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PubMed1995

Beta-2-microglobulin in diseases with high bone remodeling.

Beta2-microglobulin has been observed to behave as a biological marker of bone remodeling. We measured beta2-microglobulin and tartrate-resistant acid phosphatase (TRAP), a specific biological marker of bone remodeling, in 225 women: healthy premenopausal controls, healthy postmenopausal control, and patients with diseases characterized by enhanced bone turnover (postmenopausal osteoporosis, primary hyperparathyroidism, primary hyperthyroidism, polyostotic Paget's bone disease), and in other Paget's group before and after calcitonin treatment. Beta2-microglobulin levels differed significantly between the healthy premenopausal women (n = 20) compared with all the other groups. However, beta2-microglobulin levels did not differ significantly between healthy postmenopausal women (n = 38) and patient's with Paget's bone disease (n = 40)(P = 0.5095), or between women with postmenopausal osteoporosis (n = 30) and women with hyperthyroidism (n = 20)(P = 0.7890). TRAP concentrations differed significantly in all the groups paired except for women with Paget's bone disease and women with either hyperparathyroidism or hyperthyroidism (P = 0.5179 and 0.6993, respectively); likewise, TRAP levels did not differ significantly between the women with hyperparathyroidism and those with hypothyroidism (P = 0.7804). After calcitonin treatment, there was a 22% increase in beta2-microglobulin, a 17% decrease in TRAP, and a 39% decrease in alkaline phosphatase, all of which were significant at P < 0.0001. Our findings indicate that serum beta2-microglobulin, like osteocalcin, behaves as a biological marker of remodeling in a number of diseases with enhanced bone remodeling but not in Paget's bone disease.

Acid Phosphatase↗
PubMed1990

Histomorphometric comparison of measurements of trabecular bone remodeling in iliac crest biopsy sites and lumbar vertebrae in cats.

Trabecular bone remodeling values of the right and left iliac crest and lumbar vertebrae in cats were quantitated histomorphometrically and were compared. Healthy cats were given calcein (n = 2) or oxytetracycline (n = 2) twice for double-labeling of bone. Static and dynamic variables of bone resorption and formation were determined. Bone remodeling variables between right and left iliac crest were not significantly different (P less than 0.05). Significant differences (P less than or equal to 0.05) were not detected between values of iliac crest and lumbar vertebrae except in the percentage of osteoid surface. Percentage of osteoid surface was significantly (P less than or equal to 0.05) increased in the iliac crest compared with that in the vertebral body. Although not significantly different, values for bone formation were generally greater in the iliac crest than in the vertebral body. In healthy cats, values of trabecular bone remodeling were comparable between right and left iliac crest, and also were comparable between iliac crests and lumbar vertebrae.

Animals↗
PubMed1997

Raloxifene and estrogen: comparative bone-remodeling kinetics.

The pattern of changes in human bone remodeling produced by raloxifene (60 mg/day) was compared to that of estrogen (given as hormone replacement therapy) in 33 early postmenopausal women randomly assigned to raloxifene, estrogen, or no treatment. Remodeling was measured using calcium tracer kinetic methods employed under a constant diet and full metabolic balance conditions. Studies were performed at baseline and, to detect both early and late remodeling changes, at 4 and 31 weeks of treatment. Both raloxifene and estrogen produced a significant positive calcium balance shift at each treatment measurement point: +74 and +60 mg/day at 4 weeks, and +60 and +91 mg/day at 31 weeks for raloxifene and estrogen, respectively. Externally, this balance change was due to a highly significant fall in the urinary calcium level and marginal improvement in calcium absorption efficiency. Internally, bone resorption was significantly reduced at both measurement points: -64 and -60 mg/day at 4 weeks, and -82 and -162 mg/day at 31 weeks for raloxifene and estrogen, respectively. Bone formation was not significantly affected by either agent at 4 weeks; at 31 weeks, formation was reduced by estrogen, but not by raloxifene. Thus, at 4 weeks, the general pattern of remodeling change was identical for the two agents. At 31 weeks, remodeling suppression was greater for estrogen than for raloxifene; however, remodeling balance was the same for the two agents. We conclude that raloxifene and estrogen affect the bone remodeling apparatus similarly, and that raloxifene, therefore, is acting on bone as an estrogen agonist.

