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Structural property of bone includes micro- or nano-structural property of the trabecular and cortical bone, and macroscopic geometry. Radiological technique is useful to analyze the bone structural property;multi-detector row CT(MDCT)or high-resolution peripheral QCT(HR-pQCT)is available to analyze human bone in vivo . For the analysis of hip geometry, CT-based hip structure analysis(HSA)is available as well as DXA-based HSA. These structural parameters are related to biomechanical property, and these assessment tools provide information of pathological changes or the effects of anti-osteoporotic agents on bone.

The degree of mineralization and microstructure are regulated by bone turnover. Bone collagen enzymatic cross-links and advanced glycation end products(AGEs)are affected by various factors such as the levels of oxidative stress and glycation as well as tissue lifespan. Deterioration of bone material properties markedly advances due to increases in oxidative stress, glycation stress, reactive oxygen species, carbonyl stress associated with aging and reduced sex hormone levels, and glucocorticoid use. In this review, we described determinants of bone quality and strength.

In the malignant tumors in women, uterine cervical cancer, endometrial cancer, ovarian cancer, and breast cancer are representative diseases. The cancer treatment is classified roughly into an operation, medical treatment, and radiation therapy and has an extremely big influence on ovarian function. With the improvement in survival of cancer patients, the importance of the health care for the cancer survivors increases. It is necessary to prevent the onset of the osteoporotic fractures to maintain QOL. This paper describes the action that the malignant tumors of the women affect bone metabolism mainly from the viewpoint of ovarian function.

Impaired bone quality is associated with fragility bone fractures independently of bone mineral density. Lifestyle disease-induced osteoporosis, such as diabetes or chronic kidney disease, and glucocorticoid-induced osteoporosis are listed as the diseases affecting bone quality. TBS(trabecular bone score)developed recently will be able to evaluate the trabecular microarchitecture quickly and easily. Various clinical studies evaluated bone quality by TBS has performed. I give an outline about the diseases affecting bone quality.

Quantitative as well as qualitative bone loss occurs with aging in both men and women, leading to alterations in skeletal microarchitecture and increased fracture incidence. Sex steroids, primarily estrogen and testosterone, have been shown to play a central role in the aging process of bone. The relationship between diminishing estrogen levels in women caused by ovarian failure and the development of postmenopausal osteoporosis is widely recognized. Unexpectedly, bone mineral density at various skeletal sites in men is also better correlated with circulating levels of bioavailable estrogen than with testosterone. Recently, it is also suggested that senescent osteocytes and their senescence-associated secretory phenotype may contribute to age-related bone loss. Osteoporosis should be considered as a disease developing on the basis of the natural aging process which is modified to some degree by various genetic and environmental factors.

Physical activity plays an important role in maintaining or enhancing bone health. Jumping exercise increases bone mineral content(BMC)in prepubescent children(premenarcheal girls). Bone mineral density(BMD)is higher in adolescent athletes who are engaged in weight-bearing activities. Jumping exercise, muscle strengthening exercise, and weight-bearing plus muscle strengthening exercises increase BMD in young adults and premenopausal women. Walking, aerobic weight-bearing exercise, muscle strengthening exercise, and weight-bearing plus muscle strengthening exercises maintain or increase BMD in postmenopausal women. Proper exercise and sports activity at each life stage are important strategies for preventing osteoporosis.

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.

In osteoporosis, the risk of fracture is influenced by decrease of bone mineral density and deterioration of bone quality. The latter includes deterioration of the material and structural properties of bone. These changes arise from the influence of changes in hormonal balance, aging, changes in mechanical stress, lifestyle-related diseases, etc. on bone absorption and bone formation as the coupled functions of osteoclasts and osteoblasts. Deterioration of bone quality occurs at various levels ranging from the molecular to the tissue level, or even at the individual level, and leads to an increased fracture risk. In this chapter, bone quality evaluation using quantitative computed tomography is discussed among evaluation methods of various fracture risk.

