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While various biomechanical factors should be considered to ensure favorable bone union between the fibular and mandibular bones following mandibular reconstruction using a fibula free flap, few studies have elucidated these factors. We performed biomechanical bone remodeling analysis at the bone union area of the reconstructed mandible using clinical follow-up computed tomography (CT) images of a patient who underwent mandibular reconstruction using a fibular free flap following mandibular resection and finite element analysis (FEA) based on the patientʼs CT data. This paper summarizes our newly-developed approach to estimating patient-specific masticatory muscle forces for performing highly accurate FEA; we also present a method for developing patient-specific bone remodeling algorithms based on computer-aided engineering simulation using clinical data and FEA results. In addition, this paper introduces various studies investigating the biomechanical factors that affect bone remodeling at the bone union site, such as the magnitude of occlusal force and optimal fixation conditions of the titanium plates, by using constructed patient-specific bone remodeling algorithms. [ABSTRACT FROM AUTHOR]

We recently established the intravital imaging system for visualizing the bone tissues in living mice using two-photon excitation microscopy. By means of this system, we succeeded in visualization of direct cell-cell contact between osteoclasts and osteoblasts. In addition, we revealed that this intercellular interaction could regulate the bone remodeling. Our intravital bone imaging system would be useful for the analysis of pathology of various bone diseases and the evaluation of the effect of new drug. [ABSTRACT FROM AUTHOR]

Although the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) has been identified as a transcriptional coactivator/repressor in various cells, including bone-resorbing osteoclasts, no attention has been paid to its role in bone-forming osteoblasts. Therefore, in this study we show that Ifrd1 is a critical mediator of both osteoblastogenesis and osteoclastogenesis through its expression in osteoblasts. Ifrd1 deficiency enhanced both osteoblast differentiation and maturation, and increased the expression of Runt-related transcription factor 2 and Osterix. A coculture experiment revealed that Ifrd1 deficient osteoblasts have higher osteoprotegerin (OPG) expression and less ability to support osteoclastogenesis. These findings suggest that Ifrd1 plays a pivotal role in bone homeostasis through its expression in osteoblasts, and represents a therapeutic target for bone disease.

The bone turnover marker (BTM) measurement in osteoporosis treatment includes evaluation of bone metabolism status or evaluation of bone loss risk level, determination of fracture risk, and evaluation of drug treatment. Currently, by using the BTM, it has become possible to evaluate and select an effective treatment for osteoporosis. The BTM has become widely used as a clinical test item in actual clinical practice. Patients' low adherence to osteoporosis medication regimens increases the risk of vulnerable fractures and affects the cost effectiveness of therapeutics. A joint working group has been established, with International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and International Osteoporosis Foundation (IOF) in a central role. The joint policy document of the joint working group is intended to increase the international application of BTM in clinical medicine, and to eliminate blood type I procollagen-N-propeptide (P1NP) and type I collagen cross-linked C-telopeptide (CTX) in observational research and intervention studies, in order to eliminate the inherent uncertainty of these measurements in clinical use. Current osteoporotic drug treatment has been proven to prevent bone fractures, but poor adherence to dosage regimens is an ongoing problem in clinical practice; various attempts have been made to improve adherence. Low adherence to an osteoporosis medication regimen increases the risk of fracture, and affects cost effectiveness. The BTM is an effective indicator in monitoring reactivity to osteoporosis drug therapy, and can be used to individually evaluate guidelines for treatment continuity and medication. In addition, providing BTM information to patients has reportedly improved their adherence to therapeutics, thereby potentially improving both the outcome and cost-effectiveness of osteoporosis drug therapy.

Both lifestyle-related disease and ostepoross increase with aging;thus the number of patients with these diseases will increase in future. Because diabetes mellitus, a representative lifestyle-related disease, induces bone fragility due to deterioration of bone quality, if all of the focus is given only to bone mineral density values, we might underestimate fracture risks in the patients. Previous studies have shown that accumulation of advanced glycation end products in bone matrix, abnormal bone microstructure, and dysfunction of bone remodeling with decreased bone formation are involved in the mechanism of bone quality deterioration. However, there are no specific parameters to evaluate bone quality in clinical settings so far. Therefore, it is necessary to find patients with clinical risk factor of fracture and to perform intensive treatments for osteoporosis.

