Periprosthetic Bone Loss Research Articles

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

ABSTRACTIn 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. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Short-term success of proximal bone stock preservation in short hip stems: a systematic review of the literature.

Total hip arthroplasty is performed more frequently in younger patients nowadays, making long-term bone stock preservation an important topic. A mechanism for late implant failure is periprosthetic bone loss, caused by stress shielding around the hip stem due to different load distribution. Short stems are designed to keep the physical loading in the proximal part of the femur to reduce stress shielding. The aim of this review is to give more insight into how short and anatomic stems behave and whether they succeed in preservation of proximal bone stock.A systematic literature search was performed to find all published studies on bone mineral density in short and anatomic hip stems. Results on periprosthetic femoral bone mineral density, measured with dual-energy X-ray absorptiometry (DEXA), were compiled and analysed per Gruen zone in percentual change.A total of 29 studies were included. In short stems, Gruen 1 showed bone loss of 5% after one year (n = 855) and 5% after two years (n = 266). Gruen 7 showed bone loss of 10% after one year and –11% after two years. In anatomic stems, Gruen 1 showed bone loss of 8% after one year (n = 731) and 11% after two years (n = 227). Gruen 7 showed bone loss of 14% after one year and 15% after two years.Short stems are capable of preserving proximal bone stock and have slightly less proximal bone loss in the first years, compared to anatomic stems. Cite this article: EFORT Open Rev 2021;6:1040-1051. DOI: 10.1302/2058-5241.6.210030

Computational tibial bone remodeling over a population after total knee arthroplasty: A comparative study.

Periprosthetic bone loss is an important factor in tibial implant failure mechanisms in total knee arthroplasty (TKA). The purpose of this study was to validate computational postoperative bone response using longitudinal clinical DEXA densities. Computational remodeling outcome over a population was obtained by incorporating the strain‐adaptive remodeling theory in finite element (FE) simulations of 26 different tibiae. Physiological loading conditions were applied, and bone mineral density (BMD) in three different regions of interest (ROIs) was considered over a postoperative time of 15 years. BMD outcome was compared directly to previously reported clinical BMD data of a comparable TKA cohort. Similar trends between computational and clinical bone remodeling over time were observed in the two proximal ROIs, with most rapid bone loss taking place in the initial months after TKA and BMD starting to level in the following years. The extent of absolute proximal BMD change was underestimated in the FE population compared with the clinical subject group, which might be the result of significantly higher initial clinical baseline BMD values. Large differences in remodeling response were found in the distal ROI, in which resorption was measured clinically, but a large BMD increase was predicted by the FE models. Multiple computational limitations, related to the FE mesh, loading conditions, and strain‐adaptive algorithm, likely contributed to the extensive local bone formation. Further research incorporating subject‐specific comparisons using follow‐up CT scans and more extensive physiological knee loading is recommended to optimize bone remodeling more distal to the tibial baseplate.

Influence of alendronate therapy on the results of densitometric examination after implantation of total hip endoprosthesis

The development of aloarthroplasty of the hip is continuously rising. After implantation of a total cement-free hip endoprosthesis, often there is a periprosthetic femoral bone loss. Alendronate has been shown to be a potent inhibitor of bone resorption activity; it inhibits osteoclastic bone resorption, increases bone mass, and plays a significant role in post-implantation stabilization of the femur. The aim of this study was to determine the effect of alendronate on osteointegration of hip endoprosthesis.Material and methods: The study analyzed 10 patients operated on with implantation of a total cement-free hip endoprosthesis (THP). The included patients were examined by a radiographic method at 6 and 12 months and DXA method at 6 and 12 months. Results: The study showed differences in the values of bone mineral density and bone mineral content in the interval between 6 and 12 months in patients undergoing THP, and hence we can conclude that alendronate therapy after THP implantation reduced periprosthetic loss of bone mass and implant stiffening. Alendronate is a proven inhibitor of periprosthetic bone loss that occurs after prirmary impantation of a total cement-free hip endoprosthesis.

