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Molecular, phenotypic aspects and therapeutic horizons of rare genetic bone disorders.

Faruqi T, Dhawan N, Bahl J, Gupta V, Vohra S, Tu K, Abdelmagid SM - Biomed Res Int (2014)

Bottom Line: Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP.Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed.There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.

View Article: PubMed Central - PubMed

Affiliation: Nova Southeastern University Health Sciences Division, Fort-Lauderdale-Davie, FL 33314, USA.

ABSTRACT
A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.

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Pathogenesis of GD and potential therapeutic interventions.
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fig4: Pathogenesis of GD and potential therapeutic interventions.

Mentions: Today, there are no set guidelines for the treatment and management of GD. To prevent the production of IL-6 by proliferating vasculature, radiation therapy, and chemotherapy with interferon α-2b is commonly employed [23], although it is contraindicated in growing children. Different treatment modalities that include surgical resection, arthroplasty, calcitonin, calcium, and vitamin D have been utilized and the results are variable. Bone grafts have also been used, with a debatable successful rate. Hirayama et al. [16] reported that, despite the use of a bone graft, GD recurred in the grafted bone. In a revealing case described by Hammer et al. [24], clinical improvement followed by stabilization of the disease occurred solely after use of low-dose pamidronate therapy. To our knowledge, this is the only known case of a bisphosphonate monotherapy leading to remission of GD (Figure 4).


Molecular, phenotypic aspects and therapeutic horizons of rare genetic bone disorders.

Faruqi T, Dhawan N, Bahl J, Gupta V, Vohra S, Tu K, Abdelmagid SM - Biomed Res Int (2014)

Pathogenesis of GD and potential therapeutic interventions.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230237&req=5

fig4: Pathogenesis of GD and potential therapeutic interventions.
Mentions: Today, there are no set guidelines for the treatment and management of GD. To prevent the production of IL-6 by proliferating vasculature, radiation therapy, and chemotherapy with interferon α-2b is commonly employed [23], although it is contraindicated in growing children. Different treatment modalities that include surgical resection, arthroplasty, calcitonin, calcium, and vitamin D have been utilized and the results are variable. Bone grafts have also been used, with a debatable successful rate. Hirayama et al. [16] reported that, despite the use of a bone graft, GD recurred in the grafted bone. In a revealing case described by Hammer et al. [24], clinical improvement followed by stabilization of the disease occurred solely after use of low-dose pamidronate therapy. To our knowledge, this is the only known case of a bisphosphonate monotherapy leading to remission of GD (Figure 4).

Bottom Line: Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP.Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed.There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.

View Article: PubMed Central - PubMed

Affiliation: Nova Southeastern University Health Sciences Division, Fort-Lauderdale-Davie, FL 33314, USA.

ABSTRACT
A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.

Show MeSH
Related in: MedlinePlus