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PubMed2004

Bone remodelation markers are useful in the management of monoclonal gammopathies.

The evaluation of bone disease in multiple myeloma (MM) by conventional radiology has low reproducibility. In the last decade, several serum and urine biochemical parameters, for evaluation of bone turnover, have become available. The present study was designed to explore the value of six bone remodelation markers. It was studied in a series of 176 newly diagnosed patients with monoclonal gammopathies (107 MM and 69 monoclonal gammopathies of unknown significance (MGUS)). As control groups we used 25 patients with benign osteoporosis (BO) and 32 healthy individuals (HI). The bone markers analyzed included: bone resorption markers (BRM) (total pyridinoline, total deoxypyridinoline, free deoxypyridinoline and C-terminal telopeptide of collagen I) and bone formation markers (BFM) (bone alkaline phosphatase (bAP) and osteocalcin (OC)). Serum or urinary levels of BRM were significantly higher in MM patients than in MGUS patients, BO patients or HI (P < 0.001, respectively). BRM were higher in MM patients with lytic lesions. However, only C-terminal telopeptide discriminated MM patients without bone lesions from MGUS patients. BFM did not show significant differences in the aforementioned comparisons, although a trend toward higher values of OC and lower values of bAP in patients with early bone affectation was observed. Ratios BRM/BFM that contained bAP exhibited differences that were most significant between the MM group and other entities, as well as between the different MM subgroups. In fact, the ratios BRM/bAP provided discrimination between the MM subgroup without lyses and MGUS group (P < 0.01). BRM and BFM, especially the ratios, are useful in the evaluation of bone lesions in patients with monoclonal gammopathies.

Adult↗
PubMed1995

[Clinical usefulness of biochemical markers of bone remodeling in osteoporosis].

Osteoporosis with its various clinical expressions is characterized by abnormalities of bone remodeling that can be assessed by biochemical markers of formation and resorption. Measurements of the serum concentration of osteocalcin and bone alkaline phosphatase (formation) and of the urinary excretion of pyridinoline and its peptides (resorption) are the most efficient markers in the investigation of osteoporosis. Recent studies, some of them still in progress, allow to define the clinical use of these markers: firstly to improve the evaluation of the fracture risk, and secondly to monitor the efficacy of antiresorptive drugs.

Biomarkers↗
PubMed1993

Osteopenia and bone-remodeling abnormalities in warfarin-treated lambs.

The physiologic role of osteocalcin (OC), a vitamin K-dependent protein specific to bone, remains elusive. It has been shown that rats maintained on chronic treatment with vitamin K1 and its antagonist warfarin exhibit a marked decrease in bone osteocalcin because noncarboxylated osteocalcin does not bind to bone hydroxyapatite. To assess the role of OC in bone remodeling, we applied the warfarin model to growing lambs. We analyzed the bone changes after 3 months of concurrent warfarin and vitamin K1 treatment. Four groups of four lambs were constituted at birth and received daily a saline solution (control group, CT), 4 mg/kd/day of vitamin K1 (vitamin K group), 4 mg/kg/day of vitamin K1 + 75 or 150 mg/kg/day of warfarin (W75 and W150 group, respectively). In warfarin-treated animals, bone osteocalcin levels were decreased, both in the metaphysis (9% compared to controls) and the diaphysis (30% compared to controls) of the metacarpals. The fraction of noncarboxylated osteocalcin measured every month in the serum was significantly higher in warfarin-treated lambs than in controls at each timing point (37.6 +/- 2.6% in W75 and 48.7 +/- 5.2% in W150 versus 14.4 +/- 3.8% in controls at 3 months). Compared to non-warfarin-treated animals (NW), the main histomorphometric parameters measured on the iliac crest after tetracycline double labeling were significantly reduced in the warfarin-treated lambs: 12.2 +/- 5.2 versus 18.6 +/- 4.7% in NW (p < 0.03) for the cancellous bone area, which reflects the trabecular bone density; 14.7 +/- 6.1 versus 21.0 +/- 3.6% in NW (p < 0.03) for the eroded perimeter, and 0.315 +/- 0.064 versus 0.561 +/- 0.23 microns 3/microns 2/day in NW (p < 0.02) for the tetracycline-based bone formation rate. In conclusion, the depletion of osteocalcin in the bone of lambs induced within 3 months a marked osteopenia that resulted from a decrease in resorption and a more pronounced decrease in bone formation. Our data suggest that the presence of osteocalcin, the major gla-containing protein of bone, may be important for the maintenance of a normal bone mass and remodeling of trabecular bone.