Therapeutic Potential of Vasoactive Intestinal Peptide and its Derivative Stearyl-Norleucine-VIP in Inflammation-Induced Osteolysis.

The common use of dental and orthopedic implants calls for special attention to the immune response leading to peri-prosthetic bone loss and implant failure. In addition to the well-established microbial etiology for oral implant failure, wear debris and in particular titanium (Ti) particles (TiP) in the implant vicinity are an important trigger of inflammation and activation of bone resorption around oral and orthopedic implants, presenting an unmet medical need. Here, we employed bacterial-derived lipopolysaccharides (LPS) to model infection and TiP to model aseptic inflammation and osteolysis. We assessed inflammation in vitro by measuring IL1β, IL6 and TNFα mRNA expression in primary macrophages, osteoclastogenesis in RANKL-induced bone marrow derived pre-osteoclasts and osteolysis in vivo in a mouse calvarial model. We also assessed the trans-epithelial penetrability and safety of the tested compound in rats. Our results show that a lipophilic super-active derivative of vasoactive intestinal peptide (VIP), namely stearyl-norleucine-VIP (SNV) presented superior anti-inflammatory and anti-osteoclastogenic effects compared to VIP in vitro. In the bacterial infection model (LPS), SNV significantly reduced IL1β expression, while VIP increased IL6 expression. In the aseptic models of osteolysis, SNV showed greater suppression of in vitro osteoclastogenesis than VIP, and significantly inhibited inflammation-induced osteolysis in vivo. We also observed that expression levels of the VIP receptor VPAC-2, but not that of VPAC-1, dramatically decreased during osteoclast differentiation. Importantly, SNV previously shown to have an increased stability compared to VIP, showed here significant trans-epithelial penetration and a clean toxicological profile, presenting a novel drug candidate that could be applied topically to counter both aseptic and infection-related bone destruction.

Zoledronic acid effectively inhibited periprosthetic bone loss in patients with osteoporosis after cementless total hip arthroplasty

Zoledronic acid effectively inhibited periprosthetic bone loss in patients with osteoporosis after cementless total hip arthroplasty

Intra-operative Clodronate Rinsing Improves the Integration of the Femoral Stem in a Prospective, Double-blinded, Randomized, Placebo-controlled Clinical RSA-study

Background: Periprosthetic bone loss after Total Hip Arthroplasty (THA), detected as an early migration of the prosthesis may predict later loosening of the implant. Objective: We hypothesized that intra-operative bisphosphonate rinsing would reduce bone resorption after THA. It might therefore be possible to achieve better early fixation of the implant. Methods: Nineteen patients suffering from arthrosis were recruited in a prospective, double-blinded, randomized, placebo-controlled clinical pilot trial. Patients were operated with an uncemented Bimetric stem using tantalum markers. The femoral proximal intramedullary canal was rinsed with 1mM clodronate in nine patients and with saline in 10 patients. These patients were followed for two years using radiostereometric analysis (RSA), dual energy x-ray absorptiometry (DXA) and the Harris Hip Score (HHS). Results: We did not found any significant differences between the study groups with regards to the primary output measures (maximum total point motion, MTPM). However, there was evidence that clodronate could affect periprosthetic bone quality; a beneficial effect in BMD in Gruen zone 3 during the two-year follow-up was observed, BMD decreased less in the clodronate group (p = 0.02). The maximal x-translation of the stem at 3-24 months was significantly two-fold, being higher in the placebo group (p = 0.02). The baseline BMD and the maximal total point motion (MTPM) at 3-24 months showed a positive correlation in the clodronate group and a negative correlation in the placebo group. Conclusion: In conclusion, further studies with larger patient groups and longer follow-up periods are needed to estimate the clinical importance of these findings and further to prove if an intraoperative clodronate rinsing prior to application of femoral stem during THA can prevent periprosthetic bone loss. Clinical Trial Registration No.: NCT03803839

Factors Affecting Periprosthetic Bone Loss after Hip Arthroplasty.

