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Observations of convergence and uniqueness of node-based bone remodeling simulations.

Some investigators have indicated that mathematical theories and computational models of bone adaptation may not converge and that the density solutions from such simulations are dependent on the initial density distribution. In this study, two-dimensional finite element models were used to investigate the effect of initial density distribution on the final density distribution produced using a node-based bone remodeling simulation. The first model was a generic long bone, and the second was a proximal femur, For each model, we conducted time-dependent, node-based, linear rate-law bone remodeling simulations. Five initial density conditions were used with the generic long bone and three with the proximal femur. Remodeling simulations were performed, and the largest average nodal density differences at the end of the simulations were 0.000010 g/cm3 and 0.000006 g/cm3 for the generic long bone and proximal femur models, respectively. Results illustrate that, for a given set of loads and a given finite element model, the node-based bone adaptation algorithm can yield a unique density distribution. In conjunction with previous studies, this finding suggests that uniqueness of the density solution is dependent on both the mathematical theory and the computational implementation.

Algorithms↗

Effects of intermittent hPTH(1-34) alone and in combination with 1,25(OH)(2)D(3) or risedronate on endosteal bone remodeling in canine cancellous and cortical bone.

Therapies utilizing intermittent human parathyroid hormone(1-34) (hPTH[1-34]) in combination with other agents have recently been proposed as possible anabolic regimens for the treatment of osteoporosis. We conducted a 24 week study in aged beagle dogs to determine the effects of intermittent hPTH(1-34) administered alone or in combination with 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on the endosteal remodeling in cancellous and cortical bone. Additionally, we tested the interaction between hPTH(1-34) and a new potent bisphosphonate, risedronate. The three treatment groups were compared with a vehicle control group. Kinetic reconstruction of the remodeling unit revealed substantial differences between the groups in resorption and formation at the basic multicellular unit level. Although the estimates of final erosion depth were unaffected by treatment, tunneling resorption was noted in six of the eight dogs administered hPTH(1-34) alone. These qualitative morphological changes in the resorption lacunae were attenuated or absent in dogs administered hPTH(1-34) in combination with either 1,25(OH)(2)D(3) or risedronate. Functional periods for resorption were significantly increased, and the resorption rates were significantly decreased in the hPTH(1-34) + risedronate group. Analyses of the formative site demonstrated that the wall thickness was significantly increased and the bone balance significantly more positive in all three hPTH(1-34) treatment groups. The most positive bone balance was achieved in the combined hPTH(1-34) + risedronate group (+ 15.6 + or - 14.2 mm, p <0.05). Increases in the mineral apposition rate in the early phases of the formative period suggest that an increase in osteoblastic activity (number or function) may contribute to the increase in wall thickness. Treatment with hPTH(1-34) alone or in combination with 1,25(OH)(2)D(3) caused an approximately 2-fold increase in the activation frequency in cancellous bone, which was essentially normalized to control values by the coadministration of risedronate. The impact of these changes on the cancellous bone microstructure was significant only in the combined hPTH(1-34) + risedronate group where normalized bone turnover in the face of a positive bone balance effected a significant increase in the trabecular thickness. Analyses of sequential fluorochrome labels, administered to reconstruct the temporal changes in intracortical activation, demonstrated the presence of an apparent cyclic pattern of activation in the cortex of placebo-treated dogs. Generally, activation was increased throughout the study in dogs administered hPTH(1-34) alone or in combination. However, in the hPTH(1-34) + risedronate group, activation was significantly blunted toward the end of the study, and the cyclic pattern of activation was modulated. These data suggest that intermittent hPTH(1-34) in combination with risedronate may be superior to hPTH(1-34) in combination with 1,25(OH)(2)D(3) as a therapeutic regimen for osteoporosis due to the protective effect of this bisphosphonate on the cortical and endocortical envelope.

Animals↗

Alpha-particle doses to cells of the bone remodeling cycle from alpha-particle-emitting bone-seekers: indications of an antiresorptive effect of actinides.

