title: Low dose PTH improves metaphyseal bone healing more when muscles are paralyzed.
abstract: Stimulation of bone formation by PTH is related to mechanosensitivity. The response to PTH treatment in intact bone could therefore be blunted by unloading. We studied the effects of mechanical loading on the response to PTH treatment in bone healing. Most fractures occur in the metaphyses, therefor we used a model for metaphyseal bone injury. One hind leg of 20 male SD rats was unloaded via intramuscular botulinum toxin injections. Two weeks later, the proximal unloaded tibia had lost 78% of its trabecular contents. At this time-point, the rats received bilateral proximal tibiae screw implants. Ten of the 20 rats were given daily injections of 5 μg/kg PTH (1-34). After two weeks of healing, screw fixation was measured by pull-out, and microCT of the distal femur cancellous compartment was performed. Pull-out force provided an estimate for cancellous bone formation after trauma. PTH more than doubled the pull-out force in the unloaded limbs (from 14 to 30 N), but increased it by less than half in the loaded ones (from 30 to 44 N). In relative terms, PTH had a stronger effect on pull-out force in unloaded bone than in loaded bone (p=0.03). The results suggest that PTH treatment for stimulation of bone healing does not require simultaneous mechanical stimulation.
authors.affiliation: Orthopaedics, Department of Clinical and Experimental Medicine, Linköping University, 581 85 Linköping, Sweden. Electronic address: olof.sandberg@liu.se.
authors.forename: Olof
authors.initials: O
authors.lastname: Sandberg
authors.affiliation: Orthopaedics, Department of Clinical and Experimental Medicine, Linköping University, 581 85 Linköping, Sweden; Department of Orthopedic Surgery, University of California, San Diego, USA.
authors.forename: Brandon R
authors.initials: BR
authors.lastname: Macias
authors.affiliation: Orthopaedics, Department of Clinical and Experimental Medicine, Linköping University, 581 85 Linköping, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Aspenberg
mesh_terms: D000818:Animals; D001905:Botulinum Toxins / Q000633:toxicity; D017102:Fracture Healing / Q000187:drug effects*; D050723:Fractures, Bone / Q000188:drug therapy*; D008297:Male; D009123:Muscle Hypotonia / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010281:Parathyroid Hormone; D001905:Botulinum Toxins
keywords: Botulinum toxin; Fracture healing; Mechanical loading; Metaphyseal fracture; Parathyroid hormone