Cancer cell preferentially colonize or metastasize to bone. Although the mechanism of bone metastasis still remains poorly understood, cancer cell that metastasize to bone negatively perturb the remodeling process through a series of interactions with osteoclasts, and osteoblasts. These "vicious cycle" promote cancer progression in bone. Sensory neuron innervated in bone is regarded as component of bone microenvironment. Recent study indicated that peripheral neuron system(PNS)promote cancer progression in bone. These insights indicated sensory neuron suppression results in newly cancer treatment of bone metastasis. Here we reviewed the recent findings of interaction between cancer progression and sensory neuron activation in bone.

Recent studies of mouse genetics and human gene mutations has greatly contributed to clarifying the molecular mechanism of bone metabolism. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication among bone component cells such as osteoclasts, osteoblasts, osteocytes and endothelial cells. An imbalance of this process is often linked to various bone diseases. Thus, the elucidation of the molecular mechanisms involved in bone remodeling is critical for a deeper understanding of the maintenance of healthy skeleton and bone disease.

Exosomes are about 100nm membrane vesicles, and released from almost all cell types. They carry and transfer a wide variety of molecules, such as mRNAs, microRNAs, proteins, and lipids, as modulators of intercellular communication. Various studies have shown that this exosome-mediated intercellular communication lead to proliferation, invasion and metastasis of cancer cells. In addition to that, emerging data suggest that exosomes are also involved in physiological processes of bone remodeling and bone diseases. Increasing understanding of the working mechanism of exosomes will provide us with new therapeutic and diagnostic opportunities. Here we summarize the current research on exosomes in bone remodeling and bone diseases.

Teriparatide, recombinant human PTH(1-34), is the only anabolic agent widely used for osteoporosis. This drug is thought to promote bone formation by modulating bone remodeling system, although the detailed mechanism remains unclear. Recently, we developed a novel intravital imaging technique to visualize mature osteoclasts and mature osteoblasts simultaneously. By means of this system, we revealed the effect of teriparatide on three-dimensional distribution and cell-to-cell interactions between these cells. Advances in these imaging studies may lead to further understanding of the intercellular network in bone metabolism.

Bone remodeling consists of bone resorbing cycle and bone forming cycle to maintain bone volume and calcium homeostasis thought life. The main cells involves in bone remodeling are osteoclasts and osteoblasts. Bone resorption and bone formation are tightly coupled during bone remodeling, an imbalance of these two processes leads to either increased or decreased bone mass. Osteoclasts are multinucleated cells responsible for physiological and pathological bone resorption and thereby play an essential role in maintaining bone volume and homeostasis. Osteoclastic bone resorption is regulated by several cytokines, calcium signal, and transcription factors etc. Recent molecular dissection of genetic disorders of high increased or decreased bone mass has proven many of the crucial molecules controlling the osteoclastic bone resorption. This article reviews recent findings of molecular mechanism regarding to osteoclastic bone resorption to regulate bone remodeling.

Rheumatoid arthritis(RA)is associated with increased bone turnover and early bone loss, which lead to increased fracture risk and progressive joint destruction. Pro-inflammatory cytokines, such as IL(interleukin)-17, TNF-α(tumor necrosis factor alpha), IL-1, and IL-6 induce the expression of RANKL(receptor activation of nuclear factor κB ligand)from synovial fibroblasts. RANKL promotes osteoclasts differentiation and activation, and Denosumab, an anti-RANKL monoclonal antibody, inhibits both systemic bone loss and focal bone erosion of RA.

Bone remodeling has important roles in the functions of bone tissues, such as supporting the body and mineral storage. Osteocytes, which are the most abundant cells in bone tissues, detect the mechanical loading and regulate both bone formation by osteoblasts and bone resorption by osteoclasts. However, its mechanism is still unknown. In this review, we summarize how osteocytes detect mechanical stress and discuss the potential role of CCN2/CTGF as a novel bone remodeling factor produced by osteocytes.

Phosphorus is the second abundant mineral stored in bones, and disturbance of phosphate metabolisms results in various disease developments such as hypophosphatemic rickets. Blood phosphorus levels are regulated by dietary intake or its absorption from intestine, proximal tubular reabsorption, and number of factors plays roles for maintaining phosphate homeostasis. Vitamin D stimulates intestinal phosphorus absorption, and phosphorus promotes FGF23 secretion from osteocytes. FGF23 inhibits Cyp27b1, an enzyme to produce an active vitamin D3, 1,25(OH)2D3, through FGF receptor/Klotho complex. In this review, I will discuss about the roles of Enpp1 in regulating the FGF23-Klotho-vitamin D axis and bones.

