Denosumab prevents acetabular bone loss around an uncemented cup: analysis of secondary outcomes in a randomized controlled trial.

BACKGROUND AND PURPOSE: Uncemented total hip arthroplasty (THA) is associated with periprosthetic bone loss. In a secondary outcome analysis from a randomized controlled trial, we studied whether denosumab can prevent loss of acetabular periprosthetic bone mineral density (pBMD) in patients who received a trabecular metal cup during uncemented THA. PATIENTS AND METHODS: 64 patients (aged 35-65 years) with unilateral osteoarthritis of the hip were randomized to 2 subcutaneous injections with denosumab or placebo, given 1-3 days post-surgery and 6 months post-surgery. Acetabular pBMD was measured in 5 regions of interest (ROIs) by dual-energy X-ray absorptiometry. Serum markers for bone metabolism were analyzed. Periprosthetic osteoblastic activity, measured as standardized uptake values (SUVs) by [18F] positron emission tomography/computed tomography, was evaluated in 32 of the 64 study patients. RESULTS: After 12 months, patients treated with denosumab had higher pBMD compared with the placebo-treated patients in 4 of 5 ROIs and in sum of ROIs 1-5. After 24 months, the effect on pBMD for patients treated with denosumab declined. Serum markers declined pronouncedly up to 12 months in patients treated with denosumab, but rebounded above baseline levels after 24 months. Patients treated with denosumab had statistically significantly lower SUVs in all ROIs, except ROI 5, after 6 months. INTERPRETATION: Based on this exploratory analysis of secondary endpoints the application of denosumab seems associated with preserved acetabular pBMD, reduced bone metabolism and attenuated periprosthetic osteoblastic activity. However, given the known rebound affects after discontinuation of denosumab treatment, these effects cannot be expected to persist. If prolonged treatment or shift to other regimes would be beneficial to reduce the risk of cup loosening is yet to be investigated.

Denosumab Prevents Early Periprosthetic Bone Loss After Uncemented Total Hip Arthroplasty: Results from a Randomized Placebo-Controlled Clinical Trial.

Implant loosening is the most common indication for revision surgery after total hip arthroplasty (THA). Although bone resorption around the implants plays a pivotal role in the pathophysiology of loosening, it is unknown whether potent early inhibition of osteoclasts could mitigate this process and thus reduce the need for revision surgery. We performed a randomized, double-blind, placebo-controlled phase 2 trial in 64 patients aged 35 to 65 years with unilateral osteoarthritis of the hip. They underwent surgery with an uncemented THA and were randomized to either two subcutaneous doses of denosumab (n = 32) or placebo (n = 32) given 1 to 3 days and 6 months after surgery. Patients were followed for 24 months. Primary outcome was periprosthetic bone mineral density (BMD) of the hip at 12 months as measured by dual-energy X-ray absorptiometry (DXA). In addition, [18 F] sodium fluoride positron emission tomography/CT (F-PET) was performed in half of the patients for analysis of periprosthetic standardized uptake value (SUV). Analyses were made according to intention-to-treat principles. The trial was registered at ClinicalTrials.gov 2011-001481-18, NCT01630941. Denosumab potently inhibited early periprosthetic bone loss. After 12 months, BMD in the denosumab group was 32% (95% confidence interval [CI] 22-44) higher in Gruen zone 7 and 11% (95% CI 8-15) higher in zones 1 to 7. After 24 months, the difference in BMD between groups had decreased to 15% (95% CI 4-27) in zone 7 and 4% (95% CI 0-8) in zones 1 to 7. In both groups, SUV increased after surgery, but the increase was less pronounced in the denosumab group. Biochemical markers of bone metabolism decreased in the denosumab group in the first 12 months, but a rebound effect with marker concentrations above baseline was observed after 24 months. Denosumab potently prevents early periprosthetic bone loss after uncemented THA; however, the effect diminishes after discontinuation of treatment. Further research is needed to determine whether this bone loss will prove to be of clinical importance and, if so, whether the positive effect observed in this study could be preserved by either prolonged treatment with denosumab or additional antiresorptive treatment. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

Bone loss around a stable, partly threaded hydroxyapatite-coated cup: a prospective cohort study using RSA and DXA.

