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PubMed2003

Biochemical markers of bone metabolism: application to understanding bone remodeling in children and adolescents.

Markers of bone remodeling have been developed that provide biochemical indices that reflect changes in the rates of bone formation, resorption, and mineralization. These processes are important determinants of bone metabolism, and indicators that correspond to these processes can provide clinically relevant information. Until recently, the best way to measure parameters of bone metabolism was to perform a bone biopsy after administration of two courses of tetracycline. Bone markers offer significant potential advantages over bone biopsy. Some of these markers are protein fragments that are generated during metabolism of type I collagen, the major structural protein of bone, and are formed as this collagen is synthesized or degraded. Other markers, such as osteocalcin and alkaline phosphatase, are released from osteoblasts during bone formation. Although these markers have found significant utility in the evaluation of adults with metabolic bone diseases, their application in children has been limited due to great variability in normal ranges that reflect the changes in skeletal metabolism induced by age, growth rate, gender, and pubertal state.

Adolescent↗
PubMed1997

Effects of recombinant human bone morphogenetic protein-2 on human bone marrow cells cultured with various biomaterials.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is known to induce orthotopic and ectopic bone formation in vivo. Several in vitro studies using rat or mouse clonal cell lines have shown that rhBMP-2 may be involved in the differentiation of osteoblasts from osteoblast precursor cells or stromal cells in the bone marrow. However, there is little information available about the effects of rhBMP-2 on cultured human bone marrow cells. We investigated the effects of rhBMP-2 cultured on human bone marrow cells and osteoblastic cells on various biomaterials. Human bone cells were divided into fresh bone marrow cells, fibroblast colony-forming units (cfu-F, stromal precursors), and osteoblastic cells. The cells were cultured with or without rhBMP-2 on various biomaterials, including titanium alloy, pure titanium, cobalt alloy, and hydroxyapatite. It was found that rhBMP-2 (500 ng/mL) significantly stimulated alkaline phosphatase production by fresh bone marrow cells and cfu-F. However, when cultured on titanium alloy or pure titanium, only fresh bone marrow cells showed an increase of alkaline phosphatase production after rhBMP-2 stimulation. Production of osteocalcin, a marker of mature osteoblasts, was not stimulated by rhBMP-2 in any combinations tested. These findings suggest that rhBMP-2 may be involved in inducing the differentiation of osteoblast precursor cells into osteoblastic cells rather than stimulating further differentiation of osteoblastic cells into mature osteoblasts. In addition, grafts of fresh human bone marrow cells of cfu-F stimulated by rhBMP-2 may have the potential to promote bone formation at sites of nonunion as well as around titanium joint prostheses.

Adult↗
PubMed1992

The microcirculation of bone and marrow in the diaphysis of the rat hemopoietic long bones.

The nature of the microcirculation of the diaphyseal portion of long bones and the adjacent bone marrow is poorly understood. The purpose of this study was to describe the blood supply in the diaphyseal cortex and the relationship of the bone vascular circulation to that of the bone marrow in the growing rat. India ink-gelatin was infused in the arterial system of 3-month-old rats and the vascularization was determined from histological sections. In some studies the periosteal circulation was blocked but the nutrient and metaphyseal arteriole systems were left intact. In the growing rat, most of the vascular flow appears to be centripetally through the diaphyseal cortex and this appears to be the primary blood supply for the adjacent bone marrow. The India ink traversed the cortex and entered the marrow through osteal canals at the endocortical surface. At the marrow-endocortical bone surface interface, ink exiting from the osteal canals filled the adjacent marrow sinusoids in what appeared as "bush-like" structures. From the bone marrow the ink appeared to drain into the central vein. Some arterioles from the nutrient system were found to penetrate the inner two thirds of the cortical bone and then re-enter the bone marrow. The centripetal flow of blood and the importance of the cortical flow for perfusion of the hemopoietic tissue was further documented when periosteal flow was obstructed. In this situation, the cortical bone and adjacent bone marrow were not perfused while the nutrient system and central vein were filled with ink.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget's disease activity.