There are indications that alpha-particle-emitting bone-seekers such as plutonium or americium could enhance bone mass by suppressing bone resorption. To assess this possibility, this study calculates doses from alpha-particle emitters to the cells involved in trabecular bone turnover. Alpha-particle energy deposition in tissue from a bone surface source was calculated by Monte Carlo modeling. This was combined with bone surface cellular geometry to yield dose rates to cells during the remodeling cycle. Bone-resorbing osteoclasts receive on average 50 times the dose rate that bone-forming osteoblasts receive. Newly formed bone shields osteoblasts from alpha particles emitted by the buried deposit of alpha-particle emitters. However, at alpha-particle bone-seeking radionuclide intakes known to cause changes in remodeling (about 3700 Bq/kg body weight), the alpha-particle dose to osteoclasts corresponds to an extremely low rate of cell traversals (0.07% per cycle). It is therefore unlikely that perturbation of bone remodeling by alpha-particle bone-seeking radionuclides is directly caused by alpha-particle traversals of remodeling cells; some other indirect mechanism might be involved.

Actinoid Series Elements↗

Implementation of strain rate as a bone remodeling stimulus.

Strain rate is implemented as a stimulus for surface bone remodeling. Using idealized models for trabecular bone structures, the surface remodeling predictions using the strain rate as the stimulus are compared with the predictions using the peak strain magnitude as the stimulus. For a uniaxially loaded cruciform shape, the comparison shows that the two surface remodeling stimuli predict the same final shape under a periodic compressive load, but the two evolutionary paths to final shapes are different. Two biaxially loaded regular grid models of trabecular structure were considered, one a grid of square diamond shaped elements and the other a brick wall patterned grid. For both of these idealized trabecular structures, the comparison shows that the two surface remodeling stimuli predict the same final shape under a periodic compressive load, even from these distinctly different initial grid patterns, and the evolutionary paths to final shapes are quite different. In general the two stimuli do not predict the same remodeling and the conditions under which they do are derived. The models developed are also applied to the data from the animal experiments reported in Goldstein et al. (1991), and it is shown that the strain rate stimulus predicts bone remodeling similar to what was experimentally observed.

Animals↗

Changes in bone remodeling rate influence the degree of mineralization of bone.

Mineralization of bone matrix implies two successive steps, a primary mineralization on the calcification front followed by a slow process of secondary mineralization progressively adding about 50-60% of the mineral content on bone matrix. Our model is that antiresorptive agents prolong the lifetime of the basic structural units (BSUs) by causing a marked reduction in the birth rate of basic multicellular units (BMUs), and increase the degree of mineralization of bone (DMB) by allowing a more complete secondary mineralization. Conversely, agents or events provoking an augmentation of the birthrate of BMUs and a decrease of the lifetime of BSUs lead to resorption of new BSUs before they have fully completed their secondary mineralization, leading to the presence of incompletely mineralized BSUs and a low mean DMB value, as measured by quantitative microradiography. Measurements of DMB (distribution and mean value) under circumstances with various remodeling activities favor our model. In postmenopausal osteoporotic women treated during 2 or 3 years with alendronate (10 mg/day), an increase of the mean DMB of approximately 7 to 10% was found, due to a marked reduction in the bone remodeling. In contrast, an activation of bone remodeling as in primary hyperparathyroidism lowered the mean DMB.

Adult↗

Bone remodeling around total hip implants.

This chapter reviews the research in the computer simulation of bone remodeling caused by hip implants and also attempts to give nonmedical personnel a basic introduction to total hip arthroplasty and implant-induced bone resorption. First, a short discussion of the hip arthroplasty procedure and the results of follow-up studies are presented to motivate the study of hip prostheses. Current implant materials and technologies and future trends in implant design are reviewed. A description of what are believed to be the mechanisms of bone resorption due to femoral implantation is presented. Different mathematical theories of bone remodeling and their application to the problem of implant analysis are presented, and recent advances in the finite element modeling of bone resorption and implant micromotion are discussed.

Algorithms↗

Ovariectomy and trabecular bone remodeling in the dog.

