Denosumab leads to sustained suppression of bone turnover if given every 6 months, with escape occurring approximately 2 to 3 months after the last dose. Whilst escape from denosumab has been reported in malignancy, there has only been one reported case in the setting of osteoporosis. We present the case of a 62-year old woman with systemic sclerosis who did not respond to denosumab secondary to premature escape from suppression of bone resorption. Our patient was diagnosed with osteoporosis 15 years previously based on bone densitometry, with no prior fragility fractures. Initial treatment with oral bisphosphonates was changed to denosumab due to patient choice and intermittent compliance. Over the subsequent 5 years, she received denosumab 60 mg via subcutaneous injections every 6 months, however there was no improvement in her bone mineral density. Significantly, whilst markers of bone turnover demonstrated initial suppression at 3 months post denosumab dose, these were elevated prior to the next dose at 6 months, suggesting escape from the suppressive effects of denosumab. Although this is the second case report of escape from denosumab in osteoporosis and the first in a patient with systemic sclerosis, this phenomenon may be under-reported in patients who do not respond to denosumab. We suggest that clinicians consider the possibility of escape in patients with poor response to denosumab who are compliant, and suggest the measurement of bone turnover markers in these patients.