Bisphosphonates for the treatment of osteoporosis: insights for clinicians (original) (raw)
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Oral bisphosphonates in the treatment of osteoporosis: a review
Current Therapeutic Research, 1995
Osteoporosis is characterized by decreased bone mass and disrupted bone architecture, which reduce bone strength and increase the risk of fracture. Bisphosphonates, although poorly absorbed from the gut when given orally, are preferentially localized to the skeleton where they inhibit bone resorption. This provides the rationale for their use in the treatment of diseases of high bone turnover, such as Paget's disease and hypercalcemia of malignancy. The antiresorptive action of bisphosphonates is also useful in the management of osteoporosis, in which the rate of bone resorption exceeds that of bone formation. Cyclical etidronate and alendronate are the most extensively studied bisphosphonates in the management of osteoporosis, but limited data are also available for pamidronate, clodronate, tiludronate, and risedronate. All bisphosphonates have a similar rate of action, and their efficacy in increasing spinal bone mass in women with postmenopausal osteoporosis is broadly comparable over 2 to 3 years. The increase in spinal bone mass achieved with cyclical etidronate is associated with at least a 50% decrease in vertebral fracture rate, which is comparable to that seen with hormone replacement therapy, calcitonin, and, in preliminary data, for alendronate. Both cyclical etidronate and alendronate increase hip bone mass in patients with osteoporosis. The long-term safety data available for cyclical etidronate are generally favorable; clinical osteomalacia has not been experienced with the cyclical regimen during 7 years of treatment. Comparable long-term safety data are not yet available for the other bisphosphonates. The most common adverse events with oral bisphosphonate treatment are mild gastrointestinal disturbances, with an incidence rate generally similar to that with placebo and/or calcium. There have been reports, however, of erosive esophagitis during treatment with oral pamidronate and a higher incidence of abdominal pain during treatment with alendronate than with placebo and/or calcium; both of these compounds are amino bisphosphonates. Extensive experience with cyclical etidronate has established its long-term efficacy and safety. Long-term data are needed for the newer bisphosphonates, in order to position them correctly alongside the various other therapeutic options available for the successful management of osteoporosis.
Long-term use of bisphosphonates in osteoporosis
Women's health (London, England), 2006
The rate of bone turnover increases around the time of menopause, and new bone may be remodeled before it is has been completely mineralized. If this is left untreated, osteoporosis often develops, leading to fractures, particularly of the spine and hip, which represent an enormous burden in terms of suffering, healthcare expenditure, disabilities and death. Bisphosphonates are potent inhibitors of bone resorption, which slow or arrest progressive bone loss. Continuous treatment with bisphosphonates reduces bone turnover, improves bone microarchitecture and increases bone mass, leading to greater mechanical strength and reduced fracture risk. Since osteoporosis is a chronic, progressive condition, treatment has to continue for many years. Therefore, the efficacy and safety of bisphosphonates, particularly alendronate and risedronate, have been evaluated in many thousands of patients for up to 10 years of continuous use. These drugs remain the cornerstone of osteoporosis treatment an...
Bisphosphonates in the treatment of osteoporosis in 1997: a review
Current Therapeutic Research, 1997
Osteoporosis is characterized by a reduction of bone in the skeleton, associated with skeletal fragility and an increased risk of fracture after minimal trauma. The three major osteoporotic fractures are those of the forearm, vertebral body, and hip, although fractures of the humerus, tibia, pelvis, and ribs are also common. Osteoporotic fractures are a major cause of morbidity and mortality, and lead to increased health and social service expenditures in both sexes. The main objective in treating patients with osteoporosis is to reduce the risk of fractures. Bisphosphonates are an important group of therapeutic agents for the management of osteoporosis, as they inhibit bone resorption and increase bone density, thereby potentially decreasing fracture risk. The demonstration of a reduction in fracture incidence requires large randomized, double-masked, placebocontrolled trials with the statistical power to detect increases in bone density and a significant reduction in fracture incidence. Although cyclical etidronate apparently decreases the risk of vertebral fractures in a manner comparable with hormone replacement therapy and calcitonin, there are no randomized controlled trials that show a reduction in forearm or hip fractures. Alendronate is the only agent that has been shown in large randomized controlled trials to statistically significantly decrease the risk of symptomatic fractures of the forearm, spine, and hip by 4896, 55%, and 51%, respectively. In addition to the efficacy of any treatment for osteoporosis, compliance and tolerability must also be satisfactory. The most common adverse events with cyclical etidronate and alendronate are mild gastrointestinal disturbances, but the incidence is similar to that seen with placebo or calcium. In clinical practice, esophagitis has been rarely reported with alendronate, and in the majority of cases, this effect is related to a failure to follow the recommendations for administration. Although cyclical etidronate therapy may lead to histologic evidence of focal osteomalacia, clinical osteomalacia has not been observed when the recommended cyclical regimen has been used. Iliac crest bone biopsies show no evidence of a mineralization defect with alendronate. Long-term data on bone density and fracture incidence are needed from large-scale controlled studies with other bisphosphonates, such as clodronate, tiludronate,
Safety of Bisphosphonates in the Treatment of Osteoporosis
The American Journal of Medicine, 2009
In this review 4 experts consider the major safety concerns relating to bisphosphonate therapy for osteoporosis. Specific topics covered are skeletal safety (particularly with respect to atypical fractures and delayed healing), gastrointestinal intolerance, hypocalcemia, acute-phase (i.e., postdose) reactions, chronic musculoskeletal pain, renal safety, and cardiovascular safety (specifically, atrial fibrillation).
