Parathyroid Hormone Enhances Mechanically Induced Bone Formation, Possibly Involving L-Type Voltage-Sensitive Calcium Channels

• Published in: Endocrinology (Philadelphia) 2003-04, Vol.144 (4), p.1226-1233
• Main Authors: Li, Jiliang, Duncan, Randall L, Burr, David B, Gattone, Vincent H, Turner, Charles H
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone growth; Calcium; Calcium Channel Blockers - pharmacology; Calcium channels; Calcium channels (L-type); Calcium channels (voltage-gated); Calcium Channels, L-Type - physiology; Electric potential; Female; Fundamental and applied biological sciences. Psychology; In vivo methods and tests; Load distribution; Mechanical loading; Osteogenesis; Osteogenesis - drug effects; Osteogenesis - physiology; Parathyroid hormone; Peptide Fragments - pharmacology; Rats; Rats, Sprague-Dawley; Space life sciences; Stress, Mechanical; Teriparatide - analogs & derivatives; Teriparatide - pharmacology; Tibia; Tibia - drug effects; Tibia - physiology; Ulna; Ulna - drug effects; Ulna - physiology; Verapamil; Verapamil - pharmacology; Voltage; Weight-Bearing
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2002-220821

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 μg/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.