OBJECTIVE: To evaluate the relationship between biochemical markers of bone turnover and bone scan indices of disease activity, as well as to analyze their variations based on skeletal involvement, in Paget's disease. METHODS: Serum samples were obtained from 51 patients with Paget's disease to determine the levels of total alkaline phosphatase (total AP), bone alkaline phosphatase (bone AP), propeptide carboxyterminal of type I procollagen (PICP), propeptide aminoterminal of type I procollagen (PINP), osteocalcin, tartrate-resistant acid phosphatase, and telopeptide carboxyterminal of type I collagen. Urine samples were analyzed for levels of hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), C-terminal telopeptide of type I collagen (CTx), and N-terminal telopeptide of type I collagen (NTx). In addition, 2 semiquantitative scintigraphic indices, disease activity (AI) and disease extent (EI), were obtained. Pagetic skeletal locations were evaluated individually, with special attention to skull involvement. RESULTS: All biochemical markers correlated with the AI and the EI. Serum PINP, bone AP, and total AP showed the highest proportions of increased values among the bone formation markers (94%, 82%, and 76%, respectively). Among the bone resorption markers, urinary NTx showed the highest proportion of increased values in patients with Paget's disease (96%), compared with PYR (69%), DPYR (71%), CTx (65%), and HYP (64%). In patients with mild disease activity, serum PINP was the marker with the highest proportion of increased values (71%). In contrast, serum PICP and urinary CTx were the most discriminative markers for skull involvement. Except for higher values for most of the biochemical markers of bone turnover in flat bones, no major differences in other skeletal locations were observed. CONCLUSION: The determination of serum PINP as a marker of bone formation and urinary NTx as a marker of bone resorption provided the best biochemical profile to ascertain the extent and activity of Paget's disease. In patients with skull involvement, serum PICP and urinary CTx were shown to be the most discriminative markers.

Acid Phosphatase↗
PubMed1998

Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis.

Previous studies suggest that low bone mass is a complication of alcoholic liver disease. Nevertheless, little is known about bone mass and bone metabolism in viral cirrhosis. To evaluate the prevalence and magnitude of hepatic osteopenia in these patients, bone remodeling status, and its relationship with the severity of liver disease and serum levels of insulin-like growth factor I (IGF-I), we studied 32 consecutive patients with viral cirrhosis and no history of alcohol intake. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN), and the values were expressed as the z score. Bone metabolism markers and hormone profiles were measured. Patients with viral cirrhosis showed reduced BMD in all sites (LS: -1.27 +/- 1.06, P < .001; FN: -0.48 +/- 0.96; P < .01). Of the 32 patients, 53% met the diagnostic criteria for osteoporosis. In patients, urine deoxypyridinoline (D-Pyr) as a marker of bone resorption and serum bone alkaline phosphatase (b-AP) as a marker of bone formation were significantly higher than in control subjects (P < .001 and P < .01, respectively). Serum IGF-I was lower than in control subjects (P < .001), and significant differences were also found between patients with and without osteoporosis (P < .05). BMD in LS correlated with severity of the disease, with serum levels of IGF-I, and with urine D-Pyr. Our findings show that viral cirrhosis is a major cause of osteoporosis in men, and that low serum IGF-I levels seem to play a role in the bone mass loss in these patients. The biochemical markers of bone remodeling suggest high-turnover osteoporosis in patients with viral cirrhosis.

Adult↗
PubMed1992

Racial differences in pre- and postmenopausal bone homeostasis: association with bone density.

