Bone Resorption Process Research Articles

The role of vitamin D3 in the regulation of the mineral metabolism in experimental type 1 diabetes

Diabetes was shown to be associated with a considerable lowering of 25(OH)D3 in blood serum of mice. Vitamin D3 deficiency was correlated with impaired mineral metabolism in bone tissue, indicating the development of secondary osteoporosis. A decrease in weight, length and diameter (diaphysis, proximal metaepiphysis) of tibia in diabetic animals was observed as compared with control. Diabetes caused hypocalcemia, hypophosphatemia and increased enzymatic activity of alkaline phosphatase (ALP) and its isoenzymes in serum. This changes were accompanied by the impairments of vitamin D3 25-hydroxylase isoforms (CYP27A1 and CYP2R1) expression, which are the main enzymes of cholecalciferol biotransformation to 25(OH)D3 - precursor of hormonally active form of vitamin D3. A decrease in bone resorption processes was established after vitamin D3 administration as it is evident from normalization of bone morphometrical parameters and mineral metabolism in diabetic mice. Vitamin D3 ability to counter diabetes-induced alterations in bone tissue can be ascribed, at least in part, to its positive effects on the formation of vitamin D3 hormonally active forms.

PARTICULAR OF THE BONE METABOLISM IN CHILDREN WITH THE EXTREMITIES’ FRACTURES

35 children with extremities’ long bones fractures of the different localization were examined. The medium age (10.5 ± 2.0) years. The control group consisted of 35 healthy children: without pathology of the supporting-motor apparatus, medium age 10.5 ± 3.0. The single study of the systemic and ionized calci-um, phosphorus, magnesium and alkaline concentration and phosphatase’s activity in the blood serum was realized using automatic analyzers «Cobas 6000 SWA» (Roche Diagnostics, Switzerland). The forming and bone resorption process activity was appreciated according to the P1NP (N-terminal propeptide of type I collagen) content in the blood serum, osteocalcin аnd β-СrossLaps (β-isomerized carboxy-terminal cross-linking region of type I collagen) on the modular platform «Cobas 6000 SWA» (Roche Diagnostics,Switzerland). The mineral turnover’s regulation was determined by parathyroid hor-mone, thyrocalcitonin and 25(ОН)-D3 in the blood serum. The growth process activity was determined by content of the somatotropic hormone in the blood serum. Osteocalcin and somatotropic hormone de-termination was done by analyzer «Immulite One» (USА). The statistical processing of the obtained results was carried out with application program package Statistica 6.0 for Windows. The distribution normalcy control was performed using the Kolmogorov-Smirnov's test. Data were presented as Ме ( LQ – UQ ), where Ме is median, ( LQ – UQ ) is interquartile dis-persion. To reveal the differences between groups concerning quantitative readings the Mann–Whitney and Craskell–Wallace tests were used. The disparities were counted as statistically significant in р < 0.05. The correlation analysis was carried out by means of Spearman criterion. Children with extremities’ long bones fractures demonstrated the decrease of the bony tissue synthesis markers P1NP and calcium ions in the blood serum that speaks for the relative predominance of the resorptive activity of the bony tissue against the hypocalcaemia. There was the increase of the parathyroid hormone and somatotropic hormone levels in the blood serum in children with fractures on the back of the absence of the correlation relationship between these values and bony markers that seems to be the return of the disorders of the endocrine control of the bone-mineral turnover. The deceleration of the bony tissue synthesis may be connected with hypocalcaemia conditioned by vitamin D deficit received for most of the examined children. On the other side, rickets D is usually the cause of the secondary hyperparathyroidism that can lead to the bony resorption elevation as a whole, osteomalacia progressing and bone mass decrease and increase of the bone’s fracture risk. The up-to-date diagnostics, treatment and prophylaxis of the vitamin D deficit states in children allow to decrease the osteopenia frequency and to reveal the tendency to the fractures.