Bone Remodeling↗
PubMed1996

Bone remodeling alterations in myelodysplastic syndrome.

There is a close relationship between hematopoietic bone marrow and bone cells. Thus, the profound derangement of hematopoiesis in myelodysplastic syndromes (MDS) might be expected to affect bone cell function. We studied the dynamic histomorphometric changes in bone in 22 MDS patients to examine this relationship and analyze the influence of hematological disease on bone remodeling. Bone-regulating hormones and histomorphometry of undecalcified transiliac bone biopsies, after double tetracycline labeling, were studied. Serum calcium, phosphorus, creatinine, alkaline phophatase, osteocalcin, iPTH, 25(OH)D3, 1,25(OH)2D3, hydroxyprolinuria, and calcium/creatinine ratio in urine were normal compared with controls. Histomorphometry showed a significant decrease in osteoblast surface (Ob.S/BS) (0.30 +/- 0.40 vs. 0.8 +/- 1.1, p = 0.031), wall thickness (W.Th), (22.03 +/- 5.5 vs. 31.8 +/- 5.8, p < 0.005), osteoclast number (N.Oc/T.Ar) (0.004 +/- 0.01 vs. 0.017 +/- 0.01, p = 0.03), mineral apposition rate (MAR) (0.16 +/- 0.15 vs. 0.53 +/- 0.19, p < 0.005), bone formation rate, surface referent (BFR/BS) (0.004 +/- 0.10 vs. 0.016 +/- 0.016, p = 0.009), and activation frequency (Ac.f) (0.06 +/- 0.07 vs. 0.21 +/- 0.23, p = 0.008). An increase in mineralization lag time (MLT) (119.2 +/- 78.6 vs. 29.6 +/- 77, p < 0.005), (mean +/- SD, unpaired Student t-test) was observed. Bone volume (BV/ TV), eroded surfaces (ES/BS), and osteoid thickness (O.Th) remained unchanged. This picture of adynamic bone with decreased mineral apposition rate and markedly decreased osteoclast number is a characteristic finding in MDS patients. Thus, bone histomorphometric finding in MDS patients show the relationships and interactions between hematopoietic and bone cells.

Aged↗
PubMed2006

Ochronotic arthropathy, an approach to osteoarthritis bone remodelling.

The objective is to use hip ochronotic arthropathy for an indirect approach to osteoarthritis bone remodelling in a human joint via an identified causal chondropathy. The method is via radiology connecting pathology and nosology, based on the study of seven ochronotic femur heads excised in alcaptonuric patients. Due to the brittleness of ochronotic cartilage, bone remodelling similar to that of hip osteoarthritis exists with diffuse narrowing of the interarticular space and (except in one case modified by intermediary surgery) poorly developed osteophytes. Ochronotic arthropathy is only a privileged model of osteoarthritis bone remodelling, the pathology of which might well evidence the stages of the process, with marking by pigmented cartilage remnants Thus it may lead to various reflections in rheumatology, among others concerning the respective radiological hip images of osteoarthritis and rheumatoid arthritis. The use of the pathology-radiology files provided by hip surgery of ochronotic arthropathy might offer a useful reference model for investigating various aspects of osteoarthritis.

Arthritis, Rheumatoid↗
PubMed1982

An electron-microscopic study of the bone-remodeling sequence in the rat.

A detailed chronological electron-microscopic study of the bone remodeling sequence has been performed in the rat based on a previously described model (Tran Van et al. 1982) in which the remodeling activity is synchronized. This allowed the observation of the cellular and extracellular events during the bone remodeling process, including the activation of the sequential process and the reversal phase, intermediate between osteoclastic resorption and osteoblastic formation. Most important is the fact that throughout the whole process cells with the morphological characteristics of mononuclear phagocytes have been observed in proximity or in contact with the bone surface and/or the various bone cells. Coated pits (receptor-mediated endocytosis) are frequently observed in close apposition ot bone spicules and gap junctions are frequent between the cells. These observations suggest that, besides being likely candidates as osteoclast precursors, mononuclear phagocytes may play an important role in bone remodeling.