Bone remodeling is a fundamental mechanism of bone metabolism in tissue level. Bone remodeling demonstrates sequential phase of activation, resorption, reversal, and formation. Bone histomorphometry can make the quantitative assessment of the turnover in bone remodeling.

Modeling, adapting structures to loading by changing bone size and shapes, often takes place in bone of the fetal and developmental stages, while bone remodeling-replacement of old bone into new bone-is predominant in the adult stage. Modeling can be divided into macro-modeling(macroscopic modeling)and mini-modeling(microscopic modeling). In the cellular process of mini-modeling, unlike bone remodeling, bone lining cells, i.e., resting flattened osteoblasts covering bone surfaces will become active form of osteoblasts, and then, deposit new bone onto the old bone without mediating osteoclastic bone resorption. Among the drugs for osteoporotic treatment, eldecalcitol(a vitamin D3 analog)and teriparatide(human PTH[1-34])could show mini-modeling based bone formation. Histologically, mature, active form of osteoblasts are localized on the new bone induced by mini-modeling, however, only a few cell layer of preosteoblasts are formed over the newly-formed bone, and accordingly, few osteoclasts are present in the region of mini-modeling. In this review, histological characteristics of bone remodeling and modeling including mini-modeling will be introduced.

Sepsis is a systemic inflammatory response syndrome that occurs upon severe bacterial infection. Although the development of early treatment for sepsis improves the survival rate of sepsis patients, in the subacute phase, certain patients suffer from secondary infection due to immunosuppression. It has been reported that one of the causes of the immunocompromised state during sepsis is lymphopenia. However, the underlying mechanisms are not well understood. We found that acute inflammation induced the immunodeficiency caused by the reduction of the numbers of peripheral lymphocytes and common lymphoid progenitors(CLPs)in the bone marrow, which was associated with a dramatic decrease in the osteoblast number. Osteoblast-specific deletion of IL-7 provided evidence for the role of osteoblasts in the regulation of lymphopoiesis in systemic inflammation. An acute loss of osteoblasts in sepsis induced the disturbance of lymphocyte homeostasis, resulting in immunodeficiency.

Classical anti-resorptives such as bisphosphonates inhibit remodeling, leading to decreases in both bone resorption and formation markers. Changes in these markers are useful in predicting future bone mineral density and fracture risk to some extent. More recently developed drugs such as denosumab and odanacatib, which also fall into the category of anti-resorptives, show unique effects on modeling and remodeling. This overview summarizes action of anti-resorptives from a viewpoint of remodeling.

Bisphosphonate therapy had been spread widely in osteoporosis patients, atypical femoral fractures(AFF)were reported in these patients as the unusual effects of bisphosphonate treatment. The pathogenesis of AFF was considered to be an over suppression of bone turnover by bisphosphonate. However recent studies indicated other factors related to AFF initiation. Further studies are required to clarify the mechanism of AFF in order to resolve this adverse events in osteoporosis clinic.

Development of bone metabolism markers began about 35 years ago. Current by the osteoporosis and bone metabolism diseases diagnosis and treatment efficacy. In childhood and adolescence, bone formation and resorption were increased, but formation rate was exceeded resorption rate. To keep strength of bone, bone formation and resorption are balanced(remodeling)in the period of maturity, Bone mineral density greatly decreases and biochemical markers of bone turnover markedly increase in postmenopausal women, indicating accelerated bone remodeling because of estrogen withdrawal. On the other hand, pregnancy and breastfeeding affect bone metabolism. So, we gynecologists should be careful about bone health with understanding characteristic of bone metabolism markers.

Indeed DXA and quantitative CT both which measure bone mineral amount are well established methods to predict bone volume, but some clinical studies say that different rates of bone turnover can cause discrepancies between bone mineral density and bone volume. Bone strength is accused to not only bone mineral density but bone quality, and developments of the osteoporosis drugs have made "bone quality" more important in explaining bone strength. Bone quality refers to architecture, turnover, damage accumulation and mineralization. Turnover and microdamage at bone tissue are evaluated only by bone histomorphometry, with which it becomes possible to assess bone quality from bone tissue combination with micro-CT and vibrational spectroscopy.

