Experience With Anti-Sclerostin Antibody for Osteoporosis Patient With End-Stage Renal Disease on Hemodialysis

Background: Romosozumab is a sclerostin inhibitor indicated for treatment of postmenopausal osteoporosis. Sclerostin inhibits Wnt/Beta-catenin signaling pathway. When sclerostin is inhibited, stimulation of this pathway leads to increased bone formation and production of osteoprotegerin, which also decreases bone resorption. Patients with chronic kidney disease (CKD) demonstrate increased levels of sclerostin that negatively correlates with the rate of bone formation; however, data is lacking for use of romosozumab in this patient population. The report herein details the experience of use of romosozumab in a patient with end-stage renal disease (ESRD) on hemodialysis (HD). Clinical Case: A 37-year-old old African American male was referred after multiple rib fractures and severe non-traumatic T8 compression fracture with nerve compression. His past medical history includes lupus nephritis and cerebritis, ESRD on HD since age 22 status post (s/p) failed renal transplant, and tertiary hyperparathyroidism complicated with fracture in iliac brown tumor and mediastinal parathyromatosis s/p three parathyroid surgeries. Bone mineral density by DXA (g/cm(2), Z-score) were as follows: lumbar spine (0.700, -4.0) femoral neck (0.676, -3.8), total hip (0.628,-4.0), 1/3 radius(0.443,-6.2). No prior exposure to antiresorptive or osteoanabolic agents. Pertinent labs included serum calcium 8.5 mg/dL (nl 8.9–10.3 mg/dl), albumin 4.2 g/dL, alkaline phosphatase 319 U/L (nl 38–126), Phosphorus 3.1 mg/dL (2.4–4.7), Creatinine 5.62 mg/dl, 25-OH Vitamin D 31 ng/mL (nl 25 - 80), intact parathyroid hormone 17.9 pmol/L (nl 1.6–6.9). Patient was in excruciating pain and not a surgical candidate due to poor bone quality. Osteoanabolic therapy was recommended given the severity of osteoporosis; however, teriparatide and abaloparaitde were contraindicated given comorbidities. The patient was offered off-label use of Romosozumab with clear understanding that the drug is not approved for this indication and safety/efficacy data in ESRD is not known. The boxed warning regarding increased risk of stroke, myocardial infarction and death were discussed and patient was willing to proceed. Repeat DXA after eleven monthly doses of Romosozumab resulted in a remarkable improvement in bone mineral density at all sites: lumbar spine (+47%), femoral neck (+41%), total hip (+28%), 1/3 radius (+20%). Patient tolerated medication with no side effects or fractures. Serum calcium was monitored prior to initiation and before every dose. No doses were held due to abnormal laboratory values or side effects. Conclusion: This case report summarizes successful experience with the use of Romosozumab in one patient with ESRD on HD with favorable outcomes.