Safety of Bisphosphonates in the Treatment of Osteoporosis

School of Medicine, Creighton University, Omaha, Nebraska, USA.
The American journal of medicine (Impact Factor: 5). 03/2009; 122(2 Suppl):S22-32. DOI: 10.1016/j.amjmed.2008.12.004
Source: PubMed


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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    • "In these two controlled studies, the profile was safe, with a number of serious adverse events or deaths not significantly different in the groups treated with ZA or with PBO. A major problem with ZA was the postinfusion syndrome, which is classical with all intravenous BP following the first infusion, usually mild, and can be reduced by acetaminophen [66]. Intriguingly, an unexpected number of episodes of atrial fibrillation described as severe adverse events occurred in the ZA-treated group. "
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    ABSTRACT: During the past 2 decades, many interventions were proven effective in the management of postmenopausal osteoporosis. The objective of an anti-osteoporosis treatment is to reduce fracture rates, ideally at all skeletal sites (i.e. spine, hip, and other non-spine). The armamentarium against osteoporosis includes anti-resorptive agents (i.e. bisphosphonates, selective estrogen receptor modulators and denosumab), bone-forming agents (i.e. peptides from the parathyroid hormone family) and one agent with a dual mechanism of action (i.e. strontium ranelate). All these medications combine anti-fracture efficacy with a reasonable benefit/risk profile. However, the choice of a particular chemical entity, in one individual patient is based on the knowledge and expertise of the physician. Prioritization of drugs should be based on the individual profile of the patient, the severity of osteoporosis and the specific contraindications, warnings and precautions of use of the various available medications.
    Best Practice & Research: Clinical Endocrinology & Metabolism 12/2014; 28(6). DOI:10.1016/j.beem.2014.09.003 · 4.60 Impact Factor
    • "Hypocalcemia, usually subclinical but sometimes symptomatic, with associated increases in serum PTH levels, has been observed with the use of potent antiresorptive agents, including bisphosphonates62 and denosumab.29 "
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    ABSTRACT: Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor kappa-B ligand (RANKL), a cytokine member of the tumor necrosis factor family that is the principal regulator of osteoclastic bone resorption. Postmenopausal osteoporosis (PMO) is a systemic skeletal disease associated with high levels of RANKL, resulting in a high rate of bone remodeling and an imbalance of bone resorption over bone formation. By inhibiting RANKL in women with PMO, denosumab reduces the rate of bone remodeling, thereby increasing bone mineral density, improving bone strength, and reducing the risk of fractures. In clinical trials of women with osteoporosis and low bone mineral density, denosumab has been well tolerated, with overall rates of adverse events and serious adverse events in women treated with denosumab similar to those receiving placebo. In the largest clinical trial of denosumab for the treatment of women with PMO, there was a significantly greater incidence of cellulitis reported as a serious adverse event, with no difference in the overall incidence of cellulitis, and a significantly lower incidence of the serious adverse event of concussions with denosumab compared with placebo. The evidence supports a favorable balance of benefits versus risks of denosumab for the treatment of PMO. Assessments of the long-term safety of denosumab are ongoing. Denosumab 60 mg subcutaneously every 6 months is an approved treatment for women with PMO who are at high risk for fracture.
    Drug, Healthcare and Patient Safety 12/2011; 3(1):79-91. DOI:10.2147/DHPS.S7727
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    • "They can be treated symptomatically with paracetamol or other analgesics or antipyretics. The likelihood of experiencing this reaction can be reduced by administration of analgesics for a few days just after dosing [10]. "
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    ABSTRACT: The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug-drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug-drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture.
    Calcified Tissue International 06/2011; 89(2):91-104. DOI:10.1007/s00223-011-9499-8 · 3.27 Impact Factor
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