Animals↗
PubMedDate not supplied

In vivo effects of high-dose methotrexate on bone remodeling in rats.

Methotrexatae (MTX) is a folate antagonist. MTX osteopathy is well recognized to accompany a high-dose therapy with this drug for the treatment of childhood malignancy. Clinical tests also show that low-dose MTX used in the treatment of rheumatoid arthritis may impair bone formation in a population already predisposed to osteoporosis. However, results of clinical tests are hard to interpret, as it is necessary to take into account malignancy-induced changes in the osseous tissue, long-term immobility and concurrent administration of glucocorticosteroids. We conducted in vivo tests to evaluate the effects of oral and intramuscular administration of high dose of MTX on bone remodeling processes in rats. Effects of MTX on the processes of bone remodeling were evaluated by assessing macrometric and histomorphometric parameters as well as mechanical properties of the femur. The tests were carried out on male Wistar rats. Animals were divided into four groups, composed of 7 animals each: Control group (0.9% NaCl solution), MTX-1 po group (MTX at the dose of 1 mg/kg po daily for 10 days: every day for the first five days, and after an 18-day interval, every day for five days), MTX-1 im group (MTX at the dose of 1 mg/kg im daily for 10 days: every day for the first five days, and after an 18-day interval, every day for five days), MTX-5 im group (MTX at the dose 5 mg/kg im daily for 2 days a week for the period of four weeks). Changes in bone remodeling were examined 4 weeks after the first MTX administration. These results show that MTX administered intramuscularly at high doses inhibited the formation and mineralization of new osseous matrix and impaired mechanical properties of the femoral bone, whereas its oral administration had no effect on bone remodeling in rats.

Administration, Oral↗
PubMed1999

Serum interleukin-6 in renal osteodystrophy: relationship with serum PTH and bone remodeling markers.

Interleukin-6, synthesized by osteoblasts in response to PTH, stimulates osteoclastogenesis and bone resorption in vitro, and it has been implicated in the pathogenesis of bone loss in several clinical situations. The aim of this study was to evaluate whether serum levels of interleukin-6 were increased in patients with renal osteodystrophy, and to investigate the possible relationships between serum interleukin-6 and PTH levels on one hand, and serum interleukin-6 and bone remodeling markers on the other. Serum interleukin-6 (IL-6), intact PTH, osteocalcin, bone alkaline phosphatase (BAP) and carboxyterminal telopeptide of Type 1 collagen (ICTP) were measured in 86 uremic patients. IL-6 (median [range] 16.5 [1.0-430] pg/ml), PTH (279.8 [11-2004] pg/ml), osteocalcin (143.8 [8-921] ng/ml), BAP (20.9 [6-169] U/I) and ICTP (38.8 [1.5-181.5] microg/l) were higher than normal. IL-6 levels correlated with PTH (r= 0.22, p = 0.04) and with ICTP (r = 0.31, p = 0.004). A stronger correlation was found between PTH and circulating bone remodeling markers (r = 0.66 for osteocalcin, r = 0.56 for BAP, and r = 0.39 for ICTP). The correlation between PTH and IL-6 was stronger in those patients (n = 15) with severe secondary hyperparathyroidism (r= 0,71, p = 0.003). On the other hand, in the group of patients (n = 41) with PTH lower than 250 pg/ml, there was no correlation between IL-6 and PTH, while IL-6 correlated with ICTP (r = 0.44, p = 0.006). Serum IL-6 correlates with ICTP which suggests that it may mediate bone resorption in renal osteodystrophy.

Adult↗
PubMed1985

Age and sex dependency of the biochemical indices of bone remodelling.

