Additive effects of PTH and bisphosphonates on the bone healing response to metaphyseal implants in rats

Abstract

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.Material and 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 crossdependency was observed.Interpretation Because bisphosphonates mainly influence osteoclasts, and intermittent administration of

Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant

“…The finding that iPTH enhanced bone formation within our titanium implant is consistent with the beneficial effects of iPTH therapy on osseointegration seen in other models [17][18][19][20][21][22][23]35 . In our study, an increase in trabecular number, as opposed to trabecular thickness, appeared to be the primary structural change resulting from iPTH in the peri-implant region compared with the distal region.…”

“…Previous studies of in vivo models suggested that iPTH improves osseointegration [17][18][19][20][21][22][23][29][30][31][32][33][34] . Previous studies on osseointegration, however, had substantial limitations, including (1) use of large animals (rabbits, sheep, and dogs) with accompanying high cost, lower throughput 17,19,30,31,[35][36][37][38] , and greater humanitarian concerns compared with those related to small-animal models; (2) nonphysiologic implant placement such as in the medullary canal or extra-articular locations 18,[20][21][22]32,39 ; and (3) reliance on cortical bone support for stability 18,[20][21][22]40 . In the present study, we used a newly developed murine model with an intra-articular titanium implant that was loaded through the knee joint and supported by the cancellous bone bed of the proximal part of the tibia.…”

“…In previous animal models, iPTH enhanced implant osseointegration of nonphysiologically loaded cortical and cancellous bone in rabbits and rats [17][18][19][20][21][22][23] . These models fail to simulate the intra-articular environment and physiologic loading that accompany tibial cancellous fixation in total knee arthroplasty.…”

Angiotensin II Type 2 Receptor Blockade Increases Bone Mass

“…This direction has been pursued in the case of PTH (teriparatide). However, simultaneous treatment with PTH and bisphosphonate was not successful in improving bone mass levels (34,35). Furthermore, PTH treatment requires injection, and it has been limited to treat patients up to 2 years in western countries.…”

An approximate model for cancellous bone screw fixation

“…), or to change the interface between screw and bone. For example, it also appears feasible to change bone quality adjacent to Page 3 a screw post surgery, and improve pullout strength using an antiporotic drug, such as a bisphosphonate [4,34].…”