STUDY PURPOSE: Aseptic loosening of the acetabular component is the most common reason for revision after primary THA, and periprosthetic demineralisation has been described as a potential cause for this process. The trabeculae-oriented pattern (TOP)-cup is a flat, hydroxyapatite (HA)-coated titanium shell with a threaded rim that was developed in order to minimise periprosthetic bone loss. We hypothesised that this cup provides good primary stability and improves preservation of periprosthetic bone mineral density (BMD). BASIC PROCEDURES: A prospective cohort study on 30 patients receiving the TOP cup was carried out. Preoperative total hip BMD and postoperative periprosthetic BMD in five periprosthetic regions of interest were investigated by dual energy radiographic absorptiometry (DXA), cup migration was analysed by radiostereometry (RSA), and the Harris hips score (HHS) was determined. MAIN FINDINGS: Mean HHS increased from 49 (24-79) preoperatively to 99 (92-100) after two years. DXA after one year demonstrated substantial BMD loss in the proximal periprosthetic zones 1 (-18%), zone 2 (-16 %) and zone 3 (-9%, all p<0.001 when compared with baseline BMD determined immediately postoperatively). The bone loss in these regions did not recover after two years. RSA (performed on 16 patients) showed that only very limited micromotion of the implant occurred: Mean cranial migration was 0.01 mm (95% confidence interval (CI): -0.09-0.12) and mean inclination decreased by 0.02º (CI: -0.43-0.39) after two years. CONCLUSION: We conclude that the TOP cup provides good primary stability in the short-term. However, substantial BMD loss in proximal periprosthetic areas indicates that the design of this cup cannot prevent periprosthetic bone loss that has also been observed around other uncemented cups.

High metal ion levels after use of the ASR™ device correlate with development of pseudotumors and T cell activation.

BACKGROUND: Pseudotumors and immunologic alterations are reported in patients with elevated metal ion levels after resurfacing arthroplasty of the hip. A direct association of increased cobalt and chromium concentrations with the development of pseudotumors has not been established. QUESTIONS/PURPOSES: We hypothesized that (1) patients with higher blood cobalt and chromium concentrations are more likely to have pseudotumors develop, (2) elevated cobalt and chromium concentrations correlate with increased activation of defined T cell populations, and (3) elevated metal ion levels, small implant size, cup inclination angle, and patient age are risk factors for the development of pseudotumors. METHODS: A single-surgeon cohort of 78 patients with 84 Articular Surface Replacement(®) implants was retrospectively investigated. Between 2006 and 2010, we performed 84 THAs using the Articular Surface Replacement(®) implant; this represented 2% (84/4950) of all primary hip replacements performed during that period. Of the procedures performed using this implant, we screened 77 patients (99%) at a mean of 43 months after surgery (range, 24-60 months). Seventy-one patients were investigated using ultrasound scanning, and cobalt and chromium concentrations in whole blood were determined by high-resolution inductively coupled plasma mass spectrometry. Differential analysis of lymphocyte subsets was performed by flow cytometry in 53 patients. Results of immunologic analyses were investigated separately for patients with and without pseudotumors. Pseudotumors were found in 25 hips (35%) and were more common in women than in men (p = 0.02). Multivariable regression analysis was performed to identify risk factors for the development of pseudotumors. RESULTS: Cobalt and chromium concentrations were greater in patients with pseudotumors than in those without (cobalt, median 8.3 versus median 1.0 µg/L, p < 0.001; chromium, median 5.9 versus median 1.3 µg/L, p < 0.001). The percentage of HLA-DR(+)CD4(+) T cells was greater in patients with pseudotumors than in those without (p = 0.03), and the proportion of this lymphocyte subtype was positively correlated with cobalt concentrations (r = 0.3, p = 0.02). Multivariable regression analysis indicated that increasing cobalt levels were associated with the development of pseudotumors (p < 0.001), and that patients with larger implants were less likely to have them develop (p = 0.04); age and cup inclination were not risk factors. CONCLUSIONS: We found a distinct association of elevated metal ion concentrations with the presence of pseudotumors and a correlation of increased cobalt concentrations with the proportion of activated T helper/regulator cells. Thus, the development of soft tissue masses after metal-on-metal arthroplasty could be accompanied by activation of T cells, indicating that this complication may be partly immunologically mediated. Further investigations of immunologic parameters in larger cohorts of patients with metal-on-metal arthroplasties are warranted. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Effects of postoperative weight-bearing on body composition and bone mineral density after uncemented total hip arthroplasty.

