Anti-RANKL treatment improves screw fixation in cancellous bone in rats

Bernhardsson, Magnus; Sandberg, Olof; Aspenberg, Per

doi:10.1016/j.injury.2015.02.011

Cited by 30 publications

(33 citation statements)

References 20 publications

(26 reference statements)

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“…This new‐formed bone will form a “threaded nut” that resists the pull‐out force. The force will, therefore, be a measure of the amount and quality of the new bone (Fig ) . Osseointegration has little effect on the screw pull out force .…”

Section: Discussionmentioning

confidence: 99%

“…26 In comparison, screw pull-out models might have less variability, and are quite sensitive to bone anabolic or antiresorptive treatment. [27][28][29][30][31] Partial osteotomies allow for the study of metaphyseal fracture healing under variable conditions and can add valuable information. 32,33 A limitation is that the approach does not allow for mechanical evaluation.…”

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confidence: 99%

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Earlier effect of alendronate in mouse metaphyseal versus diaphyseal bone healing

Sandberg

Bernhardsson

Aspenberg

2016

Journal Orthopaedic Research

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Abstractwas tested by a 3-way Anova (time, site, and drug). The ultimate force was increased by 22 bisphosphonate treatment in both models. There was a significant interaction between time, 23 site and drug (p < 0.001) so that the full positive effect of alendronate was evident in the 24 metaphysis at 14 days, but first after 28 days in the diaphysis. While the early effect in the 25 metaphysis might be translated into earlier healing, the late effect in the diaphysis was due to 26 delayed remodeling of the callus, which might have less clinical importance.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Earlier effect of alendronate in mouse metaphyseal versus diaphyseal bone healing

Sandberg

Bernhardsson

Aspenberg

2016

Journal Orthopaedic Research

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“…2015). Because we have previously found that antiresorptive therapy with bisphosphonates can reduce migration, we now studied whether there was a similar effect with denosumab.…”

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confidence: 99%

Denosumab reduces early migration in total knee replacement

2017

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Background and purposeAseptic loosening is a main cause of late revision in total knee replacement (TKR). Migration of implants as measured by radiostereometric analysis (RSA) can predict future loosening. This migration is associated with bone resorption. Denosumab is a human monoclonal antibody that binds to receptors on osteoclast precursors and osteoclasts. This prevents osteoclast formation, resulting in less bone resorption in cortical and trabecular bone. We investigated whether denosumab can reduce migration of TKR, as measured with RSA.Patients and methodsIn this 2-center, randomized, double-blind placebo-controlled trial, 50 patients with osteoarthritis of the knee were treated with an injection of either denosumab (60 mg) or placebo 1 day after knee replacement surgery and again after 6 months. RSA was performed postoperatively and after 6, 12, and 24 months. The primary effect variable was RSA maximal total point motion (MTPM) after 12 months. We also measured other RSA variables and the knee osteoarthritis outcome score (KOOS).ResultsThe primary effect variable, MTPM after 12 months, showed that migration in the denosumab group was statistically significantly less than in the controls. Denosumab MTPM 12 months was reduced by one-third (denosumab: median 0.24 mm, 10% and 90% percentiles: 0.15 and 0.41; placebo: median 0.36 mm, 10% and 90% percentiles: 0.20 and 0.62). The secondary MTPM variables (6 and 24 months) also showed a statistically significant reduction in migration. There was no significant difference in MTPM for the period 12–24 months. KOOS sub-variables were similiar between denosumab and placebo after 12 and 24 months.InterpretationDenosumab reduces early migration in total knee replacement, as in previous trials using bisphosphonates. As migration is related to the risk of late loosening, denosumab may be beneficial for long-term results.

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“…2015, Sandberg and Aspenberg 2015a). Only a few articles have described metaphyseal healing, in spite of metaphyseal fractures being more common than shaft fractures in the clinic.…”

Section: Discussionmentioning

confidence: 99%

Isolated metaphyseal injury influences unrelated bones

Tätting¹,

Sandberg²,

Bernhardsson³

et al. 2017

Acta Orthopaedica

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Background and purposeFracture healing involves different inflammatory cells, some of which are not part of the traditional bone field, such as B-cells and cytotoxic T-cells. We wanted to characterize bone healing by flow cytometry using 15 different inflammatory cell markers in a mouse model of metaphyseal injury, and incidentally discovered a previously unknown general skeletal reaction to trauma.Material and methodsA bent needle was inserted and twisted to traumatize the cancellous bone in the proximal tibia of C57/Bl6 female mice. This is known to induce vivid bone formation locally in the marrow compartment. Cells were harvested from the injured region, the uninjured contralateral tibia, and the humerus. The compositions of the immune cell populations were compared to those in untraumatized control animals.ResultsTibial metaphyseal injury led to substantial changes in the cell populations over time. Unexpectedly, similar changes were also seen in the contralateral tibia and in the humerus, despite the lack of local trauma. Most leukocyte subsets were affected by this generalized reaction.InterpretationA relatively small degree of injury to the proximal tibia led to systemic changes in the immune cell populations in the marrow of unrelated bones, and probably in the entire skeleton. The few changes that were specific for the injury site appeared to relate to modulatory functions.

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Anti-RANKL treatment improves screw fixation in cancellous bone in rats

Cited by 30 publications

References 20 publications

Earlier effect of alendronate in mouse metaphyseal versus diaphyseal bone healing

Earlier effect of alendronate in mouse metaphyseal versus diaphyseal bone healing

Denosumab reduces early migration in total knee replacement

Isolated metaphyseal injury influences unrelated bones

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