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Late-onset hypogonadism(LOH)in aging male is known to represent disorder of bone metabolism, contributing to the development of secondary osteoporosis. And recent findings suggest that it is also associated with sarcopenia and frailty. Diagnosis and therapeutic approaches against LOH in aging male might be crucial not only for improving clinical symptoms of LOH but also for maintaining bone mineral density and prevention from male osteoporosis.

Chronic obstructive pulmonary disease(COPD), an inflammatory disease of the lung mainly caused by cigarette smoking, is a systemic disease associated with various extra-pulmonary comorbidities such as osteoporosis, ischemic heart disease and sarcopenia. Osteoporosis is one of such complications, and the prevalence of vertebral fractures in COPD is high even in early COPD stages. Loss of bone mineral density as well as deterioration of bone quality is common in COPD patients. However, the pathophysiology of bone fragility in COPD-associated osteoporosis is still incompletely understood. COPD patients are exposed to various disease-specific risk factors such as systemic inflammation, glucocorticoid use and vitamin D insufficiency/deficiency, accumulation of which leads to development of COPD-associated osteoporosis. Vitamin D repletion and timely intervention with anti-osteoporotics would be important to protect COPD patients from fracture.

Osteoporosis is deterioration of bone integrity caused by bone loss(bone mineral density decrease)due to failure of coupling of bone resorption and bone formation. Various pathophysiological conditions other than natural menopause or aging are involved in the development of osteoporosis. When there is a specific cause of the disease, it is referred to as secondary osteoporosis. Secondary osteoporosis is usually thought to lead to an increased risk of fracture by causing a decrease in bone mineral density. It has also should be noted that in patients receiving corticosteroids, bone mineral density independent fracture risk increases. Furthermore, now we are aware of the existence of many diseases including type 2 diabetes, which contributes to an increase in the risk of fracture irrespective of bone mineral density. Unfortunately, at present, it is difficult to quantitatively evaluate the contribution of those background diseases to fracture risks, so the establishment of guidelines on intervention for fracture prevention is still awaited.

Rickets and osteomalacia are diseases characterized by impaired mineralization of bone matrix. The same causes can result in rickets and osteomalacia. Of these, rickets develops before the closure of growth plates and presents bone deformities and growth retardation. Diagnostic criteria for rickets and osteomalacia have been published in Japan.

Thyrotoxicosis, commonly seen in a condition with Graves' disease, causes increased bone absorption and results in osteoporosis with increased bone turnover. The osteoporotic state is dominant in cortical bones with slight impairment of calcium-homeostasis, although the precise mechanism is still elusive. It ought to be recovered in accordance with the amelioration of thyroid hormone status, but past history of thyrotoxicosis might cause bone fragility, especially in post-menopausal or senile patients.

Bone metabolism disorder caused by surgery and diseases of the gastrointestinal tract has been reported formerly, however the awareness of these disorder is not high. Calcium is absorbed mainly from the duodenum to the upper jejunum, moreover gastric acid plays an important role in digestion and absorption of calcium. Therefore, it is easy to imagine that gastrectomy will cause bone metabolism disorder. Furthermore, bone metabolism disorder accompanies with inflammatory bowel disease is drawing attention in recent years. Bone metabolic disorder accompanying with gastrointestinal dysfunction is not rare, accordingly clinician needs to understand the pathological condition. In this report, we will outline bone metabolism disorder caused by gastrointestinal surgery and diseases.

Because of improved treatment of cirrhosis, patients are living longer and bone disesae such as osteoporosis is found in an increasing proportion of patients with cirrhosis. As the causes for bone diseases in cirrhosis, inhibition of vitamin D hydration and inhibition of vitamin D absorption due to decreased secretion of cholic acid have been reported, and various other causes are concerned. These bone diseases have been treated with bisphosphonates, but no definite opinion has been obtained in relation to therapeutic effects. In recent years, non-alcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)is increasing in prevalence. Relation of these deseases with osteoporosis, however, is not well known and further investigation is needed.

