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IntroductionBioactive glasses (BG) have the ability to bond directly with living tissue via the formation of a hydroxycarbonate apatite-like layer on their surface, and are therefore utilised in a variety of dental and orthopaedic applications [1,2]. However, this is not their only mechanism of action. BG can also be designed to release ions that stimulate specific cell behaviour. Indeed, we have recently reported on BG that release strontium ions, the active component of the osteoporosis drug strontium ranelate, which act to both promote osteoblast activity and inhibit osteoclast activity [3].Fluoride is widely recognised for its ability to prevent dental caries as it inhibits dentine and enamel demineralisation [4], however, it also affects the axial skeleton. That is, clinical examinations of osteoporotic patients have demonstrated that fluoride treatment stimulates bone formation [5]. Nevertheless, in placebocontrolled, double-blind clinical trials, sodium fluoride (NaF) was found not to be efficacious in preventing osteoporosis-related fractures [6,7]. In subsequent detailed analyses of these trials, fluoride's lack of efficacy was attributed to its substitution into bone apatite, creating structurally and mechanically inferior bone, as mineral crystal size and crystallinity increased [8]. Consequently, fluoride's use as an osteoporosis treatment was largely dismissed. Moreover, this seemed judicious as osteomalacia was reported in patients treated with NaF [9], and skeletal fluorosis, which is endemic in areas with high levels of fluoride in the ground water, is known to cause a range of skeletal abnormalities [10].As clinical trials with fluoride failed to demonstrate clear anti-fracture efficacy, other osteoporosis drugs have come into favour. Anti-catabolic agents such 2 as bisphosphonates, which block osteoclast-mediated bone resorption via inhibition of the mevalonate pathway [11] are widely prescribed. However, anti-catabolic agents only prevent further bone resorption and do not promote bone formation.Furthermore, long-term bisphosphonate use has been associated with osteonecrosis of the jaw [12] and atypical, low-energy femur fractures [13], which has created reluctance among some clinicians to prescribe them. Anabolic agents such as recombinant parathyroid hormone (PTH), which stimulate osteoblast-mediated bone matrix formation [14], are also often administered. However, PTH is expensive and requires daily subcutaneous injections. As a result, alternative treatments, such as inexpensive NaF, have recently been re-examined [15].In vitro studies point towards a small dosing range for NaF that will successfully promote osteoblast activity [16], and recent meta-analyses have shown that fluoride is efficacious in preventing osteoporosis-related fractures when administered at doses lower than those used in the widely reported clinical trials [17].Furthermore, in vitro studies have demonstrated that fluoride has an anabolic effect on bone, enhancing osteoblast proliferation [18, 19] and alkaline phosp...