Bone turnover markers, osteoprotegerin and RANKL cytokines in children with cystic fibrosis

Some scientific studies show decreased bone mineral density and increased fracture frequency in adult patients with cystic fibrosis (CF). The mechanism for early bone loss in CF patients are multifactorial: chronic pulmonary inflammation, malnutrition, reduced physical activity, delayed pubertal maturation. The aim of this study was to assess bone metabolism markers with special attention paid to osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) balance in CF children. The study included 35 children with diagnosed CF and 35 healthy controls aged 5-9 years (median 7.0 years). Serum levels of fat soluble vitamins were measured by chemiluminescence (vitamin D) and HPLC (vitamins A, E) methods. Concentrations of bone metabolism markers were determined by immunoenzymatic assay. Mean levels of fat soluble vitamins (A, D, E) were lower in patients with CF compared to controls. In CF children we observed a significant (p<0.01) decrease in concentration of bone formation marker (osteocalcin) and similar bone resorption markers (CTX, TRACP5b) in comparison with healthy children. The serum level of OPG was significantly lower (p<0.05) and RANKL nearly 2-fold higher in patients with CF than in the healthy ones. The ratio of OPG to RANKL was about 2-fold lower in children with CF compared to healthy peers (p<0.01). In CF children, an imbalance between bone formation and resorption processes occurs. An increase serum RANKL concentration coexisting with lower levels of OPG may be associated with intensification of bone resorption.

Arterial pseudoaneurysm as a cause of periprosthetic osteolysis mimicking an infected total hip arthroplasty

Although vascular injuries after total hip arthroplasty (THA) are uncommon, they may lead to severe complications which can result in a threat to life and limb. The different patterns of such injuries include lacerations with acute hemorrhage, arteriovenous fistula, thrombosis, and pseudoaneurysms [1, 2]. Periprosthetic osteolysis is a well known phenomenon caused by wear particle-induced bone resorption or other pathologic processes, including infection, metabolic disease, and neoplasia [3]. Nevertheless, as far as we are aware, no reports have yet been published on aneurysms associated with periprosthetic osteolysis. We present a case of a patient who developed a deep femoral artery pseudoaneurysm mimicking periprosthetic joint infection with osteolysis after total hip replacement.

Solid Tumours Show Osteotropism: Mechanisms of Bone Metastases

Bone metastases are a dismal consequence of cancer, causing severe morbidity and reducing the quality of life of patients. Solid tumours such as breast, prostate, lung and kidney cancer showed a marked osteotropism dependent on the special microenvironment provided by bone. Different cellular types are involved in the formation of bone metastases, indeed bone, immune system and tumour cells interact leading to bone lesions. During the bone resorption process, there is an intense cross-talk between immune system cells and osteoclasts (OCs). In particular, T cells release factors and cytokines, which rule osteoclastogenesis, and on the other hand, OCs produce factors that act on T cells, which are mediators of the tumour growth in bone. This review will summarize the main mechanisms of action in cancer-induced bone disease with particular regard to the cross-talk among cells of bone, tumour and immune system, focusing on factors and cytokines released by osteoclast, osteoblast, tumour cells and T cells.

임플란트 식립 후 초기 안정성의 변화

골치유 기간 중 임플란트-골 계면에서 일정 수준 이상의 미세동요가 발생하게 되면 임플란트의 골유착이 방해받게 되므로 임플란트 식립 후 초기 골반응에 관해 임플란트 안정성은 하나의 지표가 된다. 본 연구의 목적은 임플란트 식립 후 전향적인 연구를 통해 초기 임플란트 안정성 변화를 추적하여 골치유 양상을 추론하고자 하였다. 총 26명의 환자에게 식립된 30개의 임플란트를 대상으로 하악골에 1회법으로 식립 직후 1주 간격으로 12주간 공진주파수분석을 시행하여 초기 안정성의 변화를 구하였으며 식립 직후와 1개월 간격으로 변연골 흡수 정도를 방사선학적 방법으로 측정하였다. 식립 직후와 각 치유기간 동안의 ISQ값 비교에서 식립 4주에서 6주사이에 골질에 따른 차이를 보였으나(P<0.05), 6주 이후에는 골질군 간에는 임플란트 안정성 변화에 차이가 없었다(P>0.05). 방사선학적 검사에서는 변연골의 차이가 관찰기간내에 유의하게 변화하지 않았다(P>0.05). 임플란트 식립 후 초기 골치유과정은 골흡수과정에 연속적인 과정으로 4주 이후 바람직한 골치유과정이 진행됨을 공진주파수분석으로 관찰할 수 있었다. The concept of implant stability was basically originated from the relative condition of bone-implant interface and has some meanings for evaluation of that interface. In addtion, it has been used for the investigation of initial bone healing process after fixture installation because a degree of micromotion around interface can affect unfavorable clinical results. The purpose of this study is to investigate the mode of initial bone healing from fixture installation through prospective trial. Thirty fixtures were consecutively installed in mandibles of 26 patients with single tooth loss area and then healing abutment were secured for one-stage surgery meothod. Resonance frequency analysis was performed with one week interval during 12 weeks and periapical radiographs were taken at each month. Although marginal bone level change was not shown through observation period (P>0.05), statistical difference of implant stability was shown through 4 and 6 week (P<0.05) and was not shown after 6 week (P>0.05) according to the bone quality. Initial bone healing process is a successive process of bone resorption and favorable bone healing result might be postulated at 4 week interval after installation through RFA.

