The diagnosis of SCD was confirmed by electrophoresis and genetic testing for HbS variants. Clinical data included sex, age, height, and weight Z-scores based on WHO growth curves, hemoglobinopathy genotype, whether hydroxyurea was prescribed at the time of bone morbidity diagnosis, age at initial radiographic diagnosis of bone morbidity, and age upon presentation to a bone health clinic. Clinical data were extracted using a structured data form by clinicians familiar with the electronic health system. Study data were collected and managed using the REDCap electronic data capture tool hosted at the University of Alberta. The study was approved by the Research Ethics Boards (REBs) in each of the participating institutions (REB approval numbers: Stollery Children’s Hospital-Pro 0090451, CHEO-20190342, and CHU St. Currently, these centers follow approximately 750 children with SCD.
Years over which data were collected differed from center to center due to access to electronic medical records and the establishment of bone and metabolism clinics. In addition, data from 2001 to 2020 were collected retrospectively from children with SCD who were referred to the Genetic and Metabolic Bone Disease Clinic at the Children’s Hospital of Eastern Ontario (CHEO), Ottawa, Ontario. Data from 2013 to 2020 were also collected retrospectively from children with SCD who were referred to the Pediatric Bone and Metabolism Clinic at the Centre Hospitalier Universitaire Sainte-Justine (CHU St. Affected children and adolescents with SCD from 2015 to 2020 were identified at the Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, and their bone imaging reports were reviewed. This was a retrospective study of children < 18 years of age with SCD and bone morbidity followed at three Canadian tertiary pediatric centers as part of routine clinical care. Given the limited information about skeletal morbidity and its treatment in SCD, we aim to describe the skeletal features of pediatric SCD bone morbidity and the response to intravenous (IV) bisphosphonate therapy including pain management, side effects, impact on BMD, and bone histomorphometry. Major clinical questions remain unanswered such as the indication for bisphosphonate therapy in SCD, efficacy of reducing or halting bone morbidity, and safety of bisphosphonate use. Another group demonstrated improved BMD T-scores at 6 and 12 months after treatment of alendronate in adults with SCD and osteoporosis. Zoledronic acid was administered to nine adults in a study evaluating vertebral involvement in sickle cell bone disease, but the indication, response to treatment, and adverse effects of bisphosphonates were not reported. Bisphosphonates may therefore be useful in patients with SCD to treat bone morbidity and for pain control. Bisphosphonates are anti-resorptive medications used to treat osteoporosis, and act as an analgesic for bone pain in a variety of settings, including fibrous dysplasia, cancer-related AVN, and bone metastases.
ĭespite the frequency of bone morbidity in SCD, there is currently no standard of care for its prevention or treatment.
Vitamin D deficiency is present in a third of individuals with SCD which may further impair their bone health. It is attributed to vaso-occlusive episodes in the muscle and can have a fulminant presentation with acute fasciitis, necrotizing myositis, and compartment syndrome. Myositis is thought to be a rare and often overlooked complication of SCD that occurs due to infection or due to underlying bone marrow changes and bone infarct.
Extramedullary hematopoiesis leads to protrusion of the disk into the infarcted central vertebral body, creating the characteristic biconcave deformity seen in H-shaped vertebral bodies. Vertebral endplate infarcts cause H-shaped vertebral deformities due to sickling and ischemia in the vulnerable long arterial blood vessels that feed the central vertebral body. Long bones and vertebral endplates are common locations for bone infarcts however, any skeletal bone can be affected.