Corticosteroid osteoporosis

Corticosteroids are widely used and effective agents for the control of many inflammatory diseases, but corticosteroid osteoporosis is a common problem associated with their long term high dose use. Prevention of corticosteroid osteoporosis is preferable to treatment of established corticosteroid bone loss. Several large double-blind controlled clinical trials in patients with corticosteroid osteoporosis have recently been published that provide new insights into its treatment. Based upon available evidence, the rank order of choice for prophylaxis would be a bisphosphonate followed by a vitamin D metabolite or an oestrogen type medication. Calcium alone appears to be unable to prevent rapid bone loss in patients starting corticosteroids, especially with prednisolone doses at 10 mg a day or greater. If an active vitamin D metabolite is used, calcium supplementation should be avoided unless dietary calcium intake is low. Hormone replacement therapy should be considered if hypogonadism is present. Since vertebral fracture is a common and important complication of high dose corticosteroid therapy, these findings suggest that rapid bone loss and hence fractures, can be prevented by prophylactic treatment. Although the follow-up data is limited, it is likely that such therapy needs to be continued beyond 12 months whilst patients continue significant doses of corticosteroid therapy.     

Bisphosphonate therapy for secondary osteoporosis: adult perspective

BACKGROUND: A number of disease states and drugs can upset the balance between bone formation and resorption resulting in increased fracture risk. Glucocorticoids are the most recognized cause of secondary osteoporosis. Hypogonadism, weight loss, and chronic inflammation are other contributors to bone loss in a variety of disease states. Bisphosphonates are potent inhibitors of bone resorption, and there is a variety of secondary osteoporosis where they produce substantial increases in bone density and reduce fracture risk by about 50%. Upper gastrointestinal tract intolerance with oral agents and a flu-like syndrome with intravenous bisphosphonates are the principal adverse effects associated with their use. CONCLUSIONS: Numerous disease states and medications can adversely affect the skeleton. Additional effects of aging and menopause can substantially increase an individual's fracture risk. It is important that physicians assess fracture risk in susceptible patients and initiate treatment when indicated.     

Osteoporosis in systemic lupus erythematosus: prevention and treatment

The patient with systemic lupus erythematosus (SLE) is at risk of osteoporosis through several factors: the inflammatory disease itself, disease-related co-morbidity, and its treatment. Bone loss is apparent early in the disease and this may be confounded primarily by treatment with corticosteroids. Patients should be assessed for additional risk factors for osteoporosis and general lifestyle measures adopted. Bone mineral density measurement should be considered in SLE patients at high risk of osteoporosis, particularly those starting corticosteroids and in postmenopausal women. Calcium and vitamin D supplementation provide general prophylaxis and are a suitable first-line option. Hormone replacement should be used in hypogondal subjects unless contra-indicated. In subjects at high fracture risk, particularly in postmenopausal women, bisphosphonate therapy should be considered as these agents have been shown to significantly reduce vertebral fracture risk. These measures should reduce the burden of osteoporosis and fracture in patients with lupus.     

Steroid induced osteoporosis: prevention and treatment

PURPOSE: Corticosteroid induced osteoporosis (CIO) is the most frequent complication of long-term corticosteroid therapy, and the most frequent cause of secondary osteoporosis. New data from biological, epidemiological and therapeutic studies provide basis for optimal management of this bone disease. MAIN POINTS: Corticosteroids are responsible for both quantitative and qualitative deleterious effects on bone, through their effect on bone cells, mainly on osteoblasts (with both a decrease in osteoblast activity and an increase in apoptosis). Epidemiological studies have shown an increased risk of fractures related to CIO, even for low doses, and during the first 6 months of treatment. Relative risk is 1.3 and 2.6 for peripheral and vertebral fractures respectively. Bone mineral density, measured by dual-energy X-ray absorptiometry, is decreased at spine and hip; the risk of fracture is higher in CIO as compared to post-menopausal osteoporosis, for a similar bone density. Prevention of CIO needs the use of the minimal efficacious dose, and treatment of calcium, vitamin D and gonadal hormones insufficiencies. Patients at risk of fracture, as post-menopausal women with prevalent fractures, should receive a bisphosphonate. PERSPECTIVE: It may be possible to reduce the fracture risk in patients on long-term corticosteroid therapy.     