Uncoupling of osteoblast–osteoclast regulation in a chemical murine model of Gaucher disease

Gaucher disease (GD) is caused by mutations in the GBA gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to accumulation of the glycolipid glucocerebroside in the lysosomes of cells of monocyte/macrophage system. Type I GD is the mildest form and is characterized by the absence of neuronopathic affection. Bone compromise in Gaucher disease patients is the most disabling aspect of the disease. However, pathophysiological aspects of skeletal alterations are still poorly understood.The homeostasis of bone tissue is maintained by the balanced processes of bone resorption by osteoclasts and formation by osteoblasts. We decided to test whether bone resorption and/or bone formation could be altered by the use of a chemical in vitro murine model of Gaucher disease.We used two sources of cells from monocyte/macrophages lineage isolated from normal mice, splenocytes (S) and peritoneal macrophages (PM), and were exposed to CBE, the inhibitor of GCase (S-CBE and PM-CBE, respectively). Addition of both conditioned media (CM) from S-CBE and PM-CBE induced the differentiation of osteoclasts precursors from bone marrow to mature and functional osteoclasts. TNF-α could be one of the factors responsible for this effect. On the other hand, addition of CM to an osteoblast cell culture resulted in a reduction in expression of alkaline phosphatase and mineralization process. In conclusion, these results suggest implication of changes in both bone formation and bone resorption and are consistent with the idea that both sides of the homeostatic balance are affected in GD.

Three-Year Follow-Up of a Single Immediate Implant Placed in an Infected Area: A New Approach for Harvesting Autogenous Symphysis Graft

Three-Year Follow-Up of a Single Immediate Implant Placed in an Infected Area: A New Approach for Harvesting Autogenous Symphysis Graft

A 2‐D continuum model of a mixture of bone tissue and bio‐resorbable material for simulating mass density redistribution under load slowly variable in time

AbstractThe bio‐mechanical phenomena occurring in bones grafted with the inclusion of artificial materials demand the formulation of mathematical models which are refined enough to describe their not trivial behavior. A 3D theoretical model, previously developed and used in 1D space, is employed to investigate and explain possible effects resulting from 2D interactions, which may not be present in 1D case so more realistic situations are approached and discussed. The enhanced model was used to numerically analyze the physiological balance between the processes of bone apposition and resorption and material resorption in a bone sample under plain stress state. The specimen was constituted by a portion of bone living tissue and one of bio‐resorbable material and was acted by an in‐plane loading condition. The signal intensity between sensor cells and actor cells was assumed to decrease exponentially with their distance; the effects of adopting two different laws, namely an absolute and a quadratic functions, were compared. Ranges of load magnitudes were identified within which physiological states are established. A parametric analysis was carried out to evaluate the sensitivity of the model to changes of some critical quantities within physiological ranges, namely resorption rate of bio‐material, load level and homeostatic strain. In particular the spatial distribution of mass densities of bone tissue and of resorbable bio‐material and their time evolution were considered in order to analyze the biological effects due to the parameter's changes. Synthetically, these biological effects can be associated to different ratios between bone and bio‐material densities at the end of the process and to different delays in the bone growth and material resorption. These numerical analyses allowed for finding the most desirable situations in which a gradual resorption of the artificial graft occurs together with the simultaneous formation of new bone, finally leading to an almost complete substitution of the bio‐resorbable material with living tissue.

Answer to the Letter to the Editor of H. Namazi concerning “Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts” by Lange T, Stehling C, Fröhlich B, Klingenhöfer M, Kunkel P, Schneppenheim R, Escherich G, Gosheger G, Hardes J, Jürgens H, Schulte TL (2013), Eur Spine J;22(6):1417–1422

Dear Editor, We read with great interest and appreciate the comment on an additional route how Denosumab works [1]. Our article focused on the clinical application of Denosumab in aneurysmal bone cysts [2]. This comment highlights the physiological mechanisms of the effect of Denosumab and thus perfectly completes and complements our work. In general, the continuous process of bone resorption and formation underlies different mechanisms and is well balanced in the healthy skeleton. In addition to the RANKL mechanism, the Wnt/s-catenin pathway has been identified to play an important role in bone formation [3]. Long-term treatment with Denosumab has been shown to increase sclerostin levels which has been proven to lead to a depressed bone formation [4], but simultaneously DKK1 decreases which is thought to inhibit the sclerostin effect [1]. The clinical effect of Denosumab also in children will be a compound of these different pathways.

