. Bone marrow transplantation achieves phenotypic reversal and may offer protection from future protoporphyric liver disease.

Evaluation of cortical bone mass, thickness and density by z-scores in osteopenic conditions and in relation to menopause and estrogen treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meema, S.; Meema, H.E.

1982-08-01

Z-scores express, differences from normals in standard deviation units, and are particularly useful for comparison of changes where normal values are age- and sex-dependent. We determined z-scores for bone mineral mass, cortical thickness, and bone mineral density in the radius in various conditions and diseases in both sexes. In the males, z-scores were calculated for age, but in the females z-scores for menopausal status (years postmenopausal exclusive of years on estrogen treatment) were found to be more appropriate. With few exceptions, changes in a disease were of a similar order in both sexes. For bone minerals mass few mean z-scoresmore » were significantly increased, but diseases with significantly decreased mean z-scores were numerous. The usefulness of z-scores in diagnosis and study of metabolic bone disease is discussed.« less

Cochlear pathology in chronic suppurative otitis media.

PubMed

Walby, A P; Barrera, A; Schuknecht, H F

1983-01-01

Chronic suppurative otitis media (COM) is reported to cause elevation of bone-conduction thresholds either by damage to cochlear sensorineural structures or by alteration in the mechanics of sound transmission in the ear. A retrospective study was made of the medical records of 87 patients with unilateral uncomplicated COM to document that abnormality in bone conduction does exist. In a separate study the cochlear pathology in 12 pairs of temporal bones with unilateral COM was studied by light microscopy. Infected ears showed higher than normal mean bone-conduction thresholds by amounts ranging from 1 dB at 500 Hz to 9.5 dB at 4,000 Hz. The temporal bones showed no greater loss of specialized sensorineural structures in infected ears than in normal control ears. Because there is no evidence that COM caused destruction of hair cells or cochlear neurons, alteration in the mechanics of sound transmission becomes a more plausible explanation for the hearing losses.

Effects of voluntary running exercise on bone histology in type 2 diabetic rats.

PubMed

Takamine, Yuri; Ichinoseki-Sekine, Noriko; Tsuzuki, Takamasa; Yoshihara, Toshinori; Naito, Hisashi

2018-01-01

The incidence of obesity in children and adolescents, which may lead to type 2 diabetes, is increasing. Exercise is recommended to prevent and improve diabetes. However, little is known about the bone marrow environment at the onset of diabetes in the young, and it is unclear whether exercise training is useful for maintaining bone homeostasis, such as mechanical and histological properties. Thus, this study clarified the histological properties of bone and whether exercise contributes to maintaining bone homeostasis at the onset of type 2 diabetes in rats. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF; n = 21) rats as a diabetic model and Long-Evans Tokushima Otsuka (LETO; n = 18) rats as a control were assigned randomly to four groups: the OLETF sedentary group (O-Sed; n = 11), OLETF exercise group (O-Ex; n = 10), LETO sedentary group (L-Sed; n = 9), and LETO exercise group (L-Ex; n = 9). All rats in the exercise group were allowed free access to a steel running wheel for 20 weeks (5-25 weeks of age). In the glucose tolerance test, blood glucose level was higher in the O-Sed group than that in the L-Sed and L-Ex groups, and was markedly suppressed by the voluntary running exercise of O-Ex rats. The energy to fracture and the two-dimensional bone volume at 25 weeks of age did not differ significantly among the groups, though the maximum breaking force and stiffness were lower in OLETF rats. However, bone marrow fat volume was greater in O-Sed than that in L-Sed and L-Ex rats, and was markedly suppressed by wheel running in the O-Ex rats. Our results indicate that exercise has beneficial effects not only for preventing diabetes but also on normal bone remodeling at an early age.

Using cell and organ culture models to analyze responses of bone cells to mechanical stimulation.

PubMed

Pitsillides, Andrew A; Rawlinson, Simon C F

2012-01-01

Bone cells of the osteoblastic lineage are responsive to the local mechanical environment. Through integration of a number of possible loading-induced regulatory stimuli, osteocyte, osteoblast, and osteoclast behaviour is organized to fashion a skeletal element of sufficient strength and toughness to resist fracture and crack propagation. Early pre-osteogenic responses had been determined in vivo and this led to the development of bone organ culture models to elucidate other pre-osteogenic responses where osteocytes and osteoblasts retain the natural orientation, connections and attachments to their native extracellular matrix. The application of physiological mechanical loads to bone in these organ culture models generates the regulatory stimuli. As a consequence, these experiments can be used to illustrate the distinctive mechanisms by which osteocytes and osteoblasts respond to mechanical loads and also differences in these responses, suggesting co-ordinated and cooperatively between cell populations. Organ explant cultures are awkward to maintain, and have a limited life, but length of culture times are improving. Monolayer cultures are much easier to maintain and permit the application of a particular mechanical stimulation to be studied in isolation; mainly direct mechanical strain or fluid shear strains. These allow for the response of a single cell type to the applied mechanical stimulation to be monitored precisely.The techniques that can be used to apply mechanical strain to bone and bone cells have not advanced greatly since the first edition. The output from such experiments has, however, increased substantially and their importance is now more broadly accepted. This suggests a growing use of these approaches and an increasing awareness of the importance of the mechanical environment in controlling normal bone cell behaviour. We expand the text to include additions and modifications made to the straining apparatus and update the research cited to support this growing role of cell and organ culture models to analyze responses of bone cells to mechanical stimulation.

New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herlin, Maria, E-mail: maria.herlin@ki.se; Finnilä, Mikko A.J., E-mail: mikko.finnila@oulu.fi; Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu

Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr{sup −/−}) and wild-type (Ahr{sup +/+}) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serummore » levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr{sup +/+} mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr{sup −/−} mice displayed a slightly modified bone phenotype as compared with untreated Ahr{sup +/+} mice, while TCDD exposure caused only a few changes in bones of Ahr{sup −/−} mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr{sup +/+} mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation results in increased trabecular bone and softer cortical bone. • TCDD does not affect the bones of Ahr{sup –/–} mice.« less

The ability of multipotent mesenchymal stromal cells from the bone marrow of patients with leukemia to maintain normal hematopoietic progenitor cells.

PubMed

Sorokina, Tamara; Shipounova, Irina; Bigildeev, Alexey; Petinati, Nataliya; Drize, Nina; Turkina, Anna; Chelysheva, Ekaterina; Shukhov, Oleg; Kuzmina, Larisa; Parovichnikova, Elena; Savchenko, Valery

2016-09-01

The development of leukemia impairs normal hematopoiesis and marrow stromal microenvironment. The aim of the investigation was to study the ability of multipotent mesenchymal stromal cells (MSCs) derived from the bone marrow of patients with leukemia to maintain normal hematopoietic progenitor cells. MSCs were obtained from the bone marrow of 14 patients with acute lymphoblastic (ALL), 25 with myeloid (AML), and 15 with chronic myeloid (CML) leukemia. As a control, MSCs from 22 healthy donors were used. The incidence of cobblestone area forming cells (CAFC 7-8 d) in the bone marrow of healthy donor cultivated on the supportive layer of patients MSCs was measured. The ability of MSCs from AML and ALL patients at the moment of diagnosis to maintain normal CAFC was significantly decreased when compared to donors. After chemotherapy, the restoration of ALL patients' MSCs functions was slower than that of AML. CML MSCs maintained CAFC better than donors' at the moment of diagnosis and this ability increased with treatment. The ability of patients' MSCs to maintain normal hematopoietic progenitor cells was shown to change in comparison with MSCs from healthy donors and depended on nosology. During treatment, the functional capacity of patients' MSCs had been partially restored. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acoustic emission from trabecular bone during mechanical testing: the effect of osteoporosis and osteoarthritis.

PubMed

Leichter, I; Bivas, A; Margulies, J Y; Roman, I; Simkin, A

1990-01-01

This study examines the relation between the nature of acoustic emission signals emitted from cancellous bone under compression and the mechanical properties of the tissue. The examined bone specimens were taken from 12 normal, 31 osteoporotic and six osteoarthritic femoral heads. The mechanical behaviour of the osteoporotic bone specimens was found to be significantly different from that of the normal specimens both in the pre-yield and post-yield ranges. In the osteoarthritic bones only the elastic behaviour was significantly different. The rates of acoustic events before yield and beyond it were found to be significantly higher both in the osteoporotic and osteoarthritic bone specimens. The average peak amplitude of the signals was also significantly higher in the diseased bones. Stepwise regression analysis showed that a combination of the acoustic emission parameters could significantly predict some mechanical properties of the bone. The energy absorbed during compression and the ultimate compressive stress of the specimens could be estimated from the rate of pre-yield acoustic events, the average amplitude of the signals and the rate of post-yield events. However, the explanation power of the acoustic emission parameters was only moderate. The nature of acoustic emission signals was thus demonstrated to be a potential tool for assessing bone quality.

Improvement of adynamic bone disease after renal transplantation.

PubMed

Abdallah, K A; Jorgetti, V; Pereira, R C; Reis, L M dos; Pereira, L M; Corrêa, P H S; Borelli, A; Ianhez, L E; Moysés, R M A; David-Neto, E

2006-01-01

Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments.

Multi-Elemental Profiling of Tibial and Maxillary Trabecular Bone in Ovariectomised Rats

PubMed Central

Han, Pingping; Lu, Shifeier; Zhou, Yinghong; Moromizato, Karine; Du, Zhibin; Friis, Thor; Xiao, Yin

2016-01-01

Atomic minerals are the smallest components of bone and the content of Ca, being the most abundant mineral in bone, correlates strongly with the risk of osteoporosis. Postmenopausal women have a far greater risk of suffering from OP due to low Ca concentrations in their bones and this is associated with low bone mass and higher bone fracture rates. However, bone strength is determined not only by Ca level, but also a number of metallic and non-metallic elements in bone. Thus, in this study, the difference of metallic and non-metallic elements in ovariectomy-induced osteoporosis tibial and maxillary trabecular bone was investigated in comparison with sham operated normal bone by laser ablation inductively-coupled plasma mass spectrometry using a rat model. The results demonstrated that the average concentrations of 25Mg, 28Si, 39K, 47Ti, 56Fe, 59Co, 77Se, 88Sr, 137Ba, and 208Pb were generally higher in tibia than those in maxilla. Compared with the sham group, Ovariectomy induced more significant changes of these elements in tibia than maxilla, indicating tibial trabecular bones are more sensitive to changes of circulating estrogen. In addition, the concentrations of 28Si, 77Se, 208Pb, and Ca/P ratios were higher in tibia and maxilla in ovariectomised rats than those in normal bone at all time-points. The present study indicates that ovariectomy could significantly impact the element distribution and concentrations between tibia and maxilla. PMID:27338361

Osteoprotegerin inhibits bone resorption and prevents tumor development in a xenogenic model of Ewing's sarcoma by inhibiting RANKL

PubMed Central

Picarda, Gaëlle; Matous, Etienne; Amiaud, Jérôme; Charrier, Céline; Lamoureux, François; Heymann, Marie-Françoise; Tirode, Franck; Pitard, Bruno; Trichet, Valérie; Heymann, Dominique; Redini, Françoise

2013-01-01

Ewing's sarcoma (ES) associated with high osyeolytic lesions typically arises in the bones of children and adolescents. The development of multi-disciplinary therapy has increased current long-term survival rates to greater than 50% but only 20% for high risk group patients (relapse, metastases, etc.). Among new therapeutic approaches, osteoprotegerin (OPG), an anti-bone resorption molecule may represent a promising candidate to inhibit RANKL-mediated osteolytic component of ES and consequently to limit the tumor development. Xenogenic orthotopic models of Ewing's sarcoma were induced by intra-osseous injection of human TC-71 ES cells. OPG was administered in vivo by non-viral gene transfer using an amphiphilic non ionic block copolymer. ES bearing mice were assigned to controls (no treatment, synthetic vector alone or F68/empty pcDNA3.1 plasmid) and hOPG treated groups. A substantial but not significant inhibition of tumor development was observed in the hOPG group as compared to control groups. Marked bone lesions were revealed by micro-computed tomography analyses in control groups whereas a normal bone micro-architecture was preserved in the hOPG treated group. RANKL over-expressed in ES animal model was expressed by tumor cells rather than by host cells. However, TRAIL present in the tumor microenvironment may interfere with OPG effect on tumor development and bone remodeling via RANKL inhibition. In conclusion, the use of a xenogenic model of Ewing's sarcoma allowed discriminating between the tumor and host cells responsible for the elevation of RANKL production observed in this tumor and demonstrated the relevance of blocking RANKL by OPG as a promising therapy in ES. PMID:26909278

[Vitamin-resistant rickets cured by removal of a bone tumor. Review of the literature].

PubMed

François, S; Lefort, G; Poli-Merol, M L; Gaillard, D; Roussel, B; Sulmont, V; Daoud, S

1997-01-01

Rickets secondary to bone or soft tissue tumors are rare in children. Majority of the reported cases occurred in adults older than thirty. This entity can be cured after tumor removal. The authors present a case in a ten year boy and literature review. A ten year boy complained of diffuse bone and muscle weakness for two years. A diagnosis of arthritis was made but the patient continued to complain. Serum calcium level was normal (2.33 mmol/l), phosphorus was very low (0.43 mmol/l), serum alkaline phosphatase was high, parathyroid hormone and vitamin D level were normal. Urinalysis showed abnormal phosphate excretion. The absence of malabsorption, no family history of rickets or hypophosphatermy presence of a marked excess of urinary phosphate, very low serum phosphate and normal serum calcium, vitamin D and parathyroid hormone levels led us to consider a diagnosis of tumor induced osteomalacia. Radiographs showed a large round radiolucent lesion in the left superior pubic ramus and generalized demineralisation. We performed a complete tumor resection and the space was filled with bone graft. On histopathologic examination it was a benign mesenchymal tumor. Rapid reversal of biochemical anomalies, radiographs anomalies and clinical manifestation were observed after complete tumor resection. The authors have described the tumor, the osteomalacia and the pathogenesis of tumor rickets. Histologically the most common causative tumors were vascular tumors, mesenchymal tumors and non ossifying tumors. The tumor were of bone or soft tissue origin. Clinical symptoms were muscular weakness, bone and muscle pain. Biochemically there is a very low phosphate level, a normal serum calcium level as well as a normal vitamin D and PTH level. There is a significant high level of urinal phosphate. The mechanism proposed to explain oncogenic osteomalacia includes tumor secretion of phosphaturic substance other than PTH and calcitonin. Another hypothesis is a substance interfering with normal vitamin D metabolism. The pathogenesis is not clearly defined. Regardless to the mechanism of osteomalacia, complete removal of the tumor will cure the patient. A diligent search for tumors should be done in patients with vitamin D resistant rickets.

Testing Pullout Strength of Pedicle Screw Using Synthetic Bone Models: Is a Bilayer Foam Model a Better Representation of Vertebra?

PubMed

Varghese, Vicky; Krishnan, Venkatesh; Saravana Kumar, Gurunathan

2018-06-01

A biomechanical study. A new biomechanical model of the vertebra has been developed that accounts for the inhomogeneity of bone and the contribution of the pedicle toward the holding strength of a pedicle screw. Pullout strength studies are typically carried out on rigid polyurethane foams that represent the homogeneous vertebral framework of the spine. However, the contribution of the pedicle region, which contributes to the inhomogeneity in this framework, has not been considered in previous investigations. Therefore, we propose a new biomechanical model that can account for the vertebral inhomogeneity, especially the contribution of the pedicles toward the pullout strength of the pedicle screw. A bilayer foam model was developed by joining two foams representing the pedicle and the vertebra. The results of the pullout strength tests performed on the foam models were compared with those from the tests performed on the cadaver lumbar vertebra. Significant differences ( p <0.05) were observed between the pullout strength of the pedicle screw in extremely osteoporotic (0.18±0.11 kN), osteoporotic (0.37±0.14 kN), and normal (0.97±0.4 kN) cadaver vertebra. In the monolayer model, significant differences ( p <0.05) were observed in pullout strength between extremely osteoporotic (0.3±0.02 kN), osteoporotic (0.65±0.12 kN), and normal (0.99±0.04 kN) bone model. However, the bilayer foam model exhibited no significant differences ( p >0.05) in the pullout strength of pedicle screws between osteoporotic (0.85±0.08 kN) and extremely osteoporotic bone models (0.94±0.08 kN), but there was a significant difference ( p <0.05) between osteoporotic (0.94±0.08 kN) and normal bone models (1.19±0.05 kN). There were no significant differences ( p >0.05) in pullout strength between cadaver and bilayer foam model in normal bones. The new synthetic bone model that reflects the contribution of the pedicles to the pullout strength of the pedicle screws could provide a more efficacious means of testing pedicle-screw pullout strength. The bilayer model can match the pullout strength value of normal lumbar vertebra bone whereas the monolayer foam model was able to match that of the extremely osteoporotic lumbar vertebra.

Musculoskeletal Imaging Findings of Hematologic Malignancies.

PubMed

Navarro, Shannon M; Matcuk, George R; Patel, Dakshesh B; Skalski, Matthew; White, Eric A; Tomasian, Anderanik; Schein, Aaron J

2017-01-01

Hematologic malignancies comprise a set of prevalent yet clinically diverse diseases that can affect every organ system. Because blood components originate in bone marrow, it is no surprise that bone marrow is a common location for both primary and metastatic hematologic neoplasms. Findings of hematologic malignancy can be seen with most imaging modalities including radiography, computed tomography (CT), technetium 99m ( 99m Tc) methylene diphosphonate (MDP) bone scanning, fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, and magnetic resonance (MR) imaging. Because of the diversity of imaging appearances and clinical behavior of this spectrum of disease, diagnosis can be challenging, and profound understanding of the underlying pathophysiologic changes and current treatment modalities can be daunting. The appearance of normal bone marrow at MR imaging and FDG PET/CT is also varied due to dynamic compositional changes with normal aging and in response to hematologic demand or treatment, which can lead to false-positive interpretation of imaging studies. In this article, the authors review the normal maturation and imaging appearance of bone marrow. Focusing on lymphoma, leukemia, and multiple myeloma, they present the spectrum of imaging findings of hematologic malignancy affecting the musculoskeletal system and the current imaging tools available to the radiologist. They discuss the imaging findings of posttreatment bone marrow and review commonly used staging systems and consensus recommendations for appropriate imaging for staging, management, and assessment of clinical remission. © RSNA, 2017.

Impact of Dietary Intake on Bone Turnover in Patients with Phenylalanine Hydroxylase Deficiency.

PubMed

Coakley, Kathryn E; Felner, Eric I; Tangpricha, Vin; Wilson, Peter W F; Singh, Rani H

2017-01-01

Phenylalanine hydroxylase (PAH) deficiency is a genetic disorder characterized by deficiency of the PAH enzyme. Patients follow a phenylalanine-restricted diet low in intact protein, and must consume synthetic medical food (MF) to supply phenylalanine-free protein. We assessed relationships between dietary intake and nutrient source (food or MF) on bone mineral density (BMD) and bone turnover markers (BTM) in PAH deficiency. Blood from 44 fasted females 11-52 years of age was analyzed for plasma phenylalanine, serum BTM [CTx (resorption), P1NP (formation)], vitamin D, and parathyroid hormone (PTH). BTM ratios were calculated to assess resorption relative to formation (CTx/P1NP). Dual energy X-ray absorptiometry measured total BMD and age-matched Z-scores. Three-day food records were analyzed for total nutrient intake, nutrients by source (food, MF), and compliance with MF prescription. Spearman's partial coefficients (adjusted for age, BMI, energy intake, blood phenylalanine) assessed correlations. All had normal BMD for age (Z-score >-2). Sixty-four percent had high resorption and normal formation indicating uncoupled bone turnover. CTx/P1NP was positively associated with food phenylalanine (r 2 = 0.39; p-value = 0.017), energy (r 2 = 0.41; p-value = 0.011) and zinc (r 2 = 0.41; p-value = 0.014). CTx/P1NP was negatively associated with MF fat (r 2 = -0.44; p-value = 0.008), MF compliance (r 2 = -0.34; p-value = 0.056), and positively with food sodium (r 2 = 0.43; p-value = 0.014). CTx/P1NP decreased significantly with age (p-value = 0.002) and higher PTH (p-value = 0.0002). Phenylalanine was not correlated with any bone indicator. Females with PAH deficiency had normal BMD but elevated BTM, particularly resorption. More favorable ratios were associated with nutrients from MF and compliance. Younger females had less favorable BTM ratios. Promoting micronutrient intake through compliance with MF may impact bone metabolism in patients with PAH deficiency. Bone mineral density was normal in 44 females with PAH deficiency; however, bone turnover markers suggested uncoupling of bone resorption and formation, particularly in younger patients. Adequate nutrient intake from medical food and overall medical food compliance may positively impact bone turnover.

SKELETAL DYNAMICS IN MAN MEASURED BY NONRADIOACTIVE STRONTIUM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eisenberg, E.; Gordan, G.S.

Skeletal dynamics were calculated by usual dilution formulas, using stable strontium as a tracer, in 25 normal subjects, 14 athletes, 26 patients with postmenopausal osteoporosis, 28 with primary hyperparathyroidism, 3 with hyperadrenocorticism 8 with acromegaly, 7 with thyrotoxicosis, 11 with urclithiasis, 5 with Paget's disease of bone. and 1 with vitamin D poisoning. The technic requires that 10 mEq of strontium gluconate be injected intravenously and blood and urine concentrations be measured for 4 to 6 days. In normal subjects the rapidly miscible pool was equivalent to 42.7 + 1.1 L of serum, turning over at a rate of 13.5more » plus or minus 0.6 L daily, of which 3.9 + 0.2 L was excreted by the kidney and 9.6 + 0.4 L went to bone. Since only approximately 2.5% of the pool is excreted in the feces daily, fecal excretion was not measured routinely. Good reproducibility was found in 21 duplicate studies. Intense muscular exercise (athletes) was found to expand the pool greatly and to accelerate the rate of deposition in bone. Kinetically, two divergent types of osteoporosis were differentiated. A small pool and low rate of bone deposition were found in postmenopausal osteoporosis and Cushing's disease of long duration. The large pool and rapid rate of bone deposition in thyrotoxicosis was confirmed and also found in acromegaly. In these two, excessive bone resorption is postulated. Urinary excretion rate was excessive in Cushing's disease, thyrotoxicosis, and acromegaly. In hyperparathyroidism with clinically evident osteitis, expanded pools, greatly increased turnover, urinary excretion, and bone deposition rates were confirmed. In patients with normal roentgenographic appearance and phosphatase, bone involvement was shown by slight increase in bone deposition rate and microscopic foci of resorption on iliac crest biopsy. In seven patients without histological foci of resorption, the bone deposition rate was not increased. (auth)« less

Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.

PubMed

Zimran, Ari; Elstein, Deborah; Gonzalez, Derlis E; Lukina, Elena A; Qin, Yulin; Dinh, Quinn; Turkia, Hadhami Ben

2018-02-01

Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427. Copyright © 2016 Shire Human Genetic Therapies, Inc. Published by Elsevier Inc. All rights reserved.

Short-duration exercise and confinement alters bone mineral content and shape in weanling horses.

PubMed

Hiney, K M; Nielsen, B D; Rosenstein, D

2004-08-01

The hypothesis that short-duration exercise may ameliorate the decrease in bone mass observed with confinement was investigated with 18 quarter horses (nine colts and nine fillies) weaned at 4 mo of age and placed into box stalls. After a 5-wk adjustment period, individuals were grouped by age and weight, and then divided randomly into three treatment groups: 1) group housed; 2) confined with no exercise; and 3) confined with exercise. The confined and exercised groups were housed in 3.7 m x 3.7 m box stalls for the 56-d duration of the trial. The exercised group was sprinted 82 m/d, 5 d/wk, in a fenced grass alleyway. The weanlings were led down an alleyway, turned loose in a small pen, and then released and allowed to run back down the alley. The group horses were housed together in a 992-m2 drylot with free access to exercise. On d 0, 28, and 56, dorsopalmar and lateromedial radiographs of the left third metacarpal bone were taken to estimate changes in bone mineral content and cortical widths. Mean values of medial, lateral, and total radiographic bone aluminum equivalence increased over time (P < 0.05), whereas dorsal and palmar radiographic bone aluminum equivalence did not change significantly. Dorsal, medial, and total radiographic bone aluminum equivalence tended (P = 0.09) to differ by a treatment x day interaction, with values increasing over time only in the exercised group. Normalized medial and total radiographic bone aluminum equivalence tended (P < 0.1) to differ (P < 0.01) with treatment, with exercised horses having greater bone aluminum equivalence than confined horses. Dorsopalmar cortical width in exercised horses was greater than on d 56 (treatment x day; P = 0.07). The dorsopalmar medullary cavity decreased in exercised vs. group-housed horses (P = 0.027), whereas dorsal and medial cortical width tended to increase only in the exercised horses (treatment x day; P < 0.01). This study indicated that a short-duration exercise protocol might be effective in improving bone mass and therefore skeletal strength in horses.

[Homeostasis and Disorder of Musculoskeletal System.Molecular mechanism of bone metabolism and future therapeutic strategies.

PubMed

Nakashima, Tomoki

Recent studies of mouse genetics and human gene mutations has greatly contributed to clarifying the molecular mechanism of bone metabolism. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication among bone component cells such as osteoclasts, osteoblasts, osteocytes and endothelial cells. An imbalance of this process is often linked to various bone diseases. Thus, the elucidation of the molecular mechanisms involved in bone remodeling is critical for a deeper understanding of the maintenance of healthy skeleton and bone disease.

Determination of mechanical stiffness of bone by pQCT measurements: correlation with non-destructive mechanical four-point bending test data.

PubMed

Martin, Daniel E; Severns, Anne E; Kabo, J M J Michael

2004-08-01

Mechanical tests of bone provide valuable information about material and structural properties important for understanding bone pathology in both clinical and research settings, but no previous studies have produced applicable non-invasive, quantitative estimates of bending stiffness. The goal of this study was to evaluate the effectiveness of using peripheral quantitative computed tomography (pQCT) data to accurately compute the bending stiffness of bone. Normal rabbit humeri (N=8) were scanned at their mid-diaphyses using pQCT. The average bone mineral densities and the cross-sectional moments of inertia were computed from the pQCT cross-sections. Bending stiffness was determined as a function of the elastic modulus of compact bone (based on the local bone mineral density), cross-sectional moment of inertia, and simulated quasistatic strain rate. The actual bending stiffness of the bones was determined using four-point bending tests. Comparison of the bending stiffness estimated from the pQCT data and the mechanical bending stiffness revealed excellent correlation (R2=0.96). The bending stiffness from the pQCT data was on average 103% of that obtained from the four-point bending tests. The results indicate that pQCT data can be used to accurately determine the bending stiffness of normal bone. Possible applications include temporal quantification of fracture healing and risk management of osteoporosis or other bone pathologies.

Effects of calcium phosphate/chitosan composite on bone healing in rats: calcium phosphate induces osteon formation.

PubMed

Fernández, Tulio; Olave, Gilberto; Valencia, Carlos H; Arce, Sandra; Quinn, Julian M W; Thouas, George A; Chen, Qi-Zhi

2014-07-01

Vascularization of an artificial graft represents one of the most significant challenges facing the field of bone tissue engineering. Over the past decade, strategies to vascularize artificial scaffolds have been intensively evaluated using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In this work, we observed that CaP-based biomaterials implanted into rat calvarial defects showed remarkably accelerated formation and mineralization of new woven bone in defects in the initial stages, at a rate of ∼60 μm/day (0.8 mg/day), which was considerably higher than normal bone growth rates (several μm/day, 0.1 mg/day) in implant-free controls of the same age. Surprisingly, we also observed histological evidence of primary osteon formation, indicated by blood vessels in early-region fibrous tissue, which was encapsulated by lamellar osteocyte structures. These were later fully replaced by compact bone, indicating complete regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only osteoinductive, but vasculogenic, and it may have contributed to the bone regeneration, despite an absence of osteons in normal rat calvaria. Further investigation will involve how this strategy can regulate formation of vascularized cortical bone such as by control of degradation rate, and use of models of long, dense bones, to more closely approximate repair of human cortical bone.

Delayed Expression of Circulating TGF-β1 and BMP-2 Levels in Human Nonunion Long Bone Fracture Healing.

PubMed

Hara, Yoshiaki; Ghazizadeh, Mohammad; Shimizu, Hajime; Matsumoto, Hisashi; Saito, Nobuyuki; Yagi, Takanori; Mashiko, Kazuki; Mashiko, Kunihiro; Kawai, Makoto; Yokota, Hiroyuki

2017-01-01

The healing process of bone fracture requires a well-controlled multistage and sequential order beginning immediately after the injury. However, complications leading to nonunion exist, creating serious problems and costs for patients. Transforming growth factor-beta 1 (TGF-β1) and bone morphogenic protein 2 (BMP-2) are two major growth factors involved in human bone fracture healing by promoting various stages of bone ossification. In this study, we aimed to determine the role of these factors during the fracture healing of human long bones and assess their impacts on nonunion condition. We performed a comprehensive analysis of plasma TGF-β1 and BMP-2 levels in blood samples from 10 patients with proved nonunion and 10 matched patients with normal union following a predetermined time schedule. The concentrations of TGF-β1 and BMP-2 were measured at each time point using a solid-phase ELISA. TGF-β1 and BMP-2 levels were detectable in all patients. For all patients, a maximal peak for TGF-β1 was found at 3-week. In normal union group, TGF-β1 showed a maximal peak at 2-week while nonunion group had a delayed maximal peak at 3-week. Plasma levels of BMP-2 for all patients and for normal union group reached a maximal peak at 1-week, but nonunion group showed a delayed maximal peak at 2-week. In general, plasma TGF-β1 or BMP-2 level was not significantly different between normal union and nonunion groups. The expression levels of TGF-β1 and BMP-2 appeared to be delayed in nonunion patients which could play an important role in developing an early marker of fracture union condition and facilitate improved patient's management.

Evo-Devo insights from pathological networks: exploring craniosynostosis as a developmental mechanism for modularity and complexity in the human skull.

PubMed

Esteve-Altava, Borja; Rasskin-Gutman, Diego

2015-07-20

Bone fusion has occurred repeatedly during skull evolution in all tetrapod lineages, leading to a reduction in the number of bones and an increase in their morphological complexity. The ontogeny of the human skull includes also bone fusions as part of its normal developmental process. However, several disruptions might cause premature closure of cranial sutures (craniosynostosis), reducing the number of bones and producing new skull growth patterns that causes shape changes. Here, we compare skull network models of a normal newborn with different craniosynostosis conditions, the normal adult stage, and phylogenetically reconstructed forms of a primitive tetrapod, a synapsid, and a placental mammal. Changes in morphological complexity of newborn-to-synostosed skulls are two to three times less than in newborn-to-adult; and even smaller when we compare them to the increases among the reconstructed ancestors in the evolutionary transitions. In addition, normal, synostosed, and adult human skulls show the same connectivity modules: facial and cranial. Differences arise in the internal structure of these modules. In the adult skull the facial module has an internal hierarchical organization, whereas the cranial module has a regular network organization. However, all newborn forms, normal and synostosed, do not reach such kind of internal organization. We conclude that the subtle changes in skull complexity at the developmental scale can change the modular substructure of the newborn skull to more integrated modules in the adult skull, but is not enough to generate radical changes as it occurs at a macroevolutionary scale. The timing of closure of craniofacial sutures, together with the conserved patterns of morphological modularity, highlights a potential relation between the premature fusion of bones and the evolution of the shape of the skull in hominids.

[Hand and wrist bone maturation in children with central precocious puberty and idiopathic short stature].

PubMed

Wang, Anru; Yang, Fangling; Yu, Baosheng; Shan, Ye; Gao, Lanying; Zhang, Xiaoxiao; Peng, Ya

2013-07-01

To investigate the maturation of individual bones on the hand and wrist in children with central precocious puberty (CPP) and idiopathic short stature (ISS). Hand and wrist films of 25 children with CPP, 29 children with ISS and 21 normal controls were evaluated by conventional Greulich-Pyle (GP) atlas method and individual bone assessment method, in which all twenty bones of the hand and wrist were evaluated based on GP atlas, including 2 radius and ulna, 7 carpal bones, 11 metacarpal and phalangeal bones, the average bone age (BA) was calculated. The differences in groups were analyzed by independent samples t test. The differences between the two methods were analyzed by paired sample t test. The differences between BA and chronological age (CA) were analyzed by ROC with SPSS 17.0. Compared with the normal control group, the advance of BA in the CPP group was 0.70-2.26 y (1.48 ±0.78) by the GP atlas method, while that was 0.28-2.00 y(1.14 ±0.86) by the individual bone evaluation method. In all twenty bones, the advance of metacarpal and phalangeal BA was the greatest [0.34-2.06 y(1.2±0.86)]. In the ISS group,the delay of BA was 0.47-2.91 y(-1.69±1.22) by the GP atlas method, while that was 0.48-2.50 y (-1.49±1.01) by individual bone evaluation method.The delay of carpal BA was the greatest [0.59-2.73 y(-1.66±1.07)] in all twenty bones. In the ISS group and the normal control group, there were no statistic differences between the two methods. In the CPP group, statistic difference was found between two methods. There were no statistic differences for the areas under ROC curves between two methods. The advance of metacarpal and phalangeal BA is the greatest in CPP group and the delay of carpal BA is the greatest in ISS group.Both methods provide diagnostic information for bone age in CPP and ISS children.

Vitamin D

MedlinePlus

... body needs to grow and develop normally. Vitamin D helps your body absorb calcium. Calcium is one ... building blocks of bone. A lack of vitamin D can lead to bone diseases such as osteoporosis ...

Three-phase radionuclide bone imaging in sports medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rupani, H.D.; Holder, L.E.; Espinola, D.A.

Three-phase radionuclide bone (TPB) imaging was performed on 238 patients with sports-related injuries. A wide variety of lesions was encountered, but the most frequent lesions seen were stress fractures of the lower part of the leg at the junction of the middle and distal thirds of the posterior tibial cortex (42 of 79 lesions). There were no differences in the type, location, or distribution of lesions between males and females or between competitive and noncompetitive athletes. In 110 cases, bone stress lesions were often diagnosed when radiographs were normal, whereas subacute or chronic soft-tissue abnormalities had few specific scintigraphic features.more » TPB imaging provides significant early diagnostic information about bone stress lesions. Normal examination results (53 cases) exclude underlying osseous pathologic conditions.« less

Thermographic image analysis as a pre-screening tool for the detection of canine bone cancer

NASA Astrophysics Data System (ADS)

Subedi, Samrat; Umbaugh, Scott E.; Fu, Jiyuan; Marino, Dominic J.; Loughin, Catherine A.; Sackman, Joseph

2014-09-01

Canine bone cancer is a common type of cancer that grows fast and may be fatal. It usually appears in the limbs which is called "appendicular bone cancer." Diagnostic imaging methods such as X-rays, computed tomography (CT scan), and magnetic resonance imaging (MRI) are more common methods in bone cancer detection than invasive physical examination such as biopsy. These imaging methods have some disadvantages; including high expense, high dose of radiation, and keeping the patient (canine) motionless during the imaging procedures. This project study identifies the possibility of using thermographic images as a pre-screening tool for diagnosis of bone cancer in dogs. Experiments were performed with thermographic images from 40 dogs exhibiting the disease bone cancer. Experiments were performed with color normalization using temperature data provided by the Long Island Veterinary Specialists. The images were first divided into four groups according to body parts (Elbow/Knee, Full Limb, Shoulder/Hip and Wrist). Each of the groups was then further divided into three sub-groups according to views (Anterior, Lateral and Posterior). Thermographic pattern of normal and abnormal dogs were analyzed using feature extraction and pattern classification tools. Texture features, spectral feature and histogram features were extracted from the thermograms and were used for pattern classification. The best classification success rate in canine bone cancer detection is 90% with sensitivity of 100% and specificity of 80% produced by anterior view of full-limb region with nearest neighbor classification method and normRGB-lum color normalization method. Our results show that it is possible to use thermographic imaging as a pre-screening tool for detection of canine bone cancer.

Estimating differences in volumetric flat bone growth in pediatric patients by radiation treatment method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua Chiaho; Shukla, Hemant I.; Merchant, Thomas E.

2007-02-01

Purpose: To estimate potential differences in volumetric bone growth in children with sarcoma treated with intensity-modulated (IMRT) and conformal (CRT) radiation therapy using an empiric dose-effect model. Methods and Materials: A random coefficient model was used to estimate potential volumetric bone growth of 36 pelvic bones (ischiopubis and ilium) from 11 patients 4 years after radiotherapy. The model incorporated patient age, pretreatment bone volume, integral dose >35 Gy, and time since completion of radiation therapy. Three dosimetry plans were entered into the model: the actual CRT/IMRT plan, a nontreated comparable IMRT/CRT plan, and an idealized plan in which dose wasmore » delivered only to the planning target volume. The results were compared with modeled normal bone growth. Results: The model predicted that by using the idealized, IMRT, and CRT approaches, patients would maintain 93%, 87%, and 84%, respectively (p = 0.06), of their expected normal growth. Patients older than 10 years would maintain 98% of normal growth, regardless of treatment method. Those younger than 10 years would maintain 87% (idealized), 76% (IMRT), or 70% (CRT) of their expected growth (p = 0.015). Post hoc testing (Tukey) revealed that the CRT and IMRT approaches differed significantly from the idealized one but not from each other. Conclusions: Dose-effect models facilitate the comparison of treatment methods and potential interventions. Although treatment methods do not alter the growth of flat bones in older pediatric patients, they may significantly impact bone growth in children younger than age 10 years, especially as we move toward techniques with high conformity and sharper dose gradient.« less

Ectopic bone formation and chondrodysplasia in transgenic mice carrying the rat C3(1)/T{sub AG} fusion gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, J.E.; Maroulakou, I.G.; Anver, M.

Transgenic mice expressing the SV40 large T-antigen (T{sup AG}) under the regultory control of the hormone-responsive rat C3(1) prostatein promoter develop unusual bone and cartilage lesions, as well as ectopic bone and cartilage formation. Two lines of transgenic animals have been propagated in which the expression of the transgene in chondrocytes results in a mild to moderate generalized disorganization of cartilage growth which appears to affect multiple tissues, including the trachea, ear pinna and articular cartilage. The epiphyseal plates are also affected with normal architecture of the zones of proliferation and maturation, but marked elongation of the zone of hypertrophy.more » Immunocytochemistry demonstrates that expression of T{sup AG} is limited to the zone of hypertropny in the epiphyseal plates, suggesting that the chondrocytes become hormone-responsive at this particular stage of differentiation. Normal mineralization and trabecular formation in long bone appears to occur. Ectopic bone and cartilage formation occurs in the foot pads of the fore- and hind- feet over the course of several months. This is preceded by proliferation of sweat gland epithelial cells followed by the appearance of nodules of cartilage and bone. The nodules are closely associated with proliferating epithelium but are not contiguous with bony structures normally found in the feet. The roles of BMP`s, growth factors, oncogenes and hormones in the development of these lesions will be presented. These transgenic animals may provide new insights into hormone-responsiveness of chondrocytes, as well as factors involved in the processes of bone and cartilage differentiation and growth. These transgenic animals may serve as a useful model for human heterotopic bone formation.« less

Clinical efficacy of stem cell mediated osteogenesis and bioceramics for bone tissue engineering.

PubMed

Neman, Josh; Hambrecht, Amanda; Cadry, Cherie; Goodarzi, Amir; Youssefzadeh, Jonathan; Chen, Mike Y; Jandial, Rahul

2012-01-01

Lower back pain is a common disorder that often requires bony spinal fusion for long-term relief. Current arthrodesis procedures use bone grafts from autogenous bone, allogenic backed bone or synthetic materials. Autogenous bone grafts can result in donor site morbidity and pain at the donor site, while allogenic backed bone and synthetic materials have variable effectiveness. Given these limitations, researchers have focused on new treatments that will allow for safe and successful bone repair and regeneration. Mesenchymal stem cells (MSCs) have received attention for their ability to differentiate into osteoblasts, cells that synthesize the extracellular matrix and regulate matrix mineralization. Successful bone regeneration requires three elements: MSCs that serve as osteoblastic progenitors, osteoinductive growth factors and their pathways that promote development and differentiation of the cells as well as an osteoconductive scaffold that allows for the formation of a vascular network. Future treatments should strive to combine mesenchymal stem cells, cell-seeded scaffolds and gene therapy to optimize the efficiency and safety of tissue repair and bone regeneration.

Bone mineral density before and after OLT: long-term follow-up and predictive factors.

PubMed

Guichelaar, Maureen M J; Kendall, Rebecca; Malinchoc, Michael; Hay, J Eileen

2006-09-01

Fracturing after liver transplantation (OLT) occurs due to the combination of preexisting low bone mineral density (BMD) and early posttransplant bone loss, the risk factors for which are poorly defined. The prevalence and predictive factors for hepatic osteopenia and osteoporosis, posttransplant bone loss, and subsequent bone gain were studied by the long-term posttransplant follow-up of 360 consecutive adult patients with end-stage primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Only 20% of patients with advanced PBC or PSC have normal bone mass. Risk factors for low spinal BMD are low body mass index, older age, postmenopausal status, muscle wasting, high alkaline phosphatase and low serum albumin. A high rate of spinal bone loss occurred in the first 4 posttransplant months (annual rate of 16%) especially in those with younger age, PSC, higher pretransplant bone density, no inflammatory bowel disease, shorter duration of liver disease, current smoking, and ongoing cholestasis at 4 months. Factors favoring spinal bone gain from 4 to 24 months after transplantation were lower baseline and/or 4-month bone density, premenopausal status, lower cumulative glucocorticoids, no ongoing cholestasis, and higher levels of vitamin D and parathyroid hormone. Bone mass therefore improves most in patients with lowest pretransplant BMD who undergo successful transplantation with normal hepatic function and improved gonadal and nutritional status. Patients transplanted most recently have improved bone mass before OLT, and although bone loss still occurs early after OLT, these patients also have a greater recovery in BMD over the years following OLT.

Computed tomography demonstrates abnormalities of contralateral ear in subjects with unilateral sensorineural hearing loss.

