A long-lasting bisphosphonate partially protects periprosthetic bone, but does not enhance initial stability of uncemented femoral stems: A randomized placebo-controlled trial of women undergoing total hip arthroplasty

Low bone quality may compromise the success of cementless total hip arthroplasty in high-risk patients such as elderly women. Zoledronic acid is a long-lasting antiresorptive agent, which is known to reduce short-term periprosthetic bone loss. However, its effect on femoral stem stability is not well known. Forty-nine female patients with a mean age of 68 years (range, 51-85 years) scheduled to undergo cementless total hip arthroplasty due to osteoarthritis were randomized in this double-blind, placebo controlled trial to receive a single postoperative infusion of zoledronic acid or placebo. Patients were evaluated for up to four years postoperatively for femoral stem migration measured by radiostereometric analysis, bone mineral density (BMD) measured by dual X-ray absorptiometry, functional recovery, and patient-reported outcome scores. Implant survival was determined at nine years postoperatively. Zoledronic acid did not reduce the femoral stem migration that occurred predominantly during the settling period of the first 3-6 months. Subsequently, all femoral stems were radiographically osseointegrated. Zoledronic acid maintained periprosthetic BMD, while the expected loss of periprosthetic bone during the first 12 months was found in controls. Thereafter, periprosthetic BMD of Gruen zone 7 decreased even in the zoledronic acid group but remained 14.6% higher than that in the placebo group at four years postoperatively. Functional recovery was comparable across the groups. At nine years postoperatively, no revision arthroplasty had been performed. In conclusion, in women at high-risk for low BMD, zoledronic acid had a long-lasting, partially protective effect on periprosthetic bone loss, but the treatment did not enhance the initial femoral stem stability

Denosumab in Cementless Total Hip Arthroplasty: Multivariate Reanalysis of 3D Femoral Stem Migration and the Influence on Outliers

In cementless total hip arthroplasty, adequate implant stability is necessary for the success of osseointegration and rapid clinical recovery. Postoperative femoral stem migration, measured by radiostereometric analysis (RSA), defines the initial stability achieved during surgical implantation. In a recent trial of 65 postmenopausal women randomized 1:1 denosumab:placebo, denosumab failed to reduce the initial migration of a cementless femoral stem despite the successful prevention of periprosthetic bone loss. The trial applied the current RSA standard, which examined stem migration on an axis-by-axis basis and did not consider more complex three-dimensional (3D) migration. Therefore, we performed a reanalysis of the trial data using a multivariate hierarchical linear mixed model (LMM). As an additional limitation, the data included influential outliers. Women with normal bone mineral density exhibited significantly (p = 0.036) less stem subsidence compared with osteopenic and osteoporotic women. Denosumab significantly decreased the variance of stem migration in osteopenic and osteoporotic women. The mean magnitude of 3D stem migration did not differ between denosumab-treated and placebo-treated women (p = 0.820). After application of a common statistical definition for RSA outlier identification, there were eight (12%) outliers, six in the placebo group and two in the denosumab group (p = 0.149). After exclusion of the outliers, the repeated LMM analysis demonstrated a trending difference in 3D stem migration (p = 0.086), with a significant difference of z-axis rotation (valgus-varus tilt) of the femoral stem (p = 0.029). The observed effect size was small and without clinically important differences in postoperative recovery. Based on a Monte Carlo simulation with random-generated 3D migration data, multivariate LMM showed greater statistical power than univariate analyses. The application of hierarchical LMM facilitated the analysis of implant migration as a factual 3D event. The observed trend in the lower number of RSA outliers in denosumab-treated subjects warrants powered large-scale trials. </p

PET/CT to detect adverse reactions to metal debris in patients with metal-on-metal hip arthroplasty: an exploratory prospective study