The values for the bone isoenzyme of serum alkaline phosphatase peak in the first two years of age, between 6 and 7 years of age, before the end of puberty and in the postmenopause. A population between the ages of 29 and 45 provides a reference population to which all other age groupings can be compared. A significant positive correlation was found between bone isoenzyme of serum alkaline phosphatase and urinary hydroxyproline excretion in children as well as after puberty. However, in the children the urinary hydroxyproline excretion was significantly higher when compared with the bone isoenzyme of alkaline phosphatase. A significant positive correlation was found between the bone isoenzyme of alkaline phosphatase and plasma tartrate-resistant acid phosphatase, irrespective of age and sex. The biochemical indices of bone remodelling correlated significantly with the growth rate in children and adolescents. The results are in good agreement with the concept of the coupling of bone formation to bone resorption.

Acid Phosphatase↗
PubMed2007

Effect of modification of hydroxyapatite/collagen composites with sodium citrate, phosphoserine, phosphoserine/RGD-peptide and calcium carbonate on bone remodelling.

This study describes the early interface reaction of cancellous bone to a nanocrystalline hydroxyapatite cement containing type I collagen (HA/Coll) and its modifications with sodium citrate (CI), calcium carbonate (CA), phosphoserine (P) and phosphoserine plus RGD-peptide (RGD). Cylindrical implants of HA/Coll and its modifications were inserted into the tibia of Wistar rats. We analysed 6 specimens per group at days 2, 4, 7, 14 and 28. CI, P and RGD modifications showed improved material properties (finer microstructure and higher compressive strength) compared to CA and HA/Coll implants. The powder X-ray diffraction (XRD) showed that the addition of P and CI led to an increase of alpha-TCP peaks while the diffraction patterns of the non-modified cement (HA/Coll) were quite similar with that of natural bone. All of the implants healed without adverse reactions. A significantly higher number of TRAP-positive osteoclasts were observed around CI, RGD and P on day 7 compared to CA and HA/Coll. Around CI, P and RGD a significantly delayed increase of ED1-positive mononuclear cells was detected. The amount of direct bone contact after 28 days was significantly higher around CI, P and RGD compared to CA and HA/Coll implants. The addition of CI, P and RGD appears to enhance bone remodelling at the early stages of bone healing, leading to increased bone formation around HA/Coll composite cements.

Animals↗
PubMed1995

Effects of IGF-I, alone and in combination with 17 beta-oestradiol, on bone remodelling parameters in ovariectomised rats.

We studied the effects of recombinant human IGF-I (250 micrograms/day) and/or 17 beta-oestradiol (E2; 5 or 50 micrograms/kg/day), s.c., for 28 days, on plasma IGF-I and 1,25-(OH)2 vitamin D3 concentrations and on biochemical indices of bone remodelling (plasma osteocalcin, urinary pyridinolines) in 3 month-old rats that had been ovariectomised (OVX) 6 weeks before. Ten weeks after ovariectomy, plasma 1,25-(OH)2D3 was increased, but IGF-I and bone remodelling indices were within the normal range. RhIGF-I administration to OVX rats increased both IGF-I and 1,25-(OH)2D3 concentrations, as well as plasma osteocalcin and urinary pyridinoline excretion. By contrast, E2 decreased plasma IGF-I and 1,25-(OH)2D3 and the markers of bone remodelling. The combination of rhIGF-I and E2 resulted in intermediate effects. Multiple regression analysis showed that IGF-I correlated with plasma osteocalcin, and also with the urinary excretion of pyridinolines. The data shows that rhIGF-I stimulates bone remodelling in growing OVX rats, and that circulating IGF-I is a determinant of bone remodelling in vivo.

Amino Acids↗
PubMed1995

Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling.