It has been shown that diabetic patients have bone fragility independent of bone mineral density. Recently, diabetes-related bone disease is recognized as one of diabetic complications. It is reported that advanced glycation end products(AGEs)collagen cross-links, low bone turnover with osteoblastic dysfunction, and abnormality of microarchitectures such as cortical porosity and deterioration of trabecular bone structure are involved in diabetes-related bone disease. AGEs and homocysteine directly and negatively affect osteoblasts and osteocytes. Moreover, anti-diabetic drugs also affect bone metabolism. Therefore, the underlying mechanisms are very complex. In this review, we describe the effects of diabetes on bone metabolism based on the recent evidence.

Chronic obstructive pulmonary disease(COPD)is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis. Osteoporosis is extremely common in COPD patients;up to 80%prevalence of vertebral fracture has been reported. However, its low awareness has left many patients untreated. Although pathophysiology of COPD-associated osteoporosis is largely unknown, multiple risk factors for osteoporosis are present, such as smoking, low body weight, systemic inflammation, vitamin D insufficiency, hypoxia. Further research to elucidate its pathophysiology is needed. But, more importantly, increased awareness of its significance is urgently called upon.

Bone histomorphometry is defined as a quantitative evaluation of bone remodeling and bone turnover. Bone remodeling is the important mechanism for calcium metabolism and mechanical usage. The changes of bone remodeling in special condition with metabolic bone disease or osteoporosis agents have the effectiveness on bone mechanical strength.

Among the anti-osteoporotic agents clinically available in Japan, teriparatide is the only bone anabolic agent offering potent osteogenic effects. Regarding bone quality, studies have shown that teriparatide increases bone collagen content and enzymatic cross-links and decreases pentosidine, a surrogate marker of advanced glycation end-products. In addition to these improvements in bone collagen cross-links, increased bone mineral density and improvement of bone microarchitecture contribute to increases in bone strength with teriparatide administration. Teriparatide has been shown to markedly reduce the risk of new vertebral fractures in patients with osteoporosis. Recent clinical studies have suggested a role for teriparatide in accelerating healing for osteoporotic fractures. Teriparatide is promising for the prevention of vertebral collapse progression after vertebral fracture.

Obstructive sleep apnea syndrome(OSAS)is a sleep disorder characterized by repetitive upper airway collapse during sleep, causing frequent hypoxia and sleep disturbance. Known risk factors of OSAS include obesity, male sex and smoking. OSAS has been linked to various comorbidities such as hypertension, cardiovascular diseases and diabetes. Recent evidence also indicates that OSAS is associated with vitamin D insufficiency, increased bone resorption and bone loss. Thus, although increased fracture rate has not been demonstrated, OSAS is now recognized as a risk factor of osteoporosis. This review will summarize the recent reports about bone metabolic abnormalities in OSAS.

Age-related loss of skeletal muscle mass, strength and function is known as sarcopenia, and its diagnostic criteria is based on usual gait speed, grip strength, and skeletal muscle mass. Whereas underlying mechanisms of sarcopenia remains to be fully clarified, recent studies have suggested age-related changes in inflammatory status and humoral factors might contribute to the pathophysiology of sarcopenia and linkage between bone and muscle metabolism.

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.

Impairment of bone mineralization causes rickets and osteomalacia. Rickets develops with impaired mineralization of bone prior to epiphyseal closure, and so does osteomalacia after the closure of epiphyses. Pain in lower extremities and back and bone pain are usually observed in patients with osteomalacia. Chronic hypophosphatemia and/or impairment of vitamin D action are involved in the development of osteomalacia. It is of great importance to suspect osteomalacia from clinical symptoms and laboratory data, such as hypophosphatemia and/or high serum alkaline phosphatase level.

Increased fracture risks in diabetes mellitus (DM) have been attributed to deteriorated bone quality both in type 1 and 2 DM because increased risks are disproportionate to their bone mineral densities (BMD) . Although still very little is known about bone architecture in type 1 DM, recent advancement in the techniques, such as high-resolution peripheral quantitative CT (HR-pQCT) and trabecular bone score (TBS) , have revealed that, in type 2 DM, bone microstructure is compromised despite preserved BMD, which may account for high fracture risk in DM.

