title: No effect of verapamil on the local bone response to in vivo mechanical loading.
abstract: Verapamil, a calcium channel blocker, alters the intracellular calcium concentration in bone cells in vitro, while mechanical loading stimulates calcium channels. The purpose of this study was to examine the effect of systemic verapamil treatment on the bone response to in vivo external mechanical loading. Female rats (age 5-6 months) were divided into six groups. Half were verapamil treated (0.75 mg/ml drinking water) for 12 weeks. After 8 weeks of treatment, the right tibia was loaded by a four-point bending device. In one set of verapamil and control groups, the right tibia was loaded at 31.8 +/- 0.2 N (36 cycles, 2 Hz, 3 d/wk) for four weeks. A second set was loaded at 40.1 +/- 0.3 N and the third set remained nonloaded. Tibial cortical bone formation and femur bone mineral density (BMD) were evaluated. With loading, bone formation was similarly elevated in loaded tibia of verapamil and control rats (P < 0.003). However, periosteal bone formation (P < 0.001) in the nonloaded tibia, and femoral diaphysis BMD (P < 0.04) were greater in verapamil rats than in controls. We conclude that verapamil, in the dose given, does not interfere with mechanical loading (30, 40 N) at the loaded site and that the voltage-dependent calcium channels, blocked by verapamil, are not significantly involved in the local bone response to increased strain in female rats. However, verapamil increased bone formation and BMD at nonloaded sites of loaded rats. Previously unknown systemic or regional factors associated with loading may explain the potential mechanisms for this interaction and need further investigation.
authors.affiliation: Department of Orthopaedic Surgery, Karolinska Institute, Huddinge University Hospital, Sweden. eva.samnegard@karo.ki.se
authors.forename: E
authors.initials: E
authors.lastname: Samnegård
authors.forename: D M
authors.initials: DM
authors.lastname: Cullen
authors.forename: M P
authors.initials: MP
authors.lastname: Akhter
authors.forename: D B
authors.initials: DB
authors.lastname: Kimmel
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010521:Periosteum / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology*; D016474:Weight-Bearing
chemical_list: D002121:Calcium Channel Blockers; D014700:Verapamil