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The H2 blocker famotidine suppresses progression of ossification of the posterior longitudinal ligament in a mouse model.

Maeda Y, Yamamoto K, Yamakawa A, Aini H, Takato T, Chung UI, Ohba S - RMD Open (2015)

Bottom Line: Radiological and survival rate analyses were performed to assess the effects of famotidine on OPLL-like lesions and mortality in Enpp1 (ttw/ttw) mice.Oral administration of famotidine suppressed the progression of OPLL-like ectopic ossification and reduced mortality in Enpp1 (ttw/ttw) mice when administration began at 4 weeks of age, early in the development of ossification.This study points to the use of famotidine as a disease-modifying drug for ectopic ossification of spinal soft tissue, including OPLL.

View Article: PubMed Central - PubMed

Affiliation: Department of Sensory and Motor System Medicine, The University of Tokyo Graduate School of Medicine, Tokyo , Japan ; Division of Clinical Biotechnology , The University of Tokyo Graduate School of Medicine , Tokyo , Japan.

ABSTRACT

Background: Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common human myelopathy that leads to spinal cord compression. No disease-modifying drug for OPLL has been identified, whereas surgery and conservative management have been established.

Objectives: To evaluate the therapeutic potential of the H2 blocker famotidine for ectopic ossification in the cervical spine in an OPLL mouse model.

Methods: The H2 blocker famotidine was orally administered to Enpp1 (ttw/ttw) mice, a model of OPLL, at either 4 or 15 weeks of age. Radiological and survival rate analyses were performed to assess the effects of famotidine on OPLL-like lesions and mortality in Enpp1 (ttw/ttw) mice.

Results: Oral administration of famotidine suppressed the progression of OPLL-like ectopic ossification and reduced mortality in Enpp1 (ttw/ttw) mice when administration began at 4 weeks of age, early in the development of ossification.

Conclusions: This study points to the use of famotidine as a disease-modifying drug for ectopic ossification of spinal soft tissue, including OPLL.

No MeSH data available.


Related in: MedlinePlus

Radiological findings on the development of ossification of the posterior longitudinal ligament (OPLL)-like ectopic ossification in famotidine-treated Enpp1ttw/ttw mice. (A) Representative micro-CT images of cervical spines of Enpp1ttw/ttw mice treated with or without famotidine. Famotidine was orally administered from 4 weeks of age. Micro-CT was performed at the indicated weeks of age. Bars=1 mm. (B) Quantitative analyses of OPLL-like ectopic ossification in Enpp1ttw/ttw mice treated with or without famotidine from 4 weeks of age. Four male and female mice were analysed in each group (n=8). X-axes indicate ages of mice. *p<0.05.
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RMDOPEN2015000068F1: Radiological findings on the development of ossification of the posterior longitudinal ligament (OPLL)-like ectopic ossification in famotidine-treated Enpp1ttw/ttw mice. (A) Representative micro-CT images of cervical spines of Enpp1ttw/ttw mice treated with or without famotidine. Famotidine was orally administered from 4 weeks of age. Micro-CT was performed at the indicated weeks of age. Bars=1 mm. (B) Quantitative analyses of OPLL-like ectopic ossification in Enpp1ttw/ttw mice treated with or without famotidine from 4 weeks of age. Four male and female mice were analysed in each group (n=8). X-axes indicate ages of mice. *p<0.05.

Mentions: All 16 Enpp1ttw/ttw mice tested exhibited ectopic ossification of the cruciform ligament in the atlanto-occipital area by 8 weeks of age, as previously reported11; the extent of ossification increased throughout the observation period (figures 1A,B and 2). The ectopic ossification was smaller in the famotidine group than in controls (figure 1A). Quantitative analyses revealed that volume and mineral content of calcified ligaments were both significantly smaller in the famotidine group than in controls (figure 1B), but mineral density was not significantly different. Figure 2 shows individual variability of quantitative data in each group; female mice tended to have more severe ectopic ossification than male mice (see online supplementary figure S1).


