Mastocytosis is a rare cause of secondary osteoporosis. We present two cases of systemic mastocytosis being diagnosed in the setting of post-partum osteoporosis. Case 1: A 35 year old G2P2 woman who was breastfeeding presented with subacute on chronic back pain 4 weeks post-partum. Imaging confirmed the presence of multi-level vertebral fractures. T-score was -4.5 at the lumbar spine and -2.8 at the left hip. Vitamin D was 39nmol/L (N > 50), and calcium and PTH were not elevated. Screening tests for secondary osteoporosis revealed an elevated serum tryptase of 23.8ng/ml (N < 11ng/ml) and a subsequent bone marrow biopsy confirmed the presence of mastocytosis. When she was treated with a zoledronic acid infusion, she developed a sinus tachycardia, hypotension and a fever of 40°C. A recent report suggests that acute phase reactions may be a common reaction related to the use of zoledronic acid in patients with mastocytosis (1). Case 2: A 29 year old G2P1 woman who was breastfeeding presented with acute on chronic back pain 3 months post-partum upon lifting her baby. Imaging confirmed a compression fracture of lumbar vertebrae 4-5. Her average T-score was -3.19 at the lumbar spine and -1.99 at the left hip. Her Vitamin D was 54nmol/L. She received calcium and vitamin D supplements. After a further 12 months there was only marginal improvement in her bone mineral density. Re-imaging revealed new compression fractures in the thoracic spine. Her serum tryptase level was elevated at 25.7ng/ml and a diagnosis of mastocytosis was confirmed on bone marrow biopsy. She was commenced on an anti-histamine and has elected to have her osteoporosis treated with denusomab. Conclusion: Although pregnancy and lactation may contribute to bone loss, these cases suggest that in the setting of severe post-partum osteoporosis, a diagnosis of systemic mastocytosis should also be considered.