PubMed

Marcus, Sonya; Whitlow, Christopher T; Koonce, James; Zapadka, Michael E; Chen, Michael Y; Williams, Daniel W; Lewis, Meagan; Evans, Adele K

2014-02-01

Prior studies have associated gross inner ear abnormalities with pediatric sensorineural hearing loss (SNHL) using computed tomography (CT). No studies to date have specifically investigated morphologic inner ear abnormalities involving the contralateral unaffected ear in patients with unilateral SNHL. The purpose of this study is to evaluate contralateral inner ear structures of subjects with unilateral SNHL but no grossly abnormal findings on CT. IRB-approved retrospective analysis of pediatric temporal bone CT scans. 97 temporal bone CT scans, previously interpreted as "normal" based upon previously accepted guidelines by board certified neuroradiologists, were assessed using 12 measurements of the semicircular canals, cochlea and vestibule. The control-group consisted of 72 "normal" temporal bone CTs with underlying SNHL in the subject excluded. The study-group consisted of 25 normal-hearing contralateral temporal bones in subjects with unilateral SNHL. Multivariate analysis of covariance (MANCOVA) was then conducted to evaluate for differences between the study and control group. Cochlea basal turn lumen width was significantly greater in magnitude and central lucency of the lateral semicircular canal bony island was significantly lower in density for audiometrically normal ears of subjects with unilateral SNHL compared to controls. Abnormalities of the inner ear were present in the contralateral audiometrically normal ears of subjects with unilateral SNHL. These data suggest that patients with unilateral SNHL may have a more pervasive disease process that results in abnormalities of both ears. The findings of a cochlea basal turn lumen width disparity >5% from "normal" and/or a lateral semicircular canal bony island central lucency disparity of >5% from "normal" may indicate inherent risk to the contralateral unaffected ear in pediatric patients with unilateral sensorineural hearing loss. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Efficacy of Transverse Fixation and Early Exercise in the Treatment of Fourth Metacarpal Bone Fractures

PubMed Central

Moon, Suk-Ho; Kim, Hak-Soo; Jung, Sung-No

2016-01-01

Background Several techniques have been designed to treat fifth metacarpal fractures reported to be effective. However, these methods cannot be easily applied to the fourth metacarpal due to its central anatomical position. In this study, we sought to analyze the functional outcomes of patients who underwent transverse pinning for a fourth metacarpal bone fracture. Methods A total of 21 patients were selected and their charts were retrospectively reviewed. After fracture reduction, two transverse Kirchner wires were first inserted from the fifth metacarpal to the third metacarpal transversely at the distal part of the fractured bone, and then another two wires were inserted at the proximal part of the fractured bone. The splint was removed approximately one week postoperatively and the Kirchner wires were removed four to five weeks postoperatively. Patients started active and passive exercise one week after the operation. Pain visual analog scores, total active and passive motion, and the active and passive range of motion of the metacarpophalangeal joint and grip strength were evaluated. Results Dorsal angulation improved from a preoperative value of 44.2° to a postoperative value of 5.9°. Six weeks after surgery, functional recovery parameters, such as range of motion and grip strength, had improved to 98% of the function of the normal side. No major complication was observed. Conclusions We suggest that the transverse pinning of fourth metacarpal bone fractures is an effective treatment option that is less invasive than other procedures, easy to perform, requires no secondary surgery, minimizes joint and soft tissue injury, and allows early mobilization. PMID:27019812

Effect of tibial bone resection on the development of fast- and slow-twitch skeletal muscles in foetal sheep.

PubMed

West, J M; Williams, N A; Luff, A R; Walker, D W

2000-04-01

To determine if longitudinal bone growth affects the differentiation of fast- and slow-twitch muscles, the tibial bone was sectioned at 90 days gestation in foetal sheep so that the lower leg was permanently without structural support. At 140 days (term is approximately 147 days) the contractile properties of whole muscles, activation profiles of single fibres and ultrastructure of fast- and slow-twitch muscles from the hindlimbs were studied. The contractile and activation profiles of the slow-twitch soleus muscles were significantly affected by tibial bone resection (TIBX). The soleus muscles from the TIBX hindlimbs showed: (1) a decrease in the time to peak of the twitch responses from 106.2 +/- 10.7 ms (control, n = 4) to 65.1 +/- 2.48 ms (TIBX, n = 5); (2) fatigue profiles more characteristic of those observed in the fast-twitch muscles: and (3) Ca2+ - and Sr2+ -activation profiles of skinned fibres similar to those from intact hindlimbs at earlier stages of gestation. In the FDL, TIBX did not significantly change whole muscle twitch contraction time, the fatigue profile or the Ca2+ - and Sr2+ -activation profiles of skinned fibres. Electron microscopy showed an increased deposition of glycogen in both soleus and FDL muscles. This study shows that the development of the slow-twitch phenotype is impeded in the absence of the physical support normally provided by the tibial bone. We suggest that longitudinal stretch is an important factor in allowing full expression of the slow-twitch phenotype.

The effect of sensorineural hearing loss and tinnitus on speech recognition over air and bone conduction military communications headsets.

PubMed

Manning, Candice; Mermagen, Timothy; Scharine, Angelique

2017-06-01

Military personnel are at risk for hearing loss due to noise exposure during deployment (USACHPPM, 2008). Despite mandated use of hearing protection, hearing loss and tinnitus are prevalent due to reluctance to use hearing protection. Bone conduction headsets can offer good speech intelligibility for normal hearing (NH) listeners while allowing the ears to remain open in quiet environments and the use of hearing protection when needed. Those who suffer from tinnitus, the experience of perceiving a sound not produced by an external source, often show degraded speech recognition; however, it is unclear whether this is a result of decreased hearing sensitivity or increased distractibility (Moon et al., 2015). It has been suggested that the vibratory stimulation of a bone conduction headset might ameliorate the effects of tinnitus on speech perception; however, there is currently no research to support or refute this claim (Hoare et al., 2014). Speech recognition of words presented over air conduction and bone conduction headsets was measured for three groups of listeners: NH, sensorineural hearing impaired, and/or tinnitus sufferers. Three levels of speech-to-noise (SNR = 0, -6, -12 dB) were created by embedding speech items in pink noise. Better speech recognition performance was observed with the bone conduction headset regardless of hearing profile, and speech intelligibility was a function of SNR. Discussion will include study limitations and the implications of these findings for those serving in the military. Published by Elsevier B.V.

Bisphosphonates Improve Trabecular Bone Mass and Normalize Cortical Thickness in Ovariectomized, Osteoblast Connexin43 Deficient Mice

PubMed Central

Watkins, Marcus P.; Norris, Jin Yi; Grimston, Susan K.; Zhang, Xiaowen; Phipps, Roger J.; Ebetino, Frank H.; Civitelli, Roberto

2012-01-01

The gap junction protein, connexin43 (Cx43) controls both bone formation and osteoclastogenesis via osteoblasts and/or osteocytes. Cx43 has also been proposed to mediate an anti-apoptotic effect of bisphosphonates, potent inhibitors of bone resorption. We studied whether bisphosphonates are effective in protecting mice with a conditional Cx43 gene deletion in osteoblasts and osteocytes (cKO) from the consequences of ovariectomy on bone mass and strength. Ovariectomy resulted in rapid loss of trabecular bone followed by a slight recovery in wild type (WT) mice, and a similar degree of trabecular bone loss, albeit slightly delayed, occurred in cKO mice. Treatment with either risedronate (20µg/kg) or alendronate (40µg/kg) prevented ovariectomy-induced bone loss in both genotypes. In basal conditions, bones of cKO mice have larger marrow area, higher endocortical osteoclast number, and lower cortical thickness and strength relative to WT. Ovariectomy increased endocortical osteoclast number in WT but not in cKO mice. Both bisphosphonates prevented these increases in WT mice, and normalized endocortical osteoclast number, cortical thickness and bone strength in cKO mice. Thus, lack of osteoblast/osteocyte Cx43 does not alter bisphosphonate action on bone mass and strength in estrogen deficiency. These results support the notion that one of the main functions of Cx43 in cortical bone is to restrain osteoblast and/or osteocytes from inducing osteoclastogenesis at the endocortical surface. PMID:22750450

Inflammatory bowel disease causes reversible suppression of osteoblast and chondrocyte function in mice.

PubMed

Harris, Laura; Senagore, Patricia; Young, Vincent B; McCabe, Laura R

2009-05-01

Decreased bone density and stature can occur in pediatric patients with inflammatory bowel disease (IBD). Little is known about how IBD broadly impacts the skeleton. To evaluate the influence of an acute episode of IBD on growing bone, 4-wk-old mice were administered 5% dextran sodium sulfate (DSS) for 5 days to induce colitis and their recovery was monitored. During active disease and early recovery, trabecular bone mineral density, bone volume, and thickness were decreased. Cortical bone thickness, outer perimeter, and density were also decreased, whereas inner perimeter and marrow area were increased. These changes appear to maintain bone strength since measures of moments of inertia were similar between DSS-treated and control mice. Histological (static and dynamic), serum, and RNA analyses indicate that a decrease in osteoblast maturation and function account for changes in bone density. Unlike some conditions of bone loss, marrow adiposity did not increase. Similar to reports in humans, bone length decreased and correlated with decreases in growth plate thickness and chondrocyte marker expression. During disease recovery, mice experienced a growth spurt that led to their achieving final body weights and bone length, density, and gene expression similar to healthy controls. Increased TNF-alpha and decreased IGF-I serum levels were observed with active disease and returned to normal with recovery. Changes in serum TNF-alpha (increased) and IGF-I (decreased) paralleled changes in bone parameters and returned to normal values with recovery, suggesting a potential role in the skeletal response.

Recent biological trends in management of fracture non-union

PubMed Central

Emara, Khaled M; Diab, Ramy Ahmed; Emara, Ahmed Khaled

2015-01-01

Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. Currently, there is a plethora of different strategies to augment the impaired or “insufficient” bone-regeneration process, including the “gold standard” autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved “local” strategies in terms of tissue engineering and gene therapy, or even “systemic” enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications. PMID:26396938

3D surface voxel tracing corrector for accurate bone segmentation.

PubMed

Guo, Haoyan; Song, Sicong; Wang, Jinke; Guo, Maozu; Cheng, Yuanzhi; Wang, Yadong; Tamura, Shinichi

2018-06-18

For extremely close bones, their boundaries are weak and diffused due to strong interaction between adjacent surfaces. These factors prevent the accurate segmentation of bone structure. To alleviate these difficulties, we propose an automatic method for accurate bone segmentation. The method is based on a consideration of the 3D surface normal direction, which is used to detect the bone boundary in 3D CT images. Our segmentation method is divided into three main stages. Firstly, we consider a surface tracing corrector combined with Gaussian standard deviation [Formula: see text] to improve the estimation of normal direction. Secondly, we determine an optimal value of [Formula: see text] for each surface point during this normal direction correction. Thirdly, we construct the 1D signal and refining the rough boundary along the corrected normal direction. The value of [Formula: see text] is used in the first directional derivative of the Gaussian to refine the location of the edge point along accurate normal direction. Because the normal direction is corrected and the value of [Formula: see text] is optimized, our method is robust to noise images and narrow joint space caused by joint degeneration. We applied our method to 15 wrists and 50 hip joints for evaluation. In the wrist segmentation, Dice overlap coefficient (DOC) of [Formula: see text]% was obtained by our method. In the hip segmentation, fivefold cross-validations were performed for two state-of-the-art methods. Forty hip joints were used for training in two state-of-the-art methods, 10 hip joints were used for testing and performing comparisons. The DOCs of [Formula: see text], [Formula: see text]%, and [Formula: see text]% were achieved by our method for the pelvis, the left femoral head and the right femoral head, respectively. Our method was shown to improve segmentation accuracy for several specific challenging cases. The results demonstrate that our approach achieved a superior accuracy over two state-of-the-art methods.

Androgens in Women with Anorexia Nervosa and Normal-Weight Women with Hypothalamic Amenorrhea

PubMed Central

Miller, K. K.; Lawson, E. A.; Mathur, V.; Wexler, T. L.; Meenaghan, E.; Misra, M.; Herzog, D. B.; Klibanski, A.

2011-01-01

Context Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Objective Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. Design and Setting We conducted a cross-sectional study at a general clinical research center. Study Participants A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Main Outcome Measures Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Results Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Conclusions Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women. PMID:17284620

Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea.

PubMed

Miller, K K; Lawson, E A; Mathur, V; Wexler, T L; Meenaghan, E; Misra, M; Herzog, D B; Klibanski, A

2007-04-01

Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. We conducted a cross-sectional study at a general clinical research center. A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women.

On the Nature of Expansion of Paget’s Disease of Bone

DTIC Science & Technology

2012-10-01

signaling pathway. Gene expression normalized to normal adjacent bone samples. 5 Global expression analysis revealed genes downstream of the Hedgehog ... Hedgehog (Hh) signaling pathway (Figure 5). Again, as in the TLR signaling pathway, specific elements of the Hh signaling pathway showed increased...mutations upregulated expression of genes in the Hedgehog signaling pathway. 7. Discovery that an osteoblastic cell line (PSV10) derived from a PDB

Clinical Investigation and Mechanism of Air-Bone Gaps in LargeVestibular Aqueduct Syndrome

PubMed Central

Merchant, Saumil N.; Nakajima, Hideko H.; Halpin, Christopher; Nadol, Joseph B.; Lee, Daniel J.; Innis, William P.; Curtin, Hugh; Rosowski, John J.

2008-01-01

Objectives Patients with large vestibular aqueduct syndrome (LVAS) often demonstrate an air-bone gap at the low frequencies on audiometric testing. The mechanism causing such a gap has not been well elucidated. We investigated middle ear sound transmission in patients with LVAS, and present a hypothesis to explain the air-bone gap. Methods Observations were made on 8 ears from 5 individuals with LVAS. The diagnosis of LVAS was made by computed tomography in all cases. Investigations included standard audiometry and measurements of umbo velocity by laser Doppler vibrometry (LDV) in all cases, as well as tympanometry, acoustic reflex testing, vestibular evoked myogenic potential (VEMP) testing, distortion product otoacoustic emission (DPOAE) testing, and middle ear exploration in some ears. Results One ear with LVAS had anacusis. The other 7 ears demonstrated air-bone gaps at the low frequencies, with mean gaps of 51 dB at 250 Hz, 31 dB at 500 Hz, and 12 dB at 1,000 Hz. In these 7 ears with air-bone gaps, LDV showed the umbo velocity to be normal or high normal in all 7; tympanometry was normal in all 6 ears tested; acoustic reflexes were present in 3 of the 4 ears tested; VEMP responses were present in all 3 ears tested; DPOAEs were present in 1 of the 2 ears tested, and exploratory tympanotomy in 1 case showed a normal middle ear. The above data suggest that an air-bone gap in LVAS is not due to disease in the middle ear. The data are consistent with the hypothesis that a large vestibular aqueduct introduces a third mobile window into the inner ear, which can produce an air-bone gap by 1) shunting air-conducted sound away from the cochlea, thus elevating air conduction thresholds, and 2) increasing the difference in impedance between the scala vestibuli side and the scala tympani side of the cochlear partition during bone conduction testing, thus improving thresholds for bone-conducted sound. Conclusions We conclude that LVAS can present with an air-bone gap that can mimic middle ear disease. Diagnostic testing using acoustic reflexes, VEMPs, DPOAEs, and LDV can help to identify a non–middle ear source for such a gap, thereby avoiding negative middle ear exploration. A large vestibular aqueduct may act as a third mobile window in the inner ear, resulting in an air-bone gap at low frequencies. PMID:17727085

Prevent and cure disuse bone loss

NASA Technical Reports Server (NTRS)

Jee, Webster S. S.

1994-01-01

Anabolic agents like parathyroid hormone and postagladin E-like substances were studied in dogs and rats to determine their effectiveness in the prevention and cure of bone loss due to immobilization. It was determined that postagladin E2 administration prevented immobilization while at the same time it added extra bone in a dose responsive manner. Although bone mass returns, poor trabecular architecture remains after normal ambulation recovery from immobilization. Disuse related bone loss and poor trabecular architecture were cured by post-immobilization postagladin E2 treatment.

Postnatal progression of bone disease in the cervical spines of mucopolysaccharidosis I dogs

PubMed Central

Chiaro, Joseph A; Baron, Matthew D; del Alcazar, Chelsea; O’Donnell, Patricia; Shore, Eileen M; Elliott, Dawn M; Ponder, Katherine P; Haskins, Mark E; Smith, Lachlan J

2013-01-01

Introduction Mucopolysaccharidosis I (MPS I) is a lysosomal storage disorder characterized by deficient α-L-iduronidase activity leading to accumulation of poorly degraded dermatan and heparan sulfate glycosaminoglycans (GAGs). MPS I is associated with significant cervical spine disease, including vertebral dysplasia, odontoid hypoplasia, and accelerated disc degeneration, leading to spinal cord compression and kypho-scoliosis. The objective of this study was to establish the nature and rate of progression of cervical vertebral bone disease in MPS I using a canine model. Methods C2 vertebrae were obtained post-mortem from normal and MPS I dogs at 3, 6 and 12 months-of-age. Morphometric parameters and mineral density for the vertebral trabecular bone and odontoid process were determined using micro-computed tomography. Vertebrae were then processed for paraffin histology, and cartilage area in both the vertebral epiphyses and odontoid process were quantified. Results Vertebral bodies of MPS I dogs had lower trabecular bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD) than normals at all ages. For MPS I dogs, BV/TV, Tb.Th and BMD plateaued after 6 months-of-age. The odontoid process appeared morphologically abnormal for MPS I dogs at 6 and 12 months-of-age, although BV/TV and TMD were not significantly different from normals. MPS I dogs had significantly more cartilage in the vertebral epiphyses at both 3 and 6 months-of-age. At 12 months-of-age, epiphyseal growth plates in normal dogs were absent, but in MPS I dogs they persisted. Conclusions In this study we report reduced trabecular bone content and mineralization, and delayed cartilage to bone conversion in MPS I dogs from 3 months-of-age, which may increase vertebral fracture risk and contribute to progressive deformity. The abnormalities of the odontoid process we describe likely contribute to increased incidence of atlanto-axial subluxation observed clinically. Therapeutic strategies that enhance bone formation may decrease incidence of spine disease in MPS I patients. PMID:23563357

Regulation of DMT1 on Bone Microstructure in Type 2 Diabetes

PubMed Central

Zhang, Wei-Lin; Meng, Hong-Zheng; Yang, Mao-Wei

2015-01-01

Diabetic osteoporosis is gradually attracted people's attention. However, the process of bone microstructure changes in diabetic patients, and the exact mechanism of osteoblast iron overload are unclear. Therefore, the present study aimed to explore the function of DMT1 in the pathological process of diabetic osteoporosis. We build the type two diabetes osteoporosis models with SD rats and Belgrade rats, respectively. Difference expression of DMT1 was detected by using the method of immunohistochemistry and western blotting. Detection of bone microstructure and biomechanics and iron content for each group of samples. We found that DMT1 expression in type 2 diabetic rats was higher than that in normal rats. The bone biomechanical indices and bone microstructure in the rat model deficient in DMT1 was significantly better than that in the normal diabetic model. The loss of DMT1 can reduce the content of iron in bone. These findings indicate that DMT1 expression was enhanced in the bone tissue of type 2 diabetic rats, and plays an important role in the pathological process of diabetic osteoporosis. Moreover, DMT1 may be a potential therapeutic target for diabetic osteoporosis. PMID:26078704

Osteoporosis in men with idiopathic hypogonadotropic hypogonadism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finkelstein, J.S.; Klibanski, A.; Neer, R.M.

To assess the effect of testosterone deficiency on skeletal integrity in men, we determined bone density in 23 hypogonadal men with isolated gonadotropin-releasing hormone deficiency and compared those values with ones from controls. Cortical bone density, as assessed by single-photon absorptiometry of the nondominant radius, ranged from 0.57 to 0.86 g/cm2 (mean +/- SE, 0.71 +/- 0.02) in patients with fused epiphyses and from 0.57 to 0.67 g/cm2 (mean, 0.61 +/- 0.01) in patients with open epiphyses, both of which were significantly (p less than 0.001) lower than normal. Spinal trabecular bone density, as assessed by computed tomography, was similarlymore » decreased (p less than 0.0001) and ranged from 42 to 177 mg K2HPO4/cm3 (mean, 112 +/- 7). Cortical bone density was at least 2 SD below normal in 16 of 23 men, and 8 men had spinal bone densities below the fracture threshold of 80 to 100 mg K2HPO4/cm3. Osteopenia was equally severe in men with immature and mature bone ages, suggesting that abnormal bone development plays an important role in the osteopenia of men with idiopathic hypogonadotropic hypogonadism.« less

Altered [99mTc]Tc-MDP biodistribution from neutron activation sourced 99Mo.

PubMed

Demeter, Sandor; Szweda, Roman; Patterson, Judy; Grigoryan, Marine

2018-01-01

Given potential worldwide shortages of fission sourced 99 Mo/ 99m Tc medical isotopes there is increasing interest in alternate production strategies. A neutron activated 99 Mo source was utilized in a single center phase III open label study comparing 99m Tc, as 99m Tc Methylene Diphosphonate ([ 99m Tc]Tc-MDP), obtained from solvent generator separation of neutron activation produced 99 Mo, versus nuclear reactor produced 99 Mo (e.g., fission sourced) in oncology patients for which an [ 99m Tc]Tc-MDP bone scan would normally have been indicated. Despite the investigational [ 99m Tc]Tc-MDP passing all standard, and above standard of care, quality assurance tests, which would normally be sufficient to allow human administration, there was altered biodistribution which could lead to erroneous clinical interpretation. The cause of the altered biodistribution remains unknown and requires further research.

3 Tesla (1) H MR spectroscopy of hip bone marrow in a healthy population, assessment of normal fat content values and influence of age and sex.

PubMed

Pansini, Vittorio; Monnet, Aurélien; Salleron, Julia; Hardouin, Pierre; Cortet, Bernard; Cotten, Anne

2014-02-01

To evaluate in a healthy population normal spectroscopic fat content (FC) values of the hip bone marrow and to assess the influence of age and sex on bone marrow conversion. Eighty volunteers (40 men; 40 women; ages: 20-60 years; divided into four consecutive groups) underwent acetabulum, femoral head, femoral neck, greater trochanter, and diaphysis localized (1) H MR spectroscopy. FC values of each anatomical site were obtained according to the following formula: Fat content = CH2 /(CH2  + Water)*100. To assess bone marrow conversion, a spectroscopic conversion index (SCI) was calculated as FC neck/FC greater trochanter. FC values showed a gradient as follows: greater trochanter > femoral head > femoral neck > diaphysis > acetabulum in every age group both in men and in women. SCI increased with age both in men and women, showing lower values in women for every age group. We obtained normal spectroscopic FC values from different areas of the hip, according to age and sex. These values may be used as reference values to evaluate, by the means of (1) H MR spectroscopy, pathological conditions affecting hip bone marrow. Copyright © 2013 Wiley Periodicals, Inc.

Effects of salmon calcitonin on fracture healing in ovariectomized rats.

PubMed

Li, Xiaolin; Luo, Xinle; Yu, Nansheng; Zeng, Bingfang

2007-01-01

To explore the effects of salmon calcitonin on the healing process of osteoporotic fractures in ovariectomized rats. We performed this study in The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China, during the period March 2002 to December 2004. We used 120 female adult Wistar rats in this experiment, among which 90 underwent ovariectomy (OVX) and the other 30 had sham-operation. All rats had their left tibias fractured 3 months later. The 90 OVX rats were randomly divided into 3 groups with 30 in each, while the 30 sham-operated rats served as control group. After the fracture the rats had subcutaneous injection of normal saline, salmon calcitonin and estrogen, respectively. X-ray film, histological examination, bone mineral density (BMD) measurement and biomechanics testing were carried out to evaluate the fracture healing. Compared with OVX rats treated with normal saline, the rats with salmon calcitonin had significantly higher BMD values in the left tibia, higher max torque, shear stress of the left tibia 8 weeks after fracture (p<0.05), and presented with stronger callus formation, shorter fracture healing time and faster normalization of microstructure of bone trabeculae. Salmon calcitonin can, not only increase BMD in osteoporotic bone, but also enhance the bone biomechanical properties and improve the process of fracture healing in fractured osteoporotic bone.

A single injection of the anabolic bone agent, parathyroid hormone-collagen binding domain (PTH-CBD), results in sustained increases in bone mineral density for up to 12 months in normal female mice.

PubMed

Ponnapakkam, Tulasi; Katikaneni, Ranjitha; Suda, Hirofumi; Miyata, Shigeru; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert C

2012-09-01

Parathyroid hormone (PTH) is the most effective osteoporosis treatment, but it is only effective if administered by daily injections. We fused PTH(1-33) to a collagen binding domain (PTH-CBD) to extend its activity, and have shown an anabolic bone effect with monthly dosing. We tested the duration of action of this compound with different routes of administration. Normal young C57BL/6J mice received a single intraperitoneal injection of PTH-CBD (320 μg/kg). PTH-CBD treated mice showed a 22.2 % increase in bone mineral density (BMD) at 6 months and 12.8 % increase at 12 months. When administered by subcutaneous injection, PTH-CBD again caused increases in BMD, 15.2 % at 6 months and 14.3 % at 12 months. Radiolabeled PTH-CBD was concentrated in bone and skin after either route of administration. We further investigated skin effects of PTH-CBD, and histological analysis revealed an apparent increase in anagen VI hair follicles. A single dose of PTH-CBD caused sustained increases in BMD by >10 % for 1 year in normal mice, regardless of the route of administration, thus showing promise as a potential osteoporosis therapy.

Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

PubMed Central

Newman, Christopher L.; Creecy, Amy; Granke, Mathilde; Nyman, Jeffry S.; Tian, Nannan; Hammond, Max A.; Wallace, Joseph M.; Brown, Drew M.; Chen, Neal; Moe, Sharon M.; Allen, Matthew R.

2015-01-01

Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild anti-resorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared to normal controls as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. While it had little effect on cortical bone geometry it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole bone mechanical properties in CKD through its impact on skeletal material properties. PMID:26489025

Bare Bones of Bioactive Glass

NASA Technical Reports Server (NTRS)

2000-01-01

Paul Ducheyne, a principal investigator in the microgravity materials science program and head of the University of Pernsylvania's Center for Bioactive Materials and Tissue Engineering, is leading the trio as they use simulated microgravity to determine the optimal characteristics of tiny glass particles for growing bone tissue. The result could make possible a much broader range of synthetic bone-grafting applications. Even in normal gravity, bioactive glass particles enhance bone growth in laboratory tests with flat tissue cultures. Ducheyne and his team believe that using the bioactive microcarriers in a rotating bioreactor in microgravity will produce improved, three-dimensional tissue cultures. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: NASA and University of Pennsylvania Center for Bioactive Materials and Tissue Engineering.

Growth plate closure: Apex view on bone scan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giles, P.H.; Trochei, M.; Yeates, K.

1984-01-01

Angular deformities of the extremities in children following premature closure of the growth plate are well known. The deformities depend on the position of an osseus bridge which forms between the epiphysis and metaphysis. Several surgical procedures including resection of the osseus bridge have been described, however, delineation of the site of fusion is difficult to define. The commonest site of growth plate arrest is the distal femoral or proximal tibial growth plate. A new technique using the bone scan has been developed which accurately defines the area and position of these osseus bridges. Two hours after injection of technetiummore » 99m methylene diphosphonate apex views of the affected distal femoral growth plate were performed. The knee was flexed into its smallest angle. Using a pinhole collimator the gamma camera was angled to face the affected growth plate end on. The image was collected onto computer and analysed by: (I) regions of interest over segments of the growth plate to calculate the relative area of total growth plate affected: (II) generating histograms: (III) thresholding or performing isocontours to accentuate abnormal areas. The growth plate is normally uniformly increased when compared to the normal shaft of the bone. Fusion across the plate appears as an area of diminished uptake. The apex view gives a unique functional map of the growth plate such that abnormal areas are displayed, and the site, size and position of osseus fusion obtained. The technique has the potential for determining the metabolic activity of the growth plate before and after surgery. Serial studies will allow assessment of regneration of the plate and reformation of new osseus bridges.« less

Favorable effect of moderate dose caffeine on the skeletal system in ovariectomized rats.

PubMed

Folwarczna, Joanna; Pytlik, Maria; Zych, Maria; Cegieła, Urszula; Kaczmarczyk-Sedlak, Ilona; Nowińska, Barbara; Sliwiński, Leszek

2013-10-01

Caffeine, a methylxanthine present in coffee, has been postulated to be responsible for an increased risk of osteoporosis in coffee drinkers; however, the data are inconsistent. The aim of the present study was to investigate the effects of a moderate dose of caffeine on the skeletal system of rats with normal and decreased estrogen level (developing osteoporosis due to estrogen deficiency). The experiments were carried out on mature nonovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving caffeine once daily, 20 mg/kg p.o., for 4 wk. Serum bone turnover markers, bone mass, mass of bone mineral, calcium and phosphorus content, histomorphometric parameters, and bone mechanical properties were examined. Caffeine favorably affected the skeletal system of ovariectomized rats, slightly inhibiting the development of bone changes induced by estrogen deficiency (increasing bone mineralization, and improving the strength and structure of cancellous bone). Moreover, it favorably affected mechanical properties of compact bone. There were no significant effects of caffeine in rats with normal estrogen levels. In conclusion, results of the present study indicate that low-to-moderate caffeine intake may exert some beneficial effects on the skeletal system of mature organisms. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of immediate and delayed loading on peri-implant trabecular structures: a cone beam CT evaluation.

PubMed

Huang, Yan; Van Dessel, Jeroen; Liang, Xin; Depypere, Maarten; Zhong, Weijian; Ma, Guowu; Lambrichts, Ivo; Maes, Frederik; Jacobs, Reinhilde

2014-12-01

To develop a method for characterizing trabecular bone microarchitecture using cone beam computed tomography (CBCT) and to evaluate trabecular bone changes after rehabilitation using immediate versus delayed implant protocols. Six mongrel dogs randomly received 27 titanium implants in the maxillary incisor or mandibular premolar areas, following one of four protocols: (1) normal extraction socket healing; (2) immediate implant placement and immediate loading; (3) delayed implant placement and delayed loading; (4) delayed implant placement and immediate loading. The animals were euthanized at 8 weeks, and block biopsies were scanned using high resolution CBCT. Standard bone structural variables were assessed in coronal, middle, and apical levels. Coronal and middle regions had more compact, more platelike, and thicker trabeculae. Protocols (2), (3), and (4) had significantly higher values (p < 0.001) than protocol (1) for bone surface density, bone surface volume ratio, and connectivity density, while significantly lower values (p < 0.001) were found for trabecular separation and fractal dimension. However, protocols (2), (3), and (4) did not show significantly different bone remodeling. Compared with normal extraction healing, the implant protocols have an improved bone structural integration. Results do not suggest a different bone remodeling pattern when a delayed versus an immediate implant protocol is used. © 2013 Wiley Periodicals, Inc.

Flow cytometric analysis of normal and neoplastic mast cells: role in diagnosis and follow-up of mast cell disease.

PubMed

Escribano, Luis; Garcia Montero, Andres C; Núñez, Rosa; Orfao, Alberto

2006-08-01

Human mast cells (MCs) are directly derived from human pluripotent CD34+ stem and progenitor hematopoietic cells with stem cell factor being a critical growth factor supporting human MC proliferation, differentiation, and survival. Because of the advantages that flow cytometry offers (it allows rapid, objective, and sensitive multiparameter analysis of high numbers of cells from a sample, with information being provided on the basis of a single cell), it has become the method of choice in the past decade for immunophenotypic identification, enumeration, and characterization of human MCs in bone marrow and other tissue specimens.

Autophagy: a new player in skeletal maintenance?

PubMed

Hocking, Lynne J; Whitehouse, Caroline; Helfrich, Miep H

2012-07-01

Imbalances between bone resorption and formation lie at the root of disorders such as osteoporosis, Paget's disease of bone (PDB), and osteopetrosis. Recently, genetic and functional studies have implicated proteins involved in autophagic protein degradation as important mediators of bone cell function in normal physiology and in pathology. Autophagy is the conserved process whereby aggregated proteins, intracellular pathogens, and damaged organelles are degraded and recycled. This process is important both for normal cellular quality control and in response to environmental or internal stressors, particularly in terminally-differentiated cells. Autophagic structures can also act as hubs for the spatial organization of recycling and synthetic process in secretory cells. Alterations to autophagy (reduction, hyperactivation, or impairment) are associated with a number of disorders, including neurodegenerative diseases and cancers, and are now being implicated in maintenance of skeletal homoeostasis. Here, we introduce the topic of autophagy, describe the new findings that are starting to emerge from the bone field, and consider the therapeutic potential of modifying this pathway for the treatment of age-related bone disorders. Copyright © 2012 American Society for Bone and Mineral Research.

Growth of the flat bones of the membranous neurocranium: a computational model.

PubMed

Garzón-Alvarado, Diego A; González, Andres; Gutiérrez, Maria Lucia

2013-12-01

This article assumes two stages in the formation of the bones in the calvaria, the first one takes into account the formation of the primary centers of ossification. This step counts on the differentiation from mesenchymal cells into osteoblasts. A molecular mechanism is used based on a system of reaction-diffusion between two antagonistic molecules, which are BMP2 and Noggin. To this effect we used equations whose behavior allows finding Turing patterns that determine the location of the primary centers. In the second step of the model we used a molecule that is expressed by osteoblasts, called Dxl5 and that is expressed from the osteoblasts of each flat bone. This molecule allows bone growth through its borders through cell differentiation adjacent to each bone of the skull. The model has been implemented numerically using the finite element method. The results allow us to observe a good approximation of the formation of flat bones of the membranous skull as well as the formation of fontanelles and sutures. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

PubMed

Starke, Astrid; Corsenca, Alf; Kohler, Thomas; Knubben, Johannes; Kraenzlin, Marius; Uebelhart, Daniel; Wüthrich, Rudolf P; von Rechenberg, Brigitte; Müller, Ralph; Ambühl, Patrice M

2012-09-01

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

Decreased Bone Formation and Osteopenia in Lamin A/C-Deficient Mice

PubMed Central

Vidal, Christopher; McCorquodale, Thomas; Herrmann, Markus; Fatkin, Diane; Duque, Gustavo

2011-01-01

Age-related bone loss is associated with changes in bone cellularity with characteristically low levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although recent in vitro evidence has suggested a new role for proteins of the nuclear envelope in osteoblastogenesis, the role of these proteins in bone cells differentiation and bone metabolism in vivo remains unknown. In this study, we used the lamin A/C null (Lmna −/−) mice to identify the role of lamin A/C in bone turnover and bone structure in vivo. At three weeks of age, histological and micro computed tomography measurements of femurs in Lmna −/− mice revealed a significant decrease in bone mass and microarchitecture in Lmna −/− mice as compared with their wild type littermates. Furthermore, quantification of cell numbers after normalization with bone surface revealed a significant reduction in osteoblast and osteocyte numbers in Lmna −/− mice compared with their WT littermates. In addition, Lmna −/− mice have significantly lower osteoclast number, which show aberrant changes in their shape and size. Finally, mechanistic analysis demonstrated that absence of lamin A/C is associated with increase expression of MAN-1 a protein of the nuclear envelope closely regulated by lamin A/C, which also colocalizes with Runx2 thus affecting its capacity as osteogenic transcription factor. In summary, these data clearly indicate that the presence of lamin A/C is necessary for normal bone turnover in vivo and that absence of lamin A/C induces low bone turnover osteopenia resembling the cellular changes of age-related bone loss. PMID:21547077

Spontaneous progression of experimentally induced periimplantitis.

PubMed

Zitzmann, N U; Berglundh, T; Ericsson, I; Lindhe, J

2004-10-01

Periimplantitis represents an inflammatory condition that is associated with the presence of a submarginal biofilm and with advanced breakdown of soft and mineralized tissues surrounding endosseous implants. Animal models have been used to describe mechanisms involved in the pathogenesis and treatment of the soft and hard tissue lesions of periimplantitis. The aim of the present experiment was to study the presence and progression of inflammatory lesions in tissues surrounding implants exposed to "experimental periimplantitis". Five Labrador dogs were used. In each dog, 2 or 3 implants were placed in both the left and right edentulous premolar regions of the mandible. Abutment connection was performed 4 months later and a plaque control regimen was initiated and maintained for 5 months. "Experimental periimplantitis" was subsequently induced by ligature placement and plaque accumulation was allowed to progress until about 40% of the height of the supporting bone had been lost. The ligatures were removed, but plaque formation was allowed to continue for an additional 12 months. Radiographs of all implant sites were obtained before and after active "experimental periimplantitis" as well as at the end of the experiment. Biopsies were harvested from the implant sites in 3 of the dogs. The tissue samples were prepared for light microscopy and the sections were used for histometric and morphometric examinations. One implant was lost during the first 2 months of "experimental periimplantitis" and two implants were lost during the 12 months that followed ligature removal. The radiographic examination indicated that varying amounts of additional bone loss occurred in the majority of the implant sites also following ligature removal. The mucosa of all implant sites harbored inflammatory lesions that extended apically of the pocket epithelium. The lesions were separated from the marginal bone by a zone of apparently normal connective tissue. A remission of the destructive inflammatory lesion in the periimplant tissues was seen in some sites following ligature removal, but in the majority of sites additional loss of supporting bone occurred. Copyright Blackwell Munksgaard, 2004

Histomorphometric Study of New Bone Formation Comparing Defect Healing with Three Bone Grafting Materials: The Effect of Osteoporosis on Graft Consolidation.

PubMed

Zhang, Qiao; Jing, Dai; Zhang, Yufeng; Miron, Richard J

Bone grafting materials are frequently utilized in oral surgery and periodontology to fill bone defects and augment lost or missing bone. The purpose of this study was to compare new bone formation in bone defects created in both normal and osteoporotic animals loaded with three types of bone grafts from different origins. Forty-eight female Wistar rats were equally divided into control normal and ovariectomized animals. Bilateral 2.5-mm femur defects were created and filled with an equal weight of (1) natural bone mineral (NBM, BioOss) of bovine origin, (2) demineralized freeze-dried bone allograft (DFDBA, LifeNet), or (3) biphasic calcium phosphate (BCP, Vivoss). Following 3 and 6 weeks of healing, hematoxylin and eosin and TRAP staining was performed to determine new bone formation, material degradation, and osteoclast activity. All bone substitutes demonstrated osteoconductive potential at 3 and 6 weeks with higher osteoclast numbers observed in all ovariectomized animals. NBM displayed continual new bone formation with little to no sign of particle degradation, even in osteoporotic animals. DFDBA particles showed similar levels of new bone formation but rapid particle degradation rates with lower levels of mineralized tissue. BCP bone grafts demonstrated significantly higher new bone formation when compared with both NBM and DFDBA particles; however, the material was associated with higher osteoclast activity and particle degradation. Interestingly, in osteoporotic animals, BCP displayed synergistically and markedly more rapid rates of particle degradation. Recent modifications to synthetically fabricated materials were shown to be equally or more osteopromotive than NBM and DFDBA. However, the current BCP utilized demonstrated much faster resorption properties in osteoporotic animals associated with a decrease in total bone volume when compared with the slowly/nonresorbing NBM. The results from this study point to the clinical relevance of minimizing fast-resorbing bone grafting materials in osteoporotic phenotypes due to the higher osteoclastic activity and greater material resorption.

Genetics Home Reference: gnathodiaphyseal dysplasia

MedlinePlus

... can result in deterioration of the exposed bone (osteonecrosis of the jaw). Also, normal bone in areas ... Institute of Arthritis and Musculoskeletal and Skin Diseases: Osteonecrosis Educational Resources (4 links) American College of Rheumatology: ...

Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease

PubMed Central

Seeley, Erin H.; Wilson, Kevin J.; Yankeelov, Thomas E.; Johnson, Rachelle W.; Gore, John C.; Caprioli, Richard M.; Matrisian, Lynn M.; Sterling, Julie A.

2014-01-01

Bone metastases are a clinically significant problem that arises in approximately 70% of metastatic breast cancer patients. Once established in bone, tumor cells induce changes in the bone microenvironment that lead to bone destruction, pain, and significant morbidity. While much is known about the later stages of bone disease, less is known about the earlier stages or the changes in protein expression in the tumor micro-environment. Due to promising results of combining magnetic resonance imaging (MRI) and Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI IMS) ion images in the brain, we developed methods for applying these modalities to models of tumor-induced bone disease in order to better understand the changes in protein expression that occur within the tumor-bone microenvironment. Specifically, we integrated three dimensional-volume reconstructions of spatially resolved MALDI IMS with high-resolution anatomical and diffusion weighted MRI data and histology in an intratibial model of breast tumor-induced bone disease. This approach enables us to analyze proteomic profiles from MALDI IMS data with corresponding in vivo imaging and ex vivo histology data. To the best of our knowledge, this is the first time these three modalities have been rigorously registered in the bone. The MALDI mass-to-charge ratio peaks indicate differential expression of calcyclin, ubiquitin, and other proteins within the tumor cells, while peaks corresponding to hemoglobin A and calgranulin A provided molecular information that aided in the identification of areas rich in red and white blood cells, respectively. This multimodality approach will allow us to comprehensively understand the bone-tumor microenvironment and thus may allow us to better develop and test approaches for inhibiting bone metastases. PMID:24487126

THE EFFECT OF ANTISERUM, ALONE AND WITH HYDROCORTISONE, ON FOETAL MOUSE BONES IN CULTURE

PubMed Central

Fell, Honor B.; Weiss, L.