The early effects of ovariectomy (OX) on serum biochemistry and trabecular bone remodeling in the dog were investigated. Adult beagle dams were ovariectomized (n = 8) or sham-ovariectomized (n = 6) and followed for 6 months. All dogs received an iliac crest biopsy at the time of surgery to establish baseline remodeling data. A second contralateral biopsy was obtained at sacrifice. Serum osteocalcin became significantly elevated approximately 8 weeks following OX and remained elevated for the duration of the study. Histomorphometric analysis of serial transilial specimens showed that, at 6 months, OX had significantly increased the rate of bone remodeling in the ilium. Six months following OX in the dog, changes in serum biochemistry and trabecular bone remodeling in the ilium are consistent with those seen in postmenopausal women suffering from "high remodeling osteoporosis".

Animals↗

Short-term chronic fluoride administration and trabecular bone remodeling in beagles: a pilot study.

We carried out a pilot project to examine the alterations in trabecular bone remodeling activity of spayed Beagle dams exposed to 0.7 mg/kg body wt/day of sodium fluoride (NaF) for a 6 month period. The results indicated that short-term NaF administration does activate trabecular bone remodeling activity by stimulating the formation of new Basic Multicellular Units (BMUs) of bone remodeling activity. However, interference with bone cell differentiation, with the functional efficiency and/or life-span of individual osteoclasts and osteoblasts followed. Cellular toxic effects appear early with NaF administration, and as such, suggest that the increases in bone mass seen early in the course of NaF treatment may be negated by prolonged administration of this substance. However, preservation of bone mass will probably result with long-term therapy, due to decreases in numbers of bone cells, in their functional efficiencies, and in their individual life-spans.

Animals↗

Bone remodelling of a proximal femur with the thrust plate prosthesis: an in vitro case.

The key to the development of a successful implant is an understanding of the effect of bone remodelling on its long-term fixation. In this study, clinically observed patterns of bone remodelling have been compared with computer-based predictions for one particular design of prosthesis, the Thrust Plate Prosthesis (Centerpulse Orthopedics, Winterthur, Switzerland). Three-dimensional finite-element models were created using geometrical and bone density data obtained from CT scanning. Results from the bone remodelling simulation indicated that varying the relative rate of bone deposition/resorption and the interfacial conditions between the bone and the implant could produce the trend towards the two clinically observed patterns of remodelling.

Arthroplasty, Replacement, Hip↗

Bone remodeling in immediately loaded and unloaded titanium dental implants: a histologic and histomorphometric study in humans.

Remodeling is thought to prevent microdamage accumulation caused by repetitive loading and to increase the fatigue life of bone. The bone remodeling rate (BRR) is the period of time needed for new bone to replace the existing bone and to allow for the adaptation of bone to its environment. BRR is expressed as a percentage or volume of new bone within a specific time period. The aim of the present study was to evaluate bone remodeling events on submerged and immediately loaded dental implants. Twelve patients with edentulous mandibles participated in this study. All patients were rehabilitated with fixed mandibular prostheses, with 10 dental implants per patient. An additional implant was inserted in the most distal posterior mandibular jaw region. In 6 patients, these additional implants were loaded with a fixed provisional prosthesis the same day of the implant surgery and loaded. In the other 6 patients, the additional implants were left submerged and not loaded. After 6 months, all the additional implants were retrieved with a trephine. The percentage of woven and lamellar bone, number of osteoclasts and osteoblasts, and percentage of bone labeled by tetracycline at 0.5 mm and 2 mm from the implant surface were evaluated. The percentage of lamellar bone, number of osteoblasts, and percentage of bone tetracycline labeling was significantly higher in the loaded implants than in the unloaded implants (P =.0001). Also in the loaded implants, the percentage of woven and lamellar bone, number of osteoclasts and osteoblasts, and percentage of bone tetracycline labeling was significantly higher at 0.5 mm than at 2 mm from the implant surface (P =.0001). No such differences were found in unloaded implants (P =.377). In conclusion, we found that (1) loading appeared to stimulate bone remodeling at the interface, (2) a higher percentage of lamellar bone was found in loaded implants, (3) the percentage of bone labeling was higher at the interface of loaded implants, (4) no differences were found in the BRRs between immediately loaded and unloaded implants, and (5) immediate loading had not interfered on the lamellar bone formation at the interface and had not produced formation of woven bone at the interface.