Periprosthetic bone loss may lead to major complications in hip arthroplasty, including aseptic loosening, implant migration, and even periprosthetic fracture. Such a complication leads to revision surgeries, which are expensive, technically demanding, and result in a low satisfaction rate. Therefore, a study was conducted of the factors affecting the periprosthetic bone loss around the stem that caused these complications. Factors influencing periprosthetic bone loss include demographic factors such as age, sex, obesity, smoking, and comorbidity including diabetes and osteoporosis. The implant design and fixation method are also factors that are determined before surgery. In addition, there are surgical factors, such as surgical approach and surgical technique, and we wish to investigate the factors affecting periprosthetic bone loss around the stem by comparing the effects of postoperative rehabilitation protocols and osteoporosis drugs.

Perioperative patient-specific factors-based nomograms predict short-term periprosthetic bone loss after total hip arthroplasty

BackgroundAlthough medical intervention of periprosthetic bone loss in the immediate postoperative period was recommended, not all the patients experienced periprosthetic bone loss after total hip arthroplasty (THA). Prediction tools that enrolled all potential risk factors to calculate an individualized prediction of postoperative periprosthetic bone loss were strongly needed for clinical decision-making.MethodsData of the patients who underwent primary unilateral cementless THA between April 2015 and October 2017 in our center were retrospectively collected. Candidate variables included demographic data and bone mineral density (BMD) in spine, hip, and periprosthetic regions that measured 1 week after THA. Outcomes of interest included the risk of postoperative periprosthetic bone loss in Gruen zone 1, 7, and total zones in the 1st postoperative year. Nomograms were presented based on multiple logistic regressions via R language. One thousand Bootstraps were used for internal validation.ResultsFive hundred sixty-three patients met the inclusion criteria were enrolled, and the final analysis was performed in 427 patients (195 male and 232 female) after the exclusion. The mean BMD of Gruen zone 1, 7, and total were decreased by 4.1%, 6.4%, and 1.7% at the 1st year after THA, respectively. 61.1% of the patients (261/427) experienced bone loss in Gruen zone 1 at the 1st postoperative year, while there were 58.1% (248/427) in Gruen zone 7 and 63.0% (269/427) in Gruen zone total. Bias-corrected C-index for risk of postoperative bone loss in Gruen zone 1, 7, and total zones in the 1st postoperative year were 0.700, 0.785, and 0.696, respectively. The most highly influential factors for the postoperative periprosthetic bone loss were primary diagnosis and BMD in the corresponding Gruen zones at the baseline.ConclusionsTo the best of our knowledge, our study represented the first time to use the nomograms in estimating the risk of postoperative periprosthetic bone loss with adequate predictive discrimination and calibration. Those predictive models would help surgeons to identify high-risk patients who may benefit from anti-bone-resorptive treatment in the early postoperative period effectively. It is also beneficial for patients, as they can choose the treatment options based on a reasonable expectation following surgery.

The effect of TNF-α on osteoblasts in metal wear-induced periprosthetic bone loss.

AimsThis study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss.MethodsTNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA).ResultsMacrophages, lymphocytes, and endothelial cells displayed strong TNF-α immunoexpression in periprosthetic tissues containing metal wear debris. Colocalization of TNF-α with the macrophage marker CD68 and the pan-T cell marker CD3 confirmed TNF-α expression in these cells. Cobalt-treated MM6 cells secreted more TNF-α than control cells, reflecting the role of metal wear products in activating the TNF-α pathway in the myeloid cells. While TNF-α did not alter the immunoexpression of the TNF-receptor 1 (TNF-R1) in SaOs-2 cells, it increased the release of the soluble TNF-receptor 1 (sTNF-R1). There was also evidence for TNF-α-induced apoptosis. TNF-α further elicited the expression of the endoplasmic reticulum stress markers inositol-requiring enzyme (IRE)-1α, binding-immunoglobulin protein (BiP), and endoplasmic oxidoreductin1 (Ero1)-Lα. In addition, TNF-α decreased pro-collagen I α 1 secretion without diminishing its synthesis. TNF-α also induced an inflammatory response in SaOs-2 cells, as evidenced by the release of reactive oxygen and nitrogen species and the proinflammatory cytokine vascular endothelial growth factor.ConclusionThe results suggest a novel osteoblastic mechanism, which could be mediated by TNF-α and may be involved in metal wear debris-induced periprosthetic bone loss.Cite this article: Bone Joint Res 2020;9(11):827–839.

