PMID- 18715136
OWN - NLM
STAT- MEDLINE
DCOM- 20090424
LR  - 20181201
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 24
IP  - 1
DP  - 2009 Jan
TI  - Bisphosphonate therapy ameliorates hearing loss in mice lacking osteoprotegerin.
PG  - 43-9
LID - 10.1359/jbmr.080812 [doi]
AB  - Three auditory ossicles including the malleus, incus, and stapes conduct sound in 
      the middle ear from the tympanic membrane to the inner ear. Auditory ossicles are 
      massively resorbed by osteoclasts in Opg(-/-) mice, which lack osteoprotegerin 
      (OPG), a soluble decoy receptor for the osteoclastogenic cytokine RANKL. Opg(-/-) 
      mice exhibit progressive hearing loss and are a model for juvenile Paget's 
      disease. However, effects of antiresorptive treatment on auditory ossicles and on 
      hearing function in Opg(-/-) mice are unknown. We intraperitoneally injected 
      Opg(-/-) mice with bisphosphonate risedronate 5 d/wk for 9 wk. Morphology of 
      auditory ossicles was examined microscopically, radiographically, and 
      histologically. Hearing function was monitored by measuring the auditory brain 
      stem response (ABR). Control Opg(-/-) mice exhibited thinning of all three 
      ossicles and tibia. In contrast, risedronate treatment significantly inhibited 
      bone loss in auditory ossicles as well as in long bones of Opg(-/-) mice. Bony 
      fusion of the junction between the stapes and the otic capsule was reduced after 
      treatment. Moreover, ABR measurement showed that hearing in Opg(-/-) mice was 
      significantly improved by risedronate treatment. These data suggest that hearing 
      loss in pathologies characterized by excessive resorption of the auditory 
      ossicles may be prevented by bisphosphonates.
FAU - Kanzaki, Sho
AU  - Kanzaki S
AD  - Department of Otolaryngology, School of Medicine, Keio University, Tokyo, Japan.
FAU - Takada, Yasunari
AU  - Takada Y
FAU - Ogawa, Kaoru
AU  - Ogawa K
FAU - Matsuo, Koichi
AU  - Matsuo K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Diphosphonates)
RN  - 0 (Osteoprotegerin)
RN  - KM2Z91756Z (Risedronic Acid)
RN  - M2F465ROXU (Etidronic Acid)
SB  - IM
MH  - Animals
MH  - Bone Density Conservation Agents/therapeutic use
MH  - Cochlea/drug effects/physiology
MH  - Diphosphonates/*therapeutic use
MH  - Etidronic Acid/analogs & derivatives/pharmacology
MH  - Evoked Potentials, Auditory, Brain Stem
MH  - Female
MH  - Hearing
MH  - Hearing Loss/*drug therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Osteoprotegerin/*therapeutic use
MH  - Risedronic Acid
MH  - Time Factors
EDAT- 2008/08/22 09:00
MHDA- 2009/04/25 09:00
CRDT- 2008/08/22 09:00
PHST- 2008/08/22 09:00 [entrez]
PHST- 2008/08/22 09:00 [pubmed]
PHST- 2009/04/25 09:00 [medline]
AID - 10.1359/jbmr.080812 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2009 Jan;24(1):43-9. doi: 10.1359/jbmr.080812.