The effects of risedronate and exercise on osteoporotic lumbar rat vertebrae and their sensory innervation.
METHODS
Investigation of sensory innervation of rat osteoporotic lumbar vertebrae using in vitro and in vivo models.


OBJECTIVE
To investigate (1) sensory innervation of osteoporotic rat vertebrae, (2) effects of risedronate on sensory neurons, (3) effects of osteoporosis treatment on bone mineral densities (BMDs) and the sensory innervation.


BACKGROUND
Osteoporotic patients without fractures sometimes experience vague low back pain of unknown origin. The mechanisms of osteoporosis treatments against the pain are unclear.


METHODS
(1) The expression of calcitonin gene-related peptide (CGRP) immunoreactive (-ir) or transient receptor potential vanilloid 1 (TRPV1)-ir nerve fibers in vertebrae and dorsal root ganglions (DRG) innervating L3 vertebrae of Sprague Dawley rats labeled with neurotracer were examined in control, sham, and ovariectomized (OVX) rats. (2) Cultured rat neonate DRG neurons in media containing different concentrations of risedronate were immunostained for CGRP, and we measured its activity using axonal length and proportion of CGRP-ir neurons. (3) BMDs and CGRP expression in DRG neurons innervating L3 vertebrae were examined in the following 5 groups: sham (treated with saline), OVX (saline), OVX+EXE (treadmill exercise), OVX+RIS (risedronate), and OVX+RIS+EXE (risedronate and exercise).


RESULTS
(1) A few CGRP-ir or TRPV1-ir nerve fibers were observed in the bone marrow. CGRP or TRPV1 expression in DRG was elevated in the OVX group (P < 0.05). (2) The axonal length and proportion of CGRP-ir neurons were dose-dependently suppressed (P < 0.05). (3) BMDs improved and the CGRP expression decreased in the risedronate-treated groups (P < 0.05), especially in the OVX+RIS+EXE group.


CONCLUSIONS
Sensory innervation of osteoporotic rat vertebrae showed increased expression of CGRP and TRPV1 in DRG neurons. Risedronate suppressed activity of CGRP-ir neurons in vitro, improved BMD, and decreased CGRP expression, especially together with exercise in vivo.
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. sumihisa@silver.email.ne.jp
Sumihisa
S
Orita
Seiji
S
Ohtori
Takana
T
Koshi
Masaomi
M
Yamashita
Kazuyo
K
Yamauchi
Gen
G
Inoue
Munetaka
M
Suzuki
Yawara
Y
Eguchi
Hiroto
H
Kamoda
Gen
G
Arai
Tetsuhiro
T
Ishikawa
Masayuki
M
Miyagi
Nobuyasu
N
Ochiai
Shunji
S
Kishida
Masashi
M
Takaso
Yasuchika
Y
Aoki
Tomoaki
T
Toyone
Kazuhisa
K
Takahashi
D000344:Afferent Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001416:Back Pain / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002478:Cells, Cultured; D004195:Disease Models, Animal; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000294:innervation*; D009619:Nociceptors / Q000166:cytology / Q000473:pathology; D010024:Osteoporosis / Q000150:complications* / Q000503:physiopathology / Q000628:therapy*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068296:Risedronic Acid; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology
D050071:Bone Density Conservation Agents; D000068296:Risedronic Acid; D012968:Etidronic Acid