Can denosumab reduce periprosthetic bone loss after bipolar hip arthroplasty?

Can denosumab reduce periprosthetic bone loss after bipolar hip arthroplasty?

Population-based effect of total knee arthroplasty alignment on simulated tibial bone remodeling

Periprosthetic bone loss is an important factor in tibial implant failure mechanisms in total knee arthroplasty (TKA). The purpose of this study was to determine the effect of postoperative knee alignment and population variation on tibial bone remodeling, to assess long-term stability of a knee replacement. Strain-adaptive finite element (FE) remodeling simulations were conducted following kinematic and mechanical alignment of a cemented fixed-bearing implant after TKA; kinematic TKA alignment was assumed to be more consistent with the preoperative varus alignment, while mechanical alignment was defined according to the neutral mechanical axes. To account for the effect of tibial variation on the outcome, bone remodeling was considered over a population of 47 subjects. Bone mineral density (BMD) was analyzed over three regions of interest (ROIs); medial, lateral and distal. The two proximal ROIs showed an average decrease in BMD in both alignments after two years. Greater overall proximal bone loss was found in the mechanical postoperative knees in comparison with kinematically aligned implants. Bone resorption was also concentrated more medially in mechanical alignment: increased medial ROI bone loss was found in every subject compared to kinematic alignment; while in the lateral ROI, higher regional two-year BMD was found in 39 of the 47 cases (82.9%) following mechanical alignment. Two distinct remodeling pathways were identified over both alignments, based on the variance in density change over the population; displaying predominant bone apposition either around the distal tip of the keel or at the lateral cortex. This study demonstrates that correction of native varus alignment to neutral mechanical alignment leads to an increase in medial bone resorption. Large variation between specimens illustrates the benefit of population-based FE analyses over single model studies.

Raloxifene Prevents Early Periprosthetic Bone Loss for Postmenopausal Women after Uncemented Total Hip Arthroplasty: A Randomized Placebo-Controlled Clinical Trial.

ObjectiveTo examine the results of raloxifene for prevention of periprosthetic bone loss around the femoral stem in patients undergoing total hip arthroplasty (THA).MethodsBetween January 2015 and May 2017, 240 female patients between 55 and 80 years underwent primary THA and were randomly allocated to receive 60 mg raloxifene hydrochloride per day (treatment group, TG, n = 120) or placebo (control group, CG, n = 120) orally at bedtime using computer‐generated randomization sequence generation. Baseline data, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), women's quality of life (QoL) score, bone mineral density (BMD) around the prosthesis, and adverse events were compared between the two groups. The measuring range of BMD around the prosthesis was divided into seven regions of interest (ROI). The sample size was calculated to detect a mean difference in BMD of 0.15 g/cm2 with a standard deviation (SD) of 0.3. The error was set at 0.05 and the power level at 90% with additional compensation for a possible dropout rate of 20%.ResultsA total of 240 participants in the study up to 24 months after THA. There were no significant differences in the mean BMD of all the zones between groups before surgery (all P > 0.05). However, there were significant differences in the BMD of Gruen zones 4 and 7 between groups at 6 months postoperatively (both P < 0.05); there were significant differences in Gruen zones 1, 4, 6, and 7 at 12 months postoperatively (all P < 0.01); there were significant differences in Gruen zones 1, 2, 4, 6, and 7 at 24 months postoperatively (all P < 0.001). Patients taking raloxifene reported higher QoL scores, with better improvement in BMD in all areas except in zones 3 and 5 compared with the control group. There were no significant differences in WOMAC pain (P = 0.4045), WOMAC function (P = 0.4456) and women's QoL scores (P = 0.5983) between groups before surgery. However, WOMAC pain, WOMAC function and women's QoL score in the treatment group were significantly better at all time points (all P < 0.05). Patients in the treatment group showed no increased adverse events, including cardiac events, stroke, venous thromboembolism, and gynecological cancer (all P > 0.05), but did show decreased odds of breast cancer in comparison with those using a placebo (P = 0.0437).ConclusionRaloxifene can help inhibit bone loss around the prosthesis and improve the QoL of postmenopausal women after THA with no increased adverse events, and can even decrease the odds of breast cancer.