Objective: Severely handicapped children and adolescents have reduced bone mineral density and high prevalence of pathological fractures. Bone quantitative ultrasonography (QUS) is a radiation-free method for assessing bone density. It is portable and easy to use in subjects with severe bodily deformities., Methods: We evaluated 166 students (age 6-20 years) at a school for disabled children for bone mineral density using the osteo-sono-assessment index (OSI) calculated by measuring the velocity of ultrasound waves, the speed of sound (SOS) and the transmission index (TI), at the calcaneus. All examinations were performed using an AOS-100 analyzer (ALOKA Ltd., Tokyo, Japan). The Gross Motor Function Classification System (GMFCS) for cerebral palsy was also applied. We assessed OSI for dietary texture modifications and methods of feeding., Results: Those with pathological fractures tended to have lower OSI than other students. Such fractures were individually unrelated to age, sex and GMFCS. OSI was significantly higher at GMFCS level I than level II. OSI in levels I to III was equally significantly higher than that in levels IV and V. As to feeding methods, the tube feeding group tended to have lower OSI than the oral ingestion group. In the oral ingestion group, those receiving a regular diet had significantly higher OSI than the mixed-minced diet group. However, students with a gastrostomy tended to have higher OSI than those receiving gastro-nasal tube feeding., Conclusions: Gross motor function (applied GMFCS) is a major factor affecting bone mineral density. Tube feeding reduces bone mineral density. However, forced oral intake may also reduce it. In the tube feeding group, a modified diet of appropriate texture delivered via gastrostomy may be the key to improving bone mineral density.

Recent meta-analysis and some studies have shown that patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures despite their elevated bone mineral density, suggesting that poor bone quality deteriorates bone strength in T2DM patients. Bone geometry as well as bone turnover and mineralization are key components of bone quality. Limited studies have indicated that the section area and cortical thickness of diaphyses in T2DM patients are narrower and thinner than those in control subjects and that bone formation as well as mineralization in T2DM group are suppressed as compared to normal subjects. High-resolution peripheral quantitative computed tomography (HR-pQCT) revealed that T2DM patients had higher cortical pore volume in distal radius as compared to control subjects and that bone strength index estimated by finite element analysis was lower than that of control group. These results suggest that these bone quality factors are associated with bone strength in T2DM patients.

Satoyoshi syndrome is a rare disorder of unknown case characterized by progressive painful intermittent muscle spasms, alopecia, malabsorption amenorrhea and skeletal abnormalities mimicking a skeletal dysplasia.

Bone provides momentary strength and fatigue strength, and bone strength decreases with age. In elderly men and women with fragile bones osteoporotic fractures frequently occur. Fragility fracture occurs as a consequence of the decrease in momentary strength, and fragility fracture is one of the pathological fractures. In patients with the decrease in fatigue strength, insufficiency fractures frequently occurs. Insufficiency fracture is the same term as stress or fatigue fracture.

Although both microfracture and microdamage are the damages caused by bone fatigue, microfracture shows micro-callus formed during trabecular fracture healing. Microdamage shows microcracking in the bone matrix, which is detected by osteocyte network then repaired by bone remodeling. Imbalance between generation and repair of bone fatigue causes accumulation of microdamage.

While mechanical strength of bone can be explained by measures of quantity up to 60 - 80%, several additional factors called 'quality' including microarchitecture have been proposed for better prediction of fracture risks. Osteoporosis medication can exert favorable effects on bone microarchitecture and strength, and has been evaluated by micro-CT using animal models. Studies are now moving toward the in vivo study using clinical imaging. Finite element analysis has been introduced for biomechanical evaluation of the bone, and this can be also applied to in vivo data. Several aspects of these basic and clinical researches will be discussed in this review.

Among several recent interests in bone quality, two topics will be stated. First, in vivo assessment of bone microstructure has been realized by the benefit of recent developments of imaging technique and technology, which is going to be applied to assess risk of fracture and efficacy of anti-osteoporotic agents. Second, in vitro analyses of nano-structure, including microcrack and cortical porosisty, contribute to assessment of bone material and biomechanical properties.

