Sickle cell bone disease and response to intravenous bisphosphonates in children

Abstract

Summary Children with sickle cell disease (SCD) have the potential for extensive and early-onset bone morbidity. This study reports on the diversity of bone morbidity seen in children with SCD followed at three tertiary centers. IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications. Introduction To evaluate bone morbidity and the response to intravenous (IV) bisphosphonate therapy in children with SCD. Methods We conducted a retrospective review of patient records from 2003 to 2019 at three Canadian pediatric tertiary care centers. Radiographs, magnetic resonance images, and computed tomography scans were reviewed for the presence of avascular necrosis (AVN), bone infarcts, and myositis. IV bisphosphonates were offered for bone pain management. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA). Results Forty-six children (20 girls, 43%) had bone morbidity at a mean age of 11.8 years (SD 3.9) including AVN of the femoral (17/46, 37%) and humeral (8/46, 17%) heads, H-shaped vertebral body deformities due to endplate infarcts (35/46, 76%), and non-vertebral body skeletal infarcts (15/46, 32%). Five children (5/26, 19%) had myositis overlying areas of AVN or bone infarcts visualized on magnetic resonance imaging. Twenty-three children (8/23 girls) received IV bisphosphonate therapy. They all reported significant or complete resolution of bone pain. There were no reports of sickle cell hemolytic crises, pain crises, or stroke attributed to IV bisphosphonate therapy. Conclusion Children with SCD have the potential for extensive and early-onset bone morbidity. In this series, IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-022-06455-2.

Bone Health Impairment in Patients with Hemoglobinopathies: From Biological Bases to New Possible Therapeutic Strategies

“…There is no evidence regarding a specific treatment to counteract or prevent bone metabolism impairment in SCD subjects. But considering the low levels of vitamin D in these patients, it could be useful to repeat its supplementation [ 151 ]. BP can be used also in SCD patients in order to reduce pain and counteract bone impairment.…”

“…Different studies tested two different BPs in SCD, zoledronic acid and alendronate, to highlight their effect on bone. It was reported that only alendronate had the ability to increase BMD in SCD patients with OP [ 151 ]. Certainly, further research and investigations will be necessary in order to better understand the role of BPs in SCD.…”

A bone to pick-cellular and molecular mechanisms of bone pain in sickle cell disease

“…Preclinical, and clinical studies show osteoclast activation associates with both pathological bone loss and chronic bone pain ( 20 – 23 ). Interestingly, children with SCD and low BMD had improvement in chronic pain after receiving bisphosphates, an anti-resorptive medication, highlighting the role of OC activity in both low BMD and pain ( 24 ).…”

“…Fractures are common n in children and young adults with SCD ( 11 , 24 ). In one study, 46% of adults had evidence of vertebral fractures ( 11 , 12 ).…”

“…Pre-clinical studies in mouse models of SCD also show that bisphosphonates reduce markers of bone turnover and improve bone microarchitecture ( 13 ). A recent study in 46 children with SCD-related skeletal morbidity showed improvement in chronic pain after treatment with intravenous bisphosphates, highlighting the possible interaction between osteoclast activation, abnormal bone remodeling, and the development of bone pain ( 24 ). An ongoing prospective study is evaluating the effect of bisphosphonates on bone pain in adults with SCD (NCT05283148).…”