Risedronate for the prevention of fractures in postmenopausal osteoporosis

OBJECTIVE: To evaluate current scientific literature regarding the efficacy of risedronate in the prevention of vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. DATA SOURCES: Primary research articles were identified by MEDLINE search (1966-May 2001) and through secondary sources. Key search terms were risedronate, postmenopausal osteoporosis, and fractures. DATA SYNTHESIS: Osteoporosis results in a reduction of bone mineral density, increased bone fragility, and increased risk of fractures. The goal of osteoporosis therapy is not only to increase bone mass, but also to reduce the rate of fractures. Risedronate is the newest bisphosphonate to be approved for the prevention and treatment of osteoporosis. An evaluation of clinical trials using risedronate in the treatment of postmenopausal osteoporosis was performed to determine its efficacy at decreasing fracture rates. CONCLUSIONS: Risedronate is an effective and safe option for the treatment of postmenopausal osteoporosis. Risedronate significantly decreases the risk of vertebral and nonvertebral fractures in women who have had > or =1 fractures in the past. More studies are warranted to evaluate the efficacy of risedronate in women without preexisting vertebral fractures.     

THE USE OF BISPHOSPHONATES IN OSTEOPOROSIS

SUMMARY Bisphosphonates comprise a relatively new class of drug developed to inhibit bone resorption. They are used in Paget's disease and tumour bone disease and recently also in osteoporosis. In the latter, they inhibit further bone loss in postmenopausal osteoporosis as well as other types of bone loss, such as that suffered during immobilisation or steroid therapy.     

An approach to postmenopausal osteoporosis treatment: a case study review

PURPOSE: To review and discuss the clinical evaluation and therapeutic options for a postmenopausal woman with osteoporosis. DATA SOURCES: Review of scientific literature, practice guidelines, and a case study. CONCLUSIONS: To prevent and treat postmenopausal osteoporosis, women should be encouraged to perform weight-bearing exercise, to not smoke, and to optimize calcium and vitamin D intake through diet and supplements. Drug regimens are effective and well tolerated in postmenopausal women with osteoporosis. IMPLICATIONS FOR PRACTICE: Drugs currently approved by the U.S. Food and Drug Administration for the treatment of postmenopausal osteoporosis include the bisphosphonates risedronate and alendronate; the selective estrogen receptor modulator, raloxifene; and intranasal calcitonin-salmon spray. Bisphosphonates have demonstrated the most impressive fracture risk reduction in prospective clinical trials of women with postmenopausal osteoporosis. Risedronate has consistently demonstrated significant reductions in vertebral fracture risk at 1 year and in vertebral and nonvertebral fracture risk at 3 years. Alendronate has demonstrated significant reductions in vertebral and nonvertebral fracture risk after 3 years.     

Large clinical trials for osteoporosis

The prevention and treatment of osteoporosis are now a necessary goal because of the aging of the population and the social and economic costs of fracture complications. The publication of guidelines by registration agencies during the last 10 years has provided precise rules for evaluating new drugs designed for the prevention and treatment of postmenopausal osteoporosis. The benefit of combination treatment with calcium and vitamin D in osteoporotic patients has clearly been proven, especially among the oldest patients, but results of prospective studies designed for the prevention of fracture risk are conflicting. In the Fracture Intervention Trial (FIT), treatment with alendronate 10 mg/day reduces the risk of vertebral fracture by 48% and increases bone mineral density (BMD) in patients with vertebral fractures. In the Vertebral Efficacy with Risedronate Therapy Multi-National (VERT-MN) and VERT-NA (North America) studies, treatment with risedronate 5 mg/day reduces the risk of vertebral fracture by 49% and 41%, respectively. Risedronate 5 mg daly for 3 years leads to an increase in BMD. The Prevent Recurrence Of Osteoporotic Fractures (PROOF) study has shown a significant decrease in the risk of vertebral fracture in patients treated with calcitonin 200 IU. However, numerous criticisms of the methodology of this study design have been identified. Selective estrogen receptor modulators could act as agonists or antagonists of estrogens, depending on the target tissue. In the Multiple Outcomes of Raloxifene Evaluation (MORE) study, treatment with raloxifene reduces the risk of vertebral fracture by 50% in patients without prevalent vertebral fracture and by 30% in patients with prevalent vertebral fracture. PTH treatment leads to an increase in BMD and reduces the risk of vertebral fracture by 65%. Strontium ranelate has a novel mechanism of action (stimulation of bone synthesis and decrease in bone resorption), and administration of 2 g daily has a proven positive effect, leading to an increase in bone mass among women with osteoporosis. This effect was especially evident in the Spinal Osteoporosis Therapeutic Intervention phase III (SOTI) study, in which a significant decrease in the incidence of vertebral fracture of 41% over 3 years has been shown. Thus, effective therapeutic strategies now enable improved treatment of postmenopausal osteoporosis. However, this condition is still poorly diagnosed and not all patients are correctly treated. Preventing the occurrence of the first fracture should remain the prime concern.     