Adult↗

A CAD-CAM methodology to produce bone-remodelled composite femurs for preclinical investigations.

Femoral bone remodelling, following total hip arthroplasty, is a clinically observed phenomenon attributed to the changed stress environment of the postoperative implanted hip. While this process cannot be avoided, there is concern as to its consequences on the long-term survival of hip joint replacements. Previous methods of studying remodelling, such as clinical or animal-based studies, or finite element analyses, have their limitations. The aim of this study is to develop experimental specimens incorporating bone resorption features typical of clinically successful implants. This work describes the use of computer aided design/manufacturing methods (CAD-CAM) to produce these specimens, based on modifying commercially available composite femurs. The procedures are investigated and verified for two different designs of cemented prostheses (Lubinus SPII and Muller Curved). Quantitative clinical data is used to define the remodelled geometry of a CAD model of the femur for each stem design. Composite femur specimens are machined using a three-axis milling machine, where each specimen can be accurately positioned using a custom-designed jig and a digitizer system. The accuracy of the process is assessed by analysing the deviation of the digitized premachined and postmachined surfaces of each specimen in relation to the CAD model. The results demonstrate that the procedure can be used for developing in vitro specimens with bone resorption features. These specimens are proposed as a useful tool for performing preclinical trials, such as load transfer or longevity/stability testing, with the advantage of modelling a long-term clinical situation, rather than solely analysing implanted femurs in an immediate postoperative state.

Arthroplasty, Replacement, Hip↗

Low intensity pulsed ultrasound accelerated bone remodeling during consolidation stage of distraction osteogenesis.

Bone regeneration in distraction osteogenesis occurs under tensile stress with axial rhythmic distraction after osteotomy. In this study, we evaluated if the low intensity pulsed ultrasound (LIPUS) was also effective on enhancement of bone remodeling during consolidation stage of distraction osteogenesis. Open osteotomy of seventeen 18-week-old female New Zealand rabbit tibiae were performed. The distraction was applied with the rate of 1 mm per day. LIPUS (30 mW/cm(2), 1.5 MHz) was delivered for 20 min per day during 4-week consolidation stage (n=10). The animals without treatment served as sham group (n=7). Plain X-ray, peripheral quantitative computational tomography (pQCT), and torsional test were performed. Results showed that smaller radiolucent interzone of LIPUS treatment group was gradually occupied by calcified tissue in plain X-ray at week 2. The bone mineral density (BMD) measured on radiographs increased by 9.18% in the LIPUS group. Bone mineral content (BMC), hard callus volume, and bone strength index (BSI) measured by pQCT were 83%, 116%, and 94%, respectively, in LIPUS group that were significantly greater than those of the controls. At the 4th week, LIPUS-treated callus showed the development of neocorticalization in the proximal and distal region. The BMC, hard callus volume, and BSI of LIPUS group decreased and was not significantly different from control. This was also confirmed by the maximum torque of LIPUS-treated callus (1424.2+/-457.3 N . mm) obtained at week 4, which did not differ from that of the sham group (1968.8+/-895.1 N . mm). In conclusion, the effective period of LIPUS treatment was at the initial stage of consolidation, with accelerated bone formation and remodeling.

Animals↗

The course of some bone remodelling plasma metabolites in healthy horses and in horses offered a calcium-deficient diet.

An inquiry was carried out to assess the concentrations of plasma metabolites related to bone remodelling in 21 saddle horses of Warmblood breed aged 4-26 years, five draught horses of Ardennes breed aged 4-10 years, and 10 Ardennes foals aged 9-11 months. They were fed according to normal feeding practice in Belgium. The changes in some bone remodelling plasma metabolite concentrations were studied when an unbalanced diet was offered and later corrected for four Warmblood horses. Bone formation was evaluated by bone alkaline phosphatase (BALP), total alkaline phosphatase (TALP) and osteocalcin (bone gla-protein, OC). Bone resorption was assessed by hydroxyproline (HYP). Total calcium, ionized calcium, phosphorus (P) and 25-hydroxyvitamin D3 [25-(OH)D] concentrations were more or less constant. The comparison of four bone remodelling factors between the Ardennes and Warmblood horses showed higher concentrations in the Ardennes breed. Bone marker concentrations decreased according to age. The correction of the unbalanced Ca : P diet induced inconsistent effects at plasma level. The interpretation of the different bone parameters appeared to be difficult if not associated with other parameters such as a complete anamnesis and clinical examination of the animal in addition to dietary evaluation.

