Do antiosteoporotic drugs improve bone regeneration in vivo?

• Published in: European journal of trauma and emergency surgery (Munich : 2007) Vol. 46; no. 2; pp. 287 - 299
• Main Authors: Leiblein, Maximilian, Henrich, Dirk, Fervers, Florian, Kontradowitz, Kerstin, Marzi, Ingo, Seebach, Caroline
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2020; Springer Nature B.V
• Subjects: Absorptiometry, Photon; Alendronate - pharmacology; Alkaline Phosphatase - drug effects; Alkaline Phosphatase - metabolism; Animals; Biomechanical Phenomena - drug effects; Biomechanics; Blotting, Western; Bone Density - drug effects; Bone Density Conservation Agents - pharmacology; Bone Morphogenetic Protein 2 - drug effects; Bone Morphogenetic Protein 2 - genetics; Bone Regeneration - drug effects; Bony Callus - diagnostic imaging; Bony Callus - metabolism; Bony Callus - pathology; Calcium-Regulating Hormones and Agents - pharmacology; Collagen Type I - drug effects; Collagen Type I - metabolism; Critical Care Medicine; Emergency medical care; Emergency Medicine; Female; Femur - diagnostic imaging; Femur - drug effects; Femur - pathology; Femur - surgery; Fractures; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Intensive; Interleukin-6 - genetics; Macrophage Colony-Stimulating Factor - drug effects; Macrophage Colony-Stimulating Factor - genetics; Medicine; Medicine & Public Health; Original Article; Osteocalcin - drug effects; Osteocalcin - genetics; Osteogenesis - drug effects; Osteogenesis - genetics; Osteogenesis, Distraction; Osteoporosis; Parathyroid Hormone - pharmacology; Raloxifene Hydrochloride - pharmacology; RANK Ligand - drug effects; RANK Ligand - genetics; Rats; Reverse Transcriptase Polymerase Chain Reaction; Simvastatin - pharmacology; Sports Medicine; Surgery; Surgical Orthopedics; Thiophenes - pharmacology; Tomography, X-Ray Computed; Traumatic Surgery; Osteoporosis; Parathormone; Alendronate; Simvastatin; Raloxifen; Strontium ranelate; Femur defect
• ISSN: 1863-9933; 1863-9941
• DOI: 10.1007/s00068-019-01144-y

Purpose Treatment of complex fractures in the elderly is a challenge for operative reconstruction due to degraded bone structure. Early peri-operative bone anabolic treatment could improve new bone formation, avoid implant loosening and accelerate fracture healing. Methods To compare the osteoanabolic potential of different drugs after distraction osteogenesis, 168 female Sprague–Dawley rats underwent lengthening of the right femur using a monolateral external fixator. Animals were randomly divided into six groups: vehicle-injected group, PTH(1-34), raloxifen, strontium ranelate, alendronate and simvastatin. Histomorphometry, CT-scanning, DEXA- and biomechanical analysis were performed to evaluate new bone formation, callus volume, mineralisation and biomechanical strength. Expression of bone metabolic mediators and differentiation indicators of distracted and intact bone were examined by RT-PCR and western blot. Results Histological analysis showed significant increase of the bone mass after treatment with PTH(1-34), raloxifen and strontium ranelate ( p  = 0.02). Raloxifen increased bone mineral content (BMC) of the whole distracted femur significantly ( p  = 0.007). Callus volume was significantly larger in the PTH(1-34), raloxifen and simvastatin groups ( p  = 0.001) compared to control. Ultimate load of distracted new formed bone was increased in PTH(1-34) and raloxifen groups. It seems that PTH(1-34) and raloxifen have a stronger effect on bone where a repair response is activated. Strontium ranelate demonstrates similar effects to PTH regarding new bone formation but shows low values for mineralisation and biomechanical strength. Conclusion This study suggests that peri-operative treatment of complex and/or osteoporotic fractures with PTH(1-34) and raloxifen might be useful as a stimulator of bone formation and mineralisation to shorten the consolidation time in humans.