BACKGROUND: The effects of the aminobisphosphonate alendronate sodium on bone mass and markers of bone remodeling were investigated. PATIENTS AND METHODS: In a multicenter, randomized, double-blind, placebo-controlled, 2-year study, 188 postmenopausal women, aged 42 to 75 years, with low bone mineral density (BMD) of the lumbar spine were randomly assigned to 1 of 6 daily treatment groups: placebo for 2 years, alendronate 5 or 10 mg for 2 years, alendronate 20 or 40 mg for 1 year followed by placebo for 1 year, or alendronate 40 mg for 3 months followed by 2.5 mg for 21 months. All subjects were given 500 mg/d of elemental calcium as calcium carbonate. RESULTS: At each dose, alendronate produced significant reductions in markers of bone resorption and formation, and significantly increased bone mass at the lumbar spine, hip, and total body, as compared with decreases (significant at lumbar spine) in subjects receiving placebo. In the 10-mg group, mean urinary deoxypyridinoline/creatinine had declined by 47% at 3 months, and mean serum osteocalcin by 53% at 6 months. Mean changes in BMD over 24 months with 10 mg alendronate were +7.21% +/- 0.49% for the lumbar spine, +5.27% +/- 0.70% for total hip, and +2.53% +/- 0.68% for total body (each P < 0.01) compared to changes of -1.35% +/- 0.61%, -1.20% +/- 0.64% and -0.31% +/- 0.44% at these sites, respectively, with placebo treatment. Progressive increases in BMD of both lumbar spine and total hip were observed in the second year of treatment with 10 mg alendronate (both P < 0.05). CONCLUSION: Alendronate, a potent inhibitor of bone resorption, reduces markers of bone remodeling and significantly increases BMD at the lumbar spine, hip, and total body, and is well tolerated at therapeutic doses (5 or 10 mg daily) in the treatment of osteoporosis in postmenopausal women.

Adult↗
PubMed2006

Bone remodelling algorithms incorporating both strain and microdamage stimuli.

Biomechanical theories to predict bone remodelling have used either mechanical strain or microdamage as the stimulus driving cellular responses. Even though experimental data have implicated both stimuli in bone cell regulation, a mechano-regulatory system incorporating both stimuli has not yet been proposed. In this paper, we test the hypothesis that bone remodelling may be regulated by signals due to both strain and microdamage. Four mechano-regulation algorithms are studied where the stimulus is: strain, damage, combined strain/damage, and either strain or damage with damage-adaptive remodelling prioritised when damage is above a critical level. Each algorithm is implemented with both bone lining cell (surface) sensors and osteocyte cell (internal) sensors. Each algorithm is applied to prediction of a bone multicellular unit (BMU) remodelling on the surface of a bone trabecula. It is predicted that a regulatory system capable of responding to changes in either strain or microdamage but which prioritises removal of damaged bone when damage is above a critical level, is the only one that provides a plausible prediction of BMU behaviour. A mechanism for this may be that, below a certain damage threshold, osteocyte processes can sense changes in strain and fluid flow but above the threshold damage interferes with the signalling mechanism, or causes osteocyte apoptosis so that a remodelling response occurs to remove the dead osteocytes.

Animals↗
PubMed2001

Keratin particle-induced osteolysis: a mouse model of inflammatory bone remodeling related to cholesteatoma.

We implanted keratin and poly(methyl methacrylate) (PMMA) particles to the surface of mouse calvariae to produce a quantitative, localized, inflammatory bone remodeling similar to that seen in cholesteatoma. Both types of particles resulted in increased osteoclast density compared with controls. Osteoclasts infiltrated from marrow and vascular spaces and were active at the periphery of these spaces leading to significant bone remodeling, as demonstrated by the incorporation of bone-labelling fluorophores. Osteoclasts were rarely found on the surface of the calvariae, and mineral apposition rate at the ventral surface was not altered in keratin-implanted animals compared with nonoperated controls. While not useful for the study of the root cause of cholesteatoma, this model will allow the study ofpathologic bone remodeling related to cholesteatoma in a genetically defined animal.

Animals↗
PubMed1997

[Is beta 2-microglobulin a marker of bone remodeling in Paget's disease of bone?].