Age Factors↗

Bone densitometry: influence of prosthetic design and hydroxyapatite coating on regional adaptive bone remodelling.

The objective of this prospective study was to determine if bone densitometry can detect disparities in regional adaptive bone remodelling surrounding the cementless porous-coated femoral component of a hip prosthesis in two titanium alloy implants of different design . These prostheses were the S-ROM (n=69) and the Multilock (n=65). The Multilock implants consisted of two groups; 25 had a 50 micron layer of hydroxyapatite (HA) sprayed over the porous surface of the femoral component and the remaining 40 femoral components were not coated with HA. Densitometry was performed with dual energy X-ray absorptiometry (DXA) utilizing the LUNAR ORTHO software to analyse the seven Gruen zones. Bone mineral density measurements were obtained within a week of surgery as a baseline reference and at 6, 12, 24, 36 and 48 months thereafter. At 6 months there was significant mineral loss in all Gruen zones in the three prostheses. By 48 months there were differences in mineral loss between the three prostheses. In the zones adjacent to the porous surface, predominantly zones 1 and 7, the S-ROM exhibited 60% less mineral loss than the Multilock in zone 1, and there was no significant difference in zone 7. Compared to the Multilock-HA, the S-ROM lost 35% less mineral in zone 1, but the Multilock lost 70% less mineral than the S-ROM in zone 7. The Multilock-HA lost 37% and 75% less mineral than the Multilock in zones 1 and 7, respectively, i.e., hydroxyapatite coating tended to preserve bone stalk. Using the Gruen zone area measurements provided by the software, the S-ROM had significantly greater bone resorption in zone 7 at 24 months than either of the Multilocks, which did not differ from each other. In conclusion, DXA has shown differences in periprosthetic adaptive bone remodelling between implants of different design and composition as a function of time.

Absorptiometry, Photon↗

Markers of bone remodeling in the elderly subject: effects of vitamin D insufficiency and its correction.

The elderly subject is prone to both vitamin B insufficiency and calcium insufficiency due to a low calcium intake and calcium malabsorption. These two alterations may lead to secondary hyperparathyroidism, and thus to increased bone loss. We investigated 72 elderly subjects (16 men and 56 women) with vitamin D insufficiency and 25 healthy elderly women with normal vitamin D status, with respect to their indices of calcium metabolism and of bone remodeling: serum total alkaline phosphates (phosphatases), bone AP (BAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), urine hydroxyproline (HYP), and the 3-OH-pyridinium derivatives pyridinoline (PYD) and deoxypyridinoline (DPD), which are new markers of bone resorption. We then studied the modifications of these markers in the patients with vitamin D insufficiency at 3 months and 6 months after onset of a daily vitamin D and calcium supplementation. When compared with elderly subjects with normal vitamin D status, patients with vitamin D insufficiency had increased intact parathyroid hormone (iPTH) levels (60.1 +/- 10.2 vs 30.2 +/- 4.5, p < 0.001) and a high bone turnover as reflected by increased values of most serum and urine markers of bone remodeling. PYD and DPD levels were significantly correlated with all indices of bone turnover, unlike HYP, which showed no correlation with bone formation markers (AP, BAP, and BGP). A daily supplement of 800 IU vitamin D3 and 1 g of elemental calcium increased 25(OH)D levels and induced a dramatic decrease of iPTH levels; at 3 and 6 months, the mean iPTH level decreased by 50% (p < 0.0001), reaching the mean value of healthy vitamin D sufficient elderly women. All markers of bone turnover, except TRAP, decreased significantly at 3 and 6 months. The PYD/DPD ratio increased significantly at 3 and 6 months. The decrease of bone markers was more marked in patients with more severe hyperparathyroidism, the greatest variations being obtained with BAP (45%, p = 0.006) and DPD (43%, p = 0.036) levels. Most markers of bone remodeling are increased in elderly subjects with vitamin D insufficiently and vary with its correction. However, BAP and DPD are the most sensitive indicators of increased bone turnover due to secondary hyperparathyroidism.