The H2 blocker famotidine suppresses progression of ossification of the posterior longitudinal ligament in a mouse model.

Maeda Y, Yamamoto K, Yamakawa A, Aini H, Takato T, Chung UI, Ohba S - RMD Open (2015)

Radiological findings on the development of ossification of the posterior longitudinal ligament (OPLL)-like ectopic ossification in famotidine-treated Enpp1ttw/ttw mice. (A) Representative micro-CT images of cervical spines of Enpp1ttw/ttw mice treated with or without famotidine. Famotidine was orally administered from 4 weeks of age. Micro-CT was performed at the indicated weeks of age. Bars=1 mm. (B) Quantitative analyses of OPLL-like ectopic ossification in Enpp1ttw/ttw mice treated with or without famotidine from 4 weeks of age. Four male and female mice were analysed in each group (n=8). X-axes indicate ages of mice. *p<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612692&req=5

RMDOPEN2015000068F1: Radiological findings on the development of ossification of the posterior longitudinal ligament (OPLL)-like ectopic ossification in famotidine-treated Enpp1ttw/ttw mice. (A) Representative micro-CT images of cervical spines of Enpp1ttw/ttw mice treated with or without famotidine. Famotidine was orally administered from 4 weeks of age. Micro-CT was performed at the indicated weeks of age. Bars=1 mm. (B) Quantitative analyses of OPLL-like ectopic ossification in Enpp1ttw/ttw mice treated with or without famotidine from 4 weeks of age. Four male and female mice were analysed in each group (n=8). X-axes indicate ages of mice. *p<0.05.
Mentions: All 16 Enpp1ttw/ttw mice tested exhibited ectopic ossification of the cruciform ligament in the atlanto-occipital area by 8 weeks of age, as previously reported11; the extent of ossification increased throughout the observation period (figures 1A,B and 2). The ectopic ossification was smaller in the famotidine group than in controls (figure 1A). Quantitative analyses revealed that volume and mineral content of calcified ligaments were both significantly smaller in the famotidine group than in controls (figure 1B), but mineral density was not significantly different. Figure 2 shows individual variability of quantitative data in each group; female mice tended to have more severe ectopic ossification than male mice (see online supplementary figure S1).

Bottom Line: Radiological and survival rate analyses were performed to assess the effects of famotidine on OPLL-like lesions and mortality in Enpp1 (ttw/ttw) mice.Oral administration of famotidine suppressed the progression of OPLL-like ectopic ossification and reduced mortality in Enpp1 (ttw/ttw) mice when administration began at 4 weeks of age, early in the development of ossification.This study points to the use of famotidine as a disease-modifying drug for ectopic ossification of spinal soft tissue, including OPLL.

View Article: PubMed Central - PubMed

Affiliation: Department of Sensory and Motor System Medicine, The University of Tokyo Graduate School of Medicine, Tokyo , Japan ; Division of Clinical Biotechnology , The University of Tokyo Graduate School of Medicine , Tokyo , Japan.

ABSTRACT

Background: Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common human myelopathy that leads to spinal cord compression. No disease-modifying drug for OPLL has been identified, whereas surgery and conservative management have been established.

Objectives: To evaluate the therapeutic potential of the H2 blocker famotidine for ectopic ossification in the cervical spine in an OPLL mouse model.

Methods: The H2 blocker famotidine was orally administered to Enpp1 (ttw/ttw) mice, a model of OPLL, at either 4 or 15 weeks of age. Radiological and survival rate analyses were performed to assess the effects of famotidine on OPLL-like lesions and mortality in Enpp1 (ttw/ttw) mice.

Results: Oral administration of famotidine suppressed the progression of OPLL-like ectopic ossification and reduced mortality in Enpp1 (ttw/ttw) mice when administration began at 4 weeks of age, early in the development of ossification.

Conclusions: This study points to the use of famotidine as a disease-modifying drug for ectopic ossification of spinal soft tissue, including OPLL.

No MeSH data available.


Related in: MedlinePlus