1965-01-01

1. The effects of normal rabbit serum and of rabbit antiserum to whole foetal mouse tissues, on the isolated limb bones of late foetal mice were studied in organ culture, and the influence of hydrocortisone on these effects was investigated. 2. Unheated normal serum caused slight loss of metachromatic material from the cartilage matrix, and some resorption of both cartilage and bone. 3. In unheated antiserum to foetal mouse tissues, the terminal cartilage was smaller and less metachromatic than in paired controls in normal serum, while osteoclasis was so intense that in many explants the bone had almost disappeared. The amount of necrosis varied with different batches of antiserum. 4. The changes produced by normal serum and antiserum could be largely prevented by heating the sera to 57°C for 45 minutes. 5. The effects could also be inhibited by the addition of hydrocortisone to the unheated sera; as little as 0.1 µg hydrocortisone per ml of medium had a well marked protective action. 6. It is suggested that (a) unheated antiserum causes a release of lysosomal enzymes with consequent breakdown of intercellular material, (b) this release is due to an indirect action on the lysosome via an increased permeability of the cell membrane, (c) hydrocortisone does not affect the antigen-antibody reaction, but inhibits the autolytic changes that normally follow this reaction, possibly by stabilising both the lysosomal and cell membranes. PMID:14276776

Bone mineral content in the senescent rat femur: an assessment using single photon absorptiometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiebzak, G.M.; Smith, R.; Howe, J.C.

1988-06-01

The single photon absorptiometry technique was evaluated for measuring bone mineral content (BMC) of the excised femurs of the rat, and the system was used to examine the changes in cortical and trabecular bone from young adult (6 mo), mature adult (12 mo), and senescent (24 mo) male and female animals. BMC of the femur midshaft, representing cortical bone, apparently increased progressively with advancing age. The width of the femur at the scan site also increased with age. Normalizing the midshaft BMC by width partially compensated for the age-associated increase. However, when bone mineral values were normalized by the corticalmore » area at the scan site, to take into account the geometric differences in the femurs of different aged animals, maximum bone densities were found in the mature adult and these values decreased slightly in the femurs from senescent rats. In contrast, the BMC of the femur distal metaphysis, representing trabecular bone, decreased markedly in the aged rat. The loss of trabecular bone was also evident from morphological examination of the distal metaphysis. These findings indicated that bone mineral loss with age was site specific in the rat femur. These studies provided additional evidence that the rat might serve as a useful animal model for specific experiments related to the pathogenesis of age-associated osteopenia.« less

Bone Geometry as a Predictor of Tissue Fragility and Stress Fracture Risk

DTIC Science & Technology

2004-10-01

eferences ........................................................................ 11 A ppendices ...School of Medicine, New York NY Stress fractures occur among persons with normal bones, no acute injury, and are most common among elite runners and

Animal Enclosure Module (AEM)

NASA Technical Reports Server (NTRS)

1998-01-01

The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging.

PubMed

Montazel, Jean-Luc; Divine, Marine; Lepage, Eric; Kobeiter, Hicham; Breil, Stephane; Rahmouni, Alain

2003-12-01

To determine the patterns of dynamic enhancement of normal spinal bone marrow in adults at gadolinium-enhanced magnetic resonance (MR) imaging and the changes that occur with aging. Dynamic contrast material-enhanced MR imaging of the thoracolumbar spine was performed in 71 patients. The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from bone marrow enhancement time curves (ETCs). The bone marrow signal intensity on T1-weighted spin-echo MR images was qualitatively classified into three grade categories. Quantitative ETC values were correlated with patient age and bone marrow fat content grade. Statistical analysis included mean t test comparison, analysis of variance, and regression analysis of the correlations between age and quantitative MR parameters. Emax, slope, and washout varied widely among the patients. Emax values were obtained within 1 minute after contrast material injection and ranged from 0% to 430%. Emax values were significantly higher in patients younger than 40 years than in those aged 40 years or older (P <.001). These values decreased with increasing age in a logarithmic relationship (r = 0.71). Emax values decreased as fat content increased, but some overlap among the fat content grades was noted. Analysis of variance revealed that Emax was significantly related to age (younger than 40 years vs 40 years or older) (P <.001) and fat content grade (P <.001) but not significantly related to sex. Dynamic contrast-enhanced MR imaging patterns of normal spinal bone marrow are dependent mainly on patient age and fat content.

Modified Kidner procedure utilizing a Mitek bone anchor.

PubMed

Dawson, D M; Julsrud, M E; Erdmann, B B; Jacobs, P M; Ringstrom, J B

1998-01-01

The recent development of small bone suture anchors has created several potential applications in reconstructive surgery of the foot. Mitek bone anchors are simple to insert, require less aggressive dissection and surgical time than reefing of the redundant posterior tibial tendon, and are a reliable method of tendon-to-bone fixation. Mitek bone anchors are an excellent technique for the treatment of redundant tibialis posterior tendon following a modified Kidner procedure. In modified Kidner procedures involving an excessively large os tibiale externum, Mitek anchoring of the redundant tibialis posterior tendon to the navicular bone is an excellent means for secure plication of the posterior tibial tendon in cases involving intraoperative tendon laxity. A description of the Mitek Anchor System and technique of application in a modified Kinder procedure is presented. The purpose of this study was to describe patient satisfaction and long-term clinical outcomes of the modified Kinder procedure with and without the Mitek bone anchoring system. A retrospective study of the modified Kinder procedure was performed with 13 patients being evaluated, seven with Mitek anchoring and six without. The University of Maryland 100-point Painful Foot Center Scoring System was modified to be more specific to the modified Kinder procedure for assessment of subjective long-term results. Patient overall satisfaction was rated good to excellent by 85.6% of patients in the Mitek group and by 100% of patients in the non-Mitek group. Use of the Mitek anchor allowed for quicker postoperative recovery to resumption of ambulation without assistive devices (average of 3 weeks vs. 4.42 weeks) and a quicker return to pain-free ambulation in normal shoegear (average of 4 weeks vs. 6 weeks). Mitek anchoring of the tibialis posterior tendon, theoretically, increases medial arch support as evidenced by 14% of the Mitek group and 67% of the non-Mitek group requiring postoperative orthotics.

Current concepts regarding calcium metabolism and bone health in sarcoidosis.

PubMed

Baughman, Robert P; Papanikolaou, Ilias

2017-09-01

Vitamin D supplementation is widespread used in the general population. In sarcoidosis, up to 50% of patients, especially postmenopausal women and those taking corticosteroids, show evidence of increased bone fragility. The purpose of this review is to provide an evidence-based rationale on how to treat sarcoidosis patients with bone health issues. Evidence from observational studies show that decreased 25-hydroxy vitamin D is common in sarcoidosis. However, the great majority of sarcoidosis patents have normal or often elevated levels of 1,25-dihydroxy vitamin D (calcitriol), a marker associated with disease activity. High calcitriol levels may often be associated with hypercalcemia and hypercalcuria. The few interventional randomized controlled studies in the field, suggest that vitamin D supplementation may not be well tolerated because of hypercalcemia, moreover without substantial benefit on bone health and risk for fractures in these patients. Vitamin D supplementation may be withheld in sarcoidosis patients with bone fragility, unless calcitriol levels are below normal limits. A treating scheme is proposed.

Elastic intramedullary nailing and DBM-Bone marrow injection for the treatment of simple bone cysts

PubMed Central

Kanellopoulos, Anastasios D; Mavrogenis, Andreas F; Papagelopoulos, Panayiotis J; Soucacos, Panayotis N

2007-01-01

Background Simple or unicameral bone cysts are common benign fluid-filled lesions usually located at the long bones of children before skeletal maturity. Methods We performed demineralized bone matrix and iliac crest bone marrow injection combined with elastic intramedullary nailing for the treatment of simple bone cysts in long bones of 9 children with a mean age of 12.6 years (range, 4 to 15 years). Results Two of the 9 patients presented with a pathological fracture. Three patients had been referred after the failure of previous treatments. Four patients had large lesions with impending pathological fractures that interfered with daily living activities. We employed a ratio to ascertain the severity of the lesion. The extent of the lesion on the longitudinal axis was divided with the normal expected diameter of the long bone at the site of the lesion. The mean follow-up was 77 months (range, 5 to 8 years). All patients were pain free and had full range of motion of the adjacent joints at 6 weeks postoperatively. Review radiographs showed that all 7 cysts had consolidated completely (Neer stage I) and 2 cysts had consolidated partially (Neer stage II). Until the latest examination there was no evidence of fracture or re-fracture. Conclusion Elastic intramedullary nailing has the twofold benefits of continuous cyst decompression, and early immediate stability to the involved bone segment, which permits early mobilization and return to the normal activities of the pre-teen patients. PMID:17916249

Concise review: Insights from normal bone remodeling and stem cell-based therapies for bone repair.

PubMed

Khosla, Sundeep; Westendorf, Jennifer J; Mödder, Ulrike I

2010-12-01

There is growing interest in the use of mesenchymal stem cells for bone repair. As a major reason for normal bone remodeling is the removal of fatigue microcracks, advances in our understanding of this process may inform approaches to enhance fracture healing. Increasing evidence now indicates that physiological bone remodeling occurs in close proximity to blood vessels and that these vessels carry perivascular stem cells that differentiate into osteoblasts. Similarly, fracture healing is critically dependent on the ingrowth of blood vessels not only for a nutrient supply but also for the influx of osteoblasts. A number of animal and human studies have now shown the potential benefit of bone marrow-derived mesenchymal stem cells in enhancing bone repair. However, as in other tissues, the question of whether these cells improve fracture healing directly by differentiating into osteoblasts or indirectly by secreting paracrine factors that recruit blood vessels and the accompanying perivascular stem cells remains a major unresolved issue. Moreover, CD34+ cells, which are enriched for endothelial/hematopoietic cells, have also shown efficacy in various bone repair models, at least in part due to the induction of angiogenesis and recruitment of host progenitor cells. Thus, mesenchymal and nonmesenchymal stem/progenitor cells are attractive options for bone repair. It is possible that they contribute directly to bone repair, but it is also likely that they express paracrine factors in the appropriate amounts and combinations that promote and sustain the healing process.

Measurement of Lacrimal Sac Fossa Using Orbital Computed Tomography.

PubMed

Kang, Dongwan; Park, Jinhwan; Na, Jaehoon; Lee, Hwa; Baek, Sehyun

2017-01-01

To evaluate the clinical usefulness of measuring the lacrimal sac fossa length using orbital computed tomography in normal Koreans. The authors retrospectively evaluated 140 patients (70 males and 70 females) who underwent orbital computed tomography at Guro Hospital and who had no history of orbital disease or orbital trauma. Computed tomography scans of the right orbit, including the proportion of the lacrimal bone and maxillary bone that comprise the lacrimal sac fossa, were evaluated at 3 different axial planes (lower, middle, and upper levels). Additionally, the mid-point thickness and maximum thickness of the maxillary bone were measured. Finally, the authors also evaluated the relationship between nasal bone height and maxillary bone thickness in the lacrimal sac fossa. Maxillary bone thickness in the lacrimal sac fossa was thicker in males than in females at mid-point thickness and maximum thickness (P < 0.05). However, there was no significant difference in the size of the lacrimal sac fossa and the proportion of the maxillary bone between males and females.In comparisons between maxillary cross-sections, bone thickness was greater toward the upper level of the lacrimal sac fossa (P = 0.008), and the proportion of the maxillary bone was also greater (P = 0.006).Aging had a significant positive correlation with maxillary bone thickness at all 3 axial planes (P < 0.05), but there was no relationship between age and maxillary bone proportion. Nasal bone height and maxillary bone thickness were also not significantly related. In comprising the lacrimal sac fossa, the maxillary bone accounted for a bigger proportion than the lacrimal bone. Male maxillary bone thickness was greater than female thickness. The authors also observed that maxillary bone thickness increased toward the upper areas of the lacrimal sac fossa and with increasing subject age. Understanding the form and variation of a normal lacrimal sac fossa is helpful for preparing for a successful osteotomy with endoscopic dacryocystorhinostomy.

Influence of parathyroid state on calcium uptake in bone

PubMed Central

LEMON, GERARD J.; BASSINGTHWAIGHTE, JAMES B.; KELLY, PATRICK J.

2010-01-01

The exchange of calcium and strontium ions in bone was studied in control dogs, dogs made hypocalcemic by parathyroidectomy, and dogs rendered hypercalcemic by injection of parathyroid hormone. After injections of tracer into the tibial nutrient artery, extraction of tracer during transcapillary passage was measured and expressed as a fraction of 1. Extraction over the first 3 min in normal dogs was 0.46 ± 0.09 (n = 6), in hypocalcemic dogs it was increased to 0.53 ± 0.07 (n = 6), and in hypercalcemic dogs it was decreased to 0.39 ± 0.07 (n = 5). Subsequent washout was less rapid than normal in hypoparathyroid dogs and more rapid than normal in hyperparathyroid dogs. We conclude from this that the immediate volume of distribution in bone (or the number of available binding sites) for strontium diminishes as the parathyroid hormone level increases. PMID:7065174

Pathophysiology of immobilization osteoporosis

NASA Technical Reports Server (NTRS)

Doty, S. B.; DiCarlo, E. F.

1995-01-01

The reduction of gravity-related forces on the skeleton creates a type of osteoporosis that is unique because its severity is dependent on the mechanical stress bearing function of the skeleton as well as the length of time that the forces are absent or reduced. Bones that bear weight under normal conditions are more affected than bones that normally do not bear weight. The cytokine environment and the cells in the affected bones are altered in time so that stem cells produce fewer new cells and the differentiated cells tend to be less active. These alterations in the local environment of the affected parts appear to resemble those of age- and disease-associated systemic forms of osteoporosis. The osteoporosis produced as a result of the loss of normal activity however, appears to be at least partially reversible through remobilization, strenuous exercise, and--possibly in the future--cytokine therapy.

Anisotropic analysis of trabecular architecture in human femur bone radiographs using quaternion wavelet transforms.

PubMed

Sangeetha, S; Sujatha, C M; Manamalli, D

2014-01-01

In this work, anisotropy of compressive and tensile strength regions of femur trabecular bone are analysed using quaternion wavelet transforms. The normal and abnormal femur trabecular bone radiographic images are considered for this study. The sub-anatomic regions, which include compressive and tensile regions, are delineated using pre-processing procedures. These delineated regions are subjected to quaternion wavelet transforms and statistical parameters are derived from the transformed images. These parameters are correlated with apparent porosity, which is derived from the strength regions. Further, anisotropy is also calculated from the transformed images and is analyzed. Results show that the anisotropy values derived from second and third phase components of quaternion wavelet transform are found to be distinct for normal and abnormal samples with high statistical significance for both compressive and tensile regions. These investigations demonstrate that architectural anisotropy derived from QWT analysis is able to differentiate normal and abnormal samples.

Stimulation of Mucosal Mast Cell Growth in Normal and Nude Rat Bone Marrow Cultures

NASA Astrophysics Data System (ADS)

Haig, David M.; McMenamin, Christine; Gunneberg, Christian; Woodbury, Richard; Jarrett, Ellen E. E.

1983-07-01

Mast cells with the morphological and biochemical properties of mucosal mast cells (MMC) appear and proliferate to form the predominant cell type in rat bone marrow cultures stimulated with factors from antigen- or mitogen-activated lymphocytes. Conditioned media causing a selective proliferation of MMC were derived from mesenteric lymph node cells of Nippostrongylus brasiliensis-infected rats restimulated in vitro with specific antigen or from normal or infected rat mesenteric lymph node cells stimulated with concanavalin A. MMC growth factor is not produced by T-cell-depleted mesenteric lymph node cells or by the mesenteric lymph node cells of athymic rats. By contrast, MMC precursors are present in the bone marrow of athymic rats and are normally receptive to the growth factor produced by the lymphocytes of thymus-intact rats. The thymus dependence of MMC hyperplasia is thus based on the requirement of a thymus-independent precursor for a T-cell-derived growth promoter.

Quantitative analysis of rib movement based on dynamic chest bone images: preliminary results

NASA Astrophysics Data System (ADS)

Tanaka, R.; Sanada, S.; Oda, M.; Mitsutaka, M.; Suzuki, K.; Sakuta, K.; Kawashima, H.

2014-03-01

Rib movement during respiration is one of the diagnostic criteria in pulmonary impairments. In general, the rib movement is assessed in fluoroscopy. However, the shadows of lung vessels and bronchi overlapping ribs prevent accurate quantitative analysis of rib movement. Recently, an image-processing technique for separating bones from soft tissue in static chest radiographs, called "bone suppression technique", has been developed. Our purpose in this study was to evaluate the usefulness of dynamic bone images created by the bone suppression technique in quantitative analysis of rib movement. Dynamic chest radiographs of 10 patients were obtained using a dynamic flat-panel detector (FPD). Bone suppression technique based on a massive-training artificial neural network (MTANN) was applied to the dynamic chest images to create bone images. Velocity vectors were measured in local areas on the dynamic bone images, which formed a map. The velocity maps obtained with bone and original images for scoliosis and normal cases were compared to assess the advantages of bone images. With dynamic bone images, we were able to quantify and distinguish movements of ribs from those of other lung structures accurately. Limited rib movements of scoliosis patients appeared as reduced rib velocity vectors. Vector maps in all normal cases exhibited left-right symmetric distributions, whereas those in abnormal cases showed nonuniform distributions. In conclusion, dynamic bone images were useful for accurate quantitative analysis of rib movements: Limited rib movements were indicated as a reduction of rib movement and left-right asymmetric distribution on vector maps. Thus, dynamic bone images can be a new diagnostic tool for quantitative analysis of rib movements without additional radiation dose.

Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

NASA Technical Reports Server (NTRS)

Cann, Christopher; Young, Donald R.

1976-01-01

Specific mechanisms underlying weightless and hypodynamic bone loss are obscure. A principal relationship which must be affected is the balance between bone formation and bone resorption rates. In order to better define the influence of those parameters on bone loss, and also to develop measurements in other species as a useful adjunct to human research, studies were undertaken with experimental monkeys. Tests were conducted with a total of 6 adult male monkeys, weighing 10-13 kg, and approximately 10-12 yrs. of age to evaluate specifically bone formation rate during the development of disuse osteoporosis and osteopenia. Three animals were restrained in a semi-recumbent position for six months; three animals served as normal caged controls. Food intake (Purina) was held relatively constant at 200g/day for each animal. Using a Norland Bone Mineral Analyzer, bone mineral losses of 3.5 to 6% were seen in the mid-shaft of the tibia and in the distal radius. Bone loss was confirmed radiographically, with observation of thinning of the proximal tibial cortex and trabeculae in the calcaneus. Bone formation rate was determined using standard Ca-47 kinetics under metabolic balance conditions. After six months of restraint, accretion was 7.2-13.2 mg Ca/kg/day, compared to 3.2-4.1 mg Ca/kg/day in caged controls and 3-8 mg Ca/kg/day in normal adult humans. Fecal and urine calcium was 25-40% higher in restrained animals than in controls. Dietary calcium absorption decreases during restraint, and calcium turnover increases, implying a rise in bone resorption rate concommitant with the observed rise in bone accretion rate. Further studies dealing specifically with bone resorption are underway to define this more fully.

Method for fusing bone

DOEpatents

Mourant, Judith R.; Anderson, Gerhard D.; Bigio, Irving J.; Johnson, Tamara M.

1996-01-01

Method for fusing bone. The present invention is a method for joining hard tissue which includes chemically removing the mineral matrix from a thin layer of the surfaces to be joined, placing the two bones together, and heating the joint using electromagnetic radiation. The goal of the method is not to produce a full-strength weld of, for example, a cortical bone of the tibia, but rather to produce a weld of sufficient strength to hold the bone halves in registration while either external fixative devices are applied to stabilize the bone segments, or normal healing processes restore full strength to the tibia.

Aging changes in the bones - muscles - joints

MedlinePlus

... ency/article/004015.htm Aging changes in the bones - muscles - joints To use the sharing features on ... to the body. Joints are the areas where bones come together. They allow the skeleton to be ...

Bone mineral measurement using dual energy x ray densitometry

NASA Technical Reports Server (NTRS)

Smith, Steven W.

1989-01-01

Bone mineral measurements before and after space missions have shown that weightlessness greatly accelerates bone demineralization. Bone mineral losses as high as 1 to 3 percent per month were reported. Highly precise instrumentation is required to monitor this loss and thereby test the efficacy of treatment. During the last year, a significant improvement was made in Dual-Photon Absorptiometry by replacing the radioactive source with an x ray tube. Advantages of this system include: better precision, lower patient dose, better spacial resolution, and shorter scan times. The high precision and low radiation dose of this technique will allow detection of bone mineral changes of less than 1 percent with measurements conducted directly at the sites of interest. This will allow the required bone mineral studies to be completed in a shorter time with greater confidence.

Disorders of Bone Remodeling

PubMed Central

Feng, Xu; McDonald, Jay M.

2013-01-01

The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skeleton must be maintained by constant bone modeling to carry out these crucial functions throughout life. Bone remodeling involves the removal of old or damaged bone by osteoclasts (bone resorption) and the subsequent replacement of new bone formed by osteoblasts (bone formation). Normal bone remodeling requires a tight coupling of bone resorption to bone formation to guarantee no alteration in bone mass or quality after each remodeling cycle. However, this important physiological process can be derailed by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and secondary diseases, which lead to the development of various bone disorders in both women and men. We review the major diseases of bone remodeling, emphasizing our current understanding of the underlying pathophysiological mechanisms. PMID:20936937

Differential Intracochlear Sound Pressure Measurements in Normal Human Temporal Bones

NASA Astrophysics Data System (ADS)

Nakajima, Hideko Heidi; Dong, Wei; Olson, Elizabeth S.; Merchant, Saumil N.; Ravicz, Michael E.; Rosowski, John J.

2009-02-01

We present the first simultaneous sound pressure measurements in scala vestibuli and scala tympani of the cochlea in human cadaveric temporal bones. Micro-scale fiberoptic pressure sensors enabled the study of differential sound pressure at the cochlear base. This differential pressure is the input to the cochlear partition, driving cochlear waves and auditory transduction. Results showed that: pressure of scala vestibuli was much greater than scala tympani except at low and high frequencies where scala tympani pressure affects the input to the cochlea; the differential pressure proved to be an excellent measure of normal ossicular transduction of sound (shown to decrease 30-50 dB with ossicular disarticulation, whereas the individual scala pressures were significantly affected by non-ossicular conduction of sound at high frequencies); the middle-ear gain and differential pressure were generally bandpass in frequency dependence; and the middle-ear delay in the human was over twice that of the gerbil. Concurrent stapes velocity measurements allowed determination of the differential impedance across the partition and round-window impedance. The differential impedance was generally resistive, while the round-window impedance was consistent with a compliance in conjunction with distributed inertia and damping. Our techniques can be used to study inner-ear conductive pathologies (e.g., semicircular dehiscence), as well as non-ossicular cochlear stimulation (e.g., round-window stimulation) - situations that cannot be completely quantified by measurements of stapes velocity or scala-vestibuli pressure by themselves.

Nano rods for coloured glasses obtained by hybrid sol-gel coating.

PubMed

Veron, Olivier; Blondeau, Jean-Philippe; Moineau, Johanne; Aubert, Pierre-Henri; Vignolle, Caroline Andreazza; Banet, Philippe; Allam, Lévi

2011-09-01

Many new materials are now allowing new properties thanks to nanotechnology because this domain of physics gives possibilities to optimize targeted properties even if these materials react in very various influential parameters. Architectural, automotive, bone pathologies, environment, display applications are some concerned domains. The sol-gel process is a method allowing the realisation of coats at ambiant temperature, thus it is possible to realize Liquid Crystal Display (LCD), water-repellent coatings on privacy glass, antireflective coatings, hydrophobic or hydrophilic surfaces, bone tissue regeneration. In this study, the purpose is to show the thermal influence on a covered glass with a complex hybrid sol-gel solution. This coated glass is going to change color from red to orange under the heat influence. This color change effect comes from the evolution of various compounds organizations then/or from their loss during the degassing sequence. We show in spite of the complexity of the process that the responsible is mainly the organic dye. Thus the structure of the heated glass at 250 degrees C looks radically different than the heated one at 350 degrees C. SEM measurement allows to identify the surface compositions and to determine the elementary composition along the sample's cross section. TGA is used to justify a mass loss when samples are annealed. UV/Visible measurement is realized by two methods: in-line transmission to evaluate luminous flux and thus give colorimetric dot in the normalized CIE diagram and diffuse transmission to observe the size influence of the pigments. Infrared Reflectivity allows to evaluate the influence of species on the structure and to better target the nature of the lost compounds during annealing. TEM measurement proves that the obtained iron particles are nano rods for both samples.

Adenovirus 36, Adiposity, and Bone Strength in Late-Adolescent Females

PubMed Central

Laing, Emma M; Tripp, Ralph A; Pollock, Norman K; Baile, Clifton A; Della-Fera, Mary Anne; Rayalam, Srujana; Tompkins, Stephen M; Keys, Deborah A; Lewis, Richard D

2017-01-01

Adenovirus 36 (Ad36) is the only adenovirus to date that has been linked with obesity in humans. Our previous studies in late-adolescent females suggest that excess weight in the form of fat mass is associated with lower cortical bone strength. The purpose of this study was to assess the relationship between Ad36-specific antibodies, adiposity, and bone strength in our sample of late-adolescent females. A cross-sectional study of 115 females aged 18 to 19 years was performed. Participants were classified according to adiposity by dual-energy X-ray absorptiometry (body fat percentage as normal-fat [<32% body fat; n=93] or high-fat [≥ 32% body fat; n=22]), and according to the presence of Ad36-specific neutralizing antibodies. Peripheral quantitative computed tomography measured bone parameters at the 4% (trabecular bone) and 20% (cortical bone) site, and muscle cross-sectional area (MCSA) at the 66% site, from the distal metaphyses of the radius and the tibia. Bone strength was determined from volumetric bone mineral density and bone geometry to calculate bone strength index (BSI; trabecular site) and polar strength–strain index (SSI; cortical site). After adjustment for MCSA and limb length, radial SSI was lower in Ad36+ versus Ad36− subjects from the high-fat group (p<0.03), but not the normal-fat group. No significant differences were observed between groups in tibial SSI or BSI. These data support an association of adiposity and cortical bone strength at the radius with the presence of neutralizing antibodies to Ad36 in late-adolescent females. PMID:23296755

State of the art systematic review of bone disease in anorexia nervosa.

PubMed

Misra, Madhusmita; Golden, Neville H; Katzman, Debra K

2016-03-01

Low bone mineral density (BMD) is a known consequence of anorexia nervosa (AN) and is particularly concerning during adolescence, a critical time for bone accrual. A comprehensive synthesis of available data regarding impaired bone health, its determinants, and associated management strategies in AN is currently lacking. This systematic review aims to synthesize information from key physiologic and prospective studies and trials, and provide a thorough understanding of impaired bone health in AN and its management. Search terms included "anorexia nervosa" AND "bone density" for the period 1995-2015, limited to articles in English. Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group. When necessary, we included seminal papers published before 1995. AN leads to low BMD, impaired bone quality and increased fracture risk. Important determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations in other hormones that impact bone health. Weight gain and menses restoration are critical for improving bone outcomes in AN. Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in one study in adolescent females with AN; however, residual deficits persist. Bisphosphonates are potentially useful in adults with AN. To date, evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses. Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates. Further studies are necessary to determine the best strategies to normalize BMD in AN. © 2015 Wiley Periodicals, Inc.

State of the Art Systematic Review of Bone Disease in Anorexia Nervosa

PubMed Central

Misra, Madhusmita; Golden, Neville H.; Katzman, Debra K.

2016-01-01

Objective Low bone mineral density (BMD) is a known consequence of anorexia nervosa (AN) and is particularly concerning during adolescence, a critical time for bone accrual. A comprehensive synthesis of available data regarding impaired bone health, its determinants, and associated management strategies in AN is currently lacking. This systematic review aims to synthesize information from key physiologic and prospective studies and trials, and provide a thorough understanding of impaired bone health in AN and its management. Method Search terms included “anorexia nervosa” AND “bone density” for the period 1995–2015, limited to articles in English. Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group. When necessary, we included seminal papers published before 1995. Results AN leads to low BMD, impaired bone quality and increased fracture risk. Important determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations in other hormones that impact bone health. Weight gain and menses restoration are critical for improving bone outcomes in AN. Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in one study in adolescent females with AN; however, residual deficits persist. Bisphosphonates are potentially useful in adults with AN. Discussion To date, evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses. Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates. Further studies are necessary to determine the best strategies to normalize BMD in AN. PMID:26311400

Genetics Home Reference: acute promyelocytic leukemia

MedlinePlus

... acute myeloid leukemia, a cancer of the blood-forming tissue ( bone marrow ). In normal bone marrow, hematopoietic ... 7186-203. Review. Citation on PubMed de Thé H, Chen Z. Acute promyelocytic leukaemia: novel insights into ...

Homing of human B cells to lymphoid organs and B-cell lymphoma engraftment are controlled by cell adhesion molecule JAM-C.

PubMed

Doñate, Carmen; Ody, Christiane; McKee, Thomas; Ruault-Jungblut, Sylvie; Fischer, Nicolas; Ropraz, Patricia; Imhof, Beat A; Matthes, Thomas

2013-01-15

Junctional adhesion molecule C (JAM-C) is expressed by vascular endothelium and human but not mouse B lymphocytes. The level of JAM-C expression defines B-cell differentiation stages and allows the classification of marginal zone-derived (JAM-C-positive) and germinal center-derived (JAM-C-negative) B-cell lymphomas. In the present study, we investigated the role of JAM-C in homing of human B cells, using a xenogeneic nonobese diabetic/severe combined immunodeficient mouse model. Treatment with anti-JAM-C antibodies in short-term experiments reduced migration of normal and malignant JAM-C-expressing B cells to bone marrow, lymph nodes, and spleen. Blocking homing to the spleen is remarkable, as most other antiadhesion antibodies reduce homing of B cells only to bone marrow and lymph nodes. Long-term administration of anti-JAM-C antibodies prevented engraftment of JAM-Cpos lymphoma cells in bone marrow, spleen, and lymph nodes of mice. Plasmon resonance studies identified JAM-B as the major ligand for JAM-C, whereas homotypic JAM-C interactions remained at background levels. Accordingly, anti-JAM-C antibodies blocked adhesion of JAM-C-expressing B cells to their ligand JAM-B, and immunofluorescence analysis showed the expression of JAM-B on murine and human lymphatic endothelial cells. Targeting JAM-C could thus constitute a new therapeutic strategy to prevent lymphoma cells from reaching supportive microenvironments not only in the bone marrow and lymph nodes but also in the spleen.

Aluminum, iron, lead, cadmium, copper, zinc, chromium, magnesium, strontium, and calcium content in bone of end-stage renal failure patients.

PubMed

D'Haese, P C; Couttenye, M M; Lamberts, L V; Elseviers, M M; Goodman, W G; Schrooten, I; Cabrera, W E; De Broe, M E

1999-09-01

Little is known about trace metal alterations in the bones of dialysis patients or whether particular types of renal osteodystrophy are associated with either increased or decreased skeletal concentrations of trace elements. Because these patients are at risk for alterations of trace elements as well as for morbidity from skeletal disorders, we measured trace elements in bone of patients with end-stage renal disease. We analyzed bone biopsies of 100 end-stage renal failure patients enrolled in a hemodialysis program. The trace metal contents of bone biopsies with histological features of either osteomalacia, adynamic bone disease, mixed lesion, normal histology, or hyperparathyroidism were compared with each other and with the trace metal contents of bone of subjects with normal renal function. Trace metals were measured by atomic absorption spectrometry. The concentrations of aluminum, chromium, and cadmium were increased in bone of end-stage renal failure patients. Comparing the trace metal/calcium ratio, significantly higher values were found for the bone chromium/calcium, aluminum/calcium, zinc/calcium, magnesium/calcium, and strontium/calcium ratios. Among types of renal osteodystrophy, increased bone aluminum, lead, and strontium concentrations and strontium/calcium and aluminum/calcium ratios were found in dialysis patients with osteomalacia vs the other types of renal osteodystrophy considered as one group. Moreover, the concentrations of several trace elements in bone were significantly correlated with each other. Bone aluminum was correlated with the time on dialysis, whereas bone iron, aluminum, magnesium, and strontium tended to be associated with patient age. Bone trace metal concentrations did not depend on vitamin D intake nor on the patients' gender. The concentration of several trace elements in bone of end-stage renal failure patients is disturbed, and some of the trace metals under study might share pathways of absorption, distribution, and accumulation. The clinical significance of the increased/decreased concentrations of several trace elements other than aluminum in bone of dialysis patients deserves further investigation.

Association of physical performance measures with bone mineral density in postmenopausal women.

PubMed

Lindsey, Carleen; Brownbill, Rhonda A; Bohannon, Richard A; Ilich, Jasminka Z

2005-06-01

To investigate the association between physical performance measures and bone mineral density (BMD) in older women. Cross-sectional analysis. University research laboratory. Healthy postmenopausal women (N=116; mean age +/- standard deviation, 68.3+/-6.8y) in self-reported good health who were not taking medications known to affect bone, including hormone replacement therapy. Not applicable. Anthropometrics and BMD of the hip, spine, whole body, and forearm. Physical performance measures included normal and brisk 8-m gait speed, normal step length (NSL), brisk step length (BSL), timed 1-leg stance (OLS), timed sit-to-stand (STS), and grip strength. NSL, BSL, normal gait speed, brisk gait speed, OLS, and grip strength correlated significantly with several skeletal sites ( r range, .19-.38; P <.05). In multiple regression models containing body mass index, hours of total activity, total calcium intake, and age of menarche, NSL, BSL, normal and brisk gait speeds, OLS, and grip strength were all significantly associated with BMD of various skeletal sites (adjusted R 2 range, .11-.24; P <.05). Analysis of covariance showed that subjects with longer step lengths and faster normal and brisk gait speeds had higher BMD at the whole body, hip, and spine (brisk speed only). Those with a longer OLS had greater femoral neck BMD, and those with a stronger grip strength had greater BMD in the whole body and forearm ( P <.05). STS was not related to any skeletal site. Normal and brisk gait speed, NSL, BSL, OLS, and grip strength are all associated with BMD at the whole body, hip, spine, and forearm. Physical performance evaluation may help with osteoporosis prevention and treatment programs for postmenopausal women when bone density scores have not been obtained or are unavailable.

Computed Tomography of the Normal Bovine Tarsus.

PubMed

Hagag, U; Tawfiek, M; Brehm, W; Gerlach, K

2016-12-01

The objective of this study was to provide a detailed multiplanar computed tomographic (CT) anatomic reference for the bovine tarsus. The tarsal regions from twelve healthy adult cow cadavers were scanned in both soft and bone windows via a 16-slice multidetector CT scanner. Tarsi were frozen at -20 o C and sectioned to 10-mm-thick slices in transverse, dorsal and sagittal planes respecting the imaging protocol. The frozen sections were cleaned and then photographed. Anatomic structures were identified, labelled and compared with the corresponding CT images. The sagittal plane was indispensable for evaluation of bone contours, the dorsal plane was valuable in examination of the collateral ligaments, and both were beneficial for assessment of the tarsal joint articulations. CT images allowed excellent delineation between the cortex and medulla of bones, and the trabecular structure was clearly depicted. The tarsal soft tissues showed variable shades of grey, and the synovial fluid was the lowest attenuated structure. This study provided full assessment of the clinically relevant anatomic structures of the bovine tarsal joint. This technique may be of value when results from other diagnostic imaging techniques are indecisive. Images presented in this study should serve as a basic CT reference and assist in the interpretation of various bovine tarsal pathology. © 2016 Blackwell Verlag GmbH.

Correction of the mineralization defect in hyp mice treated with protease inhibitors CA074 and pepstatin

PubMed Central

Rowe, Peter S.N.; Matsumoto, Naoko; Jo, Oak D.; Shih, Remi N.J.; Oconnor, Jeannine; Roudier, Martine P.; Bain, Steve; Liu, Shiguang; Harrison, Jody; Yanagawa, Norimoto

2012-01-01

Increased expression of several osteoblastic proteases and MEPE (a bone matrix protein) occurs in X-linked hypophosphatemic rickets (hyp). This is associated with an increased release of a protease-resistant MEPE peptide (ASARM peptide), a potent inhibitor of mineralization. Cathepsin B cleaves MEPE releasing ASARM peptide and hyp osteoblast/osteocyte cells hypersecrete cathepsin D, an activator of cathepsin B. Our aims were to determine whether cathepsin inhibitors correct the mineralization defect in vivo and whether hyp-bone ASARM peptide levels are reduced after protease treatment. Normal littermates and hyp mice (n = 6) were injected intraperitoneally once a day for 4 weeks with pepstatin, CAO74 or vehicle. Animals were then sacrificed and bones plus serum removed for comprehensive analysis. All hyp mice groups (treated and untreated) remained hypophosphatemic with serum 1,25 vitamin D3 inappropriately normal. Serum PTH was significantly elevated in all hyp mice groups relative to normal mice (P = 0.0017). Untreated hyp mice had six-fold elevated levels of serum alkaline-phosphatase and two-fold elevated levels of ASARM peptides relative to normal mice (P < 0.001). In contrast, serum alkaline phosphatase and serum ASARM peptides were significantly reduced (normalized) in hyp mice treated with CA074 or pepstatin. Serum FGF23 levels remained high in all hyp animal groups (P < 0.0001). Hyp mice treated with protease inhibitors showed dramatic reductions in unmineralized osteoid (femurs) compared to control hyp mice (Goldner staining). Also, hyp animals treated with protease inhibitors showed marked and significant improvements in growth plate width (42%), osteoid thickness (40%) and cortical area (40%) (P < 0.002). The mineralization apposition rate, bone formation rate and mineralization surface were normalized by protease-treatment. High-resolution pQCT mineral histomorphometry measurements and uCT also confirmed a marked mineralization improvement. Finally, the growth plate and cortical bone of hyp femurs contained a massive accumulation of osteoblast-derived ASARM peptide(s) that was reduced in hyp animals treated with CA074 or pepstatin. This study confirms in vivo administration of cathepsin inhibitors improves bone mineralization in hyp mice. This may be due to a protease inhibitor mediated decrease in proteolytic degradation of the extracellular matrix and a reduced release of ASARM peptides (potent mineralization inhibitors). PMID:16762607

Risk Stratification for Avascular Necrosis of the Femoral Head After Internal Fixation of Femoral Neck Fractures by Post-Operative Bone SPECT/CT.

PubMed

Han, Sangwon; Oh, Minyoung; Yoon, Seokho; Kim, Jinsoo; Kim, Ji-Wan; Chang, Jae-Suk; Ryu, Jin-Sook

2017-03-01

Avascular necrosis (AVN) of the femoral head is a major complication after internal fixation of a femoral neck fracture and determines the functional prognosis. We investigated postoperative bone single-photon emission computed tomography/computed tomography (SPECT/CT) for assessing the risk of femoral head AVN. We retrospectively reviewed 53 consecutive patients who underwent bone SPECT/CT within 2 weeks of internal fixation of a femoral neck fracture and follow-up serial hip radiographs over at least 12 months. Nine patients developed femoral head AVN. In 15 patients who showed normal uptake on immediate postoperative SPECT/CT, no AVN occurred, whereas 9 of 38 patients who showed cold defects of the femoral head later developed AVN. The negative predictive value of immediate postoperative SPECT/CT for AVN was 100 %, whereas the positive predictive value was 24 %. Among 38 patients with cold defects, 1 developed AVN 3 months postoperatively. A follow-up bone SPECT/CT was performed in the other 37 patients at 2-10 months postoperatively. The follow-up bone SPECT/CT revealed completely normalized femoral head uptake in 27, partially normalized uptake in 8, and persistent cold defects in 2 patients. AVN developed in 3.7 % (1/27), 62.5 % (5/8), and 100 % (2/2) of each group, respectively. According to the time point of imaging, radiotracer uptake patterns of the femoral head on postoperative bone SPECT/CT indicate the risk of AVN after internal fixation of femoral neck fractures differently. Postoperative bone SPECT/CT may help orthopedic surgeons determine the appropriate follow-up of these patients.

Effects of vitamin D binding protein-macrophage activating factor (DBP-MAF) infusion on bone resorption in two osteopetrotic mutations.

PubMed

Schneider, G B; Benis, K A; Flay, N W; Ireland, R A; Popoff, S N

1995-06-01

Osteopetrosis is a heterogeneous group of bone diseases characterized by an excess accumulation of bone and a variety of immune defects. Osteopetrosis (op) and incisors absent (ia) are two nonallelic mutations in the rat which demonstrated these skeletal defects as a result of reduced bone resorption. Osteopetrotic (op) rats have severe sclerosis as a result of reduced numbers of osteoclasts which are structurally abnormal. The sclerosis in ia rats is not as severe as in op mutants; they have elevated numbers of osteoclasts, but they are also morphologically abnormal, lacking a ruffled border. Both of these mutations have defects in the inflammation-primed activation of macrophages. They demonstrate independent defects in the cascade involved in the conversion of vitamin D binding protein (DBP) to a potent macrophage activating factor (DBP-MAF). Because this factor may also play a role in the pathogenesis of osteoclastic dysfunction, the effects of ex vivo-generated DBP-MAF were evaluated on the skeletal system of these two mutations. Newborn ia and op rats and normal littermate controls were injected with DBP-MAF or vehicle once every 4 days from birth until 2 weeks of age, at which time bone samples were collected to evaluate a number of skeletal parameters. DBP-MAF treated op rats had an increased number of osteoclasts and the majority of them exhibited normal structure. There was also reduced bone volume in the treated op animals and an associated increased cellularity of the marrow spaces. The skeletal sclerosis was also corrected in the ia rats; the bone marrow cavity size was significantly enlarged and the majority of the osteoclasts appeared normal with extensive ruffled borders.

Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

PubMed Central

Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

2015-01-01

Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076

Medial joint line bone bruising at MRI complicating acute ankle inversion injury: what is its clinical significance?