Metal-on-metal (MoM) bearings in total hip arthroplasties and hip resurfacing arthroplasties have recently shown a new type of complication: adverse reactions to metal debris (ARMD). ARMD is characterized by local severe inflammation and tissue necrosis leading to implant failures. The gluteal muscle region is important for the patient outcome after revision surgery. This prospective positron emission tomography/computed tomography (PET/CT) study was undertaken to evaluate the characteristics of 2-deoxy-2-[18 F]fluoro-d-glucose ([18 F]FDG) and [68 Ga]Gallium citrate ([68 Ga]Citrate) PET/CT in ARMD patients. [18 F]FDG and [68 Ga]Citrate PET/CT were performed in 18 hip arthroplasty patients: 12 ARMD patients (with 16 MoM hips) and six arthroplasty controls without ARMD. Tracer uptake was evaluated visually, and maximum standardized uptake (SUVmax ) was measured in the gluteal muscle region. ARMD severity was graded by metal artefact reduction sequence-magnetic resonance imaging (MARS-MRI). Periprosthetic [18 F]FDG uptake was observed in 15 of 16 hips, [68 Ga]Citrate uptake in three of 16 hips, respectively. The distribution of tracer uptake resembled infection in three hips. In the gluteal muscle region, the SUVmax of [18 F]FDG was significantly greater in hips with moderate and severe ARMD compared with the controls (P = 0·009 for [18 F]FDG and P = 0·217 for [68 Ga]Citrate). In patients who needed revision surgery, an intraoperative finding of gluteal muscle necrosis was associated with increased local SUVmax as detected by preoperative [18 F]FDG (P = 0·039), but not by [68 Ga]Citrate (P = 0·301). In conclusion, the inflammatory reaction to metal debris in hip arthroplasty patients is best visualized with [18 F]FDG

Good stability of a cementless, anatomically designed femoral stem in aging women: a 9-year RSA study of 32 patients

Background and purpose — We previously reported a transient, bone mineral density (BMD)-dependent early migration of anatomically designed hydroxyapatite-coated femoral stems with ceramic–ceramic bearing surfaces (ABG-II) in aging osteoarthritic women undergoing cementless total hip arthroplasty. To evaluate the clinical significance of the finding, we performed a follow-up study for repeated radiostereometric analysis (RSA) 9 years after surgery.Patients and methods — Of the 53 female patients examined at 2 years post-surgery in the original study, 32 were able to undergo repeated RSA of femoral stem migration at a median of 9 years (7.8–9.3) after surgery. Standard hip radiographs were obtained, and the subjects completed the Harris Hip Score and Western Ontario and McMaster Universities Osteoarthritis Index outcome questionnaires.Results — Paired comparisons revealed no statistically significant migration of the femoral stems between 2 and 9 years post-surgery. 1 patient exhibited minor but progressive RSA stem migration. All radiographs exhibited uniform stem osseointegration. No stem was revised for mechanical loosening. The clinical outcome scores were similar between 2 and 9 years post-surgery.Interpretation — Despite the BMD-related early migration observed during the first 3 postoperative months, the anatomically designed femoral stems in aging women are osseointegrated, as evaluated by RSA and radiographs, and exhibit good clinical function at 9 years.</div

Bone Mineral Density and Cortical-Bone Thickness of the Distal Radius Predict Femoral Stem Subsidence in Postmenopausal Women

The distal radius is an optional site for evaluation of bone quality in postmenopausal women before cementless total hip arthroplasty. We hypothesized that dual-energy X-ray absorptiometry (DXA) and pulse-echo ultrasonometry of the distal radius may help discriminate subjects at high risk of femoral stem subsidence.A prospective cohort of postmenopausal women with primary hip osteoarthritis underwent total hip arthroplasty with implantation of a parallel-sided femoral stem. Postoperative stem migration was measured using radiostereometric analysis. Preoperatively, subjects had multisite DXA measurement of bone mineral density (BMD) and pulse-echo ultrasonometry of the cortical-bone thickness. The diagnostic abilities of these methods to discriminate The accuracy of the distal radius BMD and cortical-bone thickness of the distal radius were moderate (area under the curve, 0.737 and 0.726, respectively) in discriminating between Femoral stem stability and resistance to subsidence are sensitive to adequate bone stock and unaltered anatomy. DXA and pulse-echo ultrasonometry of the distal radius may help discriminate postmenopausal women at high risk of stem subsidence.</div

Mouse cathepsin K: cDNA cloning and predominant expression of the gene in osteoclasts, and in some hypertrophying chondrocytes during mouse development

