Bisphosphonates in the treatment of osteoporosis: a review of skeletal safety concerns

Abstract

The use of bisphosphonates in treatment of osteoporosis declined significantly over the past decade. There is currently great concern, among patients and physicians, about two potential skeletal adverse effects associated with bisphosphonates- jaw osteonecrosis and atypical femur fractures. This has become a major public health issue since untreated osteoporosis carries a significant burden in terms of fracture-related morbidity and mortality, and bisphosphonates, considered first-line therapy for osteoporosis, have established efficacy in fracture and mortality reduction. Areas covered: In this review we discuss current literature on osteonecrosis of the jaw and atypical femur fractures in patients with osteoporosis treated with bisphosphonates, including case definition, pathogenesis, epidemiology, risk factors, clinical presentation, management and prevention. We conducted a literature search using PubMed and PubMed Central, using the search terms 'bisphosphonates', 'osteonecrosis of the jaw', and 'atypical fractures'. We selected relevant articles including meta-analyses, clinical trials, observational studies, and major society guidelines published between 2010 and 2016, to be included in this review. A few articles published prior to 2010 were also included as references. Expert commentary: The rare skeletal side effects of bisphosphonates should not preclude their use in patients with osteoporosis and high fracture risk, as benefits significantly outweigh the risks.

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“…Ostlund et al [ 32 ] found that dissolved organic matter (DOM) limited Hg uptake from water by fish, yielding lower BCF. Higher concentrations of Hg in the leaves were measured in the contaminated areas compared to the remote areas [ 33 ].…”

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“…Although BP treatment presents advantages, BPs have a long half-life of approximately 10 years in the human body. Therefore, further research is warranted to confirm the long-term side effects of BPs, including skeletal toxicity and osteonecrosis [ 214 ].…”

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“…However, it is becoming evident that although these drugs are effective in stopping the resorption of bone and preventing osteoporosis in women, they have a low long-term compliance [23]. Furthermore, bisphosphonates induce oxidative stress [24], associated with decreased glutathione and increased lipid peroxidation end-product malondialdehyde (MDA) [25], which are probably contributing factors to atypical fractures and osteonecrosis of the jaw, two debilitating complications of bisphosphonate treatment [26][27][28][29][30][31]. Indeed, treating cultured oral fibroblasts with bisphosphonates has demonstrated increased ROS levels [32], while oxidative stress has been detected in patients with bisphosphonate-related osteonecrosis of the jaw, accompanied by an increased oxidized glutathione (GSSG)/glutathione (GSH) ratio [33].…”