Pharmacologic prevention of osteoporotic fractures

Osteoporosis is characterized by low bone mineral density and a deterioration in the microarchitecture of bone that increases its susceptibility to fracture. The World Health Organization defines osteoporosis as a bone mineral density that is 2.5 standard deviations or more below the reference mean for healthy, young white women. The prevalence of osteoporosis in black women is one half that in white and Hispanic women. In white women 50 years and older, the risk of osteoporotic fracture is nearly 40 percent over their remaining lifetime. Of the drugs that have been approved for the prevention or treatment of osteoporosis, the bisphosphonates (risedronate and alendronate) are most effective in reducing the risk of vertebral and nonvertebral fractures. Risedronate has been shown to reduce fracture risk within one year in postmenopausal women with osteoporosis and in patients with glucocorticoid-induced osteoporosis. Hormone therapy reduces fracture risk, but the benefits may not outweigh the reported risks. Teriparatide, a recombinant human parathyroid hormone, reduces the risk of new fractures and is indicated for use in patients with severe osteoporosis. Raloxifene has been shown to lower the incidence of vertebral fractures in women with osteoporosis. Salmon calcitonin is reserved for use in patients who cannot tolerate bisphosphonates or hormone therapy.     

Risedronate: a new oral bisphosphonate

BACKGROUND: Bisphosphonates have been effective in the treatment of osteoporosis and Paget's disease of bone. Risedronate, the newest oral bisphosphonate, is approved by the US Food and Drug Administration for the prevention and treatment of postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and the treatment of Paget's disease of bone. OBJECTIVE: This article reviews current studies of risedronate in osteoporosis and Paget's disease of bone and, to the extent possible, compares risedronate with other bisphosphonates and other therapies. Information on the pharmacokinetics and adverse effects of risedronate, and the drug's use in other disorders, is also reviewed. METHODS: Clinical studies and review articles concerning the use of risedronate published in the English-language literature from 1966 through October 2000 were identified through searches of MEDLINE, PREMEDLINE, and International Pharmaceutical Abstracts using the search terms risedronate and NE 58095. Recent clinical studies, review articles, and consensus statements regarding the use of other bisphosphonates were identified through searches of the same databases for this period using the search terms bisphosphonates, alendronate, osteoporosis, and Paget's disease of bone. RESULTS: The use of risedronate therapy in patients with postmenopausal osteoporosis has been shown to increase bone mineral density (BMD) and decrease the incidence of fractures compared with placebo. In glucocorticoid-induced osteoporosis, risedronate has been shown to increase BMD without having a consistently significant effect on the risk of fractures. Although there are no direct comparisons between bisphosphonates in glucocorticoid-induced osteoporosis, risedronate appears to be less effective than alendronate and more effective than etidronate in terms of effects on BMD and/or fracture risk. In Paget's disease of bone, risedronate has been reported to be more effective than etidronate in decreasing serum alkaline phosphatase levels and bone pain. Finally, risedronate has been associated with a lower incidence of gastric ulcers than alendronate. CONCLUSIONS: In terms of efficacy in the prevention and treatment of osteoporosis and the treatment of Paget's disease of bone, risedronate is comparable to alendronate, the other orally available bisphosphonate. It appears to have better gastrointestinal tolerability than alendronate and may be preferred for patients in whom this is a concern. However, direct comparative and pharmacoeconomic studies are necessary to determine risedronate's relative place in the therapy of osteoporosis and Paget's disease of bone.     