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.

Rheumatoid arthritis(RA)is an immune-mediated disease marked by chronic synovial inflammation, which leads to cartilage and bone destruction as well as systemic bone loss. Osteoporosis or the systemic bone loss associated with RA increases the risk for fragility fractures, which can affect quality of life dramatically in RA patients. Inflammatory cytokines such as TNF and IL-6 in inflamed synovium induce the differentiation of osteoclasts, while suppresses the differentiation of osteoblasts, resulting in imbalance in bone metabolism. Although RA treatment targeting inflammatory cytokines can deter the progression of cartilage and bone destruction directly or indirectly, it can not stop systemic osteoporosis. Although it is important to avoid immobility by introducing an early remission, it is necessary to thoroughly manage the risks of individuals of RA patients and to effectively use osteoporosis drugs such as anti-RANKL antibodies that also have the effect of suppressing bone erosion in RA.

In the etiology of secondary osteoporosis, only primary hyperparathyroidism is the one to which osteoporosis itself is indicated for surgery. However, there are several diseases that may give bone a good environment by surgical treatment for primary diseases such as hyperthyroidism or Cushing's syndrome, and secondary osteoporosis may improve. It is important to properly conduct differential diagnosis and to discuss and determine surgical indication.

Breast cancer is a typical hormone-dependent tumor and at the time of diagnosis more than 60% of breast cancers are positive for estrogen receptors and estrogen(E)is required for proliferation. Since breast cancer is a tumor easily to cause micrometastasis, adjuvant hormonal therapy(HT)for 5 to 10 years after surgery that suppresses the action of estrogen actively prevents recurrence is very popular. However, HT with aromatase inhibitor(AI)for postoperative postmenopausal breast cancer markedly reduces the E concentration in the body, leading to significant bone loss and fracture as known as aromatase inhibitor-induced bone loss(AIBL), a typical example of CTIBL. Under these circumstances, the usefulness of bone modifying agents as a supportive therapy to increase bone density and decrease fracture rate without interrupting the treatment of breast cancer became clear, mainly in Europe and the United States. And recently, our study revealed even in Japanese breast cancer patients denosumab injection every 6 months showed significant increase in bone density. The number of women suffering from breast cancer in Japan reaches approximately 90,000 per year, a considerable number is estimated as a preliminary group of CTIBL, so early appropriate measures are desired.

Androgen deprivation therapy(ADT)is a standard systemic therapy for prostate cancer. ADT induces bone loss(ADTIBL)and muscle loss(sarcopenia)leading to falls and farctures. There are 2 aims in bone management of prostate cancer:one is to prevent fragility fractures in patients without bone metastasis and the other is to prevent symptomatic skeletal events(SSE)which are pathologic fractures, spinal compression, radiation to bones and surgery to bones. Bone fractures and SSE are both correlated with worse overall survival(OS). Concomitant use of novel anti-androgens further increases the risk of falls and fractures. The earlier and appropiriate intervention with vitamin D and bone modifying agents(BMA)is necessary to prevent treatment related bone fractures and SSE. Bone management algorithm aids to decide the timing and doses of BMA. As for sarcopenia physical exercise and life style advices are important. Because abiraterone with glucocorticoid therapy induces stronger bone resorption, it is recommended to start denosumab simultaneously. Ra-223, bone seeking radiopharmaceuticals should not be used with abiraterone and predonisone because of high incidence of fracture and death.

Similarly to adult osteoporosis, childhood osteoporosis also is usually divided into primary and secondary causes. Primary osteoporosis includes genetic disorders represented by osteogenesis imperfecta. Secondary pediatric osteoporosis is associated with various diseases and glucocorticoid treatment, and malnutrition, impaired mobility, chronic inflammation and endocrine disorders can be risk factors. In growing children, mild osteoporosis can be spontaneously recovered by elimination of risk factors. However, initiation of treatment using drugs such as bisphosphonate should be considered in primary osteoporosis including osteogenesis imperfecta and severe secondary osteoporosis which cannot be spontaneously improved. Administration of bisphosphonate increased bone mineral density in pediatric patients, but long-term safety and efficacy need further investigation. Development of new drugs to treat osteogenesis imperfecta is underway, which include the antibodies against sclerostin and TGF-β.