PubMed

Chan, V O; Moran, D E; Shine, S; Eustace, S J

2013-10-01

To assess the incidence and clinical significance of medial joint line bone bruising following acute ankle inversion injury. Forty-five patients who underwent ankle magnetic resonance imaging (MRI) within 2 weeks of acute ankle inversion injury were included in this prospective study. Integrity of the lateral collateral ligament complex, presence of medial joint line bone bruising, tibio-talar joint effusion, and soft-tissue swelling were documented. Clinical follow-up at 6 months was carried out to determine the impact of injury on length of time out of work, delay in return to normal walking, delay in return to sports activity, and persistence of medial joint line pain. Thirty-seven patients had tears of the anterior talofibular ligament (ATFL). Twenty-six patients had medial joint line bone bruising with altered marrow signal at the medial aspect of the talus and congruent surface of the medial malleolus. A complete ATFL tear was seen in 92% of the patients with medial joint line bone bruising (p = 0.05). Patients with an ATFL tear and medial joint line bone bruising had a longer delay in return to normal walking (p = 0.0002), longer delay in return to sports activity (p = 0.0001), and persistent medial joint line pain (p = 0.0003). There was no statistically significant difference in outcome for the eight patients without ATFL tears. Medial joint line bone bruising following an acute ankle inversion injury was significantly associated with a complete ATFL tear, longer delay in the return to normal walking and sports activity, as well as persistent medial joint line pain. Its presence should prompt detailed assessment of the lateral collateral ligament complex, particularly the ATFL. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Characterization of a 5-fluorouracil-enriched osteoprogenitor population of the murine bone marrow.

PubMed

Falla, N; Van Vlasselaer; Bierkens, J; Borremans, B; Schoeters, G; Van Gorp, U

1993-12-15

In the presence of beta-glycerophosphate and vitamin C, cultures of normal mouse bone marrow cells form three-dimensional structures that stain positive with the Von Kossa technique and express alkaline phosphatase (ALP), collagen type I, and osteocalcin. Little is known about the characteristics and frequency of the cells that contribute to this phenomenon. Most likely, mature osteoblastic cells do not contribute to the nodule formation because no osteocalcin expressing cells are detected in the flushed marrow by in situ hybridization. Limiting dilution analysis shows that, in normal bone marrow, 1 of 2.2 x 10(5) cells has the potency to form a bone nodule and to express ALP, collagen, and osteocalcin in a temporal fashion. Upon in vivo treatment with 5-fluorouracil (5-FU), this frequency increases 12-fold, eg, 1 in 1.75 x 10(4) cells shows osteogenic activity. In comparison, fibroblast colony forming cells occur at a frequency of 1 of 2.5 x 10(4) or 1 of 5 x 10(3) plated cells in normal or 5-FU-treated marrow, respectively. Using density centrifugation, the majority of the osteoprogenitor cells in 5-FU marrow are found in the low-density (1.066 to 1.067 g/mL) fractions. In addition, these cells bind to nylon wool but not to plastic and aggregate in the presence of wheat germ agglutinin and soybean agglutinin. Scanning and transmission electron microscopy shows that the bone nodules in 5-FU marrow cultures are composed of fibroblastoid cells embedded in a mineralized collagen matrix. In conclusion, our results show that a quiescent cell population in the murine bone marrow with fibroblastoid characteristics contributes to the formation of bone-like nodules in vitro.

Mastocytosis: magnetic resonance imaging patterns of marrow disease.

PubMed

Avila, N A; Ling, A; Metcalfe, D D; Worobec, A S

1998-03-01

To report the bone marrow MRI findings of patients with mastocytosis and correlate them with clinical, pathologic, and radiographic features. Eighteen patients with mastocytosis had T1-weighted spin echo and short tau inversion recovery MRI of the pelvis at 0.5 T. In each patient the MR pattern of marrow disease was classified according to intensity and uniformity and was correlated with the clinical category of mastocytosis, bone marrow biopsy results, and radiographic findings. Two patients had normal MRI scans and normal bone marrow biopsies. One patient had a normal MRI scan and a marrow biopsy consistent with mastocytosis. Fifteen patients had abnormal MRI scans and abnormal marrow biopsies. There were several different MR patterns of marrow involvement; none was specifically associated with any given clinical category of mastocytosis. Fifteen of the 18 patients had radiographs of the pelvis; of those, 13 with abnormal MRI scans and abnormal marrow biopsies had the following radiographic findings: normal (nine); sclerosis (three); diffuse osteopenia (one). While radiographs are very insensitive for the detection of marrow abnormalities in mastocytosis, MRI is very sensitive and may display several different patterns of marrow involvement.

Ewing sarcoma of the rib with normal blood flow and blood pool imagings on a 3-phase bone scan.

PubMed

Alfeeli, Mahmoud A; Naddaf, Sleiman Y; Syed, Ghulam M S

2005-09-01

Ewing sarcoma is the second most common pediatric malignant bone tumor. It usually presents as a hot spot on a 3-phase bone scan as a result of increased vascularity of the tumor and new bone formation. However, aggressive Ewing sarcoma can also appear as a cold lesion. We present the features of a Ewing sarcoma of the rib on a 3-phase bone scan in a child who was being investigated for rib fracture after trauma.

Method for fusing bone

DOEpatents

Mourant, J.R.; Anderson, G.D.; Bigio, I.J.; Johnson, T.M.

1996-03-12

The present invention is a method for joining hard tissue which includes chemically removing the mineral matrix from a thin layer of the surfaces to be joined, placing the two bones together, and heating the joint using electromagnetic radiation. The goal of the method is not to produce a full-strength weld of, for example, a cortical bone of the tibia, but rather to produce a weld of sufficient strength to hold the bone halves in registration while either external fixative devices are applied to stabilize the bone segments, or normal healing processes restore full strength to the tibia.

The Biology of Bone and Ligament Healing.

PubMed

Cottrell, Jessica A; Turner, Jessica Cardenas; Arinzeh, Treena Livingston; O'Connor, J Patrick

2016-12-01

This review describes the normal healing process for bone, ligaments, and tendons, including primary and secondary healing as well as bone-to-bone fusion. It depicts the important mediators and cell types involved in the inflammatory, reparative, and remodeling stages of each healing process. It also describes the main challenges for clinicians when trying to repair bone, ligaments, and tendons with a specific emphasis on Charcot neuropathy, fifth metatarsal fractures, arthrodesis, and tendon sheath and adhesions. Current treatment options and research areas are also reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Resolution of severe, adolescent-onset hypophosphatemic rickets following resection of an FGF-23-producing tumour of the distal ulna.

PubMed

Ward, L M; Rauch, F; White, K E; Filler, G; Matzinger, M A; Letts, M; Travers, R; Econs, M J; Glorieux, F H

2004-05-01

Oncogenic hypophosphatemic osteomalacia (OHO) is an uncommon hypophosphatemic syndrome characterized by bone pain, proximal muscle weakness and rickets. It has been postulated that OHO results from overproduction of a humoral phosphaturic factor by an occult tumour. Recently, some OHO tumours have been shown to elaborate fibroblast growth factor-23 (FGF-23), which causes renal phosphate wasting when administered to mice. The purpose of this study was to undertake detailed investigations to confirm the diagnosis of OHO in a pediatric patient and to document the biochemical, radiographic and bone histological phenotype before and after tumour removal. We describe an 11-year-old, previously healthy girl with significant pain and functional disability associated with hypophosphatemic rickets. Circulating 1,25-(OH)(2) vitamin D was very low (14 pM; N: 40-140) while the FGF-23 serum level was markedly elevated [359.5 reference units (RU)/ml, N: 33-105]. An iliac bone biopsy revealed severe osteomalacia, but periosteocytic lesions, as are typical for X-linked hypophosphatemic rickets, were not seen. Sequence analyses of the PHEX and FGF23 genes were normal. A radiographic skeletal survey revealed a small exostosis of the left, distal ulnar metaphysis. A tumour was subsequently removed from this site and the pathology was consistent with benign, fibro-osseous tissue. Serum FGF-23 was normal when measured at 7 h post-operatively, while serum phosphate reached the low-normal range at 16 days following surgery. An iliac bone biopsy taken 5 months after the operation showed improvement, but not yet resolution, of the osteomalacia. Biochemical parameters of bone and mineral metabolism suggested that complete resolution of the osteomalacia was not achieved until 12 months following surgery. One year after tumour removal, the patient was pain-free and had resumed a normal level of activity. The rapid normalization of FGF-23 levels following removal of a benign tumour and the subsequent improvement in the biochemical and histological parameters of bone and mineral metabolism suggest that FGF-23 played a key role in this girl's disease.

Morphological integration in the forelimb of musteloid carnivorans

PubMed Central

Fabre, Anne-Claire; Goswami, Anjali; Peigné, Stéphane; Cornette, Raphaël

2014-01-01

The forelimb forms a functional unit that allows a variety of behaviours and needs to be mobile, yet at the same time stable. Both mobility and stability are controlled, amongst others, at the level of the elbow joint. This joint is composed of the humero-ulnar articulation, mainly involved during parasagittal movements; and the radio-ulnar articulation, mainly allowing rotation. In contrast, the humero-radial articulation allows both movements of flexion–extension and rotation. Here, we study the morphological integration between each bone of the forelimb at the level of the entire arm, as well as at the elbow joint, in musteloid carnivorans. To do so, we quantitatively test shape co-variation using surface 3D geometric morphometric data. Our results show that morphological integration is stronger for bones that form functional units. Different results are obtained depending on the level of investigation: for the entire arm, results show a greater degree of shape co-variation between long bones of the lower arm than between the humerus and either bone of the lower arm. Thus, at this level the functional unit of the lower arm is comprised of the radius and ulna, permitting rotational movements of the lower arm. At the level of the elbow, results display a stronger shape co-variation between bones allowing flexion and stability (humerus and ulna) than between bones allowing mobility (ulna and radius and humerus and radius). Thus, the critical functional unit appears to be the articulation between the humerus and ulna providing the stability of the joint. PMID:24836555

Calvarial bone harvesting with piezoelectric device.

PubMed

Gonzalez-Lagunas, Javier; Mareque, Javier

2007-11-01

We introduce the use of a piezoelectric device in order to harvest calvarial bone grafts. The vibration frequency of the instrument allows for the efficient cutting of bone without the risk of accidentally damaging the dura.

Age-related changes in bone biochemical markers and their relationship with bone mineral density in normal Chinese women.

PubMed

Pi, Yin-Zhen; Wu, Xian-Ping; Liu, Shi-Ping; Luo, Xiang-Hang; Cao, Xing-Zhi; Xie, Hui; Liao, Er-Yuan

2006-01-01

Measurements of bone biochemical markers are increasingly being used to evaluate the state of bone turnover in the management of bone metabolic diseases, especially osteoporosis. However, changes in the bone turnover rate vary with age. The aim of this study was to establish the laboratory reference range of serum bone-specific alkaline phosphatase (sBAP), serum type I collagen cross-linked C-terminal telopeptide (sCTx), and urine CTx (uCTx), based on values from 665 healthy Chinese women aged 20-80 years. We measured the levels of sBAP, sCTx, serum alkaline phosphatase (sALP), and uCTx and evaluated the age-related changes and their relationship with bone mineral density (BMD) in the anteroposterior (AP) lumbar spine, hip, and left forearm. We found significant correlations between biochemical markers and age, with coefficients of determination (R (2)) of 0.358 for sBAP, 0.126 for sCTx, 0.125 for uCTx, and 0.336 for sALP. The net changes in different biochemical markers were inversely correlated with the rates of BMD loss in the AP lumbar spine. After correction for age, body weight, and height, the levels of the markers had significant negative correlations with the BMD of the AP lumbar spine, femoral neck, and ultradistal forearm. All four biochemical markers had the highest negative correlation with BMD of the AP lumbar spine (partial correlation coefficients of -0.366, -0.296, -0.290, and -0.258 for sBAP, sCTx, uCTx, and sALP, respectively). The mean and SD values of these markers in premenopausal and postmenopausal women with normal BMD values were used as the normal reference ranges. The reference ranges of sBAP, sCTx, and uCTx for pre- vs postmenopausal women were 17.3 +/- 6.23 vs 18.9 +/- 7.52 U/l, 3.18 +/- 1.49 vs 3.23 +/- 1.57 nmol/l, and 15.5 +/- 11.4 vs 16.2 +/- 12.4 nM bone collagen equivalents/mM urinary creatinine, respectively. Levels of the bone formation marker (sBAP) and bone resorption markers (sCTx, uCTx) increased rapidly in women with osteopenia or osteoporosis, indicating that they may be sensitive markers to determine the bone turnover rate in healthy Chinese women.

Changes in neurocranium thickness in early childhood

NASA Astrophysics Data System (ADS)

Gajawelli, Niharika; Deoni, Sean; Shi, Jie; Xu, Liang; Dirks, Holly; Dean, Douglas; O'Muircheartaigh, Jonathan; Sawardekar, Siddhant; Ezis, Andrea; Nelson, Marvin D.; Wang, Yalin; Lepore, Natasha

2015-12-01

Several developmental disorders involve shape abnormalities of the neurocranium, the most common one being craniosynostosis, that affects about 1 in 2000 infants. A key step in determining how these disorders affect neurodevelopment is to establish how the brain and neurocranium co-evolve in the normally developing child. However, due to the scarcity of normally developing infant and pediatric imaging data, there have been a lack of imaging studies pertaining to normal neurocranial development. Here, taking advantage of a large data bank of high quality brain MRI from healthy children ages 0-4 years old, and of a novel conformal geometry-based analysis pipeline, we have been determining a set of statistical atlases of the neurocranium, divided into age groups. In this first part of the study, we focus more specifically on a comparison of 1 and 2 year old infants. Characterizing neurocranium shape changes will enable us to understand how the cranial bones develop in relation to brain development. This in turn will allow a better determination of the effects of neurocranial disorders, which will help inform treatment strategies.

Environmental Factors Impacting Bone-Relevant Chemokines

PubMed Central

Smith, Justin T.; Schneider, Andrew D.; Katchko, Karina M.; Yun, Chawon; Hsu, Erin L.

2017-01-01

Chemokines play an important role in normal bone physiology and the pathophysiology of many bone diseases. The recent increased focus on the individual roles of this class of proteins in the context of bone has shown that members of the two major chemokine subfamilies—CC and CXC—support or promote the formation of new bone and the remodeling of existing bone in response to a myriad of stimuli. These chemotactic molecules are crucial in orchestrating appropriate cellular homing, osteoblastogenesis, and osteoclastogenesis during normal bone repair. Bone healing is a complex cascade of carefully regulated processes, including inflammation, progenitor cell recruitment, differentiation, and remodeling. The extensive role of chemokines in these processes and the known links between environmental contaminants and chemokine expression/activity leaves ample opportunity for disruption of bone healing by environmental factors. However, despite increased clinical awareness, the potential impact of many of these environmental factors on bone-related chemokines is still ill defined. A great deal of focus has been placed on environmental exposure to various endocrine disruptors (bisphenol A, phthalate esters, etc.), volatile organic compounds, dioxins, and heavy metals, though mainly in other tissues. Awareness of the impact of other less well-studied bone toxicants, such as fluoride, mold and fungal toxins, asbestos, and chlorine, is also reviewed. In many cases, the literature on these toxins in osteogenic models is lacking. However, research focused on their effects in other tissues and cell lines provides clues for where future resources could be best utilized. This review aims to serve as a current and exhaustive resource detailing the known links between several classes of high-interest environmental pollutants and their interaction with the chemokines relevant to bone healing. PMID:28261155

High dietary cholesterol masks type 2 diabetes-induced osteopenia and changes in bone microstructure in rats.

PubMed

Lapmanee, Sarawut; Charoenphandhu, Narattaphol; Aeimlapa, Ratchaneevan; Suntornsaratoon, Panan; Wongdee, Kannikar; Tiyasatkulkovit, Wacharaporn; Kengkoom, Kanchana; Chaimongkolnukul, Khuanjit; Seriwatanachai, Dutmanee; Krishnamra, Nateetip

2014-10-01

Type 2 diabetes mellitus (T2DM) often occurs concurrently with high blood cholesterol or dyslipidemia. Although T2DM has been hypothesized to impair bone microstructure, several investigations showed that, when compared to age-matched healthy individuals, T2DM patients had normal or relatively high bone mineral density (BMD). Since cholesterol and lipids profoundly affect the function of osteoblasts and osteoclasts, it might be cholesterol that obscured the changes in BMD and bone microstructure in T2DM. The present study, therefore, aimed to determine bone elongation, epiphyseal histology, and bone microstructure in non-obese T2DM Goto-Kakizaki rats treated with normal (GK-ND) and high cholesterol diet. We found that volumetric BMD was lower in GK-ND rats than the age-matched wild-type controls. In histomorphometric study of tibial metaphysis, T2DM evidently suppressed osteoblast function as indicated by decreases in osteoblast surface, mineral apposition rate, and bone formation rate in GK-ND rats. Meanwhile, the osteoclast surface and eroded surface were increased in GK-ND rats, thus suggesting an activation of bone resorption. T2DM also impaired bone elongation, presumably by retaining the chondrogenic precursor cells in the epiphyseal resting zone. Interestingly, several bone changes in GK rats (e.g., increased osteoclast surface) disappeared after high cholesterol treatment as compared to wild-type rats fed high cholesterol diet. In conclusion, high cholesterol diet was capable of masking the T2DM-induced osteopenia and changes in several histomorphometric parameters that indicated bone microstructural defect. Cholesterol thus explained, in part, why a decrease in BMD was not observed in T2DM, and hence delayed diagnosis of the T2DM-associated bone disease.

Comparison of a novel bone-tendon allograft with a human dermis-derived patch for repair of chronic large rotator cuff tears using a canine model.

PubMed

Smith, Matthew J; Cook, James L; Kuroki, Keiichi; Jayabalan, Prakash S; Cook, Cristi R; Pfeiffer, Ferris M; Waters, Nicole P

2012-02-01

This study tested a bone-tendon allograft versus human dermis patch for reconstructing chronic rotator cuff repair by use of a canine model. Mature research dogs (N = 15) were used. Radiopaque wire was placed in the infraspinatus tendon (IST) before its transection. Three weeks later, radiographs showed IST retraction. Each dog then underwent 1 IST treatment: debridement (D), direct repair of IST to bone with a suture bridge and human dermis patch augmentation (GJ), or bone-tendon allograft (BT) reconstruction. Outcome measures included lameness grading, radiographs, and ultrasonographic assessment. Dogs were killed 6 months after surgery and both shoulders assessed biomechanically and histologically. BT dogs were significantly (P = .01) less lame than the other groups. BT dogs had superior bone-tendon, tendon, and tendon-muscle integrity compared with D and GJ dogs. Biomechanical testing showed that the D group had significantly (P = .05) more elongation than the other groups whereas BT had stiffness and elongation characteristics that most closely matched normal controls. Radiographically, D and GJ dogs showed significantly more retraction than BT dogs (P = .003 and P = .045, respectively) Histologically, GJ dogs had lymphoplasmacytic infiltrates, tendon degeneration and hypocellularity, and poor tendon-bone integration. BT dogs showed complete incorporation of allograft bone into host bone, normal bone-tendon junctions, and well-integrated allograft tendon. The bone-tendon allograft technique re-establishes a functional IST bone-tendon-muscle unit and maintains integrity of repair in this model. Clinical trials using this bone-tendon allograft technique are warranted. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Characterisation of mineralisation of bone and cartilage: X-ray diffraction and Ca and Sr K α X-ray fluorescence microscopy

NASA Astrophysics Data System (ADS)

Bradley, D. A.; Muthuvelu, P.; Ellis, R. E.; Green, E. M.; Attenburrow, D.; Barrett, R.; Arkill, K.; Colridge, D. B.; Winlove, C. P.

2007-10-01

Bone is a dynamic structure, constantly remodelling in response to changing mechanical and environmental factors. This is particularly evident in the mineral component encrusting the collagenous framework. The mineral is principally in the form of calcium apatite, but calcium can exchange with strontium, both during the cellular processes of mineralisation and resorption and by passive exchange with the deposited crystals. Mineralisation is generally characterized by densitometry, but because of the differences in absorption cross sections of calcium and strontium it can be misleading in studies of composition. In this work we have used X-ray diffraction to identify calcium and strontium apatite and X-ray fluorescence to quantify strontium and calcium distribution. With the beam characteristics available from synchrotron radiation, this has enabled us to obtain microscopic resolution on thin sections of bone and cartilage from the equine metacarpophalangeal joint. Two issues have been investigated; the first is the distribution of mineral in the bone-cartilage interface and within individual trabeculae. In trabecular bone the ratio of strontium to calcium concentration was typically 0.0035 ± 0.0020, and higher by a factor of ∼3 at the periphery than in the centre of a trabeculum (possibly reflecting the more rapid turnover of mineral in the surface layer). In the dense subchondral bone the ratio was similar, approximately doubling in the calcified cartilage. The second objective was to explore the changes in mineralisation associated with development of osteoarthrosis. We analysed lesions showing cartilage thinning and changes in the trabecular organization and density of the underlying bone. At the centre of the lesion the ratio of strontium to calcium was much lower than that in normal tissue, although the calcified cartilage still showed a higher ratio than the underlying bone. In the superficially normal tissue around the lesion the calcified cartilage returned to a normal ratio much more rapidly than the underlying bone. These data demonstrate the complex relationship between changes in cartilage and the underlying bone.

Fixation Release and the Bone Bandaid: A New Bone Fixation Device Paradigm

PubMed Central

Shayesteh Moghaddam, Narges; Jahadakbar, Ahmadreza; Amerinatanzi, Amirhesam; Skoracki, Roman; Miller, Michael; Dean, David; Elahinia, Mohammad

2017-01-01

The current gold standard of care for mandibular segmental defeat reconstruction is the use of Ti-6Al-4V immobilization hardware and fibular double barrel graft. This method is often successful immediately at restoring mandible function, however the highly stiff fixation hardware causes stress shielding of the grafted bone and stress concentration in the fixation device over time which can lead to fixation device failure and revision surgery. The purpose of reconstructive surgery could be to create normal stress trajectories in the mandible following engraftment. We investigate the use of a two stage mechanism which separates the immobilization/healing and regenerative phases of mandibular segmental defect treatment. The device includes the use of a very stiff, Ti-6Al-4V, releasable mechanism which assures bone healing. Therefore it could be released once the reconstructed boney tissue and any of its ligamentous attachments have completely healed. Underneath the released Ti-6Al-4V plate would be a pre-loaded nitinol (NiTi) wire-frame apparatus that facilitates the normal stress-strain trajectory through the engrafted bone after the graft is healed in place and the Ti-6Al-4V fixation device has been released. Due to the use of NiTi wires forming a netting that connects vascularized bone and possibly bone chips, bone grafts are also more likely to be incorporate rather than to resorb. We first evaluated a healthy adult mandible during normal mastication to obtain the normal stress-strain distribution. Then, we developed the finite element (FE) model of the mandibular reconstruction (in the M1-3 region) with the proposed fixation device during the healing (locked state) and post-healing (released state) periods. To recreate normal stress trajectory in the reconstructed mandible, we applied the Response Surface Methodology (RMS) to optimize the Bone Bandaid geometry (i.e., wire diameters and location). The results demonstrate that the proposed mechanism immobilizes the grafted bone in the locked state properly since the maximum resultant gap (21.54 micron) between the graft and host mandible surfaces are in the safe region (less than 300 micron). By considering the von Mises criteria for failure, FE analysis together with experimental studies (i.e., compressive and tensile testing on the inferior and superior fixation devices, respectively) confirm that the proposed fixation devices do not fail, showing safety factor of at least 10.3. Based on the Response Surface Methodology (RSM) technique, the optimal parameter values for the wires are achieved (0.65 mm and 1 mm for the superior and inferior wires, respectively) and the required level of preload on each wire are calculated (369.8 N and 229 N for the inferior and superior wires, respectively). The FE results for stress distribution on the reconstructed mandible during the released state closely match that of a healthy mandible. PMID:28952484

Transplantation of allogenic bone marrow in canine cyclic neutropenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dale, D.C.; Graw, R.G. Jr.

Transplantation of normal bone marrow cells to a gray collie dog with cyclic neutropenia resulted in normal granulocytopoiesis. The finding suggests that cyclic neutropenia occurs because the hematopoietic stem cells are defective. Because of the similarity of human and canine cyclic neutropenia, it also suggests that the human disease may be curable by marrow transplantation. One day before transplantation, the recipient received 1000 rads gamma irradiation from opposing /sup 60/Co sources at 9 rad/min. (CH)

Analysis of bone marrow plasma cells in patients with solitary bone plasmacytoma.

PubMed

Bhaskar, Archana; Gupta, Ritu; Sharma, Atul; Kumar, Lalit; Jain, Paresh

Local radiotherapy is the treatment of choice for solitary bone plasmacytoma (SBP) and the role of adjuvant systemic chemotherapy in preventing progression to multiple myeloma (MM) is controversial. The purpose of this study was to examine the presence of systemic disease in the form of neoplastic plasma cells (PC) in bone marrow of patients with SBP. Flow cytometric immunophenotyping of PC was carried out on bone marrow aspirate of 7 patients using monoclonal antibodies: CD19 FITC, CD45 FITC, CD20 FITC, CD52 PE, CD117 PE, CD56 PE, CD38 PerCP-Cy5.5, CD138 APC, anti-kappa (κ) FITC and anti-lambda (λ) PE. The neoplastic as well as normal PC were identified in bone marrow aspirate of all the patients at the time of diagnosis; the neoplastic PC ranged from 0.1%to 0.7% of all BM cells and 33.5% to 89.7% of total BMPC. The κ:λ ratio was normal in all the samples ranging from 0.5% to 1.6%. The present work shows the presence of systemic disease in the form of neoplastic PC in bone marrow of patients with SBP. Prospective studies would be required to study if the levels of neoplastic PC in the bone marrow may help us identify patients who are likely to progress to overt MM and benefit from systemic chemotherapy.

Bone mineral loss in young women with amenorrhoea.

PubMed Central

Davies, M C; Hall, M L; Jacobs, H S

1990-01-01

OBJECTIVE--To examine the impact of amenorrhoea on bone mineral density in women of reproductive age. DESIGN--Cross sectional study of 200 amenorrhoeic women compared with normally menstruating controls. SETTING--Teaching hospital outpatient clinic specialising in reproductive medicine. SUBJECTS--200 Women aged 16-40 with a past or current history of amenorrhoea from various causes and of a median duration of three years, and a control group of 57 age matched normal volunteers with no history of menstrual disorder. MAIN OUTCOME MEASURE--Bone mineral density in the lumbar spine (L1-L4) as measured by dual energy x ray absorptiometry. RESULTS--The amenorrhoeic group showed a mean reduction in bone mineral density of 15% (95% confidence interval 12% to 18%) as compared with controls (mean bone mineral density 0.89 (SD 0.12) g/cm2 v 1.05 (0.09) g/cm2 in controls). Bone loss was related to the duration of amenorrhoea and the severity of oestrogen deficiency rather than to the underlying diagnosis. Patients with a history of fracture had significantly lower bone density than those without a history of fracture. Ten patients had suffered an apparently atraumatic fracture. CONCLUSIONS--Amenorrhoea in young women should be investigated and treated to prevent bone mineral loss. Menopausal women with a past history of amenorrhoea should be considered to be at high risk of osteoporosis. PMID:2224267

Cortical Bone Mechanical Properties Are Altered in an Animal Model of Progressive Chronic Kidney Disease

PubMed Central

Newman, Christopher L.; Moe, Sharon M.; Chen, Neal X.; Hammond, Max A.; Wallace, Joseph M.; Nyman, Jeffry S.; Allen, Matthew R.

2014-01-01

Chronic kidney disease (CKD), which leads tocortical bone loss and increasedporosity,increases therisk of fracture. Animal models have confirmed that these changes compromise whole bone mechanical properties. Estimates from whole bone testing suggest that material properties are negatively affected, though tissue-level assessmentshavenot been conducted. Therefore, the goal of the present study was to examine changes in cortical bone at different length scales using a rat model with theprogressive development of CKD. At 30 weeks of age (∼75% reduction in kidney function), skeletally mature male Cy/+ rats were compared to their normal littermates. Cortical bone material propertieswere assessed with reference point indentation (RPI), atomic force microscopy (AFM), Raman spectroscopy,and high performance liquid chromatography (HPLC). Bones from animals with CKD had higher (+18%) indentation distance increase and first cycle energy dissipation (+8%) as measured by RPI.AFM indentation revealed a broader distribution of elastic modulus values in CKD animals witha greater proportion of both higher and lower modulus values compared to normal controls. Yet, tissue composition, collagen morphology, and collagen cross-linking fail to account for these differences. Though the specific skeletal tissue alterations responsible for these mechanical differences remain unclear, these results indicate that cortical bone material properties are altered in these animals and may contribute to the increased fracture risk associated with CKD. PMID:24911162

Calcium and bones

MedlinePlus

... as you get older. This can result in brittle, fragile bones that can break easily, even without a fall or other injury. The digestive system is normally very bad at absorbing calcium. Most people absorb only 15% to 20% of the calcium ...

[Sarcoidosis of the skeleton. Review of the literature and case report. (author's transl)].

PubMed

Uehlinger, E; Wurm, K

1976-08-01

The frequency of sarcoidosis in the skeleton varies between 3 and 36%. Skeletal sarcoidosis is rare in early stages (Löfgren-syndrom), relatively frequent in late stages. The initial phase is characterized by the formation of miliary non-caseating epitheloid-cell granulomas in the bone marrow. The invasion of the bone marrow may either be tolerated by the bone tissue or it initiates a perifocal osteosclerosis or a osteolysis. Correspondingly the X-ray of the skeleton shows normal structure or focal osteosclerosis or osteolysis. Therefore in the first case the sarcoidosis cannot be identified by X-ray. Most frequent locations are the phalanges of the fingers and toes, less common the stem skelton (skull, vertebrae, pelvis) and very rare the long tubular bones. In most cases the skeletal sarcoidosis is well tolerated. Report of a case of osteosclerotic sarcoidosis of the pelvis of a 39-years old woman with generalized sarcoidosis which was diagnozed four years earlier. The X-rays of the phalanges were normal. The biopsy of the iliac crest shows miliary sarcoid granuloma of the bone marrow and accretion of lamellar bone on the surface of the bone trabeculi with a distinct mosaic pattern. Treatment with steroids during the following five years was ineffective.

MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

PubMed Central

Lindert, Uschi; Cabral, Wayne A.; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M.; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N.; Janecke, Andreas R.; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R.; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C.; Shotelersuk, Vorasuk

2016-01-01

Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID:27380894

Methods: a comparative analysis of radiography, microcomputed tomography, and histology for bone tissue engineering.

PubMed

Hedberg, Elizabeth L; Kroese-Deutman, Henriette C; Shih, Charles K; Lemoine, Jeremy J; Liebschner, Michael A K; Miller, Michael J; Yasko, Alan W; Crowther, Roger S; Carney, Darrell H; Mikos, Antonios G; Jansen, John A

2005-01-01

This study focused on the assessment of radiography, microcomputed tomography, and histology for the evaluation of bone formation in a 15.0-mm defect in the rabbit radius after the implantation of a tissue-engineered construct. Radiography was found to be useful as a noninvasive method for obtaining images of calcified tissue throughout the time course of the experiment. With this method, however, image quality was low, making it difficult to obtain precise information about the location and quantity of the bone formed. Microcomputed tomography was used to create three-dimensional reconstructions of the bone (25-microm resolution). These reconstructions allowed for greater spatial resolution than the radiography, but did not allow for imaging of the implanted scaffold material or the surrounding, nonmineralized tissue. To visualize all materials within the defect area at the cellular level, histology was used. Histological analysis, however, is a destructive technique that did not allow for any further analysis of the samples. Each technique examined here has its own advantages and limitations, but each yields unique information regarding bone regeneration. It is only through the use of all three techniques that complete characterization of the bone growth and tissue/construct responses after implantation in vivo.

Dosimetric evaluation of nanotargeted (188)Re-liposome with the MIRDOSE3 and OLINDA/EXM programs.

PubMed

Chang, Chih-Hsien; Chang, Ya-Jen; Lee, Te-Wei; Ting, Gann; Chang, Kwo-Ping

2012-06-01

The OLINDA/EXM computer code was created as a replacement for the widely used MIRDOSE3 code for radiation dosimetry in nuclear medicine. A dosimetric analysis with these codes was performed to evaluate nanoliposomes as carriers of radionuclides ((188)Re-liposomes) in colon carcinoma-bearing mice. Pharmacokinetic data for (188)Re-N, N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine ((188)Re-BMEDA) and (188)Re-liposome were obtained for estimation of absorbed doses in normal organs. Radiation dose estimates for normal tissues were calculated using the MIRDOSE3 and OLINDA/EXM programs for a colon carcinoma solid tumor mouse model. Mean absorbed doses derived from(188)Re-BMEDA and (188)Re-liposome in normal tissues were generally similar as calculated by MIRDOSE3 and OLINDA/EXM programs. One notable exception to this was red marrow, wherein MIRDOSE3 resulted in higher absorbed doses than OLINDA/EXM (1.53- and 1.60-fold for (188)Re-BMEDA and (188)Re-liposome, respectively). MIRDOSE3 and OLINDA have very similar residence times and organ doses. Bone marrow doses were estimated by designating cortical bone rather than bone marrow as a source organ. The bone marrow doses calculated by MIRDOSE3 are higher than those by OLINDA. If the bone marrow is designated as a source organ, the doses estimated by MIRDOSE3 and OLINDA programs will be very similar.

Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Morey-Holton, E. R.; Doty, S. B.; Currier, P. A.; Tanner, S. J.; Halloran, B. P.

1994-01-01

Loss of bone mass during periods of skeletal unloading remains an important clinical problem. To determine the extent to which resorption contributes to the relative loss of bone during skeletal unloading of the growing rat and to explore potential means of preventing such bone loss, 0.1 mg P/kg alendronate was administered to rats before unloading of the hindquarters. Skeletal unloading markedly reduced the normal increase in tibial mass and calcium content during the 9 day period of observation, primarily by decreasing bone formation, although bone resorption was also modestly stimulated. Alendronate not only prevented the relative loss of skeletal mass during unloading but led to a dramatic increase in calcified tissue in the proximal tibia compared with the vehicle-treated unloaded or normally loaded controls. Bone formation, however, assessed both by tetracycline labeling and by [3H]proline and 45Ca incorporation, was suppressed by alendronate treatment and further decreased by skeletal unloading. Total osteoclast number increased in alendronate-treated animals, but values were similar to those in controls when corrected for the increased bone area. However, the osteoclasts had poorly developed brush borders and appeared not to engage the bone surface when examined at the ultrastructural level. We conclude that alendronate prevents the relative loss of mineralized tissue in growing rats subjected to skeletal unloading, but it does so primarily by inhibiting the resorption of the primary and secondary spongiosa, leading to altered bone modeling in the metaphysis.

Accumulation of rare earth elements in human bone within the lifespan.

PubMed

Zaichick, Sofia; Zaichick, Vladimir; Karandashev, Vasilii; Nosenko, Sergey

2011-02-01

For the first time, the contents of rare earth elements (REEs) in a rib bone of a healthy human were determined. The mean value of the contents of Ce, Dy, Er, Gd, La, Nd, Pr, Sm, Tb, and Yb (10 elements out of 17 total REEs), as well as the upper limit of means for Ho, Lu, Tm, and Y (4 elements) were measured in the rib bone tissue of 38 females and 42 males (15 to 55 years old) using inductively coupled plasma mass spectrometry (ICP-MS). We found age-related accumulation of REEs in the bone tissue of healthy individuals who lived in a non-industrial region. It was calculated that during a lifespan the content of REEs in a skeleton of non-industrial region residents may increase by one to two orders of magnitude. Using our results as indicative normal values and published data we estimated relative Gd accumulation in the bone tissue of patients according to magnetic resonance imaging with contrast agent and La accumulation in the bone tissue of patients receiving hemodialysis after treatment with lanthanum carbonate as a phosphate binder. It was shown that after such procedures contents of Gd and La in the bone tissue of patients are two to three orders of magnitude higher than normal levels. In our opinion, REEs incorporation may affect bone quality and health similar to other potentially toxic trace metals. The impact of elevated REEs content on bone physiology, biochemistry and morphology requires further investigation.

Microgravity

NASA Image and Video Library

2000-12-15

Paul Ducheyne, a principal investigator in the microgravity materials science program and head of the University of Pernsylvania's Center for Bioactive Materials and Tissue Engineering, is leading the trio as they use simulated microgravity to determine the optimal characteristics of tiny glass particles for growing bone tissue. The result could make possible a much broader range of synthetic bone-grafting applications. Even in normal gravity, bioactive glass particles enhance bone growth in laboratory tests with flat tissue cultures. Ducheyne and his team believe that using the bioactive microcarriers in a rotating bioreactor in microgravity will produce improved, three-dimensional tissue cultures. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: NASA and University of Pennsylvania Center for Bioactive Materials and Tissue Engineering.

Osteoporosis presenting in pregnancy, puerperium, and lactation.

PubMed

Kovacs, Christopher S

2014-12-01

To describe our current state of knowledge about the pathophysiology, incidence, and treatment of osteoporosis that presents during pregnancy, puerperium, and lactation. When vertebral fractures occur in pregnant or lactating women, it is usually unknown whether the skeleton was normal before pregnancy. Maternal adaptations increase bone resorption modestly during pregnancy but markedly during lactation. The net bone loss may occasionally precipitate fractures, especially in women who have underlying low bone mass or skeletal fragility prior to pregnancy. Bone mass and strength are normally restored postweaning. Transient osteoporosis of the hip is a sporadic disorder localized to one or both femoral heads; it is not due to generalized skeletal resorption. Anecdotal reports have used bisphosphonates, strontium ranelate, teriparatide, or vertebroplasty/kyphoplasty to treat postpartum vertebral fractures, but it is unclear whether these therapies had any added benefit over the spontaneous skeletal recovery that normally occurs after weaning. These relatively rare fragility fractures result from multifactorial causes, including skeletal disorders that precede pregnancy, and structural and metabolic stresses that can compromise skeletal strength during pregnancy and lactation. Further study is needed to determine when pharmacological or surgical therapy is warranted instead of conservative or expectant management.

Miniplates and mini-implants: bone remodeling as their biological foundation1

PubMed Central

Consolaro, Alberto

2015-01-01

Abstract The tridimensional network formed by osteocytes controls bone design by coordinating cell activity on trabecular and cortical bone surfaces, especially osteoblasts and clasts. Miniplates and mini-implants provide anchorage, allowing all other orthodontic and orthopedic components, albeit afar, to deform and stimulate the network of osteocytes to command bone design remodeling upon "functional demand" established by force and its vectors. By means of transmission of forces, whether near or distant, based on anchorage provided by miniplates, it is possible to change the position, shape and size as well as the relationship established between the bones of the jaws. Understanding bone biology and the continuous remodeling of the skeleton allows the clinician to perform safe and accurate rehabilitation treatment of patients, thus increasing the possibilities and types of intervention procedures to be applied in order to restore patient's esthetics and function. PMID:26691966

Geometric and mechanical evaluation of 3D-printing materials for skull base anatomical education and endoscopic surgery simulation - A first step to create reliable customized simulators.

PubMed

Favier, Valentin; Zemiti, Nabil; Caravaca Mora, Oscar; Subsol, Gérard; Captier, Guillaume; Lebrun, Renaud; Crampette, Louis; Mondain, Michel; Gilles, Benjamin

2017-01-01

Endoscopic skull base surgery allows minimal invasive therapy through the nostrils to treat infectious or tumorous diseases. Surgical and anatomical education in this field is limited by the lack of validated training models in terms of geometric and mechanical accuracy. We choose to evaluate several consumer-grade materials to create a patient-specific 3D-printed skull base model for anatomical learning and surgical training. Four 3D-printed consumer-grade materials were compared to human cadaver bone: calcium sulfate hemihydrate (named Multicolor), polyamide, resin and polycarbonate. We compared the geometric accuracy, forces required to break thin walls of materials and forces required during drilling. All materials had an acceptable global geometric accuracy (from 0.083mm to 0.203mm of global error). Local accuracy was better in polycarbonate (0.09mm) and polyamide (0.15mm) than in Multicolor (0.90mm) and resin (0.86mm). Resin and polyamide thin walls were not broken at 200N. Forces needed to break Multicolor thin walls were 1.6-3.5 times higher than in bone. For polycarbonate, forces applied were 1.6-2.5 times higher. Polycarbonate had a mode of fracture similar to the cadaver bone. Forces applied on materials during drilling followed a normal distribution except for the polyamide which was melted. Energy spent during drilling was respectively 1.6 and 2.6 times higher on bone than on PC and Multicolor. Polycarbonate is a good substitute of human cadaver bone for skull base surgery simulation. Thanks to short lead times and reasonable production costs, patient-specific 3D printed models can be used in clinical practice for pre-operative training, improving patient safety.

History of internal fixation with plates (part 2): new developments after World War II; compressing plates and locked plates.

PubMed

Hernigou, Philippe; Pariat, Jacques

2017-07-01

The first techniques of operative fracture with plates were developed in the 19th century. In fact, at the beginning these methods consisted of an open reduction of the fracture usually followed by a very unstable fixation. As a consequence, the fracture had to be opened with a real risk of (sometimes lethal) infection, and due to unstable fixation, protection with a cast was often necessary. During the period between World Wars I and II, plates for fracture fixation developed with great variety. It became increasingly recognised that, because a fracture of a long bone normally heals with minimal resorption at the bone ends, this may result in slight shortening and collapse, so a very rigid plate might prevent such collapse. However, as a consequence, delayed healing was observed unless the patient was lucky enough to have the plate break. One way of dealing with this was to use a slotted plate in which the screws could move axially, but the really important advance was recognition of the role of compression. After the first description of compression by Danis with a "coapteur", Bagby and Müller with the AO improved the technique of compression. The classic dynamic compression plates from the 1970s were the key to a very rigid fixation, leading to primary bone healing. Nevertheless, the use of strong plates resulted in delayed union and the osteoporosis, cancellous bone, comminution, and/or pathological bone resulted in some failures due to insufficient stability. Finally, new devices represented by locking plates increased the stability, contributing to the principles of a more biological osteosynthesis while giving enough stability to allow immediate full weight bearing in some patients.

Bone Sialoproteins and Breast Cancer Detection

DTIC Science & Technology

2004-07-01

used to follow proteolytic activity on more natural macromolecular substrates. These substrates are so highly substituted with fluorescein moieties that...uninformative for breast cancer, but does correlate with bone mineral density, parathyroid hormone and phosphorus . (Summary of Appendix II). Normal MEPE...calcium, phosphorus , vitamin D, as well as novel phosphatonin(s), and the bone and kidney organs. Candidate phosphaturic factors include MEPE; PHEX, a

Measurement of humerus and radius bone mineral content in the term and preterm infant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vyhmeister, N.R.; Linkhart, T.A.