Repair of bone and articular destruction in rheumatoid arthritis (RA) is major problem to treat RA patients recently. However bone destruction starts in early phase of disease duration in RA. Histological meta-analysis of synovium is one of a key to solve the problem in RA. We investigated synovial histology about five factors including synovial proliferation, pillonodular synovium, vascular proliferation, and fibrin deposit and lymphocyte infiltration. Disease duration and pilonodular synovium has significant correlation by multiple regression analysis (p = 0.018). Therefore pillonodular synovium is important to decrease bone destruction in RA. It is possible that biological treatment for RA is effective to bone and cartilage metabolism, however some cases do not improve bone metabolism. Further investigation needs to analyze the factors of efficacy of bone and cartilage metabolism.

Fracture in patients with glucocorticoid-induced osteoporosis (GIO) is occurred despite properly maintained bone mineral density. So the criteria of primary osteoporosis cannot be adapted to GIO. This is caused by the difference of disease's pathology. In glucocorticoid therapy, duration and total volume of dosage of the drug affects bone strength, and then the risk of fracture will be increasing. However, even if low dosage of glucocorticoid is used for the patients, the risk of fracture has increased more than that of normal people. The site of fracture is well recognized in vertebral body, hip joint, rib, and sacrum. While, the fracture in patients with rheumatoid arthritis (RA), one of the disease representing GIO, is observed in all of the body, including long bone and periarticular bone in addition to the site of fracture observed in GIO. The risk of fracture in patients with RA is increased by the glucocorticoid daily use and the functional disability.

The functional mechanism of glucocorticoid (GC)-induced osteoporosis is not fully understood. We examined to the effects of GC on bone turnover, minerals, structure, and bone strength in growing minipigs. GC administration caused prolongation of the period of bone tissue turnover in both trabecular and cortical bone and imbalance in bone formation and resorption, consequently leading to osteoporosis in growing minipigs. Bone structure were deteriorated both trabeculare and cortex. Deterioration of cortical bone rather than trabecular bone could play a role as main factor of bone fragilities in GC-induced osteoporosis.

Most of the guidelines for management of glucocorticoid-induced osteoporosis (GIOP) recommend bisphosphonates as therapeutic agents. However, bisphosphonates have a gastrointestinal side effect, and a potential risk for pregnant women and children. Moreover, an efficacy of combination therapy with proved drugs for GIOP remains to be clarified. An analog of vitamin K(2) reduced the fracture risk independent from the bone mineral densities in GIOP. Since GIOP induced bone fracture even in the high bone mass, the vitamin K(2) analog should be an effective therapeutic agent for GIOP through increasing bone strength without an increase in bone mineral density.

Bisphosphonates are now the most widely used drugs for osteoporosis. When bisphosphonate is given, the response varies directly with the rate of bone turnover at baseline. In high turnover osteoporosis there could be a gain in bone mass, but it reach a plateau after 2 to 3 years. In normal or low turnover osteoporosis bone mass is stabilized or slightly increased. The best indication of bisphosphonate use for osteoporosis is high turnover. In high turnover osteoporosis bisphosphonate therapy is effective in increasing the stiffness and the toughness (bone strength) by increasing the mean degree of mineralization of bone tissue through the prolongation of secondary mineralization. But the long-term use of bisphosphonate would result in highly mineralized bone and disturbed repair of microcracks by inhibition of bone remodeling. Intermittent use of bisphosphonate could be recommended to avoid the deterioration of bone quality.

Quantification of accumulated microdamage in bone is one of evaluation methods of bone quality. Microdamage accumulation in bone reduces some tissue material property of bone. However, microdamage is also closely associated with bone metabolism and mechanical environment of bone, and functions as accelerator of bone turnover through the detection and repair of damage.

Osteopetrosis is a genetic disorder characterized by increased bone mass due to the reduced bone resorption. It is also characterized by the discrepancy between bone mass and bone strength. In this review, I would like to introduce the up-to-date of the research and treatment of osteopetrosis.