OBJECTIVE: To investigate whether a postoperative weight-bearing regimen affects changes in bone mineral density and body composition after uncemented total hip arthroplasty, and to investigate the changes over a 5-year period after the surgical procedure. DESIGN: Secondary analysis of a previous randomized controlled trial. METHODS: A total of 39 patients were randomized to immediate full weight-bearing or partial weight-bearing for 3 months. Dual-energy X-ray absorptiometry was used to measure bone mineral density of the contralateral hip and both heels and to measure body composition. RESULTS: The weight-bearing regimen had no effect on change in bone mineral density or body composition after 3 and 12 months. At 5 years, there was a decrease in bone mineral density of 3% in the total body and 2-3% in the contralateral hip regions. At 5 years we found a decrease in total body bone mineral content of 5%, but no changes in fat mass or lean mass compared with preoperative values. CONCLUSION: The postoperative weight-bearing regimen had no effect on changes in body composition or bone mineral density. Five years after total hip arthroplasty there was a decrease in bone mineral content and bone mineral density, but no changes in lean mass or fat mass.

A prospective cohort study on the short collum femoris-preserving (CFP) stem using RSA and DXA. Primary stability but no prevention of proximal bone loss in 27 patients followed for 2 years.

BACKGROUND AND PURPOSE: Short femoral stems have been introduced in total hip arthroplasty in order to save proximal bone stock. We hypothesized that a short stem preserves periprosthetic bone mineral density (BMD) and provides good primary stability. METHODS: We carried out a prospective cohort study of 30 patients receiving the collum femoris-preserving (CFP) stem. Preoperative total hip BMD and postoperative periprosthetic BMD in Gruen zones 1-7 were investigated by dual-energy x-ray absorptiometry (DXA), stem migration was analyzed by radiostereometric analysis (RSA), and the Harris hip score (HHS) was determined. RESULTS: 2 patients were excluded intraoperatively and 1 patient was revised due to a deep infection, leaving 27 patients for analysis. The mean HHS increased from 49 (24-79) preoperatively to 99 (92-100) after 2 years. DXA after 1 year showed substantial loss of BMD in Gruen zone 7 (-31%), zone 6 (-19%), and zone 2 (-13%, p < 0.001) compared to baseline BMD determined immediately postoperatively. The bone loss in these regions did not recover after 2 years, whereas the more moderate bone loss in Gruen zones 1, 3, and 5 partially recovered. There was a correlation between low preoperative total hip BMD and a higher amount of bone loss in Gruen zones 2, 6 and 7. RSA showed minor micromotion of the stem: mean subsidence was 0.13 (95% CI: -0.28 to 0.01) mm and mean rotation around the longitudinal axis was 0.01º (95% CI: -0.1 to 0.39) after 2 years. INTERPRETATION: We conclude that substantial loss in proximal periprosthetic BMD cannot be prevented by the use of a novel type of short, curved stem, and forces appear to be transmitted distally. However, the stems showed very small migration-a characteristic of stable uncemented implants.

The effects of different weight-bearing regimes on press-fit cup stability: a randomised study with five years of follow-up using radiostereometry.

PURPOSE: There is little evidence to support immediate weight bearing after uncemented total hip arthroplasty (THA). METHODS: Thirty-seven patients with unilateral osteoarthritis of the hip received a press-fit cup. Cup stability was assessed with radiostereometry (RSA) over five years. Patients were randomised to immediate full weight bearing, or partial weight bearing for three months. RESULTS: At five years, we found no difference in micro-motion as assessed with radiostereometry. Numerically, there was more proximal translation and increased inclination with immediate weight bearing, but these values barely exceeded the precision limit for the method. Pooled data for the two groups revealed translations of 0.1-0.3 mm and rotations of 0.2-0.3° over the five year follow-up period. CONCLUSIONS: We found no adverse effects of immediate weight bearing after THA in relation to stability of these press-fit cups. Early mobilisation might have other advantages.