The disparity in fracture incidence and bone mass in women of European (white) and African (black) ancestry is of unknown etiology. To determine if racial differences in bone mass reflected racial differences in the mechanisms of bone turnover underlying bone mineral loss, we measured serum osteocalcin, serum alkaline phosphatase, fasting urinary calcium and hydroxyproline excretion, 24 h urinary excretion of calcium and sodium, and dietary intakes of calcium and vitamin D in 263 healthy pre-, peri-, and postmenopausal white and black women. In addition, radial and spinal bone density were measured cross-sectionally for comparison with biochemical measures of bone turnover. The biochemical parameters thought to reflect bone resorption (fasting urinary calcium and hydroxyproline excretions) were lower in black than in white women throughout the age and menopausal stages studied. The parameters thought to reflect bone formation (alkaline phosphatase and osteocalcin), were similar in the two racial groups among the premenopausal women, but osteocalcin was significantly lower among the peri- and postmenopausal blacks. Cross sectionally measured radial bone density increased with age in premenopausal black women, but it did not change with age in the white premenopausal subjects, a statistically significant difference. In peri- and postmenopausal women radial density declined significantly with years after menopause in both racial groups, but the rate of decline was significantly slower in the black women. Lumbar bone density in premenopausal white and black women did not change with age. After menopause lumbar bone density declined significantly and similarly in both racial groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

High dose glucocorticoid hampers bone formation and resorption after bone marrow ablation in rat.

We analyzed the effect of glucocorticoid on bone regeneration after bone marrow ablation in tibiae of 8-week-old rats. Methylprednisolone sodium succinate (MPSS) was injected intramuscularly at a dose of 100 mg/kg/day for 3 days. Tibiae on days 1, 3, 5, 7, 10, 12, and 14 after ablation were subjected to tartrate-resistant acid phosphatase staining, immunohistochemistry, in situ hybridization, and transmission electron microscopy (TEM), and measurement of the volume of newly-formed bone and the osteoclast number. MPSS significantly decreased the newly-formed bone volume on day 7, and immature bone still remained on day 10 in the MPSS-treated group. The volume of this bone was significantly higher than that in the control group. However, there were no differences between the groups in the osteoclast number, the expression of mRNAs for osteoblast differentiation markers, and alkaline phosphatase and cathepsin K judged by immunohistochemistry. TEM findings showed no difference in the form of osteoblasts, whereas osteoclasts in the MPSS-treated group had less developed ruffled borders, compared to those in the control group. These results suggest that MPSS treatment affects neither the differentiation nor the shape of osteoblasts, and does not change the osteoclast number or the cathepsin K level. However, high dose MPSS inhibits both bone formation and resorption during bone regeneration after rat tibial bone marrow ablation, and inhibits ruffled border formation in osteoclasts. These data will be useful to develop bone regenerative therapies for bone diseases due to high dose steroid administration.

Alkaline Phosphatase↗
PubMed1987

Bone matrix and marrow versus cancellous bone in rabbit radial defects.

Implants of demineralized bone matrix induce new bone formation. In order to estimate the possible clinical usefulness of this phenomenon, autologous cancellous bone grafts were compared with composite grafts of bone matrix and marrow. Cancellous bone from the tuber ischii of the rabbit was transplanted to a preformed radial defect in the same animal. On the opposite side, a similar defect was filled with a mixture of either allogenous or autogenous bone-matrix particles and autogenous bone marrow. After 25 days, calcium 45 was injected intravenously. Three days later the animals were killed. Standardized segments of the rabbit's forearms, containing the middle of the defect, were cut out, ashed, and analyzed for 45Ca activity. No side difference in 45Ca deposition was found. The callus ash weight of the allogenous matrix-transplanted side was approximately 60% of that of the cancellous bone side. This side difference of ash weights corresponds to the estimated initial mineral content of the cancellous graft. Nontransplanted defects had very low ash weight and 45Ca activity. Thus, in the rabbit, composite grafts of bone matrix and marrow produce a bone yield comparable to that of cancellous bone.

Animals↗
PubMed2000

[Heterotopic and orthotopic bone formation with a vascularized periosteal flap, a matrix and rh-BMP-2 (bone morphogenetic protein) in the rat model].