The use of bisphosphonates to meet orthopaedic challenges.

The anti-resorptive properties of bisphosphonates have been explored to manage several conditions that traditionally have required a surgical solution. In osteonecrosis, their use is predicated on the principle that bone collapse occurs during the revascularisation phase of the disease. If the associated resorptive activity were modulated, the resultant preserved joint architecture may improve clinical outcome and reduce the need for joint replacement. Pre-clinical and small-scale clinical studies have given non-conclusive support for this principle. Adequately powered clinical trials with relevant long-term endpoints are still required to firmly clarify the clinical efficacy of this treatment. Several clinical studies have shown that bisphosphonates can reduce periprosthetic bone loss and, in some situations, enhance implant fixation in the early period after joint replacement. This may be advantageous in settings where osseointegration is problematic. However, the ultimate goals of their use in joint replacement has been to reduce the incidence of late periprosthetic inflammatory osteolysis, the main cause of prosthesis failure. Population-based observational studies have associated bisphosphonate use with a lower incidence of revision surgery, supported by pre-clinical data. However, clinical trials have, to date, failed to demonstrate any efficacy for the human disease. The timing of bisphosphonate administration for secondary prevention after acute osteoporotic fracture has been subject to extensive investigation, with pre-clinical studies showing increased callus formation but decreased remodelling and no effect on the restoration of mechanical integrity of bone. Meta-analysis of clinical trial data indicates that early administration of bisphosphonate after acute fracture does not adversely affect fracture union, pain or functional outcomes. Finally, bisphosphonates have also been explored as a treatment for complex regional pain syndrome type-I. A recent meta-analysis has shown a beneficial effect on visual analogue scale pain scores, but an increase in mild adverse events.

Prophylactic efficacy on periprosthetic bone loss in calcar region after total hip arthroplasty of antiosteoporotic drugs: a network meta-analysis of randomised controlled studies

ObjectivesThe aim of this study was to evaluate the effect of antiosteoporotic drugs on preventing periprosthetic bone loss in calcar 6 and 12 months after total hip arthroplasty.MethodsThe network meta-analysis...

High periprosthetic bone mineral density measured in immediate postoperative period may not guarantee less periprosthetic bone loss in the proximal femur after cementless total hip arthroplasty \u2013 A retrospective study