Metabolic development of necrotic bone in the femoral head following resurfacing arthroplasty. A clinical [18F]fluoride-PET study in 11 asymptomatic hips.

BACKGROUND AND PURPOSE: One concern regarding resurfacing arthroplasty is the viability of the diminished femoral head and the postoperative risk of collapse, or a femoral neck fracture. (18)F-fluoride positron emission tomography (F-PET) enables us to assess bone viability despite there being a covering metal component. By F-PET studies, we recently showed the absence of metabolism in the remaining part of femoral heads, 1-4 years after surgery in 11 of 46 consecutive cases. We now present the further development of bone metabolism in these 11 cases. PATIENTS AND METHODS: 10 patients (11 chips) with previously shown loss of femoral head metabolism were evaluated by radiography and repeated F-PET scans, 3-6.5 years after surgery. The size of the area with low (18)F-fluoride PET uptake in the femoral head was compared to that in earlier PET images. RESULTS: No patients had any clinical symptoms; nor was any necrotic bone area visible in plain radiographs. On F-PET scans, 2 patients showed a diminished area with low uptake, 4 were unchanged, and 5 had enlarged areas. INTERPRETATION: Bone metabolism surrounding a volume of bone with no metabolic activity changes dynamically even 5 years after surgery. The presence of bone with minor uptake of F-tracer, indicating low or no bone metabolism, with further progression in 5 of 11 cases leads us to conclude that resurfacing THA should be used restrictively.

Implant survival and outcome after rotating-hinge total knee revision arthroplasty: a minimum 6-year follow-up.

INTRODUCTION: Data on long-time survival and clinical function of rotating hinge knee prostheses used in revision total knee arthroplasty (TKA) are scarce. METHOD: We evaluate the outcome of 42 revision TKA in 38 patients using the Endo-model rotating hinge total knee prosthesis after a minimum of 6 years, with 10-year implant survival as our primary outcome measure. Only revision TKAs performed due to aseptic loosening were included, and the Swedish Knee Arthroplasty Register was consulted in order to ensure that patients unavailable for clinical follow-up had not been revised elsewhere. Mean follow-up was after 8.8 (6-18) years, mean age at revision surgery was 72 (55-88) years, and most patients had severe medical comorbidities (n = 31). RESULTS: At follow-up, four knees had been re-revised due to aseptic loosening, and five further knees underwent re-revision due to other reasons. With implant revision due to aseptic loosening as the endpoint, 10-year survival was 89.2%, and with implant revision due to any reason 10-year survival was 65.1%. 11 patients (13 knees) eligible for clinical follow-up were evaluated according to the Hospital for Special Surgery score (HSSS), the Knee Society scores (KSS), and by plain radiography. Mean HSSS was 67 (36-90), mean KSS-knee was 85 (73-96), and mean KSS-function was 29 (0-100). Radiography showed that no implant was in need of revision. CONCLUSION: Our results indicate that revision arthroplasty of the knee with this rotating hinge prosthesis can be performed with satisfactory or good results in an elderly population with severe comorbidities.

Femoral head viability following resurfacing arthroplasty. A clinical positron emission tomography study.

Hip resurfacing (HR) carries attendant risks of avascular necrosis (AVN) and femoral neck fracture. We used fluoride positron emission tomography (PET) scans to analyze bone metabolism 2-5 years after surgery in 35 cases. Three of the patients had been clinical failures. Using PET scans in the remaining 32 cases, 7 were found to have an area of non-viable bone in the femoral head. This was seen following both posterior and antero lateral approaches. Fluoride PET is a sensitive and useful method for evaluating bone metabolism following HR.

Periprosthetic bone mineral density and fixation of the uncemented CLS stem related to different weight bearing regimes: A randomized study using DXA and RSA in 38 patients followed for 5 years.