Primary hyperparathyroidism(PHPT)is one of the common endocrine disorders, which results clinically in secondary osteoporosis. PHPT also occurs nephrolithiasis, muscle weakness, cardiac and psychiatric abnormalities even in a mild or asymptomatic disease. Parathyroidectomy(PTX)is the only definitive treatment for PHPT. In the case PTX is not choose, these patients may require intervention for management of osteoporosis and/or hypercalcemia.

In patients with chronic kidney disease(CKD), mineral metabolism abnormalities such as hyperphosphatemia, decreased 1,25-dihydroxyvitamin D, and elevated parathyroid hormone develop as kidney function declines, which lead to vascular calcification and a variety of skeletal abnormalities, collectively termed renal osteodystrophy. Because CKD patients have increased risk of bone fractures, it is important to assess fracture risk by measuring bone mineral density and bone metabolism markers. In addition to management of secondary hyperparathyroidism, medications for osteoporosis could be a reasonable option for preventing fracture.

Glucocorticoid(GC)excess is one of the most common causes of secondary osteoporosis, which can be associated with a disease(GC excess due to Cushing's syndrome)or with a treatment(GC medications). In addition to Cushing's syndrome, subclinical Cushing's syndrome, which occurs more frequently, can also increase the risk of fractures. Thus, it is important to consider these diseases when making the diagnosis for osteoporosis. GC-induced osteoporosis leads to reduction of bone mineral density and increased risk of fracture from the early stage after initiation of GC treatment, and thus requires management from the time of initiation. The 2014 revised Guidelines on the Management and Treatment of GC-induced Osteoporosis should be used routinely in the clinical settings as they introduce a scoring system that is easily adoptable.

Patients with inflammatory bowel disease (IBD) are at increased risk for osteoporosis and fracture. This is considered to be relevant to IBD-related risk factors, including intestinal inflammation, low nutrient status and the use of corticosteroids, in addition to general risk factors, such as age, gender and BMI et al. A recent meta-analysis suggests that bisphosphonate is effective and safe for the treatment of low bone mineral density and reduce risk of vertebral fractures in patients with IBD. With recent advances in medical treatment for IBD, the number of elderly IBD patients is expected to increase in future. Prevention and treatment of osteoporosis associated with IBD is essential for improving QOL of patients with IBD.

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.

With aging, insulin resistance and sarcopenia in skeletal muscle are induced, resulting in skeletal muscle aging. It is suggested that the former is one of the reasons that mitochondrial function decreases with aging, and the latter is due to endocrinologic dysfunction, neurological mechanism, nutritional deficiency and inactivity such as waste are complicatedly involved. Also, as sarcopenia progresses, the amount of physical activity further decreases, and it is also assumed that insulin resistance and sarcopenia progress synergistically. It is suggested that exercise enhances the activity and amount of mitochondria and works preventively against insulin resistance in skeletal muscle accompanying aging and it also works for prevention and amelioration of sarcopenia. On the other hand, as for nutritional supplementation, it has been reported that it works for improving sarcopenia by amino acid ingestion.

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.

Female patients with rheumatoid arthritis(RA)are at high risk for osteoporosis and fractures. In Japanese female patients with RA, age, disability, daily prednisolone dose, history of total knee replacement, and low bone mineral density are known to be risk factors for fractures, and more than 70% are reported to be vitamin D deficiency.

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.

