An update on the recent literature on sickle cell bone disease

Children's Healthcare of Atlanta and The Department of Pediatrics Emory University, Atlanta, Georgia, USA.
Current opinion in endocrinology, diabetes, and obesity (Impact Factor: 3.37). 10/2013; 20(6). DOI: 10.1097/
Source: PubMed


To summarize the findings of the recent publications on sickle cell bone disease (SBD).
Individuals with sickle cell disease (SCD) are living longer and develop progressive organ damage including SBD with age. Recent studies suggest alternative radiological diagnostics such as ultrasound and scintigraphy can detect and differentiate between different forms of SBD. MRI with or without diffusion-weighted sequences remains the gold standard. Case reports of cranio-orofacial SBD highlight the rarity of this presentation. Vitamin D deficiency is highly prevalent at all ages, but may not be an independent risk factor for avascular necrosis (AVN). Gene polymorphisms of the Annexin A gene may predict AVN in SCD. A recent study demonstrated reduced days with pain and improved physical activity quality of life following high-dose vitamin D therapy. The high rates of osteopenia and osteoporosis in SCD support the need for research addressing this rising public health problem. Lastly, results of total hip arthroplasty for AVN in SCD has improved significantly over time with the use of cementless prosthetic material and improved supportive care.
SBD remains poorly studied. Prospective randomized studies targeting predictors, diagnostics, prevention, and treatment options for SBD are sorely needed.

5 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To compare the effect of aquatic and land-based physiotherapy in reducing musculoskeletal hip and lower back pain and increasing overall physical capabilities of sickle cell disease patients.Methods Informed written consent was obtained from all volunteers who were submitted to evaluations using different functional scales: Lequesne's Algofunctional Questionnaire and Oswestry Disability Index, trunk and hip range of motion, goniometry, trunk and hip muscle strength assessment using load cell, and surface electromyography of the iliocostalis, long dorsal (longissimus), gluteus maximus, gluteus medius and tensor fasciae latae muscles. Ten patients were randomized into two groups: aquatic physiotherapy with a mean age of 42 years (range: 25–67) and conventional physiotherapy with a mean age of 49 years (range: 43–59). Both groups were submitted to a twelve-week program of two sessions weekly.ResultsAfter intervention, significant improvements were observed regarding the Lequesne index (p-value = 0.0217), Oswestry Disability Index (p-value = 0.0112), range of motion of trunk extension (p-value = 0.0320), trunk flexion muscle strength (p-value = 0.0459), hip extension and abduction muscle strength (p-value = 0.0062 and p-value = 0.0257, respectively). Range of motion of trunk and hip flexion, extension, adduction and abduction, trunk extensor muscle strength and all surface electromyography variables showed no significant statistical difference.Conclusion Physical therapy is efficient to treat musculoskeletal dysfunctions in sickle cell disease patients, irrespective of the technique; however, aquatic therapy showed a trend toward improvement in muscle strength. Further studies with a larger patient sample and longer periods of therapy are necessary to confirm these results.
    Revista Brasileira de Hematologia e Hemoterapia 11/2014; 37(2). DOI:10.1016/j.bjhh.2014.11.010
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Stem cell therapy with bone marrow-derived mononuclear cells (BMMC) is an option for improving joint function in osteonecrosis of the femoral head (ONFH). Bone marrow-derived mesenchymal stromal cell (MSC) numbers and their osteogenic differentiation are decreased in patients with ONFH. However, whether this decrease also extends to the early stages of ONFH in sickle cell disease (SCD) is still unclear. We conducted a phase I/II, non-controlled study to determine efficacy and safety of BMMCs implantation using a minimally invasive technique in SCD patients with ONFH. Eighty-nine patients were recruited and followed up for sixty months after the surgery. Clinical and radiographic findings were assessed, and data were completed by in vitro analysis. At the final follow-up (60 months), there was a significant improvement in clinical joint symptoms and pain relief as measured by the Harris Hip Score (P = 0.0005). In addition, after the BMMC implantation procedure, radiographic assessment showed disease stabilization and only 3.7 % of the treated patients did not achieve a satisfactory clinical result. The amount of fibroblast colony-forming units was 28.2 ± 13.9 / 1 million BMMCs after concentration. Flow cytometry analysis showed a significantly higher number of hematopoietic stem / endothelial progenitor cell markers in concentrated BMMCs when compared with bone marrow aspirate (BMA), indicating an enrichment of these cell types. Isolated MSCs from SCD patients with pre-collapse ONFH maintained the replicative capacity without significant loss of their specific biomolecular characteristics, multi-differentiation potential, and osteogenic differentiation activities. Cytokines and growth factors (IL8, TGF-beta, SDF-1alpha and VEGF) that mediate endogenous bone regeneration were also produced by expanded MSCs from SCD patients. The autologous BMMCs implantation with minimally invasive technique resulted in significant pain relief and halted the progression of early stages of ONFH in SCD patients. MSCs from SCD patients display biological properties that may add to the efficiency of surgical treatment in ONFH. In summary, our results indicate that infusion of BMMC enriched with stem/progenitor cells is a safe and effective treatment for the early stages of ONFH in SCD patients. NCT02448121 - Registered 15 May 2015.
    Stem Cell Research & Therapy 05/2015; 6(1):110. DOI:10.1186/s13287-015-0105-2 · 3.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects the large part of SCD patients and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL) and osteoclast recruitment (Rank) with up-regulation of Il6 as pro-resorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). In order to interfer with the development of SBD, zoledronic-acid, a potent inhibitor of osteoclast activity/osteoclastogenesis and promoter of osteogenic lineage, was used in H/R exposed mice. Zoledronic-acid markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc) and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared to either normoxic or single H/R episode SCD mice. Zoledronic-acid used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment and increased osteoclast activity resulted from local hypoxia, oxidative stress and the release of pro-resorptive cytokine such as IL6. Zoledronic acid might act on both osteoclast and osteoblast compartment as multimodal therapy to prevent SBD. Copyright © 2015 American Society of Hematology.
    Blood 09/2015; DOI:10.1182/blood-2015-04-641969 · 10.45 Impact Factor