The purpose of this study was to construct a vascularized bone graft using the osteoinductive bone morphogenetic protein (rh-BMP-2), a polylactic acid matrix (OPLA/HY), and a vascularized periosteal flap containing osteoprogenitor cells ectopically in the groin or orthotopically in a femoral defect. In the Lewis rat, periosteal flaps were harvested from the medial surface of the tibia vascularized by the saphenous artery and vein and were transferred to the groin on its vascularized pedicle. Alternatively, the periosteal flap along its pedicle was transferred between the thigh muscles to be wrapped around a femoral defect of 1 cm. The animals were divided into 10 groups (82 animals). In group 1, the periosteal flap was left empty in the groin. Groups 2 and 3 consisted of the periosteal flap and 20 micrograms rh-BMP-2, but in group 3 the vascular pedicle was ligated proximally. In group 4 the flap was harvested without the periosteal layer and turned "inside out". Groups 5 and 6 consisted of the periosteal flap and the matrix OPLA/HY +/- 20 micrograms rh-BMP-2. In the femoral defect model, bone formation was studied using the matrix OPLA/HY alone (group 7) or combined with the vascularized periosteal flap (group 8), or in combination with OPLA/HY + BMP (group 9) or OPLA/HY + BMP + the periosteal flap (group 10). The presence and density of new bone formation in the groin and femoral defect were evaluated radiologically and histologically at 4 and 8 weeks. Good bone formation in the groin chamber (ectopic) was demonstrated in the periosteal flap + OPLA/HY + BMP group. In the femoral defects, good bone formation (orthotopic) was seen in the OPLA/HY + BMP + the periosteal flap groups. However, with the presence of a vascularized periosteal flap, more bone formation along the rim of the defect was observed. This study of ectopic bone formation in the groin and orthotopic bone formation in the femoral defect demonstrates that optimal bone formation requires four factors: BMP, a biodegradable matrix, osteoprogenitor cells, and blood supply. Potentially in the future, this technique could be used to reconstruct a bony defect or a nonunion by covering the involved area with a vascularized periosteal flap and a suitable matrix combined with BMP. Alternatively, a vascularized bone graft could be prefabricated at a distant site and then transferred microsurgically into a defect.

Animals↗
PubMed2003

Increased cancellous bone in the femoral neck of patients with coxarthrosis (hip osteoarthritis): a positive remodeling imbalance favoring bone formation.

Osteoporosis is caused by an imbalance between bone resorption and formation which results in an absolute reduction in bone mass. In a previous study we highlighted a condition, osteoarthritis of the hip (coxarthrosis, cOA), where an imbalance between resorption and formation provided beneficial effects in the form of an absolute increase in bone mass. We demonstrated that the femoral neck in patients with cOA had increased cancellous bone area, connectivity and trabecular thickness which might contribute to the protection against fracture associated with the condition. The aim of the present study was to analyze forming and resorbing surfaces in coxarthritic cancellous bone to assess whether increased formation or reduced resorption could be responsible for these structural changes. Whole cross-sectional femoral neck biopsies were obtained from 11 patients with cOA and histomorphometric parameters compared with 14 age- and sex-matched cadaveric controls. The ratio of osteoid surface to bone surface was 121% ( p<0.001) higher in the cases but there was no significant difference in resorptive surface. The percentage osteoid volume to bone volume (%OV/BV; +270%, p<0.001) and osteoid width (O.Wi; +127%, p<0.001) were also higher in the cases. This study suggests that the increased cancellous bone mass seen in cases of cOA is due to increased bone formation rather than decreased bone resorption. Investigation of the cellular and biochemical basis for these changes might provide new insights into the pathogenesis of osteoarthritis and highlight novel biological mechanisms regulating bone multicellular unit (BMU) balance that could be relevant to developing new interventions against hip and other osteoporotic fractures.

Aged↗
PubMed2003

Bone mineral density and bone metabolism in Duchenne muscular dystrophy.