The purpose of Osteoporosis Liaison Service(OLS)is primary and secondary prevention of osteoporosis and fragility fracture by multiple medical occupations. Exercise instruction and exercise intervention are important factors in OLS. Exercise has effects of increasing bone density and preventing falls. In OLS, it is also necessary to disseminate knowledge on osteoporosis and fractures to the public. Main measures against locomotive syndrome(LS), meaning weakening of ambulatory ability, are exercise and nutrition, and the LS prevention campaign is thought to lead to prevention of falls. In addition, LS is in common with OLS because it aims to spread such preventive measures widely. Exercise for LS prevention can be used safely and effectively at hospitals and workshops, as well as regional comprehensive care system.

The decline in sex hormones along with aging is suggested to be involved in age-associated diseases such as cardiovascular diseases, osteoporosis, and dementia. The decrease of estrogen level after menopause is related to osteoporosis in addition to climacteric disturbance in women, while that of testosterone to sarcopenia, osteoporosis and late-onset hypogonadism in men. New treatment strategy is expected for targeting age-associated diseases against the decreased level of sex hormones.

A place of the activity of Osteoporosis Liaison Service (OLS) is classified into the in-hospital and the out-hospital. "Kotsu-Kotsu approach" is performed in our hospital for fracture inpatients as OLS. "Kotsu-Kotsu approach" can be able to performed the various and comprehensive assessment for the patients by multi medical staff, especially Osteoporosis managers. The construction of the cooperation with other facilities is propelled for activity of out-hospital. Ministry of Health, Labour and Welfare impel to establish community-based integrated care systems. Importance adds to OLS under the multi medical staff cooperation that I included the care in the community in more and more from now on. To that end, the leadership of the doctor is required.

Both osteoporosis and vascular calcification are highly prevalent in aged subjects and patients with diabetes and chronic kidney disease(CKD). Although it has long been thought that vascular calcification is a consequence of degeneration of vessel walls, recent studies unveiled the molecular mechanism of vascular calcification and identified the vascular calcification as a process similar to bone formation. With the advent of the understanding of the basis for bone remodeling, several hypotheses have been proposed for the underlying mechanism of the interaction between osteoporosis and vascular calcification. Briefly,(1)impaired bone remodeling may perturb serum calcium/phosphate, thus contributing to increased vascular calcification,(2)vascular calcification may precede osteoporosis, and(3)molecules responsible for bone remodeling, including estrogen, parathyroid hormone and vitamin D, RANK(receptor activator of nuclear factor kB), RANK ligand(RANKL), and osteoprotegerin(OPG), Wnt signaling, and loss of calcification inhibitors(matrix Gla protein)may promote vascular calcification. This review discusses the emerging role of bone remodeling factors in vascular calcification.

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.

As men are less likely than women to develop osteoporosis, male osteoporosis remains poorly understood. However, elderly men have a clearly reduced bone mineral density and increased risk for fractures. In Japan, one in four patients with osteoporosis is male. Male osteoporosis is associated with not only reduction in androgen, but also estrogen, and differs from postmenopausal osteoporosis in that decreased bone formation is involved and that age-related changes in cortical bone structure and perforation of the trabeculae of cancellous bone are unlikely to occur. The proportion of secondary osteoporosis is higher for men than women;therefore, differential diagnosis is important in the diagnosis of male osteoporosis. In addition, it is recommended that bone mineral density be measured at the femoral neck or total hip in men. Men have a worse prognosis following fractures than women, and management of male osteoporosis is highly important for extending healthy life expectancy.

Osteoporosis is a major public health issue not only in women but also in men. Risk factors for low bone mineral density(BMD)need to be identified in men. We have examined factors related to BMD in the Fujiwara-kyo Osteoporosis Risk in Men study. Smoking habit was associated with low BMD. Moderate alcohol intake(<55 g/day), greater milk intake and greater natto intake were associated with high BMD. Non-smoking, greater milk intake and greater natto intake may prevent osteoporosis in men.