1988-07-01

We compared two anatomic sites for single-photon absorptiometric measurement of bone mineral content (BMC) in term and preterm infants. The distal one third of the radius and the midportion of the humerus were evaluated for measurements of BMC with an unmodified, commercially available bone densitometer. We assessed reproducibility of BMC and bone width (BW) measurements and defined normal at-birth ranges of BMC, BW, and BMC/BW ratio for infants with gestational ages of 24 to 42 weeks. Humerus BMC correlated with gestational age, birth weight, and BW of patients and did not differ from humerus BMC values determined over the samemore » range of gestational ages at another center. Representative serial measurements of two very low birth weight (VLBW) infants are presented to demonstrate the feasibility of using humerus BMC in longitudinal studies to assess changes in bone mineralization. We conclude that bone densitometer measurements of mid-humerus BMC can be successfully performed and are preferable to similar measurements of the radius for VLBW infants. Normal humerus BMC values were defined for use in diagnosis and evaluation of the efficacy of treatment in VLBW infants who are at high risk of developing osteopenia of prematurity.« less

Anorexia Nervosa and its Associated Endocrinopathy in Young People

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2016-01-01

Anorexia nervosa (AN) is a condition of severe undernutrition associated with adaptive changes in many endocrine axes. These changes include hypogonadotropic hypogonadism, acquired growth hormone resistance with low insulin like growth factor-1 (IGF-1) levels, hypercortisolemia, altered secretion of adipokines and appetite regulating hormones, and low bone mineral density (BMD). Bone health is impaired subsequent to low BMI, decreased lean mass, and the endocrine changes described above. In addition to low areal BMD, AN is characterized by a decrease in volumetric BMD, changes in bone geometry, and reductions in strength estimates, leading to an increased risk for fracture. Weight restoration is essential for restoration of normal endocrine function; however, hypercortisolemia, high PYY levels, and ghrelin dynamics may not completely normalize. In some patients, hypogonadotropic hypogonadism persists despite weight restoration. Weight gain and menstrual recovery are critical for improving bone health in AN, however, residual deficits may persist. Physiologic estrogen replacement using transdermal, but not oral, estrogen increases bone accrual in adolescents with AN, while bisphosphonates improve BMD in adults. Recombinant human IGF-1 and teriparatide have been used in a few studies as bone anabolic therapies. More data are necessary to determine the optimal therapeutic strategies for low BMD in AN. PMID:26863308

Anorexia Nervosa: Analysis of Trabecular Texture with CT

PubMed Central

Tabari, Azadeh; Torriani, Martin; Miller, Karen K.; Klibanski, Anne; Kalra, Mannudeep K.

2017-01-01

Purpose To determine indexes of skeletal integrity by using computed tomographic (CT) trabecular texture analysis of the lumbar spine in patients with anorexia nervosa and normal-weight control subjects and to determine body composition predictors of trabecular texture. Materials and Methods This cross-sectional study was approved by the institutional review board and compliant with HIPAA. Written informed consent was obtained. The study included 30 women with anorexia nervosa (mean age ± standard deviation, 26 years ± 6) and 30 normal-weight age-matched women (control group). All participants underwent low-dose single-section quantitative CT of the L4 vertebral body with use of a calibration phantom. Trabecular texture analysis was performed by using software. Skewness (asymmetry of gray-level pixel distribution), kurtosis (pointiness of pixel distribution), entropy (inhomogeneity of pixel distribution), and mean value of positive pixels (MPP) were assessed. Bone mineral density and abdominal fat and paraspinal muscle areas were quantified with quantitative CT. Women with anorexia nervosa and normal-weight control subjects were compared by using the Student t test. Linear regression analyses were performed to determine associations between trabecular texture and body composition. Results Women with anorexia nervosa had higher skewness and kurtosis, lower MPP (P < .001), and a trend toward lower entropy (P = .07) compared with control subjects. Bone mineral density, abdominal fat area, and paraspinal muscle area were inversely associated with skewness and kurtosis and positively associated with MPP and entropy. Texture parameters, but not bone mineral density, were associated with lowest lifetime weight and duration of amenorrhea in anorexia nervosa. Conclusion Patients with anorexia nervosa had increased skewness and kurtosis and decreased entropy and MPP compared with normal-weight control subjects. These parameters were associated with lowest lifetime weight and duration of amenorrhea, but there were no such associations with bone mineral density. These findings suggest that trabecular texture analysis might contribute information about bone health in anorexia nervosa that is independent of that provided with bone mineral density. © RSNA, 2016 PMID:27797678

Anorexia Nervosa: Analysis of Trabecular Texture with CT.

PubMed

Tabari, Azadeh; Torriani, Martin; Miller, Karen K; Klibanski, Anne; Kalra, Mannudeep K; Bredella, Miriam A

2017-04-01

Purpose To determine indexes of skeletal integrity by using computed tomographic (CT) trabecular texture analysis of the lumbar spine in patients with anorexia nervosa and normal-weight control subjects and to determine body composition predictors of trabecular texture. Materials and Methods This cross-sectional study was approved by the institutional review board and compliant with HIPAA. Written informed consent was obtained. The study included 30 women with anorexia nervosa (mean age ± standard deviation, 26 years ± 6) and 30 normal-weight age-matched women (control group). All participants underwent low-dose single-section quantitative CT of the L4 vertebral body with use of a calibration phantom. Trabecular texture analysis was performed by using software. Skewness (asymmetry of gray-level pixel distribution), kurtosis (pointiness of pixel distribution), entropy (inhomogeneity of pixel distribution), and mean value of positive pixels (MPP) were assessed. Bone mineral density and abdominal fat and paraspinal muscle areas were quantified with quantitative CT. Women with anorexia nervosa and normal-weight control subjects were compared by using the Student t test. Linear regression analyses were performed to determine associations between trabecular texture and body composition. Results Women with anorexia nervosa had higher skewness and kurtosis, lower MPP (P < .001), and a trend toward lower entropy (P = .07) compared with control subjects. Bone mineral density, abdominal fat area, and paraspinal muscle area were inversely associated with skewness and kurtosis and positively associated with MPP and entropy. Texture parameters, but not bone mineral density, were associated with lowest lifetime weight and duration of amenorrhea in anorexia nervosa. Conclusion Patients with anorexia nervosa had increased skewness and kurtosis and decreased entropy and MPP compared with normal-weight control subjects. These parameters were associated with lowest lifetime weight and duration of amenorrhea, but there were no such associations with bone mineral density. These findings suggest that trabecular texture analysis might contribute information about bone health in anorexia nervosa that is independent of that provided with bone mineral density. © RSNA, 2016.

Carprofen simultaneously reduces progression of morphological changes in cartilage and subchondral bone in experimental dog osteoarthritis.

PubMed

Pelletier, J P; Lajeunesse, D; Jovanovic, D V; Lascau-Coman, V; Jolicoeur, F C; Hilal, G; Fernandes, J C; Martel-Pelletier, J

2000-12-01

To examine the effect of a nonsteroidal antiinflammatory drug, carprofen, on the structure and metabolism of cartilage and subchondral bone in the experimental osteoarthritic (OA) canine model. Experimental Groups 1 and 2 received a sectioning of the anterior cruciate ligament (ACL) of the right stifle joint, and were administered carprofen (2.2 and 4.4 mg/kg/twice daily/po, respectively) for 8 weeks beginning 4 weeks postsurgery. Group 3 received ACL sectioning and no treatment. Group 4 was composed of unoperated normal dogs. Cartilage macroscopic lesions were assessed, and their histological severity was graded. Specimens of subchondral bones were fixed, decalcified, and stained with hematoxylin/eosin. The level of metalloprotease (MMP) activity in cartilage was measured. Osteoblast cells were prepared from the subchondral bone. The level of synthesis of osteoblast biomarkers (osteocalcin, alkaline phosphatase), as well as urokinase plasminogen activator (uPA) activity and insulin-like growth factor (IGF-1) in the culture medium, was estimated. Carprofen treatment decreased the width of osteophytes (p < 0.01), the size of cartilage lesions, and the histologic severity of cartilage lesions (p < 0.008). There was no difference in the levels of MMP activity in cartilage between OA and carprofen treated groups. In OA dogs, the subchondral bone plate was thinner and was the site of an extensive remodeling process with numerous lacunae. Dogs treated with carprofen showed a marked decrease in the remodeling activity with normal plate thickness, and subchondral bone morphology resembling that of normal dogs. Osteoblasts from untreated OA dogs showed slightly higher alkaline phosphatase activities and osteocalcin release that reverted back to normal upon carprofen treatment. Moreover, uPA activity and IGF-1 levels were increased in OA dogs and were significantly reduced in carprofen treated dogs. Under therapeutic conditions, treatment with carprofen could reduce the progression of early structural changes in experimental OA. Carprofen treatment also delays and/or prevents the abnormal metabolism of subchondral osteoblasts in this model. The hypothesis of a possible link between the protective effect of carprofen and its effect on subchondral bone is of interest in the context of therapeutic intervention.

Rictor/mTORC2 loss in osteoblasts impairs bone mass and strength.

PubMed

Liu, Dong-Mei; Zhao, Lin; Liu, Ting-Ting; Jiao, Pei-Lin; Zhao, Dian-Dian; Shih, Mei-Shu; Tao, Bei; Sun, Li-Hao; Zhao, Hong-Yan; Liu, Jian-Min

2016-09-01

Mammalian target of rapamycin (mTOR) is a Ser/Thr kinase conserved through evolution that coordinates extra cellular signals associated with cell growth. Main functions of mTOR present in the form of two complexes, namely mTORC1 and mTORC2, which are distinct in their unique components, raptor and rictor. In the current study, using a Cre/loxp system, we found an anabolic effect of mTORC2 signaling on skeleton. Osteoblast differentiation was reduced, with down-regulation of mTORC2 signaling activity in primary cultures of osteoblasts that did not contain rictor. Mice with a specific deletion of rictor in mature osteoblasts showed a significant reduction in lean mass and bone mineral density by dual energy x-ray absorptiometry analysis. Micro-computed tomography, histomorphometric, and molecular biological analyses revealed a marked impairment of the cortical bone mass and microarchitecture, as well as minor changes in trabecular bone, of the Rictorob(-/-) mice. Cortical bone mass and thickness of the femoral mid-shaft were dramatically reduced, with unusual increases in porosity and marrow area in Rictorob(-/-) mice. Thinner trabeculae were found in the L4 vertebrae with relatively normal structural indices of trabecular numbers and separation. A lower rate of bone turnover was observed, as the consequence of the decreased individual osteoblast activity and bone resorption. Furthermore, these changes were associated with significantly decreased bone biomechanical properties. In conclusion, expression of rictor in osteoblasts is essential for the maintenance of normal bone remodeling and microarchitecture, especially for the maintenance of the cortical bone. Copyright © 2016 Elsevier Inc. All rights reserved.

An Evaluation of the Surgical Trauma to Intracochlear Structures After Insertion of Cochlear Implant Electrode Arrays: A Comparison by Round Window and Antero-Inferior Cochleostomy Techniques.

PubMed

Sikka, Kapil; Kairo, Arvind; Singh, Chirom Amit; Roy, T S; Lalwani, Sanjeev; Kumar, Rakesh; Thakar, Alok; Sharma, Suresh C

2017-09-01

To evaluate the extent of intracochlear damage by histologic assessment of cadaveric temporal bones after insertion of cochlear implants by: round window approach and cochleostomy approach. Cochlear implantation was performed by transmastoid facial recess approach in 10 human cadaveric temporal bones. In 5 temporal bones, electrode insertion was acheieved by round window approach and in the remaining 5 bones, by cochleostomy approach. The bones were fixed, decalcified, sectioned and studied histologically. Grading of insertion trauma was assessed. In the round window insertion group, 2 bones had to be excluded from the study: one was damaged during handling with electrode extrusion and another bone did not show any demonstrable identifiable cochlear structure. Out of the 3 temporal bones, a total of 35 sections were examined: 24 demonstrated normal cochlea, 4 had basilar membrane bulging and 7 had fracture of bony spiral lamina. In the cochleostomy group, histology of 2 bones had to be discarded due to lack of any identifiable inner ear structures. Out of the 3 bones studied, 18 sections were examined: only 3 were normal, 4 sections had some bulge in spiral lamina and 11 had fracture of bony spiral lamina. The fracture of spiral lamina and bulge of basement membrane proportion is relatively higher if we perform cochleostomy as compared to round window approach. Therefore, round window insertion is relatively less traumatic as compared to cochleostomy. However, our sample size was very small and a study with a larger sample is required to further validate these findings.

CELLS INVOLVED IN THE IMMUNE RESPONSE

PubMed Central

Singhal, Sharwan K.; Richter, Maxwell

1968-01-01

Cell suspensions of immune rabbit lymph nodes and spleen were capable of undergoing blastogenesis and mitosis and of incorporating tritiated thymidine when maintained in culture with the specific antigen in vitro. They did not respond to other, non-cross-reacting antigens. The blastogenic response obtained with immune lymph node cells could be correlated with the antibody synthesizing capacity of fragment cultures prepared from the same lymph nodes. Cell suspensions of immune bone marrow responded to non-cross-reacting antigens only whereas cell suspensions of immune thymus, sacculus rotundus, and appendix did not respond when exposed to any of the antigens tested. On the other hand, neither fragments nor cell suspensions prepared from lymph nodes, spleen, and thymus of normal, unimmunized rabbits responded with antibody formation and blastogenesis when exposed to any of the antigens. However, normal bone marrow cells responded with marked blastogenesis and tritiated thymidine uptake. The specificity of this in vitro bone marrow response was demonstrated by the fact that the injection of a protein antigen in vivo resulted in the loss of reactivity by the marrow cell to that particular antigen but not to the other, non-cross-reacting antigens. Furthermore, bone marrow cells of tolerant rabbits failed to respond to the specific antigen in vitro. It was also demonstrated that normal bone marrow cells incubated with antigen are capable of forming antibody which could be detected by the fluorescent antibody technique. This response of the bone marrow cells has been localized to the lymphocyte-rich fraction of the bone marrow. It is concluded that the bone marrow lymphocyte, by virtue of its capacity to react with blastogenesis and mitosis and with antibody formation upon initial exposure to the antigen, a capacity not possessed by lymphocytes of the other lymphoid organs, has a preeminent role in the sequence of cellular events culminating in antibody formation. PMID:4176224

Vascular Spaces in Compact Bone: A Technique to Correct a Common Misinterpretation of Structure

ERIC Educational Resources Information Center

Locke, M.; Dean, Rob L.

2003-01-01

Old bones are often discolored by the grime that infiltrates spaces in the matrix once occupied by blood vessels. This suggested that allowing dry bone to absorb colorants might be a useful way to show the three dimensional complexity of bone vascularization. The authors have developed a simple way to show blood vessels spaces in bone at a glance…

A perfusion bioreactor system efficiently generates cell-loaded bone substitute materials for addressing critical size bone defects.

PubMed

Kleinhans, Claudia; Mohan, Ramkumar Ramani; Vacun, Gabriele; Schwarz, Thomas; Haller, Barbara; Sun, Yang; Kahlig, Alexander; Kluger, Petra; Finne-Wistrand, Anna; Walles, Heike; Hansmann, Jan

2015-09-01

Critical size bone defects and non-union fractions are still challenging to treat. Cell-loaded bone substitutes have shown improved bone ingrowth and bone formation. However, a lack of methods for homogenously colonizing scaffolds limits the maximum volume of bone grafts. Additionally, therapy robustness is impaired by heterogeneous cell populations after graft generation. Our aim was to establish a technology for generating grafts with a size of 10.5 mm in diameter and 25 mm of height, and thus for grafts suited for treatment of critical size bone defects. Therefore, a novel tailor-made bioreactor system was developed, allowing standardized flow conditions in a porous poly(L-lactide-co-caprolactone) material. Scaffolds were seeded with primary human mesenchymal stem cells derived from four different donors. In contrast to static experimental conditions, homogenous cell distributions were accomplished under dynamic culture. Additionally, culture in the bioreactor system allowed the induction of osteogenic lineage commitment after one week of culture without addition of soluble factors. This was demonstrated by quantitative analysis of calcification and gene expression markers related to osteogenic lineage. In conclusion, the novel bioreactor technology allows efficient and standardized conditions for generating bone substitutes that are suitable for the treatment of critical size defects in humans. © 2015 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial Licence, which permits use, distribution and reproduction in any medium, provided the Contribution is properly cited and is not used for commercial purpose.

Evaluating bone quality in patients with chronic kidney disease

PubMed Central

Malluche, Hartmut H.; Porter, Daniel S.; Pienkowski, David

2013-01-01

Bone of normal quality and quantity can successfully endure physiologically imposed mechanical loads. Chronic kidney disease–mineral and bone disorder (CKD–MBD) adversely affects bone quality through alterations in bone turnover and mineralization, whereas bone quantity is affected through changes in bone volume. Changes in bone quality can be associated with altered bone material, structure, or microdamage, which can result in an elevated rate of fracture in patients with CKD–MBD. Fractures cannot always be explained by reduced bone quantity and, therefore, bone quality should be assessed with a variety of techniques from the macro-organ level to the nanoscale level. In this Review, we demonstrate the importance of evaluating bone from multiple perspectives and hierarchical levels to understand CKD–MBD-related abnormalities in bone quality. Understanding the relationships between variations in material, structure, microdamage, and mechanical properties of bone in patients with CKD–MBD should aid in the development of new modalities to prevent, or treat, these abnormalities. PMID:24100399

Mapping trace element distribution in fossil teeth and bone with LA-ICP-MS

NASA Astrophysics Data System (ADS)

Hinz, E. A.; Kohn, M. J.

2009-12-01

Trace element profiles were measured in fossil bones and teeth from the late Pleistocene (c. 25 ka) Merrell locality, Montana, USA, by using laser-ablation ICP-MS. Laser-ablation ICP-MS can collect element counts along predefined tracks on a sample’s surface using a constant ablation speed allowing for rapid spatial sampling of element distribution. Key elements analyzed included common divalent cations (e.g. Sr, Zn, Ba), a suite of REE (La, Ce, Nd, Sm, Eu, Yb), and U, in addition to Ca for composition normalization and standardization. In teeth, characteristic diffusion penetration distances for all trace elements are at least a factor of 4 greater in traverses parallel to the dentine-enamel interface (parallel to the growth axis of the tooth) than perpendicular to the interface. Multiple parallel traverses in sections parallel and perpendicular to the tooth growth axis were transformed into trace element maps, and illustrate greater uptake of all trace elements along the central axis of dentine compared to areas closer to enamel, or within the enamel itself. Traverses in bone extending from the external surface, through the thickness of cortical bone and several mm into trabecular bone show major differences in trace element uptake compared to teeth: U and Sr are homogeneous, whereas all REE show a kinked profile with high concentrations on outer surfaces that decrease by several orders of magnitude within a few mm inward. The Eu anomaly increases uniformly from the outer edge of bone inward, whereas the Ce anomaly decreases slightly. These observations point to major structural anisotropies in trace element transport and uptake during fossilization, yet transport and uptake of U and REE are not resolvably different. In contrast, transport and uptake of U in bone must proceed orders of magnitude faster than REE as U is homogeneous whereas REE exhibit strong gradients. The kinked REE profiles in bone unequivocally indicate differential transport rates, consistent with a double-medium diffusion model in which microdomains with slow diffusivities are bounded by fast-diffusing pathways.

Physics of ultrasonic wave propagation in bone and heart characterized using Bayesian parameter estimation

NASA Astrophysics Data System (ADS)

Anderson, Christian Carl

This Dissertation explores the physics underlying the propagation of ultrasonic waves in bone and in heart tissue through the use of Bayesian probability theory. Quantitative ultrasound is a noninvasive modality used for clinical detection, characterization, and evaluation of bone quality and cardiovascular disease. Approaches that extend the state of knowledge of the physics underpinning the interaction of ultrasound with inherently inhomogeneous and isotropic tissue have the potential to enhance its clinical utility. Simulations of fast and slow compressional wave propagation in cancellous bone were carried out to demonstrate the plausibility of a proposed explanation for the widely reported anomalous negative dispersion in cancellous bone. The results showed that negative dispersion could arise from analysis that proceeded under the assumption that the data consist of only a single ultrasonic wave, when in fact two overlapping and interfering waves are present. The confounding effect of overlapping fast and slow waves was addressed by applying Bayesian parameter estimation to simulated data, to experimental data acquired on bone-mimicking phantoms, and to data acquired in vitro on cancellous bone. The Bayesian approach successfully estimated the properties of the individual fast and slow waves even when they strongly overlapped in the acquired data. The Bayesian parameter estimation technique was further applied to an investigation of the anisotropy of ultrasonic properties in cancellous bone. The degree to which fast and slow waves overlap is partially determined by the angle of insonation of ultrasound relative to the predominant direction of trabecular orientation. In the past, studies of anisotropy have been limited by interference between fast and slow waves over a portion of the range of insonation angles. Bayesian analysis estimated attenuation, velocity, and amplitude parameters over the entire range of insonation angles, allowing a more complete characterization of anisotropy. A novel piecewise linear model for the cyclic variation of ultrasonic backscatter from myocardium was proposed. Models of cyclic variation for 100 type 2 diabetes patients and 43 normal control subjects were constructed using Bayesian parameter estimation. Parameters determined from the model, specifically rise time and slew rate, were found to be more reliable in differentiating between subject groups than the previously employed magnitude parameter.

Development of a step-down method for altering male C57BL/6 mouse housing density and hierarchical structure: Preparations for spaceflight studies

NASA Astrophysics Data System (ADS)

Scofield, David C.; Rytlewski, Jeffrey D.; Childress, Paul; Shah, Kishan; Tucker, Aamir; Khan, Faisal; Peveler, Jessica; Li, Ding; McKinley, Todd O.; Chu, Tien-Min G.; Hickman, Debra L.; Kacena, Melissa A.

2018-05-01

This study was initiated as a component of a larger undertaking designed to study bone healing in microgravity aboard the International Space Station (ISS). Spaceflight experimentation introduces multiple challenges not seen in ground studies, especially with regard to physical space, limited resources, and inability to easily reproduce results. Together, these can lead to diminished statistical power and increased risk of failure. It is because of the limited space, and need for improved statistical power by increasing sample size over historical numbers, NASA studies involving mice require housing mice at densities higher than recommended in the Guide for the Care and Use of Laboratory Animals (National Research Council, 2011). All previous NASA missions in which mice were co-housed, involved female mice; however, in our spaceflight studies examining bone healing, male mice are required for optimal experimentation. Additionally, the logistics associated with spaceflight hardware and our study design necessitated variation of density and cohort make up during the experiment. This required the development of a new method to successfully co-house male mice while varying mouse density and hierarchical structure. For this experiment, male mice in an experimental housing schematic of variable density (Spaceflight Correlate) analogous to previously established NASA spaceflight studies was compared to a standard ground based housing schematic (Normal Density Controls) throughout the experimental timeline. We hypothesized that mice in the Spaceflight Correlate group would show no significant difference in activity, aggression, or stress when compared to Normal Density Controls. Activity and aggression were assessed using a novel activity scoring system (based on prior literature, validated in-house) and stress was assessed via body weights, organ weights, and veterinary assessment. No significant differences were detected between the Spaceflight Correlate group and the Normal Density Controls in activity, aggression, body weight, or organ weight, which was confirmed by veterinary assessments. Completion of this study allowed for clearance by NASA of our bone healing experiments aboard the ISS, and our experiment was successfully launched February 19, 2017 on SpaceX CRS-10.

Development of a step-down method for altering male C57BL/6 mouse housing density and hierarchical structure: Preparations for spaceflight studies.

PubMed

Scofield, David C; Rytlewski, Jeffrey D; Childress, Paul; Shah, Kishan; Tucker, Aamir; Khan, Faisal; Peveler, Jessica; Li, Ding; McKinley, Todd O; Chu, Tien-Min G; Hickman, Debra L; Kacena, Melissa A

2018-05-01

This study was initiated as a component of a larger undertaking designed to study bone healing in microgravity aboard the International Space Station (ISS). Spaceflight experimentation introduces multiple challenges not seen in ground studies, especially with regard to physical space, limited resources, and inability to easily reproduce results. Together, these can lead to diminished statistical power and increased risk of failure. It is because of the limited space, and need for improved statistical power by increasing sample size over historical numbers, NASA studies involving mice require housing mice at densities higher than recommended in the Guide for the Care and Use of Laboratory Animals (National Research Council, 2011). All previous NASA missions in which mice were co-housed, involved female mice; however, in our spaceflight studies examining bone healing, male mice are required for optimal experimentation. Additionally, the logistics associated with spaceflight hardware and our study design necessitated variation of density and cohort make up during the experiment. This required the development of a new method to successfully co-house male mice while varying mouse density and hierarchical structure. For this experiment, male mice in an experimental housing schematic of variable density (Spaceflight Correlate) analogous to previously established NASA spaceflight studies was compared to a standard ground based housing schematic (Normal Density Controls) throughout the experimental timeline. We hypothesized that mice in the Spaceflight Correlate group would show no significant difference in activity, aggression, or stress when compared to Normal Density Controls. Activity and aggression were assessed using a novel activity scoring system (based on prior literature, validated in-house) and stress was assessed via body weights, organ weights, and veterinary assessment. No significant differences were detected between the Spaceflight Correlate group and the Normal Density Controls in activity, aggression, body weight, or organ weight, which was confirmed by veterinary assessments. Completion of this study allowed for clearance by NASA of our bone healing experiments aboard the ISS, and our experiment was successfully launched February 19, 2017 on SpaceX CRS-10. Copyright © 2018 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

[Efficacy of zoledronic acid combined with chemotherapy in treatment of skeletal metastases of non-small cell lung cancer and the bone metabolic markers].

PubMed

Hu, Xiao-ye; Zou, Qing-feng; Jin, Chuan; Li, Wei-dong; Chen, Wen-sheng; Ma, Lei

2010-06-01

To evaluate the clinical efficacy of zoledronic acid combined with chemotherapy in the management of skeletal metastasis of non-small cell lung cancer (NSCLC) and investigate the value in urine amino-terminal telopeptide of type I collagen (uNTX) and serum bone specific alkaline phosphatase (sBALP) in monitoring skeletal metastasis of NSCLC. From February, 2007 to January, 2009, 32 NSCLC patients with bone metastases received treatment with zoledronic acid at the dose of 4 mg given every 3 weeks and platinum-based chemotherapy (each cycle lasting for 3 weeks). Before and during the treatments, uNTX and sBALP were measured in these patients using ELISA and precipitation with wheat germ lectin, respectively. The patients were followed up for skeletal-related events (SREs) and status of survival. A significant decrease occurred in the pain scores and analgesic use in the patients after the therapy. SREs were not observed during the treatment. Serum creatinine and calcium levels underwent no significant variation during the treatment. Eleven patients reported 14 possible zoledronic acid-related adverse events. The concentration of uNTX and sBALP in patients with bone metastases was above the upper limit of the normal range. A positive correlation was observed between the levels of the markers and the extent of bone metastases. At the third month, uNTX and sBALP were significantly lowered, but radionuclide whole-body bone imaging showed no obvious changes. Of the 32 patients, 24 had elevated uNTX values, which became normal after the treatment in 15 patients and remained elevated in the other 9 patients. SREs occurred in these two subgroups at the rates of 53% and 89% (P=0.039), respectively. Twenty-six patients had elevated sBALP level, and 16 of them exhibited normal sBALP level after the treatment. The incidences of SREs in the patients with elevated and normal sBALP level were 50% and 90% (P=0.038), respectively. The levels of uNTX/Cr and sBALP were not correlated to the survival of the patients. Zoledronic acid combined with chemotherapy is an effective treatment for NSCLC with bone metastases. Zoledronic acid is safe and well tolerated. Urinary NTX and serum BALP have a high value in the diagnosis, therapeutic effect monitoring and SRE prediction of NSCLC with bone metastases.

[Effects of soybean isoflavone on born metabolism and morphology in animal model of osteoporosis rats].

PubMed

Yu, Qing; Su, Yi-xiang; Wang, Wen-wei; Li, An-le; Liu, Cun-li; Wang, Yi-long; Hu, Wan-li

2007-07-01

To study the effects of soybean isoflavone (SI) on born metabolism and morphology in animal model of osteoporosis rats. All 70 female Sprague-Dawley (SD) rats were randomly divided into 7 groups according to the levels of total cholesterol (TC) in serum: hyper-lipoid group, estrogen group, low-dose SI group, middle-dose SI group, high-dose SI group, sham group and normal control groups. Bilateral ovaries were extirpated except sham and normal control groups. Except the rats in normal control group, the other rats were fed with high fat diet. Body weight was weighted ad unam vice per week. The estrogen, different dose of SI or deionized water were fed with intragastric administration for 12 weeks. Vena caudalis serum were collected after being ovariectomized, administered for 4 w, 8 w and killed. Serum alkaline phosphatase (AKP) activity and bone density were measured etc. To interfere of estrogen and SI might recover AKP enzyme activity after its being ovariectomized. There almost sowed no differences between high dose SI intervention and estrogen on bone density and microstructure. Bone loss due to being ovariectomized was relieved after SI intervention. SI might protect cardiocyte myofilament and mitochondrial ultramicrostructure. There was mirror image in estrogen, high dose SI group resembling the normal control group, and there was obvious damage in hyper-lipoids group. There should be effects of high dose SI on bone metabolism and morphology in animal model of osteoporosis rats. Serum AKP enzyme activity and bone density should have significantly recovered, the serum level of calcium and phosphorus were maintained after high dose intervened but no significant effects for low dose of SI.

Evaluating The Relation of Trace Fracture Inclination and Sound Pressure Level and Time-of-flight QUS Parameters Using Computational Simulation

NASA Astrophysics Data System (ADS)

Rosa, P. T.; Fontes-Pereira, A. J.; Matusin, D. P.; von Krüger, M. A.; Pereira, W. C. A.

Bone healing is a complex process that stars after the occurrence of a fracture to restore bone optimal conditions. The gold standards for bone status evaluation are the dual energy X-ray absorptiometry and the computerized tomography. Ultrasound-based technologies have some advantages as compared to X-ray technologies: nonionizing radiation, portability and lower cost among others. Quantitative ultrasound (QUS) has been proposed in literature as a new tool to follow up the fracture healing process. QUS relates the ultrasound propagation with the bone tissue condition (normal or pathological), so, a change in wave propagation may indicate a variation in tissue properties. The most used QUS parameters are time-of-flight (TOF) and sound pressure level (SPL) of the first arriving signal (FAS). In this work, the FAS is the well known lateral wave. The aim of this work is to evaluate the relation of the TOF and SPL of the FAS and fracture inclination trace in two stages of bone healing using computational simulations. Four fracture geometries were used: normal and oblique with 30, 45 and 60 degrees. The TOF average values were 63.23 μs, 63.14 μs, 63.03 μs 62.94 μs for normal, 30, 45 and 60 degrees respectively and average SPL values were -3.83 dB -4.32 dB, -4.78 dB, -6.19 dB for normal, 30, 45 and 60 degrees respectively. The results show an inverse pattern between the amplitude and time-of-flight. These values seem to be sensible to fracture inclination trace, and in future, can be used to characterize it.

Adaptation of bone to physiological stimuli.

PubMed

Judex, S; Gross, T S; Bray, R C; Zernicke, R F

1997-05-01

The ability of bone to alter its morphology in response to local physical stimuli is predicated upon the appropriate recruitment of bone cell populations. In turn, the ability to initiate cellular recruitment is influenced by numerous local and systemic factors. In this paper, we discuss data from three ongoing projects from our laboratory that examine how physiological processes influence adaptation and growth in the skeleton. In the first study, we recorded in vivo strains to quantify the locomotion-induced distribution of two parameters closely related to bone fluid flow strain rate and strain gradients. We found that the magnitude of these parameters (and thus the implied fluid flow) varies substantially within a given cross-section, and that while strain rate magnitude increases uniformly with elevated speed, strain gradients increase focally as gait speed is increased. Secondly, we examined the influence of vascular alterations on bone adaptation by assessing bone blood flow and bone mechanical properties in an in vivo model of trauma-induced joint laxity. A strong negative correlation (r2 = 0.8) was found between increased blood flow (76%) in the primary and secondary spongiosa and decreased stiffness (-34%) following 14 weeks of joint laxity. These data suggest that blood flow and/or vascular adaptation may interact closely with bone adaptation initiated by trauma. Thirdly, we examined the effect of a systemic influence upon skeletal health. After 4 weeks old rats were fed high fat-sucrose diets for 2 yr, their bone mechanical properties were significantly reduced. These changes were primarily due to interference with normal calcium absorption. In the aggregate, these studies emphasize the complexity of bone's normal physical environment, and also illustrate the potential interactions of local and systemic factors upon the process by which bone adapts to physical stimuli.

Effects of abaloparatide-SC (BA058) on bone histology and histomorphometry: The ACTIVE phase 3 trial.

PubMed

Moreira, Carolina A; Fitzpatrick, Lorraine A; Wang, Yamei; Recker, Robert R

2017-04-01

There are a number of effective treatments for osteoporosis but most are in the antiresorptive class of compounds. Abaloparatide-SC is a new osteoanabolic agent, which increased bone mineral density and lowered the risk of osteoporosis-related fractures in the phase 3 ACTIVE trial. The objective of this report is to describe the effects of abaloparatide-SC 80μg on bone histology and histomorphometry in iliac crest bone biopsies from this trial in which participants were randomized to receive blinded daily subcutaneous injections of placebo or abaloparatide-SC 80μg/d or open-label teriparatide 20μg/d for 18months. Iliac crest bone biopsies were obtained between 12 and 18months. Qualitative histological analysis of biopsies from abaloparatide-SC-treated patients revealed normal bone microarchitecture without evidence of adverse effects on mineralization or on the formation of normal lamellar bone. There were no bone marrow abnormalities, marrow fibrosis nor was there presence of excess osteoid or woven bone. There were few significant differences among the three treatment groups in a standard panel of static and dynamic histomorphometric indices. The mineral apposition rate was higher in the teriparatide-treated group than in the placebo-treated group. The eroded surface was lower in the abaloparatide-SC-treated group than in the placebo-treated group. Cortical porosity was higher in both the abaloparatide-SC- and the teriparatide-treated groups than in the placebo-treated group. We conclude that histological and histomorphometric analysis of iliac crest bone biopsies from subjects who were treated for up to 18months with abaloparatide-SC showed no evidence of concern for bone safety. ClinicalTrials.gov number NCT01343004. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The electron microscope appearance of the subchondral bone plate in the human femoral head in osteoarthritis and osteoporosis

PubMed Central

LI, BAOHUA; MARSHALL, DEBORAH; ROE, MARTIN; ASPDEN, RICHARD M.

1999-01-01

The subchondral bone plate supports the articular cartilage in diarthrodial joints. It has a significant mechanical function in transmitting loads from the cartilage into the underlying cancellous bone and has been implicated in the destruction of cartilage in osteoarthritis (OA) and its sparing in osteoporosis (OP), but little is known of its composition, structure or material properties. This study investigated the microscopic appearance and mineral composition of the subchondral bone plate in femoral heads from patients with OA or OP to determine how these correspond to changes in composition and stiffness found in other studies. Freeze-fractured full-depth samples of the subchondral bone plate from the femoral heads of patients with osteoarthritis, osteoporosis or a matched control group were examined using back scattered and secondary emission scanning electron microscopy. Other samples were embedded and polished and examined using back-scattered electron microscopy and electron probe microanalysis. The appearances of the samples from the normal and osteoporotic patients were very similar, with the subchondral bone plate overlayed by a layer of calcified cartilage. Osteoporotic samples presented a more uniform fracture surface and the relative thicknesses of the layers appeared to be different. In contrast, the OA bone plate appeared to be porous and have a much more textured surface. There were occasional sites of microtrabecular bone formation between the trabeculae of the underlying cancellous bone, which were not seen in the other groups, and more numerous osteoclast resorption pits. The calcified cartilage layer was almost absent and the bone plate was apparently thickened. The appearance of the osteoarthritic subchondral bone plate was, therefore, considerably different from both the normal and the osteoporotic, strongly indicative of abnormal cellular activity. PMID:10473297

ATOMIC ENERGY COMMISSION PROGRESS REPORT ON BONE RESEARCH , 1960-1961

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1962-10-31

A review of osteoporosis concepts is presented. Activities in an experimental program to study osteoporosis by examining mineral metabolism in bone and by examining bone composition and density are reported. Sr/sup 85/ was administered to seven osteoporotic patients as a tracer for skeletal mineral metabolism. The activity levels in the blood and the excretion rate were measured. From these data the accretion rate and the diffusible component volume were calculated. It was found that the accretion rate was not increased in any case. The size of the diffusible component was normal in six patients and reduced in one. Concurrent experimentsmore » with estrogen administration were conducted. Over-all results indicate that in osteoporosis, the rate of bone accretion is never elevated and an effect of estrogen administration was the decrease of bone resorption rather than stimulation of bone formation. In studies of skeletal metabolism, the kinetics of Sr/sup 85/ metabolism was compared in normal subjects and patients with skeletal disorders. Various aspects of the results are analyzed and it is concluded that values obtained by kinetic studies appear to be quantitative, reproducible, and to correlate with presently established information on alterations of bone metabolism in systemic deseases. In studies of peripheral circulation and bone growth, I/sup 131tagged human serum albumin was injected in animals. The investigation was conducted to determine blood volumne turnover rate in extremities, to correlate changes in this rate with fractures and bone disorders, and to examine the method for use in evaluation of circulation under certain pathological conditions. Data and findings are included. Data are also included on in vitro mobilization of Sr/ sup 85/ during bone formation and bone density studies. (J.R.D.)« less

Prediction of low bone mass using a combinational approach of cortical and trabecular bone measures from dental panoramic radiographs.

PubMed

Kathirvelu, D; Anburajan, M

2014-09-01

The aim of this study is to extract cortical and trabecular features of the mandible and to develop a novel combinational model of mandibular cortical thickness, trabecular bone area and age in order to predict low bone mineral density or osteoporosis from a dental panoramic radiograph. The study involved 64 south Indian women (age = 52.5 ± 12.7 years) categorised into two groups (normal and low bone mineral density) based on total femur bone mineral density. The dental panoramic radiographs were obtained by a digital scanner, and measurement of total bone mineral density at the right femur was performed by a dual-energy X-ray absorptiometry scanner. The mandibular cortical thickness and panoramic mandibular index were measured bilaterally, and the mean values were considered. The region of interest of 128 × 128 pixels around the mental foramen region was manually cropped and subjected to pre-processing, normalisation and average threshold-based segmentation to determine trabecular bone area. Multiple linear regression analyses of cortical and trabecular measures along with age were performed to develop a combinational model to classify subjects as normal and low bone mineral density. The proposed approach demonstrated strong correlation (r = 0.76; p < 0.01) against the total bone mineral density and resulted in accuracy, sensitivity and positive predictive values of 0.84, 0.92 and 0.85, respectively; the receiver operating characteristic outcomes disclosed that the area under the curve was 0.89.Our results suggest that the proposed combinational model could be useful to diagnose subjects with low bone mineral density. © IMechE 2014.

UNUSUAL BONE TUMORS AFTER ROENTGEN THERAPY OF CHILDREN. Two Case Reports

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, J.; D'Angio, G.J.

1961-09-01

In a selected series of 207 children who received x-ray therapy with 1000 r or more delivered to bone, 2 subsequently developed neoplasms of bone. Both bone tumors occurred in normal ribs included in the field of treatment. The tumors were atypical; one resembled a chondrosarcoma, the other an osteoblastoma. The latent periods were thirteen and two years, respectively. Both children had postirradiation scoliosis and hypoplasia of the ilium. One also developed an osteochondroma of the ilium. (auth)

Effect of early nutritional intake on long-term growth and bone mineralization of former very low birth weight infants.

PubMed

Christmann, V; van der Putten, M E; Rodwell, L; Steiner, K; Gotthardt, M; van Goudoever, J B; van Heijst, A F J

2018-03-01

Preterm infants are at risk for impaired bone mineralization and growth in length later in life due to inadequate nutritional intake in the early postnatal period. To investigate whether increased nutritional supplementation of calcium, phosphate and protein in Very Low Birth Weight (VLBW) infants during the first 14days after birth was associated with improvement in length and bone development until 9-10years of age. Observational follow-up study of VLBW infants (birth weight<1500g or gestational age<32weeks) born in two consecutive years (eligible infants: 2004 n: 63 and 2005: n: 66). Cohort 2005 received higher intake of calcium, phosphate and protein with parenteral nutrition compared to Cohort 2004. Anthropometric data were collected during standard follow-up visits until five years, and additionally at 9-10years of age including measurements of bone mineral content, bone mineral density of the whole body and lumbar spine determined by dual-energy X-ray absorptiometry. Long-term growth trajectories of both cohorts were evaluated separately for participants born appropriate (AGA) and small for gestational age (SGA), stratified by gender. Multivariate linear regression was used to examine the effect of nutritional intake and clinical covariates on length and bone mineralization. Both cohorts achieved a catch-up in length to SDS within the normal range by 6months (length SDS: estimated mean (95% confidence interval (CI): 6months: Cohort 2004: -0.7 (-1.1, -0.3) Cohort 2005: -0.5 (-0.8, -0.2)). Bone mineral content and density were within the normal range and not different between the cohorts. SGA children achieved a catch-up in length at 5years with bone mineralization comparable to AGA children. Only for girls birth weight was significantly associated with length SDS (per gram: β 0.001; 95% CI (0.000, 0.003); p=0.03) There was no evidence of an association between early nutritional intake and bone mineralization. Children born as appropriate or small for gestational age preterm infants are able to catch up in length after the postnatal period, and achieve a normal length and bone mineralization at age nine-ten years. An improvement of calcium and phosphate intake during the first 14days after birth was not associated with improvement in length and bone development. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Histomorphometric study of tibia of rats exposed aboard American Spacelab Life Sciences 2 Shuttle Mission

NASA Technical Reports Server (NTRS)

Durnova, G.; Kaplansky, A.; Morey-Holton, E.