Mechanical stress is essential for us to maintain bone volume and structure. Immobilization and unloading, such as motor paralysis, long-term bedrest and casting of fractured area, cause rapidly remarkable bone loss. The bone remodeling disorder following immobilization demonstrates the acceleration of bone resorption and the suppression of bone formation, and molecular mechanism of the bone remodeling disorder has been gradually revealed recently. It is very difficult for us to improve the bone loss due to disuse completely. Thus, prevention of disuse osteoporosis is important. We should choose suitable treatment after considering the pathophysiology of disuse osteoporosis, and attempt early intervention as soon as possible.

Osteoporosis, which patients are estimated as more than 13 million in Japan, is mainly caused by postmenopausal osteoporosis. Estrogen deficiency induced by menopause can disturb endocrine feedback and homeostasis, followed by bone loss by increased bone resorption with high bone turnover. Recent studies using systemic or conditional Estrogen Receptor α(ERα)gene knockout mice have unveiled molecular mechanisms underlying bone metabolism. In this review, it will be discussed that direct and indirect effects of estrogen and its metabolites for bone metabolism.

Teriparatide is a bone anabolic drug that is only available in practice. It is a N-terminal fragment of parathyroid hormone(PTH). Mode of actions of teriparatide is pharmacological but not physiological as it is administered to patients with osteoporosis. Physicians need to understand the fact that treatment with teriparatide is not just like a hormone replacement but its effects on bone remodeling are pharmacological. Romosozumab, under clinical development as anti-osteoporosis drug, is a monoclonal antibody against sclerostin. Clinical data demonstrate that it temporally, but robustly activates bone formation as well as inhibits bone resorption. Thus, romosozumab is expected to have a strong anabolic action on bone remodeling.

Osteoporosis represents age-related risk about loss of independence and its treatment is mainly for maintenance of bone health and QOL as well as for fracture prevention. Recent findings suggest that bone remodeling and resorption are modulated by age-related proc- esses including decreased hormone levels and change in inflammatory status. Regulation of these age-related processes may be promising candidates for the prevention and treatment of osteoporosis.

In patients with end-stage kidney disease(ESKD), bone disorders are characterized by cortical porosity and by abnormal turnover of bone metabolism:adynamic(low turnover)bone disease and high turnover bone due to various degrees of secondary hyperparathyroidism. Abnormalities of bone metabolism are generally assessed by interview, X-ray, bone mineral density(BMD), serum phosphorus, calcium, and parathyroid hormone levels, and bone metabolic markers. Recent clinical studies have demonstrated that high turnover bone representing elevated bone metabolic markers and low BMD are independent risks of bone fractures as well as mortality among this population. Treatment of bone disorders in ESKD patients should be aiming at the normalization of mineral metabolism and the maintenance and/or improvement of BMD.

Bone remodeling is a device to accomplish "the buffering of the extracellular fluid mineral", which is one of the two major physiological functions of bone. Bone turnover is a term to express the frequency of bone remodeling, and its last step is calcification. When remodeling is induced, at first a large amount of mineral is released from bone to extracellular fluid transiently, and thereafter mineral is slowly and steadily drawn into bone. The extracellular minerals, especially calcium, are maintained by this repetition. When kidney is injured, bone turnover takes a wide spectrum from remarkably high cases to low cases. Primary calcification also shows marked individual differences. The classic renal bone diseases 5 classification clearly categorizes these disease condition, which is synonymous with renal osteodystrophy today.

Owing to the positive clinical benefits obtained with new agents, complete remission (CR) can be used as a surrogate for overall survival, and should be achieved. Although multiple myeloma is a heterogeneous disease in terms of myeloma cell- and patient-related risk factors, patients should receive the most effective combination therapy based on proteasome inhibitors and/or immunomodulatory drugs (IMiDs) as backbone medication irrespective of the risks encountered in the setting of induction therapy ("one-size-fits-all" therapy), followed by consolidation/maintenance therapy to achieve CR with the ultimate goal of extended survival. Myeloma-defining biomarkers have been established to identify high-risk smoldering myeloma requiring treatment. The development of salvage treatments yielding better outcomes for relapsed/refractory myeloma is urgently needed. Upcoming novel molecular targeting agents with different modes of action and immunotherapeutic agents will be integrated into myeloma treatment regimens with a great therapeutic impact, and further evolution of the treatment paradigm for multiple myeloma is eagerly anticipated.