About 3million men have been reported to have osteoporosis in Japan. One of known causes of osteoporosis in men is late-onset-hypogonadism. Androgen replacement therapy has been reporte to be effective in seveal literatures, however, patitiets should be excluded if prostate cancer is suspected. Addition of bisphosphpnate and active vitain D derivatives are recommended.

Chronic obstructive pulmonary disease(COPD)is a chronic inflammatory disease associated with an increase of fracture risk. Bone strength is determined by bone mass and quality.Bone quality is thought to encompass the structural and material properties of bone. Bone collagen crosslinking plays important roles in bone strength. The quantitative and qualitative deterioration of lysyl oxidase control and non enzymatic cross-links(advanced glycation end products, AGEs, pentosidine)of collagen in patients with osteoporotic femoral neck fracture and diabetes, and COPD might be affected by increased oxidative stress and glycation.

Chronic obstructive pulmonary disease(COPD)is a progressive lung disease and its prevalence increases with age. Elderly patients with COPD are known to be at increased risk of sarcopenia and osteoporosis, and this multimorbidity adversely affects progression and prognosis of COPD in parallel. Systemic inflammatory processes and serum biomarkers including cytokines and C-reactive protein might be involved in the underlying pathphyisoplogy for systemic manifestations and multimorbidity of respiratory diseases. In this review, recent insights in the association between respiratory diseases and sarcopenia are introduced, based on the pathophysiology and therapeutic implication of systemic inflammation and age-related muscle wasting.

Bone mineral density(BMD)and bone microstructure are regulated mainly by bone remodeling. In contrast, bone collagen enzymatic immature and mature cross-links and advanced glycation end products such as pentosidine and carboxyl methyl lysine are affected by various factors. Aging bone tissue is repaired in the process of bone remodeling. However, 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. To improve bone material properties in osteoporosis, we should use different drug (Saito M, Calcif Tissue Int, REVIEW, 97;242-261, 2015). In this review, we summarized determinants of bone quality and strength independent of bone remodeling.

Osteoporosis is a disease characterized by increased risks for bone fragility fractures, and is caused by various factors such as aging and menopause. Increase in the number of osteoporosis patients becomes a big concern in the developed countries. Recently, the mechanisms underlying postmenopausal osteoporosis development were being clarified, and several diseases such as respiratory diseases and diabetes were reportedly caused secondary osteoporosis. HIF1α was demonstrated required for osteoclast activation and bone loss in postmenopausal osteoporosis women. However, the roles of HIF1α on respiratory disease-related osteoporosis development remained to be elucidated.

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.

Chronic Obstructive Pulmonary Disease(COPD)is characterized by persistent airflow limitation that is associated with chronic inflammatory process caused by inhaled noxious particles such as cigarette smoke. COPD involves not only the lungs but also extrapulmonary abnormalities as systemic effects. Osteoporosis is one of major comorbidities in COPD, and is often under-diagnosed. Osteoporosis in COPD is associated with various factors including smoking, decreased body mass index, and systemic inflammation. It should be recognized that COPD is a risk factor for osteoporosis and bone fracture, and early diagnosis and management for both COPD and osteoporosis are important.

Mechanism of generalized osteoporosis associated with rheumatoid arthritis(RA)is multifactorial and following factors has been proposed:systemic effect of RA synovitis, glucocorticoids, weight loss, and endocrine changes. In addition to control of RA inflammation and management of glucocorticoid-induced osteoporosis(GIO), antiresorptive therapy, such as bisphosphonates is expected to show efficacy. Recently, anti-RANKL monoclonal antibodies have been shown to inhibit bone erosion and bone loss in combination with methotrexate in RA. GC-induced bone loss is most rapid during the initial 3 ~ 6 months and more slowly thereafter. Therefore, both primary and secondary prevention are important. The Japanese Society for Bone and Mineral Research(JSBMR)has updated the Guidelines on the Management and Treatment of GIO and has incorporated a new scoring method. By analyzing five GIO cohorts from primary and secondary prevention studies, age, GC dose, lumbar BMD, and prior fragility fractures were identified as risk factors and the fracture risk for an individual can be calculated as the sum of the scores for each risk factor. Pharmacological intervention should be started on the basis of a score of 3 as the optimal cut-off score. Both alendronate and risedronate are recommended as first-line treatment. Ibandronate,teriparatide, and active vitamin D3 derivatives are recommended as alternative option.

