Denosumab was approved for the treatment of postmenopausal osteoporosis in 2010, based on the FREEDOM study, which indicated a benefit in terms of increased bone mineral density and reduced risk of major osteoporotic fracture. In the initial clinical studies it was noted that discontinuation of denosumab can lead to a rebound of bone turnover markers and loss of accrued bone mineral density. An increased risk of fractures (multiple vertebral fractures in particular) associated with discontinuation was noted after approval and marketing of denosumab. For many patients experiencing gain in bone mineral density and fracture prevention while taking denosumab, there is no reason to stop therapy. However, discontinuation of denosumab may happen due to non-adherence; potential lack of efficacy in an individual; where reimbursement for therapy is limited to those with bone mineral density in the osteoporosis range, when assessment reveals this has been exceeded; or patient or physician concern regarding side effects. This review paper aims to discuss these concerns and to summarize the data available to date regarding sequential osteoporosis therapy following denosumab cessation to reduce the risk of multiple vertebral fracture.

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Introduction: Primary adrenal lymphoma (PAL) is a rare cause of adrenal enlargement with approximately 200 cases reported in the literature to date. It tends to affect elderly men and has a high incidence of bilateral involvement at diagnosis. We report the case of a 66 year old man, whose PAL manifested with symptomatic hypercalcaemia. A 66 year old male, originally from the Philippines, was referred to the emergency department with nausea, vomiting, weight loss and right flank pain. His past medical history was significant for hypertension, gout and stage 3b chronic kidney disease. His medications were amlodipine, losartan and febuxostat. His family history was significant for hypertension. On examination he was hypertensive (blood pressure, 160/100 mmHg) and hyperpigmented. His laboratory investigations revealed; corrected calcium of 3.79 mmol/l, undetectable PTH, vitamin D 49 nmol/l. He was treated with intravenous (IV) 0.9% saline and IV zoledronic acid and his calcium levels improved. To investigate causes of non-PTH mediated hypercalcaemia, computerised tomography of the thorax, abdomen and pelvis (CT TAP) as well as a positron emission tomography (PET) scan were performed. These demonstrated bilateral, large, metabolically active adrenal masses with no evidence of extra-adrenal disease. Differential diagnosis at this point included bilateral adrenal hyperplasia, metastases, lymphoma or adrenal TB. There were no radiological features of adrenocortical carcinoma (ACC) or phaeochromocytoma and subsequent biochemical investigations confirmed no evidence of cortisol, androgen or catecholamine excess. Adrenocorticotrophic hormone (ACTH) levels were elevated however, and a synacthen test revealed inadequate adrenal reserve (peak cortisol 214 nmol/l). The patient was commenced on maintenance steroids and with stress dose steroid cover, proceeded to adrenal biopsy. Histology confirmed diffuse large B cell non-Hodgkin’s lymphoma. Haematology became involved in his care and he commenced polychemotherapy in the form of R-CHOP, 1 week post confirmation of the diagnosis. His treatment is ongoing and he has tolerated it well with minimal side effects, except a flare of gout. Learning points: PAL should be considered in the differential diagnosis in patients with bilateral adrenal masses. Image guided adrenal biopsy is the gold standard for diagnosis, though caution must be exercised and an ACC or phaeochromocytoma should be excluded prior to biopsy. The prognosis of PAL is poor and therefore early diagnosis and prompt initiation of treatment are required to improve outcomes.