Bisphosphonate Therapy for Osteoporosis: Benefits, Risks, and Drug Holiday
The American Journal of Medicine, 2013
The amino-bisphosphonates are first-line therapy for the treatment of most patients with osteoporosis, with proven efficacy to reduce fracture risk at the spine, hip, and other nonvertebral skeletal sites. Further, bisphosphonates have been associated with a significant decrease in morbidity and increase in survival. Following the use of bisphosphonates in millions of patients in clinical practice, some unexpected possible adverse effects have been reported, including osteonecrosis of the jaw, atypical femur fractures, atrial fibrillation, and esophageal cancer. Because bisphosphonates are incorporated into the skeleton and continue to exert an antiresorptive effect for a period of time after dosing is discontinued, the concept of a drug holiday has emerged, whereby the risk of adverse effects might be decreased while the patient still benefits from antifracture efficacy. Patients receiving bisphosphonates who are not at high risk for fracture are potential candidates for a drug holiday, while for those with bone mineral density in the osteoporosis range or previous history of fragility fracture, the benefits of continuing therapy probably far outweigh the risk of harm.
Long Term Bisphosphonate Use in Osteoporotic Patients; A Step Forward, Two Steps Back
Journal of Pharmacy & …, 2012
Purpose. Bisphosphonates are the main class of drugs widely used in prevention and treatment of osteoporosis. Along with the beneficial effects, recent studies point to the harms of long-term treatment with bisphosphonates. Methods. The most relevant articles reporting serious adverse effects of bisphosphonates were selected and reviewed with the aim of assessing the risk-benefit of bisphosphonates. We searched PubMed, Web of Science, and Scopus using keywords bisphosphonates, risk of fracture, atrial fibrillation, osteonecrosis jaw, esophageal cancer, and adverse effects with no time limitation. We limited our s research to English articles. Results. Our review shows that bisphosphonates reduce vertebral fractures in short term use while in long-term can cause osteonecrosis jaw, esophageal cancer, atrial fibrillation, and increase the risk of atypical fractures and probably adynamic bone disease. There is no consensus on the time limitation of bisphosphonate usage or its long term adverse effects. Thus, more studies on long-term side effects of bisphosphonates are highly recommended. In addition, new approaches for prevention and treatment of osteoporosis seem necessary. Conclusion. Prescribers should act cautionary and consider full assessment of risk-benefit and the duration of treatment.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015
Bisphosphonates (BPs) are the most commonly used medications for osteoporosis. This ASBMR report provides guidance on BP therapy duration with a risk benefit perspective. Two trials provided evidence for long-term BP use. In the Fracture Intervention Trial Long-term Extension (FLEX), postmenopausal women receiving alendronate for 10 years had fewer clinical vertebral fractures than those switched to placebo after 5 years. In the HORIZON extension, women who received 6 annual infusions of zoledronic acid had fewer morphometric vertebral fractures compared with those switched to placebo after 3 years. Low hip T-score, between -2 and -2.5 in FLEX and below -2.5 in HORIZON extension, predicted a beneficial response to continued therapy. Hence, the Task Force suggests that after 5 years of oral BP or 3 years of intravenous BP, reassessment of risk should be considered. In women at high risk, for example, older women, those with a low hip T-score or high fracture risk score, those with pr...