Parathyroid hormone enhances mechanically induced bone formation, possibly involving L-type voltage-sensitive calcium channels.
PTH and mechanical loading might act synergistically on bone formation. We tested the in vivo effect of the L-type voltage-sensitive calcium channel (VSCC) blocker, verapamil, on bone formation induced by human PTH-(1-34) (PTH) injection with or without mechanical loading. Adult rats were divided into eight groups: vehicle, verapamil, PTH, or verapamil plus PTH with or without mechanical loading. Verapamil (100 mg/kg) was given orally 90 min before loading. PTH (80 micro g/kg) was injected sc 30 min before loading. Loading applied to tibia and ulna for 3 min significantly increased the bone formation rate on both the endocortical surface of tibia and the periosteal surface of ulna (P < 0.0001). Treatment with PTH enhanced load-induced bone formation by 53% and 76% (P < 0.001) on the endocortical and periosteal surfaces, respectively. Treatment with verapamil suppressed load-induced bone formation rate by 77% and 59% (P < 0.01). Furthermore, verapamil suppressed bone formation in rats subjected to PTH plus loading by 74% and 68% (P < 0.0001) at the tibia and ulna, respectively. In the groups without loading, neither verapamil nor PTH treatment significantly changed any bone formation parameter. This study indicates that L-type VSCCs mediate load-induced bone formation in vivo. Furthermore, PTH enhances load-induced bone adaptation through involvement of L-type VSCCs.
Li
Jiliang
J
Department of Orthopedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Duncan
Randall L
RL
Burr
David B
DB
Gattone
Vincent H
VH
Turner
Charles H
CH
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D005260:Female; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D019379:Teriparatide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013977:Tibia / Q000187:drug effects / Q000502:physiology; D014457:Ulna / Q000187:drug effects / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology; D016474:Weight-Bearing
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010446:Peptide Fragments; D019379:Teriparatide; D014700:Verapamil; C035748:parathyroid hormone (1-34)amide