Biochemical markers of bone metabolism in children with cow’s milk allergy

IntroductionPatients with cow's milk allergy (CMA) and following a cow milk protein-free diet for a long time are potentially at risk of developing bone abnormalities. To assess the balance between bone formation and resorption processes, we determined serum concentrations of osteocalcin (OC), bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX), fetuin-A, osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in children with CMA.Material and methodsThe study included 50 prepubertal children with diagnosed cow's milk allergy, who were under systematic medical and nutritional care at the Institute of Mother and Child and 40 healthy counterparts as a control group. The concentrations of bone metabolism markers were determined by immunoenzymatic assays.ResultsThe diets of all investigated children were correct in terms of phosphorus and magnesium contents but deficient in terms of calcium and vitamin D. Serum OC and CTX as well as fetuin-A concentrations were similar in both studied groups. The BALP activity was significantly (p < 0.05) higher in children with cow's milk allergy than in the controls. Serum OPG concentration was comparable in both groups, but the RANKL level was higher (p < 0.05) in CMA children than in healthy ones. Hence, the ratio of OPG/RANKL was lower in children with CMA.ConclusionsOur study demonstrates slight disturbances in the profile of bone metabolism markers in growing children with CMA. The increase in RANKL level and decrease in OPG/RANKL ratio may contribute to intensification of bone resorption in these patients.

Transforming growth factor beta 1 induces CXCL16 and leukemia inhibitory factor expression in osteoclasts to modulate migration of osteoblast progenitors

The processes of bone resorption and bone formation are tightly coupled in young adults, which is crucial to maintenance of bone integrity. We have documented that osteoclasts secrete chemotactic agents to recruit osteoblast lineage cells, contributing to coupling. Bone formation subsequent to bone resorption becomes uncoupled with aging, resulting in significant bone loss. During bone resorption, osteoclasts release and activate transforming growth factor beta 1 (TGF-β1) from the bone matrix; thus, elevated bone resorption increases the level of active TGF-β in the local environment during aging. In this study, we examined the influences of TGF-β1 on the ability of osteoclasts to recruit osteoblasts. TGF-β1 increased osteoclast expression of the chemokine CXCL16 to promote osteoblast migration. TGF-β1 also directly stimulated osteoblast migration; however, this direct response was blocked by conditioned medium from TGF-β1-treated osteoclasts due to the presence of leukemia inhibitory factor (LIF) in the medium. CXCL16 and LIF expression was dependent on TGF-β1 activation of Smad2 and Smad3. These results establish that TGF-β1 induces CXCL16 and LIF production in osteoclasts, which modulate recruitment of osteoblasts to restore the bone lost during the resorptive phase of bone turnover.

Numerical simulation of dental bone remodeling induced by implant‐supported fixed partial denture with or without cantilever extension

The current study aims to evaluate and compare the bony biomechanical response and possible long-term restorative consequences stemming from the use of two-unit fixed partial dentures (FPDs) with or without cantilever configuration. The numerical simulations of bone remodeling were performed using an adaptive strain energy density algorithm, which incorporates an overloading bone resorption process. A patient specific 3D finite element model of a maxillary bone with two absent central incisors was constructed on the basis of clinical computed tomography data. Two different implant-supported two-unit FPD models were developed. The simulated remodeling results were visualized by examining the variation of apparent bone density. Different bone responses under normal and overload conditions were compared quantitatively and qualitatively between the cantilever and non-cantilever models. The mechanical stress/strain distributions were also examined. Furthermore, the simulation results were compared with a similar clinical X-ray image of the implant site. This study revealed that bone resorption due to overloading was more severe in the cortical neck around the implant-supported cantilever FPD, as compared with the non-cantilever configuration, which is better for maintaining the overall health of bone tissue. It is expected that such simulation methodology can be helpful in improving longevity and reliability of future dental implants.