BACKGROUND: Some authors found in Paget's disease bone and in osteoporosis elevated serum levels of beta-2-microglobulin. The objective of the present work was to assess whether in patients with a different activity of Paget's disease of bone the serum values of beta-2-microglobulin before treatment and after 1,6 and 12 month's treatment with pamidronate can serve as a marker of bone metabolism and whether pamidronate treatment has an impact on the serum concentration of beta-2-microglobulin. METHODS AND RESULTS: 35 patients with Paget's disease of bone (25 men and 10 women, mean age 64 and 72 years resp.) were divided into three groups with a different activity of the disease based on the values with a different activity of the disease based on the values of the bone isoenzyme of alkaline phosphatase in serum. In all serum concentrations of beta-2- microglobulin were examined before and during treatment with pamidronate. The control group was formed by five healthy men and five healthy women, mean age 65 years, and a special group of weight drug addicts dependent on opiates (5 men and 3 women, mean age 26 years). For assessment of beta-2-microglobulin in serum the enzymic immunoassay and fluorescence detection were employed, using Abbott, IMX, MEIA system kits. The serum concentrations of the bone isoenzyme of alkaline phosphatase were assessed by the method used at the Third Medical Clinic of the First Medical Faculty Charles University Prague (8). For statistical processing the non-parametric Friedman test was used to assess the significance of differences between means (p < 0.01) and simultaneous testing at the 5% level of significance. Serum concentrations of beta-2-microglobulin in patients with Paget's disease of bone with a low activity before treatment and after 1, 6 and 12 months of pamidronate treatment were 2.02 +/- 0.9, 2.10 +/- 1.2, 1.9 +/- 1.1 and 1.98 +/- 1.4 ng/l. In patients with a medium activity of the disease the values were 1.80 +/- 0.5, 1.78 +/- 1.02, 2.2 +/- 1.1 and 1.50 +/- 0.7 ng/l. The values in patients with a high activity of the disease were 1.9 +/- 0.9, 2.02 +/- 1.2, 2.40 +/- 0.8 and 2.45 +/- 1.01 ng/l. The values of beta2-microglobulin did not differ when compared with normal values (p < 0,1). CONCLUSIONS: In patients with Paget's disease bone regardless of the different activity of the disease before treatment or after short-term or prolonged pamidronate treatment no differences were revealed in the serum levels of beta-2-microglobulin. Pamidronate treatment did not influence the concentration of beta2-microglobulin and assessment of beta2-microglobulin in Paget's disease bone is no asset.

Adult↗
PubMed2002

A study of the effect of non-linearities in the equation of bone remodeling.

In this paper, we introduced a high-order non-linear equation of bone remodeling to combine with FEM by introducing two non-linearities, i.e. the remodeling coefficient B(t) and the order of non-linear remodeling equation. The influence of each non-linearity was tested based on its mechanical and physiological implications discussed. We use two finite element models to investigate the influences of non-linearities in this equation: a plate subjected to a ramp load, and a 2D model of the cross-section of a vertebra. By importing the idea of topology optimization in engineering, their external shapes and internal density distributions were simulated from unfixed configurations. To a certain extent, the high-order non-linear equation of bone remodeling we suggested here can control the remodeling processes of bones in different stages of growth or at different anatomic sites more effectively, and make it more consistent with physiological reality, i.e. express the remodeling characteristic that bone's best morphology is adapted to its mechanical environment. Furthermore, it is likely to describe the process of bone growth and evolution.

Biomechanical Phenomena↗
PubMed1987

[An experimental study of bone remodeling influenced by mechanical stress].

Bone remodeling influenced by mechanical stresses was studied using ambulatory chickens. They were divided into four groups with the different mechanical forces applied to the leg. I: running along a circular track, II: walking or standing on one leg, III: control, IV: casting. The animals were sacrificed after 12 weeks and undecalcified cross-sections of femurs and tibias were examined using a tetracycline labeling method. Bone formation was evident at both metaphyses of the femur and at the proximal metaphysis of the tibia. More bone formation was observed at the medial quarter of both femur and tibia than in comparison with the lateral quarter. There was, however, no difference in the membraneous ossification between the medial and lateral quarters in Group II. The lack of significant cortical drift at the medial side of the femur and tibia suggests that no bending moment is generated by standing on one leg.

Animals↗