Bone quality including "structural property" and "material property" , which is strongly affected by bone remodeling and has an influence on bone biomechanical property. Structural property means macroscopical geometry, bone size, trabecular microstructure, cortical thickness and cortical porosity. Material property means mineralization, crystal size, collagen and microdamage. Although most of them are analyzed in vitro, in the future, noninvasive assessment of bone quality may help to guide therapy of osteoporosis.

While the diagnosis and management of primary osteoporosis have been established and widely utilized, these for glucocorticoid-induced osteoporosis (GIOP), i.e. a representative of secondary osteoporosis, are on their way. GIOP caused fractures at a higher bone mineral density (BMD) compared to primary osteoporosis. The cut off value of the BMD for prediction of fractures was around 80% of the young adult means (T-score; -1.5). As this value would give a useful diagnostic point for initiating treatments, measurements of BMD should be a significant tool for management of GIOP.

Ultrasonic measurements of bone status or bone mass density are generally performed using ultrasonic parameters consisting of the slope of frequency-dependent attenuation (or broadband ultrasound attenuation: BUA) and the speed of sound (SOS). Many results of in vitro laboratory measurements and in vivo clinical trials have shown the ultrasonic parameters, BUA and SOS correlate significantly with the bone mass density measured by X-ray method. However, there exists some problem inherent in the ultrasonic method on the reproducibility and the uncertainty of measured ultrasonic parameters. The ultrasonic properties of cancellous bone have been experimentally and theoretically studied by author's group to reveal problems inherent in the ultrasonic method. According to experimental and theoretical studies, two longitudinal waves, fast wave and slow wave are clearly observed. The propagation speed of the fast wave increases with the bone density and that of the slow wave decreases very slightly with the bone density. Whereas the attenuation constant of the fast wave is much higher than that of the slow wave and is almost independent of the bone density, but in contrast, the attenuation constant of the slow wave increases considerably with the bone density. Experimental results on transmitted ultrasonic wave through cancellous bone show that the amplitude of the slow wave decreases with the bone density and the amplitude of the fast wave, on the contrary, increases with the bone density. This dependence of the fast wave amplitude on the bone density can not be explained by the attenuation constant. The ultrasonic wave propagation path through cancellous bone is modelized to clarify the propagation phenomenon and to specify the causality between ultrasonic wave parameters and the bone density. The bone density is quantitatively formulated based on the modelization as a function of the amplitude and the propagation speed of the fast wave.

Recently Bone quality has been recognized as an important contributing factor of bone strength, as clearly stated in NIH (National Institute of Health) consensus development panel of 2000 that bone strength reflects both bone density and bone quality. Bone quality refers to architecture, turnover, damage accumulation, mineralization and matrix. In the treatment of osteoporosis anti-resorptive agents increase bone strength with decreasing bone turnover. It is important to control bone turnover within favorable range to increase bone strength without deterioration of bone quality.

Two experiments were carried out using 7-week-old male Wistar rats. Exp. 1: Rats in the intact group were fed with normal diet (0.5% Ca, 0.09% Mg). Ca/Mg deficient rats were fed low Ca (0.01%) diets containing 0.003, 0.015 or 0.09% Mg for 4 weeks. After 4 weeks, the bone mineral density (BMD) and maximum load in the femur were decreased in Ca/Mg deficient rats, but this was not dependent on dietary Mg concentration. The elasticity, stiffness, and Mg concentration in the femur of these rats were also decreased and Ca deposition in the kidney were increased, compared to those of normal rats, which were related to Mg concentration in the diet. From these results, Mg may play an important role in qualitative changes in bone (i.e., reduced stiffness). Exp. 2: We investigated the effects of V.K2 on the changes in BMD and bone strength in femur induced by low Ca/Mg (0.01%/0.003%) diet for 8 weeks. Compared to the intact group, Ca and Mg levels in serum and femur and cortical thickness, cortical area, and maximum load of the femoral midshaft were decreased in the Ca/Mg-deficient group. In these rats, PTH in the serum and renal Ca concentration were increased. In V.K2-treated rats, these changes in the serum Ca, Mg and PTH levels and the renal Ca concentration were improved. V.K2 also improved the decrease in maximum load in spite of no influence on the cortical thickness, cortical area and Mg concentration in the femur. These findings suggest that V.K2 may affect the qualitative change in bone.