Aged↗

Clodronate: mechanisms of action on bone remodelling and clinical use in osteometabolic disorders.

Clodronate (CI2MBP) is a non-aminated bisphosphonate that inhibits bone resorption. Studies on the mechanisms of action of this molecule on bone metabolism have been limited and only recently has information on the molecular machinery that underlies its effects on the bone remodelling process become available. Pharmacological and clinical studies have demonstrated the effectiveness of clodronate in the treatment of postmenopausal osteoporosis and in all conditions of excessive bone resorption, such as Paget's disease, hypercalcaemia of malignancy and osteolytic metastases. Clodronate is the only bisphosphonate currently available on the market for both oral and parenteral administration. Treatment with clodronate via intramuscular administration of doses of 100 mg/week has shown significant effects on bone mineral density after 6 months in patients with postmenopausal osteoporosis and these effects are maintained 3 years after the start of the treatment. In a recent controlled clinical study, a significant increase in bone mineral density was observed, associated with a 46% reduction in the incidence of vertebral fractures. However, most relevant studies have been small, unblinded and short-term and have not systematically examined the effects of the dose and dosing intervals on bone mineral density and markers of bone turnover. Ongoing controlled clinical studies may offer answers regarding potential use of clodronate in osteoporosis and also about dosage of intermittent administration. This review summarises the accumulated knowledge in the mechanisms of action of clodronate on bone remodelling. Moreover, the clinical trials on the use of clodronate in metabolic bone diseases are described in-depth. We believe that this work will help to better focus on the need for more research on a compound which has potential applications in prevention and therapy of osteoporosis. However, studies that demonstrate an effect on the rate of fractures are needed before any recommendation can be made.

Antimetabolites↗

Theoretical and numerical study of a bone remodeling model: the effect of osteocyte cells distribution.

It is well argued that osteocytes are mechanosensory cells and are involved in the regulation of bone remodeling. In previous works, the predictions from a simulation model have suggested that both the influencing distance of osteocytes and the magnitude of the mechanical loads determine the thickness of trabeculae whereas the number of osteocytes primarily affects the rate of bone remodeling. The question that remains not completely answered is: for the same number of osteocytes, what is the effect of different distributions on the remodeling process? Based on a particular regulatory bone remodeling model, the question is addressed, in part, by performing a stability analysis in connection with numerical simulations. The results allow us to demonstrate that, on one hand, we cannot reach a conclusion about the stability of the model for a nonuniform osteocyte distribution. This implies that there is no relationship between the different parameters conveying the stability of the model. On the other hand, we show that the osteocyte cell distribution has a significant influence on the bone morphology, which seems to be confirmed by simulations with real data obtained from rat tibia.

Animals↗

[Bisphosphonates and bone remodeling: effectiveness in Paget's disease, fibrous dysplasia and osteoporosis].

Paget's disease of bone, bone fibrous dysplasia and osteoporosis are characterized by abnormal bone remodeling, and frequently imply intervention of orthopedists. Recent significant medical therapeutics improvements have been obtained with the use of bisphosphonates. Theses drugs decrease bone remodeling. In Paget's disease, bisphosphonates relieve bone pain, allow lytic areas refilling and decrease complications risk with normal bone formation. In fibrous dysplasia, bone pain is alleviated, osteolytic areas are refilled and cortices are widened. In postmenopausal osteoporosis, bisphosphonates increase bone mineral density, and reduce very significantly the subsequent risk of vertebral, femoral and lower forearm fractures. Bisphosphonates are a breakthrough in Paget's disease of bone, fibrous dysplasia of bone and osteoporosis.

Bone Density↗