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Denosumab induced hypocalcaemia in the setting of palliative metastatic prostate cancer
ABSTRACTS
Results: Of the 222 samples, 90 had a known paraprotein. 70 had paraproteins quantifiable by densitometry (clearly separated monoclonal band) on HR SPEP and 56 by capillary electrophoresis. A review of the 14 samples unquantifiable by capillary electrophoresis, showed 57% had a paraprotein migrating within the b-region and only able to be clearly separated with HR SPEP. Conclusions: The improved resolution of Sebia Hydragel 15 HR gels in the b-region increases the number of paraproteins that can be accurately quantified by densitometry in this region compared to a commonly used capillary electrophoresis system. References 1. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016; 17: e328–46. 2. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15: e538–48. 3. Willrich MA, Katzmann JA. Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias. Clin Chem Lab Med 2016; 54: 907–19.
VITAMIN D STATUS IN SOUTH AUSTRALIAN CHILDREN – SEASONAL VARIABILITY AND PREVALENCE OF DEFICIENCY Sunethra Devika C. Thomas1,2, Shaw Callen1, Michael Metz1,3 1 Department of Biochemistry, Clinpath Laboratories, Kent Town, Adelaide, 2Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, and 3Women’s and Children’s Hospital, Adelaide, SA, Australia Introduction: The prevalence of rickets in Australia is low, but a broader spectrum of low vitamin D status is common in children. Mild (30–50 nmol/L) and moderate (12.5–29 nmol/L) deficiency are common in certain ethnic groups and may occur due to low intake or lack of sun exposure. This audit aims to ascertain the prevalence of vitamin D deficiency in South Australian (SA) children and to assess the effect of season and gender on vitamin D status. Method: All vitamin D measured on children (18 years) using an immunoassay method (Diasorin Liaison) for a period of 12 months were obtained from the Clinpath laboratory database. A t test was used to compare mean vitamin D between seasons. Within each month, the percentage of children with vitamin D deficiency (<50 nmol/L) and the male:female ratio within this group was calculated. Results: Vitamin D requests tripled in September compared to summer months. Prevalence of vitamin D deficiency rose in winter and the mean 25OHD value for winter was significantly lower than other seasons, correlating with average UV index. A higher proportion of girls were vitamin D deficient, however the difference did not achieve significance. Conclusions: SA children appear to be dependent on sunshine for vitamin D. Low sun exposure due to lifestyle, dress and skin pigmentation may contribute to low vitamin D status. Slightly more girls were affected than boys. There may be other gender-specific factors contributing to this gap in children.
S101
DENOSUMAB INDUCED HYPOCALCAEMIA IN THE SETTING OF PALLIATIVE METASTATIC PROSTATE CANCER Oliver Treacy1, Richard G. Ruddell1, Urs Wilgen1,2 1 Department of Chemical Pathology, Pathology Queensland Central Laboratory, Herston Hospital Campus, Herston, and 2 School of Medicine, University of Queensland, Herston, Qld, Australia An increasing number of pharmaceutical agents are being developed to combat bone loss. Care must be taken when administering any compound that targets the skeletal system, due to its integral nature in calcium homeostasis. Denosumab is one such agent, and is a monoclonal antibody medication that blocks the RANKligand receptor of osteoclasts, preventing bone resorption.1 It is indicated in the setting of conditions related to bone loss. By inhibiting the action of osteoclast-mediated bone resorption, patients may be susceptible to profound hypocalcaemia. This report will focus on a patient who is on denosumab for palliative treatment of bony metastases related to prostate cancer. These bony metastases had spread to the spine and pelvis. Denosumab was used to prevent further metastatic bone pain, as well as further bone loss due to hormone ablation therapy. However, the use of this medication was also linked to profound symptomatic hypocalcaemia, responsive only to high doses of calcium. This case highlights the need for stringent monitoring of calcium, and its associated biochemistry, in therapy involving denosumab. Reference 1. Rizzoli R, Yasothan U, Kirkpatrick P. Denosumab. Nat Rev Drug Discov 2010; 9: 591–2.
A PILOT STUDY: CALCIPROTEIN PARTICLE LEVELS IN TERM UMBILICAL CORD BLOOD AT DELIVERY Fatima Vally1, Thomas J. Cade1, Edward Smith2, Steve Holt2 1 Department of Maternity Services, Royal Women’s Hospital (RWH), Melbourne, and 2Department Nephrology, Royal Melbourne Hospital (RMH), Melbourne, Vic, Australia Neonates have high serum phosphate concentrations with reference ranges that would be considered high in adults, and similar to levels found in dialysis patients with ‘poor’ phosphate control. All mammals have well conserved mechanisms to prevent mineral precipitation. The plasma protein fetuin-A is a mineral chaperone that binds and stabilises nanocrystals of calcium and phosphate that would otherwise precipitate in plasma, forming fetuin calciprotein particles (CPP). CPP1 form as small particles <50 nm and appear harmless. CPP2 form from CPP1 over time and are larger with a more crystalline structure but are toxic to several cells. CPP2 are detected at high levels in dialysis patients. Normal adults have CPP1 levels in the range of 30–50×105 particles/mL. No studies have looked at CPP levels in neonatal cord blood. Aim: To determine the presence and type of CPP in umbilical cord blood at delivery. Methods: 10 mL of venous umbilical cord blood was collected from 10 healthy term neonates and were analysed for CPP levels using flow cytometry (at RMH). Results: CPP1 were detected in all cord samples (mean 184×105, median 73×105 particles/mL).