BackgroundTotal hip arthroplasty is the most common orthopaedic procedure for the end-stage hip diseases. Periprosthetic bone loss is closely related to the increased risk of implant loosening and periprosthetic fractures, but the predictive value of periprosthetic bone mineral density (BMD) measured immediately after surgery has not yet been investigated.MethodsFrom April 2015 to October 2017, 64 patients with femoral neck fracture, hip osteoarthritis, femoral head necrosis, or developmental dysplasia of the hip underwent unilateral total hip arthroplasty. Demographic data, bone mineral density of the hip and spine, periprosthetic BMD of 7 Gruen zones, and radiographic parameters measured preoperatively, 1 week, 3 months, and 12 months after surgery were collected. A p value < 0.05 was considered to be statistically significant.ResultsSignificant decreases of the periprosthetic BMD were found in Gruen zone 1 (− 8.0%; p < 0.05), Gruen zone 2 (− 6.3%; p < 0.05), Gruen zone 7 (− 8.6%; p < 0.05), and total Gruen zone (− 4.7%; p < 0.05) in the first postoperative year, compared with the values measured 1 week after surgery. The relationship between the preoperative BMD of the hip/spine and the BMD of Gruen zone 1 and Gruen zone 7 measured 1 week after surgery did not reach statistical significance. The multiple linear regression analysis illustrated that the bone loss in Gruen zone 7 at the end of the follow-up period was negatively affected (β = − 0.703) by the BMD of Gruen zone 7 measured 1 week after surgery, with a R2 of 0.486 (p < 0.05). Similar results were also found in Gruen zone 1 (β = − 0.448, R2 = 0.186; p < 0.05).ConclusionThere were marked decreases in periprosthetic BMD of the proximal femur in the first postoperative year. The predictive values of preoperative BMD of hip and spine on periprosthetic bone loss after THA were limited. Higher periprosthetic BMD measured in immediate postoperative period may not guarantee less periprosthetic bone loss in the proximal femur after cementless THA.

Femoral bone remodeling after short-stem total hip arthroplasty: a prospective densitometric study.

Due to improved prosthesis designs and surgical techniques, indications for total hip arthroplasty (THA) now include younger and more active patients. Preserving bone stock and soft tissue in these patients is paramount to allow for future revision. Designed for anatomical reconstruction, short femoral stems have the potential to reduce adaptive bone loss and stress shielding. To confirm this, we evaluated bone remodeling around a short femoral stem and the accuracy of hip joint reconstruction. This prospective observational study involved 46 patients with short-stem THA for clinical and radiographic analysis. We evaluated bone remodeling by Gruen zone using dual-energy X-ray absorptiometry in 45 patients and assessed the accuracy of hip joint reconstruction using caput-collum-diaphyseal angles. Additionally, we reported functional scores and pain. Patients were followed for a mean of 24.1 (SD 2.2) months. Bone mineral density increased mainly in the lateral region (Gruen zones 2 and 3) and in the distal-medial region (Gruen zone 5), suggestive of lateral loading. Most caput-collum-diaphyseal angles remained stable after surgery, especially in patients with varus hips. Harris Hip Scores improved significantly, from 57.2 (SD 20.0) pre-operatively to 97.2 (SD 4.0) at 24months post-operatively (P < 0.0001). Finally, we encountered one peri-operative dislocation but no post-operative complications. Short femoral stems successfully limited stress shielding and minimized periprosthetic bone loss without compromising primary stability. We were able to accurately reconstruct anatomical relationships in most patients. Finally, excellent clinical outcomes and low complication rates confirmed the favourable results of short-stem THA. DRKS00017076.

Effect of Denosumab on Femoral Periprosthetic BMD and Early Femoral Stem Subsidence in Postmenopausal Women Undergoing Cementless Total Hip Arthroplasty.

ABSTRACTAntiresorptive denosumab is known to improve the quality and strength of cortical bone in the proximal femurs of osteoporotic women, but its efficacy in preventing periprosthetic bone loss and reducing femoral stem migration has not been studied in women undergoing cementless total hip arthroplasty. We conducted a single‐center, randomized, double‐blinded, placebo‐controlled trial of 65 postmenopausal women with primary hip osteoarthritis and Dorr type A or B proximal femur anatomy. The patients randomly received subcutaneous injections of denosumab 60 mg or placebo once every 6 months for 12 months, starting 1 month before surgery. The primary endpoint was the change in bone mineral density (BMD) of the proximal femur (Gruen zone 7) at week 48, and the secondary endpoint was stem subsidence measured by radiostereometric analysis (RSA) at week 48. Exploratory endpoints included changes in BMDs of the contralateral hip, lumbar spine and distal radius, serum levels of bone turnover markers, walking speed, walking activity, patient‐reported outcome measures, and radiographic assessment of stem osseointegration. The participants underwent vertebral‐fracture assessment in an extension safety study at 3 years. Denosumab significantly decreased bone loss in the medial femoral neck (zone 7) and increased periprosthetic BMD in the greater trochanteric region (zone 1) and lesser trochanteric region (zone 6). Denosumab did not reduce temporary femoral stem migration. The migration occurred mainly during the settling period (0 to 12 weeks) after implantation of the prosthesis. All of the stems osseointegrated, as evaluated by RSA and radiographs. There were no intergroup differences in functional recovery. Discontinuation of denosumab did not lead to any adverse events. In conclusion, denosumab increased periprosthetic BMD in the clinically relevant regions of the proximal femur, but the treatment response was not associated with any reduction of initial stem migration. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Efficiency of Zoledronic Acid in Inhibiting Accelerated Periprosthetic Bone Loss After Cementless Total Hip Arthroplasty in Osteoporotic Patients: A Prospective, Cohort Study.