1996-01-01

Tibial bones of rats flown onboard the SLS-2 shuttle mission were studied. Trabecular bone parameters were investigated, including growth plate height, trabecular bone volume, thickness and number, and trabecular separation in the primary and secondary spongiosa. Several histomorphometric changes were noted, allowing researchers to conclude that exposure to microgravity resulted in osteopenia of spongy bone of tibial metaphysis. The roles of bone formation and bone resorption are discussed.

Process dissociation analyses of memory changes in healthy aging, preclinical, and very mild Alzheimer disease: Evidence for isolated recollection deficits.

PubMed

Millar, Peter R; Balota, David A; Maddox, Geoffrey B; Duchek, Janet M; Aschenbrenner, Andrew J; Fagan, Anne M; Benzinger, Tammie L S; Morris, John C

2017-10-01

Recollection and familiarity are independent processes that contribute to memory performance. Recollection is dependent on attentional control, which has been shown to be disrupted in early stage Alzheimer's disease (AD), whereas familiarity is independent of attention. The present longitudinal study examines the sensitivity of recollection estimates based on Jacoby's (1991) process dissociation procedure to AD-related biomarkers in a large sample of well-characterized cognitively normal middle-aged and older adults (N = 519) and the extent to which recollection discriminates these individuals from individuals with very mild symptomatic AD (N = 64). Participants studied word pairs (e.g., knee bone), then completed a primed, explicit, cued fragment-completion memory task (e.g., knee b_n_). Primes were either congruent with the correct response (e.g., bone), incongruent (e.g., bend), or neutral (e.g., &). This design allowed for the estimation of independent contributions of recollection and familiarity processes, using the process dissociation procedure. Recollection, but not familiarity, was impaired in healthy aging and in very mild AD. Recollection discriminated cognitively normal individuals from the earliest detectable stage of symptomatic AD above and beyond standard psychometric tests. In cognitively normal individuals, baseline CSF measures indicative of AD pathology were related to lower initial recollection and less practice-related improvement in recollection over time. Finally, presence of amyloid plaques, as imaged by PIB-PET, was also related to less improvement in recollection over time. These findings suggest that attention-demanding memory processes, such as recollection, may be particularly sensitive to both symptomatic and preclinical AD pathology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Fatigue behavior of porous biomaterials manufactured using selective laser melting.

PubMed

Yavari, S Amin; Wauthle, R; van der Stok, J; Riemslag, A C; Janssen, M; Mulier, M; Kruth, J P; Schrooten, J; Weinans, H; Zadpoor, A A

2013-12-01

Porous titanium alloys are considered promising bone-mimicking biomaterials. Additive manufacturing techniques such as selective laser melting allow for manufacturing of porous titanium structures with a precise design of micro-architecture. The mechanical properties of selective laser melted porous titanium alloys with different designs of micro-architecture have been already studied and are shown to be in the range of mechanical properties of bone. However, the fatigue behavior of this biomaterial is not yet well understood. We studied the fatigue behavior of porous structures made of Ti6Al4V ELI powder using selective laser melting. Four different porous structures were manufactured with porosities between 68 and 84% and the fatigue S-N curves of these four porous structures were determined. The three-stage mechanism of fatigue failure of these porous structures is described and studied in detail. It was found that the absolute S-N curves of these four porous structures are very different. In general, given the same absolute stress level, the fatigue life is much shorter for more porous structures. However, the normalized fatigue S-N curves of these four structures were found to be very similar. A power law was fitted to all data points of the normalized S-N curves. It is shown that the measured data points conform to the fitted power law very well, R(2)=0.94. This power law may therefore help in estimating the fatigue life of porous structures for which no fatigue test data is available. It is also observed that the normalized endurance limit of all tested porous structures (<0.2) is lower than that of corresponding solid material (c.a. 0.4). © 2013.

Influences of organic component on mechanical property of cortical bone with different water content by nanoindentation

NASA Astrophysics Data System (ADS)

Sun, Xingdong; Li, Lijia; Guo, Yue; Zhao, Hongwei; Zhang, Shizhong; Yu, Yang; Wu, Di; Liu, Hang; Yu, Miao; Shi, Dong; Liu, Zeyang; Zhou, Mingxing; Ren, Luquan; Fu, Lu

2018-03-01

The phenomenon that water in bone has important influences on mechanical properties of cortical bone has been known. However, the detail of the influence mechanism is not clear, especially in the component hierarchy. The main objective of this paper is to investigate the mechanical properties of deproteinization bone and cortical bone with different water content by nanoindentation experiments. The deproteinization bone is cortical bone removed organic component, and demineralization bone is cortical bone removed inorganic component. The experiments results showed that the elastic modulus and hardness all increased with the decreasing of water content in both cortical bone and deproteinization bone. However, variations of deproteinization bone were more significant than the normal one. Without organic component, the shape and size of inorganic component (hydroxyapatite particles) turned to irregular. The plastic energy of both cortical bone and deproteinization bone all decreased with the decreasing of water content and the variations range of deproteinization bone was wider than cortical bone. This research may give some deeply understanding for the studies of influence of water on mechanical properties of cortical bone.

Experiment K-6-05. The maturaton of bone and dentin matrices in rats flown on Cosmos 1887

NASA Technical Reports Server (NTRS)

Simmons, D.; Grynpas, M.; Rosenberg, G.; Durnova, G.

1990-01-01

The chemistry, hydroxyapatite crystal size, and maturation of the bone and dentin is characterized in rats exposed to microgravity for 12.5d in a Soviet Biosatellite (Cosmos-1887). Calvarial and vertebral bone ash was subnormal, but contained a normal percent composition of Ca, P, and Mg. These tissues varied from the norm by having lower Ca/P and higher Ca/Mg ratios than any of their age-matched controls (Vivarium and Synchronous Groups). Gradient density analyses (calvaria) indicated a strong shift to the lower sp.gr. fractions which was commensurate with impaired rates of matrix-mineral maturation. X-ray diffraction data were confirmatory. Bone hydroxyapatite crystal growth in Flight rats was preferentially altered in a way to reduce the dimension of their C-axis. Flight rat dentin was normal with respect to age-matched control Ca, P, Mg, and Zn concentrations and their Ca/P and Ca/Mg ratios. These observations affirm the concept that microgravity adversely affects the maturation of newly formed matrix and mineral moieties in bone.

Potential anabolic effects of androgens on bone.

PubMed

Kearns, Ann E; Khosla, Sundeep

2004-04-01

Sex steroid hormones are essential to normal skeletal growth and maintenance throughout life in both men and women. The importance of estrogens to bone health in women becomes obvious at menopause when estrogen deficiency occurs and results in accelerated bone loss. After menopause, estrogen deficiency results in drastic changes in the androgen-estrogen ratio. Thus, the relative importance of androgens after menopause may increase. Androgens also appear to be important for bone health in pre-menopausal women. Evidence from human, animal, and laboratory studies is leading to a better understanding of the effects of androgens on bone in women.

Application of synchrotron radiation computed microtomography for quantification of bone microstructure in human and rat bones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parreiras Nogueira, Liebert; Barroso, Regina Cely; Pereira de Almeida, Andre

2012-05-17

This work aims to evaluate histomorphometric quantification by synchrotron radiation computed microto-mography in bones of human and rat specimens. Bones specimens are classified as normal and pathological (for human samples) and irradiated and non-irradiated samples (for rat ones). Human bones are specimens which were affected by some injury, or not. Rat bones are specimens which were irradiated, simulating radiotherapy procedures, or not. Images were obtained on SYRMEP beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. The system generated 14 {mu}m tomographic images. The quantification of bone structures were performed directly by the 3D rendered images using a home-made software.more » Resolution yielded was excellent what facilitate quantification of bone microstructures.« less

Experiment K-310: The effect of spaceflight on osteogenesis and dentinogenesis in the mandibles of rats

NASA Technical Reports Server (NTRS)

Simmons, D. J.; Russell, J. E.; Winter, F.; Rosenberg, G. D.; Walker, W. V.

1981-01-01

Normal rates of dentinogenesis and osteogenesis in the body of the mandible were observed. The total calcium, inorganic phosphorus and hydroxyproline levels in the jaws and incisors of the flight rats were normal. Gravity density fractionation studies suggested, however, that spaceflight caused a delay in the normal maturation of bone mineral and matrix; normal values were reestablished by 6 days postflight. The teeth were spared. The circadian and ultradian patterns of dentin calcification were normal during spaceflight and recovery periods, but the enamel rhythms displayed a greater amplitude of sulfur concentrations and this abnormal calcium to sulfur ratios only during exposure to zero gravity. The rat mandible and teeth do not suffer the deficits of bone formation common to weight bearing parts of the skeleton during spaceflight. The only derangements detected were in the quality of the matrix and mineral moieties.

A Case of Osteomalacia: The Pivotal role of the Non-Decalcified Bone Biopsy

PubMed Central

Kim, Ghi Su; Bergfeld, Michele A.; Avioli, Louis V.; Teitelbaum, Steven L.

1988-01-01

A postmenopausal osteopenic woman presented with recurrent stress fractures of the feet and normal parameters of mineral homeostasis. Despite the absence of biochemical or radiographic evidence, severe osteomalacia was documented by histomorphometric analysis of a tetracycline labeled, non-decalcified bone biopsy. This observation underscores the need for specific bone biopsy confirmation of skeletal disease in patients with fracture-prone osteopenia. PMID:3154190

Denosumab for the management of bone disease in patients with solid tumors.

PubMed

Body, Jean-Jacques

2012-03-01

Many patients with advanced cancer develop bone metastases, which reduces their quality of life. Bone metastases are associated with an increased risk of skeletal-related events, which can lead to increased morbidity and mortality. In patients with bone metastases, tumor cells disrupt the normal process of bone remodeling, leading to increased bone destruction. Denosumab is a fully human monoclonal antibody against receptor activator of NF-κB ligand (RANKL), a key regulatory factor in bone remodeling. By binding to RANKL, denosumab disrupts the cycle of bone destruction. In clinical studies in patients with prostate or breast cancer and bone metastases, denosumab was superior to the current standard of care, zoledronic acid, for delaying skeletal-related events, while in patients with other solid tumors or multiple myeloma, denosumab was noninferior to zoledronic acid. This article examines the pharmacokinetics, efficacy, and safety and tolerability of denosumab for the management of bone events in patients with cancer.

Evidence for arrested bone formation during spaceflight

NASA Technical Reports Server (NTRS)

Turner, R. T.; Bobyn, J. D.; Duvall, P.; Morey, E. R.; Baylink, D. J.; Spector, M.

1982-01-01

Addressing the question of whether the bone formed in space is unusual, the morphology of bone made at the tibial diaphysis of rats before, during, and after spaceflight is studied. Evidence of arrest lines in the bone formed in space is reported suggesting that bone formation ceases along portions of the periosteum during spaceflight. Visualized by microradiography, the arrest lines are shown to be less mineralized than the surrounding bone matrix. When viewed by scanning electron microscopy, it is seen that bone fractures more readily at the site of an arrest line. These observations are seen as suggesting that arrest lines are a zone of weakness and that their formation may result in decreased bone strength in spite of normalization of bone formation after flight. The occurrence, location, and morphology of arrest lines are seen as suggesting that they are a visible result of the phenomenon of arrested bone formation.

Minimizing Interpolation Bias and Precision Error in In Vivo μCT-based Measurements of Bone Structure and Dynamics

PubMed Central

de Bakker, Chantal M. J.; Altman, Allison R.; Li, Connie; Tribble, Mary Beth; Lott, Carina; Tseng, Wei-Ju; Liu, X. Sherry

2016-01-01

In vivo μCT imaging allows for high-resolution, longitudinal evaluation of bone properties. Based on this technology, several recent studies have developed in vivo dynamic bone histomorphometry techniques that utilize registered μCT images to identify regions of bone formation and resorption, allowing for longitudinal assessment of bone remodeling. However, this analysis requires a direct voxel-by-voxel subtraction between image pairs, necessitating rotation of the images into the same coordinate system, which introduces interpolation errors. We developed a novel image transformation scheme, matched-angle transformation (MAT), whereby the interpolation errors are minimized by equally rotating both the follow-up and baseline images instead of the standard of rotating one image while the other remains fixed. This new method greatly reduced interpolation biases caused by the standard transformation. Additionally, our study evaluated the reproducibility and precision of bone remodeling measurements made via in vivo dynamic bone histomorphometry. Although bone remodeling measurements showed moderate baseline noise, precision was adequate to measure physiologically relevant changes in bone remodeling, and measurements had relatively good reproducibility, with intra-class correlation coefficients of 0.75-0.95. This indicates that, when used in conjunction with MAT, in vivo dynamic histomorphometry provides a reliable assessment of bone remodeling. PMID:26786342

Minimizing Interpolation Bias and Precision Error in In Vivo µCT-Based Measurements of Bone Structure and Dynamics.

PubMed

de Bakker, Chantal M J; Altman, Allison R; Li, Connie; Tribble, Mary Beth; Lott, Carina; Tseng, Wei-Ju; Liu, X Sherry

2016-08-01

In vivo µCT imaging allows for high-resolution, longitudinal evaluation of bone properties. Based on this technology, several recent studies have developed in vivo dynamic bone histomorphometry techniques that utilize registered µCT images to identify regions of bone formation and resorption, allowing for longitudinal assessment of bone remodeling. However, this analysis requires a direct voxel-by-voxel subtraction between image pairs, necessitating rotation of the images into the same coordinate system, which introduces interpolation errors. We developed a novel image transformation scheme, matched-angle transformation (MAT), whereby the interpolation errors are minimized by equally rotating both the follow-up and baseline images instead of the standard of rotating one image while the other remains fixed. This new method greatly reduced interpolation biases caused by the standard transformation. Additionally, our study evaluated the reproducibility and precision of bone remodeling measurements made via in vivo dynamic bone histomorphometry. Although bone remodeling measurements showed moderate baseline noise, precision was adequate to measure physiologically relevant changes in bone remodeling, and measurements had relatively good reproducibility, with intra-class correlation coefficients of 0.75-0.95. This indicates that, when used in conjunction with MAT, in vivo dynamic histomorphometry provides a reliable assessment of bone remodeling.

MR-based trabecular bone microstructure is not altered in subjects with indolent systemic mastocytosis.

PubMed

Baum, Thomas; Karampinos, Dimitrios C; Brockow, Knut; Seifert-Klauss, Vanadin; Jungmann, Pia M; Biedermann, Tilo; Rummeny, Ernst J; Bauer, Jan S; Müller, Dirk

2015-01-01

Subjects with indolent systemic mastocytosis (ISM) have an increased risk for osteoporosis. It has been demonstrated that trabecular bone microstructure analysis improves the prediction of bone strength beyond dual-energy X-ray absorptiometry-based bone mineral density. The purpose of this study was to obtain Magnetic Resonance (MR)-based trabecular bone microstructure parameters as advanced imaging biomarkers in subjects with ISM (n=18) and compare them with those of normal controls (n=18). Trabecular bone microstructure parameters were not significantly (P>.05) different between subjects with ISM and controls. These findings revealed important pathophysiological information about ISM-associated osteoporosis and may limit the use of trabecular bone microstructure analysis in this clinical setting. Copyright © 2015 Elsevier Inc. All rights reserved.

Application of the World Health Organization Fracture Risk Assessment Tool to predict need for dual-energy X-ray absorptiometry scanning in postmenopausal women.

PubMed

Chao, An-Shine; Chen, Fang-Ping; Lin, Yu-Ching; Huang, Ting-Shuo; Fan, Chih-Ming; Yu, Yu-Wei

2015-12-01

To evaluate the efficacy of the World Health Organization Fracture Risk Assessment Tool, excluding bone mineral density (pre-BMD FRAX), in identifying Taiwanese postmenopausal women needing dual-energy X-ray absorptiometry (DXA) examination for further treatment. The pre-BMD FRAX score was calculated for 231 postmenopausal women who participated in public health education workshops in the local Keelung community, Taiwan. DXA scanning and vertebral fracture assessment (VFA) were arranged for women classified as intermediate or high risk for fracture using the pre-BMD FRAX fracture probability. Pre-BMD FRAX classified 26 women as intermediate risk and 37 as having high risk for fracture. Subsequent DXA scans for these 63 women showed that 36 were osteoporotic, 19 were osteopenic, and eight had normal bone density. Concurrent VFA revealed 25 spine factures in which 14 were osteoporotic, seven were osteopenic, and four had normal bone density. The efficacy of the pre-BMD FRAX score to identify those patients with low bone mass by DXA was 87.3% (55/63). When VFA was combined with BMD to identify those patients with high risk (osteopenia, osteoporosis, or spinal fracture), the efficacy of the pre-BMD score increased to 93.7% (59/63). According to the National Osteoporosis Foundation, the overall concordance between pre-BMD FRAX and BMD, expressed through the kappa index, was 0.967. Compared with the evaluation when BMD was used alone, there was a significant increase in efficacy in identifying women who need treatment using BMD plus VFA or FRAX plus BMD. Furthermore, the highest efficacy was achieved when FRAX with BMD and VFA was used. The pre-BMD FRAX score not only efficiently predicts postmenopausal patients who are potentially at risk and might require treatment but also reduces unnecessary DXA use. Concurrent VFA during DXA use increases spine fracture detection. This improvement in diagnostic efficacy allows clinicians to provide the most appropriate therapeutic recommendation. Copyright © 2015. Published by Elsevier B.V.

Distinctive Capillary Action by Micro-channels in Bone-like Templates can Enhance Recruitment of Cells for Restoration of Large Bony Defect.

PubMed

Oh, Daniel S; Koch, Alia; Eisig, Sidney; Kim, Sahng Gyoon; Kim, Yoon Hyuk; Kim, Do-Gyoon; Shim, Jae Hyuck

2015-09-11

Without an active, thriving cell population that is well-distributed and stably anchored to the inserted template, exceptional bone regeneration does not occur. With conventional templates, the absence of internal micro-channels results in the lack of cell infiltration, distribution, and inhabitance deep inside the templates. Hence, a highly porous and uniformly interconnected trabecular-bone-like template with micro-channels (biogenic microenvironment template; BMT) has been developed to address these obstacles. The novel BMT was created by innovative concepts (capillary action) and fabricated with a sponge-template coating technique. The BMT consists of several structural components: inter-connected primary-pores (300-400 µm) that mimic pores in trabecular bone, micro-channels (25-70 µm) within each trabecula, and nanopores (100-400 nm) on the surface to allow cells to anchor. Moreover, the BMT has been documented by mechanical test study to have similar mechanical strength properties to those of human trabecular bone (~3.8 MPa)12. The BMT exhibited high absorption, retention, and habitation of cells throughout the bridge-shaped (Π) templates (3 cm height and 4 cm length). The cells that were initially seeded into one end of the templates immediately mobilized to the other end (10 cm distance) by capillary action of the BMT on the cell media. After 4 hr, the cells homogenously occupied the entire BMT and exhibited normal cellular behavior. The capillary action accounted for the infiltration of the cells suspended in the media and the distribution (active migration) throughout the BMT. Having observed these capabilities of the BMT, we project that BMTs will absorb bone marrow cells, growth factors, and nutrients from the periphery under physiological conditions. The BMT may resolve current limitations via rapid infiltration, homogenous distribution and inhabitance of cells in large, volumetric templates to repair massive skeletal defects.

Phenotypic characterization of Grm1crv4 mice reveals a functional role for the type 1 metabotropic glutamate receptor in bone mineralization.

PubMed

Musante, Ilaria; Mattinzoli, Deborah; Otescu, Lavinia Alexandra; Bossi, Simone; Ikehata, Masami; Gentili, Chiara; Cangemi, Giuliana; Gatti, Cinzia; Emionite, Laura; Messa, Piergiorgio; Ravazzolo, Roberto; Rastaldi, Maria Pia; Riccardi, Daniela; Puliti, Aldamaria

2017-01-01

Recent increasing evidence supports a role for neuronal type signaling in bone. Specifically glutamate receptors have been found in cells responsible for bone remodeling, namely the osteoblasts and the osteoclasts. While most studies have focused on ionotropic glutamate receptors, the relevance of the metabotropic glutamate signaling in bone is poorly understood. Specifically type 1 metabotropic glutamate (mGlu1) receptors are expressed in bone, but the effect of its ablation on skeletal development has never been investigated. Here we report that Grm1 crv4/crv4 mice, homozygous for an inactivating mutation of the mGlu1 receptor, and mainly characterized by ataxia and renal dysfunction, exhibit decreased body weight, bone length and bone mineral density compared to wild type (WT) animals. Blood analyses of the affected mice demonstrate the absence of changes in circulating factors, such as vitamin D and PTH, suggesting renal damage is not the main culprit of the skeletal phenotype. Cultures of osteoblasts lacking functional mGlu1 receptors exhibit less homogeneous collagen deposition than WT cells, and present increased expression of osteocalcin, a marker of osteoblast maturation. These data suggest that the skeletal damage is directly linked to the absence of the receptor, which in turn leads to osteoblasts dysfunction and earlier maturation. Accordingly, skeletal histomorphology suggests that Grm1 crv4/crv4 mice exhibit enhanced bone maturation, resulting in premature fusion of the growth plate and shortened long bones, and further slowdown of bone apposition rate compared to the WT animals. In summary, this work reveals novel functions of mGlu1 receptors in the bone and indicates that in osteoblasts mGlu1 receptors are necessary for production of normal bone matrix, longitudinal bone growth, and normal skeletal development. Copyright © 2016 Elsevier Inc. All rights reserved.

INCREASING DURATION OF TYPE 1 DIABETES PERTURBS THE STRENGTH-STRUCTURE RELATIONSHIP AND INCREASES BRITTLENESS OF BONE

PubMed Central

Nyman, Jeffry S.; Even, Jesse L.; Jo, Chan-Hee; Herbert, Erik G.; Murry, Matthew R.; Cockrell, Gael E.; Wahl, Elizabeth C.; Bunn, R. Clay; Lumpkin, Charles K.; Fowlkes, John L.; Thrailkill, Kathryn M.

2011-01-01

Type 1 diabetes (T1DM) increases the likelihood of a fracture. Despite serious complications in the healing of fractures among those with diabetes, the underlying causes are not delineated for the effect of diabetes on the fracture resistance of bone. Therefore, in a mouse model of T1DM, we have investigated the possibility that a prolonged state of diabetes perturbs the relationship between bone strength and structure (i.e., affects tissue properties). At 10, 15, and 18 weeks following injection of streptozotocin to induce diabetes, diabetic male mice and age-matched controls were examined for measures of skeletal integrity. We assessed 1) the moment of inertia (IMIN) of the cortical bone within diaphysis, trabecular bone architecture of the metaphysis, and mineralization density of the tissue (TMD) for each compartment of the femur by microcomputed tomography and 2) biomechanical properties by three point bending test (femur) and nanoindentation (tibia). In the metaphysis, a significant decrease in trabecular bone volume fraction and trabecular TMD was apparent after 10 weeks of diabetes. For cortical bone, type 1 diabetes was associated with decreased cortical TMD, IMIN, rigidity, and peak moment as well as a lack of normal age-related increases in the biomechanical properties. However, there were only modest differences in material properties between diabetic and normal mice at both whole bone and tissue-levels. As the duration of diabetes increased, bone toughness decreased relative to control. If the sole effect of diabetes on bone strength was due to a reduction in bone size, then IMIN would be the only significant variable explaining the variance in the maximum moment. However, general linear modeling found that the relationship between peak moment and IMIN depended on whether the bone was from a diabetic mouse and the duration of diabetes. Thus, these findings suggest that the elevated fracture risk among diabetics is impacted by complex changes in tissue properties that ultimately reduce the fracture resistance of bone. PMID:21185416

Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

NASA Technical Reports Server (NTRS)

Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

1996-01-01

Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human primate model.

Mechanical Unloading of Mouse Bone in Microgravity Significantly Alters Cell Cycle Gene Set Expression

NASA Astrophysics Data System (ADS)

Blaber, Elizabeth; Dvorochkin, Natalya; Almeida, Eduardo; Kaplan, Warren; Burns, Brnedan

2012-07-01

Spaceflight factors, including microgravity and space radiation, have many detrimental short-term effects on human physiology, including muscle and bone degradation, and immune system dysfunction. The long-term progression of these physiological effects is still poorly understood, and a serious concern for long duration spaceflight missions. We hypothesized that some of the degenerative effects of spaceflight may be caused in part by an inability of stem cells to proliferate and differentiate normally resulting in an impairment of tissue regenerative processes. Furthermore, we hypothesized that long-term bone tissue degeneration in space may be mediated by activation of the p53 signaling network resulting in cell cycle arrest and/or apoptosis in osteoprogenitors. In our analyses we found that spaceflight caused significant bone loss in the weight-bearing bones of mice with a 6.3% reduction in bone volume and 11.9% decrease in bone thickness associated with increased osteoclastic activity. Along with this rapid bone loss we also observed alterations in the cell cycle characterized by an increase in the Cdkn1a/p21 cell cycle arrest molecule independent of Trp53. Overexpression of Cdkn1a/p21 was localized to osteoblasts lining the periosteal surface of the femur and chondrocytes in the head of the femur, suggesting an inhibition of proliferation in two key regenerative cell types of the femur in response to spaceflight. Additionally we found overexpression of several matrix degradation molecules including MMP-1a, 3 and 10, of which MMP-10 was localized to osteocytes within the shaft of the femur. This, in conjunction with 40 nm resolution synchrotron nano-Computed Tomography (nano-CT) observations of an increase in osteocyte lacunae cross-sectional area, perimeter and a decrease in circularity indicates a potential role for osteocytic osteolysis in the observed bone degeneration in spaceflight. To further investigate the genetic response of bone to mechanical unloading in spaceflight, we conducted genome wide microarray analysis of total RNA isolated from the mouse pelvis. Specifically, 16 week old mice were subjected to 15 days spaceflight onboard NASA's STS-131 space shuttle mission. The pelvis of the mice was dissected, the bone marrow was flushed and the bones were briefly stored in RNAlater. The pelvii were then homogenized, and RNA was isolated using TRIzol. RNA concentration and quality was measured using a Nanodrop spectrometer, and 0.8% agarose gel electrophoresis. Samples of cDNA were analyzed using an Affymetrix GeneChip\\S Gene 1.0 ST (Sense Target) Array System for Mouse and GenePattern Software. We normalized the ST gene arrays using Robust Multichip Average (RMA) normalization, which summarizes perfectly matched spots on the array through the median polish algorithm, rather than normalizing according to mismatched spots. We also used Limma for statistical analysis, using the BioConductor Limma Library by Gordon Smyth, and differential expression analysis to identify genes with significant changes in expression between the two experimental conditions. Finally we used GSEApreRanked for Gene Set Enrichment Analysis (GSEA), with Kolmogorov-Smirnov style statistics to identify groups of genes that are regulated together using the t-statistics derived from Limma. Preliminary results show that 6,603 genes expressed in pelvic bone had statistically significant alterations in spaceflight compared to ground controls. These prominently included cell cycle arrest molecules p21, and p18, cell survival molecule Crbp1, and cell cycle molecules cyclin D1, and Cdk1. Additionally, GSEA results indicated alterations in molecular targets of cyclin D1 and Cdk4, senescence pathways resulting from abnormal laminin maturation, cell-cell contacts via E-cadherin, and several pathways relating to protein translation and metabolism. In total 111 gene sets out of 2,488, about 4%, showed statistically significant set alterations. These alterations indicate significant impairment of normal cellular function in the mechanically unloaded environment of space and could provide important genetic insight into the observed uncoupling of bone formation and resorption in space.

Beta 2-Microglobulin: A Novel Therapeutic Target for the Treatment of Human Prostate Cancer Bone Metastasis

DTIC Science & Technology

2009-03-14

H, Sodek J, Zhau HE, Chung LW. Human osteocalcin and bone sialoprotein mediating osteomimicry of prostate cancer cells: role of cAMP-dependent...with mesenchymal phenotype b2-m b2-Microglobulin BSP Bone sialoprotein C4-2 Lineage derivative cells from LNCaP C4-2B C4-2 cells metastasized to bone...OPN) and bone sialoprotein (BSP), and RANKL, collectively allow- ing cancer cells to survive and thrive in the bone microenvironment [7–9]. Previous

The development of curvature in the porcine radioulna

PubMed Central

Pantinople, Jess; McCabe, Kyle; Henderson, Keith; Milne, Nick

2017-01-01

Long bone curvature in animal limbs has long been a subject of interest and much work has explored why long bones should be curved. However, the ‘when’ and ‘how’ of curvature development is poorly understood. It has been shown that the rat tibia fails to attain its normal curvature if the action of muscles is removed early in life, but it is not clear if this is because the curvature fails to develop or if the bone becomes straighter without the action of muscles. No studies have examined the development of bone curvature in a normally developing quadruped, so this study tracks the course of curvature formation in the radioulna in a series of growing pigs. We also histologically examined the epiphyseal growth plates of these bones to determine if they contribute to the formation of curvature. In all three epiphyseal plates examined, the proliferative zone is thicker and more densely populated with chondrocytes on the cranial (convex) side than the caudal (concave) side. Frost’s chondral modelling theory would suggest that the cranial side of the bone is under more compression than the caudal side, and we conclude that this is due to the action of triceps extending the elbow by pulling on the olecranon process. These results support the idea that bone curvature is an adaptation to habitual loading, where longitudinal loads acting on the curved bone cause bending strains that counter the bending resulting from the habitual muscle action. PMID:28584714

Bone scanning in lymphoma. [/sup 99m/Tc tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schechter, J.P.; Jones, S.E.; Woolfenden, J.M.

1976-09-01

The results of bone scanning with the newer technetium-99m complexes were correlated with clinical, laboratory, and radiographic findings in 26 patients with malignant lymphoma (10 with Hodgkin's disease and 16 with non-Hodgkin's lymphomas). Abnormalities on bone scan compatible with lymphomatous involvement of the skeleton appeared to occur more commonly in patients with diffuse lymphomas than in patients with nodular lymphomas and were generally observed in the setting of advanced disease (15 of 23 patients). Twenty-seven (73 percent) of the 37 scans obtained were abnormal. Although abnormal scans were observed with the greatest frequency in patients with bone pain (11 ofmore » 11), bone marrow involvement (11 of 12), abnormal skeletal radiographs (11 of 11), and elevated serum alkaline phosphatase levels (5 of 6), bone scanning also detected lymphomatous involvement in patients free of pain or with normal laboratory tests. Moreover, conventional radiography was entirely normal in six (35 percent) of 17 patients with abnormal scans and revealed only nonspecific osteopenia in another two patients (12 percent). Serial bone scans in nine patients reflected their response to chemotherapy. Of the 37 scans, only one was judged falsely positive and one falsely negative. Bone scanning with /sup 99m/Tc complexes is a safe, simple, and sensitive screening procedure for detecting both extensive and focal lymphomatous involvement of the skeletal system and is a useful means of following such involvement in response to treatment.« less

The development of curvature in the porcine radioulna.

PubMed

Pantinople, Jess; McCabe, Kyle; Henderson, Keith; Richards, Hazel L; Milne, Nick

2017-01-01

Long bone curvature in animal limbs has long been a subject of interest and much work has explored why long bones should be curved. However, the 'when' and 'how' of curvature development is poorly understood. It has been shown that the rat tibia fails to attain its normal curvature if the action of muscles is removed early in life, but it is not clear if this is because the curvature fails to develop or if the bone becomes straighter without the action of muscles. No studies have examined the development of bone curvature in a normally developing quadruped, so this study tracks the course of curvature formation in the radioulna in a series of growing pigs. We also histologically examined the epiphyseal growth plates of these bones to determine if they contribute to the formation of curvature. In all three epiphyseal plates examined, the proliferative zone is thicker and more densely populated with chondrocytes on the cranial (convex) side than the caudal (concave) side. Frost's chondral modelling theory would suggest that the cranial side of the bone is under more compression than the caudal side, and we conclude that this is due to the action of triceps extending the elbow by pulling on the olecranon process. These results support the idea that bone curvature is an adaptation to habitual loading, where longitudinal loads acting on the curved bone cause bending strains that counter the bending resulting from the habitual muscle action.

Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

NASA Technical Reports Server (NTRS)

Bikle, Daniel D.; Sakata, Takeshi; Leary, Colin; Elalieh, Hashem; Ginzinger, David; Rosen, Clifford J.; Beamer, Wesley; Majumdar, Sharmila; Halloran, Bernard P.

2002-01-01

Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.

Administration of growth hormone in selectively protein-deprived rats decreases BMD and bone strength.

PubMed

Ammann, Patrick; Brennan, Tara C; Mekraldi, Samia; Aubert, Michel L; Rizzoli, René

2010-06-01

Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower IGF-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism. Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2 weeks. Bovine growth hormone (bGH, 0.5 or 2.5mg/kg of body weight) or vehicle was then administered as subcutaneous injections, twice daily, to rats on either diet for 4 weeks. At the proximal tibia, analysis of bone mineral density (BMD), maximal load and histomorphometry were performed. In addition, urinary deoxypyridinoline, plasma osteocalcin and IGF-I concentrations were measured. Weight was monitored weekly. bGH caused a dose-dependent increase in plasma IGF-I regardless of the dietary protein content. However, bGH dose-dependently decreased BMD and bone strength in rats fed the low-protein diet. There was no significant effect of bGH on BMD in rats fed the normal protein diet within this short-term treatment period, however bone formation as detected by histomorphometry was improved in this group but not the low-protein group. Osteoclast surface was increased in the low-protein bGH-treated animals only. Changes in bone turnover markers were detectable under both normal and low-protein diets. These results emphasize the major importance of dietary protein intake in the bone response to short-term GH administration, and highlight the need for further investigation into the effects of GH treatment in patients with reduced protein intake. Copyright 2010 Elsevier Inc. All rights reserved.

Phantom-less bone mineral density (BMD) measurement using dual energy computed tomography-based 3-material decomposition

NASA Astrophysics Data System (ADS)

Hofmann, Philipp; Sedlmair, Martin; Krauss, Bernhard; Wichmann, Julian L.; Bauer, Ralf W.; Flohr, Thomas G.; Mahnken, Andreas H.

2016-03-01

Osteoporosis is a degenerative bone disease usually diagnosed at the manifestation of fragility fractures, which severely endanger the health of especially the elderly. To ensure timely therapeutic countermeasures, noninvasive and widely applicable diagnostic methods are required. Currently the primary quantifiable indicator for bone stability, bone mineral density (BMD), is obtained either by DEXA (Dual-energy X-ray absorptiometry) or qCT (quantitative CT). Both have respective advantages and disadvantages, with DEXA being considered as gold standard. For timely diagnosis of osteoporosis, another CT-based method is presented. A Dual Energy CT reconstruction workflow is being developed to evaluate BMD by evaluating lumbar spine (L1-L4) DE-CT images. The workflow is ROI-based and automated for practical use. A dual energy 3-material decomposition algorithm is used to differentiate bone from soft tissue and fat attenuation. The algorithm uses material attenuation coefficients on different beam energy levels. The bone fraction of the three different tissues is used to calculate the amount of hydroxylapatite in the trabecular bone of the corpus vertebrae inside a predefined ROI. Calibrations have been performed to obtain volumetric bone mineral density (vBMD) without having to add a calibration phantom or to use special scan protocols or hardware. Accuracy and precision are dependent on image noise and comparable to qCT images. Clinical indications are in accordance with the DEXA gold standard. The decomposition-based workflow shows bone degradation effects normally not visible on standard CT images which would induce errors in normal qCT results.

Antimicrobial activity of poultry bone and meat trimmings hydrolyzates in low-sodium turkey food.

PubMed

Zanello, Pier Paolo; Sforza, Stefano; Dossena, Arnaldo; Lambertini, Francesca; Bottesini, Chiara; Nikolaev, Ilya V; Koroleva, Olga; Ciociola, Tecla; Magliani, Walter; Conti, Stefania; Polonelli, Luciano

2014-02-01

This research was aimed at the evaluation of the antimicrobial activity exerted by poultry protein hydrolyzates derived from industrial leftovers added to minced turkey meat, intended for the production of burgers for human consumption. Hydrolyzates were obtained through enzymatic hydrolysis from poultry bone and meat trimmings, as by-products from the poultry industry. Colony forming unit assays, under both laboratory and industrial conditions, were performed to assess microbial growth. Poultry protein hydrolyzates inhibited microbial growth occurring in semi-finished turkey meat during the normal retention period because of their water holding capacity resulting in a decreased water activity. Overall, the findings demonstrated that poultry protein hydrolyzates could decrease mesophilic, psychrophilic, and thermophilic bacterial growth for the entire product shelf-life. Bacterial growth inhibition obtained in minced turkey meat by addition of poultry protein hydrolyzates (1.5%), hygroscopic amino acids mixture (1.5%) or sodium chloride (1%) was similar. It is suggested that the use of hydrolyzates could allow the reduction of salt content in poultry meat based products leading to the production of low-sodium turkey food still maintaining acceptable sensory characteristics.

Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect.

PubMed

Webb, Emma A; Balasubramanian, Meena; Fratzl-Zelman, Nadja; Cabral, Wayne A; Titheradge, Hannah; Alsaedi, Atif; Saraff, Vrinda; Vogt, Julie; Cole, Trevor; Stewart, Susan; Crabtree, Nicola J; Sargent, Brandi M; Gamsjaeger, Sonja; Paschalis, Eleftherios P; Roschger, Paul; Klaushofer, Klaus; Shaw, Nick J; Marini, Joan C; Högler, Wolfgang

2017-06-01

Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Clinical and bone material phenotype description and osteoblast differentiation studies. Natural history study in pediatric research centers. Eight patients with type XIV OI. Clinical examinations included bone mineral density, radiographs, echocardiography, and muscle biopsy. Bone biopsy samples (n = 3) were analyzed using histomorphometry, quantitative backscattered electron microscopy, and Raman microspectroscopy. Cellular differentiation studies were performed on proband and control osteoblasts and normal murine osteoclasts. Type XIV OI clinical phenotype ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara, and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband lumbar spine bone density z score was reduced [median -3.3 (range -4.77 to +0.1; n = 7)] and increased by +1.7 (1.17 to 3.0; n = 3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast, and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone matrix mineralization is normal and nanoporosity low. We demonstrate a complex osteoblast differentiation defect with decreased expression of early markers and increased expression of late and mineralization-related markers. Predominance of trimeric intracellular cation channel type B over type A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover. OI type XIV has a bone histology, matrix mineralization, and osteoblast differentiation pattern that is distinct from OI with collagen defects. Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities. Copyright © 2017 Endocrine Society

Changes in Mechanical Properties of Rat Bones under Simulated Effects of Microgravity and Radiation†

NASA Astrophysics Data System (ADS)

Walker, Azida H.; Perkins, Otis; Mehta, Rahul; Ali, Nawab; Dobretsov, Maxim; Chowdhury, Parimal

The aim of this study was to determine the changes in elasticity and lattice structure in leg bone of rats which were: 1) under Hind-Limb Suspension (HLS) by tail for 2 weeks and 2) exposed to a total radiation of 10 Grays in 10 days. The animals were sacrificed at the end of 2 weeks and the leg bones were surgically removed, cleaned and fixed with a buffered solution. The mechanical strength of the bone (elastic modulus) was determined from measurement of bending of a bone when under an applied force. Two methodologies were used: i) a 3-point bending technique and ii) classical bending where bending is accomplished keeping one end fixed. Three point bending method used a captive actuator controlled by a programmable IDEA drive. This allowed incremental steps of 0.047 mm for which the force is measured. The data is used to calculate the stress and the strain. In the second method a mirror attached to the free end of the bone allowed a reflected laser beam spot to be tracked. This provided the displacement measurement as stress levels changed. Analysis of stress vs. strain graph together with solution of Euler-Bernoulli equation for a cantilever beam allowed determination of the elastic modulus of the leg bone for (i) control samples, (ii) HLS samples and (iii) HLS samples with radiation effects. To ascertain changes in the bone lattice structure, the bones were cross-sectioned and imaged with a 20 keV beam of electrons in a Scanning Electron Microscope (SEM). A backscattered detector and a secondary electron detector in the SEM provided the images from well-defined parts of the leg bones. Elemental compositions in combination with mechanical properties (elastic modulus and lattice structure) changes indicated weakening of the bones under space-like conditions of microgravity and radiation.

The Analysis of Fixed Final State Optimal Control in Bilinear System Applied to Bone Marrow by Cell-Cycle Specific (CCS) Chemotherapy

NASA Astrophysics Data System (ADS)

Rainarli, E.; E Dewi, K.

2017-04-01

The research conducted by Fister & Panetta shown an optimal control model of bone marrow cells against Cell Cycle Specific chemotherapy drugs. The model used was a bilinear system model. Fister & Panetta research has proved existence, uniqueness, and characteristics of optimal control (the chemotherapy effect). However, by using this model, the amount of bone marrow at the final time could achieve less than 50 percent from the amount of bone marrow before given treatment. This could harm patients because the lack of bone marrow cells made the number of leukocytes declining and patients will experience leukemia. This research would examine the optimal control of a bilinear system that applied to fixed final state. It will be used to determine the length of optimal time in administering chemotherapy and kept bone marrow cells on the allowed level at the same time. Before simulation conducted, this paper shows that the system could be controlled by using a theory of Lie Algebra. Afterward, it shows the characteristics of optimal control. Based on the simulation, it indicates that strong chemotherapy drug given in a short time frame is the most optimal condition to keep bone marrow cells spine on the allowed level but still could put playing an effective treatment. It gives preference of the weight of treatment for keeping bone marrow cells. The result of chemotherapy’s effect (u) is not able to reach the maximum value. On the other words, it needs to make adjustments of medicine’s dosage to satisfy the final treatment condition e.g. the number of bone marrow cells should be at the allowed level.

Physiological joint line total knee arthroplasty designs are especially sensitive to rotational placement - A finite element analysis.

