Bone Abstracts

Metatropic dysplasia (MD) was first described by Maroteaux et al. in 1966. Its name was derived from the Greek word metatropos which means ‘changing pattern’ because individuals with this diagnosis begin life with a short-limbed dysplasia and a long trunk with narrow chest, and over time their dysplasia becomes short-trunked due to progressive kyphoscoliosis¹. It is now recognized that MD is caused by gain-of-function mutations in transient receptor potential vanilloid 4 (TRPV4) and belongs to a family of dysplasias which includes: spondylometaphyseal dysplasia, Kozlowski type (SMDK), and brachyolmia². TRPV4 is a non-selective cation channel, important in the regulation of intracellular calcium. It is widely expressed in human nervous, urinary, respiratory, and musculoskeletal systems³. In our clinic, it became apparent over time that there was a higher than expected fracture frequency in MD. To explore further we designed an Institutional Review Board approved protocol for a detailed retrospective review of this patient population. Of the 20 patients evaluated at our institution in last 9 years with MD or SMDK, there were ten males and ten females. 8/20 (40%) of patients had at least one fracture, and 5/20 (25%) of patients had two or more fractures. Evidence of increased bone turnover, with elevated TRAP, NTX and osteocalcin levels were noted. When TRPR4 is over-expressed in osteoclasts in transgenic mice, increased osteoclastic numbers and increased resorption activity were noted. This resulted in bone loss and decreased bone mass in these mice⁴. Taken together with our observations, it suggests that MD is not only a disorder of the growth plate leading to dwarfism, but also a disorder of bone leading to osteopenia and fracture.

References

1. Boden SD. et al. Metatropic dwarfism. J Bone Joint Surg Am. 1987. 69(2):174–84.

2. Krakow D. et al. Mutations in the Gene Encoding TRPV4 Produce Spondylometaphyseal Dysplasia, Kozlowski Type and MD. Am J Hum Gen. 2009. 84(3):307–315.

3. Everaets et al. TRPV4: from structure to disease. Prog Biophys Mol Biol. 2010. 103(1):2–17.

4. Masuyama R. et al. Calcium/calmodulin-signaling supports TRPV4 activation in osteoclasts and regulates bone mass. J Bone Miner Res. 2012.27(8):1708–21.

Disclosure: The authors declared no competing interests.