Romosozumab Improves Bone Mineral Density and Quality of Life in Sickle Cell Associated Osteopenia and Osteoporosis

Metabolic bone disease is common in patients with sickle cell disease including low bone mineral density (BMD), osteopenia, and osteoporosis, which contribute significantly to acute and chronic pain¹. Supplementation with calcium and vitamin D and administration of bisphosphonate or denosumab may improve symptoms but does not improve BMD^2-4. In this abstract, we present a 34-year-old woman with severe sickle cell anemia complicated by frequent acute painful episodes along with chronic bone pain affecting mainly her back and hips with difficulty moving from one position to another or standing up and walking. She is on hydroxyurea, folic acid, painkillers, blood transfusion, and iron chelation. On physical examination she was in a wheelchair, looking ill, depressed, and in pain with tenderness over her vertebral column and hip joints. She estimated her quality of life (QOL) to be 3/10.

Lab. Investigations: Hb 9.6 g/dl, HCT 26.8 %, MCV 113.1 fl, WBC 7.98 x10³/uL, platelets 433 x 10³/uL, reticulocytes 4.8%, LDH 340 IU (normal 177-333), Hb A1, 0%, Hb A2, 2.2%, Hb S, 71.1%, Hb F, 26.7%, Ferritin 2325 ng/ml (15-150), Vitamin D, 21.56 ng/ml (30-100), Calcium 9.74 mg/dl (8.8-10.8), Albumin 4.44 g/dl (3.5-5.2). MRI of the vertebral column and hip joints showed generalized osteopenia with no compression or osteonecrosis. Lunar DEXA scan of the vertebral column showed BMD = 0.715 g/cm², (normal 1.315 -1.435) and T-score -4 SD (> 1), consistent with osteoporosis. Lunar DEXA scan of the hip joints showed BMD = 0.756 g/cm² (1.134 - 1.260) and T-score -3 SD (> 1), consistent with osteopenia. Our patient is well-informed about sickle cell disease and its complications including bone disease. She suggested the use of Romosozumab for one year and signed a consent form indicating that this was her suggestion without any responsibility of the medical staff. Romosozumab 210 mg SC Was given monthly along with vitamin D 50,000 IU PO weekly, Calcium 600 mg PO, BID, Hydroxyurea 1000 mg PO daily, folic acid 1 mg PO daily, deferasirox 1080 mg PO daily, and painkillers as needed. There was a gradual improvement in her pain with gradual activity and weaning of painkillers. Within three months, her pain was fading away, and her movement became almost normal, and painkillers were stopped except for occasional acetaminophen. Six months later she became free of pain, active, exercising, and even participated in a local marathon (against medical advice) and was one of the winners. She now estimates her QOL at 8-9/10. Her current Lunar DXA scan showed an increase in BMD of the vertebral column from 0.715 to 0.955 g/cm² with an increase in T-score from -4 to - 2. BMD of the hip joint increased from 0.756 to 0.882 g/cm² with an increase in T-score from -3 to -1 SD

Discussion: treatment of metabolic bone disease in patients with sickle cell disease has included Vitamin D with Calcium supplement, bisphosphonate, and denosumab with various degrees of improvement in bone pain, however, none of these have shown an increase in BMD^1-4. Our case is the first to show dramatic pain reduction and increased BMD with improved QOL.

Conclusion: Romosozumab may increase BMD, reduce bone pain, and improve QOL in sickle cell patients with metabolic disease. This finding needs confirmation through larger studies.

References:

1- Miller R G. et.al. High Prevalence and Correlates of Low Bone Mineral Density in Young Adults with Sickle Cell Disease. Am J Hematol 2006; 81: 236

2- Adewoye A H. et al. Sickle cell bone disease: Response to vitamin D and Calcium. Am J Hematol. 2008; 83: 271

3- Grimbly C. et. al. Sickle cell bone disease and response to intravenous bisphosphonates in children. Osteoporos Int. 2022; 33: 2397

4- Gaudio A. et. al. Hematological Diseases and Osteoporosis. Int J Mol Sci 2020; 21: 3538

No relevant conflicts of interest to declare.

Romosozumab in Sickle Cell associated Osteoporosis/Osteopenia