Results: Of the 222 samples, 90 had a known paraprotein. 70 had paraproteins quantifiable by densitometry (clearly separated monoclonal band) on HR SPEP and 56 by capillary electrophoresis. A review of the 14 samples unquantifiable by capillary electrophoresis, showed 57% had a paraprotein migrating within the b-region and only able to be clearly separated with HR SPEP. Conclusions: The improved resolution of Sebia Hydragel 15 HR gels in the b-region increases the number of paraproteins that can be accurately quantified by densitometry in this region compared to a commonly used capillary electrophoresis system. References 1. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016; 17: e328–46. 2. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15: e538–48. 3. Willrich MA, Katzmann JA. Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias. Clin Chem Lab Med 2016; 54: 907–19.
VITAMIN D STATUS IN SOUTH AUSTRALIAN CHILDREN – SEASONAL VARIABILITY AND PREVALENCE OF DEFICIENCY Sunethra Devika C. Thomas1,2, Shaw Callen1, Michael Metz1,3 1 Department of Biochemistry, Clinpath Laboratories, Kent Town, Adelaide, 2Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, and 3Women’s and Children’s Hospital, Adelaide, SA, Australia Introduction: The prevalence of rickets in Australia is low, but a broader spectrum of low vitamin D status is common in children. Mild (30–50 nmol/L) and moderate (12.5–29 nmol/L) deficiency are common in certain ethnic groups and may occur due to low intake or lack of sun exposure. This audit aims to ascertain the prevalence of vitamin D deficiency in South Australian (SA) children and to assess the effect of season and gender on vitamin D status. Method: All vitamin D measured on children (18 years) using an immunoassay method (Diasorin Liaison) for a period of 12 months were obtained from the Clinpath laboratory database. A t test was used to compare mean vitamin D between seasons. Within each month, the percentage of children with vitamin D deficiency (<50 nmol/L) and the male:female ratio within this group was calculated. Results: Vitamin D requests tripled in September compared to summer months. Prevalence of vitamin D deficiency rose in winter and the mean 25OHD value for winter was significantly lower than other seasons, correlating with average UV index. A higher proportion of girls were vitamin D deficient, however the difference did not achieve significance. Conclusions: SA children appear to be dependent on sunshine for vitamin D. Low sun exposure due to lifestyle, dress and skin pigmentation may contribute to low vitamin D status. Slightly more girls were affected than boys. There may be other gender-specific factors contributing to this gap in children.
S101
DENOSUMAB INDUCED HYPOCALCAEMIA IN THE SETTING OF PALLIATIVE METASTATIC PROSTATE CANCER Oliver Treacy1, Richard G. Ruddell1, Urs Wilgen1,2 1 Department of Chemical Pathology, Pathology Queensland Central Laboratory, Herston Hospital Campus, Herston, and 2 School of Medicine, University of Queensland, Herston, Qld, Australia An increasing number of pharmaceutical agents are being developed to combat bone loss. Care must be taken when administering any compound that targets the skeletal system, due to its integral nature in calcium homeostasis. Denosumab is one such agent, and is a monoclonal antibody medication that blocks the RANKligand receptor of osteoclasts, preventing bone resorption.1 It is indicated in the setting of conditions related to bone loss. By inhibiting the action of osteoclast-mediated bone resorption, patients may be susceptible to profound hypocalcaemia. This report will focus on a patient who is on denosumab for palliative treatment of bony metastases related to prostate cancer. These bony metastases had spread to the spine and pelvis. Denosumab was used to prevent further metastatic bone pain, as well as further bone loss due to hormone ablation therapy. However, the use of this medication was also linked to profound symptomatic hypocalcaemia, responsive only to high doses of calcium. This case highlights the need for stringent monitoring of calcium, and its associated biochemistry, in therapy involving denosumab. Reference 1. Rizzoli R, Yasothan U, Kirkpatrick P. Denosumab. Nat Rev Drug Discov 2010; 9: 591–2.
A PILOT STUDY: CALCIPROTEIN PARTICLE LEVELS IN TERM UMBILICAL CORD BLOOD AT DELIVERY Fatima Vally1, Thomas J. Cade1, Edward Smith2, Steve Holt2 1 Department of Maternity Services, Royal Women’s Hospital (RWH), Melbourne, and 2Department Nephrology, Royal Melbourne Hospital (RMH), Melbourne, Vic, Australia Neonates have high serum phosphate concentrations with reference ranges that would be considered high in adults, and similar to levels found in dialysis patients with ‘poor’ phosphate control. All mammals have well conserved mechanisms to prevent mineral precipitation. The plasma protein fetuin-A is a mineral chaperone that binds and stabilises nanocrystals of calcium and phosphate that would otherwise precipitate in plasma, forming fetuin calciprotein particles (CPP). CPP1 form as small particles <50 nm and appear harmless. CPP2 form from CPP1 over time and are larger with a more crystalline structure but are toxic to several cells. CPP2 are detected at high levels in dialysis patients. Normal adults have CPP1 levels in the range of 30–50×105 particles/mL. No studies have looked at CPP levels in neonatal cord blood. Aim: To determine the presence and type of CPP in umbilical cord blood at delivery. Methods: 10 mL of venous umbilical cord blood was collected from 10 healthy term neonates and were analysed for CPP levels using flow cytometry (at RMH). Results: CPP1 were detected in all cord samples (mean 184×105, median 73×105 particles/mL).