Recognizing and treating glucocorticoid-induced osteoporosis in patients with pulmonary diseases

Glucocorticoids are frequently used to treat patients with pulmonary diseases, but continuous long-term use of glucocorticoids may lead to significant bone loss and an increased risk of fragility fractures. Patients with certain lung diseases, regardless of pharmacotherapy-particularly COPD and cystic fibrosis-and patients waiting for lung transplantation are also at increased risk of osteoporosis. Fragility fractures, especially of the hip, will have substantial effects on the health and well-being of older patients. Vertebral collapse and kyphosis secondary to glucocorticoid-induced osteoporosis (GIO) may affect lung function. Identification of patients with osteopenia, osteoporosis, or fragility fractures related to osteoporosis is strongly recommended and should lead to appropriate treatment. Prevention of GIO in patients receiving continuous oral glucocorticoids is also recommended. In patients receiving either high-dose inhaled glucocorticoids or low- to medium-dose inhaled glucocorticoids with frequent courses of oral glucocorticoids, bone mineral density measurements should be performed to screen for osteopenia and osteoporosis. A bisphosphonate (risedronate or alendronate), calcium and vitamin D supplementation, and lifestyle modifications are recommended for the prevention and treatment of GIO.     

Glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Glucocorticoids cause a rapid bone loss in the first few months of use, but the most important effect of the drug is suppression of bone formation. The administration of oral glucocorticoid is associated with an increased risk of fractures at the spine and hip. The risk is related to the dose, but even small doses can increase the risk. Patients on glucocorticoid therapy lose more trabecular than cortical bone and the fractures are more frequent at the spine than at the hip. Calcium, vitamin D and activated forms of vitamin D can prevent bone loss and antiresorptive agents are effective for prevention and treatment of bone loss and to decrease fracture risk. Despite the known effects of glucocorticoids on bone, only a few patients are advised to take preventive measures and treat glucocorticoid-induced osteoporosis.     

Access to bone densitometry increases general practitioners' prescribing for osteoporosis in steroid treated patients

BACKGROUND: Availability of access to bone densitometry in the UK varies widely and there are concerns as to appropriate prescribing. Studies suggest inadequate use of osteoporosis prophylaxis in steroid users, despite recent guidelines. OBJECTIVE: To examine in a case-control study whether access to bone densitometry affects GPs' osteoporosis prescribing in high risk steroid users. METHOD: 10 general practices were included, five from primary care trusts (PCTs) with access to bone densitometry and five with limited access. Patients receiving prednisolone for >3 months were identified by database search. Patients receiving no prophylaxis other than calcium and vitamin D (Ca/D) were subsequently included. Appropriate patients in five practices were offered DXA scan (cases) and review. Patients in practices without access to scans (controls) were reviewed. GPs' opinions leading to treatment were sought by structured questionnaire. RESULTS: 132 (0.12%) patients were receiving prednisolone for >/=3 months, but no osteoporosis prophylaxis other than Ca/D. Pre-study prophylaxis ranged from 18 to 36%. Of 48 patients scanned, 21 (44%) were abnormal and 18 (38%) received new treatment. 13/44 (30%) controls received new treatment. 10/21 (48%) with abnormal scans started a bisphosphonate, compared with 7/44 (16%) controls (RR = 3, p = 0.004). No difference in risk factors for fracture was found in treated and untreated controls. CONCLUSIONS: GPs were three times more likely to start potent osteoporosis treatment after abnormal scans than GPs relying on clinical information. In practice, risk factors were not adequately assessed. Database searches may identify patients needing osteoporosis prophylaxis; however, DXA enables more appropriate patient treatment.     

Immunosuppressive therapy and the skeleton.

Glucocorticoids and other immunosuppressive drugs, such as cytoclosporine A, are increasingly used today. One of the most common clinical situations in which they are prescribed is for immunosuppression after organ transplantation. These drugs have diverse effects on the skeleton, however, and one of the most common sequelae of organ transplantation is osteoporosis and fractures. Patients treated with immunosuppressive drugs should be carefully evaluated for osteoporosis, preferably prior to or at the time of initiation of immunosuppressive therapy. They should be followed carefully with sequential bone-density measurements and biochemical indices of bone turnover. Measures to prevent bone loss should be initiated early in the course of immunosuppressive therapy.     