Very few studies on bone mineral density and bone metabolism in Duchenne muscular dystrophy (DMD) have been reported. DMD is a severe, progressive muscular disease resulting in death at a young age. No specific therapies are available, but corticosteroids induce improvement and slower progression of the disease. However, long-term steroid therapy is a serious risk factor for osteoporosis. This study was aimed at evaluating bone mineral density and calciotropic hormones in a group of children affected by DMD, with or without steroid therapy. Bone mineral density was measured by DXA scan on lumbar spine and total body. Evaluation of calcium, phosphorus, bone turnover markers and calciotropic hormones was performed. Thirty-two children affected by DMD were studied: twenty-two on long-term prednisone therapy, ten not taking corticosteroids. Bone mineral density was lower than normal for age in all patients, and even lower in the group of steroid-treated children. Trunk and lower limb bone mineral densities were more reduced than upper limb mineral density, especially in the steroid-treated subjects. A marked reduction in spine bone mineral density, hypocalciuria, low 25-hydroxyvitamin D levels, and increased bone turnover markers were observed, and even these especially in the steroid-treated group. In conclusion, decreased bone mineral density and derangement of calcium metabolism were present in DMD patients, and were worsening during corticosteroid therapy. It is thus recommended that bone and mineral metabolism be carefully evaluated in patients with DMD, so that appropriate measures could be taken, especially now that chronic corticosteroid therapy is frequently given.

25-Hydroxyvitamin D 2↗
PubMed2005

A prospective study of changes in bone turnover and bone density associated with regaining weight in women with anorexia nervosa.

Anorexia nervosa (AN) is a condition of self-induced weight loss, associated with an intense fear of gaining weight. Previous studies have shown that bone density may increase with regaining and maintaining normal weight; however, relatively little is known about the changes in bone metabolism that occur during weight restoration. We describe the effect of weight restoration and maintenance of weight over 1 year on bone mineral density (BMD) and bone turnover. We recruited women from the eating disorders services at the South West London and St George's Mental Health NHS Trust, and the Priory and Charter Nightingale Hospitals in London, UK. Details of their AN, fracture history, menstrual history and exercise were obtained by interview and case note review. Morning samples of blood and second void urine were taken for biochemical analysis. BMD was measured by DXA at the lumbar spine (LS), femoral neck (FN), distal radius (RD) and total body bone mineral content (BMC). Patients then entered the treatment program, which includes re-feeding, dietary education and psychotherapy. Over a period of 42 months, we recruited 55 women who agreed to participate in this study and underwent baseline investigations. Of these, 15 (27%) subjects achieved and then maintained their target weight for the duration of the study. At baseline for all subjects (n=55) estradiol levels were lower than the normal reference ranges (both follicular and luteal phases) in 91% of the women. Bone specific alkaline phosphatase (BSAP) concentrations were lower than the premenopausal reference range in 55% of women, and urinary deoxypyridinoline (DPD) was above the premenopausal reference range in 78% of women. Baseline lumbar spine BMD was positively related to BMI (Pearson's r=0.29, P=0.04) and inversely related to bone turnover markers: urinary DPD (Pearson's r=-0.39, P=0.01 and serum BSAP (Pearson's r=-0.3, P=0.06). The 15 patients who regained and maintained weight were followed-up for a mean duration of 69 weeks (SD 7.3, range 54 to 84 weeks). Mean BMI increased from 14.2 (1.7) to 20.2 (0.77) kg/m2 and remained stable throughout follow-up. Menstruation resumed in 8 of the 15 women. Total body BMC and LS BMD increased significantly over the duration of follow-up (by 4.3% each), but FN BMD and distal radius remained stable. Lumbar spine bone area also increased significantly, whereas FN and distal radius did not. These changes were associated with a significant increase in BSAP (P=0.01), and a non-significant trend for a decrease in DPD (P=0.10). Our findings suggest that when women are at low body weight they are in a hypo-estrogenic state, which is associated with imbalance of bone turnover (high bone resorption and low bone formation). This is reversed with weight gain and persists as target weight is maintained and is associated with increases in BMC and BMD.