BACKGROUND AND PURPOSE: There is no consensus on the best rehabilitation regime after uncemented total hip arthroplasty. Theoretically, bone ingrowth into the implant should benefit from initial partial weight bearing. We investigated whether the degree of postoperative weight bearing influences the periprosthetic bone mineral density (BMD) and/or the stability of the CLS stem. PATIENTS AND METHODS: 38 patients received an uncemented CLS stem and were randomized to either unrestricted postoperative weight bearing or to partial weight bearing for 3 months. Periprosthetic BMD was measured in the 7 Gruen zones with DXA and the stability of the femoral stem was assessed by radiostereometric analysis (RSA) after surgery and at 3, 12, 24, and 60 months. RESULTS: Periprosthetic BMD was not influenced by the type of postoperative weight bearing. BMD was reduced by 8-15% in all Gruen zones at 3 months. Restoration toward initial BMD was observed in all zones except in zone 7 (calcar region), where BMD was reduced by 22% at 5 years. Immediate weight bearing after surgery had no influence on the stability of the CLS stem, as assessed by RSA. INTERPRETATION: Immediate full weight bearing after uncemented total hip arthroplasty is safe. There is no difference in the periprosthetic BMD or in stability of the stem as measured by RSA compared to partial weight bearing for 3 months. BMD is reduced by more than 20% in the calcar region around a CLS stem after 5 years.

Osteonecrosis following resurfacing arthroplasty.

BACKGROUND AND PURPOSE: One of the main concerns regarding resurfacing arthroplasty is the viability of the remaining part of the femoral head, and the postoperative risk of a femoral neck fracture or collapse. In contrast to radiographic methods, positron emission tomography using the radiotracer [18F]-fluoride (Fluoride-PET) enables us to visualize the viability of bone in the remaining part of the head, despite the presence of the covering metal component. PATIENTS AND METHODS: This is preliminary prospective study of 14 patients who underwent an ASR resurfacing arthroplasty. Apart from clinical and radiographic analyses, all patients were analyzed by PET scan 1 week, 4 months, and 1 year after surgery. RESULTS: 1 patient had a minor region of osteonecrosis on PET scan at 1 week and at 4 months. After 1 year, the necrosis had increased to include most of the head. 2 other patients, normal at 4 months, had developed equally large osteonecrosis at 1 year. A fourth patient had a minor osteonecrosis at 1 year. None of the patients had clinical symptoms, and the necrotic areas were not visible on plain radiographs. CONCLUSIONS: We found Fluoride PET to be a sensitive and useful method for evaluation of bone metabolism at resurfacing arthroplasty. 3 of the 14 patients had developed osteonecrosis, involving most of the head at 1 year. The late onset of the phenomenon does not support the hypothesis of surgically damaged vascularity. The presence of this complication together with the lack of visibility on plain radiographs gives reason for concern.

Differences in hip bone mineral density may explain the hip fracture pattern in osteoarthritic hips.

INTRODUCTION: In patients with osteoarthritis of the hip (OAH), trochanteric fractures are much more common than femoral neck fractures. One reason may be altered bone composition in the proximal femurs. OAH often leads to a fixed external rotation of the hip, leading to difficulties in positioning during DXA measurements. We compared BMD in OAH-affected legs and healthy legs. PATIENTS AND METHODS: 40 patients with strictly unilateral OAH were cross-sectionally investigated with DXA at the hips and heels bilaterally as well as body composition of the legs. 3 regions of interest in the proximal femur were measured: femoral neck (FN), trochanter (TR), and total hip (TH). The design of the study allowed us to perform paired t-test between the OAH side and the healthy side. RESULTS: BMD was increased by 4.1% in FN, and reduced by 8.3% in TR and 4.1% in TH (p < 0.001 for all comparisons). INTERPRETATION: The differences in BMD, with decrease in the trochanter and increase in the femoral neck, may offer an explanation for the pattern of hip fractures seen in osteoarthritis. External rotation of the hip cannot explain the differences in BMD.

The effect of early weight bearing on migration pattern of the uncemented CLS stem in total hip arthroplasty.