Animals↗
PubMed1979

Studies on bone-remodeling rates on the Beagle: A comparison between similar biopsy sites on different ribs.

Two male littermate standardized colony-raised Beagles were studied to find out whether there was any statistically significant difference in the measurements of bone-remodeling determinations at similar sites on different ribs of the animal. Tetracycline fluorescent-labeling studies were performed on these animals, the midportion of the proximal, midshaft, and distal thirds being sampled from the 5th, 7th, 9th, and 11th ribs. Statistical analysis of the findings indicates that there is no significant difference in bone-remodeling activity between similar sites on alternate ribs. This fact permits studies on bone-remodeling activity in an animal to be done in which the same animal is used as its own control and in which more than two experimental biopsy samples are required.

Animals↗
PubMed2004

Investigating the effect of remodelling signal type on the finite element based predictions of bone remodelling around the thrust plate prosthesis: a patient-specific comparison.

The resorption of bone in the human femur following total hip arthroplasty is recognized to be related to the loading in the bone surrounding the prosthesis. However, the precise nature of the mechanical signal that influences the biological remodelling activity of the bone is not completely understood. In this study, a validated finite element modelling methodology was combined with a numerical algorithm to simulate the biological changes over time. This was used to produce bone remodelling predictions for an implanted thrust plate prosthesis (Centerpulse Orthopedics Limited) in a patient specific bone model. The analysis was then repeated using different mechanical signals to drive the remodelling algorithm. The results of these simulations were then compared to the patient-specific clinical data, to distinguish which of the candidate signals produced predictions consistent with the clinical evidence. Good agreement was found for a range of strain energy based signals and also deviatoric remodelling signals. The results, however, did not support the use of compressive dilatational strain as a candidate remodelling signal.

Bone Plates↗
PubMed1993

Recent advances in understanding mechanically induced bone remodeling and their relevance to orthodontic theory and practice.

This review highlights recent developments in bone cell biology, evaluates previous research, and offers future direction toward improving our understanding of events that mediate orthodontic tooth movement. The in vivo and in vitro models that have been developed to examine the responses of connective tissues and how they have contributed to our understanding of the mechanisms involved in mechanically induced bone remodeling are discussed in detail. Osteoblasts are now recognized as the cells that control both the resorptive and the formative phases of the remodeling cycle, and receptor studies have shown them to be the target cells for resorptive agents in bone. The osteoblast is perceived as a pivotal cell, controlling many of the responses of bone to stimulation with hormones and mechanical forces. It is apparent that not all the cellular responses induced by mechanically deformed tissues can be explained by the current paradigm emphasizing the importance of prostaglandin production and cAMP elevation; the mobilization of membrane phospholipids giving rise to inositol phosphates offers an alternative second messenger pathway. It is also argued from circumstantial evidence that changes in cell shape produce a range of effects mediated by membrane integral proteins (integrins) and the cytoskeleton, which may be important in transducing mechanical deformation into a meaningful biologic response.

Animals↗
PubMed2000

Molecular control of bone remodeling and osteoporosis.

Osteoprotegerin ligand (OPGL, TNFS11) and its receptor RANK (TNFRS11A) are essential for the development and activation of osteoclasts and critical regulators of physiological bone remodeling and osteoporosis. Production of OPGL by activated T cells can directly regulate osteoclastogenesis and bone remodeling. This may explain why autoimmune diseases, cancers, leukemias, asthma and chronic viral infections such as hepatitis and HIV result in systemic and local bone loss. OPGL is also the pathogenetic factor that causes bone and cartilage destruction and clinical crippling in arthritis. Inhibition of OPGL binding to RANK via the natural decoy receptor osteoprotegerin (OPG) prevents bone loss in postmenopausal osteoporosis and cancer metastases and completely blocks crippling in a rat model of arthritis. Moreover, OPG expression is induced by estrogen which provides a molecular explanation of postmenopausal osteoporosis in women.