Secondary osteoporosis: underlying disease and the risk for glucocorticoid-induced osteoporosis

BACKGROUND: Chronic diseases of many organ systems require long-term (>or=1 year) treatment with glucocorticoids. Owing to the catabolic activity of glucocorticoid therapy, osteoporosis is a potential complication. OBJECTIVES: This review discusses glucocorticoid-induced bone loss and the factors, including underlying disease, that increase the risk for osteoporosis. Therapeutic options for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) also are reviewed. METHODS: A review of the English-language literature was conducted using the MEDLINE database and proceedings from scientific meetings. Search terms including glucocorticoid-induced osteoporosis, bone loss, and fracture were used to refine the search, and preference was given to studies published after 1990. RESULTS: Long-term glucocorticoid treatment causes bone loss that is most precipitous in the first 6 months. Patients treated with glucocorticoids have additional risk factors for bone loss and osteoporosis that are associated with their primary disease. Chronic diseases can cause changes in bone metabolism, leading to bone loss in addition to that induced by glucocorticoids alone. Bone loss can be minimized through proper nutrition, weight-bearing exercise, calcium and vitamin D supplementation, and, where indicated, bisphosphonate treatment. The American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis guidelines recommend bisphosphonates for minimizing bone loss and fracture risk in patients at risk for GIO. Risedronate is indicated for the prevention and treatment of GIO, and alendronate is indicated for its treatment. Both risedronate and alendronate increase bone mineral density in patients at risk for GIO. Risedronate significantly reduces the incidence of vertebral fractures after 1 year of treatment (P<0.05). The effectiveness and tolerability of the bisphosphonates have not been established in pregnant women or pediatric patients. CONCLUSIONS: Men and women initiating long-term glucocorticoid treatment and those with GIO should be concomitantly treated with effective osteoporosis therapy to reduce fracture risk and counseled on preventive lifestyle changes.     

CRITICAL DRUG APPRAISAL: ETIDRONATE INTERMITTENT CYCLIC THERAPY FOR POSTMENOPAUSAL OSTEOPOROSIS

SUMMARY An overview of intermittent cyclical therapy with oral etidronate disodium in the treatment of postmenopausal osteoporosis is given. Etidronate has been used successfully in the treatment of Paget's disease and for the prevention and treatment of heterotopic ossification after hip replacement and spinal cord injury. It is approved for the treatment of postmenopausal osteoporosis in many European countries, Canada and Australia. Studies of such therapy indicate that etidronate significantly increases bone mass, reduces the risk of future vertebral fracture, and is safe and generally well tolerated.     

Pharmacologic and nonpharmacologic management of osteoporosis

Fractures that occur as a result of osteoporosis are associated with significant morbidity, mortality, and cost. A treatment regimen consisting of both nonpharmacologic and pharmacologic interventions can be used to decrease the risk of fracture. Nonpharmacologic interventions include calcium and vitamin D supplementation, weight-bearing exercise, muscle strengthening, and fall prevention. Pharmacologic options include: the bisphosphonates, estrogen therapy, raloxifene, salmon calcitonin, and the anabolic agent teriparatide. Although bone mineral density is used clinically to diagnose osteoporosis, it is of limited value when evaluating pharmacologic treatment; the primary indicator of treatment efficacy is fracture risk reduction. The bisphosphonates are the preferred therapy for osteoporosis. Studies have demonstrated that in postmenopausal women, both risedronate and alendronate are associated with reductions in vertebral and nonvertebral fracture risk. The newest approved bisphosphonate, ibandronate, reduces vertebral fracture risk. Studies also support a reduction in fracture risk when alendronate and risedronate are used in men with osteoporosis and patients with corticosteroid-induced osteoporosis. When used appropriately, the bisphosphonates are well tolerated. Estrogen and raloxifene decrease fracture risk in postmenopausal women with osteoporosis but are associated with thromboembolic events. Use of estrogen therapy is also limited by concerns about the safety of this type of therapy. Although the anabolic agent teriparatide is associated with reductions in vertebral and nonvertebral fractures, its use has been limited by the necessity of subcutaneous administration and its cost relative to other agents. Regardless of which treatment regimen is selected, health care providers need to emphasize the importance of compliance and adherence to improve persistence with therapy, and subsequent fracture reduction efficacy.     