An update on glucocorticoid-induced osteoporosis

In general, bone loss from glucocorticoid treatment occurs rapidly within the first 6 months of therapy. Glucocorticoids alter bone metabolism by multiple pathways; however, the bone loss is greatest in areas rich in trabecular bone. Preventive measures should be initiated early. It is the author's opinion that all subjects initiating treatment with prednisone at 7.5 mg or greater require calcium supplementation (diet plus supplement) at a dose of 1500 mg and vitamin D at a dose of 400 to 800 IU/d. If the patient is going to remain on this dose of glucocorticoid for more than 4 weeks, an antiresorptive agent should be started (e.g., estrogen, bisphosphonate, raloxifene). If a patient has established osteoporosis and is either initiating glucocorticoid therapy or is chronically treated with prednisone at 5 mg d or greater in addition to calcium and vitamin D supplementation, a potent antiresorptive agent (bisphosphonate) should be started. A bone mineral density measurement of either the lumbar spine or the hip may be helpful is assessing an individual's risk of osteoporosis, may improve compliance with treatment, and can be used to monitor the efficacy of the prescribed therapy. There is no reason to withhold treatment for glucocorticoid-induced bone loss until a bone mass measurement is taken, however. In motivated patients, a weight-bearing and resistance exercise program should be prescribed to help retain muscle strength and prevent depression. If hypercalciuria develops with glucocorticoid use, either thiazide diuretics or sodium restriction may be helpful. In patients who continue to lose bone or experience fracture's despite antiresorptive therapy while on glucocorticoids, bone-building anabolic agents (e.g., hPTH 1-34 or PTH 1-84) may be available someday soon.     

Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis

Bisphosphonates have been shown to increase bone mineral density in patients with established osteoporosis as well as those with osteopenia. The evidence conclusively shows a reduction in fracture rates in patients on the more potent nitrogen containing bisphosphonates. Indeed, significant vertebral fracture rate reduction has been demonstrated after only 1 year of therapy. Alendronate, a second-generation bisphosphonate, and risedronate, a third-generation bisphosphonate, are first line medications for the treatment of osteoporosis given their efficacy in preventing both vertebral and non-vertebral fractures. There is evidence that vertebral fractures may be prevented by intermittent cyclic therapy with etidronate. All three have been shown to increase bone mineral density in the spine, with alendronate and risedronate producing significant increases in hip bone density. Calcitonin has demonstrated the ability to reduce vertebral fracture rates with minimal changes in bone density. Calcitonin is also beneficial in reducing the bone pain associated with fractures.     

Osteoporosis disease management for fragility fracture patients: new understandings based on three years' experience with an osteoporosis care service

OBJECTIVE: To review the 3-year performance of an established osteoporosis care service and consider further improvements in an effort to reduce fragility fractures. METHODS: Osteoporosis care has been coordinated for all willing and able patients with orthopedic fragility fractures in our health system by a nurse and medical director since 2003, using a guideline-based care algorithm and task management software. Patients were followed by telephone for 2 years to monitor their status and optimize adherence to treatment. Demographics, management recommendations, clinical data, and adherence to treatment were reviewed for the 2003-2005 patient population. RESULTS: Of 1,019 patients with fragility fractures, 61% underwent osteoporosis evaluation and treatment. The remainder included 15% who refused to participate and 24% who were unable to participate for various logistical and health reasons. More patients age >80 years were unwilling or unable to participate. Bone densities (dual x-ray absorptiometry [DXA]) were normal, low, or osteoporotic in 24%, 55%, and 21% of patients, respectively, and 60% of the osteoporotic group had > or = 1 abnormal metabolic bone laboratory result. Only 17% of the total reported a previous fracture, and 47% had ever undergone DXA. Few experienced bone loss, a new fracture, or bisphosphonate intolerance during treatment. CONCLUSION: An osteoporosis care service has coordinated care for every willing and able fragility fracture patient with positive outcomes. In addition, the results suggest a high priority for earlier proactive diagnosis and intervention of the at-risk population if fractures are to be reduced.     

Advances in the management of corticosteroid-induced osteoporosis with bisphosphonates