PubMed

Moewis, Philippe; Checa, Sara; Kutzner, Ines; Hommel, Hagen; Duda, Georg N

2018-01-01

Mechanical and kinematical aligning techniques are the usual positioning methods during total knee arthroplasty. However, alteration of the physiological joint line and unbalanced medio-lateral load distribution are considered disadvantages in the mechanical and kinematical techniques, respectively. The aim of this study was to analyse the influence of the joint line on the strain and stress distributions in an implanted knee and their sensitivity to rotational mal-alignment. Finite element calculations were conducted to analyse the stresses in the PE-Inlay and the mechanical strains at the bone side of the tibia component-tibia bone interface during normal positioning of the components and internal and external mal-rotation of the tibial component. Two designs were included, a horizontal and a physiological implant. The loading conditions are based on internal knee joint loads during walking. A medialization of the stresses on the PE-Inlay was observed in the physiological implant in a normal position, accompanied by higher stresses in the mal-rotated positions. Within the tibia component-tibia bone interface, similar strain distributions were observed in both implant geometries in the normal position. However, a medialization of the strains was observed in the physiological implant in both mal-rotated conditions with greater bone volume affected by higher strains. Although evident changes due to mal-rotation were observed, the stresses do not suggest a local plastic deformation of the PE-Inlay. The strains values within most of the tibia component-tibia bone interface were in the physiological strain zone and no significant bone changes would be expected. The physiological cut on the articular aspect showed no detrimental effect compared to the horizontal implant.

The relevance of mineralization lag time in the evaluation of histologic changes in renal osteodystrophy.

PubMed

Libbey, N P; Chazan, J A; London, M R; Pono, L; Abuelo, J G

1993-04-01

We examined bone biopsies from 47 patients on chronic hemodialysis, and analyzed the histomorphometric and biochemical findings and histologic quantitation of bone aluminium, looking primarily at mineralization lag time (Mlt) to evaluate its usefulness in categorization of renal osteodystrophy (ROD). The patients were categorized as having either relatively normal Mlt (< 35 days, n = 21 patients), moderately prolonged Mlt (35-100 days, n = 13 patients) or markedly prolonged Mlt (> 100 days, n = 13 patients). The group with relatively normal Mlt showed significantly higher C-terminal parathyroid hormone (PTHc) levels (26,141 +/- 19,270 vs 7,226 +/- 6,073 and 4,434 +/- 4,000 pg/ml) than the moderately or markedly prolonged Mlt groups (p < .01) and was associated with histologic characteristics of osteitis fibrosa or mild hyperparathyroidism (BFR/BS range 0.146-0.947 mcm3/mcm2/d). The group with markedly prolonged Mlt included one patient with classic and 11 with adynamic osteomalacia (BFR/BS range 0.009-0.099) and had greater bone aluminum (Al.S/OS 35.3 +/- 26.7% vs 7.2 +/- 9.0%) than the normal Mlt group (p < .01). The group with moderately prolonged Mlt included two patients with aplastic bone disease (Mlt 80.0 and 84.6 days, and Al.S/OS 100.0 and 72.3%) and 11 patients with features of hyperparathyroidism and osteomalacia (BFR/BS range 0.068-0.243) with variable but generally intermediate bone aluminum deposition (Al.S/OS 22.5 +/- 19.9%). Like BFR/BS and other dynamic parameters Mlt correlates with morphologic types of ROD which primarily reflect bone turnover, but it may also suggest varying degrees of mineralization impairment in a spectrum ranging from high to low turnover types of ROD. Its usefulness in this respect should not be overlooked.

Anatomical Variation of the Tarsus in Common Inbred Mouse Strains.

PubMed

Richbourg, Heather A; Martin, Matthew J; Schachner, Emma R; McNulty, Margaret A

2017-03-01

Rodent models are used for a variety of orthopedic research applications; however, anatomy references include mostly artistic representations. Advanced imaging techniques, including micro-computed tomography (microCT), can provide more accurate representations of subtle anatomical characteristics. A recent microCT atlas of laboratory mouse (Mus musculus) anatomy depicts the central and tarsal bone III (T3) as a single bone, differing from previous references. Fusion of tarsal bones is generally characterized as pathological secondary to mutations associated with growth factors, and normal variation has not been documented in the mouse tarsus. Therefore, it is unclear if this fusion is a normal or a pathological characteristic. The aim of this study is to characterize the tarsus of the laboratory mouse and compare it to the rat and selected outgroup species (i.e., white-footed mouse) via microCT and histology to determine if the central and T3 are separate or fused into a single bone. Laboratory mice (C57/Bl6 [n = 17] and BalbC [n = 2]) and rats (n = 5) were scanned with microCT. A representative laboratory mouse from each strain was evaluated histologically via serial sagittal sections through the mid-tarsus. General pedal anatomy was similar between all species; however, the central and T3 bones were fused in all laboratory mice but not the rat or white-footed mouse. A band of hyaline cartilage was identified within the fused bone of the laboratory mice. We conclude that the fusion found is a normal characteristic in laboratory mice, but timing of the fusion remains ambiguous. Anat Rec, 300:450-459, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cartilage degeneration in the human patellae and its relationship to the mineralisation of the underlying bone: a key to the understanding of chondromalacia patellae and femoropatellar arthrosis?

PubMed

Eckstein, F; Putz, R; Müller-Gerbl, M; Steinlechner, M; Benedetto, K P

1993-01-01

According to the literature subchondral bone plays a significant role in the transmission of load through joints and in the pathogenesis of osteoarthrosis. Therefore the degeneration of the articular cartilage was investigated in the patellae from 30 dissecting-room specimens and of 20 patients, previously submitted to arthroscopy, and subchondral mineralisation of their underlying bone was at the same time assessed by means of CT osteoabsorptiometry. Lateral cartilage lesions were localised over highly mineralised subchondral bone; these appear to be due to long-term stress. They were mainly found in the older specimens and showed a high rate of progression with increasing age. Medially localised cartilage lesions, on the other hand, were situated in a transitional region between moderate and slight subchondral mineralisation; they may be caused by infrequent stress peaks and by shear stress in the articular cartilage, the very medial part of the joint being deprived of mechanical stimulation for much of the time. These lesions were to be found predominantly in the younger specimens and showed little progress with advancing age. Patients with lateral cartilage degeneration exhibited higher, patients with medial chondromalacia patellae lower mineralisation than normals. Their density patterns therefore indicate a different mechanical pathogenesis of the cartilage lesions in the lateral and medial facet. It could be shown that CT osteoabsorptiometry allows an assessment of the mechanical situation, present in individual femoro-patellar joints, and that this situation is highly relevant for the pathogenesis of patellar cartilage degeneration.

Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro

PubMed Central

Elbaz, Alexandre; Wu, Xiying; Rivas, Daniel; Gimble, Jeffrey M; Duque, Gustavo

2010-01-01

Abstract Although increased bone marrow fat in age-related bone loss has been associated with lower trabecular mass, the underlying mechanism responsible remains unknown. We hypothesized that marrow adipocytes exert a lipotoxic effect on osteoblast function and survival through the reversible biosynthesis of fatty acids (FA) into the bone marrow microenvironment. We have used a two-chamber system to co-culture normal human osteoblasts (NHOst) with differentiating pre-adipocytes in the absence or presence of an inhibitor of FA synthase (cerulenin) and separated by an insert that allowed unidirectional trafficking of soluble factors only and prevented direct cell–cell contact. Supernatants were assayed for the presence of FA using mass spectophotometry. After 3 weeks in co-culture, NHOst showed significantly lower levels of differentiation and function based on lower mineralization and expression of alkaline phosphatase, osterix, osteocalcin and Runx2. In addition, NHOst survival was affected by the presence of adipocytes as determined by MTS-formazan and TUNEL assays as well as higher activation of caspases 3/7. These toxic effects were inhibited by addition of cerulenin. Furthermore, culture of NHOst with either adipocyte-conditioned media alone in the absence of adipocytes themselves or with the addition of the most predominant FA (stearate or palmitate) produced similar toxic results. Finally, Runx2 nuclear binding was affected by addition of either adipocyte conditioned media or FA into the osteogenic media. We conclude that the presence of FA within the marrow milieu can contribute to the age-related changes in bone mass and can be prevented by the inhibition of FA synthase. PMID:19382912

Comparing three novel endpoints for developmental osteotoxicity in the embryonic stem cell test

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nieden, Nicole I. zur, E-mail: nicole.zurnieden@ucr.ed; Department of Cell Biology and Neuroscience and Stem Cell Center, University of California Riverside, Riverside, CA 92521; Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig

Birth defects belong to the most serious side effects of pharmaceutical compounds or environmental chemicals. In vivo, teratogens most often affect the normal development of bones, causing growth retardation, limb defects or craniofacial malformations. The embryonic stem cell test (EST) is one of the most promising models that allow the in vitro prediction of embryotoxicity, with one of its endpoints being bone tissue development. The present study was designed to describe three novel inexpensive endpoints to assess developmental osteotoxicity using the model compounds penicillin G (non-teratogenic), 5-fluorouracil (strong teratogen) and all-trans retinoic acid (bone teratogen). These three endpoints were: quantificationmore » of matrix incorporated calcium by (1) morphometric analysis and (2) measurement of calcium levels as well as (3) activity of alkaline phosphatase, an enzyme involved in matrix calcification. To evaluate our data, we have compared the concentration curves and resulting ID{sub 50}s of the new endpoints with mRNA expression for osteocalcin. Osteocalcin is an exclusive marker found only in mineralized tissues, is regulated upon compound treatment and reliably predicts the potential of a chemical entity acting as a bone teratogen. By comparing the new endpoints to quantitative expression of osteocalcin, which we previously identified as suitable to detect developmental osteotoxicity, we were ultimately able to illustrate IMAGE analysis and Ca{sup 2+} deposition assays as two reliable novel endpoints for the EST. This is of particular importance for routine industrial assessment of novel compounds as these two new endpoints may substitute previously used molecular read-out methods, which are often costly and time-consuming.« less

Metabolic bone disease in chronic renal failure. II. Renal transplant patients.

PubMed Central

Huffer, W. E.; Kuzela, D.; Popovtzer, M. M.; Starzl, T. E.

1975-01-01

Trabecular vertebral bone of renal transplant patients was quantitatively compared with bone from normal individuals and dialyzed and nondialyzed patienets with chronic renal failure reported in detail in an earlier study. Long- and short-term transplant patients have increased bone resorption and mineralization defects similar to renal osteodystrophy in dialyzed and nondialyzed patients. However, in transplant patients the magnitude of resorption is greater, and bone volume tends to decrease rather than increase. Resorptive activity in transplant patients is maximal during the first year after transplantation. Bone volume decreases continuously for at least 96 months after transplantation. Only decreased bone volume correlated with success or failure of the renal transplant. Morphologic findings in this study correlate with other clinical and morphologic data to suggest that reduction in bone volume in transplant patients results from a combination of persistent hyperparathyroidism and suppression of bone formation by steroid therapy. Images Fig 1 PMID:1091152

Maturation of bone and dentin matrices in rats flown on the Soviet biosatellite Cosmos 1887

NASA Technical Reports Server (NTRS)

Simmons, D. J.; Grynpas, M. D.; Rosenberg, G. D.

1990-01-01

We have studied the chemistry, hydroxyapatite crystal size, and maturational changes in bone and dentin from rats exposed to microgravity for 12 days in a Soviet biosatellite (Cosmos 1887). Bone ash was reduced in vertebrae (L5) but not in the non-weight-bearing calvaria or mandibles. All tissues had a relatively normal percentage composition of Ca, P, and Mg. Nevertheless, flight rat calvaria and vertebral tissues tended to exhibit lower Ca/P and higher Ca/Mg ratios that any of their weight-matched controls groups, and gradient density analysis (calvaria) indicated a strong shift to the fractions lower specific gravity that was commensurate with impaired rates of matrix-mineral maturation. X-ray diffraction data were confirmatory. Bone hydroxyapatite crystal growth in the mandibles of flight rats was preferentially altered in such a way as to reduce their size (C-axis dimension). But in the mandibular diastemal region devoid of muscle attachments, flight rat bone and dentin were normal with respect to the Ca, P, Mg, and Zn concentrations and Ca/P and Ca/Mg ratios of age-matched controls. These observations affirm the concept that while microgravity most adversely affects the maturation of newly formed matrix and mineral moieties in weight-bearing bone, such effects occur throughout the skeleton.

Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: Indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17

PubMed Central

Bank, Ruud A.; Robins, Simon P.; Wijmenga, Cisca; Breslau-Siderius, Liesbeth J.; Bardoel, Alfons F. J.; Van der Sluijs, Hans A.; Pruijs, Hans E. H.; TeKoppele, Johan M.

1999-01-01

Bruck syndrome is characterized by the presence of osteoporosis, joint contractures, fragile bones, and short stature. We report that lysine residues within the telopeptides of collagen type I in bone are underhydroxylated, leading to aberrant crosslinking, but that the lysine residues in the triple helix are normally modified. In contrast to bone, cartilage and ligament show unaltered telopeptide hydroxylation as evidenced by normal patterns of crosslinking. The results provide compelling evidence that collagen crosslinking is regulated primarily by tissue-specific enzymes that hydroxylate only telopeptide lysine residues and not those destined for the helical portion of the molecule. This new family of enzymes appears to provide the primary regulation for controlling the different pathways of collagen crosslinking and explains why crosslink patterns are tissue specific and not related to a genetic collagen type. A genome screen identified only a single region on chromosome 17p12 where all affected sibs shared a cluster of haplotypes identical by descent; this might be the BS (Bruck syndrome) locus and consequently the region where bone telopeptidyl lysyl hydroxylase is located. Further knowledge of this enzyme has important implications for conditions where aberrant expression of telopeptide lysyl hydroxylase occurs, such as fibrosis and scar formation. PMID:9927692

Synchrotron imaging reveals bone healing and remodelling strategies in extinct and extant vertebrates

PubMed Central

Anné, Jennifer; Edwards, Nicholas P.; Wogelius, Roy A.; Tumarkin-Deratzian, Allison R.; Sellers, William I.; van Veelen, Arjen; Bergmann, Uwe; Sokaras, Dimosthenis; Alonso-Mori, Roberto; Ignatyev, Konstantin; Egerton, Victoria M.; Manning, Phillip L.

2014-01-01

Current understanding of bone healing and remodelling strategies in vertebrates has traditionally relied on morphological observations through the histological analysis of thin sections. However, chemical analysis may also be used in such interpretations, as different elements are known to be absorbed and used by bone for different physiological purposes such as growth and healing. These chemical signatures are beyond the detection limit of most laboratory-based analytical techniques (e.g. scanning electron microscopy). However, synchrotron rapid scanning–X-ray fluorescence (SRS–XRF) is an elemental mapping technique that uniquely combines high sensitivity (ppm), excellent sample resolution (20–100 µm) and the ability to scan large specimens (decimetre scale) approximately 3000 times faster than other mapping techniques. Here, we use SRS–XRF combined with microfocus elemental mapping (2–20 µm) to determine the distribution and concentration of trace elements within pathological and normal bone of both extant and extinct archosaurs (Cathartes aura and Allosaurus fragilis). Results reveal discrete chemical inventories within different bone tissue types and preservation modes. Chemical inventories also revealed detail of histological features not observable in thin section, including fine structures within the interface between pathological and normal bone as well as woven texture within pathological tissue. PMID:24806709

Cervical digit in a child

PubMed Central

Tong, Min-Ji; Xiang, Guang-Heng; He, Zi-Li; Xu, Hua-Zi; Tian, Nai-Feng

2017-01-01

Abstract Background: A “digit-like” bone is a rare developmental anomaly that is usually seen in the pelvic or thoracic regions. Such an anomaly in the cervical spine is extremely rare and few cases have been reported. We present a patient with an anomalous bone posterior to a cervical vertebra. The patient was admitted to our hospital with a gradually growing hard neck mass and esthetic complaints. Physical examination, radiographs, reconstructed computed tomography, and magnetic resonance imaging revealed a digit-like bone posterior to the cervical spine. The patient was diagnosed with a “cervical digit.” Through a posterior midline approach, the anomalous bone was excised because of its gradually increasing size and esthetic complaints. Results: Intraoperatively, the bony mass was found to have a pseudoarticulation with the spinous process of C5 (the fifth cervical vertebra). The specimen consisted of normal bone and cartilage. The child returned to a normal life postoperatively with no symptoms. There was no recurrence at the 2-year follow-up. Conclusion: A congenital cervical digit is a rare deformity. A detailed clinical workup and advanced imaging examinations are useful for diagnosing such conditions. Esthetic complaints contribute to surgical indications. This is the first cervical digit managed with surgical excision of the anomalous bone and had a favorable outcome. PMID:29390517

The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli

NASA Technical Reports Server (NTRS)

Rubin, C.; Xu, G.; Judex, S.

2001-01-01

It is generally believed that mechanical signals must be large in order to be anabolic to bone tissue. Recent evidence indicates, however, that extremely low-magnitude (<10 microstrain) mechanical signals readily stimulate bone formation if induced at a high frequency. We examined the ability of extremely low-magnitude, high-frequency mechanical signals to restore anabolic bone cell activity inhibited by disuse. Adult female rats were randomly assigned to six groups: baseline control, age-matched control, mechanically stimulated for 10 min/day, disuse (hind limb suspension), disuse interrupted by 10 min/day of weight bearing, and disuse interrupted by 10 min/day of mechanical stimulation. After a 28 day protocol, bone formation rates (BFR) in the proximal tibia of mechanically stimulated rats increased compared with age-matched control (+97%). Disuse alone reduced BFR (-92%), a suppression only slightly curbed when disuse was interrupted by 10 min of weight bearing (-61%). In contrast, disuse interrupted by 10 min per day of low-level mechanical intervention normalized BFR to values seen in age-matched controls. This work indicates that this noninvasive, extremely low-level stimulus may provide an effective biomechanical intervention for the bone loss that plagues long-term space flight, bed rest, or immobilization caused by paralysis.

A systematic quality assurance study in bone densitometry devices

NASA Astrophysics Data System (ADS)

Tuncman, Duygu; Kovan, Hatice; Kovan, Bilal; Demir, Bayram; Turkmen, Cuneyt

2015-07-01

Osteoporosis is the most common metabolic bone disease and can result in devastating physical, psychosocial, and economic consequences. It occurs in women after menopause and affects most elderly. Dual-energy x-ray absorptiometry (DXA) is currently the most widely used method for the measurement of areal Bone Mineral Density (BMD) (g/cm2) .DXA is based on the variable absorption of X-ray by the different body components and uses high and low energy X-ray photons. There are two important values in the assessment of the DXA. These values are T-score and Z-score. The T-score is calculated by taking the difference between a patient's measured BMD with the mean BMD of the young normal population, matched for gender and ethnicity, and then by dividing the difference with the standard deviation (SD) of the BMD of the young normal population. T-score and also Z-score are directly depends on the Bone Mineral Density (BMD). BMD measurements should be made periodically in a patient life. But mostly, it is not possible with the same device. Therefore, in this study, for the quality assurance of bone densitometry devices, we evaluated the BMD results measured in the different Bone Densitometry (DXA) devices using a spine phantom.

Differential diagnosis of an unusual shoulder articular lesion in an ancient domestic dog (Canis lupus familiaris L., 1758).

PubMed

Lawler, D F; Rubin, D A; Evans, R H; Hildebolt, C F; Smith, K E; Widga, C; Martin, T J; Siegel, M; Sackman, J E; Smith, G K; Patel, T K

2013-12-01

A proximal humeral articular surface from an ancient domestic dog deliberate burial was examined during survey of small mammal bones from a prehistoric early Late Woodland archeological site. An unusual lesion on the caudolateral articular surface prompted micro-computed tomography to define detailed structure. Results indicate cortical or immature woven bone arising subchondrally, replacing normal trabeculae, extending through a breach in the cortical surface, and having sharp transition with surrounding normal bone. Organized bone within the lesion indicates that the dog lived for months-to-years following insult. Differential diagnoses initially included: sharp penetrating trauma; intrinsic or extrinsic blunt fracturing force; osteochondrosis or complication of an osteochondral lesion; unusual osteoarthritis; and neoplasia. Computed tomography ruled out normal or unusual osteoarthritis, and neoplasia. The nature and small size of the lesion, relatively small size of the dog, and lack of evidence for complicating infection, suggest against sharp penetrating trauma as a sole cause. The most plausible differential diagnoses include: uncommon fracture-producing force in a companion animal, and blunt intrinsic or extrinsic force causing fracture at a weak point, such as an early osteochondral lesion, that was obliterated by healing. Combined gross examination, micro-computed tomography, and archeological-anthropological influences facilitated refinement of differential diagnosis. Copyright © 2013 Elsevier Inc. All rights reserved.

MRI assessment of local acute radiation syndrome.

PubMed

Weber-Donat, G; Amabile, J-C; Lahutte-Auboin, M; Potet, J; Baccialone, J; Bey, E; Teriitehau, C; Laroche, P

2012-12-01

To describe local acute radiation syndrome and its radiological imaging characteristics. We performed a retrospective study of patients who had suffered skin and deeper radiation damage who were investigated by magnetic resonance imaging (MRI). We compared the clinical findings, C-reactive protein (CRP) levels and MRI results. A total of 22 MRI examinations were performed between 2005 and 2010 in 7 patients; 6 patients had increased CRP levels and MRI abnormalities. They were treated by surgery and local cellular therapy. One patient had no CRP or MRI abnormalities, and had a spontaneous good outcome. Eighteen abnormal MR examinations demonstrated high STIR signal and/or abnormal enhancement in the dermis and muscle tissues. Three MRI examinations demonstrated skeletal abnormalities, consistent with radionecrosis. The four normal MRI examinations were associated only with minor clinical manifestations such as pain and pigmentation disorders. MRI seems to be a useful and promising imaging investigation in radiation burns management i.e. initial lesion evaluation, treatment evaluation and complication diagnosis. MRI findings correlated perfectly with clinical stage and no false negative examinations were obtained. In particular, the association between normal MRI and low CRP level seems to be related to good outcome without specific treatment. Local acute radiation syndrome (radioepidermitis) mainly affects the skin and superficial tissues. MRI findings correspond with clinical stage (with a strong negative predictive value). MRI outperformed X-ray examination for the diagnosis of bone radionecrosis. Diffusion-weighted imaging shows low ADC in bone and soft tissue necrosis. Perfusion sequence allows assessment of tissue microcirculation impairment.

Pre-surgical CT-assessment of neurogenic myositis ossificans of the hip and risk factors of recurrence: a series of 101 consecutive patients.

PubMed

Law-Ye, Bruno; Hangard, Chloé; Felter, Adrien; Safa, Dominique; Denormandie, Philippe; Genet, François; Carlier, Robert-Yves

2016-10-18

Neurogenic Myositis Ossificans (NMO) is a rare disabling pathology characterized by peri-articular heterotopic ossifications following severe peripheral or central nervous system injuries. It results in ankylosis and vessels or nerves compressions. Our study aimed to describe the pre-operative findings of patients with NMO of the hip using biphasic computerized tomography (CT). Between 2006 and 2012, we retrospectively analyzed 101 consecutive patients with hip NMO. We analyzed all CTs and surgical reports following a standardized grid depicting the osteoma and its relations with joint capsule, vessels and nerves and bone mineralization. We studied surgical complications and recurrence during follow-up. Chi2-test and Fischer's test were performed to compare qualitative values with respectively normal and non-normal distribution. Quantitative values were analyzed with a one factor analysis of variance (ANOVA) test. Agreement between pre-surgical CT and surgical observations was evaluated with Cohen's kappa test. Correlation between pre-operative CT and surgical findings was excellent regarding relationships with vessels (0,82) and was good concerning relationships with sciatic nerves (0.62) and with joint capsule (0.68). Close contact or disruption of joint capsule (p = 0.005), joint space narrowing (p = 0.007) and bone demineralization (p < 0.001) were correlated with NMO recurrence. Biphasic enhanced-CT allows pre-operative assessment of NMO with good correlation to surgical observations and helps prevent surgical complications.

SU-E-T-13: A Comparative Dosimetric Study On Radio-Dynamic Therapy for Pelvic Cancer Treatment: Strategies for Bone Marrow Dose and Volume Reduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, C; Renmin Hospital of Wuhan University, Wuhan, Hubei Province; Wang, B

Purpose: Radio-dynamic therapy (RDT) is a potentially effective modality for local and systemic cancer treatment. Using RDT, the administration of a radio-sensitizer enhances the biological effect of high-energy photons. Although the sensitizer uptake ratio of tumor to normal tissue is normally high, one cannot simply neglect its effect on critical structures. In this study, we aim to explore planning strategies to improve bone marrow sparing without compromising the plan quality for RDT treatment of pelvic cancers. Methods: Ten cervical and ten prostate cancer patients who previously received radiotherapy at our institution were selected for this study. For each patient, ninemore » plans were created using the Varian Eclipse treatmentplanning-system (TPS) with 3D-CRT, IMRT, and VMAT delivery techniques containing various gantry angle combinations and optimization parameters (dose constraints to the bone marrow). To evaluate the plans for bone marrow sparing, the dose-volume parameters V5, V10, V15, V20, V30, and V40 for bone marrow were examined. Effective doseenhancement factors for the sensitizer were used to weigh the dose-volume histograms for various tissues from individual fractions. Results: The planning strategies had different impacts on bone marrow sparing for the cervical and prostate cases. For the cervical cases, provided the bone marrow constraints were properly set during optimization, the dose to bone marrow sparing was found to be comparable between different IMRT and VMAT plans regardless of the gantry angle selection. For the prostate cases, however, careful selection of gantry angles could dramatically improve the bone marrow sparing, although the dose distribution in bone marrow was clinically acceptable for all prostate plans that we created. Conclusion: For intensity-modulated RDT planning for cervical cancer, planners should set bone marrow constraints properly to avoid any adverse damage, while for prostate cancer one can carefully select gantry angles to improve bone marrow sparing when necessary.« less

Age-associated bone loss and intraskeletal variability in the Imperial Romans.

PubMed

Cho, Helen; Stout, Sam Darrel

2011-01-01

An Imperial Roman sample from the Isola Sacra necropolis (100-300 A.D.) offered an opportunity to histologically examine bone loss and intraskeletal variability in an urban archaeological population. Rib and femur samples were analyzed for static indices of bone remodeling and measures of bone mass. The Imperial Romans experienced normal age-associated bone loss via increased intracortical porosity and endosteal expansion, with females exhibiting greater bone loss and bone turnover rates than in males. Life events such as menopause and lactation coupled with cultural attitudes and practices regarding gender and food may have led to increased bone loss in females. Remodeling dynamics differ between the rib and femur and the higher remodeling rates in the rib may be attributed to different effective age of the adult compacta or loading environment. This study demonstrates that combining multiple methodologies to examine bone loss is necessary to shed light on the biocultural factors that influence bone mass and bone loss.

Molecular Abnormalities Underlying Bone Fragility in Chronic Kidney Disease

PubMed Central

Iwasaki, Yoshiko; Kazama, Junichiro James

2017-01-01

Prevention of bone fractures is one goal of therapy for patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney Disease: Improving Global Outcomes guidelines. CKD patients, including those on hemodialysis, are at higher risk for fractures and fracture-related death compared to people with normal kidney function. However, few clinicians focus on this issue as it is very difficult to estimate bone fragility. Additionally, uremia-related bone fragility has a more complicated pathological process compared to osteoporosis. There are many uremia-associated factors that contribute to bone fragility, including severe secondary hyperparathyroidism, skeletal resistance to parathyroid hormone, and bone mineralization disorders. Uremia also aggravates bone volume loss, disarranges microarchitecture, and increases the deterioration of material properties of bone through abnormal bone cells or excess oxidative stress. In this review, we outline the prevalence of fractures, the interaction of CKD-MBD with osteoporosis in CKD patients, and discuss possible factors that exacerbate the mechanical properties of bone. PMID:28421193

Selenium in bone health: roles in antioxidant protection and cell proliferation.

PubMed

Zeng, Huawei; Cao, Jay J; Combs, Gerald F

2013-01-10

Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Such findings may relate to roles of Se in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Elucidation of the mechanisms by which Se supports these cellular processes can lead to a better understanding of the role of this nutrient in normal bone metabolism. This article reviews the current knowledge concerning the molecular functions of Se relevant to bone health.

Selenium in Bone Health: Roles in Antioxidant Protection and Cell Proliferation

PubMed Central

Zeng, Huawei; Cao, Jay J.; Combs, Gerald F.

2013-01-01

Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Such findings may relate to roles of Se in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Elucidation of the mechanisms by which Se supports these cellular processes can lead to a better understanding of the role of this nutrient in normal bone metabolism. This article reviews the current knowledge concerning the molecular functions of Se relevant to bone health. PMID:23306191

Intercomparison of techniques for the non-invasive measurement of bone mass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohn, S.H.

1981-01-01

A variety of methods are presently available for the non-invasive measurement of bone mass of both normal individuals and patients with metabolic disorders. Chief among these methods are radiographic techniques such as radiogrammetry, photon absorptiometry, computer tomography, Compton scattering and neutron activation analysis. In this review, the salient features of the bone measurement techniques are discussed along with their accuracy and precision. The advantages and disadvantages of the various techniques for measuring bone mass are summarized. Where possible, intercomparisons are made of the various techniques.

Fundamentals of biomechanics in tissue engineering of bone.

PubMed

Athanasiou, K A; Zhu, C; Lanctot, D R; Agrawal, C M; Wang, X

2000-08-01

The objective of this review is to provide basic information pertaining to biomechanical aspects of bone as they relate to tissue engineering. The review is written for the general tissue engineering reader, who may not have a biomechanical engineering background. To this end, biomechanical characteristics and properties of normal and repair cortical and cancellous bone are presented. Also, this chapter intends to describe basic structure-function relationships of these two types of bone. Special emphasis is placed on salient classical and modern testing methods, with both material and structural properties described.

[Differential expression genes of bone tissues surrounding implants in diabetic rats by gene chip].

PubMed

Wang, Xin-xin; Ma, Yue; Li, Qing; Jiang, Bao-qi; Lan, Jing

2012-10-01

To compare mRNA expression profiles of bone tissues surrounding implants between normal rats and rats with diabetes using microarray technology. Six Wistar rats were randomly selected and divided into normal model group and diabetic group. Diabetic model condition was established by injecting Streptozotocin into peritoneal space. Titanium implants were implanted into the epiphyseal end of the rats' tibia. Bone tissues surrounding implant were harvested and sampled after 3 months to perform comprehensive RNA gene expression profiling, including 17983 for genome-wide association study.GO analysis was used to compare different gene expression and real-time PCR was used to confirm the results on core samples. The results indicated that there were 1084 differential gene expression. In the diabetic model, there were 352 enhanced expression genes, 732 suppressed expression genes. GO analysis involved 1154 different functional type. Osteoblast related gene expressions in bone tissue samples of diabetic rats were decreased, and lipid metabolism pathway related gene expression was increased.

Normal Collagen and Bone Production by Gene-targeted Human Osteogenesis Imperfecta iPSCs

PubMed Central

Deyle, David R; Khan, Iram F; Ren, Gaoying; Wang, Pei-Rong; Kho, Jordan; Schwarze, Ulrike; Russell, David W

2012-01-01

Osteogenesis imperfecta (OI) is caused by dominant mutations in the type I collagen genes. In principle, the skeletal abnormalities of OI could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. Here, we develop this approach by isolating mesenchymal cells from OI patients, inactivating their mutant collagen genes by adeno-associated virus (AAV)-mediated gene targeting, and deriving induced pluripotent stem cells (iPSCs) that were expanded and differentiated into mesenchymal stem cells (iMSCs). Gene-targeted iMSCs produced normal collagen and formed bone in vivo, but were less senescent and proliferated more than bone-derived MSCs. To generate iPSCs that would be more appropriate for clinical use, the reprogramming and selectable marker transgenes were removed by Cre recombinase. These results demonstrate that the combination of gene targeting and iPSC derivation can be used to produce potentially therapeutic cells from patients with genetic disease. PMID:22031238

Successful subtotal orbitectomy in a cat with osteoma

PubMed Central

Corgozinho, Katia B; Cunha, Simone CS; Siqueira, Ricardo S; Souza, Heloisa JM

2015-01-01

Case summary A 14-year-old Siamese neutered male cat was evaluated for anorexia and a left periorbital mass. Skull radiographic findings showed a well-defined lesion resembling new compact bone formation without destruction. A subtotal orbitectomy was indicated. The tumor was removed intact with a normal tissue margin of at least 1 cm. There were no postsurgical complications. Histopathologic examination revealed an osteoma. The cat returned to normal appetite and activity 15 days after surgery. Six months after surgery, there were no gross signs of recurrence. Relevance and novel information Periorbital tumors are infrequently diagnosed in companion animals and most are malignant. In this case, the diagnosis was orbital osteoma. The most commonly affected bone for osteoma in cats is the mandibular bone; few cases have been identified in orbital bones. Orbital surgery has the potential to be challenging owing to complex anatomy, difficult exposure and the tendency to bleed. Surgical complications are common. In this case, although the disease was advanced, subtotal orbitectomy was successfully performed. PMID:28491397

Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice.

PubMed

Kim, Misung; Na, Woori; Sohn, Cheongmin

2013-09-01

Several reports suggest that obesity is a risk factor for osteoporosis. Vitamin K plays an important role in improving bone metabolism. This study examined the effects of vitamin K1 and vitamin K2 supplementation on the biochemical markers of bone turnover and morphological microstructure of the bones by using an obese mouse model. Four-week-old C57BL/6J male mice were fed a 10% fat normal diet group or a 45% kcal high-fat diet group, with or without 200 mg/1000 g vitamin K1 (Normal diet + K1, high-fat diet + K1) and 200 mg/1000 g vitamin K2 (Normal diet + K2, high-fat diet + K2) for 12 weeks. Serum levels of osteocalcin were higher in the high-fat diet + K2 group than in the high-fat diet group. Serum OPG level of the high-fat diet group, high-fat diet + K1 group, and high-fat diet + K2 group was 2.31 ± 0.31 ng/ml, 2.35 ± 0.12 ng/ml, and 2.90 ± 0.11 ng/ml, respectively. Serum level of RANKL in the high-fat diet group was significantly higher than that in the high-fat diet + K1 group and high-fat diet + K2 group (p<0.05). Vitamin K supplementation seems to tend to prevent bone loss in high-fat diet induced obese state. These findings suggest that vitamin K supplementation reversed the high fat diet induced bone deterioration by modulating osteoblast and osteoclast activities and prevent bone loss in a high-fat diet-induced obese mice.

Stationary Apparatus Would Apply Forces of Walking to Feet

NASA Technical Reports Server (NTRS)

Hauss, Jessica; Wood, John; Budinoff, Jason; Correia, Michael; Albrecht, Rudolf

2006-01-01

A proposed apparatus would apply controlled cyclic forces to both feet for the purpose of preventing the loss of bone density in a human subject whose bones are not subjected daily to the mechanical loads of normal activity in normal Earth gravitation. The apparatus was conceived for use by astronauts on long missions in outer space; it could also be used by bedridden patients on Earth, including patients too weak to generate the necessary forces by their own efforts. The apparatus (see figure) would be a modified version of a bicycle-like exercise machine, called the cycle ergometer with vibration isolation system (CEVIS), now aboard the International Space Station. Attached to each CEVIS pedal would be a computer-controlled stress/ vibration exciter connected to the heel portion of a special-purpose pedal. The user would wear custom shoes that would amount to standard bicycle shoes equipped with cleats for secure attachment of the balls of the feet to the special- purpose pedals. If possible, prior to use of the apparatus, the human subject would wear a portable network of recording accelerometers, while walking, jogging, and running. The information thus gathered would be fed to the computer, wherein it would be used to make the exciters apply forces and vibrations closely approximating the forces and vibrations experienced by that individual during normal exercise. It is anticipated that like the forces applied to bones during natural exercise, these artificial forces would stimulate the production of osteoblasts (bone-forming cells), as needed to prevent or retard loss of bone mass. In addition to helping to prevent deterioration of bones, the apparatus could be used in treating a person already suffering from osteoporosis. For this purpose, the magnitude of the applied forces could be reduced, if necessary, to a level at which weak hip and leg bones would still be stimulated to produce osteoblasts without exposing them to the full stresses of walking and thereby risking fracture.

Dosimetric Comparison of Bone Marrow-Sparing Intensity-Modulated Radiotherapy Versus Conventional Techniques for Treatment of Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mell, Loren K.; Tiryaki, Hanifi; Ahn, Kang-Hyun

2008-08-01

Purpose: To compare bone marrow-sparing intensity-modulated pelvic radiotherapy (BMS-IMRT) with conventional (four-field box and anteroposterior-posteroanterior [AP-PA]) techniques in the treatment of cervical cancer. Methods and Materials: The data from 7 cervical cancer patients treated with concurrent chemotherapy and IMRT without BMS were analyzed and compared with data using four-field box and AP-PA techniques. All plans were normalized to cover the planning target volume with the 99% isodose line. The clinical target volume consisted of the pelvic and presacral lymph nodes, uterus and cervix, upper vagina, and parametrial tissue. Normal tissues included bowel, bladder, and pelvic bone marrow (PBM), which comprisedmore » the lumbosacral spine and ilium and the ischium, pubis, and proximal femora (lower pelvis bone marrow). Dose-volume histograms for the planning target volume and normal tissues were compared for BMS-IMRT vs. four-field box and AP-PA plans. Results: BMS-IMRT was superior to the four-field box technique in reducing the dose to the PBM, small bowel, rectum, and bladder. Compared with AP-PA plans, BMS-IMRT reduced the PBM volume receiving a dose >16.4 Gy. BMS-IMRT reduced the volume of ilium, lower pelvis bone marrow, and bowel receiving a dose >27.7, >18.7, and >21.1 Gy, respectively, but increased dose below these thresholds compared with the AP-PA plans. BMS-IMRT reduced the volume of lumbosacral spine bone marrow, rectum, small bowel, and bladder at all dose levels in all 7 patients. Conclusion: BMS-IMRT reduced irradiation of PBM compared with the four-field box technique. Compared with the AP-PA technique, BMS-IMRT reduced lumbosacral spine bone marrow irradiation and reduced the volume of PBM irradiated to high doses. Therefore BMS-IMRT might reduce acute hematologic toxicity compared with conventional techniques.« less

Skeletal response to short-term weightlessness

NASA Technical Reports Server (NTRS)

Wronski, T. J.; Morey-Holton, E. R.

1986-01-01

Male Sprague Dawley rats were placed in orbit for 7 days aboard the space shuttle. Bone histomorphometry was performed in the long bones and lumbar vertebrae of flight rats and compared to data derived from ground based control rats. Trabecular bone mass was not altered during the first week of weightlessness. Strong trends were observed in flight rats for decreased periosteal bone formation in the tibial diaphysis, reduced osteoblast size in the proximal tibia, and decreased osteoblast surface and number in the lumbar vertebra. Histologic indices of bone resorption was relatively normal in flight rats. The results indicate that 7 day of weightlessness are not of sufficient duration to induce histologicaly detectable loss of trabecular bone in rats. However, cortical and trabecular bone formation appear to be diminished during the first week of space flight.

Pathophysiology of osteoporosis: new mechanistic insights.

PubMed

Armas, Laura A G; Recker, Robert R

2012-09-01

Understanding of the pathophysiology of osteoporosis has evolved to include compromised bone strength and skeletal fragility caused by several factors: (1) defects in microarchitecture of trabeculae, (2) defective intrinsic material properties of bone tissue, (3) defective repair of microdamage from normal daily activities, and (4) excessive bone remodeling rates. These factors occur in the context of age-related bone loss. Clinical studies of estrogen deprivation, antiresorptives, mechanical loading, and disuse have helped further knowledge of the factors affecting bone quality and the mechanisms that underlie them. This progress has led to several new drug targets in the treatment of osteoporosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of spaceflight on trabecular bone in rats

NASA Technical Reports Server (NTRS)

Jee, W. S. S.; Wronski, T. J.; Morey, E. R.; Kimmel, D. B.

1983-01-01

Alterations in trabecular bone were observed in growing male Wistar rats after 18.5 days of orbital flight on the COSMOS 1129 biosatellite. Spaceflight induced a decreased mass of mineralized tissue and an increased fat content of the bone marrow in the proximal tibial and humeral metaphyses. The osteoblast population appeared to decline immediately adjacent to the growth cartilage-metaphyseal junction, but osteoclast numbers were unchanged. These results suggested that bone formation may have been inhibited during spaceflight, but resorption remained constant. With the exception of trabecular bone mass in the proximal tibia, the observed skeletal changes returned to normal during a 29-day postflight period.

Purinergic signalling in bone

PubMed Central

Rumney, Robin M. H.; Wang, Ning; Agrawal, Ankita; Gartland, Alison

2012-01-01

Purinergic signaling in bone was first proposed in the early 1990s with the observation that extracellular ATP could modulate events crucial to the normal functioning of bone cells. Since then the expression of nearly all the P2Y and P2X receptors by osteoblasts and osteoclasts has been reported, mediating multiple processes including cell proliferation, differentiation, function, and death. This review will highlight the most recent developments in the field of purinergic signaling in bone, with a special emphasis on recent work resulting from the European Framework 7 funded collaboration ATPBone, as well as Arthritis Research UK and Bone Research Society supported projects. PMID:23049524

Image segmentation and registration for the analysis of joint motion from 3D MRI

NASA Astrophysics Data System (ADS)

Hu, Yangqiu; Haynor, David R.; Fassbind, Michael; Rohr, Eric; Ledoux, William

2006-03-01

We report an image segmentation and registration method for studying joint morphology and kinematics from in vivo MRI scans and its application to the analysis of ankle joint motion. Using an MR-compatible loading device, a foot was scanned in a single neutral and seven dynamic positions including maximal flexion, rotation and inversion/eversion. A segmentation method combining graph cuts and level sets was developed which allows a user to interactively delineate 14 bones in the neutral position volume in less than 30 minutes total, including less than 10 minutes of user interaction. In the subsequent registration step, a separate rigid body transformation for each bone is obtained by registering the neutral position dataset to each of the dynamic ones, which produces an accurate description of the motion between them. We have processed six datasets, including 3 normal and 3 pathological feet. For validation our results were compared with those obtained from 3DViewnix, a semi-automatic segmentation program, and achieved good agreement in volume overlap ratios (mean: 91.57%, standard deviation: 3.58%) for all bones. Our tool requires only 1/50 and 1/150 of the user interaction time required by 3DViewnix and NIH Image Plus, respectively, an improvement that has the potential to make joint motion analysis from MRI practical in research and clinical applications.