Animals↗
PubMed2004

Peri-implant bone remodeling after total hip replacement combined with systemic alendronate treatment: a finite element analysis.

In order to decrease the peri-implant bone loss during the life-time of the implant, oral use of anti-osteoporosis drugs (like bisphosphonates) has been suggested. In this study, bone remodeling parameters identified from clinical trials of alendronate were used to simulate the effect of those drugs used after total hip arthroplasty on the peri-implant bone density. Results of the simulation show that the oral administrated drugs increase bone density around the implant and decreases, at the same time, the micromovements between the implant and the surrounding bone tissue. Incorporation of drug effect in numerical studies of bone remodeling is a promising tool especially to predetermine safe bisphosphonate doses that could be used with orthopedic implants.

Administration, Oral↗
PubMedDate not supplied

Clinical outcome and quantitative evaluation of periprosthetic bone-remodeling of an uncemented femoral component with taper design. A prospective study.

The rationale of uncemented taper stems is based on fixation in the proximal portion of the femoral diaphysis, a self-locking principle, and a low modulus of elasticity. The aim of this study was to evaluate a collarless femoral component designed to be a three-dimensional taper for press-fit insertion with regard to clinical outcome, efficacy of fixation, incidence of osteolysis, and periprosthetic bone-remodeling. The first 48 consecutive patients (50 hips) with osteoarthritis who had had primary total hip arthroplasty using the Cerafit Multicone stem and the Cerafit Triradius-M press-fit cup with alumina-alumina pairing (Ceraver Osteal, Paris, France) were followed-up for a mean of 2.3 years (2 to 2.5 years). The mean age of patients at index operations was 52.5 years. Current criteria were used for clinical and radiological assessment. Quantitative evaluation of periprosthetic bone-remodeling was prospectively assessed using computed tomography. Clinical and radiological follow-up was obtained in all hips. Forty-nine hips (98%) were clinically rated good or excellent, one hip (2%) was rated fair, owing to a persisting limp. The mean preoperative Harris Hip Score was rated 62, and it has improved to 93.5 at the time of follow-up. One hip (2%) had marked postoperative thigh pain. This pain had disappeared at 3-month follow-up. All stems showed radiological signs of stable fixation by bone ingrowth. No stem required revision. Thirty-four hips (68%) had either no change in femoral bone density or only patchy loss of bone density isolated to Gruen zones 1 and 7. Sixteen hips (32%) had some reduction of bone density isolated to zone 1. Radiolucencies without progression were found in zones 1 and 7 in 3 hips (6%), and in zone 1 alone in 3 other hips (6%). A slight cortical hypertrophy was seen in 3 hips (6%). Twenty-three hips (46%) developed radiographic appearance of bone apposition at the stem tip as partial pedestal (19 hips) and as complete pedestal (4 hips). No signs of cup loosening were detected at follow-up. Twenty-four patients (25 hips) were eligible for computed tomography. The mean decrease of the overall bone mineral density in the metaphyseal portion of the femur one year after insertion of the stem was rated 15.4%, and the mean decrease of the cortical bone mineral density was rated 17.2%. On the other hand, a mean decrease of the cortical bone mineral density of less than 5% was observed in the diaphyseal portion of the femur around the implant. The clinical and radiological results of the Cerafit Multicone stem at a mean follow-up of 2.3 years are very promising and do not contrast with those achieved using other uncemented stems with tapered design. Furthermore, results of quantitative evaluation of periprosthetic bone-remodeling were considered satisfactory favourably with others reported in the literature using stems inserted without cemented.

Adult↗
PubMed2005

Osteocalcin enhances bone remodeling around hydroxyapatite/collagen composites.

