This review addresses thickening of the bony pyramid of the nose, a condition that is caused by in-flight oxygen masks in otherwise healthy Royal Netherlands Air Force (RNLAF) F-16 pilots. The overlying skin may show temporary or permanent reddening, irritation, thickening and may become painful. Both in vitro and in vivo animal research has shown that mechanical stimuli are converted into a biochemical response through a process called mechanotransduction. Examination of the RNLAF F-16 pilots showed that the oxygen mask exerts pressure and friction on the nose. The biochemical response to chronic exposure to these stimuli results in the development of skin conditions and eventually exostoses of the bony pyramid of the nose. Painful skin conditions are most frequently observed, while the development of exostoses is rare. It lies at the extreme end of the spectrum of the pilots' nasal conditions. The suboptimal fit of their work gear probably contributes to the pilots' soft and bony tissue nasal conditions. Explaining the pathogenesis of the development of exostoses may aid in the development of preventive measures. Also, the obtained knowledge may be of use in similar occupational health issues that involve mechanical loading. Our conclusions are that areas containing osteocyte precursors and covered by a relatively thin cushioning layer are prone to develop a soft tissue and bony tissue response when they are chronically exposed to intermittently exerted, mechanical stimuli of sufficiently high magnitude. Modification of the suboptimally fitting oxygen mask-helmet assembly is needed to prevent symptoms associated with its use.