Elimination of leukemic cells from human transplants by laser nano-thermolysis

NASA Astrophysics Data System (ADS)

Lapotko, Dmitri; Lukianova, Ekaterina; Potapnev, Michail; Aleinikova, Olga; Oraevsky, Alexander

2006-02-01

We describe novel ex vivo method for elimination of tumor cells from bone marrow and blood, Laser Activated Nano-Thermolysis for Cell Elimination Technology (LANTCET) and propose this method for purging of transplants during treatment of leukemia. Human leukemic cells derived from real patients with different diagnoses (acute lymphoblastic leukemias) were selectively damaged by LANTCET in the experiments by laser-induced micro-bubbles that emerge inside individual specifically-targeted cells around the clusters of light-absorbing gold nanoparticles. Pretreatment of the transplants with diagnosis-specific primary monoclonal antibodies and gold nano-particles allowed the formation of nanoparticle clusters inside leukemic cells only. Electron microscopy found the nanoparticulate clusters inside the cells. Total (99.9%) elimination of leukemic cells targeted with specific antibodies and nanoparticles was achieved with single 10-ns laser pulses with optical fluence of 0.2 - 1.0 J/cm2 at the wavelength of 532 nm without significant damage to normal bone marrow cells in the same transplant. All cells were studied for the damage/viability with several control methods after their irradiation by laser pulses. Presented results have proved potential applicability of developed LANTCET technology for efficient and safe purging (cleaning of residual tumor cells) of human bone marrow and blood transplants. Design of extra-corporeal system was proposed that can process the transplant for one patient for less than an hour with parallel detection and counting residual leukemic cells.

Effects of molgramostim, filgrastim and lenograstim in the treatment of myelokathexis.

PubMed

Černelč, Peter; Andoljšek, Dušan; Mlakar, Uroš; Pretnar, Jože; Modic, Mojca; Zupan, Irena P; Zver, Samo

2000-01-01

Myelokathexis is a very rare form of chronic hereditary neutropenia resulting from impaired neutrophil releasing mechanism in the bone marrow. The recombinant human granulocyte-macrophage (molgramostim) and granulocyte (filgrastim, lenograstim) colony stimulating factors release the mature granulocytes from the bone marrow. We describe a 43-year-old woman suffering from myelokathexis, with the absolute neutrophil count ranging between 0.03 and 1.35 × 10 9 /L. In the period before the introduction of cytokines, the patient had more than 80 major infectious episodes. Since 1991, infections in this patient have been treated with cytokines, given in conjunction with antibiotics. Initially, she received molgramostim in a daily dose of 5 μg/kg subcutaneously, which stimulated the release of granulocytes from her bone marrow, thereby allowing successful treatment of infection. After the development of hypersensitivity, molgramostim was substituted with filgrastim. Finally, lenograstim was given a trial. With all three cytokines, the patient's neutrophil count always attained normal values already 4 hours after subcutaneous application of the drug in a dose of 5 μg/kg, the highest neutrophil levels were measured at 24 hours post-injection, and the neutrophil count was again close to the baseline value 72 hours after the treatment. A slight neutropenia was present 48 hours after the application of filgrastim. We believe that all three cytokines are equally effective in increasing the neutrophil count in venous blood of patients with myelokathexis.

Comparison of ossification of demineralized bone, hydroxyapatite, Gelfoam, and bone wax in cranial defect repair.

PubMed

Papay, F A; Morales, L; Ahmed, O F; Neth, D; Reger, S; Zins, J

1996-09-01

Demineralized bone allografts in the repair of calvarial defects are compared with other common bone fillers. This study uses a video-digitizing radiographic analysis of calvarial defect ossification to determine calcification of bone defects and its relation to postoperative clinical examination and regional controls. The postoperative clinical results at 3 months demonstrated that bony healing was greatest in bur holes filled with demineralized bone and hydroxyapatite. Radiographic analysis demonstrated calcification of demineralized bone-filled defects compared to bone wax- and Gelfoam-filled regions. Hydroxyapatite granules are radiographically dense, thus not allowing accurate measurement of true bone healing. The results suggest that demineralized bone and hydroxyapatite provide better structural support via bone healing to defined calvarial defects than do Gelfoam and bone wax.

A new animal model for bone atrophic nonunion: fixation by external fixator.

PubMed

Kaspar, Katharina; Matziolis, Georg; Strube, Patrick; Sentürk, Ufuk; Dormann, Svenja; Bail, Hermann J; Duda, Georg N

2008-12-01

A new small animal model of bone atrophic nonunion was established for investigating the process of bone regeneration by performing cauterization of the periosteum, removal of the local bone marrow, and stabilization with external fixation. The model allows the creation of an atrophic nonunion without the need for a critical size defect. Furthermore, it provides reproducible, well-defined mechanical conditions and minimized physical interference of the implant with the biological processes in the healing zone. Eighty adult Sprague-Dawley rats received an osteotomy of the left femur, stabilized with an external fixator. In half of the animals, the periosteum proximal and distal to the osteotomy was destroyed by cauterization and the adjacent bone marrow was removed (nonunion group). At 2 and 8 weeks after surgery, radiological, biomechanical, histological, and histomorphometrical analyses showed a typical physiological healing in the control group, while the nonunion group was characterized by resorption of the bone ends with some callus formation distant to the osteotomy. At both time points, the callus was composed of significantly less bone and significantly more connective tissue (p < 0.001). In addition, the torsional strength of the osteotomized femur was significantly less in the nonunion group than in the control group, which was comparable to that of the intact femur (p < 0.001). In conclusion, the present model allows the induction of an atrophic nonunion without the need of a critical size defect. It is reproducible, provides standardized biomechanical conditions, and allows minimized interaction of the implant with the healing zone.

Specialized connective tissue: bone, the structural framework of the upper extremity

PubMed Central

Weatherholt, Alyssa M.; Fuchs, Robyn K.; Warden, Stuart J.

2011-01-01

Bone is a connective tissue containing cells, fibers and ground substance. There are many functions in the body in which the bone participates, such as storing minerals, providing internal support, protecting vital organs, enabling movement, and providing attachment sites for muscles and tendons. Bone is unique because its collagen framework absorbs energy, while the mineral encased within the matrix allows bone to resist deformation. This article provides an overview of the structure and function of bone tissue from a macroscopic to microscopic level and discusses the physiological processes contributing to upper extremity bone health. It concludes by discussing common conditions influencing upper extremity bone health. PMID:22047807

[Tailored cranioplasty using CAD-CAM technology].

PubMed

Vitanovics, Dusán; Major, Ottó; Lovas, László; Banczerowski, Péter

2014-11-30

The majority of cranial defects are results of surgical intervention. The defect must be covered within resonable period of time usually after 4-6 week given the fact that the replacement of bone improve the brain circulation. Number of surgical techniques and materials are available to perform cranioplasty. Due to favorable properties we chosed ultra high molecular weight polyethylene as material. In this paper the authors show a procedure which allows tailored artificial bone replacement using state of art medical and engineering techniques. between 2004 and 2012, 19 patients were operated on cranial bone defect and a total of 22 3D custom-designed implants were implanted. The average age of patients was 35.4 years. In 12 patients we performed primary cranioplasty, while seven patients had the replacement at least once. Later the implants had to be removed due to infection or other causes (bone necrosis, fracture). All patients had native and bone-windowed 1 mm resolution CT. The 3D design was made using the original CT images and with design program. Computer controlled lathe was used to prepare a precise-fitting model. During surgery, the defect was exposed and the implant was fixed to normal bone using mini titanium plates and screws. All of our patients had control CT at 3, 6 and 12 months after surgery and at the same time neurological examination. Twenty-one polyethylene and one titanium implants were inserted. The average follow-up of the patients was 21.5 months, ranged from two to 96 months. We follow 12 patients (63.15%) more than one year. No intraoperative implant modifications had to be made. Each of the 22 implant exactly matched the bone defect proved by CT scan. No one of our patients reported aesthetic problems and we did not notice any kind of aesthetic complication. We had short term complication in three cases due to cranioplasty, subdural, epidural haemorrhage and skin defect. Polyethylene is in all respects suitable for primary and secondary cranioplasty. Combined with 3D CAD- CAM method excellent aesthetic and functional result was achieved. In our study no case of infection occured. Proper preoperative preparation is important.

What Is a Growth Disorder? (For Parents)

MedlinePlus

... hormone, which is essential for normal bone growth. Turner syndrome , one of the most common genetic growth disorders, ... chromosome. In addition to short stature, girls with Turner syndrome usually don't undergo normal sexual development because ...

The effects of chronic alcohol consumption and exercise on the skeleton of adult male rats

NASA Technical Reports Server (NTRS)

Reed, Adam H.; McCarty, Heidi L.; Evans, Glenda L.; Turner, Russell T.; Westerlind, Kim C.

2002-01-01

BACKGROUND: Lifestyle factors are known to affect skeletal development and integrity. Specifically, running has been reported to increase risk of fatigue fractures, whereas chronic alcohol consumption has been shown to reduce bone formation and bone mass. The combined effect of exercise and alcohol on the skeleton has yet to be explored, although alcohol consumption is common among certain physically active populations (e.g., military recruits, college athletes). It was hypothesized that chronic alcohol consumption would accentuate the inherent risk associated with endurance running exercise. METHODS: Six-month-old male Sprague Dawley rats were assigned to one of five groups: baseline, exercise-alcohol diet, exercise-normal diet, sham-alcohol diet, and sham-normal diet. Alcohol-fed rats (35% caloric intake) received a liquid diet ad libitum. Normal animals were pair-fed the identical diet with a maltose dextrin caloric substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16 weeks. Sham rats were placed on a stationary treadmill for matching time periods. Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days before animals were killed. Heart, soleus, and rectus femoris muscles were wet weighed to assess the effects of training. Tibiae were collected for static and dynamic histomorphometric measurements on cancellous and cortical bone. RESULTS: Muscle weights were larger in the exercised rats versus the sham rats. Alcohol had no significant effect on skeletal muscle weight but did result in larger heart weights in both alcohol-treated groups. Cancellous and periosteal bone formation rates were significantly decreased in the alcohol-fed rats versus rats on the normal diet and were associated with a significant reduction in trabecular thickness in the tibial metaphysis. Cortical and cross-sectional areas were also significantly lower in the alcohol-fed groups compared with the non-alcohol-fed groups. Exercise had no significant effect on cancellous or cortical bone measurements. CONCLUSIONS: Chronic alcohol consumption significantly reduced bone formation. Exercise had no effect on the bone and did not attenuate any of the negative effects of alcohol. The results suggest that alcohol consumption weakens the skeleton and increases the incidence of endurance-exercise-related bone injuries. Thus, individuals who are participating in endurance exercise and consuming alcohol may be at greater risk for exercise-related skeletal injuries. Further investigation of the potential for alcohol to induce detrimental effects on the hearts of individuals participating in endurance exercise is indicated.

Bones and Crohn's: estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density.

PubMed

Klaus, J; Reinshagen, M; Adler, G; Boehm, Bo; von Tirpitz, C

2008-10-23

Reduced bone mineral density (BMD) and osteoporosis are frequent in Crohn's disease (CD), but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2), is an established risk factor in postmenopausal osteoporosis. To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers. 111 male CD patients underwent osteodensitometry (DXA) of the spine (L1-L4). Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI). Testosterone (T), dihydrotestosterone (DHT), estradiol (E2), sex hormone binding globulin (SHBG), Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP) were measured in 111 patients and 99 age-matched controls. Patients had lower T, E2 and SHBG serum levels (p < 0.001) compared to age-matched controls. E2 deficiency was seen in 30 (27.0%) and T deficiency in 3 (2.7%) patients but only in 5 (5.1%) and 1 (1%) controls. Patients with E2 deficiency had significantly decreased T and DHT serum levels. Use of corticosteroids for 3 of 12 months was associated with lower E2 levels (p < 0.05). Patients with life-time steroids >10 g had lower BMD. 32 (28.8%) patients showed osteoporosis, 55 (49.5%) osteopenia and 24 (21.6%) had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p < 0.001), and patients with osteoporosis had higher ICTP levels than those with normal BMD. We found an altered hormonal status--i.e. E2 and, to a lesser extent T deficiency--in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.

The Role of Nutrition in the Changes in Bone and Calcium Metabolism During Space Flight

NASA Technical Reports Server (NTRS)

Morey-Holton, Emily R.; Arnaud, Sara B.

1995-01-01

On Earth, the primary purpose of the skeleton is provide structural support for the body. In space, the support function of the skeleton is reduced since, without gravity, structures have only mass and no weight. The adaptation to space flight is manifested by shifts in mineral distribution, altered bone turnover, and regional mineral deficits in weight-bearing bones. The shifts in mineral distribution appear to be related to the cephalic fluid shift. The redistribution of mineral from one bone to another or to and from areas in the same bone in response to alterations in gravitational loads is more likely to affect skeletal function than quantitative whole body losses and gains. The changes in bone turnover appear dependent upon changes in body weight with weight loss tending to increase bone resorption as well as decrease bone formation. During bedrest, the bone response to unloading varies depending upon the routine activity level of the subjects with more active subjects showing a greater suppression of bone formation in the iliac crest with inactivity. Changes in body composition during space flight are predicted by bedrest studies on Earth which show loss of lean body mass and increase tn body fat in adult males after one month. In ambulatory studies on Earth, exercising adult males of the same age, height, g weight, body mass index, and shoe size show significantly higher whole body mineral and lean body mass. than non-exercising subjects. Nutritional preference appears to change with activity level. Diet histories in exercisers and nonexercisers who maintain identical body weights show no differences in nutrients except for slightly higher carbohydrate intake in the exercisers. The absence of differences in dietary calcium in men with higher total body calcium is noteworthy. In this situation, the increased bone mineral content was facilitated by the calcium endocrine system. This regulatory system can be by-passed by raising dietary calcium. Increased calcium intake can increase the calcium content in normally loaded bone. However, bone with a higher calcium content still decreases proportionally to normal bone during unloading. Nutritional requirements in space should be reevaluated with respect to these adaptive changes to loading and physical activity.

Carbon nanotubes functionalized with sodium hyaluronate restore bone repair in diabetic rat sockets.

PubMed

Sá, M A; Andrade, V B; Mendes, R M; Caliari, M V; Ladeira, L O; Silva, E E; Silva, G A B; Corrêa-Júnior, J D; Ferreira, A J

2013-07-01

We evaluated the effects of sodium hyaluronate (HY) and carbon nanotubes functionalized with HY (HY-CNT) on bone repair in the tooth sockets of diabetic rats. Diabetes was induced by streptozotocin (50 mg kg(-1) i.v.), and the sockets were divided into normal control, diabetic control, diabetic treated with HY (1%), and diabetic treated with HY-CNT (100 μg ml(-1)) groups. The sockets were analyzed according to the percentage of bone formation and the number of cell nuclei. The percentage of bone trabeculae was lower in diabetic control animals (11.16 ± 5.10% vs 41.92 ± 6.34% in normal animals) after 14 days. Treating diabetic animals with HY or HY-CNT significantly increased the percentage of neoformed trabeculae (HY: 29.43 ± 3.29%; HY-CNT: 36.90 ± 3.07%). Moreover, the sockets of diabetic animals had an increased number of cell nuclei and HY or HY-CNT reduced this parameter. Our results indicate that HY and HY-CNT restore bone repair in the tooth sockets of diabetic rats, suggesting that these biomaterials are potential adjuvant therapies for the management of diabetes. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of foot shape on the three-dimensional position of foot bones.

PubMed

Ledoux, William R; Rohr, Eric S; Ching, Randal P; Sangeorzan, Bruce J

2006-12-01

To eliminate some of the ambiguity in describing foot shape, we developed three-dimensional (3D), objective measures of foot type based on computerized tomography (CT) scans. Feet were classified via clinical examination as pes cavus (high arch), neutrally aligned (normal arch), asymptomatic pes planus (flat arch with no pain), or symptomatic pes planus (flat arch with pain). We enrolled 10 subjects of each foot type; if both feet were of the same foot type, then each foot was scanned (n=65 total). Partial weightbearing (20% body weight) CT scans were performed. We generated embedded coordinate systems for each foot bone by assuming uniform density and calculating the inertial matrix. Cardan angles were used to describe five bone-to-bone relationships, resulting in 15 angular measurements. Significant differences were found among foot types for 12 of the angles. The angles were also used to develop a classification tree analysis, which determined the correct foot type for 64 of the 65 feet. Our measure provides insight into how foot bone architecture differs between foot types. The classification tree analysis demonstrated that objective measures can be used to discriminate between feet with high, normal, and low arches. Copyright (c) 2006 Orthopaedic Research Society.

Proximal Femur Mechanical Adaptation to Weight Gain in Late Adolescence: A Six-Year Longitudinal Study

PubMed Central

Petit, Moira A; Beck, Thomas J; Hughes, Julie M; Lin, Hung-Mo; Bentley, Christy; Lloyd, Tom

2008-01-01

The effect of weight gain in late adolescence on bone is not clear. Young women who consistently gained weight (n = 23) from 17 to 22 yr of age had increased BMD but a lack of subperiosteal expansion compared with stable weight peers (n = 48). Bone strength increased appropriately for lean mass in both groups but decreased relative to body weight in weight gainers, suggesting increased bone fragility in weight gainers. Introduction Weight gain leading to obesity often starts in adolescence, yet little is known about its effects on bone. We used longitudinal data to examine the effects of weight gain in late adolescence (from 17 to 22 yr of age) on proximal femur BMD, geometry, and estimates of bending strength. Materials and Methods Participants were classified as either weight gainers (WG, n = 23) or stable weight (SW, n = 48) using a random coefficients model. Weight gainers had positive increases in weight (p < 0.05) at each clinic visit from age 17 onward. Proximal femur DXA scans (Hologic QDR 2000) taken annually from 17 to 22 yr of age were analyzed for areal BMD (g/cm2), subperiosteal width (cm), and bone cross-sectional area (CSA) at the proximal femoral shaft. Cortical thickness was measured, and section modulus (Z, cm3) was calculated as a measure of bone bending strength. Total body lean (g) and fat (g) mass were measured from DXA total body scans. Results Over ages 17–22, height remained stable in both groups. Weight remained static in the SW group but increased 14% on average in the WG group (p < 0.05). After controlling for age 17 baseline values, WG had higher BMD (+2.6%), thicker cortices (+3.6%), and greater bone CSA (+2.3%). Increased BMD did not translate to greater increases in bone bending strength (Z). The SW group achieved similar gains in Z by greater subperiosteal expansion. Bone strength index (SI = Z/height) normalized for body weight remained constant in the SW group but decreased significantly in the WG group. In contrast, SI normalized to lean mass did not change over time in either group. Other variables including physical activity, nutrition, and hormone levels (estradiol, testosterone, cortisol) did not differ significantly between groups. Conclusions These data suggest that weight gain in late adolescence may inhibit the periosteal expansion known to normally occur throughout life in long bones, resulting in decreased bone strength relative to body weight. PMID:17937533

Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes

PubMed Central

Morgan, Jennifer L. L.; Skulan, Joseph L.; Gordon, Gwyneth W.; Romaniello, Stephen J.; Smith, Scott M.; Anbar, Ariel D.

2012-01-01

The ability to rapidly detect changes in bone mineral balance (BMB) would be of great value in the early diagnosis and evaluation of therapies for metabolic bone diseases such as osteoporosis and some cancers. However, measurements of BMB are hampered by difficulties with using biochemical markers to quantify the relative rates of bone resorption and formation and the need to wait months to years for altered BMB to produce changes in bone mineral density large enough to resolve by X-ray densitometry. We show here that, in humans, the natural abundances of Ca isotopes in urine change rapidly in response to changes in BMB. In a bed rest experiment, use of high-precision isotope ratio MS allowed the onset of bone loss to be detected in Ca isotope data after about 1 wk, long before bone mineral density has changed enough to be detectable with densitometry. The physiological basis of the relationship between Ca isotopes and BMB is sufficiently understood to allow quantitative translation of changes in Ca isotope abundances to changes in bone mineral density using a simple model. The rate of change of bone mineral density inferred from Ca isotopes is consistent with the rate observed by densitometry in long-term bed rest studies. Ca isotopic analysis provides a powerful way to monitor bone loss, potentially making it possible to diagnose metabolic bone disease and track the impact of treatments more effectively than is currently possible. PMID:22652567

High sodium chloride intake is associated with low bone density in calcium stone-forming patients.

PubMed

Martini, L A; Cuppari, L; Colugnati, F A; Sigulem, D M; Szejnfeld, V L; Schor, N; Heilberg, I P

2000-08-01

Although renal stone disease has been associated with reduced bone mass, the impact of nutrient intake on bone loss is unknown. The present study was undertaken to investigate the influence of nutrient intake on bone density of 85 calcium stone-forming (CSF) patients (47 male and 38 premenopausal females) aged 41+/-11 years (X+/-SD). Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry at the lumbar spine (L2-L4) and femoral neck sites, and low BMD was defined as a T score < -1 (WHO criteria). A 4-day dietary record and a 24-hour urine sample were obtained from each patient for the assessment of nutrient intake and urinary calcium (U(Ca)), sodium (U(Na)), phosphate and creatinine excretion. Forty-eight patients (56%) presented normal BMD and 37 (44%) low BMD. There were no statistical differences regarding age, weight, height, body mass index, protein, calcium and phosphorus intakes between both groups. The mean U(Ca), phosphorus and nitrogen appearance also did not differ between groups. However, there was a higher percentage of hypercalciuria among low vs normal BMD patients (62 vs 33%, p < 0.05). Low BMD patients presented a higher mean sodium chloride (NaCl) intake and excretion (UNa) than normal BMD (14+/-5 vs 12+/-4 g/day and 246+/-85 vs 204+/-68 mEq/day, respectively p < 0.05). The percentage of patients presenting NaCl intake > or = 16 g/day was also higher among low vs normal BMD patients (35 vs 12%, p < 0.05). After adjustment for calcium and protein intakes, age, weight, body mass index, urinary calcium, citrate and uric acid excretion, and duration of stone disease, multiple-regression analysis showed that a high NaCl intake (> or = 16 g/day) was the single variable that was predictive of risk of low bone density in CSF patients (odds ratio = 3.8). These data suggest that reducing salt intake should be recommended for CSF patients presenting hypercalciuria and osteopenia.

Bone modeling and cell-material interface responses induced by nickel-titanium shape memory alloy after periosteal implantation.

PubMed

Ryhänen, J; Kallioinen, M; Tuukkanen, J; Lehenkari, P; Junila, J; Niemelä, E; Sandvik, P; Serlo, W

1999-07-01

The purpose of this study was to evaluate the new bone formation, modeling and cell-material interface responses induced by nickel-titanium shape memory alloy after periosteal implantation. We used a regional acceleratory phenomenon (RAP) model, in which a periosteal contact stimulus provokes an adaptive modelling response. NiTi has thermal shape memory and superelasticity properties uncommon in other implant alloys. So far, there are insufficient data concerning the biocompatibility of NiTi as a bone implant. NiTi was compared to stainless steel (stst) and Ti-6Al-4V. The test implant was placed in contact with the intact femur periosteum, but it was not fixed inside the bone. Histomorphometry with digital image analysis was used to determine the bone formation and resorption parameters. The ultrastructural features of cell-material adhesion were analysed with scanning electron microscopy (FESEM). A typical peri-implant bone wall modelation was seen due to the normal RAP. The maximum new woven bone formation started earlier (2 weeks) in the Ti-6Al-4V group than in the NiTi (P < 0.01) group, but also decreased earlier, and at 8 weeks the NiTi (P < 0.05) and stst (P < 0.005) groups had greater cortical bone width. At 12 and 26 weeks no statistical differences were seen in the histomorphometric values. The histological response of the soft tissues around the NiTi implant was also clearly non-toxic and non-irritating. Cell adhesion and focal contacts were similar between the materials studied by FESEM. We conclude that NiTi had no negative effect on total new bone formation or normal RAP after periosteal implantation during a 26-week follow-up.

High bone turnover elevates the risk of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis

PubMed Central

Ishikawa, Koji; Nagai, Takashi; Sakamoto, Keizo; Ohara, Kenji; Eguro, Takeshi; Ito, Hiroshi; Toyoshima, Yoichi; Kokaze, Akatsuki; Toyone, Tomoaki; Inagaki, Katsunori

2016-01-01

Hypocalcemia is the most common major adverse event in patients with osteoporosis receiving the bone resorption inhibitor denosumab; however, limited information is available regarding risk factors of hypocalcemia. Therefore, this study aimed to identify the risk factors of hypocalcemia induced by denosumab treatment for osteoporosis. We retrospectively reviewed the records of patients who had received initial denosumab supplemented with activated vitamin D for osteoporosis. Serum levels of the following bone turnover markers (BTMs) were measured at baseline: bone-specific alkaline phosphatase (BAP), total N-terminal propeptide of type 1 procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and urinary cross-linked N-telopeptide of type 1 collagen (NTX). Of the 85 denosumab-treated patients with osteoporosis studied, 22 (25.9%) developed hypocalcemia. Baseline serum total P1NP, TRACP-5b, and urinary NTX were significantly higher in patients with hypocalcemia than in those with normocalcemia following denosumab administration (all P<0.01). Multivariate logistic regression analysis revealed that patients with total P1NP >76.5 μg/L, TRACP-5b >474 mU/dL, or urinary NTX >49.5 nmol bone collagen equivalent/mmol creatinine had a higher risk of hypocalcemia (P<0.01). Our study suggests that denosumab may have a greater impact on serum calcium levels in patients with postmenopausal osteoporosis with higher baseline bone turnover than in patients with postmenopausal osteoporosis with normal baseline bone turnover, because maintenance of normal serum calcium in this subgroup is more dependent on bone resorption. Close monitoring of serum calcium levels is strongly recommended for denosumab-treated patients with high bone turnover, despite supplementation with activated vitamin D and oral calcium. PMID:27980413

Treatment of Unicameral Bone Cysts of the Proximal Femur With Internal Fixation Lessens the Risk of Additional Surgery.

PubMed

Wilke, Benjamin; Houdek, Matthew; Rao, Rameshwar R; Caird, Michelle S; Larson, A Noelle; Milbrandt, Todd

2017-09-01

Little data exist to guide the treatment of unicameral bone cysts in the proximal femur. Methods of treatment include corticosteroid injections, curettage and bone grafting, and internal fixation. The authors completed a multi-institutional, retrospective review to evaluate their experience with proximal femoral unicameral bone cysts. They posed the following questions: (1) Does internal fixation reduce the risk of further procedures for the treatment of a unicameral bone cyst? (2) Is radiographic healing faster with internal fixation? Following institutional review board approval, the authors conducted a retrospective review of 36 patients treated for a unicameral bone cyst of the proximal femur at their institutions between 1974 and 2014. Medical records and radiographs were reviewed to identify patient demographics and treatment outcomes. Tumor locations included femoral neck (n=13), intertrochanteric (n=16), and subtrochanteric (n=7). Initial treatment included steroid injection (n=2), curettage and bone grafting (n=9), and internal fixation with curettage and bone grafting (n=25). Mean time was 9 months to radiographic healing and 15 months to return to full activity. The number of patients requiring additional surgeries was increased among those who did not undergo internal fixation. There was no difference in time to radiographic healing. However, time to return to normal activities was reduced if patients had received internal fixation. A significant reduction in additional procedures was observed when patients had been treated with internal fixation. Although this did not influence time to radiographic healing, patients did return to normal activities sooner. Internal fixation should be considered in the treatment of proximal femoral unicameral bone cysts. [Orthopedics. 2017; 40(5):e862-e867.]. Copyright 2017, SLACK Incorporated.

Developmental abnormalities of the occipital bone in human chondrodystrophies (achondroplasia and thanatophoric dwarfism).

PubMed

Marin-Padilla, M; Marin-Padilla, T M

1977-01-01

Specific developmental malformations have been demonstrated in the occipital bone of two chondrodysplastic disorders (achondroplasia and thanatophoric dwarfism). Analysis of these malformations indicates that the occipital bone is primary affected in these disorders. In both cases, the endochondral-derived components of the occipital bone (the basioccipital, the two lateral parts, and the planum nuchale of the squama occipitalis) have failed to grow properly and are smaller and shorter than normal. On the other hand, the planum occipitalis of the squama, which derives from intramembranous ossification, is unaffected. In addition, the nature of these abnormalities indicates that the occipital synchondroses, together with the epiphyseal plates of other bones, are primarily affected in these two chondrodysplasias. The components of the occipital bone formed between the affected synchondroses failed to grow normally. The resulting malformation of the occipital bone is undoubtedly the cause of the shortening of the posterior cerebral fossa and of the considerable narrowing of the foramen magnum often described in these chondrodysplasias. It is postulated that growth disturbances between the affected occipital bone and the unaffected central nervous system results in the inadequacy of the posterior cerebral fossa and the foramen magnum to accommodate the growing brain. Consequently, compression of the brain at the posterior cerebral fossa or the foramen magnum levels could occur and thus lead to neurologic complications such as hydrocephalus and compression of the brain stem. It is suggested that the surgical removal of the fused posterior border of the lateral parts of the occipital bone (partial nuchalectomy) for the purpose of enlarging the narrow foramen magnum may be indicated in those chondrodysplastic children who develop these types of neurologic complications.

Attenuating trabecular morphology associated with low magnesium diet evaluated using micro computed tomography.

PubMed

Tu, Shu-Ju; Wang, Shun-Ping; Cheng, Fu-Chou; Weng, Chia-En; Huang, Wei-Tzu; Chang, Wei-Jeng; Chen, Ying-Ju

2017-01-01

The literature shows that bone mineral density (BMD) and the geometric architecture of trabecular bone in the femur may be affected by inadequate dietary intake of Mg. In this study, we used microcomputed tomography (micro-CT) to characterize and quantify the impact of a low-Mg diet on femoral trabecular bones in mice. Four-week-old C57BL/6J male mice were randomly assigned to 2 groups and supplied either a normal or low-Mg diet for 8weeks. Samples of plasma and urine were collected for biochemical analysis, and femur tissues were removed for micro-CT imaging. In addition to considering standard parameters, we regarded trabecular bone as a cylindrical rod and used computational algorithms for a technical assessment of the morphological characteristics of the bones. BMD (mg-HA/cm3) was obtained using a standard phantom. We observed a decline in the total tissue volume, bone volume, percent bone volume, fractal dimension, number of trabecular segments, number of connecting nodes, bone mineral content (mg-HA), and BMD, as well as an increase in the structural model index and surface-area-to-volume ratio in low-Mg mice. Subsequently, we examined the distributions of the trabecular segment length and radius, and a series of specific local maximums were identified. The biochemical analysis revealed a 43% (96%) decrease in Mg and a 40% (71%) decrease in Ca in plasma (urine excretion). This technical assessment performed using micro-CT revealed a lower population of femoral trabecular bones and a decrease in BMD at the distal metaphysis in the low-Mg mice. Examining the distributions of the length and radius of trabecular segments showed that the average length and radius of the trabecular segments in low-Mg mice are similar to those in normal mice.

Histopathological and biomechanical evaluation of bone healing properties of DBM and DBM-G90 in a rabbit model.

PubMed

Meimandi Parizi, Abdolhamid; Oryan, Ahmad; Haddadi, Shahram; Bigham Sadegh, Amin

2015-01-01

The present study was designed to investigate the effects of DBM and DBM-G90 on bone healing in a rabbit model. Thirty male white albino rabbits were used in this study. An incision was made in all rabbits under general anesthesia directly over the radius in order to expose it. A 10-mm segmental defect was created on the middle portion of each radius. The defects of 10 rabbits (Group I) were filled with DBM Block and Strip (Zimmer, Inc., Warsaw, IN, USA), the defects of 10 rabbits (Group II) were filled with DBM soaked in G90, and the defects of 10 rabbits (Group III/control) were left empty. The rabbits were euthanized at 60 days postoperatively for histopathological and biomechanical evaluation. At the histopathologic level, the defects of the animals in the DBM and DBM-G90 groups showed more advanced healing criteria than those of the control group. In biomechanical findings, there was a statistically significant difference between the injured bones and contralateral normal bones of the control group in terms of measured strength. There was not a statistically significant difference between the treated bones of the DBM and DBM-G90 groups with contralateral normal bones, nor was there a statistically significant difference between the treated bones of the DBM and DBM-G90 groups with the treated bones of the control group, in terms of other biomechanical tests. Based on the histopathological and biomechanical findings, the DBM and DBM-G90 groups demonstrated superior osteogenic potential; however, G90 shows no superiority over DBM on bone healing.

A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.

PubMed

Neven, Ellen; De Schutter, Tineke M; Dams, Geert; Gundlach, Kristina; Steppan, Sonja; Büchel, Janine; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Behets, Geert J

2014-01-01

The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover.

A high-fat diet increases body weight and circulating estradiol concentrations but does not improve bone structural properties in ovariectomized mice.

PubMed

Cao, Jay J; Gregoire, Brian R

2016-04-01

Bone health is influenced by body mass and estrogen. The objective of the study was to determine whether high-fat diet-induced obesity affects bone structure and alters markers of bone turnover in ovariectomized (OVX) mice. We hypothesized that a high-fat diet would increase body weight gain and serum estradiol levels in OVX mice but would not improve bone structural parameter in OVX mice. Thirty-five C57BL/6 mice were either sham operated or OVX at the age of 4 months and then fed either a normal-fat diet (10% energy as fat) or a high-fat diet (45% energy as fat with extra fat from lard) ad libitum for 11 weeks. Ovariectomy increased body weight, serum tartrate-resistant acid phosphatase concentration, and expression of cathepsin K in bone; decreased serum estradiol concentration; and induced significant bone loss manifested by decreased bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number, and trabecular thickness with increased trabecular separation and structural model index (P < .01). The high-fat diet increased body weight (P < .01) in OVX mice and nonsignificantly decreased BV/TV (P = .08) and Conn.D (P = .10). Despite having similar serum estradiol concentrations and higher body weight, OVX mice consuming the high-fat diet had lower BV/TV, Conn.D, trabecular number, trabecular thickness, and higher structural model index and trabecular separation than did sham mice fed the normal-fat diet. These findings indicate that increased body weight and elevated serum estradiol concentration induced by a high-fat diet do not mitigate ovariectomy-induced bone loss in mice. Published by Elsevier Inc.

The influence of the periodontal biotype on peri-implant tissues around immediate implants with and without xenografts. Clinical and micro-computerized tomographic study in small Beagle dogs.

PubMed

Maia, Luciana P; Reino, Danilo M; Muglia, Valdir A; de Souza, Sérgio L S; Palioto, Daniela B; Novaes, Arthur B

2015-01-01

Soft tissues and buccal bone plate remodeling after immediate implantation in sockets with thin buccal bone, using the flapless approach with or without bone graft into the buccal gap, was compared between sites with thin and normal gingiva. Eight dogs had the gingiva of one side of the mandible thinned, the mandibular premolars were extracted without flaps, and 4 implants were installed in each side, positioned 1.5 mm from the buccal bone. The sites were randomly assigned into: TG (test group) = thin gingiva; TG + GM (TG with grafting material); CG (control group) = normal gingiva; and CG + GM (CG with grafting material). Buccal bone thickness (BBT), thickness of keratinized tissue (TKT), alveolar thickness (AT), gingival recession (GR), and probing depth (PD) were clinically evaluated. Within 12 weeks the dogs were sacrificed and the samples were analyzed by micro-computerized tomography. A thin BBT was observed in all the dogs. The presurgical procedures reduced TKT in the test group, with minimal changes of the AT. There were no statistically significant differences among the groups for the clinical parameters and the tomographic analysis showed similar linear and tri-dimensional bone reduction in all the groups. The thickness of the buccal bone was a fundamental factor in buccal bone plate resorption, even with flapless implantation. The decrease in gingival thickness or the addition of a biomaterial in the gap did not influence the results. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Is Greulich and Pyle atlas still a good reference for bone age assessment?

NASA Astrophysics Data System (ADS)

Zhang, Aifeng; Tsao, Sinchai; Sayre, James W.; Gertych, Arkadiusz; Liu, Brent J.; Huang, H. K.

2007-03-01

The most commonly used method for bone age assessment in clinical practice is the book atlas matching method developed by Greulich and Pyle in the 1950s. Due to changes in both population diversity and nutrition in the United States, this atlas may no longer be a good reference. An updated data set becomes crucial to improve the bone age assessment process. Therefore, a digital hand atlas was built with 1,100 children hand images, along with patient information and radiologists' readings, of normal Caucasian (CAU), African American (BLK), Hispanic (HIS), and Asian (ASI) males (M) and females (F) with ages ranging from 0 - 18 years. This data was collected from Childrens' Hospital Los Angeles. A computer-aided-diagnosis (CAD) method has been developed based on features extracted from phalangeal regions of interest (ROIs) and carpal bone ROIs from this digital hand atlas. Using the data collected along with the Greulich and Pyle Atlas-based readings and CAD results, this paper addresses this question: "Do different ethnicities and gender have different bone growth patterns?" To help with data analysis, a novel web-based visualization tool was developed to demonstrate bone growth diversity amongst differing gender and ethnic groups using data collected from the Digital Atlas. The application effectively demonstrates a discrepancy of bone growth pattern amongst different populations based on race and gender. It also has the capability of helping a radiologist determine the normality of skeletal development of a particular patient by visualizing his or her chronological age, radiologist reading, and CAD assessed bone age relative to the accuracy of the P&G method.

Assessment of Regeneration of Bone in the Extracted Third Molar Sockets Augmented Using Xenograft (CollaPlugTN Zimmer) in Comparison with the Normal Healing on the Contralateral Side.

PubMed

Ranganathan, Murugan; Balaji, M; Krishnaraj, R; Narayanan, Vivek; Thangavelu, Annamalai

2017-11-01

Alveolar bone resorption is a significant clinical problem. Bone loss in third molar region following extraction or surgical removal not only leads to periodontal problems in second molar region but also it may lead to some serious problems like increased incidence of angle fractures. In order to reduce the risks following third molar surgery, the socket should be augmented with bone grafts. In recent days guided tissue regeneration is the most accepted and successful technique followed many authors and its efficacy has been proved. Based upon our clinical experience, the use of bio absorbable collagen wound dressing such as CollaPlug TN has achieved quick healing and more primary wound coverage. Amongst the graft materials collagen is preferable due to its high biocompatibility and hemostatic ability. This study was done to assess the regeneration of bone in the extracted third molar sockets using xenograft (CollaPlug TN -Zimmer) which was compared with the normal healing on the contra lateral side. The assessment was done to analyze post-operative healing complications and to compare the bone density formed between control site and implant site radiologically. On this basis of this study, the use of collaplugTN appears to be beneficial to the patient in postoperative wound healing and also for better bone formation. The use of this material was advantageous because of its simplicity of application cost effectiveness and availability. There is enhanced wound healing and early bone formation.

Calcineurin/NFAT signaling in osteoblasts regulates bone mass.

PubMed

Winslow, Monte M; Pan, Minggui; Starbuck, Michael; Gallo, Elena M; Deng, Lei; Karsenty, Gerard; Crabtree, Gerald R

2006-06-01

Development and repair of the vertebrate skeleton requires the precise coordination of bone-forming osteoblasts and bone-resorbing osteoclasts. In diseases such as osteoporosis, bone resorption dominates over bone formation, suggesting a failure to harmonize osteoclast and osteoblast function. Here, we show that mice expressing a constitutively nuclear NFATc1 variant (NFATc1(nuc)) in osteoblasts develop high bone mass. NFATc1(nuc) mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and coordinated changes in the expression of Wnt signaling components. In contrast, viable NFATc1-deficient mice have defects in skull bone formation in addition to impaired osteoclast development. NFATc1(nuc) mice have increased osteoclastogenesis despite normal levels of RANKL and OPG, indicating that an additional NFAT-regulated mechanism influences osteoclastogenesis in vivo. Calcineurin/NFATc signaling in osteoblasts controls the expression of chemoattractants that attract monocytic osteoclast precursors, thereby coupling bone formation and bone resorption. Our results indicate that NFATc1 regulates bone mass by functioning in both osteoblasts and osteoclasts.

Solitary haemangioma of the shaft of long bones: resection and reconstruction with autologous bone graft.

PubMed

Li, Zhaoxu; Tang, Jicun; Ye, Zhaoming

2013-04-01

Bone haemangiomas are uncommon lesions, occurring in the skull or spine. A solitary haemangioma in the diaphysis of a long bone is rare. We retrospectively investigated six patients who presented with a solitary haemangioma in a long bone diaphysis. After segmental bone resection, the bone defect was replaced by a bone autograft. Patients were reviewed clinically and with radiographs. The mean follow-up was 6 years (range : 1-20 years). At the time of latest follow-up, no patient had a recurrence. Postoperative complications were one wound necrosis and one superficial wound infection. Union of the gap filling graft with the host bone was achieved in all patients at an average of 4 months (range: 3-8 months). The average Musculoskeletal Tumor Society functional score was 77% (range: 53%-90%) of normal at 6 months postoperatively, and 97% (range: 95%-99%) at the last follow-up evaluation. Segmental resection for solitary haemangioma and reconstruction with autologous bone graft can be considered as a suitable treatment option.

Emerging treatments for postmenopausal osteoporosis – focus on denosumab

PubMed Central

Geusens, Piet

2009-01-01

The pathway of the receptor activator of the nuclear factor κB ligand (RANKL), RANK and osteoprotegerin (OPG) plays a central role in coupling bone formation and resorption during normal bone turnover and in a wide spectrum of diseases characterized by disturbed bone remodeling, increased bone resorption and bone destruction (osteoporosis, Paget’s disease of bone, rheumatoid arthritis [RA], metastatic bone disease). Clinical trials indicate that denosumab, a RANKL-specific recombinant humanized monoclonal antibody, is effective in suppressing bone resorption, resulting in increase in bone mineral density (BMD) in post-menopausal women with low BMD, and has the potential to prevent progression of erosions in RA and of skeletal-related events in metastatic bone disease. The effects on fracture reduction in postmenopausal osteoporosis are awaited from the recently finished FREEDOM study. In clinical trials with denosumab, overall adverse events were similar to placebo or comparators, indicating a favorable safety profile in these diseases, which until now have been available up to 4 years, but data on long-term safety will be needed. PMID:19554095