AbstractWe have constructed cDNA clones covering the entire coding region of mouse, human and rabbit preprocathepsin K mRNA for studies on bone turnover. The clone pMCatK-1 for mouse cathepsin K shares 87% nucleotide homology with the corresponding human and rabbit sequences. Analysis of a panel of mouse tissues for tissue distribution of cathepsin K mRNA revealed the highest levels in musculoskeletal tissues: bone, cartilage and skeletal muscle. In situ hybridization of developing mouse embryos was performed to identify the cellular source of cathepsin K mRNA. The strongest mRNA signal was detected in osteoclasts of bone, identified in serial sections by positive TRAP staining. Cathepsin K mRNA was also observed in some hypertrophic chondrocytes of growth cartilages. Association of cathepsin K production with degradation of bone and cartilage matrix suggests that this enzyme and its mRNA levels could serve as markers for matrix degradation in diseases affecting these tissues

Volumetric Bone Mineral Density in Cementless Total Hip Arthroplasty in Postmenopausal Women: Effects on Primary Femoral Stem Stability and Clinical Recovery

AbstractBackgroundIn cementless total hip arthroplasty, femoral stems should preferably not migrate at all postoperatively. This goal is difficult to achieve in postmenopausal women with impaired bone quality. Here, we explored the clinical importance of initial stem migration, measured by radiostereometric analysis (RSA), in women who underwent quantitative computed tomography (CT) of the involved hip preoperatively.MethodsA prospective cohort of 65 postmenopausal women (mean age, 69 years) with hip osteoarthritis and Dorr type-A or B femoral anatomy underwent total hip arthroplasty with implantation of a tapered, single-wedge femoral stem. Volumetric bone mineral density (BMD) was measured using quantitative CT. Femoral stem translation and rotation were measured using model-based RSA within 3 days after the surgical procedure and were repeated at 3, 5, and 11 months. Postoperative recovery parameters included walking speed, walking activity, and patient‐reported outcome measures. Subjects were categorized into 2 groups according to the magnitude of initial 5-month stem subsidence (ResultsSubjects with stem subsidence of ≥2 mm (mean, 3.09 mm [95% confidence interval (CI), 2.70 to 3.47 mm]) had lower intertrochanteric volumetric BMD (p = 0.008). Subjects with subsidence of ConclusionsFemoral stem stability and resistance to subsidence were sensitive to adequate intertrochanteric volumetric BMD. Low intertrochanteric volumetric BMD was associated with greater stem migration. With initial migration, clinical recovery was slower and patient-reported outcome measures were less satisfactory.Level of EvidencePrognostic Level II. See Instructions for Authors for a complete description of levels of evidence.</p

Contributing factors to the initial femoral stem migration in cementless total hip arthroplasty of postmenopausal women

In cementless total hip arthroplasty (THA), femoral stems rely on the initial press-fit fixation against cortical bone to achieve osseointegration. Decreased bone mineral density (BMD) in postmenopausal women poses natural difficulties in achieving axial and rotational femoral stem stability. The present study examined contributing demographic, surgery-related and postoperative factors in determining the magnitude of early stem migration prior to osseointegration. A prospective cohort of 65 postmenopausal women with hip osteoarthritis (Dorr type A or B femur anatomy) underwent THA with implantation of an uncemented parallel-sided femoral component. Postoperative femoral stem translation and rotation were measured using model-based radiostereometric analysis. Based on analysis of covariance, which controlled for outliers and randomized antiresorptive treatment with denosumab or placebo, none of the analyzed demographics (including BMI) and surgery-related variables (including the stem-to-canal fil ratio) was associated with stem subsidence. Stem subsidence (mean 1.8 mm, 95% CI 1.2 to 2.4) occurred even in women with normal hip BMD. Total hip BMD and postoperative walking activity (measured three months after surgery) were significantly associated with stem rotation, and height acted as a confounding factor. The effect of walking activity on stem rotation was significant at 5 months (p = 0.0083) and at 11 months (p = 0.0117). This observation confirms the previous results of instrumented hip prostheses on torsional moments affecting stems during daily activities. High-resolution imaging modalities of local bone quality are needed to explore reasons for RSA-measurable stem subsidence even in women with normal hip BMD.</p