Corticosteroids are widely used as anti-inflammatory and immunosuppressive agents to treat a variety of chronic conditions. Long-term (>1 year) corticosteroid use can lead to bone loss, and therefore, osteopenia or osteoporosis. Corticosteroid-induced osteoporosis (CIO) leads to increased bone fragility and subsequently fractures, which, in turn, lead to a loss of physical, emotional and social health for the patient and increased costs for healthcare providers. A wealth of data exists demonstrating the efficacy of the oral bisphosphonates, etidronate, alendronate and risedronate in increasing bone mineral density in patients with CIO or preventing bone loss in patients commencing corticosteroid therapy. Data regarding fracture prevention are less clear, as statistically significant reductions in the incidence of fractures have only been reported for patient subgroups or meta-analyses. However, many treatment guidelines recommend the use of oral bisphosphonates for the prevention and treatment of CIO. These guidelines are, however, not reflected in prescribing practice, and the majority of patients do not receive adequate concomitant therapy. This review summarizes the available data for bisphosphonates in CIO. Therapeutic adherence with oral bisphosphonates is an issue, with approximately 50% of patients discontinuing therapy within the first year. The primary reasons for this are poor gastrointestinal tolerability and the frequency with which complex dosing requirements must be followed. The inconvenience of taking daily or weekly bisphosphonate therapy is of particular importance in patients with CIO who may be regularly taking several other medications. Data obtained in studies with ibandronate indicate that bisphosphonate administration by rapid intravenous injection provides an effective, well-tolerated and practical alternative to current oral regimens in the management of patients with CIO.     

The use of bisphosphonates in the treatment of osteoporosis

PURPOSE OF REVIEW: The bisphosphonates alendronate and risedronate, given orally once weekly, are the cornerstone of treatment of postmenopausal osteoporosis, as well as of male and secondary osteoporosis. They reduce significantly the risk of vertebral and nonvertebral fractures; their effects appear early, within 6-12 months, and appear to be sustained. Several questions remain unanswered, however. In addition, data on a new bisphosphonate became available in 2004. RECENT FINDINGS: The optimal duration of treatment has not been clearly established. Long-term data with alendronate are now available, indicating a persistence of alendronate effects on bone mineral density and bone turnover markers several years after stopping treatment given for 5 years. Whether these effects translate into sustained reduction of fractures needs to be further analyzed. Because of their efficacy, bisphosphonate use has been explored in other forms of osteoporosis, such as after androgen deprivation therapy for prostatic cancer. The challenge of long-term compliance with treatment of osteoporosis has triggered the use of intermittent bisphosphonate. The effects of intermittent oral and intravenous ibandronate on bone mineral density, bone turnover, and fractures have been recently reported. SUMMARY: The mechanism by which bisphosphonates improve bone strength is not yet fully understood but probably involves complex effects on different components of bone strength, such as microarchitecture.     

Effect of inappropriate and continuous therapy with alendronate for ten years on skeletal integrity - observations in two elderly patients

Alendronate is a potent aminobisphosphonate that has been used worldwide to decrease fracture risk in millions of post-menopausal women with and without osteoporosis, men with low bone mass, and in those with glucocorticoid- induced osteoporosis. A recent report of 9 patients with spontaneous atypical non-vertebral fractures during treatment with alendronate for up to 8 yr raised questions suggesting the possibility of severe suppression of bone turnover and resultant susceptibility to fracture. Our recent observations in 2 elderly women with inactive monostotic Paget's disease of bone who had been treated elsewhere continuously for this disease with alendronate for 10 yr at doses overall of 2 and 4 times the osteoporotic dose provided an opportunity to engage in the ongoing controversy over long-term safety of bisphosphonate therapy. Despite such therapy, skeletal integrity was maintained with normal bone densities and the absence of skeletal fractures. These observations do not support the suggestion of deleterious effects with longterm alendronate therapy.     

Parathyroid hormone for treatment of osteoporosis

BACKGROUND: Osteoporosis is a common condition associated with multiple deleterious consequences. No therapy entirely abolishes fracture risk. METHODS: A MEDLINE database (1966 to the present) search was performed for randomized controlled trials in humans using the keywords osteoporosis and parathyroid hormone (PTH) or parathyroid hormone and fracture. The Cochrane database was searched using the search terms osteoporosis and parathyroid hormone. RESULTS: Parathyroid hormone (usually subcutaneous) dosages varied markedly across the 20 randomized controlled trial studies retrieved. In the range of 50 to 100 micro g/d, effects may be dose-related. Results of larger trials (up to 1637 patients) were conflicting as to whether effects were limited to the spine and suggested detrimental effects on radius bone mineral density. Little data analyzed the effects of PTH in older vs younger subjects or directly compared the effects by sex. Increases in spine bone mineral density are induced by PTH in postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, and idiopathic osteoporosis. Parathyroid hormone may protect against gonadotropin-releasing hormone agonist-related bone loss. Effects are less clear at nonspine sites when PTH is used as part of combination or sequential therapies or for treatment of glucocorticoid-induced osteoporosis. Parathyroid hormone decreased the incidence of radiographically detected spinal fractures. The numbers of nonvertebral fractures were too low to be broken down by individual site. Parathyroid hormone injections were difficult for some patients to comply with. Occasionally, PTH-associated hypercalcemia may be dose-dependent, often manifesting early in treatment. An increase in cancer risk from PTH is not reported in humans. CONCLUSIONS: Parathyroid hormone decreases vertebral fractures and increases spinal bone density in postmenopausal osteoporosis and glucocorticoid-induced osteoporosis, but at the expense of a decrease in radius bone density. The long-term safety and nonvertebral fracture efficacy are unknown.     