Absorptiometry, Photon↗
PubMed2006

Watching bone cells at work: what we can see from bone biopsies.

Histomorphometric analysis of iliac bone samples is a key tool for studying bone metabolism and, to a lesser extent, bone mass and structure. Two types of bone metabolic activity can be distinguished: modeling and remodeling. Both processes are performed by the same effector cells, osteoblasts and osteoclasts, but differ in the way these cells are arranged. The main effect of remodeling is to renew bone, whereas modeling can lead to rapid changes in bone shape, size and mass. Standard histomorphometric analysis focuses on trabecular bone and therefore mainly provides information on remodeling. Remodeling activity changes markedly with age during development. This must be taken into account when histomorphometry is used in the pediatric setting. Remodeling disorders encountered in the context of pediatric renal bone disease include mineralization defects, as well as abnormally high remodeling activity due to secondary hyperparathyroidism or suppressed remodeling activity as a consequence of over-treatment. Children and adolescents with severe bone fragility should have a bone biopsy unless the diagnosis is obvious from noninvasive examinations. Histomorphometric analysis of transiliac bone biopsy samples is especially valuable in clinical studies, as this method provides safety and efficacy data that cannot be obtained in any other way.

Adolescent↗
PubMed1999

Recombinant bone morphogenetic protein-7 as an intracorporal bone growth stimulator in unstable thoracolumbar burst fractures in humans: preliminary results.

The study presented here is a pilot study in five patients with unstable thoracolumbar spine fractures treated with transpedicular OP-1 transplantation, short segment instrumentation and posterolateral fusion. Recombinant bone morphogenetic protein-7 in combination with a collagen carrier, also referred to as OP-1, has demonstrated ability to induce healing in long-bone segmental defects in dogs, rabbits and monkeys and to induce successful posterolateral spinal fusion in dogs without need for autogenous bone graft. Furthermore OP-1 has been demonstrated to be effective as a bone graft substitute when performing the PLIF maneuver in a sheep model. Five patients with single-level unstable burst fracture and no neurological impairment were treated with intracorporal OP-1 transplantation, posterior fixation (USS) and posterolateral fusion. One patient with osteomalacia and an L2 burst fracture had an additional intracorporal transplantation performed proximal to the instrumented segment, i.e. OP-1 into T 12 and autogenous bone into T 11. Follow-up time was 12-18 months. On serial radiographs, Cobb and kyphotic angles, as well as anterior, middle and posterior column heights, were measured. Serial CT scans were performed to determine the bone mineral density at fracture level. In one case, radiographic and CT evaluation after 3 and 6 months showed severe resorption at the site of transplantation, but after 12 months, new bone had started to fill in at the area of resorption. In all cases there was loss of correction with regard to anterior and middle column height and sagittal balance at the latest follow-up. These preliminary results regarding OP-1 as a bone graft substitute and stimulator of new bone formation have been disappointing, as the OP-1 device in this study was not capable of inducing an early sufficient structural bone support. There are indications to suggest that OP-1 application to a fracture site in humans might result in detrimental enhanced bone resorption as a primary event.

Adult↗
PubMed2004

Biochemical bone turnover markers are useful tools to assess changes in bone metabolism in marmosets.