Bone mass is the lifelong result of a balance between bone formation and bone resorption as shown in most metabolic bone diseases including involutional osteoporosis. To date, bone turnover has been precisely assessed by bone histomorphometry made by bone biopsy and also calcium kinetics and balance studies. However, bone histomorphometry is an invasive procedure requiring specialized laboratory for processing and evaluation, and calcium kinetics and balance studies require administration of radioisotopes and long periods of observation. Therefore, these procedures are not suitable for clinical tests of evaluation of bone turnover. Recently several biochemical parameters for bone turnover have been developed and also a number of noninvasive procedures such as single and dual photon absorptiometry, dual energy x-ray absorptiometry, computed tomography and ultrasound velocity, have been developed to quantitate bone mass more sensitively. In this symposium "Bone turnover and clinical tests" five symposists talked and discussed about some biochemical parameters for bone turnover and noninvasive procedures for measurement of bone mass.

Serum and urine chemical analyses were combined with a bone histomorphometrical study of rat metaphyses to evaluate the osteogenetic effect of intermittent administration of human parathyroid hormone (h-PTH) on steroid-induced osteopenia. Seven-month-old female Wistar rats were divided into the following 4 groups: (1) a control group: age-matched and untreated; (2) a baseline control group (BL group): given 2.5 mg/kg prednisolone subcutaneously 6 times/week for 8 weeks, at the end of which the animals were sacrificed; (3) a PTH group: in the 9th week of continuous steroid administration, 6.0 micrograms/kg h-PTH was added to the regimen; and the animals were sacrificed in the 12th week; (4) a vehicle group, as a control for the h-PTH group: only the vehicle was administered instead of PTH. At the necropsy at the end of the experiment, both tibias were collected. The undecalcified sections were stained by Villanueva bone stain and labelled with tetracycline, and the decalcified sections were stained by TRAP, and examined histomorphometrically. Serum Ca and P were not changed by any treatment. Serum 1,25 (OH)2D3 values were significantly increased in rats treated with h-PTH. There was no significant change in urinary Ca, P, or hydroxyproline excretion in any group. Histomorphometrically, the parameters related to bone formation--osteoid surface, mineralized surface and bone formation rate--were all reduced in the BL group and in the vehicle group. The bone volume was significantly lower in these group than in controls. The PTH group, on the other hand, showed increases in the osteoid surface, mineral apposition rate, and bone formation rate and the bone volume was significantly higher than in controls. The PTH group showed no increases in the osteoclast number or in the osteoclast surface. These results suggested that intermittent administration of h-PTH activated bone formation only, and increased bone volume.

We report a 63-year-old female, case of multiple sclerosis associated with lateralization of bone change. In 1969, at age 38 she lost sight in her right eye. After that, she had several episodes of remission and exacerbation. In 1992, left hemiparesis, sensory disturbance and vesicorectal disturbance appeared, and she was admitted to our hospital. Immediately, steroid pulse-therapy was initiated then steroids were tapered. Her muscle strength recovered to some degree. The left upper limb showed low skin temperature, edema and decreased circulation. In January and September of 1993, bone examinations were conducted using multiple scanning X-ray photodensitometry. Osteopenia was observed, especially in the left hand. The bone density in the right hand changed slightly during the 8-month course of the illness, but osteopenia in the left hand became more marked. The asymmetrical bone change suggested that osteopenia results from a disorder of the central nervous system, especially through autonomic disorder.

In primary hyperparathyroidism, bone remodeling is increased due to an enhanced activation frequency which is caused by excessive PTH. In mild cases, eroded, osteoid and labeled surfaces are increased. But as bone balance per remodeling cycle in cancellous bone is zero or even slightly positive, bone volume and structure are relatively maintained. In advanced cases, bone resorption is predominant in the endosteal surface of cortical bone, resulting in progressive thinning and increased porosity, cancellisation. As far cancellous bone resorption depth is deepened to occur trabecular perforation associated with fibrous tissue replacement, osteitis fibrosa.