Preventing osteoporotic fractures in older people

While fractures at the spine, wrist and hip are regarded as classical osteoporotic fractures, all fragility fractures in the elderly should be considered as osteoporotic once pathological fracture (e.g. metastatic disease) has been excluded. The assessment of fracture risk should take account of specific risk factors in addition to bone mineral density (BMD). The WHO has produced FRAX, a well validated tool that estimates the probability of a major osteoporotic fracture in the next 10 years. The algorithm is specifically designed for primary care. After age and prior fragility fracture, BMD is the next major determinant of fracture risk. Rather than scanning all individuals with a risk factor, measurements should be targeted to those whose probability of fracture lies close to the intervention threshold where knowledge of BMD will influence management. Individuals with a low trauma vertebral fracture or low BMD for age should be investigated for underlying causes of osteoporosis. Secondary causes account for up to 40% of cases of osteoporosis in women and 60% in men. The goal of osteoporosis management is to reduce the future risk of fracture. Lifestyle modification includes measures to reduce falls risk and bone loss such as exercise, adequate dietary calcium and avoidance of smoking and excessive alcohol consumption. All patients with an osteoporotic fracture and those at high risk should be assessed for falls risk. Combined therapy, with calcium and vitamin D, has been shown to reduce hip fracture risk in the frail elderly and should be considered in all older patients who are housebound or in residential care. Alendronate and risedronate are available as once-weekly preparations with evidence for significant reductions in vertebral and non-vertebral fractures. Denosumab is approved for osteoporosis in postmenopausal women at increased risk of fractures. Strontium ranelate has been shown to reduce fracture risk significantly in postmenopausal women.     

Teriparatide (rhPTH 1-34) for the treatment of osteoporosis

Osteoporosis is a skeletal disorder characterised by compromised bone strength predisposing a person to an increased risk of fracture. Osteoporosis develops through an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts resulting in increased bone loss. Numerous agents used for the prevention and treatment of osteoporosis slow bone loss by decreasing both bone resorption and formation. These include bisphosphonates, hormone replacement therapy, selective oestrogen receptor modulators and calcitonins. All reduce vertebral fracture risk and some reduce non-vertebral fracture risk, but none routinely increases bone mass and strength or restores lost bone architecture. In many respects, antiresorptive therapies halt the progression of osteoporosis. However, for patients who have osteoporosis, particularly those who have sustained their first fracture and are at high risk for subsequent fractures, there is a need to develop agents that stimulate bone formation and, thus, reverse osteoporosis. Teriparatide is the recombinant human 1-34 amino acid sequence of parathyroid hormone recently approved in the US for the treatment of men and postmenopausal women at high risk for osteoporotic fracture and in Europe for the treatment of postmenopausal women with osteoporosis. When given by once-daily injection, teriparatide increases bone mass by stimulating formation of new bone, resulting in the restoration of bone architecture.     

Osteoporosis in men and women

Osteoporosis is a cause of significant morbidity and mortality in postmenopausal women as well as men. In both men and women, increasing age and low bone mineral density (BMD) are the 2 most important independent risk factors for an initial vertebral or nonvertebral fracture. Although the prevalence of osteoporosis is greater in women, mortality after fracture is higher among men. In both men and women, the incidence of vertebral fracture increases with age, although the increase is more marked in women than in men. The diagnostic criteria for postmenopausal osteoporosis in women are well established; however, there is ongoing debate about the appropriate T-scores and BMD thresholds to diagnose osteoporosis in men. Alendronate and risedronate are considered first-line therapy for the treatment of both postmenopausal osteoporosis and male osteoporosis. The efficacy and safety of these agents have been evaluated extensively in randomized clinical trials. Studies suggest that these agents are similarly efficacious in men and women. The anabolic agent teriparatide may also be used to treat men with osteoporosis at high risk for fracture. Studies suggest that treatment with an anabolic agent like teriparatide should be followed by an antiresorptive agent.     

PTH analogues and osteoporotic fractures

Importance of the field: At present there are two parathyroid hormone (PTH) analogues (PTH 1 – 34 and PTH 1 – 84) registered for the treatment of established osteoporosis in postmenopausal women (PTH 1 – 34 and PTH 1 – 84) and in men (PTH 1 – 34 only) who are at increased risk of having a fracture.

Areas covered in this review: The efficacy and safety of PTH 1 – 34 and PTH 1 – 84 in the management of osteoporosis is evaluated by reviewing published literature and presentations from scientific meetings through to 2010.