Type 2 diabetes mellitus(DM)and other lifestyle-related diseases are associated with an increased risk of bone quality deterioration-type osteoporosis. The deterioration of bone quality in type 2 DM involves factors such as qualitative changes of collagens, reduction in bone turnover, narrow cortical bone diameter, increased cortical bone porosity, and destruction of trabecular bone microarchitecture. In mild to moderate chronic kidney disease and chronic obstructive pulmonary disease, the factors involved are thought to be hyperhomocysteinemia and deterioration of trabecular bone microarchitecture as well as cortical bone structure. Investigations of the usefulness of bone quality assessment using approaches such as the following are under way : biocheminal markers such as pentosidine and homocysteine, bone structure assessment methods such as hip structure analysis, trabecular bone score, and high-resolution peripheral quantitative computed tomography.

Tooth movement accompanies the active morphological changes of the alveolar bone that was applied mechanical force via teeth. Coordination of initial changes of periodontal membrane and subsequent bone remodeling produce dramatic tooth alignment. It is well known small bone cells support this dynamic change of tooth movement. Especially, osteocytes are thought to be mechanosensor cells in bone remodeling. This review focuses on the bone remodeling during tooth movement as well as molecular events of osteocytes in RANKL/RANK/OPG pathway. In addition, dynamics of DMP-1, MEPE and Sclerostin during orthodontic tooth movement are discussed with published literature.

Secondary osteoporosis is a bone disease characterized by decreased bone mass that predisposes fractures due to underlying disorders or medication. Disorders of the endocrine system, such as primary hyperparathyroidism, hyperthyroidism, hypogonadism, growth hormone deficiency, Cushing's syndrome, and anorexia nervosa frequently cause secondary osteoporosis. In those diseases, hormone excess or deficiency affects functions of osteoblasts, osteocyte, and osteoclasts, leading to aberrant bone remodeling. Bisphosphonates are the first-choice pharmacological agents for fracture prevention in most patients with secondary osteoporosis along with treatment of the underlying disease.

Bone histomorphometry is defined as a quantitative evaluation of bone remodeling. In bone remodeling, bone resorption and bone formation are coupled with scalloped cement lines. Another mechanism of bone formation is minimodeling which bone formation and resorption are independent. The finding of minimodeling appeared in special condition with metabolic bone disease or anabolic agents. We need further study for minimodeling feature and mechanism.

It is well known that bone tissue can change its outer shape and internal structure by remodeling according to a changing mechanical environment. However, the mechanism of bone functional adaptation induced by the collaborative metabolic activities of bone cells in response to mechanical stimuli remains elusive. In this article, we focus on the hierarchy of bone structure and function from the microscopic cellular level to the macroscopic tissue level. We provide an overview of a mathematical approach to understand the adaptive changes in trabecular morphology under the application of mechanical stress.

Bone is constantly remodeled to maintain its volume, structural integrity and strength Currently available bone anabolic agent is teriparatide. Teriparatide increases bone mass and strength via both remodeling-dependent and -independent mechanisms, although remodeling-dependent mechanism overweighs the other. Canonical Wnt signal plays an important role in enhancing osteoblast differentiation and bone formation, and its osteocyte-derived inhibitor, sclerostin, regulates bone formation via the regulation of Wnt signaling. Anti-sclerostin antibody stimulates Wnt signaling and enhances bone formation. Phase II clinical trials with anti-sclerostin antibodies, romosozumab and blosozumab, demonstrated a marked increase in bone mineral density after one year of treatment. The new modality of anabolic agents via remodeling-independent stimulation of bone formation may open up a new avenue for the treatment of osteoporosis.

Osteoporosis is a condition in which bone resorption by osteoclasts overtakes bone formation by osteoblasts ; as a result, bone density is reduced, the bone microarchitecture is damaged, and the risk of fractures is increased. To date, the increase in bone resorption has been explained by a reduction in female hormones, which control the activity of osteoclasts. More recently, however, it has become clear that a reduction in male hormones from middle age onwards, increasing age, and an increase in oxidative stress related to lifestyle-related diseases can also activate osteoclasts and reduce osteoblast function. These changes lead to both qualitative and quantitative abnormalities in collagen, which is the major bone matrix protein. In contrast to microstructure and calcification levels, among other bone-density and bone-matrix factors, which are controlled by bone remodeling, the intermolecular cross-link formation of collagen, which regulates bone-material attributes, is a mechanism independent of bone remodeling. In other words, cross-link formation is controlled by the environment surrounding the bone matrix, comprising cellular functions, oxidative stress, carbonyl stress, and glycation level. Therefore, bone quality is regulated both by bone remodeling and by a remodeling-independent mechanism, and markers for evaluating bone quality should be established.

