Session: FRI 368-390-Metabolic Bone Disease Case Reports (posters)
Poster Board FRI 389
A 65 year female with history of CKD stage 3, PCV since 1989, papillary thyroid carcinoma, total thyroidectomy and hypoparathyroidism since 1996 presented with complaints of severe myalgia, fatigue, paresthesia and critical hypocalcemia. Her corrected S. Ca 5.8 mg /dl (8.9-10.1 mg/dL) and Ionised Ca 2.9 mg/dl (4.5 - 5.4 mg/dL). Other labs showed stable creatinine 1.5 mg/dL, intact PTH 29 pg/ml(14-72pg/ml) and 25,OH vitamin D level 35ng/ml (30-100ng/ml). She was recently started on ruxolitinib 4 months ago for PCV due to worsening thrombocytosis. Since the start of ruxolitinib she had these symptoms. Follow up labs showed rapid fall in blood counts because of which ruxolitinib was stopped after 2 months. She continued to have symptoms even after stopping the drug. Her symptoms were attributed to very low S. Ca level. She was treated with multiple IV / oral calcium doses and initiated on calcitriol once her phosphorus dropped below 5.5mg/dl. The Ca level corrected and was discharged on Ca carbonate, Ca acetate and calcitriol.
The JAK family plays a vital role in maintaining normal hematopoiesis. Ruxolitinib has a target specific JAK1/2 receptor action and lack interaction with JAK3. The temporal relation of ruxolitinib initiation to the drop in counts and hypocalcemia was evident here. Once drug was discontinued, hypocalcemia persisted for 4 weeks until calcium replacement initiated. There is only one reported case of hypocalcemia with ruxolitinib where patient presented with tumor lysis, acute renal failure and hyperphosphatemia. Tumor lysis improved with expectant management however hypocalcemia persisted. Interestingly the JAK pathway is associated with Ca homeostasis and phosphate metabolism. Studies have shown JAK3 deficiency is associated with increase in 1,25 OH D3 with resultant increase in intestinal phosphate absorption and inhibition of PTH production. Our patient had hypoparathyroidism and the resultant hyperphophatemia was kept under control by phosphate binders. With ruxolitinib, it is unclear if there can be heightened sensitiveness of JAK3 inhibition in specific population with concomitant parathyroid abnormalities. Another hypothesis is the involvement of JAK- STAT pathway interaction with EGFR and PDGFR. They play a role in osteoblast differentiation and fracture repair respectively. The exact role of such interactions at present is elusive.
The case highlights a unique association of ruxolitinib to hypocalcemia. Though it is to yet to be proven whether this was a chance occurrence or a direct causal effect, it is important to keep this association in mind since ruxolitinib is increasingly being used for myelofibrosis and polycthemia patients.
Nothing to Disclose: AS, RN, GAP
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