ObjectiveTo investigate the influence of preoperative osteopenia/osteoporosis on periprosthetic bone loss after total hip arthroplasty (THA) and the efficiency of zoledronate (ZOL) treatment in periprosthetic bone preservation.MethodsThis multicenter, prospective cohort study was conducted in four centers between April 2015 and October 2017. Patients were assigned to Normal BMD, Osteopenia, and Osteoporosis+ZOL groups. Patients with osteopenia received daily oral calcium (600 mg/d) and vitamin D (0.5 μg/d), while patients in the Osteoporosis+ZOL group received additional ZOL annually (5 mg/year). Periprosthetic bone mineral density (BMD) in seven Gruen zones, radiographic parameters, Harris hip score, EuroQol 5‐Dimensions (EQ‐5D) score, and BMD in hip and spine were measured within 7 days, 3 months, 12 months postoperation and annually thereafter.ResultsA total of 266 patients were enrolled, while 81 patients that completed the first year follow‐up were involved in the statistical analysis. The mean follow‐up time was 1.3 years. There were significant decreases of mean BMD in total Gruen zones (−4.55%, P < 0.05) and Gruen zone 1 (−10.22%, P < 0.01) in patients with osteopenia during the first postoperative year. Patients in the Osteoporosis+ZOL group experienced a marked increase in BMD in Gruen zone 1 (+16%) at the first postoperative year, which had a significant difference when compared with the Normal BMD group (P < 0.05) and the Osteopenia Group (P < 0.001). Low preoperative BMD in hip and spine was predictive of bone loss in Gruen zone 1 at 12 months after THA in patients with normal BMD (R 2 = 0.40, P < 0.05).ConclusionsPatients with osteopenia are prone to higher bone loss in the proximal femur after cementless total hip arthroplasty (THA). ZOL, not solely calcium and vitamin D, could prevent the accelerated periprosthetic bone loss after THA in patients with osteopenia and osteoporosis.

Does radiopaque cement conceal periprosthetic bone loss around femoral stems?

Periprosthetic bone remodelling may increase fracture risk and deplete bone stock around hip implants. These changes are in part caused by implant design, advocating an early evaluation of bone remodelling properties of new implants. This can be done by repeated dual-energy x-ray absorptiometry (DXA) measurements. We know that radiopaque cement falsely elevates bone mineral density (BMD) in single measurements, however, its impact on repeated measurements, i.e. BMD changes is unexplored. We have therefore investigated whether the presence of radiopaque cement affect repeated BMD measurements. 33 patients eligible for total hip replacement were randomly assigned to either radiopaque or radiolucent cement. BMD changes up to 12 months were measured by DXA, in addition to Harris Hip Score, plain radiographs and radiostereometric analysis (RSA). Periprosthetic BMD declined during the first 3-6 months in all zones in both groups. The greatest reduction (14%) was seen in the proximal Gruen zones (1 and 7). We found a significant difference in Gruen zones 1 and 2, where the measured bone loss was higher in the radiolucent cement group. The presence of radiopaque agents in bone cement may influence DXA measurements of bone remodelling.ClinicalTrials.gov identifier NCT00473421.