AB0535 Effects of tocilizumab on bone density and metabolism in patients with active rheumatoid arthritis

Backgroundjuxta-articularosteoporosis, erosionsand systemic osteoporosis are the three main radiological features in patients affected by rheumatoid arthritis. A series of studies have emphasized the close relationship between disease activity and bone...

Effects of Enterococcus faecalis lipoteichoic acid on receptor activator of nuclear factor‐κB ligand and osteoprotegerin expression in periodontal ligament fibroblasts

To investigate the influence of Enterococcus faecalis lipoteichoic acid (LTA) on the key bone resorption-regulating proteins, receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in human periodontal ligament fibroblasts (PDL cells). Periodontal ligament cells were subjected to various concentrations of LTA. Cell viability was then determined by methyl thiazolyl tetrazolium (MTT) assay, whilst the expression levels of RANKL and OPG were investigated by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effect of the inhibitors [IL-1 receptor-associated kinase (IRAK)-1/4, p38 mitogen-activated protein kinase (MAPK) (SB203580)] on LTA-stimulated RANKL/OPG activation was examined. Cell viability and RANKL/OPG ratio in PDL cells were also analysed by MTT assay and Western blotting. Data were analysed using one-way anova or t-test at a significance level of P = 0.05. Cell viability was reduced significantly in the LTA group in a dose-dependent fashion (P < 0.05). In addition, LTA was found to upregulate the protein expression of RANKL, OPG and their relative ratio in PDL cells (P < 0.05). The optimal concentration of LTA used in PDL cells was determined to be 10 μg mL(-1) . Following IRAK1/4 and p38MAPK inhibition, LTA-stimulated increases of RANKL/OPG ratio were significantly reduced (P < 0.05). Enterococcus faecalis LTA could upregulate the expression of RANKL and OPG at different rates, suggesting a potential role for LTA in the bone resorption process of refractory apical periodontitis through the regulation of RANKL and OPG. In addition, IRAK1/4 and p38MAPK signalling involving RANKL/OPG may contribute to inflammatory responses from PDL cells.

Differential regulation of HIF‐mediated pathways increases mitochondrial metabolism and ATP production in hypoxic osteoclasts

Inappropriate osteoclast activity instigates pathological bone loss in rheumatoid arthritis. We have investigated how osteoclasts generate sufficient ATP for the energy-intensive process of bone resorption in the hypoxic microenvironment associated with this rheumatic condition. We show that in human osteoclasts differentiated from CD14+ monocytes, hypoxia (24 h, 2% O2): (a) increases ATP production and mitochondrial electron transport chain activity (Alamar blue, O2 consumption); (b) increases glycolytic flux (glucose consumption, lactate production); and (c) increases glutamine consumption. We demonstrate that glucose, rather than glutamine, is necessary for the hypoxic increase in ATP production and also for cell survival in hypoxia. Using siRNA targeting specific isoforms of the hypoxia-inducible transcription factor HIF (HIF-1α, HIF-2α), we show that employment of selected components of the HIF-1α-mediated metabolic switch to anaerobic respiration enables osteoclasts to rapidly increase ATP production in hypoxia, while at the same time compromising long-term survival. We propose this atypical HIF-driven metabolic pathway to be an adaptive mechanism to permit rapid bone resorption in the short term while ensuring curtailment of the process in the absence of re-oxygenation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Emerging therapies for the treatment of osteoporosis

Osteoporosis is a chronic disease of the osseous system characterized by decreased bone strength and increased fracture risk. It is due to an imbalance in the dynamic ongoing processes of bone formation and bone resorption. Currently available osteoporosis therapies like bisphosphonates, selective estrogen receptor modulators (SERMs), and denosumab are anti-resorptive agents. Parathyroid hormone analogs like teriparatide are the only anabolic agents currently approved for osteoporosis treatment. The side-effects and limited efficacy of the presently available therapies has encouraged extensive research into the pathophysiology of the disease and newer drug targets for its treatment. The novel anti-resorptive agents being developed are newer SERMs, osteoprotegerin, c-src (cellular-sarcoma) kinase inhibitors, αVβ3 integrin antagonists, cathepsin K inhibitors, chloride channel inhibitors, and nitrates. Upcoming anabolic agents include calcilytics, antibodies against sclerostin and Dickkopf-1, statins, matrix extracellular phosphoglycoprotein fragments activin inhibitiors, and endo-cannabinoid agonists. Many of these new drugs are still in development. This article provides an insight into the emerging drugs for the treatment of osteoporosis.