The effect of osteocalcin (OC), an extracellular bone matrix protein, on bone healing around hydroxyapatite/collagen composites was investigated. Cylindrical nanocrystalline hydroxyapatite implants of 2.5-mm diameter containing 2.5% biomimetically mineralized collagen type I were inserted press-fit into the tibial head of adult Wistar rats. To one implant group, 10 mug/g OC was added. Six specimens per group were analyzed at 2, 7, 14, 28, and 56 days. After 14 days, newly formed woven bone had reached the implant surface of the OC implants whereas a broad fibrous interface could still be observed around controls. Woven bone was formed directly around both implant groups after 28 days and had been replaced partially by lamellar bone around the OC implants only. No significant differences in total bone contact were seen between both groups after 56 days. The higher number of phagocytosing cells and osteoclasts characterized immunohistochemically with ED1, cathepsin D, and tartate-resistant alkaline phosphatase around the OC implants at the early stages of bone healing suggests an earlier onset of bone remodeling. The earlier and increased expression of bone-specific matrix proteins and multifunctional adhesion proteins (osteopontin, bone sialoprotein, CD44) at the interface around the OC implants indicates that OC may accelerate bone formation and regeneration. This study supports the observations from in vitro studies that OC activates both osteoclasts and osteoblasts during early bone formation.

Animals↗
PubMed2002

Bone origin of the serum complex of calcium, phosphate, fetuin, and matrix Gla protein: biochemical evidence for the cancellous bone-remodeling compartment.

We previously described the discovery of a fetuin-matrix Gla protein (MGP)-mineral complex in the serum of rats treated with the bone-active bisphosphonate etidronate and showed that the appearance of this complex in serum correlates with the inhibition of bone mineralization by etidronate. In this study we show that the inhibition of bone resorption by treatment with the hormone calcitonin, the cytokine osteoprotegerin, or the drug alendronate, completely inhibits the generation of the fetuin-mineral complex in response to etidronate injection. These observations can be explained best by the bone-remodeling compartment (BRC), a cancellous bone compartment in which the concentrations of calcium and phosphate are determined directly by the combined actions of the osteoclast and the osteoblast. When bone mineralization is acutely inhibited by etidronate, the BRC model predicts that the continuing action of osteoclasts will cause a sharp rise in the concentrations of calcium and phosphate in the aqueous solution of the BRC with the consequent spontaneous formation of calcium phosphate crystal nuclei in which growth then would be arrested by formation of a complex with fetuin. When the inhibition of bone resorption by calcitonin, osteoprotegerin, or alendronate is combined with the acute inhibition of bone mineralization with etidronate, the BRC model correctly predicts that there will no longer be a sharp rise in calcium and phosphate, and, therefore, there will no longer be the formation of the fetuin-mineral complex. The vascular nature of the BRC is supported by the observations that the fetuin component of the fetuin-mineral complex is derived from plasma fetuin and that the fetuin mineral complex appears in plasma within minutes of the inhibition of bone mineralization with etidronate.

Alendronate↗
PubMed1999

Periprosthetic bone remodelling after total knee arthroplasty: early assessment by dual energy X-ray absorptiometry.

The present investigation aims to evaluate periprosthetic bone remodelling after total knee arthroplasty by the use of dual-energy X-ray absorptiometry (DXA). Twelve patients affected by osteoarthrosis of the knee joint underwent primary total knee arthroplasty at an average age of 70.5 years. None of them had received a knee prosthesis before on the contralateral side. Anteroposterior and lateral DXA measurements of the femur, tibia and total knee (both sides) were taken 2 weeks, 3 and 9 months postoperatively. The 2-week measurement was used as an individual reference value to be compared with the 3- and 9-month findings. In addition, the contralateral knee was investigated also in order to estimate how far bone mineral loss was due to implantation or to an individual decline in bone mineral density (BMD). The comparison of BMD values after knee arthroplasty revealed a conspicuous decrease of bone density within 9 months. Bone mineral loss amounted to an average of 9.2% in anteroposterior and 17.8% in lateral DXA measurements. Lateral femur shots showed an average decrease of density of even 21.5%. In contrast, the BMD values of the contralateral knees remained almost unchanged. DXA, especially lateral shots of the femur, promises to be a suitable method for early assessment of periprosthetic bone remodelling after total knee arthroplasty.

Absorptiometry, Photon↗
PubMed1992

Bone remodelling does not decline after menopause in vertebral fracture osteoporosis.

