Safety of bisphosphonates in the treatment of osteoporosis.

School of Medicine, Creighton University, Omaha, Nebraska, USA.
The American journal of medicine (Impact Factor: 5.3). 03/2009; 122(2 Suppl):S22-32. DOI: 10.1016/j.amjmed.2008.12.004
Source: PubMed

ABSTRACT 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).

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    ABSTRACT: IMPORTANCE Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established. OBJECTIVE To test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years. DESIGN, SETTING, AND PARTICIPANTS The prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003; the present analysis includes only the placebo group. Hip and spine dual-energy x-ray absorptiometry (DXA) were measured when placebo was begun (FLEX baseline) and after 1 to 3 years of follow-up. Two biochemical markers of bone turnover, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP), were measured at FLEX baseline and after 1 and 3 years. MAIN OUTCOMES AND MEASURES Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover. RESULTS During 5 years of placebo, 94 of 437 women (22%) experienced 1 or more symptomatic fractures; 82 had fractures after 1 year. One-year changes in hip DXA, NTX, and BAP were not related to subsequent fracture risk, but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk (lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio, 2.17 [95% CI, 1.38-3.41]; total hip DXA relative hazard ratio, 1.87 [95% CI, 1.20-2.92]). CONCLUSIONS AND RELEVANCE Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years, age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years. Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and cannot be recommended. TRIAL REGISTRATION Identifier: NCT00398931.
    JAMA Internal Medicine 05/2014; 174(7). DOI:10.1001/jamainternmed.2014.1232 · 13.25 Impact Factor
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    ABSTRACT: Abstract Background: Osteoporosis affects millions of postmenopausal women worldwide. Osteoporosis-related fractures can lead to chronic pain, disability, systemic complications, and increased risk of recurrent fractures, resulting in increased healthcare costs and mortality. Because currently available therapies have unique benefit/risk profiles, challenges remain in selecting the most appropriate treatment for each osteoporotic woman. Research and Results: Bazedoxifene (BZA), a new selective estrogen receptor modulator, is being developed for postmenopausal osteoporosis. In a 3-year, global, phase 3 study, BZA significantly reduced the risk of new vertebral fractures and nonvertebral fractures in women with higher baseline fracture risk compared with placebo. In 2 extensions of this study, the efficacy of BZA in reducing vertebral fracture risk was sustained over 7 years. BZA improved lumbar spine and total hip bone mineral density compared with placebo at 3 and 5 years, and demonstrated a favorable safety/tolerability profile, with no endometrial or breast stimulation. BZA was cost-effective compared with raloxifene in a 3-year, head-to-head comparative trial. Indirect comparisons further suggest that BZA may be as effective as bisphosphonates in reducing risk of nonvertebral fractures in women at high risk of fracture. BZA demonstrated efficacy and safety for treating postmenopausal osteoporosis over 7 years, particularly in women at a higher fracture risk. Conclusion: Because of its specific pharmacologic profile, BZA may be appropriate for postmenopausal women seeking a tolerable, safe, effective, and cost-effective long-term osteoporosis treatment.
    Current Medical Research and Opinion 02/2014; DOI:10.1185/03007995.2014.890927 · 2.37 Impact Factor
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    ABSTRACT: In the United States, an estimated 19% of older men and 30% of older women are at elevated risk of osteoporotic fracture and considered to be eligible for treatment. The burden of osteoporosis is similar in Europe and is projected to rise worldwide, with aging populations and increasing fracture rates accompanying urbanization. Notwithstanding its high prevalence, osteoporosis is often underdiagnosed and undertreated. Moreover, even when the diagnosis is made and the decision is taken to treat, there are remaining challenges in implementing therapy for osteoporosis. Several patient populations are particularly challenging for clinicians to treat and require further study with regard to osteoporosis therapy. These include the very elderly, who face challenges relating to adherence; men, in whom osteoporosis remains under-recognized; patients with glucocorticoid-induced osteoporosis or renal impairment, who are at increased risk of fracture; patients with preexisting gastrointestinal problems who cannot tolerate existing orally administered osteoporosis therapies; and high-risk patients who show inadequate response to therapy. Moreover, poor adherence and poor persistence with osteoporosis medications are common and result in an increased risk of fracture, higher medical costs, and increased hospitalizations. Once the decision to institute therapy is made, patient education about osteoporosis and fracture risk should be provided. This is particularly important for men, who may not be aware that osteoporosis can be a concern. Secondary prevention programs, including fracture liaison services and bone therapy groups, can help to improve adherence to therapy. Further study is needed to guide the treatment of men, the very elderly, patients with glucocorticoid-induced osteoporosis and renal impairment, high-risk patients not well-controlled despite therapy, and patients with preexisting gastrointestinal conditions. Moreover, therapies are needed that are viewed as effective and safe by both physicians and patients, and as convenient to take by patients.
    International Journal of Women's Health 01/2014; 6:759-69. DOI:10.2147/IJWH.S53489