The bone is continuously renewed throughout adult life by the coordinated action of osteoclastic bone resorption and osteoblastic bone formation in response to various hormones, cytokines, chemokines and biomechanical external stimuli. This process, called bone remodeling, is a prerequisite for the normal bone homeostasis that maintains both bone quality and strength. An imbalance of bone resorption and bone formation is often central to metabolic bone diseases. Aging, various diseases including life-style-related diseases, and loss of mechanical stress lead to an excessive bone resorption, resulting in osteoporosis due to decreased bone mineral density and deterioration of bone quality. Therefore, the activity of both osteoclasts and osteoblasts must be tightly regulated during bone remodeling. Understanding the regulatory mechanisms of bone cells and signal transduction through bone cell communication is important for treating osteoporosis.

Bone, which support motile organ and periodontal tissue, is renewing throughout our life. This restructuring process is called "bone remodeling" , and osteoclasts and osteoblasts play a crucial role in this process. Bone remodeling is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. Alveolar bone remodeling is directly influenced by occlusal force from the teeth. Thus, the elucidation of the regulatory mechanisms involved in alveolar bone remodeling is critical for a deeper understanding of the maintenance of healthy tooth and dental disease.

The role of the hypothalamic-pituitary-thyroid axis is important in normal skeletal development, gain of bone mass, and regulation of adult bone metabolism. Hypothyroidism in childhood causes delayed bone maturation and growth disturbance and thyroid dysfunction in adult induces altered bone remodeling and an increased risk of bone fracture. Thyroid hormone actions in skeletal cells are mainly mediated by thyroid hormone receptor α (TRα) . The responses to thyroid hormone are regulated by type 2 and 3 iodothyronine deiodinase (DIO2 and DIO3) , which convert prohormone (T4) to active hormone (T3) . Euthyroid status is necessary for the homeostasis of human bone metabolism.

Decision in starting and modulating the treatment of osteoporosis is being done by bone mineral density prevalent fractures, bone turnover markers, and other clinical indicators. However, the goal for the treatment of osteoporosis has not been established. Currently, treat-to-target is the most urgent issue to be discussed in the field of osteoporosis. In this article, the present status of this discussion is reviewed.

The importance of measurement of bone metabolic markers has been increasingly recognized in the treatment of osteoporosis. Bone is a dynamic organ in which bone formation and resorption continuously occurs. Biochemical marker for bone metabolism is an non-invasive measure to assess bone metabolic state. Although the purpose of its measurement was initially hypothesized to predict rate of bone loss, the increase of bone marker by itself provides a clinically relevant marker for bone fragility. Furthermore, measurement of bone marker is known to help improve drug compliance. Recent sophistication of bone marker measurement and the increasing kinds of bone markers increase the importance of its measurement to improve osteoporosis treatment.

Bone turnover markers (BTMs) are known the bone formation marker, the bone resorption marker and the bone matrix related marker participating in bone quality, respectively. In the Guidelines for the Use of Bone Metabolic Markers in the Diagnosis and Treatment of Osteoporosis (2012 Edition) from publishing Japan Osteoporosis Society Committee, the newly and commonly BTMs were considered to give the normal reference value in Japanese people, the reevaluation of MSC, and the influence of renal function on BTMs, respectively. The flow chart of the measurement of bone resorption markers and bone formation markers when selecting drug treatment for osteoporosis, the measurement of ucOC and bone resorption markers when selecting drug treatment in osteoporosis, and the evaluation of therapeutic effects of bone antiresorption drugs using bone resorption markers were corrected newly in the guideline 2012 edition. It is thought that the BTMs have been continued more developing as essential biomarker with the treatment of osteoporosis in the future.

Bone strength depends on its structure and its material properties. Structural properties are determined by the size and shape of bone and also the microarchitecture. Material properties are determined by mineral crystallinity, collagen structure and microdamage in bone. The strength of bone is adapted to the needs of physical activities by biologic mechanisms, bone modeling and remodeling. The deterioration of bone strength in postmenopausal women is characterized by a trabecular bone deficit with poor trabecular connectivity and followed by a cortical bone deficit with trabeculation of endocortical bone and intracortical porosity due to accelerated bone remodeling. Trabecular bone is getting more fragile with age by poor adaptation to mechanical load by modeling. As a consequence, the endplate collapses and vertebral body fracture occurs. The deterioration of bone strength could be improved by osteoporosis treatment using antiresorber or teriparatide, and these drugs would decrease the risk of vertebral fracture consequently.