Bone biomarkers of ovariectomised rats after leptin therapy

Under physiological conditions, maintenance of skeletal mass is the result of a tightly coupled process of bone formation and bone resorption. Disease states, osteoporosis included, arise when this delicate balance is disrupted, such as in menopause. The aim of the present work was to study the effect of leptin supplementation on bone metabolism in ovariectomized adult female rats by measuring indices of bone biomarkers. Forty adult female albino rats were chosen as an animal model for this study and divided into the four equal groups (n=10/group): Group I (control SHAM-operated group) received a single dose of buffer solution i.p. daily for eight weeks. Group II (ovariectomy group) received a single dose of buffer solution i.p. daily for eight weeks. Group III (alendronate group): Ovariectomized rats that received alendronate 0.1 mg/kg body weight i.p. daily for eight weeks. Group IV (leptin group): Ovariectomized rats that received leptin (10 µg/kg body weight) i.p. daily for eight weeks. The obtained serum is required for determination of: Serum osteocalcin, alkaline phosphatase, calcium and phosphorous levels. The obtained data revealed that treatment with alendronate or leptin caused a significant decrease of serum osteocalcin, specific bone alkaline phosphatase and urinary deoxypyridinoline levels compared to ovariectomy group, and there was no significant difference between both drugs. Leptin prevents ovariectomy induced increases in bone turnover in rats. Leptin therapy has a significant effect in treatment of ovariectomy induced osteoporosis in rats (Tab. 1, Ref. 32).

Effects of Zinc and Strontium Substitution in Tricalcium Phosphate on Osteoclast Differentiation and Resorption.

Bone replacement materials must be able to regulate both osteoblastic synthesis of new bone and osteoclastic resorption process in order to maintain the balance of bone remodeling. Osteoclasts generate from differentiation of mononuclear cells. In the present study, we have studied the osteoclast-like-cells responses (differentiation from mononuclear cells and resorption) to beta tricalcium phosphate (β-TCP) doped with zinc (Zn) and strontium (Sr). Osteoclast-like-cells differentiation and resorption was studied in vitro using osteoclast-like-cells precursor RAW 264.7 cell, supplemented with receptor activator of nuclear factor κβ ligand (RANKL). Morphological and immunohistochemical analysis confirmed successful differentiation of osteoclast-like-cells on the doped and undoped β-TCP substrates after 8 days of culture. Cells on the substrate surface expressed specific osteoclast markers such as; actin ring, multiple nucleus, tartrate-resistant acid phosphatase (TRAP) synthesis, and vitronectin receptor. However, quantitative TRAP assay indicated the inhibiting effect of Zn on osteoclast differentiation. Although, Zn doped β-TCP restricted osteoclast-like-cells differentiation, the samples were resorbed much faster. An increased resorption pit volume was noticed on Zn doped β-TCP samples after 28 days of culture compared to pure and Sr doped β-TCP. In this work, we demonstrated that β-TCP bone substitute materials can be successfully resorbed by osteoclast-like-cells, where both osteoclast-like-cells differentiation and resorption were modulated by Zn and/or Sr doping- a much needed property for successful bone remodeling.

Longitudinal in vivo imaging of bone formation and resorption using fluorescence molecular tomography

Bone research often focuses on anatomical imaging of the bone microstructure, but in order to gain better understanding in how bone remodeling is modulated through interventions also bone formation and resorption processes should be investigated. With this in mind, the purpose of this study was to establish a longitudinal in vivo imaging approach of bone formation and resorption using fluorescence molecular tomography (FMT). In this study the reproducibility, accuracy and sensitivity of FMT for bone imaging were assessed by performing longitudinal measurements with FMT and comparing it to in vivo micro-computed tomography on a set of control mice, and mice in which load-adaptation was induced in the sixth caudal vertebra. The precision error for FMT measurements, expressed as coefficient of variation, was smaller than 16%, indicating acceptable reproducibility. A correlation was found between bone resorption measured with FMT and bone resorption rate measured with in vivo micro-computed tomography only over the first 14days (R=0.81, p<0.01), but not between bone formation measured with FMT and bone formation rate measured with in vivo micro-CT. Bone formation measured by FMT was 89–109% greater (p<0.05) for mice subjected to mechanical loading than control mice. Bone resorption was 5–8% lower, but did not reach a significant difference between groups, indicating moderate sensitivity for FMT. In conclusion, in vivo FMT in mouse tail bones is feasible but needs to be optimized for monitoring load adaptation in living mice.