There is considerable current interest in whether activators of bone remodelling, such as IL-1 and other cytokines, are involved in the pathogenesis of osteoporosis. We have therefore studied indices relating to remodelling activation in 50 patients with postmenopausal vertebral osteoporosis and 12 with hip fracture osteoporosis in comparison with 25 age- and sex-matched controls. Because of uncertainty regarding the accuracy of current biochemical markers of bone formation with respect to the estimation of whole body rates of bone formation, a 85Sr-based radioisotopic method was used. This method was previously validated by comparison with data obtained after double in vivo labelling of transiliac biopsies taken nearly simultaneously. Bone resorption was estimated from urinary hydroxyproline data. Controls selected for their continued good health showed a progressive and statistically highly significant decline in indices of bone formation with time after menopause. No such decline was seen in the vertebral fracture patients (P less than 0.005). There were no hip fracture patients within 10 years of menopause so this statistical test could not be applied appropriately to them. The hydroxyproline data were consistent with the suggestion arising from the bone formation data that remodelling declines progressively after menopause in the controls but not in the vertebral fracture patients. The data also suggested that these two fracture groups were in more negative calcium balance than the controls, this being particularly marked in the hip fracture cases. Plasma osteocalcin data correlated moderately well with the kinetic measurements of bone formation. It is concluded that vertebral fracture osteoporosis is associated with prolongation of menopausal levels of bone remodelling which is inappropriate by comparison with healthy controls.

Age Factors↗
PubMed2004

Collagen type I increases bone remodelling around hydroxyapatite implants in the rat tibia.

The early interface reaction of cancellous bone to a nanocrystalline hydroxyapatite (HA) cement containing 3 wt% collagen type I (HA/Coll) with a setting under physiological temperature and pH was observed using immunohistochemical techniques. Pure HA served as a control. Cylinders with a diameter of 2 mm were implanted into the proximal tibia of 72 adult Wistar rats. Histological sections of 6 animals were prepared after 1, 2, 4, 6, 14 and 28 days. First, osteoblast-like cells as well as a marked reaction for osteonectin, osteopontin and its ligand CD44 were observed as early as 2 days after implantation at the interface around HA/Coll implants. Further, reactivity for ED1 and cathepsin D, both markers for phagocytotic cells, appeared earlier and stronger around HA/Coll. In cell counts, a significantly higher average number of ED1- and cathepsin D-positive phagocytotic cells was observed around the HA/Coll implants on days 6 (p < 0.01), 14 and 28 (p < 0.05). The number of osteopontin-positive cells was significantly higher around HA/Coll implants at days 6 and 14 (p < 0.05). Two weeks after the implantation, first islands of newly formed woven bone were observed around the HA/Coll implant, but not around the control implant. The amount of direct bone contact after 28 days averaged 28% around pure HA and 51% around HA/Coll implants (p < 0.05). While both implants displayed a good osteoconductivity, a higher bone remodelling activity was observed around collagen-containing HA implants compared to pure HA implants. It appears that the addition of collagen to HA implants can enhance both phagocytotic and osteogenic processes. This may result in an earlier acceptance and better osseointegration of the HA/Coll implants into the surrounding tissue.

Animals↗
PubMed2001

Effect of femoral stiffness on bone remodeling after uncemented arthroplasty.

The current study examined the relationships among femoral stiffness, implant stiffness, and bone remodeling in 40 femurs retrieved at autopsy from 20 patients with unilateral uncemented hip replacements. The purpose of the study was to determine if the magnitude of periprosthetic bone loss after arthroplasty was correlated with, and could be predicted from, stem and femoral stiffness terms. For analysis, the contralateral normal femur was used as a control to represent the unremodeled condition of the in vivo implanted femur. Bone loss attributable to remodeling was quantified by video-densitometric analysis. Stiffness terms were calculated as the product of the elastic modulus and geometric properties digitized from cross-sectional slab radiographs. Femoral stiffness calculations accounted for variations in modulus attributable to patient differences in bone mineral density and geometric properties attributable to differences in the shape of individual femurs. Similarly, calculations of implant stiffness accounted for variations in implant shape. Results showed axial bone stiffness was the variable most strongly correlated with bone loss. Individual stem stiffness terms were not significantly correlated with bone loss. Multiple linear regression analysis, using stem-to-bone stiffness ratios as independent variables, accounted for 46% of the variance in bone loss data. In the regression analysis, the axial stem-to-bone stiffness ratio was the strongest correlate with bone loss. Although these results show the influence of mechanical stiffness factors on bone remodeling, other factors (hormonal status, drugs, disease, activity level) could represent the variance in bone loss data not accounted for in the study.