What the reader will gain: This review focuses on data on fracture risk reduction and safety endpoints of PTH analogues. The adverse reactions reported most are nausea, pain in the extremities, headache and dizziness.

Take home message: Exogenous PTH analogues, given as daily subcutaneous injections, stimulate bone formation, increase bone mass and bone strength, and improve calcium balance. In postmenopausal women with osteoporosis, PTH analogues reduced the risk of vertebral (PTH 1 – 34 and PTH 1 – 84) and non-vertebral fractures (only PTH 1 – 34). In men and women with glucocorticosteroid-induced osteoporosis, PTH 1 – 34 reduced the risk of vertebral fractures. In general, PTH analogues are well tolerated with an acceptable safety profile: they can be used for the prevention and treatment of fractures in postmenopausal women with severe, established osteoporosis.     

RANK ligand inhibition with denosumab for the management of osteoporosis

Receptor activator of nuclear factor-κB ligand (RANKL) is a cytokine member of the tumour necrosis factor family that is the principal final mediator of osteoclastic bone resorption. It plays a major role in the pathogenesis of postmenopausal osteoporosis, as well bone loss associated with rheumatoid arthritis, metastatic cancer, multiple myeloma, aromatase inhibitor therapy and androgen deprivation therapy. Denosumab (AMG 162) is an investigational fully human monoclonal antibody with a high affinity and specificity for RANKL. By inhibiting the action of RANKL, denosumab reduces the differentiation, activity and survival of osteoclasts, thereby slowing the rate of bone resorption. Denosumab has been shown to increase bone mineral density (BMD) and reduce bone turnover in postmenopausal women with low BMD. Denosumab is a potential treatment for osteoporosis and other skeletal disorders.     

Effects of bisphosphonate for quality and strength of bone

Bisphosphonate prevents the fracture by controlling the function of osteoclasts and inhibiting bone absorption powerfully for osteoporosis. It is shown clinically that both alendronate and risedronate reduce postmenopausal osteoporosis patient's vertebral and nonvertebral fractures. Recently it became clear that bisphosphonate not only reduces bone absorption, but also improves bone quality such as bone microarchitecture and material properties. Furthermore, we showed using finite element analysis that internal use of bisphosphonate reduces strain of the cancellous bone inside vertebral body within one year, and notably decreases the region of high strain which is easy to break. Internal use of bisphosphonate improves the bone density distribution inside vertebral body, and strengthens the structure of load support of the spine. The structural improvement of spine leads to prevention of fracture.     

Comparison of serum and urinary C-terminal telopeptide of type I collagen in aging, menopause and osteoporosis.

BACKGROUND: Urinary C-terminal telopeptide of type I collagen (u-CTx) has been reported to be a sensitive biochemical marker of bone turnover. There have been two assays for urinary CTx, which are alpha-CTx and beta-CTx. A newly developed immunoassay for serum CTx (s-CTx) is now available for assessment of bone resorption. We evaluated the effects of aging, menopause, and osteoporosis on the measurements of serum CTx and compared them to urinary CTx assays. Methods: In 79 premenopausal healthy women, 80 postmenopausal healthy women, 61 osteoporotic patients with vertebral fractures and 34 osteoporotic patients with hip fractures, s-CTx and urinary beta-CTx (u-betaCTx) were measured by ELISAs, and urinary alpha-CTx (u-alphaCTx) was measured by an RIA. RESULTS: In all subjects, s-CTx significantly correlated with both u-alphaCTx (r=0.54) and u-betaCTx (r=0.51). There was no significant difference among s-CTx, u-alphaCTx and u-betaCTx in the T-scores of the postmenopausal group over the premenopausal group. These findings indicate that the value of s-CTx, as well as urinary CTxs, reflected the increase of bone resorption associated with menopause with a high degree of sensitivity. Patients with vertebral fractures had moderately increased concentrations of bone resorption markers compared to age-matched healthy postmenopausal women (T-score; s-CTx: 0.8, u-alphaCTx: 0.9, u-betaCTx: 0.7), whereas bone resorption markers in hip fracture patients were greatly increased compared to healthy postmenopausal women (T-score; s-CTx: 1.1, u-alphaCTx: 1.3 u-betaCTx: 1.3). The T-scores of u-CTxs against the postmenopausal group in vertebral fracture group and in hip fracture group were not significantly different from those of s-CTx. CONCLUSIONS: s-CTx, as well as urinary CTxs, reflects the increase of bone resorption in patients with vertebral fractures and hip fractures.     