This study was designed to investigate whether biochemical markers of bone resorption and formation could be determined in the serum and urine of marmosets (Callithrix jacchus), using standard laboratory chemistry methods and commercially available human kits. Consequently, the findings from this study will indicate whether the techniques and kits could serve as appropriate tools for assessing changes in bone turnover in this species. Two groups of animals (n = 12/group), consisting of a comparable number of young and old male and female marmosets, were given either isotonic saline or a single dose of the bisphosphonate ibandronate (0.1 mg/kg) s.c. in order to suppress bone turnover. Blood and urine were collected at baseline and 5 days after administration. Samples were analyzed for urinary (u) and serum (s) markers of bone formation (serum osteocalcin [sOC], serum N-terminal crosslinks of human pro-collagen type I [sP1NP]) and bone resorption (urinary pyridinoline [uPYD], urinary deoxypyridinoline [uDPD], serum C-terminal crosslinks of human collagen type I (C-telopeptide) [sCTX]), intact serum parathyroid hormone (iPTH) and urinary calcium and creatinine. Levels of all the markers of bone resorption and formation decreased during the study period. As expected, the bone formation markers decreased slightly less relative to the resorption markers. The most sensitive markers were sCTX (-33%; P < or =0.001) for bone resorption, and sP1NP (-3%; P < or =0.05) for bone formation. Serum PTH levels increased by 8% ( P < or =0.05), demonstrating a physiological reaction to prevent changes in serum calcium. Although not all variables reached statistical significance within the tested interval, the applied methods and kits were considered suitable for evaluating bone turnover changes in marmosets. Thus, these methods and kits can be utilized not only during the course of pharmacological investigations but also as additional tools to assess the overall bone health of this species.

Animals↗
PubMed2005

Analysis of avian bone response to mechanical loading-Part one: Distribution of bone fluid shear stress induced by bending and axial loading.

Mechanical loading-induced signals are hypothesized to be transmitted and integrated by a bone-connected cellular network (CCN) before reaching the bone surfaces where adaptation occurs. Our objective is to establish a computational model to explore how bone cells transmit the signals through intercellular communication. In this first part of the study the bone fluid shear stress acting on every bone cell in a CCN is acquired as the excitation signal for the computational model. Bending and axial loading-induced fluid shear stress is computed in transverse sections of avian long bones for two adaptation experiments (Gross et al. in J Bone Miner Res 12:982-988, 1997 and Judex et al. in J Bone Miner Res 12:1737-1745, 1997). The computed fluid shear stress is found to be correlated with the radial strain gradient but not with bone formation. These results suggest that the radial strain gradient is the driving force for bone fluid flow in the radially distributed lacunar-canalicular system and that bone formation is not linearly related to the loading-induced local stimulus.

Animals↗
PubMed1989

Bone marrow embolism following cryosurgery of bone: an experimental study.

Cryosurgery is commonly used in medicine for treatment of benign and malignant lesions. We had clinical and experimental data indicating that cryosurgery of intact bone could cause bone marrow intravasation and embolism, i.e., particles of bone marrow entering extraosseous veins and occluding pulmonary vasculature. This study was designed to investigate the pathogenesis of bone marrow intravasation and embolism after cryosurgery. Three hypotheses on the pathogenesis of bone marrow intravasation were tested using a model of cryosurgical continuity lesion in rats and rabbits. Influence of physical and circulatory factors were excluded supporting a mechanical-biological hypothesis; the intravasation of bone marrow after cryosurgery of bone is caused by an increased intramedullary pressure. The increased intramedullary pressure is due to edema in the medullary cavity caused by cryosurgical damage to cell membranes. It is demonstrated that the bone marrow intravasates can embolize to the lungs causing respiratory insufficiency. This can be a serious complication following cryosurgery of intact bone. Prophylactic decompression of the medullary cavity can possibly prevent the rise in intramedullary pressure and thus intravasation and embolisation of bone marrow after cryosurgery of intact bone.

Animals↗
PubMed1991

Physiologically based models for bone-seeking elements. I. Rat skeletal and bone growth.

A review of features of bone structure and bone growth critical to the development of a physiologically based model of the whole-body kinetics of bone-seeking elements is presented. Allometric equations describing the volume and weight of the bone, bone marrow, and skeleton during growth of the rat from birth to maturity are derived. Weights of body calcium and bone ash are also expressed allometrically as functions of body weight during growth. The simplicity of these functions will allow them to form the basis of a flexible model of the movement of bone-seeking elements in and out of bone. Blood flow rates to bone and bone marrow are incorporated into the model of the mature skeleton. The predictions of the skeletal growth model are in good agreement with measured quantities of bone, skeletal ash, and calcium in growing rats.

Animals↗