Aged↗
PubMed1999

Clinical utility of biochemical markers of bone remodeling.

Remodeling is essential for bone health. It begins with resorption of old bone by osteoclasts, followed by the formation of new bone by osteoblasts. Remodeling is coupled (formation is linked to resorption). After middle age or perhaps beginning earlier, bone loss occurs because resorption exceeds formation. This imbalance is accentuated by estrogen deficiency as well as by many diseases and conditions. Biochemical markers that reflect remodeling and can be measured in blood or urine include resorption markers (e.g., collagen cross-links) and formation markers (e.g., alkaline phosphatase). Bone markers exhibit substantial short-term and long-term fluctuations related to time of day, phase of the menstrual cycle, and season of the year, as well as diet, exercise, and anything else that alters bone remodeling. These biological factors, in addition to assay imprecision, produce significant intra- and interindividual variability in markers. Bone marker measurements are noninvasive, inexpensive, and can be repeated often. Unfortunately, most of the studies that provided insight on clinical situations did not focus on markers as a primary endpoint. Bone markers have been useful in clinical practice and have been helpful in understanding the pathogenesis of osteoporosis and the mechanism of action of therapies. In clinical trials, markers aid in selecting optimal dose and in understanding the time course of onset and resolution of treatment effect. Clinical questions that might be answered by bone markers include diagnosing osteoporosis, identifying "fast bone losers" and patients at high risk of fracture, selecting the best treatment for osteoporosis, and providing an early indication of the response to treatment. Additional information is needed to define specific situations and cut points to allow marker results to be used with confidence in making decisions about individual patients.

Biomarkers↗
PubMed1993

Total and regional bone mass values and biochemical markers of bone remodeling in endometriosis.

OBJECTIVE: TO measure peripheral, axial, and total bone mass and to assess markers of bone remodeling in women with endometriosis, with the aim of addressing previous reports of diminished peripheral bone mass in these patients. METHODS: Whole body bone densitometry, estradiol (E2) levels, and biochemical bone markers (calcium, phosphorus, total alkaline phosphatase, tartrate-resistant acid phosphatase, and total proteins) were determined in 28 patients with endometriosis and compared with findings in 33 controls. RESULTS: There were no significant differences between the groups in bone mass at different sites or in biochemical bone markers. We observed a significant negative correlation between tartrate-resistant acid phosphatase and E2 levels (P < .001) and with total (P < .001), head (P < .01), and axial (trunk) (P < .001) bone mass. Total alkaline phosphatase did not correlate with any of the indices studied. CONCLUSIONS: Bone mass was not lower in any of the areas studied in women with endometriosis. There was a significant negative correlation of tartrate-resistant acid phosphatase with E2 and with total, head, and trunk bone mass.

Absorptiometry, Photon↗
PubMed1976

The effects of rigidity of internal fixation plates on long bone remodeling. A biomechanical and quantitative histological study.

The effect of rigidity of internal fixation plates on long bone remodeling was studied using two types of plates with considerable differences in stiffness. The plated bones were subjected to bioengineering quantitative histological, and cortical thickness studies after 9 and 12 months. The biomechanical results, together with the quantitative histological measurements of the macroscopic architecture, showed that tissue characteristics of the plated bones were similar. However, because of the larger cortical area, the less regidly plated femora can sustain significantly higher loads and energy before failure. Cortical thickness measurements also showed that rigid plate immobilization results in thinning of the cortex of the underlying bone. The experimental results suggest that cortical bone remodels according to functional stress demands, and the osteoporosis secondary to rigid plate protection is consequent to thinking of its cortex.

Animals↗