Altered mechanosensitivity can explain the substantially increased bone mass in hypoparathyroidism

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

81 Downloads (Pure)

Abstract

Hypoparathyroidism (HypoPTH) is characterized by low or absent parathyroid hormone (PTH). It is mainly associated with a drastic suppression of bone turnover by around 80% (Rubin et al., 2008) and a substantial increase in bone mass in the range of 10-32% (Rubin et al., 2008; Abugassa et al., 1993). It is known that PTH can affect bone cells, but how it would lead to such a high net formation in HypoPTH is unclear. In hyperparathyroidism studies it was found that elevated PTH up regulates RANK production in osteoblasts causing increased bone resorption via binding to RANKL expressed on osteoclasts. This suggests that during HypoPTH, RANK would be down regulated thus reducing turnover, which is in agreement with clinical measurements (Rubin et al., 2008). As a result of this reduced turnover, an increase in bone mass would be expected due to filling of the resorption space. However, given that the resorption space accounts only for approx. 5% of the total volume, this effect cannot fully explain the substantial gain in bone mass during HypoPTH As an additional effect of PTH on bone cells, we hypothesize that the sensitivity of the cells to mechanical loading is altered, as already proposed by Frost (Frost, 1987). Support for this hypothesis came later from experiments in which it was shown that osteoblast-like cells are more sensitive to mechanical stimulation in vitro (Ryder and Duncan, 2000; Carvalho et al, 1994) and in vivo (Chow et al., 1998) when PTH is added. To investigate if this hypothesis can explain the marked increase in bone mass seen with HypoPTH, we simulated the proposed effects of HypoPTH using a well established computer model for the simulation of bone remodeling. Simulations were performed for models representing bone biopsies obtained from the iliac of HypoPTH patients at different time points and compared to experimental data.
Original languageEnglish
Title of host publicationProceedings of the ASME 2011 Summer Bioengineering Conference, June 22-25, Nemacolin Woodlands Resort, Farmington, Pennsylvania, USA
PublisherAmerican Society of Mechanical Engineers
Publication statusPublished - 2011
EventASME 2011 Summer Bioengineering Conference (SBC 2011) - Farmington, United States
Duration: 22 Jun 201125 Jun 2011
http://www.asmeconferences.org/sbc2011/

Conference

ConferenceASME 2011 Summer Bioengineering Conference (SBC 2011)
Abbreviated titleSBC 2011
CountryUnited States
CityFarmington
Period22/06/1125/06/11
Other
Internet address

Fingerprint Dive into the research topics of 'Altered mechanosensitivity can explain the substantially increased bone mass in hypoparathyroidism'. Together they form a unique fingerprint.

Cite this