Is cement mantle thickness a primary cause of aseptic tibial loosening following primary total knee arthroplasty?

BACKGROUND: Aseptic tibial loosening following primary total knee replacement is one of the leading causes of long-term failure. Cement mantle thickness has been implicated as a source of aseptic tibial loosening. Therefore, the following study was designed to determine (1) what is the cement mantle thickness in patients that develop aseptic tibial loosening, and (2) is there a difference in cement mantle thickness based on the interface of failure? METHOD: This retrospective cohort included 216 patients revised for aseptic tibial loosening. Patient demographics, operative data, and clinical outcomes were recorded. A preoperative radiographic assessment was performed to determine the interface of failure and the thickness of the cement mantle using the Knee Society Radiographic Evaluation System zones. RESULTS: The average patient age was 65 years and body mass index was 33.7 kg/m2. 203 patients demonstrated radiographic failure at the implant-cement interface and 13 patients demonstrated failure at the cement-bone interface. The average cement mantle thickness of each radiographic zone for the entire cohort on the AP and lateral views was 4.4 and 4.5 mm, respectively. The average cement mantle thickness of patients that developed failure at the implant-cement interface was significantly greater than patients that failed at the cement-bone interface in each radiographic zone (p < 0.001). CONCLUSIONS: Patients that develop implant loosening at the cement-bone interface were noted to have a significantly decreased cement mantle compared to patients that failed at the implant-cement interface. Methods for decreasing tibial implant loosening should likely focus on improving the fixation at the implant-cement interface.

Varus Collapse in Total Knee Arthroplasty: Does Fixation or Bone Fail First?

INTRODUCTION: Aseptic tibial loosening is now considered the most common reason that total knee arthroplasties (TKA) fail long term. There are unique subsets of patients that fail into varus alignment of the tibial tray with collapse of the medial proximal tibia. It is currently unknown if the implant fixation fails first or if the proximal medial tibia collapses first. MATERIALS: We performed a retrospective analysis of 88 patients that were revised at our institution secondary to aseptic varus collapse of the proximal tibia. Two fellowship-trained arthroplasty surgeons performed a retrospective analysis on sequential precollapse radiographs in each patient to determine which failed first: the implant fixation (implant-cement or cement-bone interface) or the medial proximal tibia. DISCUSSION: 36/88 (40.9%) patients had a series of precollapse radiographs that could be reviewed. Failure at the implant-cement interface before varus collapse in 23 vs 22 patients, failure at the implant-cement and cement-bone interface before varus collapse in two patients, and contemporaneous failure at the implant-cement interface and varus collapse in 11 vs 12 patients were identified by reviewers one and two, respectively. CONCLUSION: The most frequent mechanism of failure identified was failure of the implant-cement interface followed by subsequent medial tibial varus collapse. Improving implant fixation may decrease the incidence of this unique failure mechanism. We advocate the use of supplemental stem fixation in high-risk patients and optimal cement techniques for all patients as methods of potentially avoiding tibial varus collapse, one of the most frequent modes of long-term failure.

Estrogen Stimulation of Pleiotrophin Enhances Osteoblast Differentiation and Maintains Bone Mass in IGFBP-2 Null Mice.

Insulin-like growth factor binding protein-2 (IGFBP-2) stimulates osteoblast differentiation but only male Igfbp2 null mice have a skeletal phenotype. The trophic actions of IGFBP-2 in bone are mediated through its binding to receptor tyrosine phosphatase beta (RPTPß). Another important ligand for RPTPß is pleiotrophin (PTN), which also stimulates osteoblast differentiation. We determined the change in PTN and RPTPß in Igfbp2-/- mice. Analysis of whole bone mRNA in wild-type and knockout mice revealed increased expression of Ptn. Rptpß increased in gene-deleted animals with females having greater expression than males. Knockdown of PTN expression in osteoblasts in vitro inhibited differentiation, and addition of PTN to the incubation medium rescued the response. Estradiol stimulated PTN secretion and PTN knockdown blocked estradiol-stimulated differentiation. PTN addition to IGFBP-2 silenced osteoblast stimulated differentiation, and an anti-fibronectin-3 antibody, which inhibits PTN binding to RPTPß, inhibited this response. Estrogen stimulated PTN secretion and downstream signaling in the IGFBP-2 silenced osteoblasts and these effects were inhibited with anti-fibronectin-3. Administration of estrogen to wild-type and Igfbp2-/- male mice stimulated an increase in both areal bone mineral density and trabecular bone volume fraction but the increase was significantly greater in the Igfbp2-/- animals. Estrogen also stimulated RPTPß expression in the null mice. We conclude that loss of IGFBP-2 expression is accompanied by upregulation of PTN and RPTPß expression in osteoblasts, that the degree of increase is greater in females due to estrogen secretion, and that this compensatory change may account for some component of the maintenance of normal bone mass in female mice.

IGFBP-2 stimulates calcium/calmodulin-dependent protein kinase kinase 2 activation leading to AMP-activated protein kinase induction which is required for osteoblast differentiation.

Insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins-2 (IGFBP-2) function coordinately to stimulate osteoblast differentiation. Induction of AMP-activated protein kinase (AMPK) is required for differentiation and is stimulated by these two factors. These studies were undertaken to determine how these two peptides lead to activation of AMPK. Enzymatic inhibitors and small interfering RNA were utilized to attenuate calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) activity in osteoblasts, and both manipulations resulted in failure to activate AMPK, thereby resulting in inhibition of osteoblast differentiation. IGFBP-2 and IGF-I stimulated an increase in CaMKK2, and inhibition of IGFBP-2 binding its receptor resulted in failure to induce CaMKK2 and AMPK activation. Injection of a peptide that contained the IGFBP-2 receptor-binding domain into IGFBP-2-/- mice activated CaMKK2 and injection of a CaMKK2 inhibitor into normal mice inhibited both CamKK2 and AMPK activation in osteoblasts. We conclude that induction of CaMKK2 by IGFBP-2 and IGF-I in osteoblasts is an important signaling event that occurs early in differentiation and is responsible for activation of AMPK, which is required for optimal osteoblast differentiation.