Additive effects of PTH and bisphosphonates on the bone healing response to metaphyseal implants in rats.
BACKGROUND
When PTH is used to increase the amount of bone in osteoporotic patients, combination with bisphosphonates is known to attenuate the response. This might be explained by the reduced number of remodeling sites after bisphosphonate treatment, which reduces the number of cells able to respond to PTH. However, in a repair situation after trauma, a large number of osteoblasts reside in the wound site. If their activity is no longer coupled to osteoclasts, decreased resorption by bisphosphonates and stimulation of osteoblastic activity by PTH should both (independently) increase bone formation. Thus, we hypothesized that in contrast to the case in osteoporosis treatment, PTH and bisphosphonates have an additive effect in situations involving bone regeneration.


METHODS
Stainless steel screws, either coated with biphosphonates or uncoated, were inserted in 46 rat tibias. This normally elicits a bone repair response, leading to a gradual increase in the strength of screw fixation. Half of the rats also received daily injections of teriparatide (PTH). Thus, there were 4 groups: control, bisphosphonate, PTH, and bisphosphonate plus PTH. Pull-out force and energy were measured after 2 weeks.


RESULTS
The combined treatment had the strongest effect. It doubled the pull-out force and tripled the pull-out energy, compared to untreated controls. Also, bisphosphonate or PTH alone increased the pull-out force and energy, although less. No treatment cross-dependency was observed.


CONCLUSIONS
Because bisphosphonates mainly influence osteoclasts, and intermittent administration of PTH mainly influences osteoblasts, our findings indicate that to a large extent these cells work without coupling in this model. It appears that bisphosphonates are unlikely to attenuate the response to PTH during the formation of new bone.
Aspenberg
Per
P
Section of Orthopedics, Department of Neuroscience and Locomotion, Faculty of Health Sciences, Linköping University, Linköping, Sweden. per.aspenberg@inr.liu.se
Wermelin
Karin
K
Tengwall
Pentti
P
Fahlgren
Anna
A
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D001863:Bone Screws; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology*; D017102:Fracture Healing / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide / Q000494:pharmacology*; D013977:Tibia / Q000187:drug effects
D050071:Bone Density Conservation Agents; D020099:Coated Materials, Biocompatible; D004164:Diphosphonates; D019379:Teriparatide