Application of anti-resorptive drugs for the treatment of osteoporosis

The applications of anti-resorptive drugs for the treatment of osteoporosis were reviewed. The aging, low bone mineral density, increased bone turnover, and prevalent fracture were risk factors for new fracture. Bisphosphonates (alendronate and risedronate) and raloxifene showed a significant reduction in relative risk for vertebral fractures. On the other hand, alendronate and risedronate were the only two therapies that had a significant pooled treatment effects on nonvertebral fracture reduction. Hip fractures in Japan increase in the age of 70 years and over. This etiology indicates that bisphosphonate might be suitable for the patients who were 70 years of age and over. There was no significant difference between alendronate and risedronate in the efficacy of the decrease of bone resorption marker.     

Measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx) in aging, menopause, and osteoporosis with fractures

We have evaluated the effect of aging, menopause, and osteoporosis on the measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx). In 18 children, 86 premenopausal healthy women, 144 postmenopausal healthy women, 74 patients with vertebral fractures and 61 patients with hip fractures, alpha-CTx excretions were measured by a RIA. The age-related changes of alpha-CTx in healthy females show that the values were extremely high before the age of 16 years and decreased between ages 16 and 29, and that after the age of 40 years, the values tended to increase and to vary widely with age. In menopause, alpha-CTx in postmenopausal subjects was significantly higher than those in premenopausal subjects. There was no significant correlation between alpha-CTx and years since menopause in 102 postmenopausal subjects. Alpha-CTx in the vertebral fracture group were higher than those in the postmenopause group, but not significantly. Alpha-CTx in the hip fracture group were significantly higher than those in postmenopause and vertebral fracture groups. In age-matched comparisons, the values of the patients with vertebral fracture and the patients with hip fracture were significantly higher than those of corresponded age-matched postmenopausal women. Alpha-CTx well reflects an increase of bone resorption associated with bone modeling at childhood and high bone resorption after the menopause and higher bone resorption in osteoporotic patients with fractures.     

Risedronate for the prevention and treatment of corticosteroid-induced osteoporosis

OBJECTIVE: To evaluate the role of risedronate in corticosteroid-induced osteoporosis. DATA SOURCES: Clinical literature was accessed through MEDLINE (1966-February 2001). Key search terms included risedronate, corticosteroid, osteoporosis, and bisphosphonate. DATA SYNTHESIS: Corticosteroid-induced osteoporosis (CIO) is clinically challenging and can lead to fractures. Risedronate, an oral bisphosphonate, has been studied for use in CIO. Trials focusing on the use of risedronate in these patients were reviewed. CONCLUSIONS: Risedronate 5 mg/d increased bone mineral density at lumbar, femoral neck, and trochanter skeletal sites in patients recently initiated on or receiving long-term corticosteroid therapy. Further investigation is needed to determine risedronate's effects on fracture prevention. The drug was well tolerated.     

Glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis is one of the major complications of long-term exposure to supraphysiological doses of glucocorticoid. It has been recognized that bone loss is rapid, particularly in the first 6 months of the therapy. The skeletal effects are both dose and duration dependent; daily glucocorticoid therapy at doses of 7.5 mg/day of prednisolone or above leads to decrease bone mass and increase risk of fractures. The mechanisms which glucocorticoid induces osteoporosis are suppression of bone formation and increase of bone resorption. Hypogonadism also contributes to this pathological condition via direct suppression of sex steroids and indirect suppression through decreased secretion of pituitary hormones. Estrogen, vitamin D and its active analogues, and calcitonin, have been therefore used to prevent glucocorticoid-induced osteoporosis; however, the effectiveness is somehow limited. Treatment with newly developed anti-resorptive amino-containing bisphosphonates such as alendronate and risedronate, showed significant increase of bone mineral density for both the prevention and the treatment of glucocorticoid-induced osteoporosis, as well as risk reduction of fractures in the patients. These bisphosphonates provide a better consequence for the treatment of glucocorticoid-induced osteoporosis.