ChemInform Abstract: Adverse Reactions and Drug-Drug Interactions in the Management of Women with Postmenopausal Osteoporosis

Division of Bone Disease, Department of Rehabilitation and Geriatrics, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
Calcified Tissue International (Impact Factor: 3.27). 06/2011; 89(2):91-104. DOI: 10.1007/s00223-011-9499-8
Source: PubMed


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.


Available from: John A Kanis
  • Source
    • "Levels were assigned to these attributes based on the current treatment using a literature review and discussion with experts (n = 5). For the side-effects of treatment, we focused on the types of common side-effects [16]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The patient's perspective is becoming increasingly important in clinical and policy decisions. In this study, we aimed to evaluate the preferences of patients with, or at risk of, osteoporosis for medication attributes, and to establish how patients trade between these attributes. A discrete choice experiment survey was designed and patients were asked to choose between two hypothetical unlabelled drug treatments (and an opt-out option) that vary in five attributes: efficacy in reducing the risk of fracture, type of potential common side-effects, mode and frequency of administration and out-of-pocket costs. An efficient experimental design was used to construct the treatment option choice sets and a mixed logit panel data model was used to estimate patients' preferences and trade-offs between attributes. A total of 257 patients with, or at risk of, osteoporosis completed the experiment. As expected, patients preferred treatment with higher effectiveness and lower cost. They also preferred either an oral monthly tablet or 6-month subcutaneous injection above weekly oral tablets, 3-month subcutaneous, 3-month intravenous or yearly intravenous injections. Patients disliked being at risk of gastro-intestinal disorders more than being at risk of skin reactions and flu-like symptoms. There was significant variation in preferences across the sample for all attributes except subcutaneous injection. This study revealed that osteoporotic patients preferred 6-month subcutaneous injection and oral monthly tablet, and disliked gastro-intestinal disorders. Moreover, patients were willing to pay a personal contribution or to trade treatment efficacy for better levels of other attributes. Preferences for treatment attributes varied across patients and this highlights the importance of clinical decision-making taking individual preferences into account to improve osteoporosis care.
    Arthritis research & therapy 01/2014; 16(1):R36. DOI:10.1186/ar4465 · 3.75 Impact Factor
  • Source
    • "Because rats and humans share similarities in skeletal responses to estrogen deficiency, the mature OVX rat is considered to be a suitable animal model for studying early postmenopauseinduced bone loss [4]. Estrogen, bisphosphonates, parathyroid hormone (PTH), or selective estrogen receptor modulators (SERMs) have been used to prevent the postmenopausal bone loss [5], but many lines evidence indicate that long-term treatments with those drugs might cause adverse reactions, such as an increased risk of ovarian and endometrial cancer [6– 9], osteonecrosis of the jaws [10], nervous system disorders [11], and venous thromboembolism [12]. Thus, an alternative therapeutic strategy with a proven efficacy and safety should be developed to prevent and treat osteoporosis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aims of this study were to evaluate the osteoprotective effect of aqueous extract from Rhizoma Dioscoreae (RDE) on rats with ovariectomy- (OVX-) induced osteopenia. Our results show that RDE could inhibit bone loss of OVX rats after a 12-week treatment. The microarray analysis showed that 68 genes were upregulated and that 100 genes were downregulated in femurs of the RDE group rats compared to those in the OVX group. The Ingenuity Pathway Analysis (IPA) showed that several downregulated genes had the potential to code for proteins that were involved in the Wnt/ β -catenin signaling pathway (Sost, Lrp6, Tcf7l2, and Alpl) and the RANKL/RANK signaling pathway (Map2k6 and Nfatc4). These results revealed that the mechanism for an antiosteopenic effect of RDE might lie in the synchronous inhibitory effects on both the bone formation and the bone resorption, which is associated with modulating the Wnt/ β -catenin signaling and the RANKL/RANK signaling.
    The Scientific World Journal 01/2014; 2014:645975. DOI:10.1155/2014/645975 · 1.73 Impact Factor
  • Source
    • "Rizzoli and colleagues recently reviewed drug–drug interactions for OP patients. These are relatively rare and although there are risks, these should be weighed against the benefits of treatment [43]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Osteoarthritis (OA) is one of the most common forms of degenerative joint disease and a major cause of pain and disability affecting the aging population. It is estimated that more than 20 million Americans and 35 to 40 million Europeans suffer from OA. Analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) are the only therapeutic treatment options for OA. Effective pharmacotherapy for OA, capable of restoring the original structure and function of damaged cartilage and other synovial tissue, is urgently needed, and research into such disease-modifying osteoarthritis drugs (DMOADs) is in progress. This is the first of three reviews focusing on OA therapeutics. This paper provides an overview of current research into potential structure-modifying drugs and more appropriately targeted pharmacological therapy. The challenges and opportunities in this area of research and development are reviewed, covering the most up-to-date initiatives, trends, and topics.
    Current Rheumatology Reports 10/2013; 15(10):364. DOI:10.1007/s11926-013-0364-9 · 2.87 Impact Factor
Show more