Microarchitectural and mechanical characterization of the sickle bone

Abstract

Individuals with sickle cell disease often experience acute and chronic bone pain due to occlusive events within the tissue vasculature that result in ischemia, necrosis, and organ degeneration. Macroscopically, sickle bone is identified in clinical radiographs by its reduced mineral density, widening of the marrow cavity, and thinning of the cortical bone due to the elevated erythroid hyperplasia accompanying the disease. However, the microstructural architecture of sickle bone and its role in mechanical functionality is largely unknown. This study utilized micro-CT and biomechanical testing to determine the relationship between the bone morphology, tissue mineral density, and trabecular and cortical microarchitecture of 10-and 21-week-old femurs from transgenic sickle male mice and littermates with sickle trait, as well as a wild-type control. While bone tissue mineral density did not vary among the genotypes at either age, variation in bone microstructure were observed. At 10 weeks, healthy and trait mice exhibited similar morphology within the cortical and trabecular bone, while sickle mice exhibited highly connected trabeculae. Within older femurs, sickle and trait specimens displayed significantly fewer trabeculae, and the remaining trabeculae had a more deteriorated geometry based on the structure model index. Thinning of the cortical region in sickle femurs contributed to the displayed flexibility with a significantly lower elastic modulus than the controls at both 10- and 21-weeks old. Wild-type and trait femurs generally demonstrated similar mechanical properties; however, trait femurs had a significantly higher modulus than sickle and wild-type control at 21-weeks. Overall, these data indicate that the progressive damage to the microvasculature caused by sickle cell disease, results in deleterious structural changes in the bone tissue's microarchitecture and mechanics.

Influence of Iron on Bone Homeostasis

“…These studies revealed that thalassemia mice exhibit the same weak bone phenotype as the thalassemia patients [93,94,95]. Similarly, sickle cell disease mice are characterized by low BMD and harmful alterations in the microarchitecture and mechanics of bones [96,97].…”

Spatiotemporal Alterations in Gait in Humanized Transgenic Sickle Mice

“…Additionally, bone complications-associated joint pain is common in SCD with about 50% adults developing avascular osteonecrosis due to loss of blood supply to the femoral head in addition to osteoporosis and osteopenia ( 12 – 14 ). Femurs from transgenic sickle mice exhibit altered microstructure with 40% reduced mechanical strength compared to control mice ( 15 ). In addition to sudden and intractable acute pain, chronic joint and back pain in combination with reduced bone strength could contribute to difficulty in mobility and subsequent postural adjustment to compensate for the pain, i.e., change in gait ( 16 ).…”

Cranial epidural hematomas: A case series and literature review of this rare complication associated with sickle cell disease

“…29 Because of the increased intramedullary hematopoiesis leading to cortical expansion and thinning of skull bones in SCD, these bones may be particularly vulnerable to bleeding associated with infarctions. 30 Evidence of bone infarction can be seen on MRI, but the number of infarctions may be underestimated because not all patients in this report had an MRI. Nonetheless, 15 patients (60.0%), including four of the five patients who presented with periorbital edema, had clear evidence of skull bone infarction.…”

“…Outside of infancy, sickling occurs most commonly in the long bones of the humerus, followed by the tibia, and then the femur, but it can also occur less commonly in skull bones . Because of the increased intramedullary hematopoiesis leading to cortical expansion and thinning of skull bones in SCD, these bones may be particularly vulnerable to bleeding associated with infarctions . Evidence of bone infarction can be seen on MRI, but the number of infarctions may be underestimated because not all patients in this report had an MRI.…”