Treating osteoporosis to prevent fractures: current concepts and future developments

Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40–70%), nonvertebral (by 25–40%) and hip fractures (by 40–53%) in postmenopausal women with osteoporosis. Due to the risk of rare side‐effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well‐proven efficacy and safety, few women at high risk of fracture are started on treatment. Case finding strategies, such as fracture risk‐based screening in primary care using the fracture risk assessment tool (FRAX) and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long‐term protection against fracture and restore BMD. For those patients, sequential treatment, starting with a bone‐building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better long‐term fracture prevention and should be the golden standard of future osteoporosis treatment.     

Prevention and treatment of glucocorticoid-induced osteoporosis

Glucocorticoid (GC) is used to treat a wide variety of inflammatory and allergic diseases, but often brings about various adverse effects, including osteoporosis and subsequent bone fracture. GC-induced osteoporosis, thereby, should be treated and also be prevented. Accumulated evidence indicates that treatment with a bisphosphonate is recommended for prevention as well as treatment of GC-induced osteoporosis in all men and postmenopausal women, in whom will receive or have received long-term GC treatment. Further studies would provide additional options for treatment or prevention of GC-induced osteoporosis.     

Treatment of osteoporosis with bisphosphonates

Bisphosphonates are safe and effective agents for treatment and prevention of osteoporosis. Alendronate and risedronate are the best studied of all agents for osteoporosis in terms of efficacy and safety. They increase bone mass. In patients who have established osteoporosis, they reduce the risk of vertebral fractures. They are the only agents shown in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures. They are approved by the US FDA for prevention of bone loss in recently menopausal women, for treatment of postmenopausal osteoporosis, and for management of glucocorticoid-induced bone loss. Other bisphosphonates (e.g., etidronate for oral use, pamidronate for intravenous infusion) are also available and can be used off-label for patients who cannot tolerate approved agents. Bisphosphonates combined with estrogen produce greater gains in bone mass compared with either agent used alone; whether there is a greater benefit of combination therapy on fracture risk is not clear. Combining a bisphosphonate with raloxifene or calcitonin is probably safe, although data on effectiveness are lacking.     

COPD and osteoporosis

Osteoporosis, with resulting fractures, is a significant problem in patients with advanced COPD. The etiology for the bone loss is diverse but includes smoking, vitamin D deficiency, low body mass index, hypogonadism, sedentary lifestyle, and use of glucocorticoids. Effective strategies to prevent bone loss and/or to treat osteoporosis include calcium and vitamin D, hormone replacement when indicated, calcitonin, and bisphosphonate administration. However, many patients remain undiagnosed until their first fracture because of the lack of recognition of the disease. With an increased awareness by pulmonologists and the increased use of preventive strategies, the impact of osteoporosis on those patients with COPD should decrease.     

The use of i. v. bisphosphonate in pregnancy-associated osteoporosis--case study.

OBJECTIVE: Diagnosis of pregnancy-associated osteoporosis is often delayed and therapeutic interventions insufficient. STUDY DESIGN: A 28-year-old patient (BMI=18.6) with no additional risks for osteoporosis experienced acute lumbosacral pain two months postpartum, while lactating. After conservative therapy, thoracic and lumbar spine were X-rayed: severe pregnancy-associated osteoporosis with vertebral fractures was diagnosed. 2-year treatment with i. v. bisphosphonate ibandronate was initiated (2 mg every 3 months) and calcium and vitamin D supplementation. RESULTS: Rapid improvement was observed. Conclusion: In cases with multiple fractures i. v. bisphosphonate leads to substantial decrease of symptoms and further fractures and significant increase of bone mass density (BMD). CONCLUSION: In severe cases of pregnancy-associated osteoporosis with multiple fractures i. v. biphosphonate therapy leads to a decrease of symptoms and fracture risk and an increase of bone mass density (BMD).