Forty-two patients (younger than 65 years) with osteoarthritis were operated on with an uncemented CLS stem and randomized to early unrestricted weight bearing combined with intensive physiotherapy or to partial weight bearing combined with self-training. Radiostereometric analysis showed 1.2 (+0.11 to -6.76) mm subsidence of the stem at 24 months in both groups. There was no significant difference in the migration pattern between the unrestricted and partial weight bearing groups. Actual loading on the operated leg, measured with the F-scan system, did not influence the migration of the stem. There was a strong correlation between the average subsidence at 3 and 24 months (r = 0.96). Early full weight bearing and active rehabilitation can be used for the uncemented CLS stem without increased risk of early loosening.

Early migration pattern of the uncemented CLS stem in total hip arthroplasties.

We performed this investigation to determine the possible migration starting immediately after surgery and the effect of different weightbearing regimens on the migration pattern of an uncemented hip stem (CLS). Stem migration was determined with radiostereometry analysis with baseline when the patients still were anesthetized. Subsequent examinations were done up to 1 year. Twenty-nine patients (mean age, 55 years; range, 26-63 years) were randomized to either unrestricted weightbearing combined with intensive physiotherapy from the first day after surgery or to partial weightbearing and a conservative training regimen for the first 3 months after surgery. At 1 week, subsidence was -0.03 mm in the unrestricted weightbearing group and 0.01 mm in the partial weightbearing group. At 1 year, subsidence was 1.01 mm in the unrestricted weightbearing group and 0.51 mm in the partial weightbearing group. One patient in the unrestricted weightbearing group had revision surgery because of aseptic loosening at 1.5 years after surgery. The CLS stem did not have any migration from the end the surgery until 1 week, but there was small migration from 1 week to 3 months after which the stem remained stable. The degree of early weightbearing did not affect the migration pattern.

Comparison of the uncemented Cone and the cemented Bimetric hip prosthesis in young patients with osteoarthritis: an RSA, clinical and radiographic study.

BACKGROUND: There is no consensus as to whether uncemented or cemented femoral stems should be used in younger patients. We compared the uncemented Cone stem to the cemented Bimetric stem in young patients with osteoarthritis. PATIENTS AND METHODS: We randomized 45 relatively young patients (< 65 years old, mean age 54 years) with osteoarthritis to either an uncemented Cone stem or a cemented Bimetric stem. All patients were followed for 2 years. Outcome was assessed by the Merle d'Aubigné score, conventional radiography and repeated radio-stereometric analysis (RSA). We also followed 81 Cone stems for 8 (7-12) years with revision as endpoint. RESULTS: The clinical outcome was excellent. No patient had postoperative thigh pain. The migration was small. The Bimetric stem was stable during the whole observation period, while the Cone stem subsided and rotated to retroversion during the first 3 months post-operatively, and then remained stable. In the follow-up study of 81 Cone stems, 1 stem was revised. INTERPRETATION: We conclude that both the cemented Bimetric stem and the uncemented Cone stem are stable and give excellent clinical results after 2 years in relatively young patients with osteoarthritis. Although designed for CDH hips, the Cone stem appears to be suitable also for patients with osteoarthitis.

The cone hip stem: a prospective study of 13 patients followed for 5 years with RSA.

We operated on 13 patients (14 hips) with dysplastic hips, mean age 42 (28-58) years, with a cementless Cone stem and followed them for 5 years, using the Merle d'Aubigné clinical score, conventional radiography and repeated radiostereometry analyses. The clinical scores improved markedly at 4 months and still more throughout the study. None of the patients complained of thigh pain. No stem showed radiographic subsidence, but 3 stems had radiolucent zones probably indicating fibrous ingrowth. Micromigration was measured at 4 months, 1, 2 and 5 years. The mean subsidence after 5 years was 0.27 mm and the mean posterior micromigration of the head was 0.74 mm. Most of the micromigration took place within the first 4 months. We conclude that the uncemented Cone stem used in dysplastic hips has shown a good clinical outcome so far and was found to be stable on conventional radiographs and using RSA technique.