Honey, I Shrunk my Bones!

 

    Vanishing bone disease, clinically known as Gorham-Stout Disease is an extraordinarily rare bone disease characterized by progressive osteolysis (bone loss) and increased proliferation of lymphatic tissue that is in close contact with the bones (National Organization for Rare Disorders). This destruction and reabsorption of bone releases minerals into the blood stream, most notable calcium whereas hypercalcemia can lead to osteoporosis, arthritis, kidney stones and impaired heart and brain function (Sadiq, Naganathan & Badireddy, 2021). The areas most commonly affected by GSD are, the ribs, spine, pelvis, skull, collarbone and jaw (National Organization for Rare Disorders). The pathophysiological understandings of GSD are concerned with an error in development of the lymphatic system, whereas bones are penetrated by lymphatic tissue, broken down, and then replaced by fibrous connective tissue (Lala et al., 2013). As a result of this phenomenon, patients with GSD often experience drastic bone deformities, vast disabilities, and are often immunocompromised, resulting in a plethora of life threatening complications (Dellinger, Garg & Olsen, 2014). Depending on the part of the body affected diagnosis can differ, but areas associated with the thoracic cage, head and neck region are considered the most severe and often result in a grim prognosis.

    While a direct factor for the motivation of lymphatic tissue to proliferate in such a manner has not been uncovered, laboratory research has alluded a possible growth factor (VEGF: Vascular Endothelial Growth Factor) that can be correlated lymphatic vessel and bone development, as well as bone destruction (Garbers, Reuther & Delling, 2011). In further referencing the destruction of bone tissue in GSD patients, osteoclast activity can be measured via CTX-1 and interleukin-6 levels in the blood stream (Lala et al., 2013). In layman’s terms, these factors have been shown to be in increased concentration in patients with GSD, which explains the increase in osteoclast activity. 

    There is very little literature on GSD and even fewer research studies, resulting in its frequent misdiagnosis and or oftentimes even going undiagnosed (National Organization for Rare Disorders). GSD does not disproportionately affect any certain population but is usually diagnosed in children and adults before the age of forty, although cases have fallen on either side of that range as well (National Organization for Rare Disorders). Treatment options are minimal, but bisphosphonate (drugs that slow bone loss) therapy and surgical intervention in the form of joint replacements have proven hopeful (Garbers, Reuther & Delling, 2011).

 

References

Blei, F., Dellinger, M. T., & Kelly, J. (2017). Gorham-Stout Disease. raredisases.org. Retrieved October 1, 2021, from https://rarediseases.org/rare-diseases/gorham-stout-disease/.

Dellinger MT, Garg N, Olsen BR. Viewpoints on vessels and vanishing bones in Gorham-Stout disease. Bone. 2014 Jun;63:47-52. doi: 10.1016/j.bone.2014.02.011. Epub 2014 Feb 26. PMID: 24583233.

Garbers E, Reuther F, Delling G. Report of a rare case of gorham-stout disease of both shoulders: bisphosphonate treatment and shoulder replacement. Case Rep Rheumatol. 2011;2011:565142. doi: 10.1155/2011/565142. Epub 2011 Oct 19. PMID: 22937447; PMCID: PMC3420766.

Lala S, Mulliken JB, Alomari AI, Fishman SJ, Kozakewich HP, Chaudry G. Gorham-Stout disease and generalized lymphatic anomaly--clinical, radiologic, and histologic differentiation. Skeletal Radiol. 2013 Jul;42(7):917-24. doi: 10.1007/s00256-012-1565-4. Epub 2013 Jan 31. PMID: 23371338.

Sadiq NM, Naganathan S, Badireddy M. Hypercalcemia. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430714/