Primary biliary cirrhosis(PBC)is a chronic autoimmune cholestatic liver disease. Metabolic bone disease is recognized in a complication of chronic liver disease, particularly in PBC. Bone disease in PBC includes osteoporosis and, osteomalacia which is more frequent in advanced liver disease. It is important that PBC occurs mainly in middle-aged women who are highest risk group in primary osteoporosis. In patients with PBC, the dysfunction in enterohepatic circulation of bile acids is associated with the impaired absorption of fats and fat soluble vitamins. Vitamin D and K deficiency leads to osteoporosis resulting in increased risk of bone fracture. This article describes the characteristic and molecular mechanism in bone disease of PBC.

Osteoporosis is defined as a condition of impairment in bone strength and predisposes individuals to an increased risk of fractures. The risk of fragility fracture is shown to be high in patients with chronic kidney disease (CKD). Osteoporosis treatment for patients with CKD G1-3 should not differ from treatment for patients without CKD, as long as there are no accompanying hyperparathyroidism and hyperphosphatemia that indicate the co-existence of CKD -mineral and bone disorder. However, there are few published data on osteoporosis treatment for patients with CKD G4, 5. So, considerations for current pharmacologic therapy (such as bisphosphonate, denosumab, teriparatide, and raloxifene) should be a thoughtful and open discussion with these patients.

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.

This article reviews the treatment strategy for the secondary osteoporosis excluding those caused by diabetes, CKD, endocrine disorders, or glucocorticoid, which proceeding articles deal with. Among numerous possible causes for such secondary osteoporosis, the author has selected osteogenesis imperfecta (OI), osteoporosis associated with gastrectomy or bariatric surgery, inflammatory bowel diseases (IBD), and chronic obstructive pulmonary disease (COPD). For OI, current standard treatment is bisphosphonates (BPs), of which efficacy for fracture inhibition has recently been of issue. Other treatment modalities, e.g. PTH, have just been explored. Osteoporosis associated with gastrectomy, bariatric surgery or IBD, have been treated with vitamin D, calcium, and BPs. Despite high fracture rates, there are almost no treatment data for osteoporosis associated with COPD.

Accumulating evidence has shown that the risk of osteoporotic fracture is increased in patients with type 1 and 2 diabetes mellitus. Measurement of bone mineral density is not a good evaluation tool for diabetes-related osteoporosis because the underlying mechanism is based on the deterioration of bone quality with accumulation of collagen cross-links of advanced glycation end products, decreased bone formation, and cortical porosity. Thus, we should choose the anti-osteoporosis drug while taking the mechanism into consideration. However, the evidence of treatments for diabetes-related osteoporosis is not sufficient so far. Therefore, further studies are necessary to solve this issue in future.

The discovery of organ-network between bone and other organs revealed that organs other than bone are intimately involved in bone remodeling. Notably, control of bone remodeling by nervous system and control of phosphate and glucose metabolism by bone are areas of intense investigation. Moreover, metabolic diseases such as diabetes and COPD are shown to be involved in the pathogenesis of osteoporosis. Thus, osteoporosis is considered to be not just a local bone disease, but a manifestation of the whole body metabolism abnormality.

Many patients with osteoporosis have complicated with CKD. It was reported that the risk of hip and vertebral fracture is higher in osteoporosis patients with CKD than without CKD. Because the drugs for osteoporosis are excreted by kidney, there are no drugs that the efficacy and safety were established for the CKD patient. I give an outline about the relationship between CKD and osteoporosis, and the note on the medical care of osteoporosis patients with CKD.