The effects of organic nitrates on osteoporosis: a systematic review

Abstract

Current treatments for osteoporosis are limited by lack of effect on cortical bone, side effects, and, in some cases, cost. Organic nitrates, which act as nitric oxide donors, may be a potential alternative. This systematic review summarizes the clinical data that reports on the effects of organic nitrates and bone. Organic nitrates, which act as nitric oxide donors, are novel agents that have several advantages over the currently available treatments for osteoporosis. This systematic review summarizes the clinical data that reports on the effects of organic nitrates on bone. We searched Medline (1966 to November 2012), EMBASE (1980 to November 2012), and the Cochrane Central Register of Controlled Trials (Issue 11, 2012). Keywords included nitrates, osteoporosis, bone mineral density (BMD), and fractures. We identified 200 citations. Of these, a total of 29 were retrieved for more detailed evaluation and we excluded 19 manuscripts: 15 because they did not present original data and four because they did not provide data on the intervention or outcome of interest. As such, we included ten studies in literature review. Of these ten studies two were observational cohort studies reporting nitrate use was associated with increased BMD; two were case control studies reporting that use of nitrates were associated with lower risk of hip fracture; two were randomized controlled trials (RCT) comparing alendronate to organic nitrates for treatment of postmenopausal women and demonstrating that both agents increased lumbar spine BMD. The two largest RCT with the longest follow-up, both of which compared effects of organic nitrates to placebo on BMD in women without osteoporosis, reported conflicting results. Headaches were the most common adverse event among women taking nitrates. No studies have reported on fracture efficacy. Further research is needed before recommending organic nitrates for the treatment of postmenopausal osteoporosis.

Serum urate levels and the risk of hip fractures: data from the Cardiovascular Health Study

“…It may also de-activate NO by reacting with it irreversibly [36]. Organic nitrates have been proposed as a treatment for osteoporosis; one that would improve BMD but also that may improve bone turnover and strength [37], although such therapies have not yet been shown to reduce the risk of fracture. It is possible that hyperuricemia may compromise bone strength indirectly, by impairing NO in the bone and increasing bone fragility and the risk of fracture.…”

The Key Role of the Blood Supply to Bone

“…Hind limb blood flow in rodents has been shown to depend largely on NO and is modulated to a lesser extent by the endothelium-derived hyperpolarising factor (109). There is strong evidence that supplementation of NO donors such as nitroglycerine (110)(111)(112)(113)(114) and isosorbide mononitrate (114)(115) increase bone mass in animals and osteoporotic patients, although there are also some conflicting studies in humans (116)(117). Whether the osteoanabolic action of NO in bone is mediated indirectly by endothelium-controlled blood perfusion, or whether it also has significant direct actions on bone cells, is still not known.…”

Urinary heavy metals, phthalates, phenols, thiocyanate, parabens, pesticides, polyaromatic hydrocarbons but not arsenic or polyfluorinated compounds are associated with adult oral health: USA NHANES, 2011–2012

“…One reason might be due to the reduction of environment lead levels in USA in recent years. The link between nitrate and bone loss has not been confirmed yet since many studies have yielded conflicting results (Jamal et al 2013), and so is the relationship of thiocyanate and bone loss. Moreover, the only paraben element associated with bone loss around the mouth is only borderline.…”